Leisure Sedentary Behavior, Physical Activities, and Cardiovascular Disease Among Individuals With Metabolic Dysfunction-Associated Fatty Liver Disease.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease is a significant risk factor for cardiovascular disease (CVD). This study assesses the association between leisure-time physical activity, sedentary behavior, and CVD risk among patients with metabolic dysfunction-associated fatty liver disease, considering genetic predisposition to CVD. METHODS: This cohort study included 157 794 participants with metabolic dysfunction-associated fatty liver disease from the UK Biobank who were free of CVD at baseline. The study measured leisure-time sedentary behaviors (watching TV, using a computer, and driving) and physical activities (walking for pleasure, light and heavy do-it-yourself activities, strenuous sports, and other exercises) in terms of frequency and duration over the 4 weeks before assessment. Both a Cox proportional hazard model and an isotemporal substitution model were utilized in the study to assess the association between leisure sedentary behavior, physical activities, and CVD risk. RESULTS: During a median 12.5 years of follow-up, 26 355 CVD cases were reported, including 19 746 coronary heart disease, 4836 stroke, and 7398 heart failure cases. High physical activity levels were linked to a significantly lower risk of CVD (21%), coronary heart disease (20%), stroke (15%), and heart failure (31%). In contrast, individuals with >6.5 h/d of sedentary behavior faced a 16% to 21% higher risk of these conditions compared with those with ≤3.5 h/d. Notably, replacing 30 minutes of inactivity with physical activity reduced CVD risks by 3% to 16%, particularly with strenuous sports. A significant interaction was observed between physical activity, sedentary behavior, and genetic predisposition in relation to stroke risk. CONCLUSIONS: Among patients with metabolic dysfunction-associated fatty liver disease, higher leisure-time physical activity levels correlate with reduced CVD risks, while increased sedentary behavior is linked to higher CVD risks. Replacing sedentary time with physical activity consistently shows benefits in reducing CVD outcomes, irrespective of genetic predisposition.

Assessing the impact of type 2 diabetes on mortality and life expectancy according to the number of risk factor targets achieved: an observational study.

BACKGROUND: Type 2 diabetes (T2D) is associated with an increased risk of premature death. Whether multifactorial risk factor modification could attenuate T2D-related excess risk of death is unclear. We aimed to examine the association of risk factor target achievement with mortality and life expectancy among patients with T2D, compared with individuals without diabetes. METHODS: In this longitudinal cohort study, we included 316 995 participants (14 162 with T2D and 302 833 without T2D) free from cardiovascular disease (CVD) or cancer at baseline between 2006 and 2010 from the UK Biobank. Participants with T2D were categorised according to the number of risk factors within target range (non-smoking, being physically active, healthy diet, guideline-recommended levels of glycated haemoglobin, body mass index, blood pressure, and total cholesterol). Survival models were applied to calculate hazard ratios (HRs) for mortality and predict life expectancy differences. RESULTS: Over a median follow-up of 13.8 (IQR 13.1-14.4) years, deaths occurred among 2105 (14.9%) participants with T2D and 18 505 (6.1%) participants without T2D. Compared with participants without T2D (death rate per 1000 person-years 4.51 [95% CI 4.44 to 4.57]), the risk of all-cause mortality among those with T2D decreased stepwise with an increasing number of risk factors within target range (0-1 risk factor target achieved: absolute rate difference per 1000 person-years 7.34 [4.91 to 9.78], HR 2.70 [2.25 to 3.25]; 6-7 risk factors target achieved: absolute rate difference per 1000 person-years 0.68 [-0.62 to 1.99], HR 1.16 [0.93 to 1.43]). A similar pattern was observed for CVD and cancer mortality. The association between risk factors target achievement and all-cause mortality was more prominent among participants younger than 60 years than those 60 years or older (P for interaction = 0.012). At age 50 years, participants with T2D who had 0-1 and 6-7 risk factors within target range had an average 7.67 (95% CI 6.15 to 9.19) and 0.99 (-0.59 to 2.56) reduced years of life expectancy, respectively, compared with those without T2D. CONCLUSIONS: Individuals with T2D who achieved multiple risk factor targets had no significant excess mortality risk or reduction in life expectancy than those without diabetes. Early interventions aiming to promote risk factor modification could translate into improved long-term survival for patients with T2D.

