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.

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.

Vitamin D status, vitamin D receptor polymorphisms, and risk of type 2 diabetes: A prospective cohort study.

CONTEXT: Vitamin D status has been associated with risk of type 2 diabetes (T2D), but evidence is scarce regarding whether such relation differs by glycemic status. OBJECTIVE: To prospectively investigate the association between serum 25-hydroxyvitamin D [25(OH)D] and risk of incident T2D across the glycemic spectrum and the modification effect of genetic variants in vitamin D receptor (VDR). METHODS: This prospective study included 379,699 participants without T2D at baseline from the UK Biobank. Analyses were performed according to glycemic status and HbA1c levels. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs. RESULTS: During a median of 14.1 years of follow-up, 6,315 participants with normoglycemia and 9,085 prediabetes patients developed T2D. Compared to individuals with 25(OH)D <25 nmol/L, the multivariable-adjusted hazard ratios (95% CIs) of incident T2D for those with 25(OH)D ≥75 nmol/L was 0.62 (0.56, 0.70) among the normoglycemia and 0.64 (0.58, 0.70) among the prediabetes. A significant interaction was observed between 25(OH)D and VDR polymorphisms among participants with prediabetes (Pinteraction=0.017), whereby the reduced HR of T2D associated with higher 25(OH)D was more prominent in those carrying T allele of rs1544410. Triglycerides levels mediated 26% and 34% of the association between serum 25(OH)D and incident T2D among participants with normoglycemia and prediabetes. CONCLUSIONS: Higher serum 25(OH)D concentrations were associated with lower T2D risk across the glycemic spectrum below the threshold for diabetes, and the relations in prediabetes were modified by VDR polymorphisms. Improving lipid profile, mainly triglycerides, accounted for part of the favorable associations.

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.

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.

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.

Birth weight, ideal cardiovascular health metrics in adulthood, and incident cardiovascular disease.

BACKGROUND: Prenatal and postnatal factors may have joint effects on cardiovascular health, and we aimed to assess the joint association of birth weight and ideal cardiovascular health metrics (ICVHMs) prospectively in adulthood with incident cardiovascular disease (CVD). METHODS: In the UK Biobank, 227,833 participants with data on ICVHM components and birth weight and without CVD at baseline were included. The ICVHMs included smoking, body mass index, physical activity, diet information, total cholesterol, blood pressure, and hemoglobin A1c. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) in men and women. RESULTS: Over a median follow-up period of 13.0 years (2,831,236 person-years), we documented 17,477 patients with incident CVD. Compared with participants with birth weights of 2.5-4.0 kg, the HRs (95% CIs) of CVD among those with low birth weights was 1.08 (1.00-1.16) in men and 1.23 (1.16-1.31) in women. The association between having a birth weight <2.5 kg and CVD risk in men was more prominent for those aged <50 years than for those of older age ( P for interaction = 0.026). Lower birth weight and non-ideal cardiovascular health metrics were jointly related to an increased risk of CVD. Participants with birth weights <2.5 kg and ICVHMs score 0-1 had the highest risk of incident CVD (HR [95% CI]: 3.93 [3.01-5.13] in men; 4.24 [3.33-5.40] in women). The joint effect (HR [95% CI]: 1.36 [1.17-1.58]) could be decomposed into 24.7% (95% CI: 15.0%-34.4%) for a lower birth weight, 64.7% (95% CI: 56.7%-72.6%) for a lower ICVHM score, and 10.6% (95% CI: 2.7%-18.6%) for their additive interaction in women. CONCLUSIONS: Birth weight and ICVHMs were jointly related to CVD risk. Attaining a normal birth weight and ideal ICVHMs may reduce the risk of CVD, and a simultaneous improvement of both prenatal and postnatal factors could further prevent additional cases in women.

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 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.

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.

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.

Immune-mediated diseases and risk of incident cardiovascular diseases: a prospective cohort study.

