Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes

Mandeep Bajaj, Swangjit Suraamornkul, Thongchai Pratipanawatr, Lou J. Hardies, Wilailak Pratipanawatr, Leonard Glass, Eugenio Cersosimo, Yoshinori Miyazaki, Ralph A. DeFronzo

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Abstract

The effect of pioglitazone on splanchnic glucose uptake (SGU), endogenous glucose production (EGP), and hepatic fat content was studied in 14 type 2 diabetic patients (age 50 ± 2 years, BMI 29.4 ± 1.1 kg/m2, HbA1c 7.8 ± 0.4%). Hepatic fat content (magnetic resonance spectroscopy) and SGU (oral glucose load-insulin clamp technique) were quantitated before and after pioglitazone (45 mg/day) therapy for 16 weeks. Subjects received a 7-h euglycemic insulin (100 mU · m-2 · min-1) clamp, and a 75-g oral glucose load was ingested 3 h after starting the insulin clamp. Following glucose ingestion, the steady-state glucose infusion rate during the insulin clamp was decreased appropriately to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in glucose infusion rate during the 4 h after glucose ingestion from the ingested glucose load. 3-[3H]glucose was infused during the initial 3 h of the insulin clamp to determine rates of EGP and glucose disappearance (Rd). Pioglitazone reduced fasting plasma glucose (10.0 ± 0.7 to 7.5 ± 0.6 mmol/l, P < 0.001) and HbA1c (7.8 ± 0.4 to 6.7 ± 0.3%, P < 0.001) despite increased body weight (83 ± 3 to 86 ± 3 kg, P < 0.001). During the 3-h insulin clamp period before glucose ingestion, pioglitazone improved Rd (6.9 ± 0.5 vs. 5.2 ± 0.5 mg · kg-1 · min-1, P < 0.001) and insulinmediated suppression of EGP (0.21 ± 0.04 to 0.06 ± 0.02 mg · kg-1 · min-1, P < 0.01). Following pioglitazone treatment, hepatic fat content decreased from 19.6 ± 3.6 to 10.4 ± 2.1%, (P < 0.005), and SGU increased from 33.0 ± 2.8 to 46.2 ± 5.1% (P < 0.005). Pioglitazone treatment in type 2 diabetes 1) decreases hepatic fat content and improves insulin-mediated suppression of EGP and 2) augments splanchnic and peripheral tissue glucose uptake. Improved splanchnic/peripheral glucose uptake and enhanced suppression of EGP contribute to the improvement in glycemic control in patients with type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)1364-1370
Number of pages7
JournalDiabetes
Volume52
Issue number6
DOIs
StatePublished - Jun 1 2003

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Bajaj, M., Suraamornkul, S., Pratipanawatr, T., Hardies, L. J., Pratipanawatr, W., Glass, L., Cersosimo, E., Miyazaki, Y., & DeFronzo, R. A. (2003). Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes. Diabetes, 52(6), 1364-1370. https://doi.org/10.2337/diabetes.52.6.1364