In depth analysis of the HIV reservoir confirms effectiveness and safety of DTG/3TC in a phase 4 randomized controlled switch trial (RUMBA).

BACKGROUND: Reducing the number of active compounds for lifelong HIV treatment is of interest, especially to reduce potential long-term side effects. So far, available data assessing viral control, support the robustness and safety of 2DR (2-drug regimen) ART compared to 3DR. However, further in-depth investigations of the viral reservoirs are mandatory to guarantee long-term safety of these regimens regarding stable intact HIV-1 DNA copies, HIV-1 RNA transcripts and sustained immunological control. METHODS: The Rumba study is the first prospective randomized controlled trial evaluating the impact of switch from 3DR to 2DR on the viral reservoir. Participants on any stable 2nd generation INSTI-based 3DR regimen with HIV-1 RNA<50 copies/ml plasma for at least 3 months were randomized to switch to dolutegravir/lamivudine (DTG/3TC, N=89) or to switch or stay on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, N=45). After 48 weeks, virological, immunological and metabolic parameters were evaluated. RESULTS: We did not observe a significant difference in change over time in the mean number of intact HIV-1 DNA copies/million CD4+ T cells with DTG/3TC compared to B/F/TAF. There was no evidence in this study that switching to DTG/3TC increased the active reservoir by HIV-1 transcription. No significant changes in pro-inflammatory cytokines or major immune cell subsets were observed. Changes in exhaustion and activation of specific cellular subsets were small and bidirectional. Metabolic outcomes are similar between the treatment regimens. CONCLUSIONS: This study confirms the safety of DTG/3TC compared to B/F/TAF through viral control after in-depth investigations of the intact HIV-1 reservoir, HIV-1 transcription and inflammatory markers.

Metabolic health in people living with type 1 diabetes in Belgium: a repeated cross-sectional study.

AIMS/HYPOTHESIS: Metabolic abnormalities such as central obesity, insulin resistance, dyslipidaemia and hypertension, often referred to as 'the metabolic syndrome' (or 'combined metabolic abnormalities'), are increasingly being identified in people living with type 1 diabetes, accelerating the risk for CVD. As a result, in recent years, treatment in people living with type 1 diabetes has shifted to improving overall metabolic health rather than glucose control alone. In Belgium, diabetes care for people living with type 1 diabetes is centrally organised. The Initiative for Quality Improvement and Epidemiology in Diabetes, imposed by the Belgian health insurance system, has systematically collected data from patients on intensive insulin therapy treated in all 101 diabetes clinics in Belgium since 2001. The aim of this real-world study is to describe the evolution of treatment and metabolic health, including the prevalence of obesity and combined metabolic abnormalities, in people living with type 1 diabetes over the past 20 years, and to compare the treatment and prevalence of complications between those with and without combined metabolic abnormalities. METHODS: We analysed data on adults (≥16 years old) living with type 1 diabetes, who were diagnosed at age ≤45 years and who had a diabetes duration ≥1 year, collected between 2001 and 2022. The evolution of HbA1c, BMI, LDL-cholesterol, systolic BP, lipid-lowering therapy and antihypertensive therapy over time was analysed. The prevalence of individual and multiple metabolic abnormalities according to various definitions of the metabolic syndrome/combined metabolic abnormalities was analysed, and the association between combined metabolic abnormalities and metabolic health indicators, complications and treatment was investigated in the 2022 data. RESULTS: The final dataset consisted of 26,791 registrations of adults living with type 1 diabetes collected between 2001 and 2022. Although glycaemic and lipid control generally improved over time, the prevalence of obesity strongly increased (12.1% in 2001 vs 21.7% in 2022, p<0.0001), as did the presence of combined metabolic abnormalities (WHO criteria: 26.9% in 2001 vs 42.9% in 2022 in women, p<0.0001; 30.4% in 2001 vs 52.1% in 2022 in men, p<0.0001; WHO criteria without albuminuria: 22.3% in 2001 vs 40.6% in 2022 in women, p<0.0001; 25.1% in 2001 vs 49.2% in 2022 in men, p<0.0001; NCEP-ATPIII criteria: 39.9% in 2005 vs 57.2% in 2022 in women, p<0.0001; 40.8% in 2005 vs 60.9% in 2022 in men, p<0.0001; IDF criteria: 43.9% in 2005 vs 59.3% in 2022 in women, p<0.001; 33.7% in 2005 vs 50.0% in 2022 in men, p<0.0001). People with combined metabolic abnormalities had higher glucose levels compared to those without combined metabolic abnormalities (HbA1c >58 mmol in men: 48.9% vs 36.9%; HbA1c >58 mmol in women: 53.3% vs 41.1%, p<0.0001). People with combined metabolic abnormalities were more often treated with adjunct therapies such as metformin, sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists. In both men and women, the presence of combined metabolic abnormalities was strongly related to the presence of eye complications, peripheral neuropathy, chronic kidney disease and CVD, corrected for age, diabetes duration and HbA1c. CONCLUSIONS/INTERPRETATION: Overweight, obesity and combined metabolic abnormalities are increasingly being identified in people living with type 1 diabetes, further accelerating the risk of microvascular and macrovascular complications. Early identification of the presence of combined metabolic abnormalities should enable therapeutic interventions to be modified towards multifactorial approaches, with attention to education on avoidance of overweight (e.g. dietary counselling) in addition to strict glycaemic control and intensification of use of antihypertensive agents and statins. Use of adjunct therapies in this population as a tool should be explored more thoroughly to reduce risk of complications.