Association of combined healthy lifestyle with risk of adverse outcomes in patients with prediabetes.

OBJECTIVE: Prediabetes and lifestyle factors have been associated with the risks of multiple adverse outcomes, but the effect of a healthy lifestyle on prediabetes-related complications remains unknown. We aimed to investigate whether the risks of multiple adverse outcomes including incident type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and chronic kidney disease (CKD) among individuals with prediabetes can be offset by a broad combination of healthy lifestyle factors. METHODS: This prospective study used data from the UK Biobank cohort. An overall lifestyle score ranging from 0 to 6 was created with 1 point for each of the 6 healthy lifestyle factors: no current smoking, moderate alcohol consumption, regular physical activity, healthy diet, no overweight or obese, and adequate sleep duration. T2DM, CVD, and CKD were ascertained during a median follow-up of 14 years. Cox proportional hazard regression models were used to estimate the associations. Sensitivity analyses were performed to test the robustness of the results. RESULTS: We included 202,993 participants without T2DM, CVD, and CKD at baseline (mean age 55.5 years [SD 8.1]; 54.7% were women). Among these participants, 6,745, 16,961, and 6,260 participants eventually developed T2DM, CVD, and CKD, respectively. Compared with the participants with normoglycaemia, those with prediabetes showed a higher risk of these adverse outcomes. In addition, those prediabetic participants with a lifestyle score of 0-1 had a significantly higher risk of T2DM (hazard ratio [HR] 16.73, 95% CI 14.24, 19.65), CVD (HR 1.96, 95% CI 1.74, 2.21), and CKD (HR 1.92, 95% CI 1.58, 2.34) compared with those with no prediabetes and a score of 5-6. Moreover, among the participants with prediabetes, the HRs for T2DM, CVD, and CKD comparing a lifestyle score of 5-6 versus 0-1 decreased to 0.43 (95% CI 0.36, 0.51), 0.52 (95% CI 0.44, 0.62), and 0.60 (95% CI 0.46, 0.79), respectively. CONCLUSIONS: Combined healthy lifestyle factors were associated with a significantly lower risk of multiple adverse outcomes, including T2DM, CVD, and CKD. This indicates that prioritising multifactorial approaches to behavioural lifestyle modification is crucial for preventing and postponing the development of complications related to prediabetes.

Long-term changes in frailty and incident type 2 diabetes: A prospective cohort study based on the UK Biobank.

AIMS: To estimate the association between long-term changes in frailty and the risk of incident type 2 diabetes (T2DM) and to evaluate the effect of preventing the worsening of frailty on the risk of T2DM. METHODS: We included 348 205 participants free of baseline T2DM and with frailty phenotype (FP) data from the UK Biobank; among them, 36 175 had at least one follow-up assessment. According to their FP score, participants were grouped into nonfrailty, prefrailty and frailty groups. Frailty assessed at baseline and at follow-up was used to derive the trajectory of frailty (ΔFP). Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Compared with those in the nonfrailty group at baseline, the HRs of T2DM for the prefrailty and frailty groups were 1.38 (95% CI 1.33-1.43) and 1.69 (95% CI 1.59-1.79), respectively (both p < 0.001), in the multivariable-adjusted model. During a median follow-up of 5.4 years after the final assessment, data for 472 T2DM patients were recorded. A 1-point increase in the final FP was associated with a 25% (95% CI 1.14-1.38; p < 0.001) increased risk of T2DM. For the trajectory of frailty, each 0.5-point/year increase in ΔFP was associated with a 52% (95% CI 1.18-1.97; p < 0.001) greater risk of T2DM, independent of the FP score at baseline. Compared with those that remained in the nonfrailty group, the greatest risk of T2DM over time was prefrailty aggravation (HR 3.03, 95% CI 2.00-4.58; p < 0.001). Using the frailty index did not materially change the results. CONCLUSIONS: Long-term changes in frailty were associated with the risk of incident T2DM, irrespective of baseline frailty status. Preventing the worsening of frailty may reduce T2DM risk.

