Lifestyle Intervention Trial in High Metabolic Risk Chinese

In this single-blind, randomized trial, about 1200 eligible volunteers, who have higher metabolic syndrome (MetS) risk and aged 20-65 years, will be assigned to one of three smartphone-based lifestyle intervention arms: 1) Routine education; 2) Programmed-smartphone intervention; and 3) Programmed-smartphone plus dietitian intervention. Before and after 6-month intervention, "PhenFlex test" (PFT) will be performed to examine and quantify improved metabolic flexibility. This intervention trial will be conducted by researchers in Shanghai Institute of Nutrition and Health of the Chinese Academy of Sciences (CAS) collaborating with Zhejiang University affiliated Sir Run Run Shaw Hospital. The study protocol was approved by the Ethics Committees in Shanghai Institutes of Nutrition and Health, and in Sir Run Run Shaw Hospital. The main aims of this study are to determine 1) efficacy of lifestyle interventions with different intensity in reducing MetS and its risk factors; 2) improved metabolic responses or flexibility defined by PFT-based homeostasis index; and 3) major genetic and nongenetic determinants for the efficacy of interventions among high MetS risk Chinese.

Metabolic syndrome, a cluster of multiple metabolic disturbances, including central obesity, dyslipidemia, hypertension, and hyperglycemia, is associated with 2-5-fold heightened risks of CVD and T2D. Compelling evidence showed that lifestyle intervention is one of effective approaches for preventing and controlling cardiometabolic diseases. However, there were considerably variations among different interventions and different persons. With widely available smartphone and APP-connected wearable devises, it is possible to provide programmed nutrition and lifestyle education to help participants achieve intervention targets, and closely monitor compliance. However, few studies investigated the efficacy of lifestyle interventions with programmed smartphone and APP-connected wearable devises in MetS management. Moreover, since present disease-based diagnoses and biomarkers may not adequately define health status, the concept of "re-redefining health" has attracted growing attention. The phenotypic flexibility and "PhenFlex test" are one of approaches to measure individuals' adaptive capacity to maintain hemostatic condition after having a standardized challenge drinker. To date, the PFT has been studied among 10,000 subjects in western countries and few studies, if any, have conducted in Chinese who have different genetic background and dietary patterns. It remains to be established whether and to what extent that the PFT-based hemostatic index system can precisely evaluate the metabolic health in Chinese. In the current trial, approximate 1200 subjects with MetS risks will be randomly assigned to one of three smartphone-based lifestyle intervention arms: 1) Routine education; 2) Programmed-smartphone intervention; and 3) Programmed-smartphone plus dietitian intervention. The intervention duration will be 6-month and then have 2-year follow-up. During starting and end of 6-month intervention, we will include PFT during the physical examination hold in the Sir Run Run Shaw Hospital. All the subjects will be given a standardized challenge drinker (75g glucose, 60 fat and 20g protein). Fasting and multiple postprandial time points samples (blood, t=0,1,3h) and urine and feces will be collected to measure clinical and omics markers like metabolomics, gut microbiota and SNPs. Finally, the homeostasis index will be built to estimate improvement of individual metabolic health after the intervention. In conclusion, this study will provide scientific evidence and novel insights about the effectiveness of new intervention strategies and precise diagnostic and assessment system for cardiometabolic management.

Weight will be assessed by Seca-255 (ScalesGalore) during each visit ,weight will also be assessed by Wi-Fi scale at home

Both systolic pressure and diastolic pressure will be assessed using electronic blood pressure monitor (Omron J750)during each visit and at home

Inclusion Criteria: Volunteers at high metabolic risk aged 20-65 who didn't participate in other studies in 3 months before the current research, having a certain level of education and normal cognitive ability, taking good care of himself/herself at least meet three of the following criterions(NCEP- ATPIII, for Asian Americans): Waist circumference ≥90 cm (men), ≥ 80 cm (women). total triglyceride ≥ 1.7 mmol/L. HDL-c <1.03 mmol/L in men, <1.3 mmol/L in women. systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 85mmHg. Fasting plasma glucose ≥ 5.6 mmol/L. Exclusion Criteria: Fasting glucose>7.0mmol/L or diagnosed diabetes or taking insulin or other blood glucose-lowering drugs Diagnosed phase three hypertension or can't lowering SBP under 160mmHg after anti-hypertension drugs Fasting blood TG≥ 5.7 mmol/L or fasting LDL-C≥ 4.9 mmol/L or taking lipid-lowering drugs Pregnancy or lactation Obvious drug changing in three months before research History of drug or alcohol abuse or other substance abuse (Alcohol abuse is defined as more than 40 g/day of alcohol for woman, and more than 80g/day for man) Severe kidney and liver diseases (blood biomarkers such as alt, serum creatinine is 1.5 times over the scope of normal setting) Severe Gastrointestinal diseases (such as severe diarrhea, constipation, severe digestive tract inflammation, active peptic ulcer, acute cholecystitis, etc.) Having surgeries within one year before research such as heart stents implanted surgery (expect for appendicitis or hernia operation) Severe cardiovascular disease (e.g., heart failure, myocardial infarction, cerebral infarction, and acute myocarditis, severe arrhythmia, received the intervention therapy, etc.) Cancer or receiving radiotherapy and chemotherapy within 5 years Severe pituitary or thyroid diseases Suffering from AIDS, hepatitis A, hepatitis B and other infectious diseases Mental disorders or current use of antidepressants

Sir Run Run Shaw Hospital;Hangzhou Dianzi University;China Jiliang University; Zhejiang Sci-Tech University