Unveiling the connection between gut microbiome and metabolic health in individuals with chronic spinal cord injury.

Accumulating evidence has revealed that alterations in the gut microbiome following spinal cord injury (SCI) exhibit similarities to those observed in metabolic syndrome. Considering the causal role of gut dysbiosis in metabolic syndrome development, SCI-induced gut dysbiosis may be a previously unidentified contributor to the increased risk of cardiometabolic diseases, which has garnered attention. With a cross-sectional design, we evaluated the correlation between gut microbiome composition and functional potential with indicators of metabolic health among 46 individuals with chronic SCI. Gut microbiome communities were profiled using next-generation sequencing techniques. Indices of metabolic health, including fasting lipid profile, glucose tolerance, insulin resistance, and inflammatory markers, were assessed through fasting blood tests and an oral glucose tolerance test. We used multivariate statistical techniques (i.e., regularized canonical correlation analysis) to identify correlations between gut bacterial communities, functional pathways, and metabolic health indicators. Our findings spotlight bacterial species and functional pathways associated with complex carbohydrate degradation and maintenance of gut barrier integrity as potential contributors to improved metabolic health. Conversely, those correlated with detrimental microbial metabolites and gut inflammatory pathways demonstrated associations with poorer metabolic health outcomes. This cross-sectional investigation represents a pivotal initial step toward comprehending the intricate interplay between the gut microbiome and metabolic health in SCI. Furthermore, our results identified potential targets for future research endeavors to elucidate the role of the gut microbiome in metabolic syndrome in this population.NEW & NOTEWORTHY Spinal cord injury (SCI) is accompanied by gut dysbiosis and the impact of this on the development of metabolic syndrome in this population remains to be investigated. Our study used next-generation sequencing and multivariate statistical analyses to explore the correlations between gut microbiome composition, function, and metabolic health indices in individuals with chronic SCI. Our results point to potential gut microbial species and functional pathways that may be implicated in the development of metabolic syndrome.

Positive Effects of Physical Activity on Insulin Signaling.

Physical activity is integral to metabolic health, particularly in addressing insulin resistance and related disorders such as type 2 diabetes mellitus (T2DM). Studies consistently demonstrate a strong association between physical activity levels and insulin sensitivity. Regular exercise interventions were shown to significantly improve glycemic control, highlighting exercise as a recommended therapeutic strategy for reducing insulin resistance. Physical inactivity is closely linked to islet cell insufficiency, exacerbating insulin resistance through various pathways including ER stress, mitochondrial dysfunction, oxidative stress, and inflammation. Conversely, physical training and exercise preserve and restore islet function, enhancing peripheral insulin sensitivity. Exercise interventions stimulate ß-cell proliferation through increased circulating levels of growth factors, further emphasizing its role in maintaining pancreatic health and glucose metabolism. Furthermore, sedentary lifestyles contribute to elevated oxidative stress levels and ceramide production, impairing insulin signaling and glucose metabolism. Regular exercise induces anti-inflammatory responses, enhances antioxidant defenses, and promotes mitochondrial function, thereby improving insulin sensitivity and metabolic efficiency. Encouraging individuals to adopt active lifestyles and engage in regular exercise is crucial for preventing and managing insulin resistance and related metabolic disorders, ultimately promoting overall health and well-being.

Deletion of Impdh2 in adipocyte precursors limits the expansion of white adipose tissue and enhances metabolic health with overnutrition.