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.

Association patterns of ketone bodies with the risk of adverse outcomes according to diabetes status.

AIM: To investigate the associations between ketone bodies (KB) and multiple adverse outcomes including cardiovascular disease (CVD), chronic kidney disease (CKD) and all-cause mortality according to diabetes status. METHODS: This prospective study included 222 824 participants free from CVD and CKD at baseline from the UK Biobank. Total KB including ß-hydroxybutyrate, acetoacetate and acetone were measured by nuclear magnetic resonance. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between KB and adverse outcomes among participants with normoglycaemia, prediabetes and type 2 diabetes, respectively. RESULTS: During a mean follow-up of 14.1 years, 24 088 incident CVD events (including 17 303 coronary heart disease events, 5172 stroke events and 5881 heart failure [HF] events), 8605 CKD events and 15 813 deaths, were documented. Higher total KB significantly increased the risk of HF among participants with normoglycaemia (HR, 1.32 [95% CI, 1.17-1.49], per 10-fold increase in total KB) and prediabetes (1.35 [1.04-1.76]), and increased the risk of CKD among those with normoglycaemia (1.20 [1.09-1.33]). Elevated KB levels were associated with an increased risk of all-cause mortality across the glycaemic spectrum (1.32 [1.23-1.42] for normoglycaemia, 1.45 [1.24-1.71] for prediabetes and 1.47 [1.11-1.94] for diabetes). Moreover, a significant additive interaction between KB and diabetes status was observed on the risk of death (P = .009), with 4.9% of deaths attributed to the interactive effects. CONCLUSIONS: Our study underscored the variation in association patterns between KB and adverse outcomes according to diabetes status and suggested that KB could interact with diabetes status in an additive manner to increase the risk of mortality.

Nonlinear relationship between body mass index and serum uric acid: An observational and Mendelian randomization study among Chinese adults.

BACKGROUND AND AIMS: Conflicting evidence exists on the relationship between body mass index (BMI) and serum uric acid (SUA), and importantly, the causal role of BMI in SUA remains unclear. We aimed to evaluate the BMI-SUA relationship and its causality among Chinese adults using observational and Mendelian randomization (MR) analyses. METHODS AND RESULTS: Study included 6641 adults from East China. A genetic risk score based on 14 BMI-associated East Asian variants was formulated. One-sample MR and non-linear MR analyses assessed the causal link between BMI_GRS and SUA levels. Mean BMI levels were 24.8 (SD 3.4) and 24.3 (SD 3.6) kg/m2 in men and women, respectively. Spline models revealed gender-specific BMI-SUA associations: a reverse J-shape for men and a J-shape for women (P-values for nonlinearity <0.05). In men, BMI showed a positive correlation with SUA levels when BMI was below 29.6 kg/m2 (beta coefficient 19.1 [95 % CI 15.1, 23.0] µmol/L per 1-SD increase in BMI), while in women, BMI exhibited a negative correlation with SUA levels when the BMI was less than 21.7 kg/m2 (beta coefficient -12.9 [95 % CI -21.6, -4.1] µmol/L) and a positive correlation when BMI exceeded 21.7 kg/m2 (beta coefficient 13.3 [95 % CI 10.9, 15.8] µmol/L). Furthermore, MR analysis suggested non-linear BMI-SUA link in women but not men. CONCLUSION: Our study indicates a non-linear correlation between BMI and SUA in both genders. It is noteworthy that in women, this correlation may have a causal nature. Nevertheless, further longitudinal investigations are required to authenticate our findings.

Cardiovascular health, sleeping duration, and risk of mortality in current and former smokers.

