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Cited by 727Diabetes Treatment and ManagementPeroxisome Proliferator-Activated ReceptorsDiabetes, Cardiovascular Risks, and Lipoproteins

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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  • Reductions in hepatic steatosis with both pioglitazone and rosiglitazone ameliorate hepatic insulin resistance.

    “Reductions in hepatic steatosis with both pioglitazone and rosig litazone ameliorate hepatic insulin resistance.134,135”

    From Lipid-induced insulin resistance: unravelling the mechanism (2010) · cites this paper as [134]

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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
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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