Integrated Bioinformatics Analysis Revealed Immune Checkpoint Genes Relevant to Type 2 Diabetes.

Objective: Chronic low-grade inflammation of the pancreatic islets is the characteristic of type 2 diabetes (T2D), and some of the immune checkpoints may play important roles in the pancreatic islet inflammation. Thus, we aim to explore the immune checkpoint genes (ICGs) associated with T2D, thereby revealing the role of ICGs in the pathogenesis of T2D based on bioinformatic analyses. Methods: Differentially expressed genes (DEGs) and immune checkpoint genes (ICGs) of islets between T2D and control group were screened from datasets of the Gene Expression Omnibus (GEO). A risk model was built based on the coefficients of ICGs calculated by ridge regression. Functional enrichment analysis and immune cell infiltration estimation were conducted. Correlations between ICGs and hub genes, T2D-related disease genes, insulin secretion genes, and beta cell function-related genes were analyzed. Finally, we conducted RT-PCR to verify the expression of these ICGs. Results: In total, pancreatic islets from 19 cases of T2D and 84 healthy subjects were included. We identified 458 DEGs. Six significantly upregulated ICGs (CD44, CD47, HAVCR2, SIRPA, TNFSF9, and VTCN1) in T2D were screened out. These ICGs were significantly correlated with several hub genes and T2D-related genes; furthermore, they were correlated with insulin secretion and ß cell function-related genes. The analysis of immune infiltration showed that the concentrations of eosinophils, T cells CD4 naive, and T cells regulatory (Tregs) were significantly higher, but CD4 memory resting T cells and monocytes were lower in islets of T2D patients. The infiltrated immune cells in T2D pancreatic islet were associated with these six ICGs. Finally, the expression levels of four ICGs were confirmed by RT-PCR, and three ICGs were validated in another independent dataset. Conclusion: In conclusion, the identified ICGs may play an important role in T2D. Identification of these differential genes may provide new clues for the diagnosis and treatment of T2D.

Self-Reported Outdoor Light Exposure Time and Incident Heart Failure.

BACKGROUND: A healthy lifestyle is an important factor for preventing heart failure. However, the association between outdoor light exposure time and heart failure is still unknown. The aim of this study was to examine the association between outdoor light exposure time and the incidence of heart failure. METHODS AND RESULTS: This cohort study included participants from the UK Biobank recruited from 2006 to 2010 who were 40 to 70 years of age and free of heart failure at baseline. The mean follow-up time was 12.61 years. The outdoor light exposure time was self-reported at baseline. A restricted cubic spline was performed to examine the potential nonlinear relationship between outdoor light exposure and the incidence of heart failure. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% CIs. During a mean follow-up of 12.61 years, 13 789 participants were first diagnosed with heart failure. There was a nonlinear (J-shaped) trend between outdoor light time and heart failure risk. Cox proportional hazard regression models showed that, compared with participants who received an average of 1.0 to 2.5 hours of outdoor light per day, those with <1.0 hours or >2.5 hours had a higher risk of heart failure after the model was adjusted for age and sex (<1.0 hours: HR, 1.27 [95% CI, 1.18-1.36]; >2.5 hours: HR, 1.11 [95% CI, 1.07-1.15]). These associations were still significant in the fully adjusted models (<1.0 hours: HR, 1.10 [95% CI, 1.03-1.18]; >2.5 hours: HR, 1.07 [95% CI, 1.03-1.11]). CONCLUSIONS: We found a J-shaped association between outdoor light exposure time and the risk of incident heart failure, suggesting that moderate exposure to outdoor light may be a prevention strategy for heart failure.

Associations of a proinflammatory diet, habitual salt intake, and the onset of type 2 diabetes: A prospective cohort study from the UK Biobank.