BACKGROUND AND AIMS: To investigate the associations of ideal cardiovascular health metrics (ICVHMs) with all-cause mortality among former and current smokers compared with never smokers. METHODS AND RESULTS: A total of 378,147 participants [mean age (SD) years: 56.3 (8.1); 47.2 % men] were included from the UK Biobank cohort. The ICVHMs were combined Life's simple 7 from the American Heart Association and sleep duration time. The association was explored using COX regression models. During a median follow-up of 13.3 years, we documented 24,594 deaths. Compared with never smokers, among former smokers, the multivariable-adjusted hazard ratio (HR) for all-cause mortality was 1.82 (95%CI 1.71-1.92) for participants who had ≤2 ICVHMs and 1.03 (0.97-1.10) for participants who had ≥6 ICVHMs; among current smokers, the HRs for mortality were 2.74 (2.60-2.89) and 2.18 (1.78-2.67). The phenomenon was more pronounced among participants younger than 60 years [HR (95%CI), 1.82 (1.71-1.95) for ≤2 ICVHMs vs 1.04 (0.96-1.12) for ≥6 ICVHMs with age ≥60 years and 1.83 (1.62-2.06) vs 0.98 (0.88-1.11) with age <60 years among former smokers; 2.66 (2.49-2.85) vs 2.44 (1.84-3.24) with age ≥60 years and 2.85 (2.62-3.10) vs 1.96 (1.47-2.61) with age <60 years among current smokers]. In addition, the HR for mortality of each 1-number increment in ICVHMs was 0.87 (0.86-0.89) among former smokers and 0.91 (0.89-0.94) among current smokers. CONCLUSION: Our findings indicated the importance of adherence to have more ICVHMs in the mortality risk among former smokers, and priority of smoking cessation in current smokers. IMPLICATIONS: Studies have found that former smokers still have higher risks of lung cancer and all-cause mortality than never-smokers. The next question is whether the effects of previous or current smoking could be ameliorated by eight ideal cardiovascular health metrics (ICVHMs). We aim to explore whether ICVHMs may counteract the risk of all-cause mortality among former and current smokers. The results showed that only former smokers with ≥6 ICVHMs exhibited a comparable risk of all-cause mortality with never smokers. Furthermore, current smokers even having ≥6 ICVHMs still exhibited a higher risk of all-cause mortality compared with never smokers.

Self-reported childhood adversity, unhealthy lifestyle and risk of new-onset chronic kidney disease in later life: A prospective cohort study.

BACKGROUND: The prospective relation of childhood adversity with the risk of chronic kidney disease (CKD) remains unclear. We aimed to investigate the association of childhood adversity with new-onset CKD and examine the potential modifications by unhealthy lifestyle on this association. METHODS: A total of 115,453 adults without prior CKD at baseline were included from UK Biobank (2006-2010). Childhood adversity was retrospectively evaluated through online Childhood Trauma Screener in 2016. Six common lifestyle factors including smoking, body mass index, sleep, diet, physical activity and alcohol consumption, were combined into an unhealthy lifestyle score. New-onset CKD was the primary outcome. RESULT: The average age of participants in the study was 55.3 (SD, 7.7) years, and 39.3% of them were male. During a median follow-up duration of 14.1 years, 1905 participants developed new-onset CKD. Childhood adversity was significantly positively related with the risk of new-onset CKD in dose-response pattern. Each additional type of childhood adversity was associated with a 12% increment in the risk of developing CKD (adjusted hazard ratio (HR)1.12; 95% CI 1.08, 1.16). Among participants with high unhealthy lifestyle score, those with 4-5 types of childhood adversity increased the 1.73-fold risk of incident CKD (95% CI 1.17, 2.54) compared with those free of any childhood adversity. However, no statistically significant interaction was observed between unhealthy lifestyle and childhood adversity for new-onset CKD (P interaction = 0.734). CONCLUSIONS: Childhood adversity was significantly associated with an increased risk of new-onset CKD in a dose-response pattern regardless of unhealthy lifestyle.

Long-term exposure to ambient air pollution and risk of microvascular complications among patients with type 2 diabetes: a prospective study.

