Markers of tissue-specific insulin resistance predict the worsening of hyperglycemia, incident type 2 diabetes and cardiovascular disease.

ABSTRACT

We investigated the ability of surrogate markers of tissue-specific insulin resistance (IR, Matsuda IR, Adipocyte IR, Liver IR) to predict deterioration of hyperglycemia, incident type 2 diabetes and cardiovascular events in the Metabolic Syndrome in Men (METSIM) Study. The METSIM Study includes 10,197 Finnish men, aged 45-73 years, and examined in 2005-2010. A total of 558 of 8,749 non-diabetic participants at baseline were diagnosed with new-onset diabetes and 239 with a new CVD event during a 5.9-year follow-up of this cohort (2010-2013). Compared to fasting plasma insulin level, Matsuda IR (IR in skeletal muscle) and Adipocyte IR were significantly better predictors of 2-hour plasma glucose and glucose area under the curve after adjustment for confounding factors. Liver IR was the strongest predictor of both incident type 2 diabetes (hazard ratio = 1.83, 95% confidence interval 1.68-1.98) and cardiovascular events (hazard ratio = 1.31, 95% confidence interval 1.15-1.48). Hazard ratios for fasting insulin were 1.37 (95% confidence interval 1.32-1.42) and 1.11 (95% confidence interval 1.00-1.24), respectively. Tissue-specific markers of IR, Matsuda IR and Adipocyte IR, were superior to fasting plasma insulin level in predicting worsening of hyperglycemia, and Liver IR was superior to fasting insulin level in predicting incident type 2 diabetes and cardiovascular events.