Effect of Pioglitazone on Cardiometabolic Risk in Patients With Obstructive Sleep Apnea

Am J Cardiol. 2017 Apr 15;119(8):1205-1210. doi: 10.1016/j.amjcard.2016.12.034. Epub 2017 Jan 25.

Abstract

Prevalence of insulin resistance is increased in patients with obstructive sleep apnea (OSA). Because insulin resistance is an independent predictor of cardiovascular disease (CVD), this study was initiated to see if pioglitazone administration would improve insulin sensitivity and thereby decrease risk of CVD in overweight/obese, nondiabetic, insulin-resistant patients with untreated OSA. Patients (n = 30) were administered pioglitazone (45 mg/day) for 8 weeks, and measurements were made before and after intervention of insulin action (insulin-mediated glucose uptake by the insulin suppression test), C-reactive protein, lipid/lipoprotein profile, and gene expression profile of periumbilical subcutaneous fat tissue. Insulin sensitivity increased 31% (p <0.001) among pioglitazone-treated subjects, associated with a decrease in C-reactive protein concentration (p ≤0.001), a decrease in plasma triglyceride, and increase in high-density lipoprotein cholesterol concentrations (p ≤0.001), accompanied by significant changes in apolipoprotein A1 and B concentrations and lipoprotein subclasses known to decrease CVD risk. In addition, subcutaneous adipose tissue gene expression profile showed a 1.6-fold (p <0.01) increase in GLUT4 expression and decreased expression in 5 of 9 inflammatory genes (p <0.05). In conclusion, enhanced insulin sensitivity can significantly decrease multiple cardiometabolic risk factors in patients with untreated OSA, consistent with the view that coexisting insulin resistance plays an important role in the association between OSA and increased risk of CVD.

MeSH terms

  • Adult
  • Aged
  • Apolipoproteins A / blood
  • Apolipoproteins B / blood
  • Blood Glucose / analysis
  • C-Reactive Protein / analysis
  • Cholesterol, HDL / blood
  • Female
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Resistance / physiology*
  • Male
  • Middle Aged
  • Overweight / physiopathology
  • Pioglitazone
  • RNA / metabolism
  • Sleep Apnea, Obstructive / physiopathology*
  • Subcutaneous Fat / metabolism
  • Thiazolidinediones / therapeutic use*
  • Triglycerides / blood

Substances

  • Apolipoproteins A
  • Apolipoproteins B
  • Blood Glucose
  • Cholesterol, HDL
  • Glucose Transporter Type 4
  • Hypoglycemic Agents
  • SLC2A4 protein, human
  • Thiazolidinediones
  • Triglycerides
  • RNA
  • C-Reactive Protein
  • Pioglitazone