The equilibrium between the hypertrophic growth of existing adipocytes and adipogenesis is vital in managing metabolic stability in white adipocytes when faced with overnutrition. Adipogenesis has been established as a key player in combating metabolic irregularities caused by various factors. However, the benefits of increasing adipogenesis-mediated white adipose tissue (WAT) expansion for metabolic health regulation remain uncertain. Our findings reveal an increase in Impdh2 expression during the adipogenesis phase, both in vivo and in vitro. Xmp enhances adipogenic potential by fostering mitotic clonal expansion (MCE). The conditional knockout of Impdh2 in adipocyte progenitor cells(APCs) in adult and aged mice effectively curbs white adipose tissue expansion, ameliorates glucose tolerance, and augments energy expenditure under high-fat diet (HFD). However, no significant difference is observed under normal chow diet (NCD). Concurrently, the knockout of Impdh2 in APCs significantly reduces the count of new adipocytes induced by HFD, without affecting adipocyte size. Mechanistically, Impdh2 regulates the proliferation of APCs during the MCE phase via Xmp. Exogenous Xmp can significantly offset the reduction in adipogenic abilities of APCs due to Impdh2 deficiency. In summary, we discovered that adipogenesis-mediated WAT expansion, induced by overnutrition, also contributes to metabolic abnormalities. Moreover, the pivotal role of Impdh2 in regulating adipogenesis in APCs offers a novel therapeutic approach to combat obesity.

Breastfeeding is associated with enhanced intestinal gluconeogenesis in infants.

BACKGROUND: Breastfeeding (BF) confers metabolic benefits to infants, including reducing risks of metabolic syndrome such as obesity and diabetes later in life. However, the underlying mechanism is not yet fully understood. Hence, we aim to investigate the impacts of BF on the metabolic organs of infants. METHODS: Previous literatures directly studying the influences of BF on offspring's metabolic organs in both animal models and humans were comprehensively reviewed. A microarray dataset of intestinal gene expression comparing infants fed on breastmilk versus formula milk was analyzed. RESULTS: Reanalysis of microarray data showed that BF is associated with enhanced intestinal gluconeogenesis in infants. This resembles observations in other mammalian species showing that BF was also linked to increased gluconeogenesis. CONCLUSIONS: BF is associated with enhanced intestinal gluconeogenesis in infants, which may underpin its metabolic advantages through finetuning metabolic homeostasis. This observation seems to be conserved across species, hinting its biological significance.

Association between being large for gestational age and cardiovascular metabolic health in children conceived from assisted reproductive technology: a prospective cohort study.

BACKGROUND: To the best of our knowledge, no study has investigated the potential joint effect of large for gestational age (LGA) and assisted reproductive technology (ART) on the long-term health of children. METHODS: This was a prospective cohort study that recruited children whose parents had received ART treatment in the Center for Reproductive Medicine, Shandong Provincial Hospital, affiliated to Shandong University, between January 2006 and December 2017. Linear mixed model was used to compare the main outcomes. The mediation model was used to evaluate the intermediary effect of body mass index (BMI). RESULTS: 4138 (29.5%) children born LGA and 9910 (70.5%) children born appropriate for gestational age (AGA) were included in the present study. The offspring ranged from 0.4 to 9.9 years. LGAs conceived through ART were shown to have higher BMI, blood pressure, fasting blood glucose, fasting insulin, and homeostatic model assessment of insulin resistance values, even after controlling for all covariates. The odds of overweight and insulin resistance are also higher in LGA subjects. After adjusting for all covariates, LGAs conceived through ART had BMI and BMI z-scores that were 0.48 kg/m2 and 0.34 units greater than those of AGAs, respectively. The effect of LGA on BMI was identified as early as infancy and remained consistently significant throughout pre-puberty. CONCLUSIONS: Compared to AGA, LGA children conceived from ART were associated with increased cardiovascular-metabolic events, which appeared as early as infancy and with no recovery by pre-puberty.

Effect of exercise alone and in combination with time-restricted eating on cardiometabolic health in menopausal women.

There is a need to investigate the effect of lifestyle modifications on cardiometabolic health-related issues that occur during menopause. The aim of this study was to compare the effect of resistance and endurance circuit training program alone (exercise group, n = 34) with the effect of time-restricted eating (16:8) combined with a training program (combination group, n = 28) on cardiometabolic health in 62 menopausal women (aged 51.3 ± 4.69 years). Testing was conducted before and after a 12-week period and included an assessment of body composition, glycemic control, lipid panel, blood pressure, and anthropometric measurements. Decreases in body mass index and systolic blood pressure were significantly greater in the combination group than in the exercise group (F(1,60) = 4.482, p = 0.038, η2 = 0.07; F(1,57) = 5.215, p = 0.026, η2 = 0.08, respectively, indicating moderate effects). There were significant decreases in fat mass (p = 0.001, r = 0.654), glucose level (p = 0.017, r = 0.459), insulin level (p = 0.013, r = 0.467), homeostatic model assessment for insulin resistance (p = 0.009, r = 0.499), waist circumference (p = 0.002, r = 0.596), and waist-to-height ratio (p = 0.003, r = 0.588) (indicating moderate effect) in the combination group, while there were no significant changes in the exercise group. There were no changes in lipid panel indicators in either group. This is the first study to investigate the effect of time-restricted eating combined with exercise in menopausal women. The results of the study provide evidence that the combination of time-restricted eating and exercise leads to a greater body mass index reduction than exercise alone in menopausal women.Trial registration: ClinicalTrials.gov, NCT06138015 registered 18 November 2023-Retrospectively registered, https://clinicaltrials.gov/study/NCT06138015 .

