Abstract
Interactions between genetic- and lifestyle factors may be of specific importance for the development of type 2 diabetes. Only a few earlier studies have evaluated interaction effects for the combination of family history of diabetes and presence of risk factors related to lifestyle. We explored whether 60-year-old men and women from Stockholm with a parental history of diabetes are more susceptible than their counterparts without a parental history of diabetes to the negative influence from physical inactivity, overweight or smoking regarding risk of developing type 2 diabetes. The study comprised 4232 participants of which 205 men and 113 women had diabetes (the vast majority type 2 diabetes considering the age of study participants) and 224 men and 115 women had prediabetes (fasting glucose 6.1–6.9 mmol/l). Prevalence odds ratios (OR) with 95% confidence intervals (95% CI) were calculated using logistic regression. Biologic interaction was analyzed using a Synergy index (S) score. The crude OR for type 2 diabetes associated with a parental history of diabetes was 2.4 (95% CI 1.7–3.5) in men and 1.4 (95% CI 0.9–2.3) in women. Adjustments for overweight, physical inactivity and current smoking had minimal effects on the association observed in men whereas in women it attenuated results. In men, but not in women, a significant interaction effect that synergistically increases the risk of developing type 2 diabetes was observed for the combination of BMI>30 and a parental history of diabetes, S 2.4 (95% CI 1.1–5.1). No signs of interactions were noted for a parental history of diabetes combined with physical inactivity and smoking, respectively. In conclusion, obesity in combination with presence of a parental history of diabetes may be particularly hazardous in men as these two factors were observed to synergistically increase the risk of developing type 2 diabetes in men.
Highlights
Type 2 diabetes is a major public health problem in both developing- and industrialized countries [1]
Out of the 4232 cohort participants, one man and two women were excluded from the analyses because they had no glucose value registered and they had left the question about presence of diabetes blank
Our results in men agree with those reported from a population-based cohort study performed in southern Germany reporting an age- and body mass index (BMI)-adjusted HR in men of 2.54
Summary
Type 2 diabetes is a major public health problem in both developing- and industrialized countries [1]. Previous studies suggest that genetic factors as well as an array of different lifestyle factors are associated with the onset of type 2 diabetes [3,4,5]. Recent genome-wide association studies have identified 12 new independent loci associated with type 2 diabetes [7] and at present a total of about 50 loci associated with type 2 diabetes have been identified [8,9] Combined, these loci only account for about 10% of the observed familial clustering in Europeans [8]. A hereditary component is suggested from a number of studies that assessed the influence of a family history of diabetes on risk of type 2 diabetes; most studies report a two- to six fold increased relative risk of type 2 diabetes and the associations appear to be independent of lifestyle factors [10,11]. Results from earlier studies are not consistent regarding the magnitude of sex specific associations [12,13,14]
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