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.

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.

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.

Investigating the shared genetic architecture between schizophrenia and body mass index.

Evidence for reciprocal comorbidity of schizophrenia (SCZ) and body mass index (BMI) has grown in recent years. However, little is known regarding the shared genetic architecture or causality underlying the phenotypic association between SCZ and BMI. Leveraging summary statistics from the hitherto largest genome-wide association study (GWAS) on each trait, we investigated the genetic overlap and causal associations of SCZ with BMI. Our study demonstrated a genetic correlation between SCZ and BMI, and the correlation was more evident in local genomic regions. The cross-trait meta-analysis identified 27 significant SNPs shared between SCZ and BMI, most of which had the same direction of influence on both diseases. Mendelian randomization analysis showed the causal association of SCZ with BMI, but not vice versa. Combining the gene expression information, we found that the genetic correlation between SCZ and BMI is enriched in six regions of brain, led by the brain frontal cortex. Additionally, 34 functional genes and 18 specific cell types were found to have an impact on both SCZ and BMI within these regions. Taken together, our comprehensive genome-wide cross-trait analysis suggests a shared genetic basis including pleiotropic loci, tissue enrichment, and shared function genes between SCZ and BMI. This work provides novel insights into the intrinsic genetic overlap of SCZ and BMI, and highlights new opportunities and avenues for future investigation.

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.

A hybrid energy harvesting approach for transmission lines based on triboelectric nanogenerator and micro thermoelectric generator.

To effectively detect faults in transmission lines, monitoring the operating status of these lines is imperative. However, providing power to monitoring devices for transmission line status presents a significant challenge. In this research, a hybrid energy harvesting approach based on micro thermoelectric generator (MTEG) and triboelectric nanogenerator (TENG) is proposed, and a theoretical model for MTEG-TENG hybrid energy harvesting is established. This study develops an integrated energy harvesting prototype, which incorporates oscillating-TENG (O-TENGs), MTEGs, and a power management control unit. This prototype not only harvests energy from the vibrations of transmission lines but also converts the lines thermal energy into electricity. The Experiment results show that the maximum open-circuit voltages of O-TENG and MTEG reach 80.3 V and 1.094 V, respectively. Compared to a single MTEG energy harvesting device, the prototype of the MTEG-TENG hybrid energy harvesting device demonstrates a 5.36% improvement in energy harvesting and battery charging performance. Consequently, this approach achieves self-powered monitoring with excellent stability and lower manufacturing costs. It provides an efficient and durable power approach for transmission line status monitoring devices.

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.

Accelerated biological aging, mediating amino acids, and risk of incident type 2 diabetes: a prospective cohort study.

PURPOSE: Aging plays an important role in type 2 diabetes mellitus (T2DM). But the association between accelerated biological age and T2DM, and the mechanisms underlying this association remains unclear. Thus, this study aimed to examine the associations of biological aging with T2DM, and explore the potential mediation effect of amino acids. METHODS: This prospective cohort study included 95,773 participants in the UK Biobank who were free of diabetes at baseline. Biological age was measured from clinical traits using PhenoAgeAccel. Cox proportional hazard models were used to estimate the hazard ritios (HRs) and 95% confidence intervals (CIs), and mediation analysis was used to explore the mediation effect of amino acids. RESULTS: During a median follow-up of 14.02 years, 6,347 incident T2DM cases were recorded. After multivariable adjustment for sociodemographic characteristics, lifestyle factors, and other risk factors of T2DM, participants with older biological age were at increased risk of incident T2DM (30% increase per standard deviation of PhenoAgeAccel, 95% CI: 28.0-33.0%). Additionally, higher branched chain amino acids (BCAAs) including isoleucine and leucine, aromatic amino acids (AAAs) including phenylalanine and tyrosine, were associated with increased PhenoAgeAccel and risk of incident T2DM; while glutamine and glycine were inversely associated. Alanine, glutamine, glycine, phenylalanine, tyrosine, isoleucine, leucine, and total concentration of branched-chain amnio acids could partially explain the associations between PhenoAgeAccel and T2DM. CONCLUSION: Accelerated biological aging was associated with increased risk of incident T2DM independent of chronological age and may be a risk factor of T2DM, partially mediated by several amino acids.

