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  • 1.
    Abadpour, Shadab
    et al.
    Oslo University Hospital, Oslo, Norway.
    Halvorsen, Bente
    Oslo University Hospital, Oslo, Norway.
    Sahraoui, Afaf
    University of Oslo, Oslo, Norway.
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology.
    Aukrust, Pål
    Oslo University Hospital, Oslo, Norway.
    Scholz, Hanne
    Oslo University Hospital, Oslo, Norway.
    Interleukin-22 reverses human islet dysfunction and apoptosis triggered by hyperglycemia and LIGHT2018In: Journal of Molecular Endocrinology, ISSN 0952-5041, E-ISSN 1479-6813, Vol. 60, no 3, p. 171-183Article in journal (Refereed)
    Abstract [en]

    Interleukin (IL)-22 has recently been suggested as an anti-inflammatory cytokine that could protect the islet cells from inflammation- and glucose-induced toxicity. We have previously shown that the tumor necrosis factor family member, LIGHT can impair human islet function at least partly via pro-apoptotic effects. Herein, we aimed to investigate the protective role of IL-22 on human islets exposed to the combination of hyperglycemia and LIGHT. First, we found up-regulation of LIGHT receptors (LTβR and HVEM) in engrafted human islets exposed to hyperglycemia (>11 mM) for 17 days post transplantation by using a double islet transplantation mouse model as well as in human islets cultured with high glucose (HG) (20mM glucose) + LIGHT in vitro and this latter effect was attenuated by IL-22. The effect of HG + LIGHT impairing glucose stimulated insulin secretion was reversed by IL-22. The harmful effect of HG + LIGHT on human islet function seemed to involve enhanced endoplasmic reticulum stress evidenced by up-regulation of p-IRE1α and BiP, elevated secretion of pro-inflammatory cytokines (IL-6, IL-8, IP-10 and MCP-1) and the pro-coagulant mediator tissue factor (TF) release and apoptosis in human islets, whereas all these effects were at least partly reversed by IL-22. Our findings suggest that IL-22 could counteract the harmful effects of LIGHT/hyperglycemia on human islet cells and potentially support the strong protective effect of IL-22 on impaired islet function and survival.

  • 2.
    Abadpour, Shadab
    et al.
    Oslo Univ Hosp, Dept Transplant Med, Sognsvannsveien 20, Oslo 0027, Norway.;Oslo Univ Hosp, Inst Surg Res, Sognsvannsveien 20, Oslo 0027, Norway.;Univ Oslo, Inst Basic Med Sci, Ctr Excellence, Hybrid Technol Hub, Oslo, Norway..
    Tyrberg, Bjorn
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden..
    Schive, Simen W.
    Oslo Univ Hosp, Dept Transplant Med, Sognsvannsveien 20, Oslo 0027, Norway.;Oslo Univ Hosp, Inst Surg Res, Sognsvannsveien 20, Oslo 0027, Norway..
    Huldt, Charlotte Wennberg
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden..
    Gennemark, Peter
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden.;Univ Linköping, Dept Biomed Engn, Linköping, Sweden..
    Ryberg, Erik
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden..
    Ryden-Bergsten, Tina
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden..
    Smith, David M.
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden.;AstraZeneca, BioPharmaceut R&D, Discovery Sci, Hit Discovery, Cambridge, England..
    Korsgren, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Clinical Immunology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Skrtic, Stanko
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Gothenburg, Sweden..
    Scholz, Hanne
    Oslo Univ Hosp, Dept Transplant Med, Sognsvannsveien 20, Oslo 0027, Norway.;Oslo Univ Hosp, Inst Surg Res, Sognsvannsveien 20, Oslo 0027, Norway.;Univ Oslo, Inst Basic Med Sci, Ctr Excellence, Hybrid Technol Hub, Oslo, Norway..
    Winzell, Maria Sorhede
    AstraZeneca, BioPharmaceut R&D, Res & Early Dev Cardiovasc Renal & Metab, Peppredsleden 1, Gothenburg 43183, Sweden..
    Inhibition of the prostaglandin D2-GPR44/DP2 axis improves human islet survival and function2020In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 63, no 7, p. 1355-1367Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Inflammatory signals and increased prostaglandin synthesis play a role during the development of diabetes. The prostaglandin D-2 (PGD(2)) receptor, GPR44/DP2, is highly expressed in human islets and activation of the pathway results in impaired insulin secretion. The role of GPR44 activation on islet function and survival rate during chronic hyperglycaemic conditions is not known. In this study, we investigate GPR44 inhibition by using a selective GPR44 antagonist (AZ8154) in human islets both in vitro and in vivo in diabetic mice transplanted with human islets. Methods Human islets were exposed to PGD(2) or proinflammatory cytokines in vitro to investigate the effect of GPR44 inhibition on islet survival rate. In addition, the molecular mechanisms of GPR44 inhibition were investigated in human islets exposed to high concentrations of glucose (HG) and to IL-1 beta. For the in vivo part of the study, human islets were transplanted under the kidney capsule of immunodeficient diabetic mice and treated with 6, 60 or 100 mg/kg per day of a GPR44 antagonist starting from the transplantation day until day 4 (short-term study) or day 17 (long-term study) post transplantation. IVGTT was performed on mice at day 10 and day 15 post transplantation. After termination of the study, metabolic variables, circulating human proinflammatory cytokines, and hepatocyte growth factor (HGF) were analysed in the grafted human islets. Results PGD(2) or proinflammatory cytokines induced apoptosis in human islets whereas GPR44 inhibition reversed this effect. GPR44 inhibition antagonised the reduction in glucose-stimulated insulin secretion induced by HG and IL-1 beta in human islets. This was accompanied by activation of the Akt-glycogen synthase kinase 3 beta signalling pathway together with phosphorylation and inactivation of forkhead box O-1and upregulation of pancreatic and duodenal homeobox-1 and HGF. Administration of the GPR44 antagonist for up to 17 days to diabetic mice transplanted with a marginal number of human islets resulted in reduced fasting blood glucose and lower glucose excursions during IVGTT. Improved glucose regulation was supported by increased human C-peptide levels compared with the vehicle group at day 4 and throughout the treatment period. GPR44 inhibition reduced plasma levels of TNF-alpha and growth-regulated oncogene-alpha/chemokine (C-X-C motif) ligand 1 and increased the levels of HGF in human islets. Conclusions/interpretation Inhibition of GPR44 in human islets has the potential to improve islet function and survival rate under inflammatory and hyperglycaemic stress. This may have implications for better survival rate of islets following transplantation.

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    FULLTEXT01
  • 3.
    Abadpour, Shadab
    et al.
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Tyrberg, Bjorn
    AstraZeneca, Sweden.
    Schive, Simen W.
    Oslo Univ Hosp, Norway.
    Wennberg Huldt, Charlotte
    AstraZeneca, Sweden.
    Gennemark, Peter
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. AstraZeneca, Sweden.
    Ryberg, Erik
    AstraZeneca, Sweden.
    Ryden-Bergsten, Tina
    AstraZeneca, Sweden.
    Smith, David M.
    AstraZeneca, Sweden; AstraZeneca, England.
    Korsgren, Olle
    Uppsala Univ, Sweden.
    Skrtic, Stanko
    AstraZeneca, Sweden; Univ Gothenburg, Sweden.
    Scholz, Hanne
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Winzell, Maria Sorhede
    AstraZeneca, Sweden.
    Inhibition of the prostaglandin D-2-GPR44/DP2 axis improves human islet survival and function2020In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 63, no 7, p. 1355-1367Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Inflammatory signals and increased prostaglandin synthesis play a role during the development of diabetes. The prostaglandin D-2 (PGD(2)) receptor, GPR44/DP2, is highly expressed in human islets and activation of the pathway results in impaired insulin secretion. The role of GPR44 activation on islet function and survival rate during chronic hyperglycaemic conditions is not known. In this study, we investigate GPR44 inhibition by using a selective GPR44 antagonist (AZ8154) in human islets both in vitro and in vivo in diabetic mice transplanted with human islets. Methods Human islets were exposed to PGD(2) or proinflammatory cytokines in vitro to investigate the effect of GPR44 inhibition on islet survival rate. In addition, the molecular mechanisms of GPR44 inhibition were investigated in human islets exposed to high concentrations of glucose (HG) and to IL-1 beta. For the in vivo part of the study, human islets were transplanted under the kidney capsule of immunodeficient diabetic mice and treated with 6, 60 or 100 mg/kg per day of a GPR44 antagonist starting from the transplantation day until day 4 (short-term study) or day 17 (long-term study) post transplantation. IVGTT was performed on mice at day 10 and day 15 post transplantation. After termination of the study, metabolic variables, circulating human proinflammatory cytokines, and hepatocyte growth factor (HGF) were analysed in the grafted human islets. Results PGD(2) or proinflammatory cytokines induced apoptosis in human islets whereas GPR44 inhibition reversed this effect. GPR44 inhibition antagonised the reduction in glucose-stimulated insulin secretion induced by HG and IL-1 beta in human islets. This was accompanied by activation of the Akt-glycogen synthase kinase 3 beta signalling pathway together with phosphorylation and inactivation of forkhead box O-1and upregulation of pancreatic and duodenal homeobox-1 and HGF. Administration of the GPR44 antagonist for up to 17 days to diabetic mice transplanted with a marginal number of human islets resulted in reduced fasting blood glucose and lower glucose excursions during IVGTT. Improved glucose regulation was supported by increased human C-peptide levels compared with the vehicle group at day 4 and throughout the treatment period. GPR44 inhibition reduced plasma levels of TNF-alpha and growth-regulated oncogene-alpha/chemokine (C-X-C motif) ligand 1 and increased the levels of HGF in human islets. Conclusions/interpretation Inhibition of GPR44 in human islets has the potential to improve islet function and survival rate under inflammatory and hyperglycaemic stress. This may have implications for better survival rate of islets following transplantation.

    Download full text (pdf)
    fulltext
  • 4. Abbas, S
    et al.
    Linseisen, J
    Rohrmann, S
    Beulens, JWJ
    Buijsse, B
    Amiano, P
    Ardanaz, E
    Balkau, B
    Boeing, H
    Clavel-Chapelon, F
    Fagherazzi, G
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Gavrila, D
    Grioni, S
    Kaaks, R
    Key, TJ
    Khaw, KT
    Kuehn, T
    Mattiello, A
    Molina-Montes, E
    Nilsson, PM
    Overvad, K
    Quiros, JR
    Rolandsson, Olov
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Sacerdote, C
    Saieva, C
    Slimani, N
    Sluijs, I
    Spijkerman, AMW
    Tjonneland, A
    Tumino, R
    van der A, DL
    Zamora-Ros, R
    Sharp, SJ
    Langenberg, C
    Forouhi, NG
    Riboli, E
    Wareham, NJ
    Dietary vitamin D intake and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition: the EPIC-InterAct study2014In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 68, no 2, p. 196-202Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/OBJECTIVES: Prospective cohort studies have indicated that serum vitamin D levels are inversely related to risk of type 2 diabetes. However, such studies cannot determine the source of vitamin D. Therefore, we examined the association of dietary vitamin D intake with incident type 2 diabetes within the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in a heterogeneous European population including eight countries with large geographical variation.

    SUBJECTS/METHODS: Using a case-cohort design, 11 245 incident cases of type 2 diabetes and a representative subcohort (N = 15 798) were included in the analyses. Hazard ratios (HR) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using a Prentice-weighted Cox regression adjusted for potential confounders. Twenty-four-hour diet-recall data from a subsample (N = 2347) were used to calibrate habitual intake data derived from dietary questionnaires.

    RESULTS: Median follow-up time was 10.8 years. Dietary vitamin D intake was not significantly associated with the risk of type 2 diabetes. HR and 95% CIs for the highest compared to the lowest quintile of uncalibrated vitamin D intake was 1.09 (0.97-1.22) (P-trend = 0.17). No associations were observed in a sex-specific analysis. The overall pooled effect (HR (95% CI)) using the continuous calibrated variable was 1.00 (0.97-1.03) per increase of 1 mg/day dietary vitamin D.

    CONCLUSIONS: This observational study does not support an association between higher dietary vitamin D intake and type 2 diabetes incidence. This result has to be interpreted in light of the limited contribution of dietary vitamin D on the overall vitamin D status of a person.

  • 5.
    Abdalla, Mohammed A.
    et al.
    Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School (HYMS), The University of Hull, Hull, UK.
    Shah, Najeeb
    Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School (HYMS), The University of Hull, Hull, UK.
    Deshmukh, Harshal
    Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School (HYMS), The University of Hull, Hull, UK.
    Sahebkar, Amirhossein
    Biotechnology Research Centre, Mashhad University of Medical Sciences, Pharmaceutical Technology Institute, Mashhad, Iran; Mashhad University of Medical Sciences I Applied Biomedical Research Centre, Mashhad, Iran; The University of Western Australia I School of Medicine, Perth, Western Australia, Australia.
    Östlundh, Linda
    United Arab Emirate University I College of Medicine and Health Sciences, The National Medical Library, Al Ain, United Arab Emirates.
    Al-Rifai, Rami H.
    United Arab Emirate University I College of Medicine and Health Sciences, Al Ain, United Arab Emirates.
    Atkin, Stephen L.
    RCSI Medical University of Bahrain I School of Postgraduate Studies and Research, Bahrain, Kingdom of Bahrain.
    Sathyapalan, Thozhukat
    Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School (HYMS), The University of Hull, Hull, UK.
    Effect of pharmacological interventions on lipid profiles and C-reactive protein in polycystic ovary syndrome: A systematic review and meta-analysis2022In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 96, no 4, p. 443-459Article, review/survey (Refereed)
    Abstract [en]

    Context: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age. It is associated with dyslipidaemia and elevated plasma C-reactive protein (CRP), which increase the risks of cardiovascular disease (CVD).

