Leucocyte telomere length and risk of type 2 diabetes mellitus: new prospective cohort study and literature-based meta-analysis.

BACKGROUND: Short telomeres have been linked to various age-related diseases. We aimed to assess the association of telomere length with incident type 2 diabetes mellitus (T2DM) in prospective cohort studies. METHODS: Leucocyte relative telomere length (RTL) was measured using quantitative polymerase chain reaction in 684 participants of the prospective population-based Bruneck Study (1995 baseline), with repeat RTL measurements performed in 2005 (n = 558) and 2010 (n = 479). Hazard ratios for T2DM were calculated across quartiles of baseline RTL using Cox regression models adjusted for age, sex, body-mass index, smoking, socio-economic status, physical activity, alcohol consumption, high-density lipoprotein cholesterol, log high-sensitivity C-reactive protein, and waist-hip ratio. Separate analyses corrected hazard ratios for within-person variability using multivariate regression calibration of repeated measurements. To contextualise findings, we systematically sought PubMed, Web of Science and EMBASE for relevant articles and pooled results using random-effects meta-analysis. RESULTS: Over 15 years of follow-up, 44 out of 606 participants free of diabetes at baseline developed incident T2DM. The adjusted hazard ratio for T2DM comparing the bottom vs. the top quartile of baseline RTL (i.e. shortest vs. longest) was 2.00 (95% confidence interval: 0.90 to 4.49; P = 0.091), and 2.31 comparing the bottom quartile vs. the remainder (1.21 to 4.41; P = 0.011). The corresponding hazard ratios corrected for within-person RTL variability were 3.22 (1.27 to 8.14; P = 0.014) and 2.86 (1.45 to 5.65; P = 0.003). In a random-effects meta-analysis of three prospective cohort studies involving 6,991 participants and 2,011 incident T2DM events, the pooled relative risk was 1.31 (1.07 to 1.60; P = 0.010; I2 = 69%). CONCLUSIONS/INTERPRETATION: Low RTL is independently associated with the risk of incident T2DM. To avoid regression dilution biases in observed associations of RTL with disease risk, future studies should implement methods correcting for within-person variability in RTL. The causal role of short telomeres in T2DM development remains to be determined.

Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis.

OBJECTIVE: To assess the association between leucocyte telomere length and risk of cardiovascular disease. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Studies published up to March 2014 identified through searches of Medline, Web of Science, and Embase. ELIGIBILITY CRITERIA: Prospective and retrospective studies that reported on associations between leucocyte telomere length and coronary heart disease (defined as non-fatal myocardial infarction, coronary heart disease death, or coronary revascularisation) or cerebrovascular disease (defined as non-fatal stroke or death from cerebrovascular disease) and were broadly representative of general populations--that is, they did not select cohort or control participants on the basis of pre-existing cardiovascular disease or diabetes. RESULTS: Twenty four studies involving 43,725 participants and 8400 patients with cardiovascular disease (5566 with coronary heart disease and 2834 with cerebrovascular disease) were found to be eligible. In a comparison of the shortest versus longest third of leucocyte telomere length, the pooled relative risk for coronary heart disease was 1.54 (95% confidence interval 1.30 to 1.83) in all studies, 1.40 (1.15 to 1.70) in prospective studies, and 1.80 (1.32 to 2.44) in retrospective studies. Heterogeneity between studies was moderate (I(2) = 64%, 41% to 77%, Phet<0.001) and was not significantly explained by mean age of participants (P = 0.23), the proportion of male participants (P = 0.45), or distinction between retrospective versus prospective studies (P = 0.32). Findings for coronary heart disease were similar in meta-analyses restricted to studies that adjusted for conventional vascular risk factors (relative risk 1.42, 95% confidence interval 1.17 to 1.73); studies with ≥ 200 cases (1.44, 1.20 to 1.74); studies with a high quality score (1.53, 1.22 to 1.92); and in analyses that corrected for publication bias (1.34, 1.12 to 1.60). The pooled relative risk for cerebrovascular disease was 1.42 (1.11 to 1.81), with no significant heterogeneity between studies (I(2) = 41%, 0% to 72%, Phet = 0.08). Shorter telomeres were not significantly associated with cerebrovascular disease risk in prospective studies (1.14, 0.85 to 1.54) or in studies with a high quality score (1.21, 0.83 to 1.76). CONCLUSION: Available observational data show an inverse association between leucocyte telomere length and risk of coronary heart disease independent of conventional vascular risk factors. The association with cerebrovascular disease is less certain.

