Abstract

We hypothesized that individuals with type 2 diabetes and low insulin resistance in combination with impaired beta cell function at diabetes diagnosis have lower mortality compared to those with high insulin resistance in combination with preserved beta cell function. In this prospective cohort study, 864 individuals with type 2 diabetes (median age 60 years) had fasting glucose and fasting C-peptide measured at the time of diabetes diagnosis or up to five years before diagnosis. Insulin resistance was estimated with HOMA-%S and beta cell function with HOMA-%B. Four groups based on the median of HOMA-%S and HOMA-%B were formed: 1) low HOMA-%S and high HOMA-%B, 2) low HOMA-%S and low HOMA-%B, 3) high HOMA-%S and high HOMA-%B, and 4) high HOMA-%S and low HOMA-%B (reference group). Mortality was registered during a median follow up of 15 years after diabetes diagnosis, and the associations between the four groups and mortality was estimated with Cox regression adjusted for gender and age at diabetes diagnosis (model 1) and adjusted for gender, age at diabetes diagnosis, smoking, hypertension, BMI and total cholesterol (model 2). Group 1 had higher total mortality (model 2: HR 1.58, 95% CI 1.06−2.36) compared to the reference group 4. Group 1 was also associated with higher cardiovascular mortality (model 1: HR 2.24, 95% CI 1.08−4.66), but this difference was no longer significant in model 2. Insulin resistance in combination with preserved beta cell function at the time of diabetes diagnosis is an independent risk factor for total mortality. Insulin resistance in combination with preserved beta cell function increases the risk for cardiovascular mortality but not independent of conventional risk factors. Thus, treatment of type 2 diabetes should focus not only on normalizing blood glucose levels but also improve insulin resistance. Disclosure J. Otten: None. B. Tavelin: None. S. Söderberg: None. O. Rolandsson: None.

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