Associations of metabolic changes and polygenic risk scores with cardiovascular outcomes and all-cause mortality across BMI categories: a prospective cohort study.

BACKGROUND: Associations between metabolic status and metabolic changes with the risk of cardiovascular outcomes have been reported. However, the role of genetic susceptibility underlying these associations remains unexplored. We aimed to examine how metabolic status, metabolic transitions, and genetic susceptibility collectively impact cardiovascular outcomes and all-cause mortality across diverse body mass index (BMI) categories. METHODS: In our analysis of the UK Biobank, we included a total of 481,576 participants (mean age: 56.55; male: 45.9%) at baseline. Metabolically healthy (MH) status was defined by the presence of < 3 abnormal components (waist circumstance, blood pressure, blood glucose, triglycerides, and high-density lipoprotein cholesterol). Normal weight, overweight, and obesity were defined as 18.5 ≤ BMI < 25 kg/m2, 25 ≤ BMI < 30 kg/m2, and BMI ≥ 30 kg/m2, respectively. Genetic predisposition was estimated using the polygenic risk score (PRS). Cox regressions were performed to evaluate the associations of metabolic status, metabolic transitions, and PRS with cardiovascular outcomes and all-cause mortality across BMI categories. RESULTS: During a median follow-up of 14.38 years, 31,883 (7.3%) all-cause deaths, 8133 (1.8%) cardiovascular disease (CVD) deaths, and 67,260 (14.8%) CVD cases were documented. Among those with a high PRS, individuals classified as metabolically healthy overweight had the lowest risk of all-cause mortality (hazard ratios [HR] 0.70; 95% confidence interval [CI] 0.65, 0.76) and CVD mortality (HR 0.57; 95% CI 0.50, 0.64) compared to those who were metabolically unhealthy obesity, with the beneficial associations appearing to be greater in the moderate and low PRS groups. Individuals who were metabolically healthy normal weight had the lowest risk of CVD morbidity (HR 0.54; 95% CI 0.51, 0.57). Furthermore, the inverse associations of metabolic status and PRS with cardiovascular outcomes and all-cause mortality across BMI categories were more pronounced among individuals younger than 65 years (Pinteraction < 0.05). Additionally, the combined protective effects of metabolic transitions and PRS on these outcomes among BMI categories were observed. CONCLUSIONS: MH status and a low PRS are associated with a lower risk of adverse cardiovascular outcomes and all-cause mortality across all BMI categories. This protective effect is particularly pronounced in individuals younger than 65 years. Further research is required to confirm these findings in diverse populations and to investigate the underlying mechanisms involved.

Metabolically healthy obesity, transition from metabolic healthy to unhealthy status, and carotid atherosclerosis.

BACKGROUND: Evidence of the effects of metabolically healthy obesity (MHO) on atherosclerosis is limited; the transition effects of metabolic health and obesity phenotypes have been ignored. We examined the association between metabolic health and the transition to atherosclerosis risk across body mass index (BMI) categories in a community population. METHODS: This cross-sectional study was based on a national representative survey that included 50,885 community participants aged ≥40 years. It was conducted from 01 December 2017 to 31 December 2020, in 13 urban and 13 rural regions across Hunan China. Metabolic health was defined as meeting less than three abnormalities in blood pressure, glucose, high-density lipoprotein cholesterol, triglycerides, or waist circumference. The participants were cross-classified at baseline based on their metabolic health and obesity. In addition, the relationship between atherosclerosis and transitions in metabolic health status based on 4733 participants from baseline to the second survey after 2 years was considered. The relationship between metabolic health status and the risk of transition to Carotid atherosclerosis (CA) was assessed using logistic regression and Cox proportional hazards regression analyses. RESULTS: In this study, the mean age of the participants was 60.7 years (standard deviation [SD], 10.91), 53.0% were female, and 51.2% had CA. As compared with metabolically healthy normal weight (MHN), those with MHO phenotype (odd ratio [OR] 1.10, 95% confidence interval [CI] 1.02-1.21), metabolically unhealthy normal weight (OR 1.27, 95% CI 1.19-1.35), metabolically unhealthy overweight (OR 1.41, 95% CI 1.33-1.48), and metabolically unhealthy obese (OR 1.54, 95% CI 1.44-1.64) had higher risk for CA. However, during the follow-up of 2 years, almost 33% of the participants transitioned to a metabolically unhealthy status. As compared with stable healthy normal weight, transition from metabolically healthy to unhealthy status (hazard ratios [HR] 1.21, 95% [CI] 1.02-1.43) and stable metabolically unhealthy overweight or obesity (MUOO) (HR 1.32, 95% CI 1.17-1.48) were associated with higher risk of CA. CONCLUSIONS: In the community population, obesity remains a risk factor for CA despite metabolic health. However, the risks were highest for metabolically unhealthy status across all BMI categories. A large proportion of metabolically healthy overweight or participants with obesity converts to an unhealthy phenotype over time, which is associated with an increased risk of CA.