    Objective: To review the existing evidence on the effects of different pharmacological interventions on lipid profiles and CRP of women with PCOS.

    Data Sources: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library, and Web of Science in April 2020 and updated the results in March 2021.

    Study Selection: The study included randomized controlled trials (RCTs) and follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA).

    Data Extraction: Two independent researchers extracted data and assessed for risk of bias using the Cochrane risk of bias tool. Covidence systematic review software were used for blinded screening and study selection.

    Data Synthesis: In 29 RCTs, there were significant reductions in triglycerides with atorvastatin versus placebo [mean difference (MD): -0.21 mmol/L; 95% confidence interval (CI): -0.39, -0.03, I-2 = 0%, moderate grade evidence]. Significant reductions were seen for low-density lipoprotein cholesterol (LDL-C) with metformin versus placebo [standardized mean difference (SMD): -0.41; 95% CI: -0.85, 0.02, I-2 = 59%, low grade evidence]. Significant reductions were also seen for total cholesterol with saxagliptin versus metformin (MD: -0.15 mmol/L; 95% CI: -0.23, -0.08, I-2 = 0%, very low grade evidence). Significant reductions in C-reactive protein (CRP) were seen for atorvastatin versus placebo (MD: -1.51 mmol/L; 95% CI: -3.26 to 0.24, I-2 = 75%, very low-grade evidence).

    Conclusion: There were significant reductions in the lipid parameters when metformin, atorvastatin, saxagliptin, rosiglitazone and pioglitazone were compared with placebo or other agents. There was also a significant reduction of CRP with atorvastatin.

  • 6.
    Abdalla, Mohammed A.
    et al.
    Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School (HYMS), University of Hull, Hull, UK.
    Shah, Najeeb
    Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School (HYMS), University of Hull, Hull, UK.
    Deshmukh, Harshal
    Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School (HYMS), University of Hull, Hull, UK.
    Sahebkar, Amirhossein
    Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; School of Medicine, University of Western Australia, Perth, Australia.
    Östlundh, Linda
    College of Medicine and Health Sciences, The National Medical Library, United Arab Emirates University, Al Ain, United Arab Emirates.
    Al-Rifai, Rami H.
    College of Medicine and Health Sciences, Institute of Public Health, United Arab Emirates University, Al Ain, United Arab Emirates.
    Atkin, Stephen L.
    School of Postgraduate Studies and Research, RCSI Medical University of Bahrain, Busaiteen, Kingdom of Bahrain.
    Sathyapalan, Thozhukat
    Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School (HYMS), University of Hull, Hull, UK.
    Impact of pharmacological interventions on anthropometric indices in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials2022In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 96, no 6, p. 758-780Article, review/survey (Refereed)
    Abstract [en]

    Context: Polycystic ovary syndrome (PCOS) is a heterogeneous condition affecting women of reproductive age and is associated with increased body weight.

    Objective: To review the literature on the effect of different pharmacological interventions on the anthropometric indices in women with PCOS.

    Data sources: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library, and the Web of Science in April 2020 with an update in PubMed in March 2021.

    Study selection: The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)2020.

    Data extraction: Reviewers extracted data and assessed the risk of bias using the Cochrane risk of bias tool.

    Results: 80 RCTs were included in the meta-analysis. Metformin vs placebo showed significant reduction in the mean body weight (MD: -3.13 kg; 95% confidence interval [CI]: -5.33 to -0.93, I-2 = 5%) and the mean body mass index (BMI) (MD: -0.75 kg/m(2); 95% CI: -1.15 to -0.36, I-2 = 0%). There was a significant reduction in the mean BMI with orlistat versus placebo (MD: -1.33 kg/m(2); 95% CI: -2.16 to -0.66, I-2 = 0.0%), acarbose versus metformin (MD: -1.26 kg/m(2); 95% CI: -2.13 to -0.38, I-2 = 0%), and metformin versus pioglitazone (MD: -0.91 kg/m(2); 95% CI: -1.62 to -0.19, I-2 = 0%). A significant increase in the mean BMI was also observed in pioglitazone versus placebo (MD: + 2.59 kg/m(2); 95% CI: 1.78-3.38, I-2 = 0%) and in rosiglitazone versus metformin (MD: + 0.80 kg/m(2); 95% CI: 0.32-1.27, I-2 = 3%). There was a significant reduction in the mean waist circumference (WC) with metformin versus placebo (MD: -1.21 cm; 95% CI: -3.71 to 1.29, I-2 = 0%) while a significant increase in the mean WC with pioglitazone versus placebo (MD: + 5.45 cm; 95% CI: 2.18-8.71, I-2 = 0%).

    Conclusion: Pharmacological interventions including metformin, sitagliptin, pioglitazone, rosiglitazone orlistat, and acarbose have significant effects on the anthropometric indices in women with PCOS.

  • 7.
    Abdalla, Mohammed A.
    et al.
    Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School (HYMS), The University of Hull, Hull, UK.
    Shah, Najeeb
    Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School (HYMS), The University of Hull, Hull, UK.
    Deshmukh, Harshal
    Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School (HYMS), The University of Hull, Hull, UK.
    Sahebkar, Amirhossein
    Biotechnology Research Centre, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran.
    Östlundh, Linda
    College of Medicine and Health Sciences, The National Medical Library, United Arab Emirate University, Al Ain, United Arab Emirates.
    Al-Rifai, Rami H.
    College of Medicine and Health Sciences, Institute of Public Health, United Arab Emirate University, Al Ain, United Arab Emirates.
    Atkin, Stephen L.
    School of Postgraduate Studies and Research, RCSI Medical University of Bahrain, Busaiteen, Kingdom of Bahrain.
    Sathyapalan, Thozhukat
    Department of Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School (HYMS), The University of Hull, Hull, UK.
    Impact of pharmacological interventions on insulin resistance in women with polycystic ovary syndrome: A systematic review and meta-analysis of randomized controlled trials2022In: Clinical Endocrinology, ISSN 0300-0664, E-ISSN 1365-2265, Vol. 96, no 3, p. 371-394Article, review/survey (Refereed)
    Abstract [en]

    Objective: Polycystic ovary syndrome (PCOS) is a complex endocrine condition affecting women of reproductive age. It is characterized by insulin resistance and is a major risk factor for type 2 diabetes mellitus (T2DM). The objective was to review the literature on the effect of different pharmacological interventions on insulin resistance in women with PCOS.

    Design: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane library and the Web of Science in April 2020 and updated in March 2021. The study follows the 2020 Preferred Reporting Items for Systematic reviews and Meta-ana. Reviwers extracted data and assessed the risk of bias using the Cochrane risk of bias tool.

    Results: In 58 randomized controlled trials there were significant reductions in the fasting blood glucose (FBG) with metformin versus placebo (standardized mean difference [SMD]: -0.23; 95% confidence interval [CI]: -0.40, -0.06; I-2 = 0%, low-grade evidence), and acarbose versus metformin (mean difference [MD]: -10.50 mg/dl; 95% CI: -15.76, -5.24; I-2 = 0%, low-grade evidence). Significant reductions in fasting insulin (FI) with pioglitazone versus placebo (SMD: -0.55; 95% CI: -1.03, -0.07; I-2 = 37%; p = .02, very-low-grade evidence). A significant reduction in homoeostatic model assessment of insulin resistance (HOMA-IR) was seen with exenatide versus metformin (MD: -0.34; 95% CI: -0.65, -0.03; I-2 = 0%, low-grade evidence). No effect on homoeostatic model assessment of beta cells (HOMA-B) was observed.

    Conclusions: Pharmacological interventions, including metformin, acarbose, pioglitazone and exenatide have significant effects on FBG, FI, HOMA-IR but not on HOMA-B.

  • 8.
    Abdalla, Mohammed Altigani
    et al.
    Allam Diabetes Centre, Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School (HYMS), University of Hull, Hull, UK.
    Shah, Najeeb
    Allam Diabetes Centre, Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School (HYMS), University of Hull, Hull, UK.
    Deshmukh, Harshal
    Allam Diabetes Centre, Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School (HYMS), University of Hull, Hull, UK.
    Sahebkar, Amirhossein
    Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Medicine, The University of Western Australia, Perth WA, Australia.
    Östlundh, Linda
    National Medical Library, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
    Al-Rifai, Rami H.
    Institute of Public Health, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.
    Atkin, Stephen L.
    School of Postgraduate Studies and Research, RCSI Medical University of Bahrain, Busaiteen, Kingdom of Bahrain.
    Sathyapalan, Thozhukat
    Academic Diabetes, Endocrinology and Metabolism, Allam Diabetes Centre Hull Royal Infirmary Anlaby Road HU3 2JZ, Hull, UK.
    Impact of metformin on the clinical and metabolic parameters of women with polycystic ovary syndrome: a systematic review and meta-analysis of randomised controlled trials2022In: Therapeutic Advances in Endocrinology and Metabolism, ISSN 2042-0188, Vol. 13, article id 20420188221127142Article, review/survey (Refereed)
    Abstract [en]

    Context: Polycystic ovary syndrome (PCOS) is one of the commonest endocrine disorders affecting women of reproductive age, and metformin is a widely used medication in managing this condition.

    Aim: To review the available literature comprehensively on the therapeutic impact of metformin on the clinical and metabolic parameters of women with PCOS.

    Data source: We searched PubMed, MEDLINE, Scopus, Embase, Cochrane Library and the Web of Science and selected sources for grey literature from their inception to April 2020. An updated search in PubMed was performed in June 2022.

    Data synthesis: Two reviewers selected eligible studies and extracted data, and the review is reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA).

    Results: In 24 eligible randomised controlled trials (RCTs) involving 564 participants who received metformin therapy, metformin was associated with significant reduction in body weight by 3.13 kg (95% CI: -5.33, -0.93), body mass index (BMI) by 0.82 kg/m(2) (95% CI: -1.22, -0.41), fasting blood glucose [standardised mean difference (SMD): -0.23; 95% CI: -0.40, -0.06], low-density lipoprotein cholesterol (LDL-C) (SMD: -0.41; 95% CI: -0.85, 0.03), total testosterone (SMD: -0.33; 95% CI: -0.49, -0.17), androstenedione (SMD: -0.45; 95% CI: -0.70, -0.20), 17-hydroxyprogesterone (17-OHP) (SMD: -0.58; 95% CI: -1.16, 0.00) and increase the likelihood of clinical pregnancy rate [odds ratio (OR): 3.00; 95% CI: 1.95, 4.59] compared with placebo.

    Conclusion: In women with PCOS, metformin use has shown a positive impact in reducing body weight, BMI, total testosterone, androstenedione, 17-OHP, LDL-C, fasting blood glucose and increasing the likelihood of pregnancy in women with PCOS.

  • 9.
    Abdullahi Mohamed, Mohamed
    Mälardalen University, School of Sustainable Development of Society and Technology.
     GLP-1 REGULATES PROLIFERATION OF GLP-1 SECRETING CELLS THROUGH A FEEDBACK MECHANISM2010Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Abstract

    Background and aim:

    Diabetes mellitus (DM) is a chronic and progressive illness that affects all type of populations and ages. According to World health organization (WHO) by 2030 it will be 366 million people effected world wild. Many new drugs are Glucagon-like peptide-1 (GLP-1) based therapy for treatment of type 2diabetes. GLP-1 is released from the intestinal L-cells, and is a potent stimulator of glucose-dependent insulin secretion. The aim of this study was to investigate the effect of GLP-1 and its stable analogs on cell proliferation of GLP-1 secreting GLUTag cells.

    Material and methods:

    GluTag cells were incubated for 48h in DMEM medium containing (0.5% fetal bovine serum and 100 IU/ml penicillin and 100 μg/ml streptomycin and 3mM glucose concentration) in the present or absence of the agents. DNA synthesis was measured using 3H- thymidine incorporation and Ki67 antigen staining. Western blot were performed to investigate the present of GLP-1 receptor in GLUTag cells.

    Results/conclusions:

    These results suggest that GLP-1 regulates proliferation of the GLP-1-secreting cell through a feedback mechanism via its receptor. Since serum GLP-1 levels are decreased in type 2 diabetic patients, the effect of GLP-1 on the GLP-1-secreting cell proliferation suggested here provides a novel beneficial long-term effect of the incretin-based drugs in clinical practice i.e. through increase of the GLP-1-secreting cell mass, augmenting the incretin effect. In addition, the feedback mechanism action of GLP-1 reveals a new insight in regulation manner of the L-cell proliferation.