AIM: To explore the relationship between proinflammatory diet, habitual salt intake and the onset of type 2 diabetes. METHODS: This prospective study was conducted among 171 094 UK Biobank participants who completed at least one 24-h dietary questionnaire and were free of diabetes at baseline. Participants were followed up until 1 March 2023 for type 2 diabetes incidence, with diagnosis information obtained from linked medical records. An Energy-adjusted Diet Inflammatory Index (E-DII) was calculated based on 28 food parameters. Habitual salt intake was determined through the self-reported frequency of adding salt to foods. The associations between E-DII, habitual salt intake and type 2 diabetes incidence were tested by the Cox proportional hazard regression model. RESULTS: Over a median follow-up period of 13.5 years, 6216 cases of type 2 diabetes were documented. Compared with participants with a low E-DII (indicative of an anti-inflammatory diet), participants with a high E-DII (indicative of a proinflammatory diet) had an 18% heightened risk of developing type 2 diabetes. The association between E-DII and type 2 diabetes tends to be linear after adjustment for major confounders. Participants with a proinflammatory diet and always adding salt to foods had the highest risk of type 2 diabetes incidence (hazard ratio 1.60, 95% confidence interval 1.32-1.94). CONCLUSIONS: Our findings indicate that a proinflammatory diet and higher habitual salt intake were associated with an increased risk of type 2 diabetes. These results support the public health promotion of an anti-inflammatory diet and reducing salt intake to prevent the onset of type 2 diabetes.

Obesity Patterns, Metabolic Abnormality, and Diabetic Kidney Disease in Patients with Type 2 Diabetes.

Objective: Obesity has been identified as a risk factor for chronic kidney disease. However, the impact of obesity, with or without a metabolically healthy condition, on diabetic kidney disease (DKD) remains unclear. We aimed to examine the associations of obesity patterns and metabolic abnormalities with the prevalence of DKD. Methods: This cross-sectional study included 4079 patients with type 2 diabetes from eleven communities in Shanghai, China. General obesity was assessed by body mass index (BMI) and abdominal obesity assessed by waist-to-hip ratio. Metabolic abnormalities were determined according to the Adult Treatment Panel III criteria. DKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2 or urinary albumin-creatinine ratio ≥30 mg/g. Poisson regression model with inverse probability of treatment weighting was used to estimate prevalence ratios (PRs) and 95% CIs. Results: Higher BMI and WHR were each associated with a greater prevalence of DKD after mutual adjustment. When considered jointly, patients with both general obesity and abdominal obesity had the highest odds of DKD (PR 1.51, 95% CI 1.29-1.76). The associations of BMI and WHR with prevalent DKD were mainly observed in patients with use of antidiabetic drugs but not in those without drug use. Compared with normal-weight patients with 0-1 metabolic abnormality, patients who were overweight or obese with 0-1 metabolic abnormality showed increased odds of DKD. The PRs (95% CI) of DKD for patients with both overweight/obesity and abdominal obesity who had 0-1, 2, and 3 metabolic abnormalities were 1.59 (1.20-2.10), 1.68 (1.29-2.18), and 2.16 (1.67-2.78), respectively, relative to those with normal BMI and no abdominal obesity who had 0-1 metabolic abnormality. Conclusion: BMI and WHR were positively associated with DKD prevalence. Obesity composite and metabolic abnormalities had an additive effect on the odds of DKD. Further longitudinal studies are warranted to elucidate the role of obesity and metabolic abnormalities in the development of DKD.

Association of follicle-stimulating hormone with lipid profiles in older women: a cross-sectional SPECT-China study.

AIMS: Follicle-stimulating hormone (FSH) is associated with higher risks of metabolic syndrome and diabetes in menopausal women. We aimed to investigate whether FSH was associated with the lipid profile in women older than 55 years. DESIGN: The data were obtained from a cross-sectional study. PARTICIPANTS: Our data were from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors (China, including Shanghai and Zhejiang, Jiangxi and Anhui provinces). A total of 1795 women older than 55 years were selected. METHODS: Morning serum sex hormones and lipid profiles were measured. Linear and logistic regression analyses were used to analyse the data. RESULTS: Lower FSH was associated with lower high-density lipoprotein cholesterol (HDL-C) and higher triglycerides (TG), total cholesterol (TC)/HDL-C ratio and low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio (all p for trend <0.05) after adjusting for age and other sex hormones. After further adjustment for body mass index, diabetes and hypertension, the associations of FSH with the lipid profile weakened, but the associations of FSH quartiles with HDL-C and the TC/HDL-C ratio were still significant (both p for trend <0.05). Compared with women in the highest FSH quartile, the odds of low HDL-C (HDL-C<1.04 mmol/L) in women in the lowest FSH quartile were 5.25 (95% CI 1.60 to 17.26) (p for trend <0.05) in the fully adjusted model, and the odds of TC≥6.22 mmol/L, TGs≥2.26 mmol/L and LDL-C≥4.14 mmol/L were not significant. Luteinising hormone did not show a significant association with dyslipidaemia. CONCLUSION: Lower FSH was associated with a worse lipid profile in women older than 55. Diabetes, adiposity and hypertension mostly explained the association of FSH with TGs and the LDL-C/HDL-C ratio but only partially explained the associations of FSH with HDL-C and the TC/HDL-C ratio.

