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Plasma fetuin-A levels and the risk of type 2 diabetes.

Stefan N, Fritsche A, Weikert C, Boeing H, Joost HG, Häring HU, Schulze MB - Diabetes (2008)

Bottom Line: The association remained significant after adjustment for sex, BMI, waist circumference, and lifestyle risk factors (RR for 10 mug/ml 1.03 [1.01-1.06]).Adjustment for glucose, triglycerides, HDL cholesterol, A1C, gamma-glutamyltransferase, or high-sensitivity C-reactive protein or mutual adjustment for these biomarkers did not appreciably change this result (RR for 10 mug/ml full adjusted model 1.05 [1.02-1.07]).Furthermore, fetuin-A was associated with increased diabetes risk particularly in individuals with elevated plasma glucose.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University of Tübingen, Tübingen, Germany.

ABSTRACT

Objective: The liver-secreted protein fetuin-A induces insulin resistance in animals, and circulating fetuin-A is elevated in insulin resistance and fatty liver in humans. We investigated whether plasma fetuin-A levels predict the incidence of type 2 diabetes in a large prospective, population-based study.

Research design and methods: A case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study comprising 27,548 subjects was designed. We randomly selected a subcohort of 2,500 individuals of whom 2,164 were diabetes free at baseline and had anamnestic, anthropometrical, and metabolic data for analysis. Of the 849 incident diabetic case subjects identified in the full cohort during 7 years of follow-up, 703 remained for analyses after similar exclusions.

Results: Plasma fetuin-A levels were positively associated with diabetes risk after adjustment for age (relative risk [RR] for extreme quintiles 1.75 [95% CI 1.32-2.31]; RR for 10 mug/ml 1.04 [1.03-1.06]). The association remained significant after adjustment for sex, BMI, waist circumference, and lifestyle risk factors (RR for 10 mug/ml 1.03 [1.01-1.06]). Adjustment for glucose, triglycerides, HDL cholesterol, A1C, gamma-glutamyltransferase, or high-sensitivity C-reactive protein or mutual adjustment for these biomarkers did not appreciably change this result (RR for 10 mug/ml full adjusted model 1.05 [1.02-1.07]). Furthermore, fetuin-A was associated with increased diabetes risk particularly in individuals with elevated plasma glucose.

Conclusions: Our data suggest that fetuin-A is an independent risk factor of type 2 diabetes.

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Related in: MedlinePlus

Schematic overview of the effects of circulating fetuin-A on target tissues. Increase in obesity, particularly in visceral fat mass, results in an increase of liver fat. By yet-unknown mechanisms, this is associated with increased production of fetuin-A (11,23). Elevated circulating fetuin-A directly inhibits insulin signaling in muscle and liver (7–9) and results in systemic subclinical and adipose tissue inflammation (19). Under a normal β-cell function, fetuin-A–induced insulin resistance and effects of subclinical inflammation on the β-cells may be compensated; however, the existence of impaired β-cell function results in fetuin-A–induced type 2 diabetes.
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f4: Schematic overview of the effects of circulating fetuin-A on target tissues. Increase in obesity, particularly in visceral fat mass, results in an increase of liver fat. By yet-unknown mechanisms, this is associated with increased production of fetuin-A (11,23). Elevated circulating fetuin-A directly inhibits insulin signaling in muscle and liver (7–9) and results in systemic subclinical and adipose tissue inflammation (19). Under a normal β-cell function, fetuin-A–induced insulin resistance and effects of subclinical inflammation on the β-cells may be compensated; however, the existence of impaired β-cell function results in fetuin-A–induced type 2 diabetes.

Mentions: Interestingly, the association between circulating fetuin-A and type 2 diabetes was modified by the existence of elevated glucose levels. A positive association was observed among participants with elevated plasma glucose levels within the nondiabetic range, whereas fetuin-A was not associated with diabetes risk among participants with normal glucose levels. Fasting hyperglycemia largely results from impaired function of the β-cells to secrete insulin, the major factor involved in the pathogenesis of type 2 diabetes (28). Our findings therefore support that fetuin-A itself or fetuin-A–induced insulin resistance may lead to a deterioration of insulin secretion and ultimately to a decompensation of glucose homeostasis, particularly in subjects who already display impaired β-cell function (Fig. 4). Thus, measurement of plasma fetuin-A may be particularly important for the evaluation of the individual risk of type 2 diabetes in these individuals who already have a high risk for the disease. Conversely, adequate β-cell function may protect individuals who are characterized by normal fasting glycemia from the detrimental effects of higher fetuin-A levels.


