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Few studies have investigated the relationship between rLTL and mortality in patients with type 2 diabetes in a large prospective study, particularly in the Asian population. This study investigates the relationship between rLTL and the risk of death in Chinese patients with type 2 diabetes.Consecutive Chinese patients with type 2 diabetes (N = 5349) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using a quantitative polymerase chain reaction. Mortality and clinical outcomes were obtained based on ICD-9 codes.The mean (SD) age of the subjects was 57.5 (13.3) years and mean (SD) follow-up duration was 13.4 (5.5) years. Baseline rLTL was significantly shorter in the 1925 subjects who subsequently died compared with the remaining subjects (4.3 ± 1.2 vs. 4.7 ± 1.2, P 0.001). Shorter rLTL was associated with a higher risk of mortality (HR: 1.19 (1.14-1.23), P 0.001), which remained significant after adjusting for traditional risk factors.Shorter rLTL was significantly associated with an increased risk of all-cause and CVD mortality in patients with type 2 diabetes, independent of established risk factors. Telomere length may be a useful biomarker for mortality risk in patients with type 2 diabetes.

To assess the development of treatment failure in Chinese patients with type 2 diabetes mellitus (T2DM) initiated on metformin or sulphonylurea (SU) monotherapy, with consideration of various potential sources of biases.A 1:1-matched new metformin and SU user cohort on immortal time and mean propensity score after multiple imputation was selected from a cohort of 5889 Chinese patients with T2DM. Treatment failure was defined as progression to (i) combination oral anti-hyperglycemia drug therapy, (ii) insulin use, or (iii) a treatment haemoglobin A1c (HbA1c)7.5% (58 mmol/mol). Stratified Cox regression analysis on the matched pairs was employed to examine the associations between initial monotherapy and onset of treatment failure.Of 554 new metformin and 840 new SU users, 380 were matched. During a median follow-up duration of 3 years, 173 (45.6%) metformin users and 220 (57.9%) SU users experienced treatment failure (annual failure rates of 15% and 19%, respectively). The median time from monotherapy starting to treatment failure was 3.0 [inter-quartile range (IQR): 1.8-5.4] years for metformin users, versus 1.8 (IQR: 0.9-4.1) years for SU users (p0.001). Stratified Cox regression analysis showed significantly lower risk of treatment failure for metformin users (HR [95% CI], 0.62[0.47-0.81]; p0.001). Consistent results were found in analyses based on traditional adjustment schemes with or without imputation.By systematically incorporating new-user design, multiple imputation and matching methods, we found that Chinese patients with T2DM initiated on metformin monotherapy were associated with a significant delay in the onset of treatment failure compared to SU monotherapy.

Background Diabetes is associated with an increased risk of cancer. This study aimed to evaluate associations between recently reported type 2 diabetes (T2D) susceptibility genetic variants and cancer risk in a prospective cohort of Chinese patients with T2D. Methods Seven single nucleotide polymorphisms (SNP) in IGF2BP2 , CDKAL1 , SLC30A8 , CDKN2A/B , HHEX and TCF7L2 , all identified from genome-wide association studies of T2D, were genotyped in 5900 T2D patients [age mean±SD=57±13 years, % males=46] without any known cancer at baseline. Associations between new-onset of cancer and SNPs were tested by Cox proportional hazard models with adjustment of conventional risk factors. Results During the mean follow-up period of 8.5±3.3 years, 429 patients (7.3%) developed cancer. Of the T2D-related SNPs, the G-alleles of HHEX rs7923837 (hazard ratio [HR] (95% C.I.)=1.34 (1.08–1.65); P =6.7×10 −3 under dominant model) and TCF7L2 rs290481 (HR (95% C.I.)=1.16 (1.01–1.33); P =0.040 under additive model) were positively associated with cancer risk, while the G-allele of CDKAL1 rs7756992 was inversely associated (HR (95% C.I.)=0.80 (0.65–1.00); P =0.048 under recessive model). The risk alleles of these significant SNPs exhibited combined effect on increasing cancer risk (per-allele HR (95% C.I.)=1.25 (1.12–1.39); P =4.8×10 −5 ). The adjusted cancer risk was 2.41 (95% C.I. 1.23–4.69) for patients with four risk alleles comparing to patients without risk allele. Conclusions T2D-related variants HHEX rs7923837, TCF7L2 rs290481 and CDKAL1 rs7756992 increased cancer risk in patients with diabetes. Impact Our findings provide novel insights into the pathogenesis of cancer in diabetes.

Aims We examined the risk association between single nucleotide polymorphisms (SNPs) in eleven candidate genes with type 2 diabetes (T2D). T2D-associated polymorphisms were also examined for prediction of incident CHD. Methods 113 tagging SNPs were genotyped in stage 1 (467 T2D cases, 290 controls), and 15 SNPs were analyzed in the final cohort (1462 T2D cases, 600 controls). Three T2D-associated SNPs were further tested for prediction of CHD within a subset of 1417 T2D cases free of CHD at enrolment. Results In the case–control analysis, PPARG rs1801282 (Pro12Ala) (OR = 1.48 (1.02–2.16)), ADIPOQ rs1063539 (OR = 1.17 (1.01–1.35)), and HNF4A rs1884614 (OR = 1.16 (1.00–1.32) were associated with T2D (Pallelic