Physical Activity, Genetic Susceptibility, and the Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes

• Published in: The journal of clinical endocrinology and metabolism Vol. 105; no. 11; pp. 1 - e4123
• Main Authors: Hjort, Rebecka, Ahlqvist, Emma, Andersson, Tomas, Alfredsson, Lars, Carlsson, Per-Ola, Grill, Valdemar, Groop, Leif, Martinell, Mats, Sørgjerd, Elin Pettersen, Tuomi, Tiinamaija, Åsvold, Bjørn Olav, Carlsson, Sofia
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01.11.2020; Copyright Oxford University Press
• Subjects: Adult; Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics; ANDIS; Autoimmune diseases; Body fat; Body Mass Index; Case-Control Studies; Clinical Medicine; Clinical s; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - physiopathology; Disease susceptibility; Drb1 protein; Endocrinology and Diabetes; Endokrinologi och diabetes; Exercise; Exercise - physiology; Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi; Gene Frequency; gene-environment interaction; Genetic aspects; Genetic Predisposition to Disease; Genetic research; Genotype; Genotypes; Histocompatibility antigen HLA; Histocompatibility antigens; HLA Antigens - genetics; HLA histocompatibility antigens; Humans; Hälsovetenskap; Incidence; Insulin; Klinisk medicin; LADA; latent autoimmune diabetes in adults; Latent Autoimmune Diabetes in Adults - epidemiology; Latent Autoimmune Diabetes in Adults - genetics; Latent Autoimmune Diabetes in Adults - physiopathology; Medical and Health Sciences; Medicin och hälsovetenskap; Norway - epidemiology; Physical activity; Physical fitness; population-based; Prospective Studies; Risk; Risk assessment; Risk factors; Sweden - epidemiology; Transcription Factor 7-Like 2 Protein - genetics; Type 2 diabetes; Norway; Sweden; LADA; latent autoimmune diabetes in adults; type 2 diabetes; population-based; gene-environment interaction; physical activity
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgaa549

Abstract 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.