Cardiometabolic Risk Factors

Background: As of 2021, almost 45 million people in the United States were foreign-born immigrants. South Asians, including people from Bhutan, are the fastest-growing immigrant subgroup in the US. Their income and education levels are higher than the US average. Yet they have worse physical and mental health outcomes than their White US-born counterparts. These risks include type 2 diabetes and obesity. Objective: This natural history study will explore how life experiences and environmental factors affect heart health and metabolism among Bhutanese people living in the US. Eligibility: Adults aged 18 years or older who identify as Bhutanese and live in the US. Design: Participants will be recruited and screened by the Bhutanese Community of Central Ohio (BCCO). They will have 1 visit to the BCCO s Arogya Clinic in Reynoldsburg. The visit will last 2 hours. Participants will take a survey; they may use either English or Nepali. They will answer questions about their background; their experiences living in the US; and how their customs and habits might have changed. They will also be asked about their experiences with discrimination; their mental health and well-being; their community; quality of life; and overall physical health. The survey will take 60 minutes. Participants will also speak with a researcher. They will be asked how they feel about providing biological samples; these may include saliva, blood, and urine. Their answers will be audio recorded.

Background: As of 2021, almost 45 million people in the United States were foreign-born immigrants. South Asians, including people from Bhutan, are the fastest-growing immigrant subgroup in the US. Their income and education levels are higher than the US average. Yet they have worse physical and mental health outcomes than their White US-born counterparts. These risks include type 2 diabetes and obesity. Objective: This natural history study will explore how life experiences and environmental factors affect heart health and metabolism among Bhutanese people living in the US. Eligibility: Adults aged 18 years or older who identify as Bhutanese and live in the US. Design: Participants will be recruited and screened by the Bhutanese Community of Central Ohio (BCCO). They will have 1 visit to the BCCO s Arogya Clinic in Reynoldsburg. The visit will last 2 hours. Participants will take a survey; they may use either English or Nepali. They will answer questions about their background; their experiences living in the US; and how their customs and habits might have changed. They will also be asked about their experiences with discrimination; their mental health and well-being; their community; quality of life; and overall physical health. The survey will take 60 minutes. Participants will also speak with a researcher. They will be asked how they feel about providing biological samples; these may include saliva, blood, and urine. Their answers will be audio recorded.

Insulin resistance is an early etiological factor in the development of type-2 diabetes (T2D), which constitutes a large societal health burden with an expected additional rise in the years to come. Skeletal muscle is the body's largest lean tissue mass and the major site of glucose disposal in response to insulin stimulation. Prior studies have suggested that a fast skeletal muscle phenotype, including a predominant fast muscle fiber composition, reduced capillary density, low fat oxidation and muscle oxidative capacity may be implicated in insulin resistance and TD2 development. However, key questions pertain in relation to the cause and effect of these relationships as well as the interaction with potential confounders and effect-modifiers including life-style factors (e.g. diet and physical activity levels) and general participant characteristics (e.g. body composition and training status). In the present project, we therefore aim to derive muscle fiber type and extensively map the proteomic signature of the early stages of insulin resistance in a large cross-sectional study using a young and apparently healthy cohort prior to T2D development, including a thorough participant characterization. We will recruit \~250 participants (men and women) in the age of 20-30 years and conduct extensive phenotyping and tissue sampling across one laboratory-based test day and a scan visit, as well as measurements of physical activity level and glucose handling in free-living conditions with wearable sensors. The study has a longitudinal aspect as participants will be re-invited at 5-year intervals for up to 20 years to delineate the trajectory of metabolic health in relation to muscle phenotype measures. The results of the project are expected to lead to significant advancements in our understanding of the importance of muscle phenotype for early-stage insulin resistance and metabolic health trajectories. Such understanding has potentially important clinical implications, as it can open new avenues for targeted interventions and individualized early preventive strategies to counter or delay the progression of insulin resistance and associated metabolic and cardiovascular disorders.

Ultra-processed food (UPF) intake has been related to negative health effects and incresed energy intake in previous intervention studies. Thus, previous studies have seen weight gain from higher UPF intake which obscures the potentital to see effects on cardiometabolic biomarkers, independent of weight changes. The overall aim of this project is to study the causal effects of a high UPF diet, compared to a nutrient-matched low UPF diet, on appetite and cardiometabolic health in a weight-stable context.

