Shortened Leukocyte Telomere Length is Associated with Glycemic Progression in Type 2 Diabetes: A Prospective and Mendelian Randomization Analysis.

ObjectiveSeveral studies support associationsbetween relative leukocyte telomere length (rLTL), a biomarker of biologicalaging and type 2 diabetes. This studyinvestigates the relationship between rLTL and the risk of glycaemicprogression in patients with type 2 diabetes.Research Design and MethodsIn this cohortstudy, consecutive Chinese patients with type2 diabetes (N=5,506) from the Hong KongDiabetes Register with stored baseline DNA and available follow-up data werestudied. rLTL was measured using a quantitativepolymerase chain reaction. Glycaemic progression was defined as the new need forexogenous insulin. ResultsThe mean(SD) age of the 5,349 subjects was57.0(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 progressedto 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 glycaemicprogression (HR (95%CI) for each unit decrease (approximate to0.2 kilobases):1.10 (1.06-1.14)), which remained significant after adjusting for confounders. BaselinerLTL was independently associated with glycaemic exposure during follow-up (Beta=-0.05(-0.06- -0.04)). Each 1 kilobase decreasein absolute LTL was on average associated with a 1.69-fold higher risk ofdiabetes progression (95%CI: 1.35-2.11). Two-sample MR analysis showed per1-unit genetically decreased rLTL was associated with a 1.38-foldhigher risk of diabetes progression (95%CI: 1.12-1.70).ConclusionsShorter rLTL was significantly associated with anincreased risk of glycaemic progression in individuals with type 2 diabetes,independent of established risk factors. Telomere length may be a usefulbiomarker for glycaemic progression in people with type 2 diabetes.