Contrasting associations of insulin resistance with diabetes, cardiovascular disease and all-cause mortality in the elderly: PROSPER long-term follow-up

Aims/hypothesis Insulin resistance is commonly proposed as a precursor to both type 2 diabetes and cardiovascular disease (CVD), yet few studies have directly compared insulin resistance with both outcomes simultaneously and determined whether associations with each outcome differ in strength or are comparable. We assessed the association of fasting insulin and HOMA-IR with incident CVD and diabetes in older people. Methods In the long-term follow-up of the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) cohort, HOMA-IR measurement was available in 4,742 older people (70–82 years) without diabetes at baseline. Of these, 283 developed diabetes during the 3.2 year within-trial follow-up, while 1,943 all-cause deaths, 470 CHD deaths (identified from death records) and 590 fatal/non-fatal CVD events (identified from medical record linkage in the Scottish participants) occurred during an extended 8.6 years of total follow-up. Cause-specific Cox proportional-hazards models were fitted using multivariable models. Results Higher HOMA-IR was associated with incident diabetes: HR 4.80 (95% CI 3.14, 7.33) comparing extreme thirds after adjustment for confounders. However, HOMA-IR in the top third was not associated with all-cause mortality, CHD mortality or fatal/non-fatal CVD: HR 1.02 (95% CI 0.90, 1.17), 1.03 (0.79, 1.36) and 0.94 (0.74, 1.20), respectively. Results were similar when fasting insulin was considered as an exposure. Conclusions/interpretation Our data support insulin resistance as a predictor of diabetes in later life but, perhaps surprisingly, suggest this pathway is of negligible importance to CVD outcomes in the elderly.