Acquired risk factors and incident atrial fibrillation according to age and genetic predisposition.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is the most common sustained arrhythmia in adults. Investigations of risk factor profiles for AF according to age and genetic risk groups are essential to promote individualized strategies for the prevention and control of AF. METHODS: A total of 409 661 participants (mean age, 56 years; 46% men) free of AF at baseline and with complete information about risk factors were included from the UK Biobank cohort. The hazard ratios and population-attributable risk (PAR) percentages of incident AF associated with 23 risk factors were examined, including 3 social factors, 7 health behaviours, 6 cardiometabolic factors, 6 clinical comorbidities, and the genetic risk score (GRS), across 3 age groups (40-49, 50-59, and 60-69 years) and 3 genetic risk groups (low, moderate, and high GRS). RESULTS: After a follow-up of 5 027 587 person-years, 23 847 participants developed AF. Most cardiometabolic factors and clinical comorbidities showed a significant interaction with age, whereby the associations were generally strengthened in younger groups (Pinteraction < .002). However, only low LDL cholesterol, renal dysfunction, and cardiovascular disease showed a significant interaction with genetic risk, and the associations with these factors were stronger in lower genetic risk groups (Pinteraction < .002). Cardiometabolic factors consistently accounted for the largest number of incident AF cases across all age groups (PAR: 36.2%-38.9%) and genetic risk groups (34.0%-41.9%), with hypertension and overweight/obesity being the two leading modifiable factors. Health behaviours (PAR: 11.5% vs. 8.7%) and genetic risk factors (19.1% vs. 14.3%) contributed to more AF cases in the 40-49 years group than in the 60-69 years group, while the contribution of clinical comorbidities remained relatively stable across different age groups. The AF risk attributable to overall cardiometabolic factors (PAR: 41.9% in the low genetic risk group and 34.0% in the high genetic risk group) and clinical comorbidities (24.7% and 15.9%) decreased with increasing genetic risk. The impact of social factors on AF was relatively low across the groups by age and genetic risk. CONCLUSIONS: This study provided comprehensive information about age- and genetic predisposition-related risk factor profiles for AF in a cohort of UK adults. Prioritizing risk factors according to age and genetic risk stratifications may help to achieve precise and efficient prevention of AF.

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.

Oral micronized progesterone versus vaginal progesterone for luteal phase support in fresh embryo transfer cycles: a multicenter, randomized, non-inferiority trial.

STUDY QUESTION: Does oral micronized progesterone result in a non-inferior ongoing pregnancy rate compared to vaginal progesterone gel as luteal phase support (LPS) in fresh embryo transfer cycles? SUMMARY ANSWER: The ongoing pregnancy rate in the group administered oral micronized progesterone 400 mg per day was non-inferior to that in the group administered vaginal progesterone gel 90 mg per day. WHAT IS KNOWN ALREADY: LPS is an integrated component of fresh IVF, for which an optimal treatment regimen is still lacking. The high cost and administration route of the commonly used vaginal progesterone make it less acceptable than oral micronized progesterone; however, the efficacy of oral micronized progesterone is unclear owing to concerns regarding its low bioavailability after the hepatic first pass. STUDY DESIGN, SIZE, DURATION: This non-inferiority randomized trial was conducted in eight academic fertility centers in China from November 2018 to November 2019. The follow-up was completed in April 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1310 infertile women who underwent their first or second IVF cycles were enrolled. On the day of hCG administration, the patients were randomly assigned to one of three groups for LPS: oral micronized progesterone 400 mg/day (n = 430), oral micronized progesterone 600 mg/day (n = 440) or vaginal progesterone 90 mg/day (n = 440). LPS was started on the day of oocyte retrieval and continued till 11-12 weeks of gestation. The primary outcome was the rate of ongoing pregnancy. MAIN RESULTS AND THE ROLE OF CHANCE: In the intention-to-treat analysis, the rate of ongoing pregnancy in the oral micronized progesterone 400 mg/day group was non-inferior to that of the vaginal progesterone gel group [35.3% versus 38.0%, absolute difference (AD): -2.6%; 95% CI: -9.0% to 3.8%, P-value for non-inferiority test: 0.010]. There was insufficient evidence to support the non-inferiority in the rate of ongoing pregnancy between the oral micronized progesterone 600 mg/day group and the vaginal progesterone gel group (31.6% versus 38.0%, AD: -6.4%; 95% CI: -12.6% to -0.1%, P-value for non-inferiority test: 0.130). In addition, we did not observe a statistically significant difference in the rate of live births between the groups. LIMITATIONS, REASONS FOR CAUTION: The primary outcome of our trial was the ongoing pregnancy rate; however, the live birth rate may be of greater clinical interest. Although the results did not show a difference in the rate of live births, they should be confirmed by further trials with larger sample sizes. In addition, in this study, final oocyte maturation was triggered by hCG, and the findings may not be extrapolatable to cycles with gonadotropin-releasing hormone agonist triggers. WIDER IMPLICATIONS OF THE FINDINGS: Oral micronized progesterone 400 mg/day may be an alternative to vaginal progesterone gel in patients reluctant to accept the vaginal route of administration. However, whether a higher dose of oral micronized progesterone is associated with a poorer pregnancy rate or a higher rate of preterm delivery warrants further investigation. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by a grant from the National Natural Science Foundation of China (82071718). None of the authors have any conflicts of interest to declare. TRIAL REGISTRATION NUMBER: This trial was registered at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/) with the number ChiCTR1800015958. TRIAL REGISTRATION DATE: May 2018. DATE OF FIRST PATIENT'S ENROLMENT: November 2018.

