Effect of insulin versus triple oral therapy on the progression of hepatic steatosis in type 2 diabetes

J Investig Med. 2012 Oct;60(7):1059-63. doi: 10.2310/JIM.0b013e3182621c5f.

Abstract

Background: Hyperinsulinemia has been associated with hepatic fat deposition and ensuing insulin resistance. It is unknown if treatment with exogenous insulin in patients with type 2 diabetes, who are most prone to hepatic fat accumulation, would promote the occurrence or worsening of nonalcoholic fatty liver disease.

Methods: Patients with treatment-naive type 2 diabetes (N = 16) were treated with insulin and metformin for a 3-month lead-in period, then assigned triple oral therapy (metformin, glyburide, and pioglitazone) or continued treatment with insulin and metformin. Hepatic triglyceride content (HTC)-measured by magnetic resonance spectroscopy, serum lipids, glucose, liver function tests, and inflammatory and thrombotic biomarkers were followed for a median of 31 months.

Results: The 45% decline in HTC during the lead-in period persisted through the follow-up period with no difference between treatment groups at the end of the study (5.26 ± 4.21% in the triple oral therapy vs 7.47 ± 7.40% for insulin/metformin), whereas glycemic control was comparable.

Conclusions: Improvements in HTC with initial insulin/metformin therapy persisted through the median 31-month follow-up period regardless of the treatment. More importantly, insulin-based treatment did not appear to promote or worsen nonalcoholic fatty liver disease.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Disease Progression*
  • Fatty Liver / complications*
  • Fatty Liver / drug therapy*
  • Female
  • Follow-Up Studies
  • Glyburide / pharmacology
  • Glyburide / therapeutic use
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / administration & dosage
  • Insulin / pharmacology
  • Insulin / therapeutic use*
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Metformin / pharmacology
  • Metformin / therapeutic use
  • Middle Aged
  • Pioglitazone
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use
  • Triglycerides / metabolism
  • Young Adult

Substances

  • Hypoglycemic Agents
  • Insulin
  • Thiazolidinediones
  • Triglycerides
  • Metformin
  • Glyburide
  • Pioglitazone