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Objective: Insulin resistance and hyperuricemia, established risk factors of type 2 diabetes (T2DM), are highly correlated, but their complex relationships are not well understood. This study aims to examine the temporal relationship between uric acid (UA) and insulin and their joint impact on T2DM in middle-aged adults. Research Design and Methods: The longitudinal cohort consisted of 1351 non-diabetic adults (979 whites and 372 blacks; 41.2% males, mean age=36.1 years at follow-up) who had serum UA and insulin measured twice at baseline and follow-up over 7.7 years on average. The cross-lagged analysis model was used to examine the temporal relationship between UA and insulin. The general mediation analysis models were constructed to examine the mediating effects of UA and insulin on incident T2DM identified in the outcome survey 12.2 years after the follow-up survey. Results: After adjusting for age, race, sex, body mass index, smoking, alcohol drinking and follow-up years, the path coefficient from baseline UA to follow-up insulin was 0.082 (p

Background: The associations of age-related changes in body weight and waist circumferences with cardiovascular disease (CVD) and mortality remain unclear. Methods: We assessed changes in weight and waist circumference from baseline survey and resurvey among 27 964 participants in the China Kadoorie Biobank (CKB, 2004-2008) and Dongfeng-Tongji Cohort (DF-TJ, 2008-2013). We used Cox proportional hazards models to evaluate the associations between adiposity changes and the subsequent risks of incident CVD, CVD mortality and all-cause mortality. Findings: On average, during a median of 3·4 years from baseline to resurvey, participants experienced a weight loss of 0·6 kg, accompanied by a 2·1 cm increase in waist circumference. We identified 3589 incident CVD cases, 485 CVD deaths, and 1283 all-cause deaths during the follow-up in the CKB (2008-2016) and DF-TJ (2013-2016). Weight loss and waist gain were associated with increased risks of those outcomes in the two cohorts. In particular, compared with participants who had stable waist (waist change -2·0 to 7·0 cm) and weight (weight change -2·5 to 2·5 kg), those who gained waist but lost weight (waist circumference change >7·0 cm, weight change ≤ -2·5 kg) had the highest risk of incident CVD, CVD mortality and all-cause mortality, with the pooled multivariate hazard ratios (HRs) of 1·41 (95% CI, 1·13 to 1·75), 2·48 (1·40 to 4·37), and 1·71 (1·16 to 2·51), respectively. Among the weight-stable participants, waist circumference was linearly associated with CVD risk, with 17% higher risk (HR 1·17, 1·04 to 1·32) for those gained waist while 13% lower risk (HR 0·87, 0·77 to 0·99) for those lost waist compared to waist-stable participants. Interpretation: Increased waist circumference with concurrent weight loss is significantly associated with increased risks of CVD morbidity, CVD mortality, and all-cause mortality among Chinese middle-aged and elderly adults. Funding Statement: This work was partly supported by grants from the Foundation of National Key Programs of Research and Development of China (2016YFC0900800, 2016YFC0900500, 2017YFC0907501 and 2017YFC0907504), the National Natural Science Foundation of China (91643202 and 81390540), the 111 Project and the Program for Changjiang Scholars and Innovative Research Team in University. The China Kadoorie Biobank baseline survey and the first resurvey were supported by the Kadoorie Charitable Foundation in Hong Kong. The long-term follow-up has been supported by the UK Wellcome Trust (grants 088158/Z/09/Z, 104085/Z/14/Z), and the Chinese Ministry of Science and Technology (2011BAI09B01). The British Heart Foundation, UK Medical Research Council, and Cancer Research provide core funding to the Clinical Trial Service Unit and Epidemiological Studies Unit at Oxford University for the project. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The CKB study was approved by the ethics committees or institutional review boards at the University of Oxford, the Chinese Center for Disease Control and Prevention (China CDC), the Chinese Academy of Medical Sciences. The DF-TJ cohort was approved by the ethics committees of Tongji Medical College and the Sinopharm Dongfeng General Hospital. All participants provided written informed consents.

Background: Glucosamine is a common supplement for treating osteoarthritis, while its effectiveness on osteoarthritis and joint pain continues to be debated. Recently emerging evidence from animal studies and cross-sectional studies in humans suggest that glucosamine may have potential benefits on reduction of cardiovascular disease (CVD) and mortality; however, evidence from prospective studies is lacking. Methods: In the UK biobank cohort study, a total of 466,039 participants without CVD at baseline completed the questionnaire on supplement use, including glucosamine, were analyzed in this study. These participants were enrolled from 2006 to 2010 and followed up to 2016. Cox proportional hazards models were used to compare hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CVD events in participants who did and did not use glucosamine. Findings: During a median of 7·0 years of follow-up, we documented 10,204 incident cases of CVD events, 3,060 cases of CVD death, 5,745 cases of CHD and 3,263 cases of stroke. After adjustment for age, sex, body mass index, race, lifestyle factors, dietary intakes, medication use and other supplements use, glucosamine use was associated with significantly reduced risks of total CVD events (HR: 0·85: 95% confidence interval [CI], 0·80-0·90), CVD death (HR: 0·78: 95% [CI], 0·70-0·87), CHD (HR: 0·82: 95% [CI], 0·76-0·88) and stroke (HR: 0·91: 95% [CI], 0·83-1·00). In addition, the associations of glucosamine use with risks of total CVD events and CHD were more pronounced in smokers than non-smokers (P-interaction=0·018 and 0·004, respectively). Interpretation: Beyond its original use for treating osteoarthritis, habitual use of glucosamine supplement was associated with significantly reduced risks of CVD events, especially among smokers. Further investigations in both prospective cohorts and clinical trials are warranted to verify our findings. Funding: The study was supported by grants from the National Heart, Lung, and Blood Institute (HL071981, HL034594, HL126024), the National Institute of Diabetes and Digestive and Kidney Diseases (DK115679, DK091718, DK100383, DK078616). Declaration of Interest: We declare no competing interests. Ethical Approval: All participants provided written informed consent and the study was approved by the NHS National Research Ethics Service. The present analysis was approved by the Tulane University (New Orleans, Louisiana) Institutional Review Board. Data from 502, 616 participants were available for our study.

Background: The transcription factor 7-like 2 gene (TCF7L2) is the strongest locus associated by the variant rs7903146 with type 2 diabetes (T2D) identified to date. Whether diet/lifestyle intervention modifies genetic effect of TCF7L2 variant on glucose homeostasis and adiposity is still controversial. Objective: To quantify the modification effects of the diet/lifestyle interventions on genetic association of TCF7L2 variant rs7903146 with glycemic control and adiposity changes in randomized controlled trials (RCTs). Design A large collaborative analysis of individual-participant data from seven RCTs. Setting RCTs conducted in adults reporting changes in glycemic traits, body weight, or waist circumference by TCF7L2 rs7903146 after dietary/lifestyle-based interventions. Gene-treatment interaction models were fitted to individual participant data from all studies, using allele dose coding for genetic effects and a common set of covariates. Results: We included seven eligible RCTs for the joint analysis (n=4,114 participants). Overall, a significant interaction between TCF7L2 rs7903146 and diet/lifestyle interventions on decrease in fasting glucose was observed. Compared with control, diet/lifestyle interventions reduced fasting glucose by -0.17 (95% CI, -0.32 to -0.02) mmol/L (test for heterogeneity: I2=45.1%, p