Comparing the Effect of a High SFA Diet and High Fructose Diet on Hepatic Insulin Sensitivity
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- Hepatic insulin sensitivity measured by hyperinsulinemic-euglycemic clamp.
研究概览
简要总结
High rates of de novo lipogenesis (DNL) and high saturated fatty acid (SFA) fraction in the liver both have been associated with poor metabolic health and hepatic insulin resistance. Interestingly, the end product of DNL is mainly SFA. So far it is unknown whether it is the process of DNL or the accumulation of SFA per se that leads to hepatic insulin resistance. Therefore, it is of interest to compare the effect of a diet that modifies directly hepatic SFA content (4-week high SFA diet) and a diet that changes SFA indirectly by modifying rates of DNL (4-week high fructose diet). To this end, 18 overweight/obese, but otherwise healthy, males and females will take part in the randomized dietary interventions. The primary outcome is hepatic insulin sensitivity (suppression of EGP during clamp) upon a 4-week high SFA diet versus a 4-week fructose diet.
详细描述
Rationale: High rates of de novo lipogenesis (DNL) and high saturated fatty acid (SFA) fraction in the liver both have been associated with poor metabolic health and hepatic insulin resistance. Interestingly, the end product of DNL is mainly SFA. So far it is unknown whether it is the process of DNL or the accumulation of SFA per se that leads to hepatic insulin resistance. This is a clinically relevant question, as it will give novel insights towards the best strategy for prevention and treatment of hepatic insulin resistance. Therefore, it is of interest to compare the effect of a diet that modifies directly hepatic SFA content (high SFA diet) and a diet that changes SFA indirectly by modifying rates of DNL (high fructose diet).
Objective: To determine the effect of a 4-week high SFA diet compared to a 4-week high fructose diet on hepatic insulin sensitivity, on hepatic SFA fraction and DNL.
Study design: This is a randomized intervention study comparing the effects of a 4-week high SFA diet compared to a 4-week high fructose diet on hepatic insulin sensitivity.
Study population: 24 overweight/obese, but otherwise healthy, males and females (BMI 27-38 kg/m2), 45-75 years, will participate in the study. Of these 24 included participants, 18 are expected to meet the study criteria and take part in the measurements following the screening, of these 14 need to complete the study.
Intervention: Participants follow a 4-week high SFA diet and a 4-week high fructose diet.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 45 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Participants are able to provide signed and dated written informed consent prior to any study specific procedures
- •Participants should have suitable veins for cannulation or repeated venipuncture
- •Women are post-menopausal (defined as at least 1 year post cessation of menses)
- •Aged ≥ 45 and ≤ 75 years
- •Body mass index (BMI) 27 - 38 kg/m2
- •Stable dietary habits (no weight loss or gain >5kg in the past 3 months)
- •Sedentary lifestyle (not more than 2 hours of sports per week)
- •No signs of active cardiovascular disease, liver or kidney malfunction
- •Liver fat content ≥ 2% weight/weight.
排除标准
- •Type 2 diabetes
- •Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator
- •Patients with congestive heart failure and and/or severe renal and or liver insufficiency or another condition that may interfere with outcomes measured in this study.
- •Any contra-indication MRI scanning
- •Alcohol consumption of >2 servings per day for men and >1 servings per day for woman
- •Smoking in the past 6 months
- •Men: Hb <8.4 mmol/L, Women: Hb <7.8 mmol/l
- •Vegetarian, vegan, food intolerant to common foods (e.g. gluten intolerant, lactose intolerant)
- •Medication use that may influence outcome parameters
- •A medical doctor will judge participation eligibility based on the medical history questionnaire, medication use and fasting blood parameters. If the medical doctor advises that a volunteer cannot participate, the volunteer will be excluded from enrollment.
结局指标
主要结局
Hepatic insulin sensitivity measured by hyperinsulinemic-euglycemic clamp.
时间窗: after 28 days of each diet
difference in EGP suppression after the high SFA diet and the high fructose diet
次要结局
- Hepatic fat composition measured by proton magnetic resonance spectroscopy(first day of each diet - after 28 days of each diet)
- De novo lipogenesis measured by deuterated water(after 25 days of each diet)