Impact of Plasma Lipids on β Cell Function and Insulin Sensitivity
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Glucose control
研究概览
简要总结
The investigators aim to evaluate whether and to what extent glucose tolerance, beta cell function, insulin clearance, and glucose metabolic fluxes change in response to an acute increase in plasma triglycerides during lipid infusion, independently of free fatty acid (FFA) levels, in nondiabetic subjects.
详细描述
Mild hypertriglyceridemia is associated with reduced glucose tolerance and increased risk of type 2 diabetes, independent of obesity, in both cross-sectional and prospective studies. It is unclear whether this association is direct or mediated by circulating lipid substrates of triglycerides (free fatty acids, or FFA) and which are the mechanisms involved.
To comprehensively examine the effects of mild acute hypertriglyceridemia on major glucose homeostatic mechanisms involved in diabetes progression, two dual-labeled oral glucose tolerance tests (OGTT) during 5-hour intravenous infusions of either 20% Intralipid or normal saline will be performed in healthy lean volunteers. Lipid-induced changes in glucose tolerance and insulin metabolism will be evaluated.
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
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •age 18-65 years
- •Body mass index (BMI) 18-35 kg/m2
- •both women and men
排除标准
- •chronic or acute diseases
- •any medications
- •pregnancy
结局指标
主要结局
Glucose control
时间窗: At the end of the 5-hour lipid infusion
Incremental area under the curve (AUC) of plasma glucose in response to the oral glucose tolerance test (OGTT)
Beta cell glucose sensitivity
时间窗: At the end of the 5-hour lipid infusion
Beta cell glucose sensitivity calculated by mathematical modeling of insulin secretion rate (ISR) and plasma glucose concentrations during the oral glucose tolerance test (OGTT)
Insulin clearance
时间窗: At the end of the 5-hour lipid infusion
Insulin clearance calculated as the ratio between insulin secretion rate (ISR) and plasma insulin levels
Rate of oral glucose appearance (RaO)
时间窗: At the end of the 5-hour lipid infusion
The rate of oral glucose appearance (RaO) will be assessed from the time course of the plasma tracer/tracee ratio of 6,6-\[2H2\]glucose and \[U-13C\]glucose
Endogenous glucose production (EGP)
时间窗: At the end of the 5-hour lipid infusion
The endogenous glucose production (EGP) will be assessed from the time course of the plasma tracer/tracee ratio of 6,6-\[2H2\]glucose and \[U-13C\]glucose
Insulin sensitivity
时间窗: At the end of the 5-hour lipid infusion
Insulin sensitivity estimated by an OGTT-derived surrogate index (Matsuda index)
Insulin secretion
时间窗: At the end of the 5-hour lipid infusion
Insulin secretion rate (ISR) estimated from C-peptide deconvolution at fasting and in response to the oral glucose tolerance test (OGTT)
次要结局
未报告次要终点
研究者
Andrea Natali
Full Professor
Azienda Ospedaliero, Universitaria Pisana