The Impact of Adipose Tissue Insulin Resistance and Abdominal Obesity on Hepatic Fatty Acid Metabolism in Type 1 Diabetes
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- hepatic NEFA uptake
研究概览
简要总结
Steatotic liver disease associated with metabolic dysfunction (MASLD) is a disease caused by excess fat storage in the liver. Excessive fat delivery to the liver and MASLD typically occurs in people with abdominal obesity and type 2 diabetes. Type 1 diabetes (T1D) is also associated with a marked increase in the release of fat from adipose tissues and MASLD is increased in T1D and significantly increases the risk of heart, kidney and eye diseases.
详细描述
It is a parallel study design between T1D and controls. The outcomes will be assessed between T1D vs. controls during the metabolic visit.
The metabolic visit will last 9 hours: it will be a test meal with perfusion of stable tracers, blood sampling, PET acquisitions using radiopharmaceuticals (18FTHA and 11C-palmitate) and MRI acquisitions.
In total, 32 participants will be recruited:
- 16 living with T1D and abdominal obesity
- 16 with normoglycemia
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •16 individuals living with T1D and abdominal obesity, as defined by the International Diabetes Federation country/ethnic group-specific criteria (https://www.idf.org/e-library/consensus-statements/60- [1]. Treatment for T1D will be intensive insulin therapy on continuous pump perfusion with continuous glucose monitoring.
- •16 individuals with normoglycemia (i.e., HbA1c below 6.0%) matched for sex, age (± 5 years), waist circumference (± 3 cm), and menopausal status.
排除标准
- •less than 70% of time in glycemic range (for T1D);
- •history of primary dyslipidemia (LDL-cholesterol over 5 mmol/L or TG over 10 mmol/L) or uncontrolled high blood pressure (over 160/100 mmHg) precluding the withdrawal of lipid lowering and anti-hypertensive agents as per protocol;
- •presence of overt cardiovascular, liver or renal disease (except microalbuminuria without reduced kidney function), or other uncontrolled medical conditions;
- •use of any medication other than insulin that may affect lipid or carbohydrate metabolism and that cannot be stopped prior to testing;
- •current or planned pregnancy within the next 6 months;
- •any contraindication to MRI.
- •Being allergic to eggs
- •Smoking (>1 cigarette/day) and/or consumption of >2 alcoholic beverages per day
- •Having participated to a research study with exposure to radiation in the last year before the start of the study
结局指标
主要结局
hepatic NEFA uptake
时间窗: At baseline of Visit 2 (V2)
using 11C-palmitate PET
次要结局
- postprandial hepatic Dietary Fatty Acid uptake(At V2 (from time 0 to +360 minutes))
- Hepatic triglyceride content(At V2 (-200 minutes))
- Endogenous Glucose production and meal glucose systemic flux(At V2 (from time 0 to +360 minutes))
- Insulin secretion(At V2 (from time 0 to +360 minutes))
- Insulin resistance/ sensitivity(At V2 (from time 0 to +360 minutes))
- Adipose Tissue DFA trapping and postprandial palmitate flux(At V2 (from time 0 to +360 minutes))
- hepatic fatty acid oxidation, esterification and secretion into VLDL(At baseline)
- Glycerol turnover(At visit 2 (from time 0 to +360 minutes))
- Total substrate utilisation(At visit 2 (from time 0 to +360 minutes).)
- metabolite response(At visit 2 (from time 0 to +360 minutes))
- hormonal response(At visit 2 (from time 0 to +360 minutes))
- plasma NEFA NEFA flux(At visit 2 (from time 0 to +360 minutes))
- plasma distribution of DFA metabolites(At visit 2 (from time 0 to +360 minutes))
- Adipose tissue Insulin Resistance index(At visit 2 (from time 0 to +360 minutes))
研究者
André Carpentier
Tenure professor
Université de Sherbrooke