Cited by 726Diabetes Treatment and ManagementPeroxisome Proliferator-Activated ReceptorsDiabetes, Cardiovascular Risks, and Lipoproteins

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Effect of Pioglitazone on Abdominal Fat Distribution and Insulin Sensitivity in Type 2 Diabetic Patients

Miyazaki, Yoshinori, Mahankali, Archana, Matsuda, Masafumi, Mahankali, Srikanth, Hardies, Jean, Cusi, Kenneth, Mandarino, Lawrence J., DeFronzo, Ralph A.·2002·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jcem.87.6.8567

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Abstract

We examined the effect of pioglitazone on abdominal fat distribution to elucidate the mechanisms via which pioglitazone improves insulin resistance in patients with type 2 diabetes mellitus. Thirteen type 2 diabetic patients (nine men and four women; age, 52 +/- 3 yr; body mass index, 29.0 +/- 1.1 kg/m(2)), who were being treated with a stable dose of sulfonylurea (n = 7) or with diet alone (n = 6), received pioglitazone (45 mg/d) for 16 wk. Before and after pioglitazone treatment, subjects underwent a 75-g oral glucose tolerance test (OGTT) and two-step euglycemic insulin clamp (insulin infusion rates, 40 and 160 mU/m(2).min) with [(3)H]glucose. Abdominal fat distribution was evaluated using magnetic resonance imaging at L4-5. After 16 wk of pioglitazone treatment, fasting plasma glucose (179 +/- 10 to 140 +/- 10 mg/dl; P < 0.01), mean plasma glucose during OGTT (295 +/- 13 to 233 +/- 14 mg/dl; P < 0.01), and hemoglobin A(1c) (8.6 +/- 0.4% to 7.2 +/- 0.5%; P < 0.01) decreased without a change in fasting or post-OGTT insulin levels. Fasting plasma FFA (674 +/- 38 to 569 +/- 31 microEq/liter; P < 0.05) and mean plasma FFA (539 +/- 20 to 396 +/- 29 microEq/liter; P < 0.01) during OGTT decreased after pioglitazone. In the postabsorptive state, hepatic insulin resistance [basal endogenous glucose production (EGP) x basal plasma insulin concentration] decreased from 41 +/- 7 to 25 +/- 3 mg/kg fat-free mass (FFM).min x microU/ml; P < 0.05) and suppression of EGP during the first insulin clamp step (1.1 +/- 0.1 to 0.6 +/- 0.2 mg/kg FFM.min; P < 0.05) improved after pioglitazone treatment. The total body glucose MCR during the first and second insulin clamp steps increased after pioglitazone treatment [first MCR, 3.5 +/- 0.5 to 4.4 +/- 0.4 ml/kg FFM.min (P < 0.05); second MCR, 8.7 +/- 1.0 to 11.3 +/- 1.1 ml/kg FFM(.)min (P < 0.01)]. The improvement in hepatic and peripheral tissue insulin sensitivity occurred despite increases in body weight (82 +/- 4 to 85 +/- 4 kg; P < 0.05) and fat mass (27 +/- 2 to 30 +/- 3 kg; P < 0.05). After pioglitazone treatment, sc fat area at L4-5 (301 +/- 44 to 342 +/- 44 cm(2); P < 0.01) increased, whereas visceral fat area at L4-5 (144 +/- 13 to 131 +/- 16 cm(2); P < 0.05) and the ratio of visceral to sc fat (0.59 +/- 0.08 to 0.44 +/- 0.06; P < 0.01) decreased. In the postabsorptive state hepatic insulin resistance (basal EGP x basal immunoreactive insulin) correlated positively with visceral fat area (r = 0.55; P < 0.01). The glucose MCRs during the first (r = -0.45; P < 0.05) and second (r = -0.44; P < 0.05) insulin clamp steps were negatively correlated with the visceral fat area. These results demonstrate that a shift of fat distribution from visceral to sc adipose depots after pioglitazone treatment is associated with improvements in hepatic and peripheral tissue sensitivity to insulin.

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Authors: Miyazaki, Y., Mahankali, A., Matsuda, M., Mahankali, S., Hardies, J., Cusi, K., Mandarino, L. J., & DeFronzo, R. A.
Affiliations: The University of Texas at San Antonio Health Science Center (US)
Corresponding author: DeFronzo, Ralph A.
ORCID: Matsuda, Masafumi
Mahankali, Srikanth
Cusi, Kenneth
Mandarino, Lawrence J.
DeFronzo, Ralph A.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2002-06-01
Volume: 87
Issue: 6
Pages: 2784-2791
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jcem.87.6.8567
OpenAlex: W2062560800
Cited by: 726
References: 48
Citations by year: 2026: 7 · 2025: 14 · 2024: 17 · 2023: 21 · 2022: 15 · 2021: 20 · 2020: 24 · 2019: 20 · 2018: 14 · 2017: 24 · 2016: 29 · 2015: 26 · 2014: 25 · 2013: 39 · 2012: 36
FWCI: 22.99
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (DK 24092)
National Center for Research Resources (M01RR01346, M01RR001346)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords: pioglitazone, type 2 diabetes, insulin resistance, abdominal fat distribution, visceral adipose tissue, hepatic insulin resistance, endogenous glucose production, free fatty acids, insulin sensitivity
MeSH terms: Abdomen, Pioglitazone, Adipose Tissue, Adult, Aged, Blood Glucose, Body Weight, Diabetes Mellitus, Type 2, Female, Glucose, Humans, Hypoglycemic Agents, Insulin, Insulin Resistance, Male, Middle Aged, Regression Analysis, Thiazoles, Glucose Clamp Technique, Thiazolidinediones

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Effect of Pioglitazone on Abdominal Fat Distribution and Insulin Sensitivity in Type 2 Diabetic Patients

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