Integrated analysis of probability of type 2 diabetes mellitus with polymorphisms and methylation of SLC30A8 gene: a nested case-control study.

To estimate the associations between single-nucleotide polymorphisms (SNPs) and methylation of SLC30A8 gene and T2DM risk, and the interactions among SNPs, methylation, and environmental factors on T2DM risk. We genotyped 9 SNPs and tested methylation at 46 CpG loci of SLC30A8 in the baseline DNA of 290 T2DM cases and 290 matched controls nested in the Rural Chinese Cohort Study. A conditional logistic regression model was used to estimate the associations between SNPs and SLC30A8 methylation and T2DM risk. Multifactor Dimensionality Reduction analysis was used to estimate the effect of interactions among SNPs, methylation, and environment on T2DM risk. Probability of T2DM was decreased with rs11558471 (GG vs. AA, OR = 0.55, 95% CI 0.32, 0.96), with rs13266634 (TT vs. CC, OR = 0.55, 95% CI 0.32, 0.94), with rs3802177 (AA vs. GG, OR = 0.54, 95%CI 0.31, 0.94), and its probability was increased with rs2466293 of SLC30A8 (GA vs. AA, OR = 1.63, 95% CI 1.08-2.47). Its probability was also significantly associated with methylation of CG9 and CG45 (OR = 0.56 [95% CI 0.33-0.97] and 1.61 [95%CI 1.03--2.51]). T2DM probability was significantly associated with the interaction effect between rs2466293 and hypertension (p = 0.045). T2DM probability was also significantly associated with the combination effects of rs2466293 with BMI, hypertension, and hypertriglyceridemia, with the combination effects of hypertriglyceridemia with rs11558471, rs13266634, and methylation of CG45.

Fried-food consumption and risk of overweight/obesity, type 2 diabetes mellitus, and hypertension in adults: a meta-analysis of observational studies.

Recent studies have reported conflicting associations of fried-food consumption and risk of overweight/obesity, type 2 diabetes mellitus (T2DM) and hypertension, and a meta-analysis is not available. We aimed to explore the association between fried-food consumption and risk of overweight/obesity, T2DM and hypertension in adults through a meta-analysis. We searched PubMed, EMBASE, and Web of Science for studies published up to 17 June 2020. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random-effects models. In comparing the highest to lowest fried-food intake, the pooled RRs (95% CIs) were 1.16 (1.07-1.25; I2 = 71.0%, Pheterogeneity < 0.001) for overweight/obesity (cohort: 1.19 [0.97-1.47], n = 2; cross-sectional: 1.14 [1.03-1.27], n = 9), 1.07 (0.90-1.27; 84.7%) for T2DM (cohort: 1.01 [0.89-1.15], n = 9; case-control: 2.33 [1.80-3.01], n = 1), and 1.20 (1.05-1.38; I2=91.8%) for hypertension (cohort: 1.06 [0.98-1.15], n = 8; cross-sectional: 2.16 [0.59-7.87], n = 3). Our meta-analysis indicates fried-food consumption is associated with increased risk of overweight/obesity and hypertension but not T2DM in adults, but the findings should be interpreted with caution due to high heterogeneity and unstable subgroup analyses of this meta-analysis. More studies are warranted to investigate the total fried-food consumption and these health outcomes.

Metabolic Score for Visceral Fat: a novel predictor for the risk of type 2 diabetes mellitus.

To investigate the association between the Metabolic Score for Visceral Fat (METS-VF) and risk of type 2 diabetes mellitus (T2DM) and compare the predictive value of the METS-VF for T2DM incidence with other obesity indices in Chinese people. A total of 12 237 non-T2DM participants aged over 18 years from the Rural Chinese Cohort Study of 2007-2008 were included at baseline and followed up during 2013-2014. The cox proportional hazards regression was used to calculate hazard ratios (HR) and 95 % CI for the association between baseline METS-VF and T2DM risk. Restricted cubic splines were used to model the association between METS-VF and T2DM risk. Area under the receiver operating characteristic curve (AUC) analysis was used to evaluate the ability of METS-VF to predict T2DM incidence. During a median follow-up of 6·01 (95 % CI 5·09, 6·06) years, 837 cases developed T2DM. After adjusting for potential confounding factors, the adjusted HR for the highest v. lowest METS-VF quartile was 5·97 (95 % CI 4·28, 8·32), with a per 1-sd increase in METS-VF positively associated with T2DM risk. Positive associations were also found in the sensitivity and subgroup analyses, respectively. A significant nonlinear dose-response association was observed between METS-VF and T2DM risk for all participants (Pnonlinearity = 0·0347). Finally, the AUC value of METS-VF for predicting T2DM was largest among six indices. The METS-VF may be a reliable and applicable predictor of T2DM incidence in Chinese people regardless of sex, age or BMI.

