Tumor necrosis factor α and insulin resistance in obese type 2 diabetic patients

Y. Miyazaki, R. Pipek, L. J. Mandarino, Ralph A. DeFronzo

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

The relationship between basal serum tumor necrosis factor alpha (TNFα) levels and peripheral tissue (muscle) sensitivity to insulin was examined in 63 subjects with normal glucose tolerance (NGT), 18 subjects with impaired glucose tolerance (IGT), and 123 patients with type 2 diabetes mellitus (T2DM). The BMI was similar in NGT (28.8 ± 0.7 kg/m2), IGT (31.1 ± 1.0), and T2DM (30.0 ± 0.4) groups. The fasting serum TNFα concentration in T2DM (4.4 ± 0.2 pg/ml) was significantly higher than in NGT (3.1 ± 0.2) and IGT (3.4 ± 0.2; both P < 0.05). In T2DM the fasting plasma glucose (FPG = 183 ± 5 mg/dl) and insulin (FPI = 17 ± 1 μU/ml) concentrations were significantly higher than in NGT (FPG = 95 ± 1; FPI = 10 ± 1) and IGT (FPG = 100 ± 2; FPI = 13 ± 1; all P < 0.01). The rate of total body insulin-mediated glucose disposal (Rd; 40 mU/m2 min euglycemic insulin clamp in combination with 3H-glucose) was reduced in T2DM (102 ± 3 mg/m2 min) compared with NGT (177 ± 10) and IGT (151 ± 14; both P < 0.01). The serum TNFα concentration was inversely correlated with Rd (r = -0.47, P < 0.0001) and positively correlated with both FPG (r = 0.32, P = 0.004) and FPI (r = 0.32, P = 0.004) in NGT plus IGT. No correlation was observed between serum TNFα and Rd (r = -0.02), FPG (r = 0.15), or FPI (r = 0.15) in T2DM. In stepwise multiple regression analysis using age, sex, BMI, FPG, FPI and serum TNFα concentration as independent variables, only BMI and serum TNFα concentration were significant and independent predictors of Rd (r2 = 0.29, P < 0.0001) in the NGT plus IGT group, while FPG and FPI were significant and independent predictors of Rd (r2 = 0.13, P < 0.0001) in T2DM. These results suggest that: (i) an increase in circulating TNFα concentration is associated with peripheral insulin resistance and increased plasma glucose and insulin levels prior to the onset of type 2 diabetes; and (ii) the further deterioration in peripheral insulin resistance in T2DM (compared with NGT and IGT) is unrelated to the increase in serum TNFα concentration.

Original languageEnglish (US)
Pages (from-to)88-94
Number of pages7
JournalInternational Journal of Obesity
Volume27
Issue number1
DOIs
StatePublished - Jan 1 2003
Externally publishedYes

Fingerprint

tumor necrosis factors
glucose tolerance
insulin resistance
Insulin Resistance
Glucose Intolerance
Tumor Necrosis Factor-alpha
Type 2 Diabetes Mellitus
Glucose
noninsulin-dependent diabetes mellitus
tumor necrosis factor-alpha
Serum
insulin
Insulin
Vascular Resistance
glucose
Fasting
fasting
Glucose Clamp Technique
Regression Analysis
muscle tissues

Keywords

  • Insulin sensitivity
  • Tumor necrosis factor α
  • Type 2 diabetes

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Public Health, Environmental and Occupational Health
  • Endocrinology
  • Food Science
  • Endocrinology, Diabetes and Metabolism

Cite this

Tumor necrosis factor α and insulin resistance in obese type 2 diabetic patients. / Miyazaki, Y.; Pipek, R.; Mandarino, L. J.; DeFronzo, Ralph A.

In: International Journal of Obesity, Vol. 27, No. 1, 01.01.2003, p. 88-94.

Research output: Contribution to journalArticle

Miyazaki, Y. ; Pipek, R. ; Mandarino, L. J. ; DeFronzo, Ralph A. / Tumor necrosis factor α and insulin resistance in obese type 2 diabetic patients. In: International Journal of Obesity. 2003 ; Vol. 27, No. 1. pp. 88-94.
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