Insulin treatment affects leukocyte telomere length in patients with type 2 diabetes: 6-year longitudinal study

Objective: Many studies demonstrated a close relationship between type 2 diabetes mellitus (T2DM) and leukocyte telomere length (LTL). However, how the LTL changes in T2DM and what are the potential causal factors in it, particularly in patients during a long period treatment, have not been studied. Here we performed a longitudinal observation of LTL in trained T2DM patients during a 6-year follow-up and evaluated the possible risk factors that were associated with LTL alteration. Methods: Seventy-six patients with T2DM were enrolled in this 6-year longitudinal study. The enrolled patients had no severe complication and had never received insulin therapy by the time. Patients were scheduled to visit once every one or two months and their medication changes were recorded. The LTL at the time when patients were enrolled was used as baseline, which was compared with the LTL at 6 year. Multivariable linear regression and exact logistic regression model were adopted to identify independent predictors of telomere length change and telomere length shortening, respectively. Results: Sixty-four patients were successfully followed up. Although mean LTL decreased after 6 years, 30% (19/64) of patients demonstrated LTL lengthening and 70% (45/64) of patients demonstrated LTL shortening. Among them, 18 Patients received insulin treatment during the 6 years. Of these 18 patients, 16 patients showed decreased LTL and only two showed increased LTL. Linear regression analysis demonstrated that change in telomere length during the 6 years was associated inversely with insulin use (beta-coefficients: -0.587, 95% CI: -0.198, -0.085, P < 0.001). Exact logistic regression analysis showed insulin use (OR: 17355, 95% CI: 2.659, 35.627, P = 0.013) and LDL-C(OR: 3.493, 95% CI: 1.559, 10.063, P = 0.007)were independent predicts of telomere length shortening. Conclusions: LTL may increase as well as decrease in T2DM who received antidiabetic treatment. Insulin use may accelerate telomere attrition. Insulin use and LDL-C can predict telomere shortening. (C) 2019 Elsevier Inc. All rights reserved.