Iron Depletion Therapy for Type 2 DM and NAFLD

National Institutes of Health (NIH)

Status and phase

Completed

Phase 2

Conditions

Diabetes Mellitus

Non-Alcoholic Fatty Liver Disease

Treatments

Procedure: blood donation

Study type

Interventional

Funder types

NIH

Identifiers

NCT00230087

DK 61728-S1 (completed)

Details and patient eligibility

About

The purpose of this study is to find out whether lowering the amount of iron in the body will result in less resistance to insulin and improved liver function in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease. This may result in better diabetes control and/or a decrease in the amount of liver fat.

Full description

Nonalcoholic fatty liver disease (NAFLD) is a common liver disease in the United States. NAFLD can lead to severe liver disease in some patients. Patients with NAFLD develop resistance to the normal action of insulin. Insulin is important for processing sugar and fat and increased resistance to insulin leads to fat in the liver. There is a correlation between the amount of iron in a person's body and the ability of insulin to work properly. Several small studies suggest that removal of iron may improve both diabetes and NAFLD by lowering insulin resistance.

The goal of this pilot study is to determine the effect of iron depletion on insulin sensitivity in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease. This study will be performed as an ancillary P&F study to the NASH CRN; all participants will be recruited from the NASH CRN Database Study. Secondary outcome measures will include the effect of iron depletion on hepatic necroinflammation, markers of oxidative stress and intrahepatic fat content. Insulin resistance will be directly measured using a two-step hyperinsulinemic euglycemic clamp procedure, before and after iron depletion by phlebotomy. Oral glucose tolerance tests will also be performed in order to evaluate the efficacy of using the indirect, but less cumbersome, HOMA model to derive values of insulin resistance in this patient cohort. This study will advance our understanding of the role of body iron stores in the pathophysiology of type 2 diabetes mellitus and non-alcoholic fatty liver disease. If iron depletion results in improved insulin sensitivity, reduced hepatic necroinflammation and/or intrahepatic fat content, a large scale, randomized, controlled trial of iron depletion in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease will be planned.

Enrollment

15 estimated patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Histological evidence of NAFLD and enrollment in NASH CRN Database Study
Type 2 DM treated with diet or a stable dose of non-insulin sensitizing oral hypoglycemic agents for > 3 mo.
Hemoglobin HbA1c level ≤ 8 %
Serum ALT levels ≥1.3 x ULN
Between 18-65 years of age

Exclusion Criteria

Hereditary hemochromatosis or hepatic iron overload defined as any of the following:
- 2+ iron on hepatic iron staining
- Hepatic Iron Index ≥ 1.9
- C282Y homozygous or C282Y/H63D compound heterozygous HFE genotype
Use of insulin or thiazolidinediones for the treatment of diabetes
Use of anti-NASH drugs (thiazolidinediones, vitamin E, UDCA, SAM-e, betaine, milk thistle, gemfibrozil, anti-TNF therapies, probiotics)
Serum ferritin <50μg/L
Serum transferrin-iron saturation <10 %
Hemoglobin <10 mg/L
Hematocrit <38 %
Voluntary blood donation or therapeutic phlebotomy within the previous twelve months (except routine lab tests)
Pregnant or lactating women
Prior history of coronary artery disease, myocardial infarction, exertional dyspnea or chronic chest pain at rest.
Evidence of myocardial infarction as determined by an ECG