Plasma fetuin-A levels and the risk of type 2 diabetes.

Stefan N, Fritsche A, Weikert C, Boeing H, Joost HG, Häring HU, Schulze MB - Diabetes (2008)

Schematic overview of the effects of circulating fetuin-A on target tissues. Increase in obesity, particularly in visceral fat mass, results in an increase of liver fat. By yet-unknown mechanisms, this is associated with increased production of fetuin-A (11,23). Elevated circulating fetuin-A directly inhibits insulin signaling in muscle and liver (7–9) and results in systemic subclinical and adipose tissue inflammation (19). Under a normal β-cell function, fetuin-A–induced insulin resistance and effects of subclinical inflammation on the β-cells may be compensated; however, the existence of impaired β-cell function results in fetuin-A–induced type 2 diabetes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2551687&req=5

f4: Schematic overview of the effects of circulating fetuin-A on target tissues. Increase in obesity, particularly in visceral fat mass, results in an increase of liver fat. By yet-unknown mechanisms, this is associated with increased production of fetuin-A (11,23). Elevated circulating fetuin-A directly inhibits insulin signaling in muscle and liver (7–9) and results in systemic subclinical and adipose tissue inflammation (19). Under a normal β-cell function, fetuin-A–induced insulin resistance and effects of subclinical inflammation on the β-cells may be compensated; however, the existence of impaired β-cell function results in fetuin-A–induced type 2 diabetes.
Mentions: Interestingly, the association between circulating fetuin-A and type 2 diabetes was modified by the existence of elevated glucose levels. A positive association was observed among participants with elevated plasma glucose levels within the nondiabetic range, whereas fetuin-A was not associated with diabetes risk among participants with normal glucose levels. Fasting hyperglycemia largely results from impaired function of the β-cells to secrete insulin, the major factor involved in the pathogenesis of type 2 diabetes (28). Our findings therefore support that fetuin-A itself or fetuin-A–induced insulin resistance may lead to a deterioration of insulin secretion and ultimately to a decompensation of glucose homeostasis, particularly in subjects who already display impaired β-cell function (Fig. 4). Thus, measurement of plasma fetuin-A may be particularly important for the evaluation of the individual risk of type 2 diabetes in these individuals who already have a high risk for the disease. Conversely, adequate β-cell function may protect individuals who are characterized by normal fasting glycemia from the detrimental effects of higher fetuin-A levels.

Bottom Line: The association remained significant after adjustment for sex, BMI, waist circumference, and lifestyle risk factors (RR for 10 mug/ml 1.03 [1.01-1.06]).Adjustment for glucose, triglycerides, HDL cholesterol, A1C, gamma-glutamyltransferase, or high-sensitivity C-reactive protein or mutual adjustment for these biomarkers did not appreciably change this result (RR for 10 mug/ml full adjusted model 1.05 [1.02-1.07]).Furthermore, fetuin-A was associated with increased diabetes risk particularly in individuals with elevated plasma glucose.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, University of Tübingen, Tübingen, Germany.

ABSTRACT

Objective: The liver-secreted protein fetuin-A induces insulin resistance in animals, and circulating fetuin-A is elevated in insulin resistance and fatty liver in humans. We investigated whether plasma fetuin-A levels predict the incidence of type 2 diabetes in a large prospective, population-based study.

Research design and methods: A case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study comprising 27,548 subjects was designed. We randomly selected a subcohort of 2,500 individuals of whom 2,164 were diabetes free at baseline and had anamnestic, anthropometrical, and metabolic data for analysis. Of the 849 incident diabetic case subjects identified in the full cohort during 7 years of follow-up, 703 remained for analyses after similar exclusions.

Results: Plasma fetuin-A levels were positively associated with diabetes risk after adjustment for age (relative risk [RR] for extreme quintiles 1.75 [95% CI 1.32-2.31]; RR for 10 mug/ml 1.04 [1.03-1.06]). The association remained significant after adjustment for sex, BMI, waist circumference, and lifestyle risk factors (RR for 10 mug/ml 1.03 [1.01-1.06]). Adjustment for glucose, triglycerides, HDL cholesterol, A1C, gamma-glutamyltransferase, or high-sensitivity C-reactive protein or mutual adjustment for these biomarkers did not appreciably change this result (RR for 10 mug/ml full adjusted model 1.05 [1.02-1.07]). Furthermore, fetuin-A was associated with increased diabetes risk particularly in individuals with elevated plasma glucose.

Conclusions: Our data suggest that fetuin-A is an independent risk factor of type 2 diabetes.

Show MeSH
Related in: MedlinePlus