OBJECTIVES: Disorders of immune system may impact cardiovascular health; however, comprehensive study is lacking. We aimed to analyse the association of total and 20 individual immune-mediated diseases (IMDs) with risk of incident cardiovascular disease (CVD). METHODS: In this prospective cohort study, 414 495 participants (55.6% women; mean age 55.9 years) from UK Biobank with baseline assessment at 2006-10 were included. Among them, 21 784 participants had prevalent IMDs. Information on IMDs at baseline and incidence of CVDs during follow-up were recorded. Cox proportional hazard models were used to estimate the association between IMDs and CVDs risk. RESULTS: During the median follow-up of 12.1 years, there were 6506 cases of CVDs in participants with IMDs (29.9%) and 77 699 cases in those without IMDs (19.8%). After multivariable adjustment, participants with IMDs were significantly associated with an increased risk of total CVD [hazard ratio (HR) 1.57; 95% CI 1.52-1.61]. Among the 20 IMDs, 16 showed significant associations with CVD (all P < 0.0025 after Bonferroni correction), with HR ranging from 1.34 (1.16-1.54) for celiac disease to 2.75 (2.10-3.61) for SLE. Participants with any IMD exposure had a higher risk of all individual CVD events, with HR ranging from 1.34 (1.14-1.58) for cerebral hemorrhage to 1.80 (1.54-2.11) for pericardium diseases. IMD duration <5, 5-10 and >10 years was associated with 55%, 59% and 56% increased risk of total CVD, respectively. CONCLUSION: Total and individual IMDs were associated with an increased risk of overall CVDs. It is important to consider primary prevention of CVD in patients with IMD and dysregulation of immune system in the cardiovascular health.

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.

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.

Associations of artificially sweetened beverages, sugar-sweetened beverages, and pure fruit/vegetable juice with visceral adipose tissue mass.

OBJECTIVE: To test the associations of sugar-sweetened beverage, artificially sweetened beverage, and pure fruit/vegetable juice consumption with visceral adipose tissue (VAT) mass at baseline and follow-up and to determine whether BMI and genetic risk of VAT mass modified the associations. METHODS: A total of 203,348 participants from UK Biobank with consumption data on three beverages were included. Participants were categorized into nonconsumers and consumers with >0-1, >1-2 and >2 L/week. A sex-specific prediction model was used to calculate VAT mass. A weighted genetic risk score for high VAT mass was calculated. RESULTS: The participants with a sugar-sweetened beverage and artificially sweetened beverage consumption of >2 L/week had the greatest B values [B (95% CI): 24.02 (16.53, 31.51) and 60.81 (52.08, 69.54) in men, respectively; 10.20 (5.92, 14.48) and 24.72 (20.80, 28.64) in women]. Low and moderate intake of pure fruit/vegetable juices showed a significantly inverse association with VAT mass in men [-10.52 (-15.37, -5.67); -6.46 (-11.27, -1.65)] and women [-6.70 (-8.99, -4.41); -5.93 (-8.33, -3.54)]. Regarding changes in VAT mass, participants who consumed >2 L/week of sugar-sweetened beverages and artificially sweetened beverages had greater changes. BMI but not genetic risk modified the associations between beverage intake and VAT mass, which were strengthened in participants with BMI ≥25 kg/m2 for sugar-sweetened and artificially sweetened beverage consumption. CONCLUSIONS: Higher consumption of sugar-sweetened beverages or artificially sweetened beverages was associated with greater VAT mass regardless of genetic risk. Mild-to-moderate intake of pure fruit/vegetable juices was linked to lower VAT mass.

Life's Essential 8 and risk of non-communicable chronic diseases: Outcome-wide analyses.

