Relationship between insulin resistance, inflammation and liver cell apoptosis in patients with severe obesity

Diabetes Metab Res Rev. 2010 Mar;26(3):187-92. doi: 10.1002/dmrr.1070.

Abstract

Background: In obesity, insulin resistance appears frequently after activation of proinflammatory molecules. Caspase-generated cytokeratin-18 (CK-18) fragments are produced during the apoptosis of hepatic cells. The main objective in the present study is to investigate the relationship between insulin resistance and caspase-generated CK-18 fragments in patients with severe obesity.

Methods: Sixty-two patients selected for bariatric surgery were clinically studied (sex, age, weight, waist diameter, body mass index, arterial pressure and type 2 diabetes mellitus) and analytic parameters were measured in blood (glucose concentration, cholesterol, triglycerides, insulin, glycosylated hemoglobin, aspartate aminotransferase, alanine aminotransferase, high-sensitivity C-reactive protein, adiponectin, interleukin 6, interleukin 18 and CK-18 fragments). Patient group division was based on 70th percentile of insulin resistance as measured by homeostasis model assessment (HOMA) and also according to liver histology.

Results: Patients with greater insulin resistance (percentile > 70th) showed higher values of CK-18 fragments, interleukin 6 and transaminases. A positive correlation between the HOMA score, value of CK-18 fragments and triglyceride level was found. A correlation between CK-18 fragments with interleukin 6, triglycerides and transaminases was also observed. HOMA score and value of CK-18 fragments correlated with the degree of liver fibrosis.

Conclusions: Greater degree of insulin resistance induces apoptosis of hepatic cells as measured by the serum levels of CK-18 fragments.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Apoptosis / physiology*
  • Blood Glucose
  • Blood Pressure
  • Body Mass Index
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fibrosis / pathology
  • Hepatocytes / metabolism*
  • Hepatocytes / pathology
  • Humans
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Insulin / blood
  • Insulin Resistance / physiology*
  • Interleukin-18 / blood
  • Interleukin-6 / blood
  • Keratin-18 / blood
  • Lipids / blood
  • Liver / pathology
  • Male
  • Middle Aged
  • Obesity / metabolism*
  • Obesity / pathology
  • Odds Ratio
  • Patient Selection
  • Statistics, Nonparametric

Substances

  • Blood Glucose
  • Insulin
  • Interleukin-18
  • Interleukin-6
  • Keratin-18
  • Lipids