Liver and Metabolic Effects of Insulin Pump Therapy in Diabetics Type 2 with Non-alcoholic Hepatic Steatosis

NCT04270656 | Completed

• 1 other identifier: RC19_0449
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 9

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.

Conditions

Type 2 Diabetes (T2D)

Outcome Measures

Primary Outcomes (1)

• Variation of hepatic steatosis, between the insulin pump therapy (CSII) vs Multi injection treatement (MDI) groups.

  Change of fatty liver by MRI quantification

  6 months

Secondary Outcomes (22)

• In the CSII group : avantage of an insulin pump treatment on the fatty liver between inclusion and the 6th month,

  6 months

• 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 hepatic biological parameters and non-invasive biomarkers of fatty liver (FLI) and of fibrosis of the liver (FIB-4 and NAFLD Score),

  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 insulin sensitivity

  6 months

Study Arms (2)

Insulin pump therapy

EXPERIMENTAL

Procedure: Insulin pump therapy

Multi-injection treatment ( MDI ).

ACTIVE COMPARATOR

Procedure: Multi-injection treatment ( MDI ).

Interventions

Insulin pump therapy PROCEDURE

5-day hospitalization in case of randomization in the insulin pump group (insulin pump establishing in according to the recommendations of the HAS)

Insulin pump therapy

Multi-injection treatment ( MDI ). PROCEDURE

Corresponds to an outpatient visit if the patient is randomized into the multi-injection group

Multi-injection treatment ( MDI ).

Eligibility Criteria

• Age: 37 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• % ≥ 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 ...)

You may not qualify if:

• 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

Sponsors & Collaborators

• Nantes University Hospital: lead
• University Hospital, Angers: collaborator

Study Sites (9)

CHU

Angers, 49933, France

Location

CHU

Caen, 14033, France

Location

CHU

Dijon, 21000, France

Location

CHU

La Rochette, 17019, France

Location

Hospices Civils

Lyon, 69495, France

Location

Nantes UH

Nantes, 44093, France

Location

CHU

Poitiers, 86000, France

Location

CHU de Rennes

Rennes, 35203, France

Location

CHU

Toulouse, 31059, France

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2020
• First Posted: February 17, 2020
• Study Start: February 5, 2021
• Primary Completion: September 23, 2024
• Study Completion: September 23, 2024
• Last Updated: October 17, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (9)