    GLP-1(7-36) increased cell proliferation in GLUTag cells, an effect which was blocked by the GLP-1 receptor antagonist exendin(9-39). The GLP-1 receptor was expressed in GluTag cells.

    Keywords:

    Incretin hormone, GLP-1, GLP-1 receptor, Exendin-4, Diabetes

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  • 10.
    Abels, M.
    et al.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Riva, M.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Poon, W.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Bennet, H.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Nagaraj, V.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Dyachok, Oleg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Isomaa, B.
    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Social Serv & Hlth Care, Jacobstad, Finland..
    Tuomi, T.
    Folkhalsan Res Ctr, Helsinki, Finland.;Dept Med, Helsinki, Finland..
    Ahren, B.
    Lund Univ, Ctr Diabet, Lund, Sweden..
    Tengholm, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Fex, M.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Renstrom, E.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Groop, L.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Lyssenko, V.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Wierup, N.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    CART is a novel glucose-dependent peptide with antidiabetic actions in humans2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no Suppl. 1, p. S279-S280Article in journal (Other academic)
  • 11.
    Abels, Mia
    et al.
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Riva, Matteo
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Bennet, Hedvig
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Ahlqvist, Emma
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Dyachok, Oleg
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Nagaraj, Vini
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Shcherbina, Liliya
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Fred, Rikard G.
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Poon, Wenny
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Sorhede-Winzell, Maria
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Fadista, Joao
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Lindqvist, Andreas
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Kask, Lena
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Sathanoori, Ramasri
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Dekker-Nitert, Marloes
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Kuhar, Michael J.
    Emory Univ, Yerkes Res Ctr, Atlanta, GA 30322 USA..
    Ahren, Bo
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Wollheim, Claes B.
    Univ Med Ctr, Dept Cell Physiol & Metab, Geneva, Switzerland..
    Hansson, Ola
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Tengholm, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Fex, Malin
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Renström, Erik
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Groop, Leif
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden..
    Lyssenko, Valeriya
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden.;Steno Diabet Ctr AS, Gentofte, Denmark..
    Wierup, Nils
    Lund Univ, Ctr Diabet, Skane Univ Hosp, Lund, Sweden.;Lund Univ, Ctr Diabet, Skane Univ Hosp, Malmo, Sweden.;Lund Univ, Clin Res Ctr 91 12, Ctr Diabet, Skane Univ Hosp,Dept Clin Sci Malmo,Unit Neuroend, Jan Waldenstroms Gata 35, S-20502 Malmo, Sweden..
    CART is overexpressed in human type 2 diabetic islets and inhibits glucagon secretion and increases insulin secretion2016In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 59, no 9, p. 1928-1937Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis Insufficient insulin release and hyperglucagonaemia are culprits in type 2 diabetes. Cocaine- and amphetamine-regulated transcript (CART, encoded by Cartpt) affects islet hormone secretion and beta cell survival in vitro in rats, and Cart(-/-) mice have diminished insulin secretion. We aimed to test if CART is differentially regulated in human type 2 diabetic islets and if CART affects insulin and glucagon secretion in vitro in humans and in vivo in mice. Methods CART expression was assessed in human type 2 diabetic and non-diabetic control pancreases and rodent models of diabetes. Insulin and glucagon secretion was examined in isolated islets and in vivo in mice. Ca2+ oscillation patterns and exocytosis were studied in mouse islets. Results We report an important role of CART in human islet function and glucose homeostasis in mice. CART was found to be expressed in human alpha and beta cells and in a subpopulation of mouse beta cells. Notably, CART expression was several fold higher in islets of type 2 diabetic humans and rodents. CART increased insulin secretion in vivo in mice and in human and mouse islets. Furthermore, CART increased beta cell exocytosis, altered the glucose-induced Ca2+ signalling pattern in mouse islets from fast to slow oscillations and improved synchronisation of the oscillations between different islet regions. Finally, CART reduced glucagon secretion in human and mouse islets, as well as in vivo in mice via diminished alpha cell exocytosis. Conclusions/interpretation We conclude that CART is a regulator of glucose homeostasis and could play an important role in the pathophysiology of type 2 diabetes. Based on the ability of CART to increase insulin secretion and reduce glucagon secretion, CART-based agents could be a therapeutic modality in type 2 diabetes.

  • 12.
    Abrahamsson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    On the Impact of Bariatric Surgery on Glucose Homeostasis2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Obesity has grown to epidemic proportions, and in lack of efficient life-style and medical treatments, the bariatric surgeries are performed in rising numbers. The most common surgery is the Gastric Bypass (GBP) surgery, with the Biliopancreatic diversion with duodenal switch (DS) as an option for the most extreme cases with a BMI>50 kg/m2.

    In paper I 20 GBP-patients were examined during the first post-operative year regarding the natriuretic peptide, NT-ProBNP, which is secreted from the cardiac ventricles. Levels of NT-ProBNP quickly increased during the first post-surgery week, and later established itself on a higher level than pre-surgery.

    In paper II we report of 5 patient-cases after GBP-surgery with severe problems with postprandial hypoglycaemia that were successfully treated with GLP-1-analogs. The effect of treatment could be observed both symptomatically and in some cases using continuous glucose measuring systems (CGMS).

    In paper III three groups of subjects; 15 post-GBP patients, 15 post-DS, and 15 obese controls were examined for three days using CGMS during everyday life. The post-GBP group had high glucose variability as measured by MAGE and CONGA, whereas the post-DS group had low variability. Both post-operative groups exhibited significant time in hypoglycaemia, about 40 and 80 minutes per day <3.3mmol/l and 20 and 40 minutes < 2.8mmol/l, respectively, longer time for DS-group. Remarkably, only about 20% of these hypoglycaemic episodes were accompanied with symptoms.

    In Paper IV the hypoglycaemia counter regulatory system was investigated; 12 patients were examined before and after GBP-surgery with a stepped hypoglycaemic hyperinsulinemic clamp. The results show a downregulation of symptoms, counter regulatory hormones (glucagon, cortisol, epinephrine, norepinephrine, growth hormone), incretin hormones (GLP-1 and GIP), and sympathetic nervous response.

    In conclusion patients post bariatric surgery exhibit a downregulated counter regulatory response to hypoglycaemia, accompanied by frequent asymptomatic hypoglycaemic episodes in everyday life. Patients suffering from severe hypoglycaemic episodes can often be treated successfully with GLP-1-analogues.

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  • 13. Abrahamsson, Niclas
    et al.
    Borjesson, Joey Lau
    Sundbom, Magnus
    Wiklund, Urban
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Karlsson, F. Anders
    Eriksson, Jan W.
    Gastric Bypass Reduces Symptoms and Hormonal Responses in Hypoglycemia2016In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 9, p. 2667-2675Article in journal (Refereed)
    Abstract [en]

    Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.

  • 14.
    Abrahamsson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Engström, Britt Edén
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Karlsson, Anders F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Hypoglycemia in everyday life after gastric bypass and duodenal switch2015In: European Journal of Endocrinology, ISSN 0804-4643, E-ISSN 1479-683X, Vol. 173, no 1, p. 91-100Article in journal (Refereed)
    Abstract [en]

    Design: Gastric bypass (GBP) and duodenal switch (DS) in morbid obesity are accompanied by marked metabolic improvements, particularly in glucose control. In recent years, episodes of severe late postprandial hypoglycemia have been increasingly described in GBP patients; data in DS patients are scarce. We recruited three groups of subjects; 15 GBP, 15 DS, and 15 non-operated overweight controls to examine to what extent hypoglycemia occurs in daily life. Methods: Continuous glucose monitoring (CGM) was used during 3 days of normal activity. The glycemic variability was measured by mean amplitude of glycemic excursion and continuous overall net glycemic action. Fasting blood samples were drawn, and the patients kept a food and symptom log throughout the study. Results: The GBP group displayed highly variable CGM curves, and 2.9% of their time was spent in hypoglycemia (< 3.3 mmol/l, or 60 mg/dl). The DS group had twice as much time in hypoglycemia (5.9%) and displayed CGM curves with little variation as well as lower HbA1c levels (29.3 vs 35.9 mmol/mol, P < 0.05). Out of a total of 72 hypoglycemic episodes registered over the 3-day period, 70 (97%) occurred in the postprandial state and only about one-fifth of the hypoglycemic episodes in the GBP and DS groups were accompanied by symptoms. No hypoglycemias were seen in controls during the 3-day period. Conclusion: Both types of bariatric surgery induce marked, but different, changes in glucose balance accompanied by frequent, but mainly unnoticed, hypoglycemic episodes. The impact and mechanism of hypoglycemic unawareness after weight-reduction surgery deserves to be clarified.

  • 15.
    Abrahamsson, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Lau Börjesson, Joey
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sundbom, Magnus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Wiklund, Urban
    Umea Univ, Biomed Engn, Dept Radiat Sci, Umea, Sweden.
    Karlsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Eriksson, Jan W.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Gastric bypass reduces symptoms and hormonal responses to hypoglycemia2016In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 65, no 9, p. 2667-2675Article in journal (Refereed)
    Abstract [en]

    Gastric bypass (GBP) surgery, one of the most common bariatric procedures, induces weight loss and metabolic effects. The mechanisms are not fully understood, but reduced food intake and effects on gastrointestinal hormones are thought to contribute. We recently observed that GBP patients have lowered glucose levels and frequent asymptomatic hypoglycemic episodes. Here, we subjected patients before and after undergoing GBP surgery to hypoglycemia and examined symptoms and hormonal and autonomic nerve responses. Twelve obese patients without diabetes (8 women, mean age 43.1 years [SD 10.8] and BMI 40.6 kg/m(2) [SD 3.1]) were examined before and 23 weeks (range 19-25) after GBP surgery with hyperinsulinemic-hypoglycemic clamp (stepwise to plasma glucose 2.7 mmol/L). The mean change in Edinburgh Hypoglycemia Score during clamp was attenuated from 10.7 (6.4) before surgery to 5.2 (4.9) after surgery. There were also marked postsurgery reductions in levels of glucagon, cortisol, and catecholamine and the sympathetic nerve responses to hypoglycemia. In addition, growth hormone displayed a delayed response but to a higher peak level. Levels of glucagon-like peptide 1 and gastric inhibitory polypeptide rose during hypoglycemia but rose less postsurgery compared with presurgery. Thus, GBP surgery causes a resetting of glucose homeostasis, which reduces symptoms and neurohormonal responses to hypoglycemia. Further studies should address the underlying mechanisms as well as their impact on the overall metabolic effects of GBP surgery.

  • 16.
    Acerini, Carlo L.
    et al.
    University of Cambridge, England.
    Wac, Katarzyna
    University of Geneva, Switzerland.
    Bang, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Lehwalder, Dagmar
    Merck KGaA, Germany.
    Optimizing Patient Management and Adherence for children receiving Growth Hormone2017In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 8, article id 313Article in journal (Refereed)
    Abstract [en]

    Poor adherence with growth hormone (GH) therapy has been associated with worse clinical outcomes, which in children relates specifically to their linear growth and loss of quality of life. The "360 degrees GH in Europe" meeting, held in Lisbon, Portugal, in June 2016 and funded by Merck KGaA (Germany), examined many aspects of GH diseases. The three sessions, entitled "Short Stature Diagnosis and Referral," "Optimizing Patient Management," and "Managing Transition," each benefited from three guest speaker presentations, followed by an open discussion and are reported as a manuscript, authored by the speakers. Reported here is a summary of the proceedings of the second session, which reviewed the determinants of GH therapy response, factors affecting GH therapy adherence and the development of innovative technologies to improve GH treatment in children. Response to GH therapy varies widely, particularly in regard to the underlying diagnosis, although there is little consensus on the definition of a poor response. If the growth response is seen to be less than expected, the possible reasons should be discussed with patients and their parents, including compliance with the therapy regimen. Understanding and addressing the multiple factors that influence adherence, in order to optimize GH therapy, requires a multi-disciplinary approach. Because therapy continues over many years, various healthcare professionals will be involved at different periods of the patients journey. The role of the injection device for GH therapy, frequent monitoring of response, and patient support are all important for maintaining adherence. New injection devices are incorporating electronic technologies for automated monitoring and recording of clinically relevant information on injections. Study results are indicating that such devices can at least maintain GH adherence; however, acceptance of novel devices needs to be assessed and there remains an on-going need for innovations.