BACKGROUND: Patients with type 2 diabetes (T2D) may disproportionately suffer the adverse cardiovascular effects of air pollution, but relevant evidence on microvascular outcome is lacking. We aimed to examine the association between air pollution exposure and the risk of microvascular complications among patients with T2D. METHODS: This prospective study included 17 995 participants with T2D who were free of macro- and micro-vascular complications at baseline from the UK Biobank. Annual average concentrations of particulate matter (PM) with diameters <2.5 µm (PM2.5), <10 µm (PM10), nitrogen dioxide (NO2) and nitrogen oxides (NOx) were assessed using land use regression models. Cox proportional hazards regression was used to estimate the associations of air pollution exposure with incident diabetic microvascular complications. The joint effects of the air pollutant mixture were examined using quantile-based g-computation in a survival setting. RESULTS: In single-pollutant models, the adjusted hazard ratios (95% confidence intervals) for composite diabetic microvascular complications per interquartile range increase in PM2.5, PM10, NO2 and NOx were 1.09 (1.04-1.14), 1.06 (1.01-1.11), 1.07 (1.02-1.12) and 1.04 (1.00-1.08), respectively. Similar significant results were found for diabetic nephropathy and diabetic neuropathy, but not for diabetic retinopathy. The associations of certain air pollutants with composite microvascular complications and diabetic nephropathy were present even at concentrations below the World Health Organization limit values. Multi-pollutant analyses demonstrated that PM2.5 contributed most to the elevated risk associated with the air pollutant mixture. In addition, we found no interactions between air pollution and metabolic risk factor control on the risk of diabetic microvascular complications. CONCLUSIONS: Long-term individual and joint exposure to PM2.5, PM10, NO2 and NOx, even at low levels, was associated with an increased risk of diabetic microvascular complications, with PM2.5 potentially being the main contributor.

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.

Life's Essential 8 and risks of cardiovascular morbidity and mortality among individuals with type 2 diabetes: A cohort study.

BACKGROUND: The association of cardiovascular health levels, as measured by the Life's Essential 8 score, with cardiovascular disease (CVD) incidence and mortality among individuals with type 2 diabetes (T2D) has not been fully elucidated. METHODS: This cohort study included 15,118 participants with T2D from the UK Biobank who were free of CVD and cancer at baseline. The cardiovascular health of participants was evaluated using the Life's Essential 8 score, categorizing their health levels into low, moderate, and high based on this assessment. RESULTS: During a median follow-up period of 13.0 years, we observed a total of 4421 cases of CVD, comprising 3467 cases of coronary heart disease (CHD), 811 cases of stroke, 1465 cases of heart failure (HF), and 523 cases of CVD mortality. Compared to participants with low cardiovascular health, those with high cardiovascular health had a 52 %, 50 %, 47 %, 67 %, and 51 % lower risk of CVD, CHD, stroke, HF, and CVD mortality, respectively. Among the components of the Life's Essential 8 score, body mass index showed the highest population attributable risk of 12.1 %. Similar findings were observed in joint analyses of cardiovascular health and diabetes severity status. CONCLUSIONS: This study emphasizes the importance of maintaining good cardiovascular health among individuals with T2D to reduce their risk of CVD incidence and mortality.

The effects of vitamin D and gene polymorphisms on susceptibility to thyroid peroxidase antibody positivity.

