Singapore Adult Metabolism Study - Phase 2 (SAMS2)

Singapore Adult Metabolism Study - Phase 2 (SAMS2) was an interventional study where hundreds of donors aged 21-45 were recruited to participate in a 16-week weight loss program. Study individuals selected (see below for more detailed selection standards) were sedentary (exercise 1 or fewer times a week), obese or overweight with a body fat mass greater than 24% and a BMI between 23-35 kg/m2. For this study, we adjusted BMI definition for Asian population, based on the WHO Consultation 2002, and the BMI cut-off is 23 kg/m2 for overweight and 27.5 kg/m2 for obese. The weight loss program included a combination of dietary interventions, structured exercise sessions, and additional physical activity performed in participants' own time. Energy and protein requirements were calculated based on each participant's weight, height, and physical activity level, with the goal of achieving a 40% calorie deficit. Participants' calorie intake was tracked using food recalls and questionnaires. Additionally, subjects attended structured exercise sessions at least three times per week, supervised by a coach. Each session consisted of 90 minutes of aerobic and strength training exercises, designed to burn approximately 500 kcal per session. To monitor daily physical activity, participants wore pedometers throughout the study. In total, the exercise sessions (500 kcal per session) and daily physical activity (targeting an additional 500 kcal) were aimed at achieving a total caloric expenditure of 2000 kcal per week. We collected clinical data and skeletal muscle biopsies from 54 overweight/obese Asian individuals before and after a 16-week lifestyle intervention, which resulted in an average ~10% weight loss, accompanied by a ~30% increase in insulin-stimulated glucose uptake. Improvements were observed in 118 of 252 clinical traits and six blood lipids. Transcriptomic analysis of paired skeletal muscle biopsies identified 505 differentially expressed genes enriched in mitochondrial function and insulin sensitivity. Thousands of muscle-specific e/sQTLs were detected pre- and post- intervention, including hundreds of lifestyle-responsive e/sQTLs. Notably, approximately 4.2% of eQTLs and 7.3% of sQTLs showed Asian specificity. Joint analysis with GWAS identified 16 putative metabolic risk genes. Our study reveals gene-by-lifestyle interactions and how lifestyle modulates gene regulation in skeletal muscle.]]>
Inclusion Criteria:Aged 21-45AsianBMI is 23 kg/m² for overweight and 27.5 kg/m² for obese.Exclusion Criteria:Participants were excluded if they suffered from ischemic heart disease, epilepsy or insulin allergy, as part of the study involved using glucose clamps and insulin infusion protocols to avoid the risk of precipitating epileptic attacks or aggravating such underlying conditions. Participants with bleeding diathesis or inaccessible veins were excluded as phlebotomy and venipunctures for venous access are required for the study. Participants on treatment for hypertension, dyslipidemia, and diabetes mellitus were excluded as the study's purpose was to examine the degree of physiological and metabolic changes among an overtly healthy group, and being on treatment would interfere with the interpretation of these parameters. Participants with metabolic syndrome were included if they had not been treated for the abovementioned conditions. These participants were included as it is expected that a significant number of overweight and obese participants with metabolic syndrome may be asymptomatic and thus appear overtly healthy. Capturing such variations in the population would be useful for studying the effects of weight loss. Participants with significant recent changes in body weight or actively attempting to lose weight through dieting, bariatric surgery, or anti-obesity drugs were excluded, given the need to recruit participants with stable weight of a given narrow distribution of body mass index. Participants on glucocorticoids or any drugs known to alter insulin resistance (e.g., ACE inhibitors, protease inhibitors, metformin, etc.) were excluded to avoid confounding factors in the measurement of insulin sensitivity and insulin resistance required in this study. Participants on an investigational drug in the past 6 months were excluded as it would not be predictable if the agent affected insulin resistance. Participants with contraindications to Dual X-ray Absorptiometry (DEXA) and Magnetic resonance imaging (MRI) (e.g., Cardiac pacemaker, metallic implants, or suffering from claustrophobia) as the study entails the use of the DEXA and MRI. Participants with psychological, eating, or motivational disorders were excluded from the study to increase weight loss rates during the intervention. Participants whose birth records were unavailable or mothers are deceased and hence unable to provide accurate birth weight data were excluded. Participants from the extreme birthweight range (below the 5th percentile or above the 95th percentile) were excluded as extreme birth weights may impact the risk of diabetes.]]>