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  • 17.
    Adam, Sumaiya
    et al.
    Univ Pretoria, Fac Hlth Sci, Sch Med, Dept Obstet & Gynecol, Pretoria, South Africa.;Univ Pretoria, Fac Hlth Sci, Diabet Res Ctr, Pretoria, South Africa..
    McIntyre, Harold David
    Univ Queensland, Mater Hlth, Mater Hlth Campus, South Brisbane, Qld, Australia..
    Tsoi, Kit Ying
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China..
    Kapur, Anil
    World Diabet Fdn, Copenhagen, Denmark..
    Ma, Ronald C.
    Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China.;Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Peoples R China..
    Dias, Stephanie
    South African Med Res Council, Biomed Res & Innovat Platform BRIP, Cape Town, South Africa..
    Okong, Pius
    St Francis Hosp Nsambya, Dept Obstet & Gynecol, Kampala, Uganda..
    Hod, Moshe
    Helen Schneider Hosp Women, Rabin Med Ctr, Petah Tiqwa, Israel.;Tel Aviv Univ, Sackler Fac Med, Tel Aviv, Israel..
    Poon, Liona C.
    Chinese Univ Hong Kong, Prince Wales Hosp, Dept Obstet & Gynecol, Hong Kong, Peoples R China..
    Smith, Graeme N.
    Queens Univ, Kingston Hlth Sci Ctr, Dept Obstet & Gynecol, Kingston, ON, Canada..
    Bergman, Lina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Clinical Obstetrics. Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Obstet & Gynecol, Gothenburg, Sweden; Stellenbosch Univ, Dept Obstet & Gynecol, Cape Town, South Africa.
    Algurjia, Esraa
    World Assoc Trainees Obstet & Gynecol WATOG, Paris, France.;Elwya Matern Hosp, Baghdad, Iraq..
    O'Brien, Patrick
    UCL, Inst Womens Hlth, London, England..
    Medina, Virna P.
    Univ Valle, Univ Libre, Fac Hlth, Dept Obstet & Gynecol,Clin Imbanaco Quiron Salud, Cali, Colombia..
    Maxwell, Cynthia, V
    Univ Toronto, Maternal Fetal Med, Sinai Hlth, Toronto, ON, Canada.;Univ Toronto, Womens Coll Hosp, Ontario, ON, Canada..
    Regan, Lesley
    Imperial Coll London, London, England..
    Rosser, Mary L.
    Columbia Univ, Dept Obstet & Gynecol, Irving Med Ctr, New York, NY USA..
    Jacobsson, Bo
    Sahlgrens Univ Hosp, Dept Obstet & Gynecol, Gothenburg, Sweden.;Inst Publ Hlth, Dept Genet & Bioinformat, Domain Hlth Data & Digitalisat, Oslo, Norway..
    Hanson, Mark A.
    Univ Hosp Southampton, Inst Dev Sci, Southampton, Hants, England.;Univ Southampton, NIHR Southampton Biomed Res Ctr, Southampton, Hants, England..
    O'Reilly, Sharleen L.
    Univ Coll Dublin, Natl Matern Hosp, UCD Perinatal Res Ctr, Sch Med, Dublin, Ireland.;Univ Coll Dublin, Sch Agr & Food Sci, Dublin, Ireland..
    McAuliffe, Fionnuala M.
    Univ Coll Dublin, Natl Matern Hosp, UCD Perinatal Res Ctr, Sch Med, Dublin, Ireland..
    Pregnancy as an opportunity to prevent type 2 diabetes mellitus: FIGO Best Practice Advice2023In: International Journal of Gynecology & Obstetrics, ISSN 0020-7292, E-ISSN 1879-3479, Vol. 160, no S1, p. 56-67Article in journal (Refereed)
    Abstract [en]

    Gestational diabetes (GDM) impacts approximately 17 million pregnancies worldwide. Women with a history of GDM have an 8-10-fold higher risk of developing type 2 diabetes and a 2-fold higher risk of developing cardiovascular disease (CVD) compared with women without prior GDM. Although it is possible to prevent and/or delay progression of GDM to type 2 diabetes, this is not widely undertaken. Considering the increasing global rates of type 2 diabetes and CVD in women, it is essential to utilize pregnancy as an opportunity to identify women at risk and initiate preventive intervention. This article reviews existing clinical guidelines for postpartum identification and management of women with previous GDM and identifies key recommendations for the prevention and/or delayed progression to type 2 diabetes for global clinical practice.

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  • 18.
    Adamo, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Gunnarsson, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Eeg-Olofsson, Katarina
    Strigård, Karin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Brännström, Fredrik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Department of Surgery, Södertälje Hospital, Södertälje, Sweden.
    Risk for developing perianal abscess in type 1 and type 2 diabetes and the impact of poor glycemic control2021In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 36, no 5, p. 999-1005Article in journal (Refereed)
    Abstract [en]

    Purpose: The primary aim of this study was to see whether perianal abscess rate differs between patients with type 1 and type 2 diabetes. A secondary aim was to determine whether poor glycemic control increases the risk for perianal abscess.

    Methods: Data from the Swedish National Diabetes Registry and the Swedish National Patient Registry between January 2008 and June 2015 were matched. The risk for anal abscess was evaluated in univariate and multivariate analyses with type of diabetes, HbA1c level, BMI, and various diabetes complications as independent factors.

    Results: Patients with type 1 diabetes had a lower rate of perianal abscess than patients with type 2 diabetes when adjusted for HbA1c, sex, and age (OR 0.65; 95% CI 0.57–0.73). The risk for perianal abscess increased with higher HbA1c. Incidence of perianal abscess was also elevated in diabetes patients with complications related to poor glycemic control such as ketoacidosis and coma (OR 2.63; 95% CI 2.06–3.35), gastroparesis, and polyneuropathy (OR 1.81; 95% CI 1.41–2.32).

    Conclusions: The prevalence of perianal abscess was higher among patients with type 2 diabetes than those with type 1, suggesting that metabolic derangement may be more important than autoimmune factors. Poor glycemic control was associated with higher risk for perianal abscess.

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  • 19.
    Adler, Dana
    et al.
    Bar Ilan University, Israel.
    Shapira, Zehavit
    Bar Ilan University, Israel.
    Weiss, Shimon
    Bar Ilan University, Israel ; University of California, Los Angeles, USA..
    Shainberg, Asher
    Bar Ilan University, Israel.
    Katz, Abram
    Swedish School of Sport and Health Sciences, GIH, Department of Physiology, Nutrition and Biomechanics.
    Weak Electromagnetic Fields Accelerate Fusion of Myoblasts.2021In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, no 9, article id 4407Article in journal (Refereed)
    Abstract [en]

    Weak electromagnetic fields (WEF) alter Ca2+ handling in skeletal muscle myotubes. Owing to the involvement of Ca2+ in muscle development, we investigated whether WEF affects fusion of myoblasts in culture. Rat primary myoblast cultures were exposed to WEF (1.75 µT, 16 Hz) for up to six days. Under control conditions, cell fusion and creatine kinase (CK) activity increased in parallel and peaked at 4-6 days. WEF enhanced the extent of fusion after one and two days (by ~40%) vs. control, but not thereafter. Exposure to WEF also enhanced CK activity after two days (almost four-fold), but not afterwards. Incorporation of 3H-thymidine into DNA was enhanced by one-day exposure to WEF (~40%), indicating increased cell replication. Using the potentiometric fluorescent dye di-8-ANEPPS, we found that exposure of cells to 150 mM KCl resulted in depolarization of the cell membrane. However, prior exposure of cells to WEF for one day followed by addition of KCl resulted in hyperpolarization of the cell membrane. Acute exposure of cells to WEF also resulted in hyperpolarization of the cell membrane. Twenty-four hour incubation of myoblasts with gambogic acid, an inhibitor of the inward rectifying K+ channel 2.1 (Kir2.1), did not affect cell fusion, WEF-mediated acceleration of fusion or hyperpolarization. These data demonstrate that WEF accelerates fusion of myoblasts, resulting in myotube formation. The WEF effect is associated with hyperpolarization but WEF does not appear to mediate its effects on fusion by activating Kir2.1 channels.

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  • 20.
    Adolfsson, Eva Thors
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Diabetes Nursing Research.
    Rosenblad, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Wikblad, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Diabetes Nursing Research.
    The Swedish National Survey of the Quality and Organization of Diabetes Care in Primary Healthcare—Swed-QOP2010In: Primary Care Diabetes, ISSN 1751-9918, E-ISSN 1878-0210, Vol. 4, no 2, p. 91-97Article in journal (Refereed)
    Abstract [en]

    AIM:

    To describe the quality and organization of diabetes care in primary healthcare in Sweden regarding resources and ways of working.

    METHOD:

    A questionnaire was used to collect data from all 921 primary healthcare centres (PHCCs) in Sweden. Of these, 74.3% (n=684) responded to the questionnaire covering list size of the PHCCs, number of diabetic patients, personnel resources and ways of working.

    RESULTS:

    The median list size reported from the PHCCs was 9,000 patients, 294 of whom were diabetic patients. The majority (72%) of PHCCs had diabetes-responsible general practitioners (GPs) and almost all (97%) had diabetes specialist nurses (DSNs) with some degree of postgraduate education in diabetes. The PHCCs reported that they used regional/local diabetes guidelines (93%), were engaged in call-recall diabetic reviews by GP(s) (66%) and DSN(s) (89%), checked that patients had participated in the reviews by GP(s) (69%) and DSN(s) (78%), arranged group education programmes (23%) and reported data to a National Diabetes Register (82%).

    CONCLUSIONS:

    The presence of diabetes-responsible GP(s) and DSN(s) who use guidelines may contribute to good and equal quality of care. It is, however, necessary to improve the call-recall system and there is an urgent need for all diabetic patients to receive patient education.

  • 21.
    Adolfsson, Peter
    et al.
    Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Pediatrics, The Hospital of Halland Kungsbacka, Kungsbacka, Sweden.
    Hanas, Ragnar
    Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Pediatrics, NU Hospital Group, Uddevalla, Sweden.
    Zaharieva, Dessi P.
    Division of Endocrinology, Department of Pediatrics, School of Medicine, Stanford University, Stanford, CA, USA.
    Dovc, Klemen
    Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia; Department of Pediatric Endocrinology, Diabetes and Metabolic Diseases, University Children's Hospital, Ljubljana, Slovenia.
    Jendle, Johan
    Örebro University, School of Medical Sciences.
    Automated Insulin Delivery Systems in Pediatric Type 1 Diabetes: A Narrative Review2024In: Journal of Diabetes Science and Technology, E-ISSN 1932-2968, article id 19322968241248404Article, review/survey (Refereed)
    Abstract [en]

    This narrative review assesses the use of automated insulin delivery (AID) systems in managing persons with type 1 diabetes (PWD) in the pediatric population. It outlines current research, the differences between various AID systems currently on the market and the challenges faced, and discusses potential opportunities for further advancements within this field. Furthermore, the narrative review includes various expert opinions on how different AID systems can be used in the event of challenges with rapidly changing insulin requirements. These include examples, such as during illness with increased or decreased insulin requirements and during physical activity of different intensities or durations. Case descriptions give examples of scenarios with added user-initiated actions depending on the type of AID system used. The authors also discuss how another AID system could have been used in these situations.

  • 22.
    Adolfsson, Peter
    et al.
    Department of Pediatrics, The Hospital of Halland, Kungsbacka, Sweden.; Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden..
    Hartvig, Niels Væver
    Data Science, Novo Nordisk A/S, Søborg, Denmark.
    Kaas, Anne
    Medical & Science, and Novo Nordisk A/S, Søborg, Denmark..
    Møller, Jonas Bech
    Digital Health, Novo Nordisk A/S, Søborg, Denmark.
    Hellman, Jarl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Increased Time in Range and Fewer Missed Bolus Injections After Introduction of a Smart Connected Insulin Pen2020In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 22, no 10, p. 709-718Article in journal (Refereed)
    Abstract [en]

    Background: This observational study investigated whether the connected NovoPen® 6 could influence insulin regimen management and glycemic control in people with type 1 diabetes (T1D) using a basal-bolus insulin regimen and continuous glucose monitoring in a real-world setting. Methods: Participants from 12 Swedish diabetes clinics downloaded pen data at each visit (final cohort: n = 94). Outcomes included time in range (TIR; sensor glucose 3.9-10.0 mmol/L), time in hyperglycemia (>10 mmol/L), and hypoglycemia (L1: 3.0- <3.9 mmol/L; L2: <3.0 mmol/L). Missed bolus dose (MBD) injections were meals without bolus injection within -15 and +60 min from the start of a meal. Outcomes were compared between the baseline and follow-up periods (≥5 health care professional visits). Data were analyzed from the first 14 days following each visit. For the TIR and total insulin dose analyses (n = 94), a linear mixed model was used, and for the MBD analysis (n = 81), a mixed Poisson model was used. Results: TIR significantly increased (+1.9 [0.8; 3.0]95% CI h/day; P < 0.001) from baseline to follow-up period, with a corresponding reduction in time in hyperglycemia (-1.8 [-3.0; -0.6]95% CI h/day; P = 0.003) and L2 hypoglycemia (-0.3 [-0.6; -0.1]95% CI h/day; P = 0.005), and no change in time in L1 hypoglycemia. MBD injections decreased by 43% over the study (P = 0.002). Change in MBD injections corresponded to a decrease from 25% to 14% based on the assumption that participants had three main meals per day. Conclusions: Our study highlights the potential benefit on glycemic control and dosing behavior when reliable insulin dose data from a connected pen contribute to insulin management in people with T1D.