Joint effect of physical activity and blood lipid levels on all-cause and cardiovascular disease mortality: The Rural Chinese Cohort Study.

BACKGROUND AND AIMS: We aimed to evaluate the joint effect of physical activity (PA) and blood lipid levels on all-cause and cardiovascular disease (CVD) mortality. METHODS AND RESULTS: We analyzed 17,236 participants from the Rural Chinese Cohort Study. Cox's proportional-hazards regression models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) between the joint effect of PA and blood lipid levels and risk of all-cause and CVD mortality. Restricted cubic splines were used to estimate the dose-response relationship of PA with risk of all-cause and CVD mortality. During a median follow-up of 6.01 years there were 1106 deaths (484 from CVD) among participants. For all-cause mortality, compared with the group with dyslipidemia and extremely light PA (ELPA), the HRs with dyslipidemia and light PA (LPA), moderate PA (MPA), and heavy PA (HPA) were 0.56 (95% CI 0.45-0.70), 0.59 (0.46-0.75), and 0.59 (0.45-0.78), respectively, while the HRs of groups with normal lipid levels and ELPA, LPA, MPA, and HPA were 0.88 (0.72-1.04), 0.59 (0.48-0.73), 0.53 (0.41-0.67), and 0.38 (0.29-0.50), respectively. We observed similar effects on CVD mortality. Restricted cubic splines showed a curvilinear relationship between PA and risk of all-cause and CVD mortality with normal lipid levels and with dyslipidemia. CONCLUSION: Higher PA reduces the risk of all-cause and CVD mortality. Higher levels of PA are needed in the population.

Independent and joint associations of non-exercise cardiorespiratory fitness and obesity with risk of type 2 diabetes mellitus in the Rural Chinese Cohort Study.

BACKGROUND AND AIMS: An association between cardiorespiratory fitness (CRF) and type 2 diabetes mellitus (T2DM) has not been established in the Chinese population. This study aimed to estimate the independent and joint associations of CRF and obesity with T2DM incidence in the rural Chinese population. METHODS AND RESULTS: We conducted a prospective study of 11,825 non-T2DM subjects among rural Chinese adults. Cox regression models were used to estimate the independent and joint associations between CRF and obesity exposure on T2DM. Restricted cubic splines were used to model the dose-response association. During a median follow-up of 6.01 years, 835 participants developed T2DM. In comparison to quartile 1 of CRF, the multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) of quartiles 2, 3, 4 were 0.75 (0.61-0.91), 0.54 (0.43-0.68), and 0.42 (0.32-0.55), respectively. When stratified by sex, the results were similar. Joint analyses showed that overweight/obesity-unfit individuals had a 2.28 times higher risk of developing T2DM than the normal weight-fit referent (HR 2.28, 95% CI 1.84-2.83; Pinteraction <0.001). The risk for the overweight/obesity-fit category (HR 1.61, 95% CI 1.21-2.15) was larger than for the normal weight-unfit category (HR 1.38, 95% CI 0.97-1.95) versus the normal weight-fit referent. Similar joint associations for waist circumference and CRF with T2DM were also observed. CONCLUSION: A negative association was observed between CRF and risk of T2DM. Overweight/obese or abdominal obesity and unfit participants showed the highest risks of T2DM. It is therefore strongly recommended that fitness-enhancing be encouraged for the prevention of T2DM, especially among obesity participants.

Association of ABCG1 gene methylation and its dynamic change status with incident type 2 diabetes mellitus: the Rural Chinese Cohort Study.