Age-Related Gut Microbiota Transplantation Disrupts Myocardial Energy Homeostasis and Induces Oxidative Damage.

BACKGROUND: Aging-related energy homeostasis significantly affects normal heart function and disease development. The relationship between the gut microbiota and host energy metabolism has been well established. However, the influence of an aged microbiota on energy metabolism in the heart remains unclear. OBJECTIVE: The objective of this was to explore the effects of age-related microbiota composition on energy metabolism in the heart. METHODS: In this study, we used the fecal microbiota transplantation (FMT) method. The fecal microbiota from young (2-3 mo) and aged (18-22 mo) donor mice were transplanted into separate groups of young (2-3 mo) recipient mice. The analysis utilized whole 16S rRNA sequencing and plasma metabolomics to assess changes in the gut microbiota composition and metabolic potential. Energy changes were monitored by performing an oral glucose tolerance test, biochemical testing, body composition analysis, and metabolic cage measurements. Metabolic markers and markers of DNA damage were assessed in heart samples. RESULTS: FMT of an aged microbiota changed the composition of the recipient's gut microbiota, leading to an elevated Firmicutes-to-Bacteroidetes ratio. It also affected overall energy metabolism, resulting in elevated plasma glucose concentrations, impaired glucose tolerance, and epididymal fat accumulation. Notably, FMT of an aged microbiota increased the heart weight and promoted cardiac hypertrophy. Furthermore, there were significant associations between heart weight and cardiac hypertrophy indicators, epididymal fat weight, and fasting glucose concentrations. Mechanistically, FMT of an aged microbiota modulated the glucose metabolic pathway and induced myocardial oxidative damage. CONCLUSIONS: Our findings suggested that an aged microbiota can modulate metabolism and induce cardiac injury. This highlights the possible role of the gut microbiota in age-related metabolic disorders and cardiac dysfunction.

Current research progress, opportunities, and challenges of Limosillactobacillus reuteri-based probiotic dietary strategies.

Limosillactobacillus reuteri (L. reuteri), a type of Lactobacillus spp., stands out as the most extensively researched probiotic. Its remarkable intestinal adhesion has led to widespread applications in both the food and medical sectors. Notably, recent research highlights the probiotic efficacy of L. reuteri sourced from breast milk, particularly in influencing social behavior and mitigating atopic dermatitis. In this review, our emphasis is on surveying recent literature regarding the promotion of host's health by L. reuteri. We aim to provide a concise summary of the latest regulatory effects and potential mechanisms attributed to L. reuteri in the realms of metabolism, brain- and immune-related functions. The mechanism through which L. reuteri promotes host health by modulating the intestinal microenvironment primarily involves promoting intestinal epithelial renewal, bolstering intestinal barrier function, regulating gut microbiota and its metabolites, and suppressing inflammation and immune responses. Additionally, this review delves into new technologies, identifies shortcomings, and addresses challenges in current L. reuteri research. Finally, the application prospects of L. reuteri are provided. Therefore, a better understanding of the role and mechanisms of L. reuteri will contribute significantly to the development of new probiotic functional foods and enable precise, targeted interventions for various diseases.

The relationship between the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and metabolic health status in adolescents with overweight and obesity: results from a cross-sectional study in Iran.

Few studies investigated the association between Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and metabolic health status, particularly among adolescents. The present study was designed to investigate the association of MIND diet with metabolic health status in Iranian adolescents with overweight/obesity. This cross-sectional study was done among 203 adolescents with overweight/obesity (12-18 years) in Isfahan, Iran. A validated FFQ was applied to collect dietary intakes. Anthropometric indices and blood pressure were also measured by standard procedures. Fasting blood samples were obtained to determine serum insulin, glucose and lipid profile. To categorise participants as being with metabolically healthy overweight/obesity (MHO) or metabolically unhealthy overweight/obesity (MUO), two methods including International Diabetes Federation (IDF) criteria and IDF plus Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) were applied. Participants had a mean age of 13·98 years and 50·2 % of them were girls. In fully adjusted models, participants with highest MIND diet adherence had lower odds of MUO status based on IDF (OR = 0·20; 95 % CI 0·08, 0·51) and IDF/HOMA-IR (OR = 0·22; 95 % CI 0·08, 0·59) criteria. Stratified analyses revealed that this association was stronger among girls and was only significant among individuals with overweight. An inverse association was also found between MIND diet score and odds of hyperglycaemia and insulin resistance (IR). Higher MIND diet adherence was associated with lower odds MUO in adolescents with overweight/obesity. Inverse associations were also found between MIND diet and odds of hyperglycaemia and IR. Future longitudinal prospective studies are necessary to confirm our results.