BACKGROUND: Life's Simple 7, the former construct of cardiovascular health (CVH) has been used to evaluate adverse non-communicable chronic diseases (NCDs). However, some flaws have been recognized in recent years and Life's Essential 8 has been established. In this study, we aimed to analyze the association between CVH defined by Life's Essential 8 and risk of 44 common NCDs and further estimate the population attributable fractions (PAFs) of low-moderate CVH scores in the 44 NCDs. METHODS: In the UK Biobank, 170,726 participants free of 44 common NCDs at baseline were included. The Life's Essential 8 composite measure consists of four health behaviours (diet, physical activity, nicotine exposure, and sleep) and four health factors (body mass index, non-high density lipoprotein cholesterol, blood glucose, and blood pressure), and the maximum CVH score was 100 points. CVH score was categorized into low, moderate, and high groups. Participants were followed up for 44 NCDs diagnosis across 10 human system disorders according to the International Classification of Diseases 10th edition (ICD-10) code using linkage to national health records until 2022. Cox proportional hazard models were used in this study. The hazard ratios (HRs) and PAFs of 44 NCDs associated with CVH score were examined. RESULTS: During the median follow-up of 10.85 years, 58,889 incident NCD cases were documented. Significant linear dose-response associations were found between higher CVH score and lower risk of 25 (56.8%) of 44 NCDs. Low-moderate CVH (<80 points) score accounted for the largest proportion of incident cases in diabetes (PAF: 80.3%), followed by gout (59.6%), sleep disorder (55.6%), chronic liver disease (45.9%), chronic kidney disease (40.9%), ischemic heart disease (40.8%), chronic obstructive pulmonary disease (40.0%), endometrium cancer (35.8%), lung cancer (34.0%), and heart failure (34.0%) as the top 10. Among the eight modifiable factors, overweight/obesity explained the largest number of cases of incident NCDs in endocrine, nutritional, and metabolic diseases (35.4%), digestive system disorders (21.4%), mental and behavioral disorders (12.6%), and cancer (10.3%); however the PAF of ideal sleep duration ranked first in nervous system (27.5%) and neuropsychiatric disorders (9.9%). CONCLUSIONS: Improving CVH score based on Life's Essential 8 may lower risk of 25 common NCDs. Among CVH metrics, normal weight may especially important to prevent new cases of metabolic diseases, NCDs in digestive system and mental and behavioral disorders, and cancer.

SGLT2 inhibition, circulating metabolites, and atrial fibrillation: a Mendelian randomization study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors have shown promise in reducing the risk of atrial fibrillation (AF). However, the results are controversial and the underlying metabolic mechanism remains unclear. Emerging evidence implied that SGLT2 inhibitors have extra beneficial metabolic effects on circulating metabolites beyond glucose control, which might play a role in reducing the risk of AF. Hence, our study aimed to investigate the effect of circulating metabolites mediating SGLT2 inhibition in AF by Mendelian randomization (MR). METHODS: A two-sample and two-step MR study was conducted to evaluate the association of SGLT2 inhibition with AF and the mediation effects of circulating metabolites linking SGLT2 inhibition with AF. Genetic instruments for SGLT2 inhibition were identified as genetic variants, which were both associated with the expression of SLC5A2 gene and glycated hemoglobin level (HbA1c). Positive control analysis on type 2 diabetes mellitus (T2DM) was conducted to validate the selection of genetic instruments. RESULTS: Genetically predicted SGLT2 inhibition (per 1 SD decrement in HbA1c) was associated with reduced risk of T2DM (odds ratio [OR] = 0.63 [95% CI 0.45, 0.88], P = 0.006) and AF (0.51 [0.27, 0.97], P = 0.039). Among 168 circulating metabolites, two metabolites were both associated with SGLT2 inhibition and AF. The effect of SGLT2 inhibition on AF through the total concentration of lipoprotein particles (0.88 [0.81, 0.96], P = 0.004) and the concentration of HDL particles (0.89 [0.82, 0.97], P = 0.005), with a mediated proportion of 8.03% (95% CI [1.20%, 14.34%], P = 0.010) and 7.59% ([1.09%, 13.34%], P = 0.011) of the total effect, respectively. CONCLUSIONS: This study supported the association of SGLT2 inhibition with a reduced risk of AF. The total concentration of lipoprotein particles and particularly the concentration of HDL particles might mediate this association. Further mechanistic and clinical studies research are needed to understand the mediation effects of circulating metabolites especially blood lipids in the association between SGLT2 inhibition and AF.