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Circulating fibroblast growth factor-21 is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance.

Chavez AO, Molina-Carrion M, Abdul-Ghani MA, Folli F, Defronzo RA, Tripathy D - Diabetes Care (2009)

Bottom Line: RESULTS Subjects with type 2 diabetes, subjects with IGT, and obese subjects with NGT were insulin resistant compared with lean subjects with NGT.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Diabetes, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

ABSTRACT
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-[(3)H] 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 correlated 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.

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Plasma FGF-21 concentration in lean subjects with NGT and obese subjects with NGT, IGT, and type 2 diabetes (T2DM). Data are means ± SE. *P < 0.05 vs. lean NGT.
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Figure 1: Plasma FGF-21 concentration in lean subjects with NGT and obese subjects with NGT, IGT, and type 2 diabetes (T2DM). Data are means ± SE. *P < 0.05 vs. lean NGT.

Mentions: Plasma FGF-21 was higher in obese subjects with NGT versus lean subjects with NGT (4.92 ± 0.17 vs. 3.88 ± 0.30 ng/ml, P = 0.04). Subjects with IGT (5.22 ± 0.23 ng/ml, P < 0.05 vs. lean subjects with NGT) and type 2 diabetes (5.27 ± 0.23, P < 0.05 vs. lean subjects with NGT) also had increased plasma FGF-21 levels (Fig. 1). Plasma FGF-21 concentration correlated with A1C (r = 0.325, P = 0.04), fasting plasma glucose (r = 0.312, P = 0.05), and 2-h glucose (r = 0.414, P = 0.01). There was also a direct association between plasma FGF-21 and BMI (r = 0.456, P < 0.001) in the entire group. A recent report (25) demonstrated elevated plasma FGF-21 levels in patients with chronic kidney disease. We did not observe any correlation between plasma FGF-21 and either glomerular filtration rate (r = 0.089, P = NS) or serum creatinine (r = 0.277, P = 0.08).


Circulating fibroblast growth factor-21 is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance.

Chavez AO, Molina-Carrion M, Abdul-Ghani MA, Folli F, Defronzo RA, Tripathy D - Diabetes Care (2009)

Plasma FGF-21 concentration in lean subjects with NGT and obese subjects with NGT, IGT, and type 2 diabetes (T2DM). Data are means ± SE. *P < 0.05 vs. lean NGT.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2713625&req=5

Figure 1: Plasma FGF-21 concentration in lean subjects with NGT and obese subjects with NGT, IGT, and type 2 diabetes (T2DM). Data are means ± SE. *P < 0.05 vs. lean NGT.
Mentions: Plasma FGF-21 was higher in obese subjects with NGT versus lean subjects with NGT (4.92 ± 0.17 vs. 3.88 ± 0.30 ng/ml, P = 0.04). Subjects with IGT (5.22 ± 0.23 ng/ml, P < 0.05 vs. lean subjects with NGT) and type 2 diabetes (5.27 ± 0.23, P < 0.05 vs. lean subjects with NGT) also had increased plasma FGF-21 levels (Fig. 1). Plasma FGF-21 concentration correlated with A1C (r = 0.325, P = 0.04), fasting plasma glucose (r = 0.312, P = 0.05), and 2-h glucose (r = 0.414, P = 0.01). There was also a direct association between plasma FGF-21 and BMI (r = 0.456, P < 0.001) in the entire group. A recent report (25) demonstrated elevated plasma FGF-21 levels in patients with chronic kidney disease. We did not observe any correlation between plasma FGF-21 and either glomerular filtration rate (r = 0.089, P = NS) or serum creatinine (r = 0.277, P = 0.08).

Bottom Line: RESULTS Subjects with type 2 diabetes, subjects with IGT, and obese subjects with NGT were insulin resistant compared with lean subjects with NGT.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.

View Article: PubMed Central - PubMed

Affiliation: Division of Diabetes, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

ABSTRACT
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-[(3)H] 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 correlated 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.

Show MeSH
Related in: MedlinePlus