Association of sleep patterns and cardiovascular disease risk is modified by glucose tolerance status.

AIMS: To investigate whether the association between sleep patterns and cardiovascular disease (CVD) risk differs according to glucose tolerance status. MATERIALS AND METHODS: This prospective study included 358,805 participants initially free of CVD from the UK Biobank. We created a sleep score based on five sleep factors (sleep duration, chronotype, insomnia, snoring, and daytime sleepiness) with one point for each unhealthy factor. Cox proportional hazards models were used to examine the association between sleep and incident CVD, including coronary heart disease (CHD) and stroke, according to normal glucose tolerance (NGT), prediabetes, and diabetes. RESULTS: During a median follow-up of 12.4 years, 29,663 incident CVD events were documented. There was a significant interaction between sleep score and glucose tolerance status on CVD (P for interaction = 0.002). Each 1 point increment in sleep score was associated with a 7% (95% confidence interval 6%-9%), 11% (8%-14%), and 13% (9%-17%) higher risk of CVD among participants with NGT, prediabetes, and diabetes, respectively. Similar interaction patterns were observed for CHD and stroke. Among the individual sleep factors, sleep duration and insomnia significantly interacted with glucose tolerance status on CVD outcomes (all P for interaction <0.05). All five unhealthy sleep factors accounted for 14.2% (8.7%-19.8%), 19.5% (7.4%-31.0%), and 25.1% (9.7%-39.3%) of incident CVD cases among participants with NGT, prediabetes, and diabetes, respectively. CONCLUSIONS: The CVD risk associated with a poor sleep pattern was exacerbated across glucose intolerance status. Our findings emphasise the importance of integrating sleep management into a lifestyle modification programme, particularly in people with prediabetes or diabetes.

Association between Life's Essential 8 score and risk of premature mortality in people with and without type 2 diabetes: A prospective cohort study.

AIMS: To evaluate the association of cardiovascular health (CVH), measured by Life's Essential 8 score, with the risk of premature mortality and to determine the patterns of CVH-related differences in life expectancy among people with and without type 2 diabetes (T2D). MATERIALS AND METHODS: This prospective study included 309,789 participants (age 56.6 ± 8.1 years; 46% men) enroled in the UK Biobank. The Life's Essential 8 composite measure consists of four health behaviours (diet, physical activity, nicotine exposure, and sleep) and four health factors (BMI, non-HDL cholesterol, blood glucose, and blood pressure), and the maximum CVH score was 100 points. CVH was categorised into low, moderate, and high groups. Premature death was defined as death before the age of 75. Cox proportional hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and life expectancy was estimated. RESULTS: During a median follow-up of 12.7 years, 13,683 cases of premature death were documented. Compared to participants with low CVH, the multivariable HRs (95% CIs) of premature death were 0.59 (0.56-0.62) and 0.42 (0.39-0.45) for the moderate and high CVH groups, respectively. This association was stronger in participants with T2D compared with those without T2D. At the age of 50 years, compared to low CVH groups, high CVH was associated with a gain of 9.79 (9.70-9.87) and 5.58 (5.48-5.67) additional life years for men with and without T2D, respectively. The corresponding life gain for women with and without T2D was 24.21 (24.13-24.27) and 10.18 (10.10-10.27), respectively. CONCLUSIONS: Maintaining an ideal Life's Essential 8 score may provide more benefits for people with T2D than for those without T2D, including a lower risk of premature death and an increased lifespan.

High prevalence of metabolic diseases, liver steatosis and fibrosis among Chinese psychiatric patients.

BACKGROUND: We aimed to investigate the differences of metabolic disorders between the general population and psychiatric patients, with an emphasis on the prevalence and influencing factors of liver fibrosis in psychiatric patients. METHODS: A total of 734 psychiatric patients and 734 general population matched for age, sex, and BMI were enrolled from Shanghai, China. All participants underwent blood pressure, glucose, lipid profile measurements, and anthropometric parameters including body weight, height and waist circumference. FibroScan examinations were also performed on psychiatric patients. Liver steatosis and fibrosis were diagnosed by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) by professional staff. RESULTS: Compared with the general population, psychiatric patients revealed significantly higher burden of metabolic disorders. The overall prevalence of liver steatosis (CAP ≥ 233 dB/m) and fibrosis (LSM ≥ 7.0 kPa) was 48.7% and 15.5% in psychiatric patients. Psychiatric patients with liver steatosis or fibrosis showed worse metabolic profile. Meanwhile, the prevalence of liver fibrosis was also significantly higher in patients with overweight, central obesity, diabetes, hypertension, metabolic syndrome, and liver steatosis. In logistic regression analyses, age, BMI and visceral adiposity index were independent risk factors for liver fibrosis in psychiatric patients. Additionally, antipsychotic medication was suggested to be associated with an increased risk of liver fibrosis in psychiatric patients with liver steatosis. CONCLUSIONS: Prevalence of liver steatosis and fibrosis is high in Chinese psychiatric patients. Those with antipsychotic polypharmacy and obesity are at high risk, and may benefit from early liver assessment in preventing fibrosis progression.

