Liver and Metabolic Effects of Insulin Pump Therapy in a Population of Type 2 Diabetics with Non-alcoholic Hepatic Steatosis
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 46
- 试验地点
- 13
- 主要终点
- Variation of hepatic steatosis, between the insulin pump therapy (CSII) vs Multi injection treatement (MDI) groups.
研究概览
简要总结
The prevalence of fatty liver disease (NAFLD: Non-Alcoholic Fatty Liver Disease or to a more severe degree NASH: Non-Alcoholic SteatoHepatitis) reached 40-70% in subjects with type 2 diabetes (T2D). NAFLD can be easily detected by performing a hepatic ultrasonography. The presence of a NAFLD is positively correlated with the severity of insulin resistance and dysglycemia in this population. The presence of NAFLD worsens the prognosis of T2D with an increased cardiovascular risk. This hepatic impairment would also increase the risk of microvascular complications, especially nephropathy. Conversely, T2D increases the risk of transition from NAFLD to NASH and then to hepatic fibrosis and its related complications (cirrhosis, hepatocellular carcinoma). The risk of progression of liver steatosis to fibrosis is also more important as diabetes and insulin resistance are more severe.
In addition to diabetes and insulin resistance, other risk factors are associated with more severe liver damage such as changes in microbiota. Indeed, it has already been described a smaller amount of bacteroides in the microbiota of subjects with T2D and the most severe hepatic impairment. The treatment of NAFLD/NASH is poorly codified without approved drugs in this indication, while many phase 3 trials with candidate drugs are undergoing. Life-style measures (physical activity and low carbohydrate/calorie diet) can limit the progression from NAFLD to more severe liver fibrosis. Some bariatric surgery studies have also shown good results in this situation. Pharmacological interventions are also reported with proven efficacy of pioglitazone, vitamin E and orlistat.
The OPT2MISE study has recently shown the superiority of insulin pump (or continuous sub-cutaneous insulin infusion: CSII) compared to multiple daily insulin injections (MDI) to improve glycemic control in a population of patients with T2D in failure of well-titrated MDI. In addition, treatment with CSII showed a 45% decrease in insulin resistance (assessed by HOMA-IR) in a population of newly diagnosed T2D.
In light of these data, investigators hypothesize that the introduction of insulin pump treatment in a population of subjects with T2D and NAFLD, by improving insulin sensitivity, could reduce fatty liver content compared to standard MDI treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 37 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male / female 35/70 years (including ranges) with T2D ≥ 1 year
- •Benefiting from the indication of use of the free Freestyle glucose meter
- •Treatment with multi-injection insulin therapy comprising a daily injection of basal insulin (Glargine U100, Glargine U300, Degludec) and at least 2 daily injections of an insulin analogue (lispro, aspart or glulisine) +/- metformin, dipeptidyl peptidase-4 (DPP4) and/or sodium-glucose cotransporter type 2 (SGLT2) at a dose stable for at least 3 months.
- •For women of childbearing age, oestro-progestative pill, IUD, implant.
- •11% ≥ HbA1c ≥ 6.5%
- •Presence of hepatic steatosis according to the ultrasonography
- •Absence of chronic alcoholic intoxication
- •Absence of chronic viral hepatitis or other chronic liver diseases (eg hemochromatosis ...)
排除标准
- •Type 1 diabetes
- •Contraindication to pump treatment
- •Treatment with anti-diabetics or other than metformin, dipeptidyl peptidase-4 (DPP4) and/or sodium-glucose cotransporter type 2 (SGLT2)
- •Treatment with basal inulin of Levemir
- •Contraindication to performing MRI
- •Chronic alcohol abuse (after alcohol consumption> 20g / day in men and> 10g / day in women) according to the medical examination
- •Chronic viral hepatitis based on HBV and HCV serology results
- •Hemochromatosis according to the martial assessment
- •Other toxic or drug hepatitis
- •Severe hepatic pathology: hepatic cirrhosis, hepatocellular carcinoma
- •Severe renal insufficiency (MDRD <30 ml / min)
- •Severe and progressive cardiovascular pathology
- •Treatment (permanent or intermittent) with glucocorticoids
- •Treatment known to improve hepatic steatosis (glitazone, vitamin E, orlistat)
- •history or bariatric surgery project for the duration of the study
- •Drug treatment likely to cause hepatic steatosis (amiodarone, carbamazepine, tamoxifen, valproate, clozapine, anti-retroviral drugs) unless the dose has been stable for ≥ 3 months
- •Guardianship, curatorship or safeguard of justice
结局指标
主要结局
Variation of hepatic steatosis, between the insulin pump therapy (CSII) vs Multi injection treatement (MDI) groups.
时间窗: 6 months
Change of fatty liver by MRI quantification
次要结局
- In the CSII group : avantage of an insulin pump treatment on the fatty liver (quantified by MRI), between inclusion and the 12th month,(12 months)
- Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on CRPus(6 months)
- Calculation of the specificity values of the FLI for the detection of fatty liver in this population, by using the quantification of hepatic MRI as Gold Standard.(6 months)
- Calculation of the positive predictive values of the FLI for the detection of fatty liver in this population, by using the quantification of hepatic MRI as Gold Standard.(6 months)
- Calculation negative predictive values of the FLI for the detection of fatty liver in this population, by using the quantification of hepatic MRI as Gold Standard.(6 months)
- Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on glycemic balance(6 months)
- Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months, on hepatic biological parameters and non-invasive biomarkers of fatty liver (FLI) and of fibrosis of the liver (FIB-4 and NAFLD Score),(6 months)
- In the CSII group : avantage of an insulin pump treatment on the fatty liver between inclusion and the 6th month,(6 months)
- Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on the total daily insulin dose(6 months)
- Calculation of the sensitivity values of the FLI for the detection of fatty liver in this population,(6 months)
- Safety analysis at 6 months: comparison the first 6 months, in the CSII and MDI groups:(6 months)
- Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on insulin sensitivity(6 months)
- Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition(6 months)
- Evaluation of quality of life(6 months)