Effect of pioglitazone treatment on brown adipose tissue volume and activity and hypothalamic gliosis in patients with type 2 diabetes mellitus: a proof-of-concept study

Acta Diabetol. 2019 Dec;56(12):1333-1339. doi: 10.1007/s00592-019-01418-2. Epub 2019 Sep 10.

Abstract

Aims: This study aimed to evaluate the effect of pioglitazone on brown adipose tissue function and hypothalamic gliosis in humans. Brown adipose tissue and the hypothalamus are regarded as important potential pharmacological targets to metabolic diseases, and defining the impact of current therapies on their structure and/or function could provide therapeutic advance in this field.

Methods: Six patients with type 2 diabetes were treated for 24 weeks with pioglitazone 30 mg/day as an add-on therapy. Brown adipose tissue glucose uptake and volume were determined using 18F-FDG PET/CT scans; hypothalamic gliosis was determined using MRI scans; blood was collected for hormone and biochemistry measurements. All tests were performed at inclusion and six months after pioglitazone introduction.

Results: Pioglitazone treatment led to a significant 3% body mass increase. There were neither changes in cold-induced brown adipose tissue glucose uptake and volume nor changes in hypothalamic gliosis.

Conclusions: This is a proof-of-concept study that provides clinical evidence for a lack of action of a thiazolidinedione, pioglitazone, to promote homogeneous and measurable changes in brown adipose tissue volume and also in hypothalamic gliosis after 6 months of treatment.

Keywords: Brown adipose tissue; Glucose intolerance; Hypothalamus; Insulin resistance; Obesity.

Publication types

  • Clinical Trial

MeSH terms

  • Adipose Tissue, Brown / diagnostic imaging
  • Adipose Tissue, Brown / drug effects*
  • Adipose Tissue, Brown / pathology
  • Adult
  • Aged
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / pathology
  • Drug Therapy, Combination
  • Female
  • Fluorodeoxyglucose F18
  • Gliosis / diagnosis
  • Gliosis / pathology
  • Gliosis / prevention & control*
  • Humans
  • Hypothalamus / diagnostic imaging
  • Hypothalamus / drug effects*
  • Hypothalamus / pathology*
  • Male
  • Middle Aged
  • Obesity / complications
  • Obesity / diagnosis
  • Obesity / drug therapy
  • Obesity / pathology
  • Organ Size / drug effects
  • Overweight / complications
  • Overweight / diagnosis
  • Overweight / drug therapy
  • Overweight / pathology
  • Pioglitazone / administration & dosage
  • Pioglitazone / pharmacology*
  • Positron Emission Tomography Computed Tomography
  • Proof of Concept Study
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / pharmacology

Substances

  • Thiazolidinediones
  • Fluorodeoxyglucose F18
  • 2,4-thiazolidinedione
  • Pioglitazone