In a single-blind, randomised, placebo-controlled crossover manner, this study aims to assess the impact of a high-fat mixed meal containing a whey protein (WP)-enriched milk fat globule membrane (MFGM) powdered ingredient on markers of heart and brain health in the fed state among middle-to-older-aged, postmenopausal women living with overweight and at moderate risk for cardiovascular disease. Participants will attend two \~8 hour study visits, where they will consume a high-fat meal containing a WP-enriched MFGM powdered ingredient or a placebo WP-based powdered ingredient. Each visit will involve anthropometric measurements and periodic assessments of heart health, including blood pressure and blood vessel stiffness measurements, blood sample collections, as well as computer-based tests measuring mood and cognition (brain function) over a 6-hour postprandial period.

1. This proposed double-blind placebo controlled randomized controlled trial incorporates recent advances in management of heart failure and portal hypertension using the SGLT-2 inhibitor i.e. EMPAGLIFLOZIN. The drug has been found to be useful in large trials on heart failure with preserved ejection fraction in the general population with improvement in MASLD progression, with improvement in body weight and hepatic steatosis but no change in liver fibrosis. 2. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to reduce the development and progression of heart failure in patients with type 2 diabetes and in those with heart failure and a reduced and preserved ejection fraction. In patients with cirrhosis safety of empagliflozin in a dose of 10 mg has been demonstrated. 3. Prevention of decompensation related events in cirrhosis is the key endpoint of any liver-directed therapy as the median survival in the compensated state exceeds 10 years but median survival in the decompensated state approximates 1.5 years. Previous data has demonstrated the risk of hepatic decompensation acute kidney injury and poor survival in patients with cirrhosis and heart failure with preserved ejection fraction (HFpEF) i.e. LVDD a large subset of whom meet criteria for CCM.

Controversy remains around the role of ultra-processed food (UPF) consumption and health outcomes. A key question that remains to be answered is: when diet quality is the same, does food processing itself have any independent health effects? The current application aims to isolate the health effects of food processing from those of diet quality through the conduct of a dietary intervention study.

The goal of this observational study is to learn if a non-contact facial scan using artificial intelligence (AI) can be used to check health status in adults living in urban areas such as Jakarta. The facial scan uses a method called remote photoplethysmography (rPPG), which measures small changes in blood flow from the face using a camera. The main questions this study aims to answer are: 1. How close are the results from the facial scan to standard medical measurements, such as heart rate, breathing rate, blood pressure, and oxygen levels? 2. Can the facial scan estimate other health indicators, such as blood sugar, lipid profile, HbA1c, and hemoglobin levels? 3. Is there a relationship between the facial scan results and mental health, such as stress, anxiety, and depression? Participants will take part in several simple and mostly non-invasive procedures: 1. Answer questionnaires about their mental health and daily habits 2. Have basic health checks, such as blood pressure, heart rate, and body measurements 3. Provide a blood sample for laboratory testing 4. Complete a facial scan using a camera for about 1 to 3 minutes Researchers will compare the results from the facial scan with standard clinical and laboratory tests to see how well the technology works. This study may help develop a simple and accessible screening tool that can be used for early detection of health risks. It may also support the use of digital health and telemedicine in community and clinical settings.