Sweetened beverages and incident heart failure.

AIMS: Recent studies have demonstrated the associations of the consumption of different beverages with cardiometabolic diseases, whereas no studies have investigated such associations in heart failure (HF). Thus, this study aimed to explore the associations of the consumption of sugar-sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and pure fruit/vegetable juices (PJs) with the risk of incident HF. METHODS AND RESULTS: This prospective cohort study included 209 829 participants in the UK Biobank who completed at least one 24-h diet questionnaire and who were free of baseline HF. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). During a median follow-up of 9.9 years, 4328 incident HF cases were recorded. Compared to corresponding non-consumers, individuals who consumed >2 L/week SSBs or ASBs had an increased risk of HF (HR: 1.22, 95% CI: 1.08-1.38 and HR: 1.30, 95% CI: 1.16-1.47, respectively) in the multivariate adjusted model. An inverse association was observed between the consumption of >0-1 L/week PJs and the risk of HF (HR, 0.90; 95% CI, 0.83-0.98). Additionally, a significant interaction was observed between PJ consumption and sleep duration on HF risk (P for interaction = 0.030). CONCLUSIONS: Increased consumption of SSBs or ASBs may be an independent risk factor for HF, whereas moderate intake of PJs may have a protective effect on HF.

High intake of sugar-sweetened or artificially sweetened beverages was associated with an increased risk of heart failure, and moderate intake of pure fruit/vegetable juices was inversely associated with incident heart failure. Consumption of artificially sweetened beverages is a risk factor for heart failure; thus, it may not be a safe alternative to sugar. Moderate consumption of pure fruit/vegetable juices may be a preventive strategy for heart failure.

Association Between Uric Acid to HDL Cholesterol Ratio and Diabetic Complications in Men and Postmenopausal Women.

Aim: Previous studies have implicated the uric acid to high-density lipoprotein cholesterol (HDL-C) ratio (UHR) was associated with type 2 diabetes. However, the association between UHR and diabetes-related vascular damages is still unclear. Methods: The total of 4551 patients with type 2 diabetes from the cross-sectional Environmental Pollutant Exposure and Metabolic Diseases in Shanghai study (METAL study) were enrolled. UHR was calculated as uric acid to HDL-C ratio. Cardiovascular disease (CVD) was defined as previously diagnosed with stroke, coronary heart disease, or peripheral arterial disease. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate ≤60 mL/min/1.73 m2 and/or urinary albumin to creatinine ratio ≥30 mg/g. Fundus image was examined by trained individuals and degree of diabetic retinopathy (DR) was evaluated. Results: UHR was positively correlated with CVD (OR = 1.28, 95% CI: 1.02-1.61) and CKD (OR = 1.78, 95% CI: 1.39-2.27) after adjusting for all confounders. No association was found between UHR and DR. In stratified analyses, UHR was predominantly correlated with CVD in diabetic patients with age older than 65 (OR = 1.41, 95% CI: 1.08-1.85), female (OR = 1.43, 95% CI: 1.06-1.94) and BMI≥24kg/m2 (OR = 1.57, 95% CI: 1.17-2.11). A 1-SD increment of UHR was also positively associated with CVD (OR 1.26, 95% CI 1.03, 1.15) and CKD (OR 1.28, 95% CI 1.20,1.39). UHR was positively associated with CKD in all subgroups analysis. No significant interaction effect was observed between UHR and all subgroup variables in CVD and CKD risk. Conclusion: Our study reported a positive association between the UHR and diabetic-related vascular complications in men and postmenopausal women. The relationship between the UHR and DR seems to be uncertain and requires further investigation. And no significant interaction effect was observed between the UHR and all subgroup variables in CVD and CKD risk.

Blood Lead Level Is Associated with Visceral Adipose Dysfunction in Patients with Type 2 Diabetes.

