Shortened Leukocyte Telomere Length Is Associated With Glycemic Progression in Type 2 Diabetes: A Prospective and Mendelian Randomization Analysis
Several studies support associations between relative leukocyte telomere length (rLTL), a biomarker of biological aging and type 2 diabetes. This study investigates the relationship between rLTL and the risk of glycaemic progression in patients with type 2 diabetes.
Research Design and Methods
In this cohort study, consecutive Chinese patients with type 2 diabetes (N=5,506) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using a quantitative polymerase chain reaction. Glycaemic progression was defined as the new need for exogenous insulin.
The mean(SD) age of the 5,349 subjects was 57.0(13.3) years and mean(SD) follow-up was 8.8(5.4) years. Baseline rLTL was significantly shorter in the 1,803 subjects who progressed to insulin requirement compared to the remaining subjects (4.43±1.16 vs. 4.69±1.20). Shorter rLTL was associated with a higher risk of glycaemic progression (HR (95%CI) for each unit decrease (approximate to 0.2 kilobases): 1.10 (1.06-1.14)), which remained significant after adjusting for confounders. Baseline rLTL was independently associated with glycaemic exposure during follow-up (Beta=-0.05(-0.06- -0.04)). Each 1 kilobase decrease in absolute LTL was on average associated with a 1.69-fold higher risk of diabetes progression (95%CI: 1.35-2.11). Two-sample MR analysis showed per 1-unit genetically decreased rLTL was associated with a 1.38-fold higher risk of diabetes progression (95%CI: 1.12-1.70).
Shorter rLTL was significantly associated with an increased risk of glycaemic progression in individuals with type 2 diabetes, independent of established risk factors. Telomere length may be a useful biomarker for glycaemic progression in people with type 2 diabetes.