Personalized Glucose Optimization Through Nutritional Intervention
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 242
- 试验地点
- 2
- 主要终点
- Disposition index
研究概览
简要总结
Maintaining well-controlled blood glucose concentrations is essential in the prevention of chronic cardiometabolic diseases. The blood glucose response to dietary and/or lifestyle patterns may vary between individuals. Insulin resistance in specific metabolic organs such as skeletal muscle, adipose tissue or the liver may underlie differential blood glucose responses.
This dietary intervention study aims to obtain insight into the metabolic and lifestyle determinants of postprandial blood glucose responses, and to establish the effect of macronutrient manipulation of a 12-week dietary intervention on blood glucose homeostasis in metabolically different subgroups an its relationship to physical and mental performance and well-being.
详细描述
Study design: this study is a double-blinded, randomised, controlled, parallel design dietary intervention study. The study will be conducted at Maastricht University and Wageningen University and Research, the Netherlands.
Study population: the study population will consist of 240 men and women between 40-75 years old, with a BMI 25-40 kg/m2. Participants will be either muscle insulin resistant (MIR) or liver insulin resistant (LIR), as classified by an oral glucose tolerance test (OGTT) during the screening procedure. A subgroup of 80 participants will be selected for detailed metabolic phenotyping.
Intervention: for 12 weeks, participants will receive either a diet optimal for MIR (high in mono-unsaturated fatty acids) or a diet optimal for LIR (high in protein and fiber, low in fat) with respect to changes in disposition index. Participants will be randomly allocated to one of the two diets. Detailed laboratory and daily life phenotyping will be done pre- and post intervention.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •BMI 25 to <40 kg/m2
- •Predominantly muscle (MIR) or liver (LIR) insulin resistant
- •Weight stability for at least 3 months (+/- 3 kg)
排除标准
- •Pre-diagnosis of type 1 or type 2 diabetes mellitus
- •Renal or hepatic malfunctioning (pre-diagnosis or determined based on alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) and creatinine values)
- •Gastrointestinal diseases or abdominal surgery (allowed i.e.: appendectomy, cholecystectomy)
- •Food allergies, intolerances (including gluten/lactose intolerance) and/or dietary restrictions interfering with the study (including special diets, vegetarians and eating disorders)
- •Cardiovascular diseases (e.g. heart failure) or cancer (e.g. non-invasive skin cancer allowed)
- •High blood pressure (untreated >160/100 mmHg, drug-regulated >140/90 mmHg)
- •Diseases affecting glucose and/or lipid metabolism (e.g. pheochromocytoma, Cushing's syndrome, acromegaly)
- •Anemia defined as hemoglobin (Hb) men <8.5 and women <7.5 mmol/l
- •Diseases with a life expectation shorter than 5 years
- •Major mental disorders
- •Drug treated thyroid diseases (well substituted hypothyroidism is allowed inclusion)
- •Other physical/mental conditions that could interfere with study outcomes
- •Medication known to interfere with study outcomes (e.g. peroxisome proliferator-activated receptor-α (PPAR-α) or PPAR-γ agonists (fibrates), sulfonylureas, biguanides, α-glucosidase inhibitors, thiazolidinediones, repaglinide, nateglinide and insulin, chronic use of NSAIDs)
- •Use of anticoagulants
- •Use of antidepressants (stable use ≥ 3 months prior to and during the study is allowed)
- •Use of statins (stable use ≥ months prior to and during study allowed)
- •Use of β-blockers (only for the extensive phenotyping participants)
- •Chronic corticosteroids treatment (>7 consecutive days of treatment)
- •Use of antibiotics within 3 months prior to the study
- •Participation in regular sports activities (>4 hours per week)
- •Having a restricted dietary pattern interfering with the study diets (e.g. vegan or Atkins diet)
- •Plans to lose weight
- •Abuse of alcohol (alcohol consumption >14 units/week) and/or drugs (cannabis included)
- •Not willing to limit alcohol consumption to 7 drinks per week
- •Regular smoking (including use of e-cigarettes)
- •Use of strong vitamins or dietary supplements (e.g. pre- or probiotics) expected to interfere with the study outcomes
- •Pregnant or lactating women who are planning to become pregnant
- •Inability to comply with the study diet
- •Blood donation within the last 3 months
- •Participation in possibly interfering studies within the last 3 months
- •Inability to understand study information and/or communicate with staff
- •Unwillingness to be randomized or sign informed consent
- •Unwillingness to save data for 15 years
研究组 & 干预措施
Optimal diet
Participants will follow a diet for a total duration of 12 weeks, optimal for their metabolic phenotype. For participants with muscle insulin resistance (MIR) this will be a diet high in monounsaturated fatty acids, for participants with liver insulin resistance (LIR) this will be a diet high in protein and fiber and low in fat.