Influence of consuming coffee and other beverages in adolescence on risk of type 2 diabetes in adulthood.

BACKGROUND: Dietary strategies for type 2 diabetes (T2DM) prevention have mainly focused on solid foods and nutrients. Emanating evidence suggests that beverage consumption in adulthood may also influence T2DM development, whereas the role of beverages during adolescence remains unknow. OBJECTIVE: To examine adolescent beverages consumption, and their changes from adolescence to adulthood in relation to T2DM risk in adulthood. METHODS: This prospective cohort study, conducted within the Nurses' Health Study II (NHS II), enrolled 41,317 women who completed a food-frequency questionnaire (FFQ) regarding their diet in high school and had no diabetes, cardiovascular disease, or cancer at baseline (1997). Beverage consumption including coffee, tea, regular or diet soda, fruit juice or milk, was assessed using the FFQ. Cox proportional hazards models were utilized to estimate hazard ratios (HRs) for the association between beverage consumption in adolescence and risk of incident type 2 diabetes (T2DM) in adulthood, adjusting for potential confounders. RESULTS: During 725,650 person-years of follow-up, 2,844 participants developed T2DM. After adjustment for demographic, lifestyle and dietary risk factors, comparing ≥ 1 serving/day with non-consumers, adolescent coffee [HR, 0.86 (95% confidence interval: 0.75 to 0.98); P-trend = 0.02)] and orange juice [HR, 0.83 (0.71 to 0.96); P-trend = 0.0008)] consumption was associated with lower T2DM risk, whereas, regular soda [HR, 1.37 (1.20 to 1.57); P-trend < 0.0001)] and iced tea [HR, 1.41 (1.21 to 1.65); P-trend < 0.0001)] intake was associated with higher T2DM risk. Increased coffee intake from adolescence to adulthood in 1991 was associated with a lower T2DM risk [HR, 0.70 (0.61 to 0.80); P-trend < 0.0001), comparing ≥ + 3 servings/day with no change], whereas the opposite was observed for increased regular soda [HR, 1.20 (1.06 to 1.35); P-trend = 0.004), comparing ≥ + 1 or more servings/week with no change)] and diet soda consumption [HR, 1.59 (1.41 to 1.80); P-trend = 0.0002), comparing ≥ + 2 servings/day with no change]. CONCLUSION: Adolescent consumption of coffee or orange juice intake was associated with a lower risk of T2DM, whereas the opposite was observed for intake of regular soda or iced tea. In addition, increased coffee intake was associated with a lower diabetes risk, whereas the opposite was observed for regular or diet soda intake. These data highlight a potentially important role of beverage intake at early life in the etiology of diabetes during adulthood.

Plant-based diet adherence is associated with metabolic health status in adults living with and without obesity.

PURPOSE: Metabolic health phenotypes exist across the body mass index spectrum. Diet may be an important modifiable risk factor, yet limited research exists on dietary patterns in this context. We investigated associations between dietary patterns, reflecting dietary quality, healthfulness and inflammatory potential, and metabolic health phenotypes in adults living with and without obesity. METHODS: This cross-sectional study included 2,040 middle- to older-aged men and women randomly selected from a large primary care centre. The Dietary Approaches to Stop Hypertension score, Healthy Eating Index, Dietary Inflammatory Index, overall, healthful and unhealthful plant-based dietary indices and Nutri-Score were derived from validated food frequency questionnaires. Descriptive and logistic regression analyses were used to examine diet score relationships with metabolic health phenotypes (Metabolically Healthy/Unhealthy Obese (MHO/MUO) and Non-Obese (MHNO/MUNO)), defined using three separate metabolic health definitions, each capturing different aspects of metabolic health. RESULTS: In fully adjusted models, higher unhealthful plant-based dietary scores were associated with a lower likelihood of MHO (OR = 0.96, 95% CI: 0.93-1.00, p = 0.038) and MHNO (OR = 0.97, 95% CI: 0.95-0.99, p = 0.006). Higher Nutri-Score values were associated with an increased likelihood of MHNO (OR = 1.06, 95% CI: 1.01-1.13, p = 0.033). CONCLUSION: These findings provide evidence that more unhealthful plant-based diets may be linked with unfavourable metabolic health status, irrespective of BMI.

