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The effect of pioglitazone on the liver: role of adiponectin.
Diabetes Care. 2006 Oct; 29(10):2275-81.DC

Abstract

OBJECTIVE

Diabetic hyperglycemia results from insulin resistance of peripheral tissues and glucose overproduction due to increased gluconeogenesis (GNG). Thiazolidinediones (TZDs) improve peripheral insulin sensitivity, but the effect on the liver is less clear. The goal of this study was to examine the effect of TZDs on GNG.

RESEARCH DESIGN AND METHODS

Twenty sulfonylurea-treated type 2 diabetic subjects were randomly assigned (double-blind study) to receive pioglitazone (PIO group; 45 mg/day) or placebo (Plc group) for 4 months to assess endogenous glucose production (EGP) (3-(3)H-glucose infusion), GNG (D2O technique), and insulin sensitivity by two-step hyperinsulinemic-euglycemic clamp (240 and 960 pmol/min per m2).

RESULTS

Fasting plasma glucose (FPG) (10.0 +/- 0.8 to 7.7 +/- 0.7 mmol/l) and HbA1c (9.0 +/- 0.4 to 7.3 +/- 0.6%) decreased in the PIO and increased in Plc group (P < 0.05 PIO vs. Plc). Insulin sensitivity increased approximately 40% during high insulin clamp after pioglitazone (P < 0.01) and remained unchanged in the Plc group (P < 0.05 PIO vs. Plc). EGP did not change, while GNG decreased in the PIO group (9.6 +/- 0.7 to 8.7 +/- 0.6 micromol x min(-1) x kg(ffm)(-1)) and increased in the Plc group (8.0 +/- 0.5 to 9.6 +/- 0.8) (P < 0.05 PIO vs. Plc). Change in FPG correlated with change in GNG flux (r = 0.63, P < 0.003) and in insulin sensitivity (r = 0.59, P < 0.01). Plasma adiponectin increased after pioglitazone (P < 0.001) and correlated with delta FPG (r = -0.54, P < 0.03), delta GNG flux (r = -0.47, P < 0.05), and delta insulin sensitivity (r = 0.65, P < 0.005). Plasma free fatty acids decreased after pioglitazone and correlated with delta GNG flux (r = 0.54, P < 0.02). From stepwise regression analysis, the strongest determinant of change in FPG was change in GNG flux.

CONCLUSIONS

Pioglitazone improves FPG, primarily by reducing GNG flux in type 2 diabetic subjects.

Authors+Show Affiliations

Stable Isotope Lab, Institute of Clinical Physiology-CNR, via Moruzzi 1, 56100 Pisa, Italy. amalia@ifc.cnr.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

17003306

Citation

Gastaldelli, Amalia, et al. "The Effect of Pioglitazone On the Liver: Role of Adiponectin." Diabetes Care, vol. 29, no. 10, 2006, pp. 2275-81.
Gastaldelli A, Miyazaki Y, Mahankali A, et al. The effect of pioglitazone on the liver: role of adiponectin. Diabetes Care. 2006;29(10):2275-81.
Gastaldelli, A., Miyazaki, Y., Mahankali, A., Berria, R., Pettiti, M., Buzzigoli, E., Ferrannini, E., & DeFronzo, R. A. (2006). The effect of pioglitazone on the liver: role of adiponectin. Diabetes Care, 29(10), 2275-81.
Gastaldelli A, et al. The Effect of Pioglitazone On the Liver: Role of Adiponectin. Diabetes Care. 2006;29(10):2275-81. PubMed PMID: 17003306.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The effect of pioglitazone on the liver: role of adiponectin. AU - Gastaldelli,Amalia, AU - Miyazaki,Yoshinori, AU - Mahankali,Archana, AU - Berria,Rachele, AU - Pettiti,Maura, AU - Buzzigoli,Emma, AU - Ferrannini,Eleuterio, AU - DeFronzo,Ralph A, PY - 2006/9/28/pubmed PY - 2007/1/6/medline PY - 2006/9/28/entrez SP - 2275 EP - 81 JF - Diabetes care JO - Diabetes Care VL - 29 IS - 10 N2 - OBJECTIVE: Diabetic hyperglycemia results from insulin resistance of peripheral tissues and glucose overproduction due to increased gluconeogenesis (GNG). Thiazolidinediones (TZDs) improve peripheral insulin sensitivity, but the effect on the liver is less clear. The goal of this study was to examine the effect of TZDs on GNG. RESEARCH DESIGN AND METHODS: Twenty sulfonylurea-treated type 2 diabetic subjects were randomly assigned (double-blind study) to receive pioglitazone (PIO group; 45 mg/day) or placebo (Plc group) for 4 months to assess endogenous glucose production (EGP) (3-(3)H-glucose infusion), GNG (D2O technique), and insulin sensitivity by two-step hyperinsulinemic-euglycemic clamp (240 and 960 pmol/min per m2). RESULTS: Fasting plasma glucose (FPG) (10.0 +/- 0.8 to 7.7 +/- 0.7 mmol/l) and HbA1c (9.0 +/- 0.4 to 7.3 +/- 0.6%) decreased in the PIO and increased in Plc group (P < 0.05 PIO vs. Plc). Insulin sensitivity increased approximately 40% during high insulin clamp after pioglitazone (P < 0.01) and remained unchanged in the Plc group (P < 0.05 PIO vs. Plc). EGP did not change, while GNG decreased in the PIO group (9.6 +/- 0.7 to 8.7 +/- 0.6 micromol x min(-1) x kg(ffm)(-1)) and increased in the Plc group (8.0 +/- 0.5 to 9.6 +/- 0.8) (P < 0.05 PIO vs. Plc). Change in FPG correlated with change in GNG flux (r = 0.63, P < 0.003) and in insulin sensitivity (r = 0.59, P < 0.01). Plasma adiponectin increased after pioglitazone (P < 0.001) and correlated with delta FPG (r = -0.54, P < 0.03), delta GNG flux (r = -0.47, P < 0.05), and delta insulin sensitivity (r = 0.65, P < 0.005). Plasma free fatty acids decreased after pioglitazone and correlated with delta GNG flux (r = 0.54, P < 0.02). From stepwise regression analysis, the strongest determinant of change in FPG was change in GNG flux. CONCLUSIONS: Pioglitazone improves FPG, primarily by reducing GNG flux in type 2 diabetic subjects. SN - 0149-5992 UR - https://www.unboundmedicine.com/medline/citation/17003306/The_effect_of_pioglitazone_on_the_liver:_role_of_adiponectin_ L2 - http://care.diabetesjournals.org/cgi/pmidlookup?view=long&amp;pmid=17003306 DB - PRIME DP - Unbound Medicine ER -