Mechanisms for Hyperglycemia in the Metabolic Syndrome: The Key Role of β-Cell Dysfunction

Hyperglycemia in Type 2 diabetes represents a steady‐state re‐regulation of plasma glucose to a higher‐than‐normal level after an overnight fast. The underlying pathophysiology represents an interaction between impaired β‐cell function and peripheral and hepatic insulin resistance which leads to abn...

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Bibliographic Details
Published in:Annals of the New York Academy of Sciences 1999-11, Vol.892 (1), p.73-83
Main Author: PORTE Jr, DANIEL
Format: Article
Language:English
Subjects:
Diabetes Mellitus, Type 2 - etiology
Diabetes Mellitus, Type 2 - metabolism
Glucose Intolerance - metabolism
Humans
Hyperglycemia - etiology
Hyperglycemia - metabolism
Hyperinsulinism - etiology
Hyperinsulinism - metabolism
Insulin Resistance
Islets of Langerhans - metabolism
Risk Factors
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Summary:Hyperglycemia in Type 2 diabetes represents a steady‐state re‐regulation of plasma glucose to a higher‐than‐normal level after an overnight fast. The underlying pathophysiology represents an interaction between impaired β‐cell function and peripheral and hepatic insulin resistance which leads to abnormal hepatic glucose production. Subjects with the Metabolic Syndrome are at an increased risk for Type 2 diabetes and often have one or both of these disorders present even when glucose tolerance is normal. Thus, sophisticated measures of β‐cell function and insulin sensitivity demonstrate a high frequency in populations characterized as having a high prevalence of atherosclerosis, central obesity, hypertension, and dyslipidemia with or without impaired glucose tolerance. Hyperglycemia compensates for the impairment of β‐cell function and therefore, in our view, the β‐cell is the critical factor in its development. Hyperinsulinemia, a curvilinear compensation for insulin resistance that is closely correlated with central adiposity, is another important predictor of hyperglycemia. In a Japanese‐American population followed for five years, impaired β‐cell function was present at baseline and preceded the accumulation of intraabdominal fat in those who developed Type 2 diabetes five years later. This interaction between these two pathophysiologic abnormalities in this sequence supports the hypothesis that β‐cell dysfunction contributes to the development of central adiposity by reduced CNS insulin signaling.
ISSN:0077-8923
1749-6632
DOI:10.1111/j.1749-6632.1999.tb07786.x