干预措施: Optimal diet (Other)
Suboptimal diet
Participants will follow a diet for a total duration of 12 weeks, suboptimal for their metabolic phenotype. For participants with liver insulin resistance (LIR) this will be a diet high in monounsaturated fatty acids, for participants with muscle insulin resistance (MIR) this will be a diet high in protein and fiber and low in fat.
干预措施: Suboptimal diet (Other)
结局指标
主要结局
Disposition index
时间窗: Change from baseline at week 12 dietary intervention
The primary objective of this study is to establish the effect of a metabolically targeted, optimal versus suboptimal macronutrient manipulated 12-week dietary intervention on the change in disposition index, a composite marker of first phase insulin secretion and insulin sensitivity during a 2-hour 7-points oral glucose tolerance test (OGTT). Disposition index will be calculated as follows: \[Insulin sensitivity index (ISI) \* (AUC30 min insulin / AUC30 min glucose)\], where AUC30 min is the area under the curve between 0 and 30 minutes of the OGTT for insulin (pmol/l) and glucose (mmol/l), respectively, and ISI is defined as: \[10,000 ÷ square root of (fasting plasma glucose (mmol/l) x fasting insulin (pmol/l)) x (mean glucose (mmol/l) x mean insulin (pmol/l))\]. Higher values represent a higher insulin sensitivity.
次要结局
- Mean 24h glucose concentrations(Change from baseline at week 12 dietary intervention)
- Self-reported fatigue(Change from baseline at week 12 dietary intervention)
- Self-reported physical activity(Change from baseline at week 12 dietary intervention)
- Subcutaneous adipose tissue biopsy(Change from baseline at week 12 dietary intervention)
- Intervention effects on all above outcomes within the LIR and MIR group.(Change from baseline at week 12 dietary intervention)
- DNA analysis(Baseline)
- Insulin sensitivity(Change from baseline at week 12 dietary intervention)
- Blood pressure(Change from baseline at week 12 dietary intervention)
- Fasting blood lipid spectrum(Change from baseline at week 12 dietary intervention)
- Substrate oxidation(Change from baseline at week 12 dietary intervention)
- Oral microbiota composition(Change from baseline at week 12 dietary intervention)
- Self-reported sleep quality over a 1 month period(Change from baseline at week 12 dietary intervention)
- Self-reported intestinal health(Change from baseline at week 12 dietary intervention)
- Glucose incremental area under the curve (iAUC)(Change from baseline at week 12 dietary intervention)
- Glucose tolerance(Change from baseline at week 12 dietary intervention)
- Muscle insulin sensitivity(Change from baseline at week 12 dietary intervention)
- Hepatic insulin sensitivity(Change from baseline at week 12 dietary intervention)
- Hip circumferences(Change from baseline at week 12 dietary intervention)
- Fasting circulating metabolic markers(Change from baseline at week 12 dietary intervention)
- Self-reported self efficacy in physical activity(Change from baseline at week 12 dietary intervention)
- Self-reported daytime sleepiness(Change from baseline at week 12 dietary intervention)
- Self-reported eating rate(Change from baseline at week 12 dietary intervention)
- The frequency and duration of hypo- and hyperglycemia(Change from baseline at week 12 dietary intervention)
- Body composition(Change from baseline at week 12 dietary intervention)
- Waist circumference(Change from baseline at week 12 dietary intervention)
- Body fat distribution(Change from baseline at week 12 dietary intervention)
- Self-reported sleep behaviour(Change from baseline at week 12 dietary intervention)
- Skeletal muscle biopsy(Change from baseline at week 12 dietary intervention)
- Postprandial circulating metabolic markers(Change from baseline at week 12 dietary intervention)
- Energy expenditure(Change from baseline at week 12 dietary intervention)
- Fecal microbiota composition(Change from baseline at week 12 dietary intervention)
- Self-reported perceived stress(Change from baseline at week 12 dietary intervention)
- Self-reported sedentary behaviour(Change from baseline at week 12 dietary intervention)
- Physical activity patterns(Change from baseline at week 12 dietary intervention)
- Cognitive performance(Change from baseline at week 12 dietary intervention)
- Carotid artery reactivity(Change from baseline at week 12 dietary intervention)
- Self-reported quality of life(Change from baseline at week 12 dietary intervention)
- Advanced glycation end-product (AGE) accumulation(Change from baseline at week 12 dietary intervention)
- Fasting immune metabolism (PBMCs)(Change from baseline at week 12 dietary intervention)
- Food preferences(Change from baseline at week 12 dietary intervention)