Objective Time-dependent covariates are generally available as longitudinal data were collected periodically in the cohort study. To examine whether time-dependent triglyceride to high-density lipoprotein cholesterol (TG/ HDL-C) ratio could predict the future risk of type 2 diabetes mellitus (T2DM) and assess its potential impact on the risk of T2DM incidence.Research design and methods This study enrolled 1460 participants without T2DM aged 55 or above in 1992 in the Beijing Longitudinal Study of Aging during 25 years. The questionnaire data were collected in nine surveys from 1992 to 2017. Physical examination and blood laboratory tests including TG and HDL-C concentrations were measured in five surveys. Incident T2DM cases were confirmed via a self-reported history of T2DM or the fasting plasma glucose level.Results 119 new cases of T2DM were identified. In the Cox regression analysis with time-dependent TG/HDL-C ratios and covariates, the adjusted hazard ratios (95% confidence interval) of T2DM incidence were 1.90 (1.12 to 3.23), 2.75 (1.58 to 4.80) and 2.84 (1.69 to 4.77), respectively, for those with TG/HDL-C ratios (both TG and HDL-C were expressed in millimole per liter) in the ranges of 0.87-1.30, 1.31-1.74 and ≥1.75, compared with individuals with TG/HDL-C ratios <0.87. The similar results of subdistribution hazard ratios were obtained by performing the Fine-Gray model with time-dependent TG/ HDL-C ratios. This positive association and the statistically significant trend with increased risk of T2DM incidence in the three categories of elevated TG/HDL-C ratio was confirmed by multiple sensitivity analyses. Furthermore, the T2DM discriminatory power of TG/HDL-C ratio combining with other risk factors was moderately high. Conclusions We found that time-dependent TG/HDL-C ratios were positively associated with the risk of T2DM risk. The elevated TG/HDL-C ratios increased the future risk of T2DM incidence. Lowering the TG/HDL-C ratio could assist in the prevention of diabetes for older adults. ► Lowering TG/HDL-C ratio could assist to prevent T2DM in the general population, and monitoring lipid profile deserves more attention in clinical practice. on July 5, 2020 by guest. Protected by copyright.

Background and purpose Elevated C‐reactive protein (CRP) is associated with an increased risk of ischaemic stroke (IS). However, the causality of this association is uncertain. The aim is to investigate whether genetically raised plasma CRP concentration levels are associated with IS on the basis of the Mendelian randomization method. Methods Based on the National Center for Biotechnology Information single nucleotide polymorphism (SNP) database, the Chinese online genetic database as well as previously published studies, four CRP‐associated SNP alleles (rs1130864, rs1205, rs876537 and rs3093059) with minor allele frequency ≥0.15 were selected and the concentration levels of CRP were measured in 378 first‐ever IS patients and 613 healthy controls. Results Three SNPs were chosen and used as instrumental variables. The adjusted odds ratios (ORs) [95% confidence interval (95% CI)] of IS per addition of the modelled allele were 1.07 (0.79–1.45) for rs876537, 0.99 (0.73–1.35) for rs1205 and 1.08 (0.71–1.65) for rs3093059. The OR (95% CI) of IS for plasma CRP ≥2.0 mg/l was 2.19 (1.06–4.53) compared with <2.0 mg/l. The adjusted OR (95% CI) of IS per genetically predicted 10% higher CRP concentration, based on the three SNPs as the instruments, was 1.02 (0.94–1.11). Furthermore, similar results were obtained with adjusted ORs (95% CI) of 1.00 (0.88–1.13) and 1.04 (0.93–1.16), respectively, for large‐artery atherosclerosis and small‐artery occlusion per genetically predicted 10% higher CRP concentration. Conclusions This Mendelian randomization study provides no clear support that elevated CRP concentration is causally associated with the risk of IS.

Background Many contradictory conclusions pertaining to the telomere length in peripheral leukocyte chromosomes as a potential biomarker for ischemic stroke (IS) risk have been reported by the various observational studies in previous years. This study aims to investigate whether the leukocyte telomere length is associated with an increased IS risk or not, based on the Mendelian randomization (MR) approach. Methods Based on the NHGRI-EBI GWAS Catalog database, the Chinese online genetic database as well as the previous published studies, twelve single nucleotide polymorphisms (SNPs) with minor allele frequency ≥ 0.05 were selected and the leukocyte telomere length was measured in 431 first-ever IS patients and 304 healthy controls (quantitative polymerase chain reaction). To explore linear and non-linear effect of telomere length on the IS risk, we preformed the linear MR analysis (the inverse-variance weighted method, the maximum likelihood method, and the mode-based estimation method), and the non-linear MR analysis (semiparametric method with three tests for non-linearity, including the quadratic test, Cochran’s Q test, and the fractional polynomial test). Results Two verified SNPs (rs11125529 and rs412658) were chosen as instrumental variables. In linear MR analysis, the adjusted odds ratios and 95% confidence intervals of IS for genetically predicted telomere lengths, based on the two SNPs, were 1.312 (0.979 to 1.759), 1.326 (0.932 to 1.888) and 1.226 (0.844 to 1.781) for the inverse-variance weighted method, the maximum likelihood method, and the mode-based estimation method, respectively. Three tests for nonlinearity failed to reject the null exactly, indicating that the relationship between telomere length and IS risk is unlikely to be non-linear. Conclusion This MR study based on individual data does not provide strong evidence for a positive linear or non-linear effect of telomere length on the IS risk.

Age-related disease burdens increased over time, and whether plasma peptides can be used to accurately predict age in order to explain the variation in biological indicators remains inadequately understood. Here we first developed a biological age model based on plasma peptides in 1890 Chinese Han adults. Based on mass spectrometry, 84 peptides were detected with masses in the range of 0.6-10.0 kDa, and 13 of these peptides were identified as known amino acid sequences. Five of these thirteen plasma peptides, including fragments of apolipoprotein A-I (m/z 2883.99), fibrinogen alpha chain (m/z 3060.13), complement C3 (m/z 2190.59), complement C4-A (m/z 1898.21), and breast cancer type 2 susceptibility protein (m/z 1607.84) were finally included in the final model by performing a multivariate linear regression with stepwise selection. This biological age model accounted for 72.3% of the variation in chronological age. Furthermore, the linear correlation between the actual age and biological age was 0.851 (95% confidence interval: 0.836-0.864) and 0.842 (95% confidence interval: 0.810-0.869) in the training and validation sets, respectively. The biological age based on plasma peptides has potential positive effects on primary prevention, and its biological meaning warrants further investigation.

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