The association between the triglyceride-glucose index and vitamin D status: a systematic review and meta-analysis.

OBJECTIVE: This study aims to explore the association between the triglyceride-glucose (TyG) index and vitamin D status to enhance our understanding of how vitamin D status relates to metabolic health and to provide evidence for the early diagnosis of vitamin D deficiency (VDD) using the TyG index. METHODS: We conducted a comprehensive search in various databases, including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine disc, China Science and Technology Journal Database, and Wanfang Data to gather articles published from the inception of these databases until February 19, 2024. We assessed the quality of included studies using the Newcastle-Ottawa Scale (NOS) for case-control studies and the Agency for Healthcare Research and Quality (AHRQ) methodology checklist for cross-sectional studies. Statistical analyses in this study were conducted using conversion methods for non-standard data formats and consolidation techniques for combining multiple groups. The Fisher transformation method was used for correlation coefficients. We used a random-effects model considering the inherent clinical heterogeneity among the studies, and assessed statistical heterogeneity with the Cochrane Q test and I2 statistic, complemented by subgroup analyses and sensitivity analysis. RESULTS: Our meta-analysis selected a total of nine studies. The analysis revealed that patients with vitamin D deficiency (VDD group) exhibited a significantly higher TyG index than those without deficiency (no-VDD group), with a mean difference (MD) of 0.16 (95% CI: 0.10 to 0.23, I2 = 93%). This association was particularly pronounced among patients with type 2 diabetes (T2DM), showing an MD of 0.15 (95% CI: 0.05 to 0.26, I2 = 55%). Additionally, a negative correlation was observed between the TyG index and vitamin D levels, with a correlation coefficient (r) of -0.236 (95% CI: -0.310 to -0.159, I2 = 91%). Excluding each study sequentially in the sensitivity analyses did not significantly alter the outcomes. CONCLUSIONS: Our findings demonstrate a significant association between the TyG index and vitamin D status across diverse populations, including those with T2DM, subclinical hypothyroidism (SCH), and metabolic associated fatty liver disease (NAFLD). Our results reveal a notable disparity in the TyG index between vitamin D deficient and non-deficient groups, suggesting that vitamin D may play a critical role in metabolic health. These findings highlight the need for further research to explore the underlying mechanisms and clinical implications of vitamin D in the context of various metabolic disorders.

Postprandial triglycerides across the aging spectrum: A secondary analysis utilizing an abbreviated fat tolerance test.

BACKGROUND & AIMS: Elevated postprandial triglycerides are an independent cardiovascular disease risk factor and observed in older adults. However, differences in postprandial triglycerides across the spectrum of adulthood remain unclear. METHODS AND RESULTS: We performed a secondary analysis of six studies where adults (aged 18-84 years; N = 155) completed an abbreviated fat tolerance test (9 kcal/kg; 70% fat). Differences in postprandial triglycerides were compared in those ≥50 and <50 years and by decade of life, adjusting for sex and BMI. Compared to those <50 years, participants ≥50 years had higher fasting, 4 h, and Δ triglycerides from baseline (p's < 0.05). When examining triglyceride parameters by decade, no differences were observed for fasting triglycerides, but 50 s, 60 s, and 70s-80 s displayed greater 4 h and Δ triglycerides versus 20 s (p's ≤ 0.001). The frequency of adverse postprandial triglyceride responses (i.e., ≥220 mg/dL) was higher in participants ≥50 versus <50 years (p < 0.01), and in 60 s compared to all other decades (p = 0.01). CONCLUSION: Older age was generally associated with higher postprandial triglycerides, with no divergence across the spectrum of older adulthood. In our sample, postprandial triglyceride differences in older and younger adults were driven by those >50 years relative to young adults in their 20 s. REGISTRATION: N/A (secondary analysis).

Genetic correlations between liver fat content, metabolic health, and adiposity distribution in the Fels Longitudinal Study.

