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

Research output: Contribution to journalArticle

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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
Externally publishedYes

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pioglitazone
Viscera
Type 2 Diabetes Mellitus
Fats
Glucose
Liver
Insulin

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., ... 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

Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes. / Bajaj, Mandeep; Suraamornkul, Swangjit; Pratipanawatr, Thongchai; Hardies, Lou J.; Pratipanawatr, Wilailak; Glass, Leonard; Cersosimo, Eugenio; Miyazaki, Yoshinori; Defronzo, Ralph A.

In: Diabetes, Vol. 52, No. 6, 01.06.2003, p. 1364-1370.

Research output: Contribution to journalArticle

Bajaj, M, Suraamornkul, S, Pratipanawatr, T, Hardies, LJ, Pratipanawatr, W, Glass, L, Cersosimo, E, Miyazaki, Y & Defronzo, RA 2003, 'Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes', Diabetes, vol. 52, no. 6, pp. 1364-1370. https://doi.org/10.2337/diabetes.52.6.1364
Bajaj M, Suraamornkul S, Pratipanawatr T, Hardies LJ, Pratipanawatr W, Glass L et al. Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes. Diabetes. 2003 Jun 1;52(6):1364-1370. https://doi.org/10.2337/diabetes.52.6.1364
Bajaj, Mandeep ; Suraamornkul, Swangjit ; Pratipanawatr, Thongchai ; Hardies, Lou J. ; Pratipanawatr, Wilailak ; Glass, Leonard ; Cersosimo, Eugenio ; Miyazaki, Yoshinori ; Defronzo, Ralph A. / Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes. In: Diabetes. 2003 ; Vol. 52, No. 6. pp. 1364-1370.
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N2 - 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.

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