Abstract

OBJECTIVE- Predictors of insulin resistance have hitherto only been examined in cross-sectional studies without information on lifestyle factors. Few studies have measured insulin sensitivity (IS) directly and compared different metabolic and lifestyle predictors in a large population.

RESEARCH DESIGN AND METHODS- We aimed at investigating independent long-term predictors of IS in a large population-based sample (The ULSAM cohort) of 50-year old men who conducted a euglycemic clamp 20 years later (n=770). Subjects with diabetes and treatment of cardiovascular disease at baseline were excluded. In linear regression models, metabolic (BMI, triglycerides, HDL-cholesterol, glucose and blood pressure) and lifestyle factors (physical activity, smoking, saturated fat biomarker and socioeconomic status) were independent variables at baseline (age 50) and IS dependent variable at follow-up (age 70). A sub-sample including only normal-weight men from the initial population were also examined (n=440).

RESULTS- BMI was the strongest predictor also after adding metabolic factors. One SD (±2.8) BMI increase corresponded to a mean 19% decrease of IS. After adding lifestyle factors, all factors except triglycerides and smoking were significant predictors. BMI remained the strongest predictor (β=-0.67, 95% CI -0.83 to -0.51, P<0.0001) followed by physical activity, HDL-C, saturated fat and socioeconomic status (all P<0.05). BMI remained the strongest predictor also in normal-weight subjects (P<0.001). Also after adjusting for baseline insulin concentrations, BMI remained the strongest predictor (P<0.001).

CONCLUSIONS- Multiple factors independently predict IS 20 years later, including novel factors such as saturated fat and socioeconomic status. BMI is however the single strongest predictor, even in normal-weight subjects.