Pioglitazone reduces epicardial fat and improves diastolic function in patients with type 2 diabetes

Alexander J. Moody, Marjorie Molina-Wilkins, Geoffrey D. Clarke, Aurora Merovci, Carolina Solis-Herrera, Eugenio Cersosimo, Robert J. Chilton, Patricia Iozzo, Amalia Gastaldelli, Muhammad Abdul-Ghani, Ralph A. DeFronzo

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: To examine the effect of pioglitazone on epicardial (EAT) and paracardial adipose tissue (PAT) and measures of diastolic function and insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). Methods: Twelve patients with T2DM without clinically manifest cardiovascular disease and 12 subjects with normal glucose tolerance (NGT) underwent cardiac magnetic resonance imaging to quantitate EAT and PAT and diastolic function before and after pioglitazone treatment for 24 weeks. Whole-body insulin sensitivity was measured with a euglycaemic insulin clamp and the Matsuda Index (oral glucose tolerance test). Results: Pioglitazone reduced glycated haemoglobin by 0.9% (P < 0.05), increased HDL cholesterol by 7% (P < 0.05), reduced triacylglycerol by 42% (P < 0.01) and increased whole-body insulin-stimulated glucose uptake by 71% (P < 0.01) and Matsuda Index by 100% (P < 0.01). In patients with T2DM, EAT (P < 0.01) and PAT (P < 0.01) areas were greater compared with subjects with NGT, and decreased by 9% (P = 0.03) and 9% (P = 0.09), respectively, after pioglitazone treatment. Transmitral E/A flow rate and peak left ventricular flow rate (PLVFR) were reduced in T2DM versus NGT (P < 0.01) and increased following pioglitazone treatment (P < 0.01-0.05). At baseline normalized PLVFR inversely correlated with EAT (r = −0.45, P = 0.03) but not PAT (r = −0.29, P = 0.16). E/A was significantly and inversely correlated with EAT (r = −0.55, P = 0.006) and PAT (r = −0.40, P = 0.05). EAT and PAT were inversely correlated with whole-body insulin-stimulated glucose uptake (r = −0.68, P < 0.001) and with Matsuda Index (r = 0.99, P < 0.002). Conclusion: Pioglitazone reduced EAT and PAT areas and improved left ventricular (LV) diastolic function in T2DM. EAT and PAT are inversely correlated (PAT less strongly) with LV diastolic function and both EAT and PAT are inversely correlated with measures of insulin sensitivity.

Original languageEnglish (US)
Pages (from-to)426-434
Number of pages9
JournalDiabetes, Obesity and Metabolism
Volume25
Issue number2
DOIs
StatePublished - Feb 2023

Keywords

  • diastolic function
  • epicardial and paracardial fat
  • insulin sensitivity
  • pioglitazone
  • type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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