To explore whether DNA methylation of the ATP-binding cassette G1 (ABCG1) gene and its dynamic change are associated with incident type 2 diabetes mellitus (T2DM). We conducted a nested case-control study with 286 pairs of T2DM cases and matched controls nested in the Rural Chinese Cohort Study. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for incident T2DM risk according to ABCG1 methylation level at baseline and its dynamic change at follow-up examination. Spearman's rank correlation coefficients were used to analyze the association between ABCG1 methylation and its possible risk factors in the control group. We found that T2DM risk increased by 16% (OR = 1.16, 95% CI = 1.02-1.31) with each 1% increase in DNA methylation levels of the ABCG1 loci CpG13 and CpG14. DNA methylation change of the ABCG1 locus CpG15 during the 6-year follow-up was associated with increased T2DM risk: T2DM risk increased by 78% in the upper tertile group (methylation gain ≥5%) versus lower tertile group (methylation gain <1%) (OR = 1.78, 95% CI = 1.01-3.15). Furthermore, body mass index was positively correlated with the DNA methylation level of the ABCG1 loci CpG13, CpG14 and CpG15. In conclusion, DNA methylation levels of the ABCG1 loci CpG13 and CpG14 and the methylation gain of locus CpG15 were positively associated with incident T2DM risk, which may suggest a possible etiologic pattern for T2DM and potentially improve T2DM prediction in rural Chinese people.

Chinese visceral adiposity index: A reliable indicator of visceral fat function associated with risk of type 2 diabetes.

BACKGROUND: The evidence of the association between Chinese visceral adiposity index (CVAI) and risk of type 2 diabetes mellitus (T2DM) is limited. We explored the association of CVAI with T2DM and directly compared with the predictive power of CVAI with other visceral obesity indices (visceral adiposity index, waist to height ratio, waist circumference and body mass index) based on a large prospective study. METHODS: We conducted a population-based study of 12 237 Chinese participants. Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between CVAI and T2DM. RESULTS: During follow-up (median: 6.01 years), the incidence of T2DM was 3.29, 7.34, 12.37 and 23.72 per 1000 person-years for quartiles 1, 2, 3 and 4 of CVAI, respectively. The risk of T2DM was increased with quartiles 2, 3 and 4 vs quartile 1 of CVAI (HR 2.12 [95% CI 1.50-3.00], 2.94 [2.10-4.13] and 5.01 [3.57-7.04], Ptrend < 0.001). Per-SD increase in CVAI was associated with a 72% increased risk of T2DM (HR 1.72 [95% CI 1.56-1.88]). Sensitivity analyses did not alter the association. The area under receiver operating characteristic curve was significantly higher for CVAI than other visceral obesity indices (all P <.001). Similar results were observed in stratified analyses by sex. CONCLUSIONS: Our findings show a positive association between CVAI and risk of T2DM. CVAI has the best performance in predicting incident T2DM, so the index might be a reliable and applicable indicator identifying people at high risk of T2DM.

Chinese visceral adiposity index, a novel indicator of visceral obesity for assessing the risk of incident hypertension in a prospective cohort study.

The present study aimed to investigate the association of the Chinese visceral adiposity index (CVAI) and its 6-year change with hypertension risk and compare the ability of CVAI and other obesity indices to predict hypertension based on the Rural Chinese Cohort Study. Study participants were randomly recruited by a cluster sampling procedure, and 10 304 participants ≥18 years were included. Modified Poisson regression was used to derive adjusted relative risks (RR) and 95 % CI. We identified 2072 hypertension cases during a median of 6·03 years of follow-up. The RR for the highest v. lowest CVAI quartile were 1·29 (95 % CI 1·05, 1·59) for men and 1·53 (95 % CI 1·22, 1·91) for women. Per-sd increase in CVAI was associated with hypertension for both men (RR 1·09, 95 % CI 1·02, 1·16) and women (RR 1·14, 95 % CI 1·06, 1·22). Also, the area under the receiver operating characteristic curve value for hypertension was higher for CVAI than the four other obesity indices for both sexes (all P < 0·05). Finally, per-sd increase in CVAI change was associated with hypertension for both men (RR 1·26, 95 % CI 1·16, 1·36) and women (RR 1·23, 95 % CI 1·15, 1·30). Similar results were observed in sensitivity analyses. CVAI and its 6-year change are positively associated with hypertension risk. CVAI has better performance in predicting hypertension than other visceral obesity indices for both sexes. The current findings suggest CVAI as a reliable and applicable predictor of hypertension in rural Chinese adults.