We aimed to explore whether an elevated blood lead level (BLL) is associated with visceral adipose dysfunction in patients with type 2 diabetes mellitus (T2DM). Four thousand one hundred and fourteen diabetic participants were enrolled from seven communities in Shanghai in 2018 in the cross-sectional METAL study. BLL was measured by graphite furnace atomic absorption spectrometry. Visceral adiposity index (VAI) and lipid accumulation product (LAP)were calculated by simple anthropometric and biochemical parameters. We found that medians (IQR) of BLL were 26.0 µg/L (18.0-37.0) for men and 25.0 µg/L (18.0-35.0) for women, respectively. In men, each doubling of BLL was associated with a 2.0% higher VAI (95% CI, 0.6 to 3.5%) and 1.8% higher LAP (95% CI, 0.2 to 3.3%) after full adjustment. Using the lowest BLL quartile as the referent group, significant positive trends were observed for BLL with VAI and LAP. In women, each doubling of BLL was associated with a 1.9% higher LAP (95% CI, 0.6 to 3.1%). Additionally, there was a marginally significant positive association between BLL and VAI, either using log2-transformed concentrations as continuous variables or categorized in quartiles. In conclusion, lead exposure is associated with visceral adipose dysfunction in patients with T2DM. Further prospective studies are warranted to confirm our findings.

The associations of total testosterone with probable nonalcoholic steatohepatitis and nonalcoholic fatty liver disease fibrotic progression in men with type 2 diabetes: a cross-sectional study.

BACKGROUND: Testosterone has an impact on metabolic disorders and men with type 2 diabetes mellitus (T2DM) are predisposed to hypogonadism; meanwhile, patients with T2DM have higher risk of NAFLD. Therefore, we speculate that testosterone may affect the progression of NAFLD in T2DM patients and we aim to investigate whether total testosterone is associated with NAFLD progression in men with T2DM. METHODS: A cross-sectional study. A total of 1782 male participants with T2DM were enrolled from seven communities in Shanghai. Probable nonalcoholic steatohepatitis (NASH) was defined by the concurrence of NAFLD and metabolic syndrome (MetS). NAFLD fibrosis score was used to identify patients with probable advanced fibrosis. Multinomial logistic regression and ordinal logistic regression was used to measure the association of total testosterone (independent variable) and the progression category of NAFLD (dependent variable). RESULTS: In male, TT quartiles were negatively associated with probable NASH (Q1 vs. Q4 OR 2.07 95% CI 1.31-3.28, P for trend = 0.001) and inflammatory progression of NAFLD with OR of 1 SD increment of ln (TT) 0.81 (95% CI 0.72-0.92, P for trend < 0.001), but positively with fibrotic progression (Q1 vs. Q4 OR 0.45, 95% CI 0.29-0.72, P for trend = 0.001) with OR of 1 SD increment of ln (TT) 1.24 (95% CI 1.07-1.45). According to stratified analyses, for inflammatory progression, the interactions of age strata, duration of diabetes strata, and dyslipidemia status with 1 SD increment of ln (TT) were significant (P for interaction 0.007, 0.003, and 0.012, respectively); as for fibrotic progression, we found no interactions (all P for interaction ≥ 0.05). CONCLUSIONS: Different associations between TT and inflammatory and fibrotic progression of NAFLD in male were observed, suggesting different roles of TT in inflammatory and fibrotic stages of NAFLD.

Exposure to lead and cadmium is associated with fasting plasma glucose and type 2 diabetes in Chinese adults.

AIMS: Exposure to lead and cadmium has been associated with type 2 diabetes, but the results are largely inconsistent, and little is known about their joint effect. We aimed to investigate the associations of lead and cadmium co-exposure with fasting plasma glucose (FPG) and type 2 diabetes. MATERIALS AND METHODS: The study included 5732 participants aged ≥18 years from 16 communities in East China. Blood levels of lead and cadmium were determined using graphite furnace atomic absorption spectrometry. Multivariable linear and logistic regression models were performed to evaluate the associations of lead and cadmium alone or in combination with FPG and diabetes. RESULTS: The median (interquartile range) values of blood lead and cadmium were 40.0 (26.8-57.9) and 1.70 (0.56-3.60) µg/L, respectively. After adjustment for potential confounders, blood lead levels were positively associated with FPG (difference comparing extreme lead quartiles = 0.11 [95% CI: 0.03, 0.20] mmol/L) and prevalent diabetes (odds ratio [OR] = 1.35 [95% CI: 1.03, 1.78]). The association between lead and diabetes was observed among participants with high cadmium, but not among those with low cadmium (P for interaction = 0.03). In the joint analysis, compared with participants with low levels of blood lead and cadmium, participants with high levels of two metals had a 0.16 (95% CI: 0.07, 0.25) mmol/L increase in FPG and a 51% (OR = 1.51, 95% CI: 1.15, 1.99) increase in odds of diabetes. CONCLUSIONS: Our findings suggest that lead and cadmium co-exposure is significantly associated with elevated FPG and type 2 diabetes in the general population.