The purpose of this Phase 1 research study is to answer two questions: (1) How frequent should periods of prolonged sedentary time be interrupted? and (2) What is the appropriate duration or length of time of these breaks in sedentary time? To address these questions, this project will conduct a state-of-the-art adaptive dose finding study under controlled laboratory conditions to determine the minimally effective dose (the smallest dose) that yields cardiometabolic benefit for two separate sedentary break elements (frequency and duration). Study findings will ultimately determine how often and for how long people should break up periods of prolonged sedentary time to transiently improve established cardiovascular risk factors; key foundational information critical to the success of future long-term trials and ultimately public health guidelines. Primary Aim: To determine the minimally effective dose combination(s) of frequency and duration needed to provide cardiometabolic benefit during an 8-hour experimentation period. Specifically, the study will determine: 1a. For each fixed duration, the minimum sedentary break frequency (e.g., every 30 min, 60 min, 120 min) that demonstrates a reduction in systolic BP, diastolic BP, or glucose compared with a sedentary control condition. 1b. For each fixed frequency, the minimum sedentary break duration (e.g., activity breaks of 1 min, 5 min, 10 min) that demonstrates a reduction in systolic BP, diastolic BP, or glucose compared with a sedentary control. Secondary Aim: It is also critical to public health strategy to assess the acceptability/feasibility of various sedentary break doses as too high a dose will yield poor uptake. To address this need, the maximally tolerated dose (the highest dose that does not cause undue physical/psychological distress) for frequency and duration of sedentary breaks will also be determined via assessment of 4 constructs: physical exhaustion/fatigue, affect (e.g., mood, emotion), tolerability (e.g., completion of dose protocol), and safety (e.g., hypoglycemia). Maximally tolerated dose will be defined as the highest dose where \<20% of participants exhibit an adverse outcome.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is the new clinical term introduced in 2023 to redefine what was formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD). It is defined as fatty liver confirmed by imaging or biopsy, accompanied by at least one cardiometabolic risk factor (e.g., hyperglycemia, dyslipidemia, hypertension, or obesity). Its pathological progression ranges from simple steatosis to steatohepatitis, primarily driven by excessive energy intake, hepatic lipid accumulation, and insulin resistance. MASLD is currently the most prevalent chronic liver disease globally, with a prevalence rate of approximately 30-40%. However, there is no satisfactory pharmacological treatment, leaving lifestyle modification as the primary therapeutic approach. Many patients struggle to effectively adjust their habits, leading to persistent hepatic inflammation and damage, which may eventually progress to end-stage diseases such as cirrhosis and hepatocellular carcinoma. In many developed countries, MASLD has become the leading indication for liver transplantation, imposing a heavy burden on healthcare systems. Gut dysbiosis is closely linked to MASLD. An imbalance in the gut microbiota disrupts the gut-liver axis, leading to impaired intestinal mucosal barrier function. This allows bacterial components to enter the circulation, further triggering hepatic inflammation and abnormal lipid metabolism. Consequently, modulating the gut microbiota is considered a potential therapeutic strategy. Over the past decade, probiotics, prebiotics, and synbiotics have been extensively studied as non-pharmacological treatments for NAFLD. Multiple studies indicate that these products can reduce liver enzymes (AST, ALT), insulin resistance (HOMA-IR), and inflammatory markers (hs-CRP, TNF-α). The most effective combinations typically involve Lactobacillus, Bifidobacterium, and Streptococcus, with a recommended duration of approximately 12 weeks. However, the impact of these products on liver fibrosis, hepatic fat accumulation, and cardiometabolic risk factors remains inconclusive. The probiotic product to be tested consists of Lactobacillus salivarius AP-32, Lactobacillus rhamnosus bv-77, Bifidobacterium animalis CP-9, and Lactobacillus reuteri GL-104. This formulation complies with food safety regulations. In clinical studies, it had been proven as an effective adjuvant method that increased beneficial gut bacteria such as Akkermansia muciniphila and improved the control of blood glucose, lipids, and inflammatory markers. Study Objectives This study aims to investigate the efficacy of this probiotic product as an adjuvant therapy alongside lifestyle modifications in adult patients with MASLD. We will evaluate its impact on: 1. The degree of liver fibrosis and steatosis 2. Cardiometabolic risk factors (BMI, waist circumference, blood lipids, and blood glucose). 3. Inflammatory markers. 4. Gut microbiota composition.

This prospective, open-label, single-arm, single-center interventional pilot trial aims to evaluate the efficacy and safety of low-dose semaglutide for weight loss and cardiometabolic improvement in obese Pakistani adults without type 2 diabetes mellitus. The study will be conducted at the Asian Institute of Medical Sciences (AIMS), Hyderabad, Sindh, Pakistan. A total of 60 obese adults aged 18 years or older with a body mass index (BMI) of 27.5 kg/m² or greater according to World Health Organization Asian cutoffs and without type 2 diabetes mellitus (fasting blood glucose \<126 mg/dL and HbA1c \<6.5%) will be enrolled. Eligible participants will receive once-weekly subcutaneous semaglutide following a standard dose titration schedule of 0.25 mg weekly for four weeks, 0.5 mg weekly for four weeks, and 1.0 mg weekly for the remaining 16 weeks, for a total treatment duration of 24 weeks. All participants will receive standardized lifestyle counseling, including a hypocaloric diet with a 500-750 kcal/day deficit and at least 150 minutes per week of moderate-intensity physical activity. The primary outcome is the percentage change in body weight from baseline to 24 weeks. Secondary outcomes include changes in body mass index, waist circumference, systolic and diastolic blood pressure, lipid profile (total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides), liver enzymes (alanine aminotransferase and aspartate aminotransferase), and quality of life. Safety will be assessed through continuous monitoring of adverse events and adverse drug reactions with causality assessment using the Naranjo Adverse Drug Reaction Probability Scale. Clinical and laboratory assessments will be conducted at baseline, 12 weeks, and 24 weeks. Data will be analyzed using descriptive and inferential statistics, including paired t-tests or non-parametric equivalents and repeated measures analysis, with a significance level of p \< 0.05. The study will be conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki, with approval from the AIMS Institutional Review Board and written informed consent obtained from all participants. The trial aims to generate locally relevant clinical evidence on the effectiveness and safety of low-dose semaglutide for obesity management in non-diabetic Pakistani adults.

