Insulin resistance as a predictor of age-related diseases

The current study was initiated to evaluate the ability of insulin resistan ce to predict a variety of age-related diseases. Baseline measurements of i nsulin resistance and related variables were made between 1988-1995 in 208 apparently healthy, nonobese (body mass index < 30 kg/m(2)) individuals, wh o were then evaluated 4-11 yr later (mean +/- SEM = 6.3 +/- 0.2 yr) for the appearance of the following age-related diseases: hypertension, coronary h eart disease, stroke, cancer, and type 2 diabetes. The effect of insulin re sistance on the development of clinical events was evaluated by dividing th e study group into tertiles of insulin resistance at baseline and comparing the events in these 3 groups. Clinical endpoints (n = 40) were identified in 37 individuals (18%) of those evaluated, including 12 with hypertension, 3 with hypertension + type 2 diabetes, 9 with cancer, 7 with coronary hear t disease, 4 with stroke, and 2 with type 2 diabetes. Twenty-eight out of t he total 40 clinical events were seen in 25 individuals (36%) in the most i nsulin-resistant tertile, with the other 12 occurring in the group with an intermediate degree of insulin resistance. Furthermore, insulin resistance was an independent predictor of all clinical events, using both multiple lo gistic regression and Cox's proportional hazards analysis. The fact that an age-related clinical event developed in approximately 1 out of 3 healthy i ndividuals in the upper tertile of insulin resistance at baseline, followed for an average of 6 yr, whereas no clinical events were observed in the mo st insulin-sensitive tertile, should serve as a strong stimulus to further efforts to define the role of insulin resistance in the genesis of age-rela ted diseases.