Joint exposure to positive affect, life satisfaction, broad depression, and neuroticism and risk of cardiovascular diseases: A prospective cohort study.

BACKGROUND AND AIMS: Psychologic wellbeing can impact cardiovascular health. We aimed to evaluate the joint association of multiple psychologic wellbeing factors with cardiovascular diseases (CVD) and examine whether this association was modified by genetic susceptibility. METHODS: In the UK Biobank, 126,255 participants free of CVD (coronary heart disease [CHD], stroke, and heart failure [HF]) at baseline, who completed a questionnaire on psychological factors, were included. The psychological wellbeing score was calculated by four factors: happiness, life satisfaction, broad depression, and neuroticism. Cox proportional hazard models were used to assess the association between the psychological wellbeing score and CVD risk. RESULTS: During the median follow-up of 11.5 years, 10,815 participants had newly diagnosed CVDs. Low life satisfaction, the presence of depression, and neuroticism score ≥1 were significantly associated with an increased risk of CVD in the multivariable-adjusted model. Through decreasing the psychological wellbeing score, there were significant increasing linear trends in the risk of CVD, CHD, stroke, and HF (all p for trend < 0.001). Participants with the lowest psychological wellbeing score had the highest risk for CVD (HR 1.51, 95% CI 1.42-1.61). Women were more susceptible to worse psychological wellbeing status for CVD than men (p for interaction = 0.009). The associations of the psychological wellbeing score with CVD were consistent across genetic risk (p for interaction >0.05). When considered jointly, participants exposed to high-risk psychological wellbeing and genetic status had a 2.70-fold (95% CI 2.25-3.24) risk for CHD. CONCLUSIONS: Joint exposure to multiple psychological wellbeing factors was associated with increased risks of incident CVD in an additive manner, regardless of genetic susceptibility.

Cardiovascular and renal burdens among patients with MAFLD and NAFLD in China.

Background/Purpose: Metabolic associated fatty liver disease (MAFLD) was proposed as a new definition to put emphasis on the metabolic aspects of nonalcoholic fatty liver disease (NAFLD). We aim to compare the cardiovascular and renal burden between MAFLD and NAFLD patients. Methods: 12183 participants were enrolled in East China. The cardiovascular burden (Framingham risk score and previous cardiovascular diseases (CVD)) and renal burden (eGFR and chronic kidney disease (CKD)) were measured. Results: The risk of hypertension, dyslipidemia, diabetes, overweight/obesity, and central obesity of MAFLD patients were higher than those of NAFLD. Patients with MAFLD have a similar or higher beta coefficients in Framingham risk score [beta (95%CI): male 0.062 (0.055,0.069) vs 0.041 (0.033,0.048); female 0.014 (0.012,0.016) vs 0.012 (0.01,0.014)], and higher odds ratio in previous CVD [odds ratio (95%CI): male 1.50 (1.22,1.85) vs 1.35 (1.1,1.66); female 1.58 (1.33,1.87) vs 1.45 (1.22,1.72)], compared with those with NAFLD. However, compared with males with MAFLD, the odds ratio of CKD was higher in those with NAFLD [eGFR: -2.731 (-3.422, -2.041) vs-3.578 (-4.268, -2.887). CKD: 1.44 (1.05,1.96) vs 1.56 (1.14,2.12)]. In female, CKD was only marginally associated with NAFLD [0.8 (0.62,1.02), P=0.075], but not MAFLD [0.87 (0.68,1.11), P=0.268]. Conclusions: Patients with MAFLD have a similar or higher risk of future and previous CVD compared with those with NAFLD, but the risk of CKD was higher in male with NAFLD.

Lead exposure and impaired glucose homeostasis in Chinese adults: A repeated measures study with 5 years of follow-up.