Randomized, double-blind, parallel, placebo-controlled clinical trial designed and conducted to evaluate the effect of daily consumption of ginger, on parameters related to inflammation, oxidative stress, and endothelial damage in adults with excess adiposity.

Randomized, double-blind, parallel, placebo-controlled clinical trial designed and conducted to evaluate the effect of daily consumption of ginger, on parameters related to inflammation, oxidative stress, and endothelial damage in adults with excess adiposity.

The purpose of this research study is to pilot test five different, group based and remotely delivered programs designed to support healthy eating and regular physical activity. Each group will contain information and support for healthy eating and physical activity. Groups may also include support to 1) eat with more awareness of hunger and fullness, 2) improve how people think and feel about their bodies, and/or 3) identify ways to be physically active that are more enjoyable. Each group will include a unique combination of these components and the goal is to assess overall satisfaction and engagement with each of the programs.

The primary aim of this study is to compare the acute glycemic effects of two novel, alternative physical activity (PA) strategies (dispersed post-meal PA, PA snacks) to a no PA condition and to exercise sessions representing the PA guidelines (standard 30-minute walking bout performed under fasting and under postprandial conditions and a standard 30-minute resistance training session) among sedentary breast cancer survivors who are currently receiving hormone therapies and age- and BMI-matched postmenopausal women without a history of cancer. The secondary aim is to determine whether the alternative PA strategies are acceptable and feasible in the free-living setting. An exploratory aim is to determine whether the outcomes differ between women with and without a history of breast cancer and use of aromatase inhibitors. The investigators hypothesize that: 1. Dispersed PA and PA snacks will result in greater reductions in 24-hour glucose and postprandial glucose compared to the no-PA baseline and similar reductions to a standard 30-minute bouts of walking; 2. The alternative PA strategies will be more feasible and have greater acceptability by cancer survivors compared to the standard 30-minute bout of walking or resistance training; and 3. The different PA strategies will have similar effects on glycemic outcomes for both breast cancer survivors and cancer-free controls. The resistance exercise session is an exploratory trial as the effects of it on acute glycemic control are understudied.

The goal of this randomized controlled clinical trial is to investigate the effects of vitamin D3 supplementation on cardiometabolic risk in Chinese adolescents with overweight/obesity and vitamin D deficiency. The main question it aims to answer whether vitamin D3 supplementation can improve cardiovascular metabolic health. Participants in the intervention group will receive vitamin D3. The control group will receive vitamin D placebo. Researchers will compare the change in cardiometabolic risk from baseline to post-intervention at 12 weeks between the intervention and control groups.

This cross-sectional study aims to investigate the associations between dietary intake, cardiometabolic health markers, and gut microbiota composition in Singapore adults.

Given the escalating high burdens of overeight and obesity, and related commobidies in Asia, Asian women with overweight/obesity is an important group for targeted intervention in promoting health and wellbeing. A study focused on Asian women at reproductive or early post-menopausal age can inform effective strategies for promoting healthy diet and lifetyle and for optimizing health not only among these women but also for their children and partners. The Mediterranean diet has beneficial effects on cardiometabolic and reproductive health. So far, evidence on the Mediterranean diet and its health benefits mostly come from Western populations. Studies evaluating health effects of Mediterranean diet in Asian population are scant. This study aims to investigate the beneficial effects of a healthy, Mediterranean-inspired localized diet (i.e., Asian-Mediterranean diet) on women's health, such as cardiometabolic health with potential mechanisms through modulating gut and brain health.