Association between shift work and risk of metabolic syndrome: A systematic review and meta-analysis.

AIMS: A comprehensive assessment of the association of shift work with risk of metabolic syndrome (MetS) through a systematic review and meta-analysis has not been reported. We aimed to evaluate the relationship from observational studies. DATA SYNTHESIS: We searched PubMed, Embase, and Web of Science databases from inception to December 16, 2020. Articles were chosen according to established inclusion criteria. Studies with data on men and women and different types of shift work were treated as independent studies. Relative risks (RRs) and 95% confidence intervals (CIs) were pooled by using random-effects models with heterogeneity (I2) > 50%; otherwise, a fixed-effects model was used. A total of 7192 articles was searched from PubMed, Embase and Web of science. Finally, we included 23 articles (38 studies) in this meta-analysis. The pooled RRs and 95% CI of MetS risk with shift work, 1-shift work, 2-shift work, and 3-shift work versus non-shift work were 1.30 (95% CI 1.19-1.41), 0.95 (95% CI 0.82-1.11), 1.19 (95% CI 0.91-1.56) and 1.17 (95% CI 1.00-1.37), respectively. The results from subgroup analyses stratified by sex, age, and region supported our overall findings that shift work is a risk factor for MetS. CONCLUSIONS: This meta-analysis suggests that shift work increases risk of MetS. Higher risk of MetS was found in the shift workers who were 2-shift or 3-shift or women or Asian workers.

Association of BMI with cardiovascular disease incidence and mortality in patients with type 2 diabetes mellitus: A systematic review and dose-response meta-analysis of cohort studies.

AIMS: The relation of body mass index (BMI) with cardiovascular disease (CVD) and mortality has been extensively investigated in the general population but is less clear in individuals with type 2 diabetes mellitus (T2DM). We performed a meta-analysis of cohort studies to quantitatively evaluate the association of BMI with CVD incidence and mortality in patients with T2DM. DATA SYNTHESIS: PubMed and Embase databases were searched for relevant cohort articles published up to June 8, 2020. Restricted cubic splines were used to evaluate the potential linear or non-linear dose-response associations. We identified 17 articles (21 studies) with 1,349,075 participants and 57,725 cases (49,354 CVD incidence and 8371 CVD mortality) in the meta-analysis. We found a linear association between BMI and risk of CVD incidence (Pnon-linearity = 0.182); the pooled RR for CVD incidence was 1.12 (95% CI, 1.04-1.20) with a 5-unit increase in BMI. We found an overall nonlinear relationship between BMI and CVD mortality (Pnon-linearity < 0.001). The lowest risk was at BMI about 28.4 kg/m2, with increased mortality risk for higher BMI values; the RR with a 5-unit increase in BMI was 0.87 (95% CI, 0.79-0.96) and 1.11 (95% CI, 1.04-1.18) for BMI ≤28.4 kg/m2 and BMI >28.4 kg/m2, respectively. CONCLUSIONS: In individuals with T2DM, BMI may have a positive linear association with risk of CVD incidence but a nonlinear association with CVD mortality. Our results can provide evidence for weight control and lifestyle intervention for preventing and managing cardiovascular disease in T2DM.

Solid fuel use and cardiovascular events: A systematic review and meta-analysis of observational studies.

Although solid fuel use has been increasingly linked to cardiovascular events (CVEs), conclusions have been inconsistent. We systematically searched 3 databases (PubMed, Embase, and Web of Science) up to July 3, 2020, to identify English language reports that assessed the association of solid fuel use with CVEs. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated with a random-effects model. Subgroup analyses and sensitivity analyses were conducted to explore the potential sources of heterogeneity and to test the stability of the results. We finally included 13 observational studies (8 cohort, 3 cross-sectional, and 2 case-control studies comprising 791,220 participants) in the meta-analysis. The risk of CVEs was increased 21% with the highest versus the lowest solid fuel use (highest/lowest, RRpooled  = 1.21, 95% CI: 1.10-1.34). As for the subgroup analyses on study design, the pooled RR for cohort studies, case-control studies, and cross-sectional studies were 1.11 (95%CI: 1.03-1.19), 4.80 (95%CI: 2.22-10.39), and 1.46 (95%CI: 0.82-2.62), respectively. The results of this study suggested that high solid fuel use was associated with increased CVE risk, and that reducing the use of solid fuel will be important for improving the health of the populations in developing countries.

