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Increased Risk For Impaired Glucose Tolerance and Metabolic Syndrome For Relatives of Type 2 Diabetics

Posted: Thursday, March 18, 2004

Mounting evidence suggests that type 2 diabetes is not just a disorder of glucose metabolism; the combination of diabetic glucose tolerance, insulin resistance, and increased weight is thought to play a major pathophysiological role in the "metabolic syndrome", a clustering of cardiovascular risk factors. Moreover, this clustering may not only occur in those with diabetic glucose tolerance, but also in persons with impaired glucose tolerance.

Michael A. Nauck, of the Diabetes Center Bad Lauterberg, Harz, Germany, and colleagues performed a 25-year follow-up study to characterize the association of oral glucose tolerance with components of the metabolic syndrome in subjects with a clear genetic burden for developing type 2 diabetes.

The original cohort included 686 first-degree relatives of type 2 diabetes patients followed in a long-term study for the development of impaired glucose tolerance or diabetes. The present analysis included 135 survivors from this cohort who were available for the study and did not have known type 2 diabetes. All participants underwent a 75-g oral glucose tolerance test and were evaluated for anthropomorphic data, blood pressure, insulin and C-peptide concentrations, and parameters of lipid metabolism.

Of the 135 participants, 71 were found to have normal glucose tolerance, 22 had impaired glucose tolerance, and 42 had diabetic glucose tolerance as classified by WHO criteria. Impaired and diabetic glucose tolerance were significantly associated with advanced age (P = .001), increased weight (P = .005), high waist-hip ratio (P = .001), systolic hypertension (P = .031), elevated basal insulin (P < .001) and C-peptide concentrations (P < .001), elevated free fatty acid levels (P < .001) and triglycerides (P = .017), and low HDL-cholesterol (P < .003). No associations were found with total and LDL-cholesterol.

As a rule, abnormalities in 1 parameter were associated with significant differences in a number of other parameters belonging to the metabolic syndrome, but an association between dyslipidemia and hypertension was less apparent. The presence of 3 or more abnormalities was associated with significant deteriorations in all other components of the metabolic syndrome analyzed.

"The association of type 2 diabetes with other cardiovascular risk factors makes it necessary to include preventive measures regarding these characteristics in standard patient education programs," the researchers propose. In addition, they suggest that a modified perception of type 2 diabetes as part of a metabolic syndrome rather than an isolated derangement of glucose metabolism may aid in the identification of candidate genes for this disease.