Milk Protein Feeding After Aerobic Exercise in Older Adults With Pre-diabetes Taking the Biguanide Metformin
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- Insulin Sensitivity
研究概览
简要总结
The investigators propose that post-exercise milk protein feeding will enhance the mitochondrial protein synthesis (biogenesis) response to an exercise-training program. In addition, the investigators propose that this stimulatory effect of protein feeding will overcome the potential blunting effect of metformin on exercise responses. The investigators will investigate these outcomes over a 12-week exercise-training program in older adults with pre-diabetes with or without metformin treatment.
详细描述
This is a randomized, placebo controlled, double blind study. 60 men and women over the age of 55 with indications of pre-diabetes will be recruited for participation and randomly assigned to one of four 12 week exercise training programs: 1)Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of Metformin. 2) Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of Metformin. 3) Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of matching placebo. 4) Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of placebo.
Daily administration of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week 4 during a 12 week exercise training program. The titration dosing scheme and taking metformin/placebo with meals will help reduce the most common side effects (i.e.,gastrointestinal discomfort). If participants experience gastrointestinal discomfort, the dose will be lowered to 1500 mg/day.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 55 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •55 years or older
- •Individuals with Prediabetes defined as impaired fasting glucose (100 to 126 mg/dl), HbA1c (5.7-6.4%), and/or impaired glucose tolerance defined as 2 hour postprandial blood glucose of 140 to 200 mg/dl.
排除标准
- •Medications contraindicated with Metformin (Dofetilide, Lamotrigine, Pegvisomant, Somatropin, Trimethoprim, Trospium, Gatifloxacin, Cephalexin, Cimetidine, Dalfampridine)
- •Recent (less than 6 weeks) or planned imaging that requires IV contrast,
- •Renal dysfunction creatinine ≥ 1.3 mg/dL in men or ≥ 1.2 mg/dL in women
- •Alanine Aminotransferase (ALT) levels exceed 52 IU/L
- •Heart, Kidney or Liver Disease
- •Type I or Type II Diabetes
- •Anti-coagulant therapy (warfarin/heparin)
- •Lung/respiratory dysfunction
- •Medications affecting primary outcomes
- •Lactose Intolerant
- •Tobacco Use
- •Heavy Alcohol Use
- •Lidocaine Allergy
研究组 & 干预措施
Metformin/Carbohydrate
Daily oral administration of Metformin with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week 4. Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of Metformin.
干预措施: Metformin (Drug)
Metformin/Carbohydrate
Daily oral administration of Metformin with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week 4. Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of Metformin.
干预措施: Carbohydrate Beverage (Dietary Supplement)
Placebo/Carbohydrate
Daily oral administration of matching placebo with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of matching placebo will begin as one tablet for the first week and will increase by one tablet/day/week until reaching 4 tablets by week 4. Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of matching placebo.
干预措施: Placebo (Drug)
Placebo/Carbohydrate
Daily oral administration of matching placebo with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of matching placebo will begin as one tablet for the first week and will increase by one tablet/day/week until reaching 4 tablets by week 4. Supervised aerobic exercise 3 days per week followed by a carbohydrate drink along with daily oral administration of matching placebo.
干预措施: Carbohydrate Beverage (Dietary Supplement)
Metformin/Protein
Daily oral administration of Metformin with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week. Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of Metformin
干预措施: Metformin (Drug)
Metformin/Protein
Daily oral administration of Metformin with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week. Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of Metformin
干预措施: Protein Beverage (Dietary Supplement)
Placebo/Protein
Daily oral administration of Metformin with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week. Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of placebo.
干预措施: Placebo (Drug)
Placebo/Protein
Daily oral administration of Metformin with a 12-week exercise training program consisting of 3 days per week of aerobic exercise training. The dose of Metformin will begin as one 500 mg tablet for the first week and will increase by 500 mg/day/week until reaching 2000 mg/day by week. Supervised aerobic exercise 3 days per week followed by a protein drink along with daily oral administration of placebo.
干预措施: Protein Beverage (Dietary Supplement)
结局指标
主要结局
Insulin Sensitivity
时间窗: Baseline and 12 weeks
Oral glucose tolerance test was used to measure whole-body insulin sensitivity. These data are reported as the mean at baseline (pre) and the mean at 12 weeks (post).
Mitochondrial Function
时间窗: Baseline and 12 weeks
Oxygen consumption was assessed via high-resolution mitochondrial respirometry in permeabilized skeletal muscle. This outcome was assessed via 2 different protocols; Protocol 1 was a substrate-uncoupler-inhibitor titration (SUIT) and Protocol 2 was an adenosine diphosphate (ADP) titration. These data are reported as the percent change from baseline compared to 12 weeks.
Protein Synthesis
时间窗: 12 weeks
Incorporation of deuterium into proteins to calculate cumulative synthesis rates. Protein synthesis was measured in sub cellular fractions of skeletal muscle including mixed, cytoplasmic and mitochondrial enriched fractions. These data are reported as the mean at 12 weeks.
Body Composition
时间窗: Baseline and 12 weeks
Dual energy x-ray absorptiometry was used to assess fat-free and fat mass. These data are reported as the mean at baseline (pre) and mean at 12 weeks (post).
Peak Aerobic Capacity
时间窗: Baseline and 12 weeks
Indirect calorimetry was used to measure peak oxygen consumption during a maximal, graded exercise test. These data are reported as the percent change from baseline compared to 12 weeks.
DNA Synthesis
时间窗: Baseline and 12 weeks
Incorporation of Deuterium Oxide into DNA will be measured before and after the 12 week interventions.
Glucose Tolerance
时间窗: Baseline and 12 weeks
Oral glucose tolerance test was used to measure glucose tolerance. These data are reported as the mean at baseline (pre) and the mean at 12 weeks (post).
次要结局
- Intracellular Signaling Proteins(Baseline and 12 weeks)
- Glucose Profiles From Real-Time Continuous Glucose Monitoring(Baseline, Weeks 6-8, 12 weeks)
研究者
Benjamin Miller
Associate Professor
Colorado State University