Premium
Effect of Pioglitazone on the Metabolic and Hormonal Response to a Mixed Meal in Type II Diabetes
Author(s) -
Gastaldelli A,
Casolaro A,
Pettiti M,
Nannipieri M,
Ciociaro D,
Frascerra S,
Buzzigoli E,
Baldi S,
Mari A,
Ferrannini E
Publication year - 2007
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100034
Subject(s) - medicine , endocrinology , pioglitazone , type 2 diabetes , insulin , glycemic , postprandial , insulin resistance , glucagon , meal , diabetes mellitus , adiponectin
We explored the mechanisms by which a 4‐month, placebo‐controlled pioglitazone treatment (45 mg/day) improves glycemic control in type II diabetic patients (T2D, n =27) using physiological testing (6‐h mixed meal) and a triple tracer technique ([6,6‐ 2 H 2 ]glucose infusion, 2 H 2 O and [6‐ 3 H]glucose ingestion) to measure endogenous glucose production (EGP), gluconeogenesis (GNG), insulin‐mediated glucose clearance and β ‐cell glucose sensitivity (by c‐peptide modeling). Compared to sex/age/weight‐matched non‐diabetic controls, T2D patients showed inappropriately (for prevailing insulinemia) raised glucose production (1.05[0.53] vs 0.71[0.36]mmol min −1 kg ffm −1 p M , P =0.03) because of enhanced GNG (73.1±2.4 vs 59.5±3.6%, P <0.01) persisting throughout the meal, reduced insulin‐mediated glucose clearance (6[5] vs 12[13]ml min −1 kg ffm −1 n M −1 , P <0.005), and impaired β ‐cell glucose‐sensitivity (27[38] vs 71[37]pmol min −1 m −2 m M −1 , P =0.002). Compared to placebo, pioglitazone improved glucose overproduction ( P =0.0001), GNG and glucose underutilization ( P =0.05) despite lower insulinemia. GNG improvement was quantitatively related to raised adiponectin. β ‐cell glucose sensitivity was unchanged. In mild‐to‐moderate T2D, pioglitazone monotherapy decreased fasting and post‐prandial glycemia, principally via inhibition of gluconeogenesis, improved hepatic and peripheral insulin resistance. Clinical Pharmacology & Therapeutics (2007) 81 , 205–212. doi: 10.1038/sj.clpt.6100034