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  • 23.
    Adolfsson, Peter
    et al.
    Göteborg Pediatric Growth Research Center, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden; The Queen Silvia Children's Hospital, Göteborg, Sweden.
    Ornhagen, Hans
    Swedish Sports Diving Federation, Idrottshuset, Farsta, Sweden.
    Eriksson, Bengt M.
    Hyperbaric Medicine, Department of Anesthesiology, Karolinska Universitetssjukhuset, Stockholm, Sweden.
    Gautham, Raghavendhar
    Medtronic Diabetes, Northridge CA, USA.
    Jendle, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden; Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden.
    In-vitro performance of the Enlite sensor in various glucose concentrations during hypobaric and hyperbaric conditions2012In: Journal of Diabetes Science and Technology, E-ISSN 1932-2968, Vol. 6, no 6, p. 1375-1382Article in journal (Refereed)
    Abstract [en]

    Background: There is a need for reliable methods of glucose measurement in different environmental conditions. The objective of this in vitro study was to evaluate the performance of the Enlite® Sensor when connected to either the iPro™ Continuous Glucose Monitor recording device or the Guardian® REAL-Time transmitting device, in hypobaric and hyperbaric conditions.

    Methods: Sixteen sensors connected to eight iPro devices and eight Guardian REAL-Time devices were immersed in three beakers containing separate glucose concentrations: 52, 88, and 207 mg/dl (2.9, 4.9, and 11.3 mmol/liter). Two different pressure tests were conducted: a hypobaric test, corresponding to maximum 18000 ft/5500 m height, and a hyperbaric test, corresponding to maximum 100 ft/30 m depth. The linearity of the sensor signals in the different conditions was evaluated.

    Results: The sensors worked continuously, and the sensor signals were collected without interruption at all pressures tested. When comparing the input signals for glucose (ISIGs) and the different glucose concentrations during altered pressure, linearity (R(2)) of 0.98 was found. During the hypobaric test, significant differences (p < .005) were seen when comparing the ISIGs during varying pressure at two of the glucose concentrations (52 and 207 mg/dl), whereas no difference was seen at the 88 mg/dl glucose concentration. During the hyperbaric test, no differences were found.

    Conclusions: The Enlite Sensors connected to either the iPro or the Guardian REAL-Time device provided values continuously. In hyperbaric conditions, no significant differences were seen during changes in ambient pressure; however, during hypobaric conditions, the ISIG was significantly different in the low and high glucose concentrations.

  • 24.
    Adolfsson, Peter
    et al.
    Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sweden .
    Strömgren, Agneta
    The Hospital of Halland, Sweden .
    Mattsson, Stig
    Faculty of Health Sciences and Medicine, Örebro University Hospital, Sweden .
    Chaplin, John E.
    Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sweden.
    Jendle, Johan
    Faculty of Health Sciences and Medicine, Örebro University Hospital, Orebro, Sweden.
    Education and individualized support regarding exercise and diabetes improves glucose control and level of physical activity in type 1 diabetes individuals2015In: Journal of Endocrinology Diabetes & Obesity, E-ISSN 2333-6692, Vol. 3, no 2, p. 1071-1077Article in journal (Refereed)
    Abstract [en]

    Background: Physical activity is advocated in all individuals with diabetes. However, good glycemic control can be difficult to achieve due to exercise induced glucose excursions.

    Objective: To evaluate the impact on glucose control of a structured diabetes education concerning physical activity, delivered via the web/internet together with telemedical care (individualized feedback by phone).

    Methods: Eighty-two individuals with type 1 (T1D) were included in the pre-race intervention and randomized into two groups: intervention (I) (n=48) and control (C) (n=48). Both groups received web-based training of sports and nutrition in relation to diabetes. The intervention group also received structured and individualized feedback on two different occasions. HbA1c was measured at baseline, after 3 and 6 months when a 45 km cross-country skiing race (the HalvVasa) was performed. Only the individuals attending the skiing race were eligible to be included in the study. Level of Physical Activity (LPA), Multidimensional Health Locus of Control (MHLC) and Confidence In Diabetes Self-care (CIDS) were assessed at baseline and after 7 months.

    Results: HbA1c at start was 58.5 ± 10.0 (I) respectively 60.7 ± 9.5 (C) mmol/mol. At 3 months 56.7 ± 8.7 (I) respectively 61.0 ± 9.6 (C) mmol/mol and at 6 months 55.7 ± 8.1 (I) respectively 60.3 ± 9.7 (C) mmol/mol. A significant in (I) at 3 months: 2.2 ± 3.8 mmol/mol (0.7-3.7, 95% CI), (p<0.05) and after 6 months: 2.8 ± 5.5 mmol/mol (0.5-5.0, 95% CI), (p<0.05). No reduction was seen in (C). However between the two groups no difference was noted. The LPA was increased in 52% of the participants in (I) respectively 7% in (C), a significant difference, p<0.05. No differences were seen regarding HbA1c or LPA in the control group.

    Conclusion: Education and individualized feedback, delivered via telemedicine, to physical active individuals with T1D resulted in improvements in glycemic control within the intervention group and improved level of physical activity and locus of control when compared to the control group(12) (PDF) Education and individualized support regarding exercise and diabetes improves glucose control and level of physical activity in type 1 diabetes individuals.

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    Education and individualized support regarding exercise and diabetes improves glucose control and level of physical activity in type 1 diabetes individuals
  • 25.
    Adolfsson, Peter
    et al.
    Gothenburg Pediatric Growth Research Center, Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy,University of Gothenburg, Gothenburg, Sweden.
    Örnhagen, Hans
    Swedish Sports Diving Federation, Farsta, Sweden.
    Eriksson, Bengt M.
    Hyperbaric Medicine, Department of Anesthesiology, Karolinska University Hospital, Solna, Sweden.
    Cooper, Ken
    Medtronic Diabetes (Sensor R&D), Northridge CA, USA.
    Jendle, Johan
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital, Örebro, Sweden; Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden.
    Continuous glucose monitoring: a study of the Enlite sensor during hypo- and hyperbaric conditions2012In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 14, no 6, p. 527-532Article in journal (Refereed)
    Abstract [en]

    Background: The performance and accuracy of the Enlite(™) (Medtronic, Inc., Northridge, CA) sensor may be affected by microbubble formation at the electrode surface during hypo- and hyperbaric conditions. The effects of acute pressure changes and of prewetting of sensors were investigated.

    Materials and Methods: On Day 1, 24 sensors were inserted on the right side of the abdomen and back in one healthy individual; 12 were prewetted with saline solution, and 12 were inserted dry. On Day 2, this procedure was repeated on the left side. All sensors were attached to an iPro continuous glucose monitoring (CGM) recorder. Hypobaric and hyperbaric tests were conducted in a pressure chamber, with each test lasting 105 min. Plasma glucose values were obtained at 5-min intervals with a HemoCue(®) (Ängelholm, Sweden) model 201 glucose analyzer for comparison with sensor glucose values.

    Results: Ninety percent of the CGM systems operated during the tests. The mean absolute relative difference was lower during hyperbaric than hypobaric conditions (6.7% vs. 14.9%, P<0.001). Sensor sensitivity was slightly decreased (P<0.05) during hypobaric but not during hyperbaric conditions. Clarke Error Grid Analysis showed that 100% of the values were found in the A+B region. No differences were found between prewetted and dry sensors.

    Conclusions: The Enlite sensor performed adequately during acute pressure changes and was more accurate during hyperbaric than hypobaric conditions. Prewetting the sensors did not improve accuracy. Further studies on type 1 diabetes subjects are needed under various pressure conditions.

  • 26.
    Adolfsson, Peter
    et al.
    Gothenburg Pediatric Growth Research Center, Department of Pediatrics, Institute for the Health of Women and Children, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Örnhagen, Hans
    Swedish Sports Diving Federation, Farsta, Sweden.
    Jendle, Johan
    Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden; Faculty of Health Sciences, Örebro University Hospital, Örebro, Sweden.
    Accuracy and reliability of continuous glucose monitoring in individuals with type 1 diabetes during recreational diving2009In: Diabetes Technology & Therapeutics, ISSN 1520-9156, E-ISSN 1557-8593, Vol. 11, no 8, p. 493-497Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: This study evaluated the accuracy and function of the Continuous Glucose Monitoring System (CGMS, Minneapolis, MN) during recreational scuba diving in individuals with type 1 diabetes.

    METHODS: Twenty-four adults, 12 with type 1 diabetes and 12 healthy controls, were studied during five recreational scuba dives performed on three consecutive days. All the participants used the CGMS on all the days and during all the dives. Comparisons were made between plasma glucose at specific time intervals and the CGMS.

    RESULTS: The recording by the CGMS was robust, with few sensor problems. The mean sensor survival time was >48 h. Eighty-five percent of the individuals used one sensor during the entire length of the trial. The overall mean absolute difference (MAD) within the group with diabetes was 14.4 +/- 6%, and the corresponding daily figures were 23.2 +/- 19.3% on day 1, 11.6 +/- 4.5% on day 2, and 11.2 +/- 5.7% on day 3. A significant improvement regarding MAD when day 1 was compared with day 2 and 3 (P < 0.05). With a limit set at 70 mg/dL, hypoglycemia pre- and post-dive was detected with a positive predictive value of 0.39, negative predictive value of 0.98, sensitivity of 0.64, and specificity of 0.94.

    CONCLUSIONS: We demonstrate that the CGMS was used with accuracy in such difficult conditions as scuba diving and provided robust information on glucose variations.

  • 27.
    Adolfsson, Peter
    et al.
    Gothenburg Pediatric Growth Research Centre, Department of Pediatrics, Institute for the Health of Women and Children, the Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden.
    Örnhagen, Hans
    Swedish Sportsdiving Federation, Farsta, Sweden.
    Jendle, Johan
    Endocrine and Diabetes Center, Karlstad Hospital, Karlstad, Sweden; Department of Clinical Medicine, Örebro University Hospital, Örebro, Sweden.
    The benefits of continuous glucose monitoring and a glucose monitoring schedule in individuals with type 1 diabetes during recreational diving2008In: Journal of Diabetes Science and Technology, E-ISSN 1932-2968, Vol. 2, no 5, p. 778-784Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Our objective is to evaluate the Medtronic CGMS continuous glucose monitoring system and plasma glucose (PG) measurement performed in a monitoring schedule as tools to identify individuals with type 1 diabetes at risk when diving.

    METHODS: We studied 24 adults, 12 type 1 diabetes subjects and 12 controls, during 5 recreational scuba dives performed on 3 consecutive days. The CGMS was used by all participants on all the days and all the dives. Comparisons were made between PG performed in a monitoring schedule during the days of diving, self-monitored blood glucose (SMBG) performed 2 weeks prior to diving, and the CGMS during the study.

    RESULTS: One hundred seventeen dives were performed. Hypoglycemia (<70 mg/dl) was found in six individuals and on nine occasions. However, no symptoms of hypoglycemia were present during or immediately postdiving. In one case, repetitive hypoglycemia prediving gave rise to a decision not to dive. None of the dives were aborted. The number of hypoglycemic episodes, 10 min prediving or immediately postdiving, were related to the duration of diabetes, r = 0.83 and p =0.01, and the percentage of SMBG values below target (<72 mg/dl), r = 0.65 and p =0.02. Moreover, the number of hypoglycemic episodes was also related to the total duration below low limit (<70 mg/dl), measured by the CGMS, r =0.74 and p =0.006.

    CONCLUSION: Safe dives are possible to achieve by well-informed, well-controlled individuals with type 1 diabetes. Using downloaded SMBG, CGMS, and repetitive PG in a monitoring schedule, it is possible to identify those subjects who are suitable for diving.

  • 28.
    af Geijerstam, Peder
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum.
    Engvall, Jan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Heart Center, Department of Clinical Physiology in Linköping.
    Östgren, Carl Johan
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Region Östergötland, Primary Care Center, Primary Health Care Center Ekholmen.
    Nyström, Fredrik
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum.
    Rådholm, Karin
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Kärna. The George Institute for Global Health, University of New South Wales, Sydney, Australia.
    Home Blood Pressure Compared With Office Blood Pressure in Relation to Dysglycemia2022In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 35, no 9, p. 810-819Article in journal (Refereed)
    Abstract [en]

    Background: Masked hypertension is more common in individuals with type 2 diabetes than in individuals with normoglycemia. We aimed to explore if there is a discrepancy between office blood pressure (office BP) and home blood pressure monitoring (HBPM) in relation to HbA1c as well as glycemic status in 5,029 middle-aged individuals.

    Methods: HBPM was measured in a subsample of 5,029 participants in The Swedish CardioPulmonary BioImage Study (SCAPIS), a population-based cohort of 50–64 years old participants. Both office BP and HBPM were obtained after 5 minutes’ rest using the semiautomatic Omron M10-IT oscillometric device. White coat effect was calculated by subtracting systolic HBPM from systolic office BP. Participants were classified according to glycemic status: Normoglycemia, prediabetes, or diabetes based on fasting glucose, HbA1c value, and self-reported diabetes diagnosis.

    Results: Of the included 5,025 participants, 947 (18.8%) had sustained hypertension, 907 (18.0%) reported taking antihypertensive treatment, and 370 (7.4%) had diabetes mellitus. Both systolic office BP and HBPM increased according to worsened glycemic status (P for trend 0.002 and 0.002, respectively). Masked hypertension was more prevalent in participants with dysglycemia compared with normoglycemia (P = 0.036). The systolic white coat effect was reversely associated with HbA1c (P = 0.012).

