Brief Report
Mean leukocyte telomere length shortening and type 2 diabetes mellitus: a case-control study

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Recent data have implicated leukocyte telomere length shortening as a potential risk predictor for type 2 diabetes mellitus (T2DM) and its associated phenotypes. However, to date, epidemiologic data are scarce. Using a case-control study from a community-based population sample of the Boston metropolitan area (all whites: 424 controls and 432 cases), we examined the relationship of mean leukocyte telomere repeat copy number to single gene copy number (TSR) and T2DM. Associations of loge-transformed TSR with age, race, sex, body mass index (BMI), current smoking status, fasting insulin levels, fasting glucose levels, and hemoglobin A1c (HbA1c) were examined by multivariable linear regression analysis. A logistic regression analysis was performed to evaluate the association of loge-transformed TSR with T2DM with or without adjustment for potential confounders. The loge-transformed TSR was significantly shorter in the white cases than the white controls (P = 0.003). In a multivariable linear regression analysis, an inverse association of loge-transformed TSR with BMI was observed (P = 0.04). Furthermore, in a multivariable logistic regression analysis, decreased loge-transformed TSR was significantly associated with T2DM (adjusted odds ratio = 1.748; 95% confidence interval [CI] = 1.015–3.012; P = 0.044). In summary, the current investigation has shown an association of mean leukocyte telomere length shortening with T2DM in white subjects. If corroborated in other studies, our findings suggest the potential importance of telomere biology in T2DM.

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Subjects

The study population has been described previously.10 In brief, T2DM subjects and control unrelated subjects were recruited from the Boston metropolitan area; these participants were identified through physicians and clinics associated with the Partners Healthcare System and through newspaper advertisements. Subjects reported their medication history, personal and family history of diseases, smoking status, physical activity, and other lifestyle exposures. Blood pressure, height, weight, waist

Results

The clinical and demographic characteristics of the study participants are shown in Table I. As expected, the case subjects had a higher prevalence of traditional risk factors than did the control subjects. The observed loge-TSR was significantly smaller in the cases than the controls (P = 0.003; Table I). In a multivariable linear regression analysis among the control subjects, an inverse association was observed between the loge-TSR and BMI (P = 0.04; Table II). Moreover, in the logistic

Conclusions

The current investigation has shown that mean leukocyte telomere shortening was associated with T2DM. We also found an inverse association between mean leukocyte telomere length and BMI among our control subjects, thus in concordance with previous reports.12, 13, 14, 15, 16 However, we did not find any association of mean leukocyte telomere length with several diabetes-related intermediate phenotypes among our control subjects; this may be partly because of the current stringent selection

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