BMI and risk of all-cause mortality in normotensive and hypertensive adults: the rural Chinese cohort study.

OBJECTIVE: The impact of baseline hypertension status on the BMI-mortality association is still unclear. We aimed to examine the moderation effect of hypertension on the BMI-mortality association using a rural Chinese cohort. DESIGN: In this cohort study, we investigated the incident of mortality according to different BMI categories by hypertension status. SETTING: Longitudinal population-based cohort. PARTICIPANTS: 17 262 adults ≥18 years were recruited from July to August of 2013 and July to August of 2014 from a rural area in China. RESULTS: During a median 6-year follow-up, we recorded 1109 deaths (610 with and 499 without hypertension). In adjusted models, as compared with BMI 22-24 kg/m2, with BMI ≤ 18, 18-20, 20-22, 24-26, 26-28, 28-30 and >30 kg/m2, the hazard ratios for mortality in normotensive participants were 1·92 (95% CI 1·23, 3·00), 1·44 (95% CI 1·01, 2·05), 1·14 (95% CI 0·82, 1·58), 0·96 (95% CI 0·70, 1·31), 0·96 (95% CI 0·65, 1·43), 1·32 (95% CI 0·81, 2·14) and 1·32 (95% CI 0·74, 2·35), respectively, and in hypertensive participants were 1·85 (95% CI 1·08, 3·17), 1·67 (95% CI 1·17, 2·39), 1·29 (95% CI 0·95, 1·75), 1·20 (95% CI 0·91, 1·58), 1·10 (95% CI 0·83, 1·46), 1·10 (95% CI 0·80, 1·52) and 0·61 (95% CI 0·40, 0·94), respectively. The risk of mortality was lower in individuals with hypertension with overweight or obesity v. normal weight, especially in older hypertensives (≥60 years old). Sensitivity analyses gave consistent results for both normotensive and hypertensive participants. CONCLUSIONS: Low BMI was significantly associated with increased risk of all-cause mortality regardless of hypertension status in rural Chinese adults, but high BMI decreased the mortality risk among individuals with hypertension, especially in older hypertensives.

Loss of tumor intrinsic PD-L1 confers resistance to drug-induced apoptosis in human colon cancer.

Colorectal cancer (CRC) with BRAF (V600E) is associated with microsatellite instability (MSI) that predicts response to immune checkpoint inhibitors. We demonstrated the interrogation of TCGA RNA-seq human datasets revealed that BRAFV600E tumors had significantly higher Programmed Death Ligand 1 (PD-L1) mRNA compared to non-mutated BRAF CRCs. Also, MSI-H tumors were evaluated as higher PD-L1 than MSS CRCs. Inhibition of MEK/ERK by cobimetinib or CDK inhibitor dinaciclib was shown to attenuate mutant BRAF-induced PD-L1 coincident with reduced c-JUN and YAP expression whose combined knockdown reduced PD-L1. Using TCGA datasets, PD-L1 mRNA expression in human colon cancers was significantly associated with YAP expression. The deletion of PD-L1 can reduce tumor cell growth shown by clonogenic assay. Analysis of the role of PD-L1 as a mediator of chemosensitivity was then performed. Knockout of PD-L1 was shown to attenuate the induction of DNA double-strand breaks (pH2AX) and caspase-3 cleavage by 5-fluorouracil (5-FU) and paclitaxel compared to parental CRC cells. Results were confirmed in PD-L1 knockout MC38 murine CRC cells where re-expression of wild-type PD-L1 promoted DNA damage and apoptosis. We also performed the clonogenic assay and flow cytometry to prove that loss of PD-L1 attenuated DNA damage and apoptosis induced by diverse anti-cancer drugs that could be reversed by restoration of wild-type PD-L1. Mechanistically, knockout of PD-L1 reduced chemosensitivity in association with reductions in p-AKT and in BH3-only proteins BIM and BIK, rather than STAT3 in CRC cells. However, STAT3 had a significant role in melanoma, which shows the heterogeneity of cancers. In summary, BRAFV600E can upregulate PD-L1 expression that was induced by c-jun and YAP to enhance chemotherapy-induced apoptosis. Together, we demonstrate a potential role for PD-L1 as a regulator of chemotherapy-induced apoptosis whose deletion or suppression confers chemoresistance. These findings expand the understanding of PD-L1 functions to include nonimmune mechanisms and suggest the potential use of PD-L1 as a biomarker of response to cytotoxic chemotherapy.

