Circulating Fibroblast Growth Factor-21 Is Elevated in Impaired Glucose Tolerance and Type 2 Diabetes and Correlates With Muscle and Hepatic Insulin Resistance

被引:356
作者
Chavez, Alberto O. [1 ]
Molina-Carrion, Marjorie [1 ]
Abdul-Ghani, Muhammad A. [1 ]
Folli, Franco [1 ]
DeFronzo, Ralph A. [1 ]
Tripathy, Devjit [1 ]
机构
[1] Univ Texas Hlth Sci Ctr San Antonio, Div Diabet, San Antonio, TX 78229 USA
关键词
FREE FATTY-ACID; METABOLIC-RATE; FGF-21; LEVELS; BETA-KLOTHO; FGF21; FIBROBLAST-GROWTH-FACTOR-19; SENSITIVITY; EXPRESSION; MELLITUS; CLAMP;
D O I
10.2337/dc09-0684
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE - Fibroblast growth factor (FGF)-21 is highly expressed in the liver and regulates hepatic glucose production and lipid metabolism in rodents. However, its role in the pathogenesis of type 2 diabetes in humans remains to be defined. The aim of this study was to quantitate circulating plasma FGF-21 levels and examine their relationship with insulin sensitivity in subjects with varying degrees of obesity and glucose tolerance. RESEARCH DESIGN AND METHODS - Forty-one subjects (8 lean with normal glucose tolerance [NGT], 9 obese with NGT, 12 with impaired fasting glucose [IFG]/impaired glucose tolerance [IGT], and 12 type 2 diabetic subjects) received an oral glucose tolerance test (OGTT) and a hyperinsulinemic-euglycemic clamp (80 mU/m(2) per min) combined with 3-[H-3] glucose infusion. RESULTS - Subjects with type 2 diabetes, subjects with IGT, and obese subjects with NGT were insulin resistant compared with lean subjects with NGT. Plasma FGF-21 levels progressively increased from 3.9 +/- 0.3 ng/ml in lean subjects with NGT to 4.9 +/- 0.2 in obese subjects with NGT to 5.2 +/- 0.2 in subjects with IGT and to 5.3 +/- 0.2 in type 2 diabetic subjects. FGF-21 levels correlated inversely with whole-body (primarily reflects muscle) insulin sensitivity (r = -0.421, P = 0.007) and directly with the hepatic insulin resistance index (r = 0.344, P = 0.034). FGF-21 levels also cot-related with measures of glycemia (fasting plasma glucose [r = 0.312, P = 0.05], 2-h plasma glucose [r = 0.414, P = 0.01], and A1C [r = 0.325, P = 0.04]). CONCLUSIONS - Plasma FGF-21 levels are increased in insulin-resistant states and correlate with hepatic and whole-body (muscle) insulin resistance. FGF-21 may play a role in pathogenesis of hepatic and whole-body insulin resistance in type 2 diabetes.
引用
收藏
页码:1542 / 1546
页数:5
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