Abstract

Aims/hypothesisExcessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies.MethodsAnalyses were based on incident cases of LADA (n = 425) and type 2 diabetes (n = 1420), and 1704 randomly selected control participants from a Swedish case–control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984–2008). We present adjusted ORs and HRs with 95% CI.ResultsIn the Swedish data, obesity was associated with an increased risk of LADA (OR 2.93, 95% CI 2.17, 3.97), which was even stronger for type 2 diabetes (OR 18.88, 95% CI 14.29, 24.94). The association was stronger in LADA with low GAD antibody (GADA; <median) (OR 4.25; 95% CI 2.76, 6.52) but present also in LADA with high GADA (OR 2.14; 95% CI 1.42, 3.24). In the Swedish data, obese vs normal weight LADA patients had lower GADA levels, better beta cell function, and were more likely to have low-risk HLA-genotypes. The combination of overweight and family history of diabetes (FHD) conferred an OR of 4.57 (95% CI 3.27, 6.39) for LADA and 24.51 (95% CI 17.82, 33.71) for type 2 diabetes. Prospective data from HUNT indicated even stronger associations; HR for LADA was 6.07 (95% CI 3.76, 9.78) for obesity and 7.45 (95% CI 4.02, 13.82) for overweight and FHD.Conclusions/interpretationOverweight/obesity is associated with increased risk of LADA, particularly when in combination with FHD. These findings support the hypothesis that, even in the presence of autoimmunity, factors linked to insulin resistance, such as excessive weight, could promote onset of diabetes.

Highlights

  • Overweight and obesity are major risk factors for type 2 diabetes [1], and the association between excessive weight and insulin resistance is well known

  • The analytical sample for the present study consisted of all individuals recruited until July 2016 and with complete information on BMI, age, sex, family history of diabetes (FHD), physical activity and smoking (98.2% of the study sample): 425 individuals with latent autoimmune diabetes in adults (LADA), 1420 individuals with type 2 diabetes and 1704 control participants (95% of participants came from Scania and 5% came from Uppsala)

  • The results indicate that LADA in 31–56% of individuals could be attributed to overweight/obesity, compared with 70–82% of all those with type 2 diabetes

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Summary

Introduction

Overweight and obesity are major risk factors for type 2 diabetes [1], and the association between excessive weight and insulin resistance is well known. Insulin resistance has been postulated to be an independent risk factor for type 1 diabetes [4, 5]. Adiposity could potentially affect risk via beta cell autoimmunity; adipokines, which are secreted from excessive fat tissue, have been shown to be involved in various immune-mediating processes [6]. Subsequent prospective studies have reported a twofold increased risk of type 1 diabetes in obese children [7] and obese adults [8], while others find no association [9]. An association is further supported by the coincident increases in childhood obesity and type 1 diabetes incidence [10, 11]

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