Dose-response association between adult height and all-cause mortality: a systematic review and meta-analysis of cohort studies.

BACKGROUND: We conducted a systematic review and meta-analysis from published cohort studies to examine the association of adult height and all-cause mortality and to further explore the dose-response association. METHODS: PubMed, The Cochrane Library, The Ovid, CNKI, CQVIP and Wanfang databases were searched for articles published from database inception to 6 February 2018. We used the DerSimonian-Laird random-effects model to estimate the quantitative association between adult height and all-cause mortality and the restricted cubic splines to model the dose-response association. RESULTS: We included 15 articles, with 1 533 438 death events and 2 854 543 study participants. For each 5-cm height increase below the average, the risk of all-cause mortality was reduced by 7% [relative risk (RR) = 0.93, 95% confidence interval (CI), 0.89-0.97] for men and 5% (RR = 0.95, 95% CI, 0.90-0.99) for women. All-cause mortality had a U-shaped association with adult height, the lowest risk occurring at 174 cm for men and 158 cm for women (both Pnonlinearity < 0.001). Relative to the shortest adult height (147 cm for men and 137 cm for women), men at 174 cm had a 47% lower likelihood of all-cause mortality and women at 158 cm a 33% lower risk of all-cause mortality. CONCLUSIONS: Our study suggests that the relation between adult height and all-cause mortality is approximately U-shaped in both men and women.

Dose-Response Association Between High-Density Lipoprotein Cholesterol and Stroke: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

INTRODUCTION: Studies investigating the effect of high-density lipoprotein cholesterol (HDL-C) on stroke and stroke subtypes have reached inconsistent conclusions. The purpose of our study was to clarify the dose-response association between HDL-C level and risk of total stroke and stroke subtypes by a systematic review and meta-analysis. METHODS: We performed a systematic search of PubMed, Embase, and Web of Science databases through July 30, 2020, for prospective cohort studies that reported the HDL-C-stroke association and extracted the estimate that was adjusted for the greatest number of confounding factors. Restricted cubic splines were used to evaluate the linear and nonlinear dose-response associations. RESULTS: We included 29 articles, which reported on 62 prospective cohort studies including 900,501 study participants and 25,678 with stroke. The summary relative risk per 1-mmol/L increase in HDL-C level for total stroke was 0.82 (95% CI, 0.76-0.89; I2 = 42.9%; n = 18); ischemic stroke (IS), 0.75 (95% CI, 0.69-0.82; I2 = 50.1%; n = 22); intracerebral hemorrhage (ICH), 1.21 (95% CI, 1.04-1.42; I2 = 33.4%; n = 10); and subarachnoid hemorrhage (SAH), 0.98 (95% CI, 0.96-1.00; I2 = 0%; n = 7). We found a linear inverse association between HDL-C level and risk of total stroke and SAH, a nonlinear inverse association for IS risk, but a linear positive association for ICH risk. The strength and the direction of the effect size estimate for total stroke, IS, ICH, and SAH remained stable for most subgroups. We found no publication bias with Begg's test and Egger's test for the association of HDL-C level with risk of total stroke, IS, and ICH. CONCLUSION: A high HDL-C level is associated with reduced risk of total stroke and IS and an increased risk of ICH.

Baseline serum albumin and its dynamic change is associated with type 2 diabetes risk: A large cohort study in China.

