Shortened Leukocyte Telomere Length Is Associated With Glycemic Progression in Type 2 Diabetes: A Prospective and Mendelian Randomization Analysis.
Shortened Leukocyte Telomere Length Is Associated With Glycemic Progression in Type 2 Diabetes: A Prospective and Mendelian Randomization Analysis.
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DOI：
10.2337/dc21-1609
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发表时间：
2022-03-01
期刊：
影响因子：
16.2
通讯作者：
Ma RCW
中科院分区：
文献类型：
--
作者：
Cheng F;Luk AO;Shi M;Huang C;Jiang G;Yang A;Wu H;Lim CKP;Tam CHT;Fan B;Lau ESH;Ng ACW;Wong KK;Carroll L;Lee HM;Kong AP;Keech AC;Chow E;Joglekar MV;Tsui SKW;So WY;So HC;Hardikar AA;Jenkins AJ;Chan JCN;Ma RCW
一些研究支持相对白细胞端粒长度（rLTL）之间的关联，rLTL是生物衰老和2型糖尿病的生物标志物。本研究探讨了rLTL与2型糖尿病患者血糖进展风险的关系。在这项队列研究中，研究了来自香港糖尿病登记册的连续2型糖尿病患者（N = 5506），这些患者具有存储的基线DNA和可用的随访数据。采用定量PCR法测定rLTL。血糖进展被定义为对外源性胰岛素的新需求。5349名受试者的平均（SD）年龄为57.0（13.3）岁，平均（SD）随访时间为8.8（5.4）年。与其他受试者相比，1803名进展到胰岛素需求的受试者的基线rLTL显著缩短（4.43±1.16比4.69±1.20）。较短的rLTL与较高的血糖进展风险相关（每单位下降的风险比[95% CI][至~ 0.2千碱基]:1.10[1.06-1.14]），在调整混杂因素后仍然显著。基线rLTL与随访期间血糖暴露独立相关（β = - 0.05[- 0.06至- 0.04]）。绝对LTL每降低1千碱基，糖尿病进展的风险平均增加1.69倍（95% CI 1.35-2.11）。双样本孟德尔随机化分析显示，每1个单位遗传rLTL降低与糖尿病进展风险增加1.38倍相关（95% CI 1.12-1.70）。在2型糖尿病患者中，较短的rLTL与血糖进展风险增加显著相关，与已确定的危险因素无关。端粒长度可能是2型糖尿病患者血糖进展的有用生物标志物。
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 glycemic progression in patients with type 2 diabetes. 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 quantitative PCR. Glycemic 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 with the remaining subjects (4.43 ± 1.16 vs. 4.69 ± 1.20). Shorter rLTL was associated with a higher risk of glycemic progression (hazard ratio [95% CI] for each unit decrease [to ∼0.2 kilobases]: 1.10 [1.06–1.14]), which remained significant after adjusting for confounders. Baseline rLTL was independently associated with glycemic exposure during follow-up (β = −0.05 [−0.06 to −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 Mendelian randomization 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 glycemic progression in individuals with type 2 diabetes, independent of established risk factors. Telomere length may be a useful biomarker for glycemic progression in people with type 2 diabetes.
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DOI：
10.1038/nrg3246
发表时间：
2012-10
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1126/science.aaz6876
发表时间：
2020-09-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Demanelis K;Jasmine F;Chen LS;Chernoff M;Tong L;Delgado D;Zhang C;Shinkle J;Sabarinathan M;Lin H;Ramirez E;Oliva M;Kim-Hellmuth S;Stranger BE;Lai TP;Aviv A;Ardlie KG;Aguet F;Ahsan H;GTEx Consortium;Doherty JA;Kibriya MG;Pierce BL
通讯作者：
Pierce BL
影响因子：
7.7
作者：
Dalgard, Christine;Benetos, Athanase;Aviv, Abraham
通讯作者：
Aviv, Abraham
影响因子：
8.2
作者：
Verhulst, Simon;Dalgard, Christine;Benetos, Athanase
通讯作者：
Benetos, Athanase
影响因子：
8.3
作者：
Jeanclos, E;Schork, NJ;Aviv, A
通讯作者：
Aviv, A