Experimental studies suggest the diabetogenic effects of lead, but relevant data in humans are limited and have been primarily based on cross-sectional study design. We aimed to prospectively examine the association between lead exposure and glucose homeostasis in general population using repeated measurements. This cohort study included 5505 Chinese adults free of glucose-lowering medication use at baseline in 2014 and followed up 5 years later. Blood lead and glucose metabolic traits including fasting plasma glucose (FPG), fasting serum insulin, the homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA of beta-cell function (HOMA-B) were measured at baseline and follow-up. Linear mixed models and linear regression models were performed to evaluate the associations between blood lead and markers of glucose homeostasis. After full adjustment for confounders including BMI, an interquartile range (IQR) increase in blood lead levels was associated with a 2.26 % increase in FPG (95 % CI: 0.16 %, 4.39 %) and an 11.3 % decrease in HOMA-B (95 % CI: - 19.1 %, - 2.71 %) in women. The odds ratios of hyperglycemia and beta-cell dysfunction corresponding to an IQR increase in blood lead levels were 1.39 (95 % CI: 0.99, 1.95) and 1.74 (95 % CI: 1.00, 3.03), respectively. Similar results were found for 5-year changes of glucose metabolic markers. Compared with the first quartile of baseline lead levels, the highest lead quartile was associated with an additional 3.03 % increase in FPG (95 % CI: 0.84 %, 5.26 %) and an additional 13.3 % decrease in HOMA-B (95 % CI: - 20.4 %, - 5.53 %) in women during follow-up. We observed no overall associations between blood lead levels and glucose metabolic markers in men. Our findings provide suggestive evidence that environmental exposure to lead might contribute to sex-dependent disruption of glucose homeostasis in general adult population.

The Association Between Hypertriglyceridemic-Waist Phenotype and Chronic Kidney Disease in Patients with Type 2 Diabetes: A Cross-Sectional METAL Study.

Background: The aim of this study was measuring the association between the hypertriglyceridemic-waist (HTGW) phenotype and chronic kidney disease in a large type 2 diabetes population. Methods: A total of 4254 diabetic patients from the cross-sectional Environmental Pollutant Exposure and Metabolic Diseases in Shanghai (METAL) study were enrolled. The hypertriglyceridemic-waist (HTGW) phenotype was defined as the presence of an elevated waist circumference (WC) and elevated triglyceride (TG) concentration. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2 or urinary albumin creatinine ratio (uACR) more than 30 mg/g. Linear and multiple logistic regression models were used for measuring the association between HTGW phenotype and chronic kidney disease. Results: The prevalence of CKD was 29% and 35.8% in total participants and participants with HTGW phenotype, respectively. Subjects in the HTGW phenotype group were more likely to have CKD (OR 1.47, 95% CI: 1.11, 1.95) compared with subjects in the normal waist circumference and normal triglycerides (NTNW) group. HTGW phenotype was both associated with the increasing risk of decreased eGFR (OR 1.31, 95% CI: 1.02, 1.75) and elevated uACR (OR 1.57, 95% CI: 1.18, 2.11). Furthermore, the stratified analysis showed that the strongest positive association between HTGW phenotype and CKD presence was found in the subgroup of presence of hypertension. The associations were all fully adjusted for age, sex, BMI, current smoking, current drinking and other confounding factors. Conclusion: Our study suggested a positive association between the HTGW phenotype and CKD in Chinese type 2 diabetes patients. Further prospective studies are needed to confirm our findings and to investigate the underlying biological mechanisms.

Joint Exposure to Positive Affect, Life Satisfaction, Depressive Symptoms, and Neuroticism and Incident Type 2 Diabetes.

CONTEXT: Whether the psychological wellbeing status could be a risk factor for type 2 diabetes is unclear. OBJECTIVE: We aimed to measure the association between combined psychological wellbeing factors and type 2 diabetes and investigate whether this association was modified by genetic predisposition. METHODS: Prospective cohort study from the UK Biobank. In total, 127 496 participants who completed a psychological wellbeing questionnaire and did not have type 2 diabetes at baseline (2006-2010) were included; among them, 88 584 (69.5%) were analyzed to determine their genetic predisposition. The main outcome measure was incident type 2 diabetes. RESULTS: During the median follow-up of 10.0 years, 2547 incident type 2 diabetes cases were documented. Moderate to extreme unhappiness, satisfaction score ≤3, presence of broad depression, and a neuroticism score ≥3 were all significantly and independently associated with an increased risk of diabetes. When considered as a combination indicator, compared with individuals in the highest quartile of the psychological wellbeing score, the fully adjusted hazard ratios (95% CI) of type 2 diabetes were 1.41 (1.21-1.65) in the third quartile, 1.45 (1.24-1.69) in the second quartile, and 1.73 (1.48-2.01) in the lowest quartile. In the stratified analysis, we observed significant interactions between age and physical activity, and type 2 diabetes (Pinteraction < .001 and 0.049, respectively). However, there was no significant interaction between the psychological wellbeing score and genetic susceptibility to diabetes (Pinteraction = .980). CONCLUSION: Worse overall psychological wellbeing was associated with a significantly increased risk of type 2 diabetes in a dose-response fashion regardless of genetic predisposition.