BACKGROUND: The study aimed to investigate the associations of baseline serum albumin level and its dynamic change with type 2 diabetes mellitus (T2DM) risk in a large Chinese cohort study. METHODS: This cohort study included 30 442 adults without T2DM at first entry, who completed at least one follow-up of annual examinations between 2009 and 2016. Serum albumin level was measured at baseline and at every annual check-up. The dynamic change in serum albumin level (∆ALB) was calculated by subtracting serum albumin level at baseline from that at the last follow-up. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox regression models. RESULTS: During 7 years of follow-up, we identified 1634 T2DM events. From the lowest to the highest quartile of serum albumin level, adjusted HRs (95% CI) were 1.00 (reference), 0.96 (0.94, 1.01), 0.98 (0.95, 1.02) and 0.88 (0.85, 0.98), respectively. As compared with stable change in serum albumin (-0.2 ≤ ∆ALB <1.0 g/L), the risk of T2DM increased for ∆ALB < -2.0 g/L (HR 1.44, 95% CI 1.24-1.68) and decreased for ∆ALB ≥3.0 g/L (0.81, 0.68-0.97) after adjusting for potential confounding factors. Restricted cubic splines showed a linear dose-response association between baseline serum albumin level and T2DM risk (Pnonlinearity 0.715) and a nonlinear dose-response association between ∆ALB and T2DM risk (Pnonlinearity 0.011). CONCLUSIONS: Baseline serum albumin level appears to be inversely associated with T2DM risk. Adults with reduced serum albumin level could be early identified for diabetes risk in clinical practice.

Association of total sedentary behaviour and television viewing with risk of overweight/obesity, type 2 diabetes and hypertension: A dose-response meta-analysis.

AIMS: To explore the quantitative dose-response association of total sedentary behaviour and television viewing with overweight/obesity, type 2 diabetes and hypertension in a meta-analysis. MATERIALS AND METHODS: We searched three databases to identify English-language reports that assessed the association of total sedentary behaviour or television viewing with the aforementioned health outcomes. Restricted cubic splines were used to evaluate possible linear or non-linear associations of total sedentary behaviour and television viewing with these health outcomes. RESULTS: We included 48 articles (58 studies) with a total of 1 071 967 participants in the meta-analysis; 21 (six cohort and 15 cross-sectional) studies examined the association of total sedentary behaviour with overweight/obesity, 23 (13 cohort and 10 cross-sectional) studies examined the association with type 2 diabetes and 14 (one cohort and 13 cross-sectional) studies examined the association with hypertension. We found linear associations between total sedentary behaviour and type 2 diabetes (Pnon-linearity = 0.190) and hypertension (Pnon-linearity = 0.225) and a non-linear association between total sedentary behaviour and overweight/obesity (Pnon-linearity = 0.003). For each 1-h/d increase in total sedentary behaviour, the risk increased by 5% for type 2 diabetes and 4% for hypertension. We also found linear associations between television viewing and type 2 diabetes (Pnon-linearity = 0.948) and hypertension (Pnon-linearity = 0.679) and a non-linear association for overweight/obesity (Pnon-linearity = 0.007). For each 1-h/d increase in television viewing, the risk increased by 8% for type 2 diabetes and 6% for hypertension. CONCLUSIONS: High levels of total sedentary behaviour and television viewing were associated with overweight/obesity, type 2 diabetes and hypertension.

Sugar and artificially sweetened beverages and risk of obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality: a dose-response meta-analysis of prospective cohort studies.

Although consumption of sugar-sweetened beverages (SSBs) and artificially sweetened beverages (ASBs) has increasingly been linked with obesity, type 2 diabetes mellitus, hypertension, and all-cause mortality, evidence remains conflicted and dose-response meta-analyses of the associations are lacking. We conducted an updated meta-analysis to synthesize the knowledge about their associations and to explore their dose-response relations. We comprehensively searched PubMed, EMBASE, Web of Science, and Open Grey up to September 2019 for prospective cohort studies investigating the associations in adults. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated for the dose-response association. Restricted cubic splines were used to evaluate linear/non-linear relations. We included 39 articles in the meta-analysis. For each 250-mL/d increase in SSB and ASB intake, the risk increased by 12% (RR = 1.12, 95% CI 1.05-1.19, I2 = 67.7%) and 21% (RR = 1.21, 95% CI 1.09-1.35, I2 = 47.2%) for obesity, 19% (RR = 1.19, 95% CI 1.13-1.25, I2 = 82.4%) and 15% (RR = 1.15, 95% CI 1.05-1.26, I2 = 92.6%) for T2DM, 10% (RR = 1.10, 95% CI 1.06-1.14, I2 = 58.4%) and 8% (RR = 1.08, 95% CI 1.06-1.10, I2 = 24.3%) for hypertension, and 4% (RR = 1.04, 95% CI 1.01-1.07, I2 = 58.0%) and 6% (RR = 1.06, 95% CI 1.02-1.10, I2 = 80.8%) for all-cause mortality. For SSBs, restricted cubic splines showed linear associations with risk of obesity (Pnon-linearity = 0.359), T2DM (Pnon-linearity = 0.706), hypertension (Pnon-linearity = 0.510) and all-cause mortality (Pnon-linearity = 0.259). For ASBs, we found linear associations with risk of obesity (Pnon-linearity = 0.299) and T2DM (Pnon-linearity = 0.847) and non-linear associations with hypertension (Pnon-linearity = 0.019) and all-cause mortality (Pnon-linearity = 0.048). Increased consumption of SSBs and ASBs is associated with risk of obesity, T2DM, hypertension, and all-cause mortality. However, the results should be interpreted cautiously because the present analyses were based on only cohort but not intervention studies.

