PMID- 32835373 OWN - NLM STAT- MEDLINE DCOM- 20210216 LR - 20211221 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 105 IP - 11 DP - 2020 Nov 1 TI - Physical Activity, Genetic Susceptibility, and the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes. PG - e4112-23 LID - dgaa549 [pii] LID - 10.1210/clinem/dgaa549 [doi] AB - PURPOSE: Physical activity (PA) has been linked to a reduced risk of type 2 diabetes by reducing weight and improving insulin sensitivity. We investigated whether PA is associated with a lower incidence of latent autoimmune diabetes in adults (LADA) and whether the association is modified by genotypes of human leukocyte antigen (HLA), transcription factor 7-like 2 (TCF7L2)-rs7903146, or the fat mass and obesity-associated gene, FTO-rs9939609. METHODS: We combined data from a Swedish case-control study and a Norwegian prospective study including 621 incident cases of LADA and 3596 cases of type 2 diabetes. We estimated adjusted pooled relative risks (RRs) and 95% CI of diabetes in relation to high (>/= 30 minutes of moderate activity 3 times/week) self-reported leisure time PA, compared to sedentariness. RESULTS: High PA was associated with a reduced risk of LADA (RR 0.61; CI, 0.43-0.86), which was attenuated after adjustment for body mass index (BMI) (RR 0.90; CI, 0.63-1.29). The reduced risk applied only to noncarriers of HLA-DQB1 and -DRB1 (RR 0.49; CI, 0.33-0.72), TCF7L2 (RR 0.62; CI, 0.45-0.87), and FTO (RR 0.51; CI, 0.32-0.79) risk genotypes. Adjustment for BMI attenuated but did not eliminate these associations. For type 2 diabetes, there was an inverse association with PA (RR 0.49; CI, 0.42-0.56), irrespective of genotype. MAIN CONCLUSIONS: Our findings indicate that high PA is associated with a reduced risk of LADA in individuals without genetic susceptibility. CI - (c) Endocrine Society 2020. FAU - Hjort, Rebecka AU - Hjort R AD - Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. FAU - Ahlqvist, Emma AU - Ahlqvist E AD - Department of Clinical Sciences in Malmo, Clinical Research Centre, Lund University, Malmo, Sweden. FAU - Andersson, Tomas AU - Andersson T AD - Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. AD - Center for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden. FAU - Alfredsson, Lars AU - Alfredsson L AD - Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. AD - Center for Occupational and Environmental Medicine, Region Stockholm, Stockholm, Sweden. FAU - Carlsson, Per-Ola AU - Carlsson PO AD - Department of Medical Sciences, Uppsala University, Uppsala, Sweden. FAU - Grill, Valdemar AU - Grill V AD - Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. FAU - Groop, Leif AU - Groop L AD - Department of Clinical Sciences in Malmo, Clinical Research Centre, Lund University, Malmo, Sweden. AD - Institute for Molecular Medicine Finland FIMM, Helsinki University, Helsinki, Finland. FAU - Martinell, Mats AU - Martinell M AD - Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden. FAU - Sorgjerd, Elin Pettersen AU - Sorgjerd EP AD - HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. AD - Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. FAU - Tuomi, Tiinamaija AU - Tuomi T AD - Department of Clinical Sciences in Malmo, Clinical Research Centre, Lund University, Malmo, Sweden. AD - Institute for Molecular Medicine Finland FIMM, Helsinki University, Helsinki, Finland. AD - Division of Endocrinology, Abdominal Center, Helsinki University Hospital, Research Program for Diabetes and Obesity, University of Helsinki, and Folkhalsan Research Center, Helsinki, Finland. FAU - Asvold, Bjorn Olav AU - Asvold BO AD - HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. AD - Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. AD - K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway. FAU - Carlsson, Sofia AU - Carlsson S AD - Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. LA - eng PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (HLA Antigens) RN - 0 (TCF7L2 protein, human) RN - 0 (Transcription Factor 7-Like 2 Protein) RN - EC 1.14.11.33 (Alpha-Ketoglutarate-Dependent Dioxygenase FTO) RN - EC 1.14.11.33 (FTO protein, human) SB - IM MH - Adult MH - Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics MH - Body Mass Index MH - Case-Control Studies MH - Diabetes Mellitus, Type 2/epidemiology/*genetics/physiopathology MH - Exercise/*physiology MH - Gene Frequency MH - *Genetic Predisposition to Disease MH - Genotype MH - HLA Antigens/genetics MH - Humans MH - Incidence MH - Latent Autoimmune Diabetes in Adults/epidemiology/*genetics/physiopathology MH - Norway/epidemiology MH - Prospective Studies MH - Risk MH - Sweden/epidemiology MH - Transcription Factor 7-Like 2 Protein/genetics PMC - PMC7947966 OTO - NOTNLM OT - LADA OT - gene-environment interaction OT - latent autoimmune diabetes in adults OT - physical activity OT - population-based OT - type 2 diabetes EDAT- 2020/08/25 06:00 MHDA- 2021/02/17 06:00 PMCR- 2020/08/24 CRDT- 2020/08/25 06:00 PHST- 2020/05/22 00:00 [received] PHST- 2020/08/17 00:00 [accepted] PHST- 2020/08/25 06:00 [pubmed] PHST- 2021/02/17 06:00 [medline] PHST- 2020/08/25 06:00 [entrez] PHST- 2020/08/24 00:00 [pmc-release] AID - 5896587 [pii] AID - dgaa549 [pii] AID - 10.1210/clinem/dgaa549 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2020 Nov 1;105(11):e4112-23. doi: 10.1210/clinem/dgaa549.