Non-alcoholic fatty liver disease, sleep behaviors, and incident type 2 diabetes.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is associated with incident type 2 diabetes; however, the extent to which NAFLD may confer its risk remains uncertain, especially in Europeans. Emerging evidence suggests that sleep behaviors are linked to NAFLD and diabetes. We aimed to measure whether sleep behaviors modified the association between NAFLD and incident type 2 diabetes. METHODS: This prospective cohort study included 365 339 participants without type 2 diabetes at baseline in UK Biobank data. Five sleep behaviors, including sleep duration, insomnia, snoring, chronotype, and daytime sleepiness, were collected from the questionnaire. Overall sleep patterns were created by summing the five scores. Liver steatosis was based on the fatty liver index. RESULTS: During a median follow up of 11.0 years, we documented 8774 patients with incident type 2 diabetes. NAFLD was significantly associated with increased diabetes risk. Sleeping 7-8 h/day, no insomnia, no self-reported snoring, and no frequent daytime sleepiness were independently associated with incident type 2 diabetes, with a 20%, 18%, 16%, and 31% lower risk, respectively. About 33.8% and 33.5% of type 2 diabetes events in this cohort could be attributed to NAFLD and poor sleep pattern, respectively. Participants with NAFLD and poor sleep pattern showed the highest risk of type 2 diabetes (relative risk 3.17, 95% confidence interval 2.80, 3.59). Sleep pattern (healthy, intermediate, and poor) did not significantly modify the association between NAFLD and type 2 diabetes. However, when studying separately, we found a significant interaction between NAFLD and insomnia on the risk of incident type 2 diabetes (P for interaction = 0.003). CONCLUSION: In this large prospective study, both NAFLD and some sleep behaviors were risk factors for type 2 diabetes. Although overall sleep pattern did not modify the association between NAFLD and type 2 diabetes, certain sleep behavior, especially insomnia, showed the modification effect.

Chronic lead exposure induces fatty liver disease associated with the variations of gut microbiota.

BACKGROUND: Lead (Pb) has been suggested as an endocrine-disrupting chemical. However, few studies have investigated the association between chronic Pb exposure and fatty liver disease. OBJECTIVES: We aimed to investigate the association of chronic Pb exposure with fatty liver disease and whether the variations of the gut microbiota involve in the mechanism of the fatty liver disease induced by chronic Pb exposure. METHODS: We conducted a cross-sectional study of 3066 rural participants in East China. Blood lead level (BLL) was detected, and abdominal ultrasonography was used to diagnose hepatic steatosis. Both the definition of non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) were used. Wistar rats were randomly divided into two groups and each group was exposed to 0 or 0.05% w/v Pb through drinking water for 28 weeks. The relevant parameters of hepatic lipid metabolism and gut microbiota were analyzed. RESULTS: In humans, after adjusting for potential confounders, the odds of having NAFLD and MAFLD were significantly increased by 54% and 52% in the participants in the fourth BLL quartile (OR 1.54, 95% CI 1.24, 1.91 and OR 1.52, 95% CI 1.22, 1.89). In the rats, chronic Pb exposure induced the increased visceral fat, hepatic steatosis, and dysbiosis of the gut microbiota, including the decrease of richness, diversity, evenness and phylogenetic diversity of the gut microbiota and the significant alternations of the gut microbiota composition, particularly, the decrease of the relative abundance of Coprococcus and Oscillospira at the genus level. CONCLUSIONS: Chronic Pb exposure could induce fatty liver disease, which may be associated with the variations of the gut microbiota.

Sleep Patterns, Genetic Susceptibility, and Incident Chronic Kidney Disease: A Prospective Study of 370 671 Participants.