BACKGROUND: The etiology of Hashimoto's thyroiditis (HT) involves genetic and environmental factors. There is a lack of clarity regarding the relationship between Vitamin D and HT. This study aimed to investigate the effect of Vitamin D and gene polymorphisms on thyroid peroxidase antibody (TPOAb) positivity. METHODS: A total of 9,966 participants were included from a survey conducted in East China from 2014 to 2016. We measured the levels of 25(OH)D, thyroid hormones and autoimmune antibodies. rs11675434, rs9277555, and rs301799 were genotyped. Based on these 3 SNPs, a weighted genetic risk score was calculated for TPOAb. RESULTS: The proportion of females in the TPOAb-positive group was greater than that in the TPOAb-negative group (74.2% vs. 57.2%, P<0.001). Vitamin D levels were lower in the TPOAb-positive group than in the TPOAb-negative group (40.07±11.87 vs. 40.80±12.84, P=0.01). The GG genotype of rs9277555 and the TT genotype of rs11675434 were correlated with the risk of TPOAb positivity (OR=1.34, 95% CI 1.13-1.59, P=0.001; OR=1.29, 95% CI 1.06-1.58, P=0.01). TPOAb-GRS was associated with TPOAb positivity (OR=3.17, 95% CI 1.72-5.84; P<0.001). When stratified by Vitamin D group, the association between TPOAb-GRS and TPOAb positivity existed only in the Vitamin D deficiency group (OR=3.41, 95% CI 1.73-6.70 P<0.001) but not in the control group (OR=2.45, 95% CI 0.59-10.19, P=0.22). CONCLUSIONS: This study suggested that TPOAb-GRS was associated with TPOAb positivity in the Han Chinese population, mainly due to rs9277555 and rs11675434. The hereditary effect of TPOAb positivity differed depending on Vitamin D status.

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.

Clinical risk factors and cancer risk of thyroid imaging reporting and data system category 4 A thyroid nodules.

PURPOSE: Beyond the Thyroid Imaging Reporting and Data System (TIRADS) classification of thyroid nodules, additional factors must be weighed in the decision to perform fine needle aspiration (FNA). In this study, we aimed to identify risk factors for malignancy in patients with ultrasound-classified Chinese-TIRADS (C-TIRADS) 4 A nodules. METHODS: Patients who underwent thyroid FNA at our institution between May 2021 and September 2022 were enrolled. We collected demographic data, including age, sex, previous radiation exposure, and family history. An in-person questionnaire was used to collect lifestyle data, such as smoking habits and alcohol consumption. Body mass index (BMI) was calculated. The serum levels of thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroglobulin antibody (TGAb) were measured. Prior to FNA, ultrasonic inspection reports were reviewed. The cytologic diagnoses for FNA of thyroid nodules followed the Bethesda System for Reporting Thyroid Cytopathology (2017). RESULTS: Among the 252 C-TIRADS 4 A nodules, 103 were malignant. Compared to those in the benign group, the patients in the malignant group had a younger age (42.2 ± 13.6 vs. 51.5 ± 14.0 years, P < 0.001). Logistic regression showed that advanced age was associated with a lower risk of malignancy in C-TIRADS 4 A nodules (OR = 0.95, 95% CI 0.93 ~ 0.97, P < 0.001). We demonstrated a decreased risk of malignancy in patients with 48.5 years or older. CONCLUSION: Advanced age was associated with a decreased risk of malignancy in patients with C-TIRADS 4 A nodules. This study indicated that in addition to sonographic characteristics, patient age should be considered when assessing the risk of malignancy.

Dietary pattern modifies the risk of MASLD through metabolomic signature.

Background & Aims: The EAT-Lancet Commission in 2019 advocated a plant-centric diet for health and environmental benefits, but its relation to metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. We aimed to discover the metabolite profile linked to the EAT-Lancet diet and its association with MASLD risk, considering genetic predisposition. Methods: We analyzed data from 105,752 UK Biobank participants with detailed dietary and metabolomic information. We constructed an EAT-Lancet diet index and derived a corresponding metabolomic signature through elastic net regression. A weighted polygenic risk score for MASLD was computed from associated risk variants. The Cox proportional hazards model was employed to estimate hazard ratios (HRs) and 95% CIs for the risk of MASLD (defined as hospital admission or death). Results: During a median follow-up period of 11.6 years, 1,138 cases of MASLD were documented. Participants in the highest group for the EAT-Lancet diet index had a multivariable HR of 0.79 (95% CI 0.66-0.95) for MASLD compared to the lowest group. The diet's impact was unaffected by genetic predisposition to MASLD (p = 0.42). Moreover, a robust correlation was found between the metabolomic signature and the EAT-Lancet diet index (Pearson r = 0.29; p <0.0001). Participants in the highest group for the metabolomic signature had a multivariable HR of 0.46 (95% CI 0.37-0.58) for MASLD, in comparison to those in the lowest group. Conclusions: Higher intake of the EAT-Lancet diet and its associated metabolite signature are both linked to a reduced risk of MASLD, independently of traditional risk factors. Impact and implications: Our analysis leveraging the UK Biobank study showed higher adherence to the EAT-Lancet diet was associated with a reduced risk of metabolic dysfunction-associated steatotic liver disease (MASLD). We identified a unique metabolite signature comprising 81 metabolites associated with the EAT-Lancet diet, potentially underlying the diet's protective mechanism against MASLD. These findings suggest the EAT-Lancet diet may offer substantial protective benefits against MASLD.