BACKGROUND AND AIMS: Hepatic steatosis is known to be heritable, but its genetic basis is mostly uncharacterized. Steatosis is associated with metabolic and adiposity features; recent studies hypothesize that shared genetic effects between these traits could account for some of the unexplained heritability. This study aimed to quantify these genetic associations in a family-based sample of non-Hispanic white adults. METHODS AND RESULTS: 704 participants (18-95 years, 55.8% female) from the Fels Longitudinal Study with an MRI assessment of liver fat were included. Quantitative genetic analyses estimated the age- and sex-adjusted heritability of individual traits and the genetic correlations within trait pairs. Mean liver fat was 5.95% (SE = 0.23) and steatosis (liver fat >5.56%) was present in 29.8% of participants. Heritability (h2± SE) of steatosis was 0.72 ± 0.17 (p = 6.80e-6). All other traits including liver enzymes, fasting glucose, HOMA-IR, visceral and subcutaneous adipose tissue (VAT, SAT), body mass index, body fat percent, waist circumference, lipids and blood pressure were also heritable. Significant genetic correlations were found between liver fat and all traits except aspartate aminotransferase (AST), and among most trait pairs. Highest genetic correlations were between liver fat and HOMA-IR (0.85 ± 0.08, p = 1.73e-8), fasting glucose and ALT (0.89 ± 0.26, p = 6.68e-5), and HOMA-IR with: waist circumference (0.81 ± 0.12, p = 3.76e-6), body fat percent (0.78 ± 0.12 p = 2.42e-5) and VAT (0.73 ± 0.07, p = 6.37e-8). CONCLUSIONS: Common genes may exist between liver fat accumulation, metabolic features and adiposity phenotypes.

A pre-post trial to examine biological mechanisms of the effects of time-restricted eating on symptoms and quality of life in bipolar disorder.

BACKGROUND: The primary objective of this trial is to examine the mechanisms of time-restricted eating (TRE) as an adjunct to psychiatric care for people with bipolar disorder (BD) with sleep or circadian disruptions. This study builds on prior studies of circadian disruption in BD as well as growing evidence that TRE improves circadian functioning. METHODS: One-hundred fifty participants diagnosed with BD 1 or II will be recruited via advertising in the local community. Main inclusion criteria include: obtaining medical treatment for BD; current sleep or circadian problems; self-reported eating period of ≥ 12 h; no eating disorder or other health conditions that would hinder or limit the safety of following TRE; and not currently experiencing a mood episode, acute suicidality, psychosis, alcohol or substance use disorder. Participants will be asked to complete a baseline period in which daily food intake is logged online for two weeks. After baseline, participants will be asked to follow TRE for 8 weeks and to continue to complete daily food logging during this time. Symptom severity interviews will be conducted by phone or videoconference at baseline, mid-intervention (6 weeks post-baseline), end of intervention (10 weeks post-baseline), and 6 months post-baseline. Self-rated symptom severity and quality of life data will be gathered online at the same time points as symptom severity interviews, and at 16 weeks post-baseline (6 weeks after the TRE period ends). To assess potential mechanisms of change, we will examine the change in diurnal amplitude of 'clock' gene expression as a primary mediator at 8 weeks compared to baseline. We will further test whether diurnal amplitude of clock gene expression is predictive above and beyond the role of two covariate potential mediators, glucose tolerance and inflammation at 8 weeks relative to baseline. To provide an index of whether TRE successfully decreases emotional lability, participants will be asked to complete 5 mood assessments per day for 7 days at baseline and at 10 weeks. These mood assessments will be optional. DISCUSSION: The planned research will provide novel and important information on whether TRE improves sleep/circadian rhythm problems, along with reductions in mood symptoms and improvements in quality of life, for individuals with BD. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT06555406.

Ultra-processed foods intake in relation to metabolic health status, serum brain-derived neurotrophic factor and adropin levels in adults.

BACKGROUND: In recent years, there has been a lot of discussion over the impact of ultra-processed foods (UPFs) intake on overall health of subjects. However, the association between UPFs intake and metabolic unhealthy (MU) status is still in a state of ambiguity. The current study assessed the relationship between UPFs intake and MU status with regard to brain-derived neurotrophic factor (BDNF) and adropin levels. METHODS: A sample of Iranian adults (aged 20-65 years) was selected to participate in this cross-sectional study using a multistage cluster random-sampling method. UPFs intake was assessed by a validated food frequency questionnaire and NOVA classification. Concentrations of metabolic parameters, BDNF and adropin were determined through fasting blood samples. MU status was assessed according to the criteria proposed by Wildman. RESULTS: The overall prevalence of MU phenotype among study participants (n = 527) was 42.5%. Higher intake of UPFs was associated with elevated odds of MU status in multivariable-adjusted model (ORT3 vs. T1=1.88; 95%CI: 1.02-3.45). Moreover, a positive association was observed between UPFs intake and hypertriglyceridemia after controlling all confounders (ORT3 vs. T1=2.07; 95%CI: 1.15-3.73). However, each tertile increase in UPFs intake was not significantly associated with serum BDNF ([Formula: see text]=0.15; 95%CI: -0.05, 0.34; P = 0.14) and adropin ([Formula: see text]=-1.37; 95%CI: -6.16, 3.42; P = 0.58) levels in multivariable-adjusted linear regression models. CONCLUSION: Our findings suggested that higher consumption of UPFs was related to increased likelihood of MU status among a sample of Iranian adults. Further longitudinal studies are needed to verify the directionality and generalizability of the results to all adult populations.