OBJECTIVES: Unhealthy sleep behaviors may be potential risk factors for chronic kidney disease (CKD). We aimed to examine the associations of combined sleep patterns and genetic susceptibility with incident CKD. METHODS: This large-scale prospective cohort study included 370,671 participants without CKD at baseline (2006-2010) in UK Biobank data. Five sleep behaviors were made up of sleep duration, insomnia, snoring, chronotype, and daytime sleepiness according to questionnaire. Overall sleep patterns by summing the five scores were created. Weighted genetic risk score of kidney function was calculated. Incident CKD was recorded from death register, primary care, and hospital inpatient records. A subset of 41,130 individuals who participated both the initial assessment visit and follow-up visit (2012+) was also used. RESULTS: During a median follow-up of 10.6 years (about 3.9 million person-years), we documented 6,365 patients with incident CKD. In five sleep behaviors, sleep 7-8 h/day, free of insomnia and no frequent daytime sleepiness were independently associated with incident CKD, with a 12% (95%CI 7-16), 9% (3-14), 13% (9-18) lower risk, respectively. Compared to those with a sleep score of 0-1, participants with a score of 5 had a 21% (10-31%) lower risk of CKD. 17.1% of CKD in this cohort could be attributed to total poor sleep pattern. Participants with high genetic risk and intermediate or poor sleep pattern showed the highest risk of CKD (OR = 2.58, 95%CI 2.24-2.96; OR = 2.59, 95%CI 2.02-3.32, respectively), although there was no significant interaction between sleep patterns and genetic risk categories. Among individuals who participated both the initial assessment visit and follow-up visit, we found that the association between amelioration of sleep pattern and risk of CKD was significant after fully adjustment (OR = 0.60, 95%CI 0.36-0.99), compared with group of stable sleep pattern. CONCLUSION: In this large prospective study, participants with a healthy sleep pattern was associated with a significant reduction of incident CKD risk no matter they had a high, intermediate, or low genetic risk.

Association between sex hormone-binding globulin and kidney function in men: results from the SPECT-China study.

BACKGROUND: The association between sex hormone-binding globulin (SHBG) and renal function has rarely been reported in men. We aimed to investigate the above association in a community-based Chinese population. METHODS: A total of 5027 men were included from the survey on prevalence for metabolic diseases and risk factors, which is a population-based study conducted from 2014 to 2016 in Eastern China. The estimated glomerular filtration rate (eGFR) was calculated according to the chronic kidney disease Epidemiology Collaboration equation. Low eGFR was defined as eGFR <60 mL·min -1 ·1.73 m -2 . RESULTS: After adjusting for age, smoking, metabolic factors, and testosterone, through increasing quartiles of SHBG, a significantly positive association between SHBG quartiles and eGFR was detected in men (Q1 vs. Q4, ß -2.53, 95% confidence interval -3.89, -1.17, Ptrend < 0.001). Compared with the highest quartile of SHBG, SHBG in the lowest quartile was associated with 96% higher odds of low eGFR (odds ratio 1.96, 95% confidence interval 1.10, 3.48) in the model after full adjustment. According to the stratified analyses, the associations between a 1-standard deviation increase in serum SHBG and the prevalence of low eGFR were significant in men aged ≥60 years old, waist circumference <90 cm, diabetes (no), hypertension (yes), dyslipidemia (no), and nonalcoholic fatty liver disease (no). CONCLUSIONS: Lower serum SHBG levels were significantly associated with lower eGFR and a higher prevalence of low eGFR in Chinese men independent of demographics, lifestyle, metabolic-related risk factors, and testosterone. Large prospective cohort and basic mechanistic studies are warranted in the future.

Moderation effect of economic status in the association between early life famine exposure and MAFLD in adulthood.

BACKGROUND & AIMS: The double burden of malnutrition (DBM) in China resulted in high prevalence of diet-related non-communicable diseases. The aim of this study was to analyse the moderation of economic status in the association between early famine exposure and metabolic dysfunction associated with fatty liver disease (MAFLD) in adulthood. METHODS: 10 190 participants in the SPECT-China study enrolled from 2014 to 2016 were included in this study. Participants with fetal famine exposure (birth year 1959-1962) or early-childhood famine exposure (birth year 1955-1958) formed the exposure group. The associations with MAFLD were assessed via regression analyses. RESULTS: In men, economic status could not moderate the association between early life famine and MAFLD after adjusting for age, excess alcohol drinking, current smokers, famine severity, waist circumference, diabetes, hypertension, and dyslipidemia (P for interaction = .52). However, in women and in the total population, economic status could moderate the association between early life famine and MAFLD after adjusting for the above confounders (P for interaction = .01). In the total population and in women, early life famine exposure was associated with MAFLD in both low economic status and high economic status. However, in men, early life famine exposure was not associated with MAFLD in low economic status, while in high economic status, early-childhood famine exposure was associated with MAFLD. CONCLUSIONS: Economic status could moderate the association between early life famine exposure and MAFLD in total population and in women.