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

Rebecka Hjort,Tiinamaija Tuomi,Leif Groop,Mats Martinell,Lars Alfredsson,Per-Ola Carlsson,Elin Pettersen Sørgjerd,Bjørn Olav Åsvold,Sofia Carlsson,Emma Ahlqvist,Tomas Andersson,Valdemar Grill

doi:10.1210/clinem/dgaa549

Abstract

PurposePhysical 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.MethodsWe 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.ResultsHigh 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 ConclusionsOur findings indicate that high PA is associated with a reduced risk of LADA in individuals without genetic susceptibility.

Highlights

We investigated whether Physical activity (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
Comparing controls from ESTRID to the genetic controls from Epidemiological Investigation of Rheumatoid Arthritis (EIRA) showed that the latter were more likely to be female; this was handled by matching to the diabetes cases
The lower incidence was eliminated after adjustment for body mass index (BMI), suggesting that a potential effect is mediated by reduced adiposity, alternatively that BMI is confounding the association between LADA and PA

Summary

Introduction

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

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