    Conclusions: The systolic white coat effect was reversely associated with HbA1c, and the prevalence of masked hypertension increased with dysglycemia.

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  • 29.
    af Geijerstam, Peder
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum.
    Janryd, Fredrik
    Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum.
    Nyström, Fredrik
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine.
    Smoking and cardiovascular disease in patients with type 2 diabetes: a prospective observational study2023In: Journal of Cardiovascular Disease, ISSN 2330-4596, E-ISSN 2330-460X, Vol. 24, no 11, p. 802-807Article in journal (Refereed)
    Abstract [en]

    Background

    Cigarette smoking is a major risk factor for cardiovascular disease. In type 2 diabetes mellitus (T2D), medications such as antihypertensives and statins can reduce the increased cardiovascular risk. The aim of this study was to evaluate the impact of cigarette smoking on major adverse cardiovascular event (MACE) and all-cause mortality in patients with T2D in a relatively well treated Swedish cohort.

    Methods

    Seven hundred and sixty-one patients with T2D aged 55–66 years were followed in the prospective observational CArdiovascular Risk factors in patients with DIabetes – a Prospective study in Primary care (CARDIPP) study. Baseline data included blood samples of markers of dysglycemia and inflammation, blood pressure as well as questionnaire responses regarding cigarette smoking. Participants were followed for incidence of MACE and all-cause mortality.

    Results

    Of the included 663 participants, the mean age was 60.6 (SD 3.1) years and 423 (63.8%) were men. Levels of C-reactive protein and vitamin D, as well as the proportion of participants treated with antihypertensives, acetylic salicylic acid, statins, and diabetes medications, were similar between smokers and nonsmokers. Median follow-up time was 11.9 (Q1–Q3 10.8–12.7) years. Cigarette smoking was associated with all-cause mortality [hazard ratio 2.24 (95% confidence interval, 95% CI 1.40–3.56), P < 0.001], but not MACE [hazard ratio 1.30 (95% CI 0.77–2.18), P = 0.328].

    Conclusion

    In patients with T2D, cigarette smoking was not associated with an increased risk of MACE. This raises the question of whether cardioprotective drugs in individuals with T2D to some degree mitigate the cardiovascular harm of smoking, even though they do not affect other dire consequences of smoking.

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  • 30.
    af Geijerstam, Peder
    et al.
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum.
    Joelsson, Annelie
    Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum.
    Rådholm, Karin
    Linköping University, Department of Health, Medicine and Caring Sciences, Division of Prevention, Rehabilitation and Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Kärna. The George Institute for Global Health, University of New South Wales, Sydney, Australia.
    Nyström, Fredrik H
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Cityhälsan Centrum. Linköping University, Department of Health, Medicine and Caring Sciences, Division of Diagnostics and Specialist Medicine.
    A low dose of daily licorice intake affects renin, aldosterone, and home blood pressure in a randomized crossover trial2024In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 119, no 3, p. 682-691Article in journal (Refereed)
    Abstract [en]

    Background

    Licorice, through the effects of glycyrrhizic acid (GA), raises blood pressure (BP). The World Health Organization has suggested that 100 mg GA/d would be unlikely to cause adverse effects, but of 13 previously published studies none have been randomized and controlled and independently quantified the GA content.

    Objective

    Our aim was to analyze the effects on home BP of a daily licorice intake containing 100 mg GA.

    Methods

    Healthy volunteers were randomly assigned to start with either licorice or a control product in a nonblinded, 2 × 2 crossover study. Home BP was measured daily, and blood samples were collected at the end of each 2-wk period.

    Results

    There were 28 participants and no dropouts. The median age was 24.0 y (interquartile range 22.8–27.0 y). During the licorice compared with control intake period, the systolic home BP increased [mean difference: 3.1 mm Hg (95% confidence interval [CI]: 0.8, 5.4 mm Hg) compared with −0.3 mm Hg (95% CI: −1.8, 1.3 mm Hg); P = 0.018] and renin and aldosterone were suppressed [mean change: −30.0% (95% CI: −56.7%, −3.3%) compared with 15.8% (95% CI: −12.8%, 44.4%); P = 0.003; and −45.1% (95% CI: −61.5%, −28.7%) compared with 8.2% (95% CI: −14.7%, 31.1%); P <0.001, respectively]. In the quartile of participants with the most pronounced suppression of renin and aldosterone, N-terminal prohormone of brain natriuretic peptide concentration increased during the licorice compared with control period [mean change: 204.1% (95% CI: −11.6%, 419.7%) compared with 72.4% (95% CI: −52.2%, 197.1%); P = 0.016].

    Conclusions

    We found licorice to be more potent than previously known, with significant increases in BP, after a daily intake of only 100 mg GA. Thus, the safe limit of intake of this substance might need to be reconsidered.

  • 31.
    Agardh, Carl-David
    et al.
    Lund University, Lund, Sweden.
    Ahrén, Bo
    Lund University, Lund, Sweden.
    Hanås, Ragnar
    Jansson, Stefan
    Örebro University Hospital. Örebro University, School of Medical Sciences. Uppsala University, Uppsala, Sweden.
    Smith, Ulf
    Gothenburg University, Gothenburg, Sweden.
    Toft, Eva
    Karolinska Institutet, Stockholm, Sweden.
    Östenson, Claes-Göran
    Karolinska Institutet, Stockholm, Sweden.
    Varning för okritisk användning av överviktskirurgi vid typ 2-diabetes2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 25, p. 1208-1209Article in journal (Refereed)
    Abstract [sv]

    Överviktskirurgi diskuteras nu som ett behandlingsalternativ även för patienter med typ 2-diabetes där BMI inte överstiger nuvarande indikationsgräns 35 kg/m2. Artikelförfattarna vill varna för en sådan utveckling i avvaktan på kritisk värdering av denna typ av kirurgi.

  • 32.
    Agebratt, Christian
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Ström, Edvin
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Romu, Thobias
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Dahlqvist Leinhard, Olof
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics.
    Borga, Magnus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Leandersson, Per
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Occupational and Environmental Medicine Center.
    Nyström, Fredrik H.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    A Randomized Study of the Effects of Additional Fruit and Nuts Consumption on Hepatic Fat Content, Cardiovascular Risk Factors and Basal Metabolic Rate2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 1, p. e0147149-Article in journal (Refereed)
    Abstract [en]

    Background

    Fruit has since long been advocated as a healthy source of many nutrients, however, the high content of sugars in fruit might be a concern.

    Objectives

    To study effects of an increased fruit intake compared with similar amount of extra calories from nuts in humans.

    Methods

    Thirty healthy non-obese participants were randomized to either supplement the diet with fruits or nuts, each at +7 kcal/kg bodyweight/day for two months. Major endpoints were change of hepatic fat content (HFC, by magnetic resonance imaging, MRI), basal metabolic rate (BMR, with indirect calorimetry) and cardiovascular risk markers.

    Results

    Weight gain was numerically similar in both groups although only statistically significant in the group randomized to nuts (fruit: from 22.15±1.61 kg/m2 to 22.30±1.7 kg/m2, p = 0.24 nuts: from 22.54±2.26 kg/m2 to 22.73±2.28 kg/m2, p = 0.045). On the other hand BMR increased in the nut group only (p = 0.028). Only the nut group reported a net increase of calories (from 2519±721 kcal/day to 2763±595 kcal/day, p = 0.035) according to 3-day food registrations. Despite an almost three-fold reported increased fructose-intake in the fruit group (from 9.1±6.0 gram/day to 25.6±9.6 gram/day, p<0.0001, nuts: from 12.4±5.7 gram/day to 6.5±5.3 gram/day, p = 0.007) there was no change of HFC. The numerical increase in fasting insulin was statistical significant only in the fruit group (from 7.73±3.1 pmol/l to 8.81±2.9 pmol/l, p = 0.018, nuts: from 7.29±2.9 pmol/l to 8.62±3.0 pmol/l, p = 0.14). Levels of vitamin C increased in both groups while α-tocopherol/cholesterol-ratio increased only in the fruit group.

    Conclusions

    Although BMR increased in the nut-group only this was not linked with differences in weight gain between groups which potentially could be explained by the lack of reported net caloric increase in the fruit group. In healthy non-obese individuals an increased fruit intake seems safe from cardiovascular risk perspective, including measurement of HFC by MRI.

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  • 33.
    Aguggia, Julieta P.
    et al.
    Natl Univ La Plata, Argentine Res Council CONICET, Multidisciplinary Inst Cell Biol IMBICE, Lab Neurophysiol, La Plata, Buenos Aires, Argentina.;Natl Univ La Plata, Sci Res Commiss, Prov Buenos Aires CIC PBA, La Plata, Buenos Aires, Argentina..
    Cornejo, Maria P.
    Natl Univ La Plata, Argentine Res Council CONICET, Multidisciplinary Inst Cell Biol IMBICE, Lab Neurophysiol, La Plata, Buenos Aires, Argentina.;Natl Univ La Plata, Sci Res Commiss, Prov Buenos Aires CIC PBA, La Plata, Buenos Aires, Argentina..
    Fernandez, Gimena
    Natl Univ La Plata, Argentine Res Council CONICET, Multidisciplinary Inst Cell Biol IMBICE, Lab Neurophysiol, La Plata, Buenos Aires, Argentina.;Natl Univ La Plata, Sci Res Commiss, Prov Buenos Aires CIC PBA, La Plata, Buenos Aires, Argentina..
    De Francesco, Pablo N.
    Natl Univ La Plata, Argentine Res Council CONICET, Multidisciplinary Inst Cell Biol IMBICE, Lab Neurophysiol, La Plata, Buenos Aires, Argentina.;Natl Univ La Plata, Sci Res Commiss, Prov Buenos Aires CIC PBA, La Plata, Buenos Aires, Argentina..
    Mani, Bharath K.
    UT Southwestern Med Ctr, Ctr Hypothalam Res, Dept Internal Med, Dallas, TX USA..
    Cassano, Daniela
    Natl Univ La Plata, Argentine Res Council CONICET, Multidisciplinary Inst Cell Biol IMBICE, Lab Neurophysiol, La Plata, Buenos Aires, Argentina.;Natl Univ La Plata, Sci Res Commiss, Prov Buenos Aires CIC PBA, La Plata, Buenos Aires, Argentina..
    Cabral, Agustina
    Natl Univ La Plata, Argentine Res Council CONICET, Multidisciplinary Inst Cell Biol IMBICE, Lab Neurophysiol, La Plata, Buenos Aires, Argentina.;Natl Univ La Plata, Sci Res Commiss, Prov Buenos Aires CIC PBA, La Plata, Buenos Aires, Argentina..
    Valdivia, Spring
    Natl Univ La Plata, Argentine Res Council CONICET, Multidisciplinary Inst Cell Biol IMBICE, Lab Neurophysiol, La Plata, Buenos Aires, Argentina.;Natl Univ La Plata, Sci Res Commiss, Prov Buenos Aires CIC PBA, La Plata, Buenos Aires, Argentina..
    Garcia Romero, Guadalupe
    Natl Univ La Plata, Argentine Res Council CONICET, Multidisciplinary Inst Cell Biol IMBICE, Lab Neurophysiol, La Plata, Buenos Aires, Argentina.;Natl Univ La Plata, Sci Res Commiss, Prov Buenos Aires CIC PBA, La Plata, Buenos Aires, Argentina..
    Reynaldo, Mirta
    Natl Univ La Plata, Argentine Res Council CONICET, Multidisciplinary Inst Cell Biol IMBICE, Lab Neurophysiol, La Plata, Buenos Aires, Argentina.;Natl Univ La Plata, Sci Res Commiss, Prov Buenos Aires CIC PBA, La Plata, Buenos Aires, Argentina..
    Fehrentz, Jean-Alain
    Univ Montpellier, Fac Pharm, Inst Biomol Max Mousseron, UMR 5247 CNRS,ENSCM, Montpellier, France..
    Zigman, Jeffrey M.
    UT Southwestern Med Ctr, Ctr Hypothalam Res, Dept Internal Med, Dallas, TX USA..
    Perello, Mario
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Functional Pharmacology and neuroscience. Natl Univ La Plata, Argentine Res Council CONICET, Multidisciplinary Inst Cell Biol IMBICE, Lab Neurophysiol, La Plata, Buenos Aires, Argentina.;Natl Univ La Plata, Sci Res Commiss, Prov Buenos Aires CIC PBA, La Plata, Buenos Aires, Argentina..
    Growth hormone secretagogue receptor signaling in the supramammillary nucleus targets nitric oxide-producing neurons and controls recognition memory in mice2022In: Psychoneuroendocrinology, ISSN 0306-4530, E-ISSN 1873-3360, Vol. 139, article id 105716Article in journal (Refereed)
    Abstract [en]

    Ghrelin is a stomach-derived hormone that acts via the growth hormone secretagogue receptor (GHSR). Recent evidence suggests that some of ghrelin's actions may be mediated via the supramammillary nucleus (SuM). Not only does ghrelin bind to cells within the mouse SuM, but ghrelin also activates SuM cells and intra-SuM ghrelin administration induces feeding in rats. In the current study, we aimed to further characterize ghrelin action in the SuM. We first investigated a mouse model expressing enhanced green fluorescent protein (eGFP) under the promoter of GHSR (GHSR-eGFP mice). We found that the SuM of GHSR-eGFP mice contains a significant amount of eGFP cells, some of which express neuronal nitric oxide synthase. Centrally-, but not systemically-, injected ghrelin reached the SuM, where it induced c-Fos expression. Furthermore, a 5-day 40% calorie restriction protocol, but not a 2-day fast, increased c-Fos expression in non-eGFP+ cells of the SuM of GHSR-eGFP mice, whereas c-Fos induction by calorie restriction was not observed in GHSR-deficient mice. Exposure of satiated mice to a binge-like eating protocol also increased c-Fos expression in non-eGFP+ cells of the SuM of GHSR-eGFP mice in a GHSR-dependent manner. Finally, intra-SuM-injected ghrelin did not acutely affect food intake, locomotor activity, behavioral arousal or spatial memory but increased recognition memory. Thus, we provide a compelling neuroanatomical characterization of GHSR SuM neurons and its behavioral implications in mice.