Miscarriage and future maternal cardiovascular disease: a systematic review and meta-analysis.

CONTEXT: The 2011 American Heart Association guidelines identified pregnancy complications as a risk factor for cardiovascular disease in women. However, miscarriage was not mentioned within the guidelines, and there is no consensus on the association between miscarriage and future risk of cardiovascular disease. OBJECTIVE: To confirm or refute the association, a meta-analysis of published papers was conducted. DATA SOURCES: PubMed, Web of Knowledge and Scopus were systematically searched to identify appropriate articles. Reference lists were then hand searched for additional relevant titles. STUDY SELECTION: To be included, articles had to assess the association between miscarriage and subsequent cardiovascular disease in otherwise healthy women. Only women who had miscarriages were considered exposed. Pooled association measures, using random effects meta-analysis, were calculated for coronary heart disease and cerebrovascular disease. Publication bias and between-study heterogeneity were evaluated. DATA EXTRACTION: Two authors individually reviewed all studies and extracted data on patient and study characteristics along with cardiovascular outcomes. RESULTS: 10 studies were identified, with 517 504 individuals included in the coronary heart disease meta-analysis and 134 461 individuals in the cerebrovascular disease analysis. A history of miscarriage was associated with a greater odds of developing coronary heart disease, OR (95% CI) =1.45 (1.18 to 1.78), but not with cerebrovascular disease, OR=1.11 (0.72 to 1.69). There was a strong association between recurrent miscarriage and coronary heart disease OR=1.99 (1.13 to 3.50). Evidence was found for moderate between-study heterogeneity and publication bias in the coronary heart disease analysis. CONCLUSIONS: The meta-analysis indicates that a history of miscarriage or recurrent miscarriage is associated with a greater risk of subsequent coronary heart disease.

Iodine status in a Sherpa community in a village of the Khumbu region of Nepal.

OBJECTIVE: To assess the iodine status of Sherpa residents living in Kunde village, Khumbu region, Nepal. DESIGN: Prevalence of goitre was determined by palpation. Urinary iodine concentrations (UIC) were determined in casual morning samples, and thyroid-stimulating hormone (TSH) in finger-prick blood samples on filter paper. Dietary and demographic data were obtained via questionnaire, and selected foods analysed for iodine. SETTING: Khumbu region is an area of low soil iodine in Nepal, where the prevalence of goitre was greater than 90% in the 1960s prior to iodine intervention. SUBJECTS: Two hundred and fifteen of 219 permanent residents of Kunde were studied. RESULTS: Overall prevalence of goitre was 31% (Grade 1 goitre, 27.0%; Grade 2, 4.2%). When adjusted to a world population, goitre prevalence was 27% (95% CI 23, 32%); Grade 2 goitre prevalence was 2.8% (95% CI 1.0, 4.6%). Median UIC was 97 microg/l, but only 75 microg/l in women of childbearing age. Thirty per cent had UIC < 50 microg/l and 52% had UIC < 100 microg/l, while 31% of children aged <14 years had UIC > 300 microg/l. Ten per cent of participants had TSH concentrations >5 microU/ml. CONCLUSIONS: The prevalence of severe iodine deficiency has decreased since the 1960s, but mild iodine deficiency persists, particularly in women of childbearing age. The consumption of high-iodine uncooked instant noodles and flavour sachets by school-aged children contributed to their low prevalence of goitre and excessive UIC values. This finding may obscure a more severe iodine deficiency in the population, while increasing the risk of iodine-induced hyperthyroidism in children. Ongoing monitoring is essential.