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NCT Number: NCT04270656

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

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.

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Key information

Conditions

Type 2 Diabetes (T2D) Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

37 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

CHU, Angers, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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)

Multi-injection treatment ( MDI ).

Procedure

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

Primary outcomes

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

    Time frame: 6 months

    Change of fatty liver by MRI quantification

Secondary outcomes

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

    Time frame: 6 months

    Variation of hepatic steatosis (MRI quantization by gradient echo sequences & centralized reading

  2. In the CSII group : avantage of an insulin pump treatment on the fatty liver (quantified by MRI), between inclusion and the 12th month,

    Time frame: 12 months

    Variation of hepatic steatosis (MRI quantization by gradient echo sequences & centralized reading

  3. 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),

    Time frame: 6 months

    Liver fonction (AST ; ALAT ; GGT ; PAL ; Ferritin) Test-fibrosis score criteria (FIB- 4 and NAFLD Score) ; FLI

  4. Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on insulin sensitivity

    Time frame: 6 months

    dosage of plasma adiponectin

  5. Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on insulin sensitivity

    Time frame: 6 months

    calculation of the modified HOMA-IR index (peptide C, blood sugar),

  6. Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on glycemic balance

    Time frame: 6 months

    HbA1c dosages

  7. Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on the total daily insulin dose

    Time frame: 6 months

    daily insulin dose record

  8. Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition

    Time frame: 6 months

    total cholesterol

  9. Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition

    Time frame: 6 months

    LDL-cholesterol

  10. Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition

    Time frame: 6 months

    HDL-cholesterol

  11. Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition

    Time frame: 6 months

    triglycerides (TG)

  12. Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition

    Time frame: 6 months

    fatty-free acids

  13. Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on lipid profile • the inflammatory condition

    Time frame: 6 months

    ApoB,

  14. Evaluate the effectiveness of a CSII vs MDI treatment, between randomization and 6 months on CRPus

    Time frame: 6 months

    Ultra-sensitive C-reactive protein (CRPus)

  15. Evaluation of quality of life

    Time frame: 6 months

    DTSQ

  16. Evaluation of quality of life

    Time frame: 6 months

    SF36

  17. Safety analysis at 6 months: comparison the first 6 months, in the CSII and MDI groups:

    Time frame: 6 months

    Reporting by patient of all severe hypoglycemia during the study

  18. Safety analysis at 6 months: comparison the first 6 months, in the CSII and MDI groups:

    Time frame: 6 months

    Reporting by the patient of all episode of ketoacidosis during the study

  19. Calculation of the sensitivity values of the FLI for the detection of fatty liver in this population,

    Time frame: 6 months

    quantification of hepatic MRI as Gold Standard.

  20. 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.

    Time frame: 6 months

    quantification of hepatic MRI as Gold Standard.

  21. 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.

    Time frame: 6 months

    quantification of hepatic MRI as Gold Standard.

  22. 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.

    Time frame: 6 months

    quantification of hepatic MRI as Gold Standard.

Sponsors and collaborators

Lead sponsor

Nantes University Hospital

Other

Collaborators

  • University Hospital, Angers

Registry information

Official study title

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

Acronym: STEATO-POMPE

Important dates

Study start
2021
Primary completion
2024
Study completion
2024
First posted
Feb 17, 2020
Registry last updated
Oct 17, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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