  • 34.
    Ahlgren, Kerstin M
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Fall, Tove
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Landegren, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Grimelius, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    von Euler, Henrik
    Sundberg, Katarina
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lobell, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hedhammar, Åke
    Andersson, Göran
    Hansson-Hamlin, Helene
    Lernmark, Åke
    Kämpe, Olle
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Autoimmunity. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lack of evidence for a role of islet autoimmunity in the aetiology of canine diabetes mellitus2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 8, p. e105473-Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS:

    Diabetes mellitus is one of the most common endocrine disorders in dogs and is commonly proposed to be of autoimmune origin. Although the clinical presentation of human type 1 diabetes (T1D) and canine diabetes are similar, the aetiologies may differ. The aim of this study was to investigate if autoimmune aetiology resembling human T1D is as prevalent in dogs as previously reported.

    METHODS:

    Sera from 121 diabetic dogs representing 40 different breeds were tested for islet cell antibodies (ICA) and GAD65 autoantibodies (GADA) and compared with sera from 133 healthy dogs. ICA was detected by indirect immunofluorescence using both canine and human frozen sections. GADA was detected by in vitro transcription and translation (ITT) of human and canine GAD65, followed by immune precipitation. Sections of pancreata from five diabetic dogs and two control dogs were examined histopathologically including immunostaining for insulin, glucagon, somatostatin and pancreas polypeptide.

    RESULTS:

    None of the canine sera analysed tested positive for ICA on sections of frozen canine or human ICA pancreas. However, serum from one diabetic dog was weakly positive in the canine GADA assay and serum from one healthy dog was weakly positive in the human GADA assay. Histopathology showed marked degenerative changes in endocrine islets, including vacuolisation and variable loss of immune-staining for insulin. No sign of inflammation was noted.

    CONCLUSIONS/INTERPRETATIONS:

    Contrary to previous observations, based on results from tests for humoral autoreactivity towards islet proteins using four different assays, and histopathological examinations, we do not find any support for an islet autoimmune aetiology in canine diabetes mellitus.

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  • 35.
    Ahlqvist, E.
    et al.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Karajamaki, A.
    Vaasa Cent Hosp, Primary Hlth Care, Vaasa, Finland..
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Storm, P.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Dorkhan, M.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Vikman, P.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Prasad, R. B.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Aly, D. Mansour
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Shaat, N.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Lindholm, E.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Tuomi, T.
    Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland..
    Rosengren, A. H.
    Lund Univ, Ctr Diabet, Malmo, Sweden..
    Groop, L.
    Lund Univ, Ctr Diabet, Malmo, Sweden.;Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland..
    Clustering of diabetes into novel subgroups provides improved prediction of outcome2017In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S117-S117Article in journal (Other academic)
  • 36.
    Ahlqvist, Emma
    et al.
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Storm, Petter
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Käräjämäki, Annemarie
    Department of Primary Health Care, Vaasa Central Hospital, Finland.
    Martinell, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Dorkhan, Mozhgan
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Carlsson, Annelie
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital, SE-22185 Lund, Sweden.
    Vikman, Petter
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Prasad, Rashmi
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Mansour Aly, Dina
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Almgren, Peter
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Wessman, Ylva
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Shaat, Nael
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Spegel, Peter
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Mulder, Hindrik
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Lindholm, Eero
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Melander, Olle
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Hansson, Ola
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Malmqvist, Ulf
    Clinical Research and Trial Center, Lund University Hospital, Sweden.
    Lernmark, Åke
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Lahti, Kaj
    Department of Primary Health Care, Vaasa Central Hospital, Finland.
    Forsén, Tom
    Department of Primary Health Care, Vaasa Central Hospital, Finland.
    Tuomi, Tiinamaija
    Abdominal Center, Endocrinology, Helsinki University Central Hospital; Research Program for Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
    Rosengren, Anders
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Groop, Leif
    Lund University Diabetes Centre, Department of Clinical Sciences, Lund University, Skåne University Hospital.
    Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables2018In: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 6, no 5, p. 361-369Article in journal (Refereed)
    Abstract [en]

     Background

    Diabetes is presently classified into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous. A refined classification could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis.

    Methods

    We did data-driven cluster analysis (k-means and hierarchical clustering) in patients with newly diagnosed diabetes (n=8980) from the Swedish All New Diabetics in Scania cohort. Clusters were based on six variables (glutamate decarboxylase antibodies, age at diagnosis, BMI, HbA1c, and homoeostatic model assessment 2 estimates of β-cell function and insulin resistance), and were related to prospective data from patient records on development of complications and prescription of medication. Replication was done in three independent cohorts: the Scania Diabetes Registry (n=1466), All New Diabetics in Uppsala (n=844), and Diabetes Registry Vaasa (n=3485). Cox regression and logistic regression were used to compare time to medication, time to reaching the treatment goal, and risk of diabetic complications and genetic associations.

    Findings

    We identified five replicable clusters of patients with diabetes, which had significantly different patient characteristics and risk of diabetic complications. In particular, individuals in cluster 3 (most resistant to insulin) had significantly higher risk of diabetic kidney disease than individuals in clusters 4 and 5, but had been prescribed similar diabetes treatment. Cluster 2 (insulin deficient) had the highest risk of retinopathy. In support of the clustering, genetic associations in the clusters differed from those seen in traditional type 2 diabetes.

    Interpretation

    We stratified patients into five subgroups with differing disease progression and risk of diabetic complications. This new substratification might eventually help to tailor and target early treatment to patients who would benefit most, thereby representing a first step towards precision medicine in diabetes.

  • 37.
    Ahlström, Stina
    et al.
    Natl Board Forens Med, Dept Forens Med, Uppsala, Sweden; Linköping Univ, Fac Med & Hlth Sci, Dept Biomed & Clin Sci, Div Drug Res, Linköping, Sweden.
    Thiblin, Ingemar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Forensic Medicine. Natl Board Forens Med, Dept Forens Med, Uppsala, Sweden.
    Jönsson, Anna K.
    Linköping Univ, Fac Med & Hlth Sci, Dept Biomed & Clin Sci, Div Drug Res, Linköping, Sweden; Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linköping, Sweden.
    Green, Henrik
    Linköping Univ, Fac Med & Hlth Sci, Dept Biomed & Clin Sci, Div Drug Res, Linköping, Sweden; Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linköping, Sweden.
    Characteristics of post-mortem beta-hydroxybutyrate-positivet cases: A retrospective study on age, sex and BMI in 1407 forensic autopsies2021In: Forensic Science International, ISSN 0379-0738, E-ISSN 1872-6283, Vol. 325, article id 110878Article in journal (Refereed)
    Abstract [en]

    Background

    Post-mortem biochemistry, including the analysis of beta-hydroxybutyrate (BHB), is increasingly employed in forensic medicine, especially in conditions such as diabetes and chronic alcoholism. However, not much is known about the associations between age, body mass index (BMI), and sex and BHB concentrations in ketoacidotic conditions.

    Aim

    To retrospectively study the association between age, BMI and sex in several conditions, such as diabetic ketoacidosis (DKA), alcoholic ketoacidosis (AKA), and elevated post-mortem BHB concentrations.

    Methods

    1407 forensic autopsy cases analysed for BHB were grouped by diagnosis: DKA, AKA, HHS [hyperosmolar hyperglycaemic state], acidosis NOS [not otherwise specified], or hypothermia. Age, sex, BMI and the concentrations of blood alcohol, vitreous glucose and blood BHB were recorded.

    Results

    Cases of AKA and DKA were most numerous (184 and 156, respectively). In DKA and in its male subgroup, cases with severe ketosis (BHB>1000 µg/g) were younger and had a lower BMI than those with moderate ketosis (BHB 250–1000 µg/g) and controls (P<0.001). In DKA and in its female subgroup, cases with moderate ketosis cases were older (P = 0.0218 and P = 0.0083) than controls. In AKA and in its male subgroup, cases with severe ketosis had a lower BMI than those with moderate ketosis (P = 0.0391 and P = 0.0469) and controls (P<0.001). Cases with moderate ketosis had a lower BMI than controls (P<0.001).

    Conclusions

    BHB concentration is associated with BMI in DKA and AKA, and with both BMI and age in DKA. Constitutional factors should, therefore, be considered in potential AKA and DKA cases.

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  • 38. Ahmad, S.
    et al.
    Heraclides, A.
    Sun, Q.
    Elgzyri, T.
    Rönn, T.
    Ling, C.
    Isomaa, B.
    Eriksson, K.-F.
    Groop, L.
    Franks, P. W.
    Hansson, O.
    Telomere length in blood and skeletal muscle in relation to measures of glycaemia and insulinaemia2012In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 29, no 10, p. e377-e381Article in journal (Refereed)
  • 39. Ahmad, S
    et al.
    Poveda, A
    Shungin, D
    Barroso, I
    Hallmans, G
    Renström, F
    Franks, P W
    Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits: the GLACIER Study2016In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 9, p. 1346-1352Article in journal (Refereed)
  • 40. Ahmad, S
    et al.
    Poveda, A
    Shungin, Dmitry
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Umeå University, Faculty of Medicine, Department of Odontology. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Lund University, Malmö, Sweden.
    Barroso, I
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Lund University, Malmö, Sweden.
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Center, Lund University, Malmö, Sweden; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
    Established BMI-associated genetic variants and their prospective associations with BMI and other cardiometabolic traits: the GLACIER Study2016In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 9, p. 1346-1352Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Recent cross-sectional genome-wide scans have reported associations of 97 independent loci with body mass index (BMI). In 3541 middle-aged adult participants from the GLACIER Study, we tested whether these loci are associated with 10-year changes in BMI and other cardiometabolic traits (fasting and 2-h glucose, triglycerides, total cholesterol, and systolic and diastolic blood pressures).

    METHODS: A BMI-specific genetic risk score (GRS) was calculated by summing the BMI-associated effect alleles at each locus. Trait-specific cardiometabolic GRSs comprised only the loci that show nominal association (P⩽0.10) with the respective trait in the original cross-sectional study. In longitudinal genetic association analyses, the second visit trait measure (assessed ~10 years after baseline) was used as the dependent variable and the models were adjusted for the baseline measure of the outcome trait, age, age(2), fasting time (for glucose and lipid traits), sex, follow-up time and population substructure.

    RESULTS: The BMI-specific GRS was associated with increased BMI at follow-up (β=0.014 kg m(-2) per allele per 10-year follow-up, s.e.=0.006, P=0.019) as were three loci (PARK2 rs13191362, P=0.005; C6orf106 rs205262, P=0.043; and C9orf93 rs4740619, P=0.01). Although not withstanding Bonferroni correction, a handful of single-nucleotide polymorphisms was nominally associated with changes in blood pressure, glucose and lipid levels.

    CONCLUSIONS: Collectively, established BMI-associated loci convey modest but statistically significant time-dependent associations with long-term changes in BMI, suggesting a role for effect modification by factors that change with time in this population.

