Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients

Yoshinori Miyazaki, Archana Mahankali, Masafumi Matsuda, Srikanth Mahankali, Jean Hardies, Kenneth Cusi, Lawrence J. Mandarino, Ralph A. DeFronzo

Research output: Contribution to journalArticle

553 Citations (Scopus)

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/m2), 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/m2·min) with [3H]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 A1c (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 ± 31μEq/liter; P < 0.05) and mean plasma FFA (539 ± 20 to 396 ± 29 μEq/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 μU/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 cm2; P < 0.01) increased, whereas visceral fat area at L4-5 (144 ± 13 to 131 ± 16 cm2; 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.

Original languageEnglish (US)
Pages (from-to)2784-2791
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume87
Issue number6
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

pioglitazone
Abdominal Fat
Insulin Resistance
Fats
Insulin
Glucose
Intra-Abdominal Fat
Glucose Tolerance Test
Clamping devices
Plasmas
Fasting
Liver
Glucose Clamp Technique

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Miyazaki, Y., Mahankali, A., Matsuda, M., Mahankali, S., Hardies, J., Cusi, K., ... DeFronzo, R. A. (2002). Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. Journal of Clinical Endocrinology and Metabolism, 87(6), 2784-2791. https://doi.org/10.1210/jc.87.6.2784

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.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 87, No. 6, 2002, p. 2784-2791.

Research output: Contribution to journalArticle

Miyazaki, Y, Mahankali, A, Matsuda, M, Mahankali, S, Hardies, J, Cusi, K, Mandarino, LJ & DeFronzo, RA 2002, 'Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients', Journal of Clinical Endocrinology and Metabolism, vol. 87, no. 6, pp. 2784-2791. https://doi.org/10.1210/jc.87.6.2784
Miyazaki, Yoshinori ; Mahankali, Archana ; Matsuda, Masafumi ; Mahankali, Srikanth ; Hardies, Jean ; Cusi, Kenneth ; Mandarino, Lawrence J. ; DeFronzo, Ralph A. / Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. In: Journal of Clinical Endocrinology and Metabolism. 2002 ; Vol. 87, No. 6. pp. 2784-2791.
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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/m2), 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/m2·min) with [3H]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 A1c (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 ± 31μEq/liter; P < 0.05) and mean plasma FFA (539 ± 20 to 396 ± 29 μEq/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 μU/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 cm2; P < 0.01) increased, whereas visceral fat area at L4-5 (144 ± 13 to 131 ± 16 cm2; 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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AU - Miyazaki, Yoshinori

AU - Mahankali, Archana

AU - Matsuda, Masafumi

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AU - Hardies, Jean

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N2 - 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/m2), 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/m2·min) with [3H]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 A1c (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 ± 31μEq/liter; P < 0.05) and mean plasma FFA (539 ± 20 to 396 ± 29 μEq/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 μU/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 cm2; P < 0.01) increased, whereas visceral fat area at L4-5 (144 ± 13 to 131 ± 16 cm2; 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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