Associations of Sugar-Sweetened Beverages, Artificially Sweetened Beverages, and Pure Fruit Juice With Nonalcoholic Fatty Liver Disease: Cross-sectional and Longitudinal Study.

OBJECTIVE: We aimed to test the associations of sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), and pure fruit juice (PJ) consumption with the risk of nonalcoholic fatty liver disease (NAFLD). METHODS: Data for 136 277 UK Biobank participants who completed the dietary questionnaire and did not have a history of liver disease were included. Logistic regression was used for the cross-sectional setting where NAFLD was defined by a fatty liver index (FLI) ≥60. Cox proportional hazard regression was used for the longitudinal setting where hospitalized NAFLD was defined as hospital admission with Internationl Classification of Diseases-10 codes K76.0 and K75.8. RESULTS: Compared with 0 L/wk for corresponding beverages, multivariate-adjusted odds ratios (95% confidence intervals) for NAFLD in consumption ≤1, 1 to 2, and >2 L/wk were 1.06 (1.02-1.10), 1.24 (1.19-1.29), and 1.42 (1.35-1.49) for SSB; 1.43 (1.37-1.50), 1.73 (1.65-1.82), and 2.37 (2.25-2.50) for ASB, and 0.87 (0.84-0.89), 0.91 (0.88-0.94), and 1.07 (1.02-1.13) for PJ, respectively. Consumption of SSB and ASB were both positively correlated with FLI (P for line < .001). During a median follow-up of 10.2 years, 1043 cases of hospitalized NAFLD were recorded. ASB consumption of 1 to 2 and >2 L/wk was associated with a 22% (0.99-1.50) and 35% (1.11-1.65) increased risk of hospitalized NAFLD, respectively (P for trend = .002). However, the associations of SSB and PJ with the risk of hospitalized NAFLD were not significant. CONCLUSIONS: Consumption of SSB, ASB, and PJ were all related to the risk of NAFLD. Excessive consumption of ASBs was associated with an increased risk of incident hospitalized NAFLD.

T Cell Subsets are Associated with Clinical Activity and Efficacy of 4.5g Intravenous Glucocorticoid for Moderate-To-Severe Thyroid-Associated Ophthalmopathy.

BACKGROUND: Intravenous glucocorticoid (IVGC) remains the main treatment for moderate-to-severe and active thyroid-associated ophthalmopathy (TAO). However, a substantial number (20-30%) of active moderate-to-severe TAO patients may not respond to IVGC. Some patients may have disease progression despite IVGC treatment or relapse after steroid withdrawal. OBJECTIVES: To analyze risk factors for clinical activity and predictive factors for clinical outcomes of 4.5 g IVGC therapy in patients with moderate-to-severe TAO. DESIGN AND METHODS: Our study was performed in two steps: step 1 involved 110 moderate-to-severe TAO patients and analyzed risk factors for TAO activity; step 2 involved 53 active moderate-to-severe TAO patients from step 1 who were treated with 4.5 g IVGC therapy and analyzed predictive factors for clinical outcomes of IVGC therapy. Multivariate logistic regression analysis was used to identify the independent predictors and establish the predictive model. RESULTS: Abnormal TRAb (OR = 4.717; P = 0.019) and the percentage of CD3+CD4+ T cell (OR = 1.092; P = 0.028) were independently associated with the activity of moderate-to-severe TAO patients. The pretreatment CAS-max in both eyes (OR = 7.221; P = 0.013) and the percentage of pretreatment CD3+T cell (OR = 0.718; P = 0.037) were independently associated with therapeutic efficacy. The pretreatment CAS-max in both eyes (OR = 156.53; P = 0.028) and the percentage of post-treatment CD3+T cell (OR = 0.554; P = 0.043) were independently associated with therapeutic efficacy. Besides, multivariable prediction models were established, which were better in the forecasting aspect than single-variable prediction models. CONCLUSIONS: Based on the findings of this study, we should monitor the peripheral blood T cell subsets for TAO, which could be helpful to timely judge the condition of clinical manifestation and effect of treatment for TAO patients. Multivariable prediction models have been established, which have great significance for clinical work.

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.