  • 41. Ahmad, S
    et al.
    Zhao, W
    Renström, F
    Rasheed, A
    Zaidi, M
    Samuel, M
    Shah, N
    Mallick, N H
    Shungin, D
    Zaman, K S
    Ishaq, M
    Rasheed, S Z
    Memon, F-ur-R
    Hanif, B
    Lakhani, M S
    Ahmed, F
    Kazmi, S U
    Deloukas, P
    Frossard, P
    Franks, P W
    Saleheen, D
    A novel interaction between the FLJ33534 locus and smoking in obesity: a genome-wide study of 14 131 Pakistani adults2015In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 40, no 1, p. 186-190Article in journal (Refereed)
  • 42.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Harvard Med Sch, Div Prevent Med, Brigham & Womens Hosp, Boston, MA 02115 USA;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
    Ahluwalia, Tarunveer S.
    Steno Diabet Ctr Copenhagen, Gentofte, Denmark.
    Editorial: The Role of Genetic and Lifestyle Factors in Metabolic Diseases2019In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 10, article id 475Article in journal (Other academic)
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    FULLTEXT01
  • 43.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Harvard Med Sch, Prevent Med Div, Brigham & Womens Hosp, Boston, MA 02115 USA;Harvard TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
    Fatima, Syeda Sadia
    Aga Khan Univ, Dept Biol & Biomed Sci, Karachi, Pakistan.
    Rukh, Gull
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Smith, Caren E.
    Tufts Univ, Res Ctr Aging, Jean Mayer US Dept Agr, Nutr & Genom Lab, Boston, MA 02111 USA.
    Gene Lifestyle Interactions With Relation to Obesity, Cardiometabolic, and Cardiovascular Traits Among South Asians2019In: Frontiers in Endocrinology, E-ISSN 1664-2392, Vol. 10, article id 221Article, review/survey (Refereed)
    Abstract [en]

    The rapid rise of obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) during the last few decades among South Asians has been largely attributed to a major shift in lifestyles including physical inactivity, unhealthy dietary patterns, and an overall pattern of sedentary lifestyle. Genetic predisposition to these cardiometabolic risk factors may have interacted with these obesogenic environments in determining the higher cardiometabolic disease prevalence. Based on the premise that gene-environment interactions cause obesity and cardiometabolic diseases, we systematically searched the literature and considered the knowledge gaps that future studies might ful fill. We identified only seven published studies that focused specifically on gene-environment interactions for cardiometabolic traits in South Asians, most of which were limited by relatively small sample and lack of replication. Some studies reported that the differences in metabolic response to higher physical activity and low caloric diet might be modified by genetic risk related to these cardiometabolic traits. Although studies on gene lifestyle interactions in cardiometabolic traits report significant interactions, future studies must focus on more precise assessment of lifestyle factors, investigation of a larger set of genetic variants and the application of powerful statistical methods to facilitate translatable approaches. Future studies should also be integrated with findings both using mechanistic studies through laboratory settings and randomized clinical trials for clinical outcomes.

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  • 44. Ahmad, Shafqat
    et al.
    Hammar, Ulf
    Kennedy, Beatrice
    Salihovic, Samira
    Ganna, Andrea
    Lind, Lars
    Sundström, Johan
    Ärnlöv, Johan
    Dalarna University, School of Health and Welfare, Medical Science. Karolinska Institutet, Stockholm.
    Berne, Christian
    Fall, Tove
    Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome: a Multi-Cohort Non-Targeted Metabolomics Observational and Mendelian Randomization Study2022In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 71, no 2, p. 329-339Article in journal (Refereed)
    Abstract [en]

    Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity with circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data was generated by non-targeted ultra-performance liquid-chromatography coupled to time-of-flight mass-spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N=1,135), PIVUS (N=970), and TwinGene (N=2,059). We assessed associations between general adiposity measured as body mass index (BMI) and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We employed MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N=7,373), the CHARGE consortium (N=8,631), the Framingham Heart Study (N=2,076) and the DIRECT consortium (N=3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (p-value <0.05) of increased general adiposity and reduced levels of arachidonic acid, dodecanedioic acid and lysophosphatidylcholine (P-16:0) as well as with increased creatine levels. The replication effort provided support for a causal association of adiposity on reduced levels of arachidonic acid (p-value 0.03). Adiposity is associated with variation of large parts of the circulating metabolome, however causality needs further investigation in well-powered cohorts.

  • 45.
    Ahmad, Shafqat
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hammar, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kennedy, Beatrice
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Salihovic, Samira
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. School of Medical Sciences, Örebro University, Örebro, Sweden.
    Ganna, Andrea
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. The George Institute for Global Health, Sydney, Australia.
    Ärnlöv, Johan
    Division of and Primary Care, Department of Neurobiology, Care Sciences, and Society, Karolinska Institutet; School of Health and Social Studies, Dalarna University.
    Berne, Christian
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Magnusson, Patrik KE
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet.
    Larsson, Susanna C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Medical epidemiology. Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden..
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome: A Multi-Cohort Nontargeted Metabolomics Observational and Mendelian Randomization Study2022In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 71, no 2, p. 329-339Article in journal (Refereed)
    Abstract [en]

    Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity with circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data was generated by non-targeted ultra-performance liquid-chromatography coupled to time-of-flight mass-spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N=1,135), PIVUS (N=970), and TwinGene (N=2,059). We assessed associations between general adiposity measured as body mass index (BMI) and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We employed MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N=7,373), the CHARGE consortium (N=8,631), the Framingham Heart Study (N=2,076) and the DIRECT consortium (N=3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (p-value <0.05) of increased general adiposity and reduced levels of arachidonic acid, dodecanedioic acid and lysophosphatidylcholine (P-16:0) as well as with increased creatine levels. The replication effort provided support for a causal association of adiposity on reduced levels of arachidonic acid (p-value 0.03). Adiposity is associated with variation of large parts of the circulating metabolome, however causality needs further investigation in well-powered cohorts.

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    supplementary material
  • 46.
    Ahmad, Shafqat
    et al.
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, EpiHubben, MTC-huset, Uppsala, Sweden; Preventive Medicine Division, Harvard Medical School, Brigham and Women's Hospital, Boston, MA, United States.
    Hammar, Ulf
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, EpiHubben, MTC-huset, Uppsala, Sweden.
    Kennedy, Beatrice
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, EpiHubben, MTC-huset, Uppsala, Sweden.
    Salihovic, Samira
    Örebro University, School of Medical Sciences. Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, EpiHubben, MTC-huset, Uppsala, Sweden.
    Ganna, Andrea
    Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Lind, Lars
    Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala, Sweden.
    Sundström, Johan
    Department of Medical Sciences, Clinical Epidemiology, Uppsala University, Uppsala, Sweden; The George Institute for Global Health, Sydney, Australia.
    Ärnlöv, Johan
    Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet, Stockholm, Sweden; School of Health and Social Studies, Dalarna University, Falun, Sweden.
    Berne, Christian
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, EpiHubben, MTC-huset, Uppsala, Sweden.
    Risérus, Ulf
    Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
    Magnusson, Patrik Ke.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Larsson, Susanna C.
    Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Fall, Tove
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, EpiHubben, MTC-huset, Uppsala, Sweden.
    The Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome: a Multi-Cohort Non-Targeted Metabolomics Observational and Mendelian Randomization Study2022In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 71, no 2, p. 329-339Article in journal (Refereed)
    Abstract [en]

    Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity with circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data was generated by non-targeted ultra-performance liquid-chromatography coupled to time-of-flight mass-spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N=1,135), PIVUS (N=970), and TwinGene (N=2,059). We assessed associations between general adiposity measured as body mass index (BMI) and central body fat distribution measured as waist-to-hip ratio adjusted for BMI (WHRadjBMI) with 210 annotated metabolites. We employed MR analysis to assess causal effects. Lastly, we attempted to replicate the MR findings in the KORA and TwinsUK cohorts (N=7,373), the CHARGE consortium (N=8,631), the Framingham Heart Study (N=2,076) and the DIRECT consortium (N=3,029). BMI was associated with 77 metabolites, while WHRadjBMI was associated with 11 and 3 metabolites in women and men, respectively. The MR analyses in the Swedish cohorts suggested a causal association (p-value <0.05) of increased general adiposity and reduced levels of arachidonic acid, dodecanedioic acid and lysophosphatidylcholine (P-16:0) as well as with increased creatine levels. The replication effort provided support for a causal association of adiposity on reduced levels of arachidonic acid (p-value 0.03). Adiposity is associated with variation of large parts of the circulating metabolome, however causality needs further investigation in well-powered cohorts.

  • 47. Ahmad, Shafqat
    et al.
    Rukh, Gull
    Varga, Tibor V.
    Ali, Ashfaq
    Kurbasic, Azra
    Shungin, Dmitry
    Ericson, Ulrika
    Koivula, Robert W.
    Chu, Audrey Y.
    Rose, Lynda M.
    Ganna, Andrea
    Qi, Qibin
    Stančáková, Alena
    Sandholt, Camilla H.
    Elks, Cathy E.
    Curhan, Gary
    Jensen, Majken K.
    Tamimi, Rulla M.
    Allin, Kristine H.
    Jørgensen, Torben
    Brage, Soren
    Langenberg, Claudia
    Aadahl, Mette
    Grarup, Niels
    Linneberg, Allan
    Paré, Guillaume
    Magnusson, Patrik K. E.
    Pedersen, Nancy L.
    Boehnke, Michael
    Hamsten, Anders
    Mohlke, Karen L.
    Pasquale, Louis T.
    Pedersen, Oluf
    Scott, Robert A.
    Ridker, Paul M.
    Ingelsson, Erik
    Laakso, Markku
    Hansen, Torben
    Qi, Lu
    Wareham, Nicholas J.
    Chasman, Daniel I.
    Hallmans, Göran
    Hu, Frank B.
    Renström, Frida
    Orho-Melander, Marju
    Franks, Paul W.
    Gene × Physical Activity Interactions in Obesity: Combined Analysis of 111,421 Individuals of European Ancestry2013In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 9, no 7, p. e1003607-e1003607Article in journal (Refereed)
  • 48. Ahmad, Shafqat
    et al.
    Varga, Tibor V.
    Franks, Paul W.
    Gene <b>×</b> Environment Interactions in Obesity: The State of the Evidence2013In: Human Heredity, ISSN 0001-5652, E-ISSN 1423-0062, Vol. 75, no 2-4, p. 106-115Article in journal (Refereed)
  • 49. Ahmad, Shafqat
    et al.
    Zhao, Wei
    Renström, Frida
    Rasheed, Asif
    Samuel, Maria
    Zaidi, Mozzam
    Shah, Nabi
    Mallick, Nadeem Hayyat
    Zaman, Khan Shah
    Ishaq, Mohammad
    Rasheed, Syed Zahed
    Memon, Fazal-ur-Rheman
    Hanif, Bashir
    Lakhani, Muhammad Shakir
    Ahmed, Faisal
    Kazmi, Shahana Urooj
    Frossard, Philippe
    Franks, Paul W.
    Saleheen, Danish
    Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan: the PROMIS study2015In: BMC Medical Genetics, E-ISSN 1471-2350, Vol. 16, no 1, article id 114Article in journal (Refereed)
  • 50.
    Ahmadi, Shilan Seyed
    et al.
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; Uddevalla Cent Hosp, Sweden.
    Pivodic, Aldina
    Stat Konsultgrp, Sweden; Univ Gothenburg, Sweden.
    Svensson, Ann-Marie
    Ctr Registers Reg Vastra Gotaland, Sweden.
    Wedel, Hans
    Univ Gothenburg, Sweden.
    Rathsman, Björn
    Sachs Children & Youth Hosp, Sweden.
    Nyström, Thomas
    Karolinska Inst, Sweden.
    Ludvigsson, Johnny
    Linköping University, Department of Biomedical and Clinical Sciences, Division of Children's and Women's Health. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, H.K.H. Kronprinsessan Victorias barn- och ungdomssjukhus.
    Lind, Marcus
    Univ Gothenburg, Sweden; Sahlgrens Univ Hosp, Sweden; NU Hosp Grp, Sweden.
    Risk factors for nephropathy in persons with type 1 diabetes: a population-based study2022In: Acta Diabetologica, ISSN 0940-5429, E-ISSN 1432-5233, Vol. 59, p. 761-772Article in journal (Refereed)
    Abstract [en]

    Aims Albuminuria is strongly associated with risk of renal dysfunction, cardiovascular disease and mortality. However, clinical guidelines diverge, and evidence is sparse on what risk factor levels regarding blood pressure, blood lipids and BMI are needed to prevent albuminuria in adolescents and young adults with type 1 diabetes. Methods A total of 9347 children and adults with type 1 diabetes [mean age 15.3 years and mean diabetes duration 1.4 years at start of follow-up] from The Swedish National Diabetes Registry were followed from first registration until end of 2017. Levels for risk factors for a risk increase in nephropathy were evaluated, and the gradient of risk per 1 SD (standard deviation) was estimated to compare the impact of each risk factor. Results During the follow-up period, 8610 (92.1%) remained normoalbuminuric, 737 (7.9%) individuals developed micro- or macroalbuminuria at any time period of whom 132 (17.9% of 737) individuals developed macroalbuminuria. Blood pressure &gt;= 140/80 mmHg was associated with increased risk of albuminuria (p &lt;= 0.0001), as were triglycerides &gt;= 1.0 mmol/L (p = 0.039), total cholesterol &gt;= 5.0 mmol/L (p = 0.0003), HDL &lt; 1.0 mmol/L (p = 0.013), LDL 3.5- &lt; 4.0 mmol/L (p = 0.020), and BMI &gt;= 30 kg/m(2) (p = 0.033). HbA1c was the strongest risk factor for any albuminuria estimated by the measure gradient of risk per 1 SD, followed by diastolic blood pressure, triglycerides, systolic blood pressure, cholesterol and LDL. In patients with HbA1c &gt; 65 mmol/mol (&gt; 8.1%), blood pressure &gt; 140/70 mmHg was associated with increased risk of albuminuria. Conclusions Preventing renal complications in adolescents and young adults with type 1 diabetes need avoidance at relatively high levels of blood pressure, blood lipids and BMI, whereas very tight control is not associated with further risk reduction. For patients with long-term poor glycaemic control, stricter blood pressure control is advocated.

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