Sweetened Beverages, Genetic Susceptibility, and Incident Atrial Fibrillation: A Prospective Cohort Study.

BACKGROUND: An association between sweetened beverages and several cardiometabolic diseases has been reported, but their association with atrial fibrillation (AF) is unclear. We aimed to investigate the associations between consumption of sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), and pure fruit juice (PJ) and risk of consumption with AF risk and further evaluate whether genetic susceptibility modifies these associations. METHODS: A total of 201 856 participants who were free of baseline AF, had genetic data available, and completed a 24-hour diet questionnaire were included. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During a median follow-up of 9.9 years, 9362 incident AF cases were documented. Compared with nonconsumers, individuals who consumed >2 L/wk of SSB or ASB had an increased risk of AF (HR, 1.10 [95% CI, 1.01-1.20] and HR, 1.20 [95% CI, 1.10-1.31]) in the multivariable-adjusted model. A negative association was observed between the consumption of ≤1 L/wk of PJ and the risk of AF (HR, 0.92 [95% CI, 0.87-0.97]). The highest HRs (95% CIs) of AF were observed for participants at high genetic risk who consumed >2 L/wk of ASB (HR, 3.51 [95% CI, 2.94-4.19]), and the lowest HR were observed for those at low genetic risk who consumed ≤1 L/wk of PJ (HR, 0.77 [95% CI, 0.65-0.92]). No significant interactions were observed between the consumption of SSB, ASB, or PJ and genetic predisposition to AF. CONCLUSIONS: Consumption of SSB and ASB at >2 L/wk was associated with an increased risk for AF. PJ consumption ≤1 L/wk was associated with a modestly lower risk for AF. The association between sweetened beverages and AF risk persisted after adjustment for genetic susceptibility to AF. This study does not demonstrate that consumption of SSB and ASB alters AF risk but rather that the consumption of SSB and ASB may predict AF risk beyond traditional risk factors.

Association between glycemia risk index and arterial stiffness in type 2 diabetes.

AIM: This study aims to investigate the association of glycemia risk index (GRI), a novel composite metric derived from continuous glucose monitoring (CGM), with arterial stiffness in patients with type 2 diabetes. MATERIALS AND METHODS: A total of 342 adults with type 2 diabetes were enrolled between April and June 2023 from 11 communities in Shanghai, China. Medical examinations, including measurements of anthropometric parameters, blood pressure, and venous blood samples were conducted. Brachial-ankle pulse wave velocity (baPWV) was examined to evaluate arterial stiffness. All the participants underwent a 14 day CGM recording and GRI was calculated from the CGM data. RESULTS: The mean age was 70.3 ± 6.8 years, and 162 (47.4%) were male. Participants with a higher baPWV had significantly higher levels of GRI and hyperglycemia component (both P for trend < 0.05). Linear regression revealed the significant positive linear associations of the GRI with baPWV in unadjusted or adjusted models (All P < 0.05). In the multivariable logistic analysis, each increase in the GRI quartile was associated with a 1.30-fold (95% CI 1.01-1.68, P for trend < 0.05) higher prevalence of increased arterial stiffness after adjustment for age, sex, BMI, diabetes duration, current smoking status, blood pressure, and lipid profile. Subgroup analyses showed that the association between the GRI quartiles and increased arterial stiffness was stronger among participants with a diabetes duration ≥15 years (P for interaction = 0.014). CONCLUSION: Glycemia risk index assessed by continuous glucose monitoring is associated with increased arterial stiffness in type 2 diabetes.