Modifiable risk factors and long term risk of type 2 diabetes among individuals with a history of gestational diabetes mellitus: prospective cohort study

Abstract Objectives To evaluate the individual and combined associations of five modifiable risk factors with risk of type 2 diabetes among women with a history of gestational diabetes mellitus and examine whether these associations differ by obesity and genetic predisposition to type 2 diabetes. Design Prospective cohort study. Setting Nurses’ Health Study II, US. Participants 4275 women with a history of gestational diabetes mellitus, with repeated measurements of weight and lifestyle factors and followed up between 1991 and 2009. Main outcome measure Self-reported, clinically diagnosed type 2 diabetes. Five modifiable risk factors were assessed, including not being overweight or obese (body mass index <25.0), high quality diet (top two fifths of the modified Alternate Healthy Eating Index), regular exercise (≥150 min/week of moderate intensity or ≥75 min/week of vigorous intensity), moderate alcohol consumption (5.0-14.9 g/day), and no current smoking. Genetic susceptibility for type 2 diabetes was characterised by a genetic risk score based on 59 single nucleotide polymorphisms associated with type 2 diabetes in a subset of participants (n=1372). Results Over a median 27.9 years of follow-up, 924 women developed type 2 diabetes. Compared with participants who did not have optimal levels of any of the risk factors for the development of type 2 diabetes, those who had optimal levels of all five factors had >90% lower risk of the disorder. Hazard ratios of type 2 diabetes for those with one, two, three, four, and five optimal levels of modifiable factors compared with none was 0.94 (95% confidence interval 0.59 to 1.49), 0.61 (0.38 to 0.96), 0.32 (0.20 to 0.51), 0.15 (0.09 to 0.26), and 0.08 (0.03 to 0.23), respectively (P trend <0.001). The inverse association of the number of optimal modifiable factors with risk of type 2 diabetes was seen even in participants who were overweight/obese or with higher genetic susceptibility (P trend <0.001). Among women with body mass index ≥25 (n=2227), the hazard ratio for achieving optimal levels of all the other four risk factors was 0.40 (95% confidence interval 0.18 to 0.91). Among women with higher genetic susceptibility, the hazard ratio of developing type 2 diabetes for having four optimal factors was 0.11 (0.04 to 0.29); in the group with optimal levels of all five factors, no type 2 diabetes events were observed. Conclusions Among women with a history of gestational diabetes mellitus, each additional optimal modifiable factor was associated with an incrementally lower risk of type 2 diabetes. These associations were seen even among individuals who were overweight/obese or were at greater genetic susceptibility.