Life course influences on insulin resistance - Findings from the British Women's Heart and Health Study

OBJECTIVE - To assess the independent associations of a broad range of early life risk factors and adult obesity with adult insulin resistance. RESEARCH DESIGN AND METHODS - This was a cross-sectional study of 1,394 women, aged 60-79 years, from 23 British towns. RESULTS - There was a strong (independent of confounding factors, other early life factors, and adult waist-to-hip ratio) inverse association between birth weight and insulin resistance in women in the highest third of BMI (>28.77 kg/m(2)): -0.12 (95% CI -0.19 to -0.04) log homeostasis model assessment (HOMA) score per 1 SD birth weight, but no association between birth weight and insulin resistance in women in the two lowest thirds of BMI (P for interaction = 0.04). Offspring birth weight, own leg length, and childhood manual social class did not interact with adult obesity and were all independently inversely associated with insulin resistance: -0.05 (-0.09 to -0.01) log HOMA score per I SD offspring birth weight, -0.09 (-0.12 to -0.06) log HOMA score per 1SD leg length, and a -0.07 (-0.14 to 0.00) difference in log HOMA score between manual and nonmanual childhood social class. Childhood manual social class and shorter leg length were both independently associated with adverse lipid profiles. BMI and waist-to-hip ratio were independently positively associated with insulin resistance and with all other components of the insulin resistance syndrome. CONCLUSIONS - insulin resistance is an important risk factor for type 2 diabetes and coronary heart disease. Our results suggest that genetic factors, intrauterine environment, early childhood, and adult environmental factors are all relevant in determining adult insulin resistance.