Association of homocysteine level with risk of stroke: A dose-response meta-analysis of prospective cohort studies.

BACKGROUND AND AIMS: Homocysteine (Hcy) level has been increasingly linked with stroke and ischemic stroke (IS). However, a dose-response meta-analysis of prospective cohort studies of the association is lacking. We aimed to explore the quantitative dose-response association of Hcy level with stroke and IS in a meta-analysis of prospective cohort studies. METHODS AND RESULTS: We performed a systematic search of PubMed, Embase and Web of Science databases up to April 25, 2019 for prospective cohort studies assessing the association of Hcy level with stroke and IS. We used random-effect models to estimate the pooled relative risk (RRs) (with 95% confidence intervals [CIs]) for the association of Hcy with risk of stroke and IS. Restricted cubic splines were used to evaluate possible linear or nonlinear association of Hcy level with stroke and IS. We included 10 prospective cohort studies (7 articles) with 11,061 participants in the meta-analysis. Hcy level was associated with increased risk of stroke (RR = 1.58, 95% CI 1.25-2.00, I2 = 39.5%) and IS (RR = 1.54, 95% CI 1.21-1.97, I2 = 36.4%) for the highest versus the lowest categories. We found a linear association between Hcy level and stroke (Pnonlinearity = 0.660) and IS (Pnonlinearity = 0.981). For each 1-µmol/L increase in Hcy, the pooled RR was 1.06 (95% CI 1.01-1.12, I2 = 59.0%) for stroke and 1.05 (95% CI 1.00-1.11, I2 = 58.6%) for IS. CONCLUSION: This meta-analysis indicated that elevated Hcy level was associated with increased risk of stroke and IS.

Association of weight-adjusted-waist index with incident hypertension: The Rural Chinese Cohort Study.

AIMS: To explore the association between WWI and the incidence of HTN in the Rural Chinese Cohort Study. METHODS AND RESULTS: We examined data for 10,338 non-hypertensive participants (39.49% men) aged ≥ 18 years from the Rural Chinese Cohort Study who completed a baseline examination during 2007-2008 and follow-up during 2013-2014. WWI was calculated as waist circumference (cm) divided by the square root of weight (kg). Multiple logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the probability of HTN across four WWI categories. Restricted cubic splines analysis was used to model the dose-response association of WWI and HTN. A total of 2078 participants had HTN during a median follow-up of 6 years. After adjusting for potential confounders, as compared with the lowest WWI category (<9.94 cm/√kg), with WWI 9.94 to 10.42, 10.42 to 10.91 and ≥ 10.91 cm/√kg, the ORs (95% CIs) for HTN were 1.12 (0.93-1.35), 1.40 (1.17-1.69) and 1.50 (1.24-1.82), respectively. Results of the sensitivity analyses were robust. The ORs were generally consistent on subgroup analysis by sex, smoking status, systolic blood pressure and diastolic blood pressure. Multiple logistic regression models with restricted cubic splines showed a non-linear positive association between WWI and HTN (Pnonlinearity < 0.001). CONCLUSION: The highest WWI category was significantly associated with increased risk of HTN. Our findings may facilitate the development and promotion of obesity prevention strategies aimed at reducing the risk of HTN and provide evidence for healthcare policy in rural China.