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 (Ͼ28.77 kg/m 2 ): Ϫ0.12 (95% CI Ϫ0.19 to Ϫ0.04) 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 ϭ 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: Ϫ0.05 (Ϫ0.09 to Ϫ0.01) log HOMA score per 1 SD offspring birth weight, Ϫ0.09 (Ϫ0.12 to Ϫ0.06) log HOMA score per 1 SD leg length, and a Ϫ0.07 (Ϫ0.14 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.
Diabetes Care 26:97-103, 2003S everal lines of research suggest that the pathogenesis of both type 2 diabetes and coronary heart disease begin in early life. Autopsy studies of U.S. combatants killed in the Korean and Vietnamese wars found that 77 and 45%, respectively, of the young men in these studies (mean age 22 years) had atherosclerosis (1,2). Low birth weight (3,4), childhood social class (5), and adult leg length (an indicator of childhood environmental exposures (6 -8) have all been found to predict type 2 diabetes and coronary heart disease in later life. Insulin resistance appears to be an important mediating factor in all of these associations.One explanation for the association between low birth weight and both type 2 diabetes and coronary heart disease is that poor intrauterine nutrition leads to not only small birth size but also, depending upon the timing of the nutritional deprivation, to "program" changes in glucoseinsulin metabolism leading to insulin resistance and increased diabetes and coronary heart disease risk in later life (9).An alternative theory, the fetal insulin hypothesis, suggests that genetic polymorphisms that lead to both increased insulin resistance and insulin-mediated impaired fetal growth underlie the association between birth weight and diabetes and coronary heart disease (4,10). This latter h...