Clinical trial NCT04270656: Liver and Metabolic Effects of Insulin Pump Therapy in Diabetics Type 2 with Non-alcoholic Hepatic Steatosis
Official title: Liver and Metabolic Effects of Insulin Pump Therapy in a Population of Type 2 Diabetics with Non-alcoholic Hepatic Steatosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 2 Diabetes (T2D)
Lead sponsor: Nantes University Hospital
Sponsor class: OTHER
Collaborators: name: University Hospital, Angers
First posted: 2020-02-17
Enrollment: 46
Sex: ALL
Minimum age (years): 37
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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 ...)

Exclusion Criteria:

* 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

Primary outcomes:
measure: Variation of hepatic steatosis, between the insulin pump therapy (CSII) vs Multi injection treatement (MDI) groups.
timeFrame: 6 months
Secondary outcomes:
measure: In the CSII group : avantage of an insulin pump treatment on the fatty liver between inclusion and the 6th month,
timeFrame: 6 months
measure: In the CSII group : avantage of an insulin pump treatment on the fatty liver (quantified by MRI), between inclusion and the 12th month,
timeFrame: 12 months
measure: 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),
timeFrame: 6 months
measure: Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on insulin sensitivity
timeFrame: 6 months
measure: Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on insulin sensitivity
timeFrame: 6 months
measure: Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on glycemic balance
timeFrame: 6 months
measure: Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on the total daily insulin dose
timeFrame: 6 months
measure: Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition
timeFrame: 6 months
measure: Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition
timeFrame: 6 months
measure: Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition
timeFrame: 6 months
measure: Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition
timeFrame: 6 months
measure: Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition
timeFrame: 6 months
measure: Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition
timeFrame: 6 months
measure: Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on CRPus
timeFrame: 6 months
measure: Evaluation of quality of life
timeFrame: 6 months
measure: Evaluation of quality of life
timeFrame: 6 months
measure: Safety analysis at 6 months: comparison the first 6 months, in the CSII and MDI groups:
timeFrame: 6 months
measure: Safety analysis at 6 months: comparison the first 6 months, in the CSII and MDI groups:
timeFrame: 6 months
measure: Calculation of the sensitivity values of the FLI for the detection of fatty liver in this population,
timeFrame: 6 months
measure: 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.
timeFrame: 6 months
measure: 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.
timeFrame: 6 months
measure: 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.
timeFrame: 6 months
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU
city: Caen
country: France
facility: CHU
city: Dijon
country: France
facility: CHU
city: La Rochette
country: France
facility: CHU
city: Lyon
country: France
facility: Hospices Civils
city: Nantes
country: France
facility: Nantes UH
city: Poitiers
country: France
facility: CHU
city: Rennes
country: France
facility: CHU de Rennes
city: Toulouse
country: France
facility: CHU
Study officials:
References: