Source: Diabetes  |  Posted 8 years ago

People with abnormal fasting and post-challenge hyperglycaemia appear to have different rates of progression to diabetes; therefore, these 2 measurements may represent distinct phenotypic pathways in the evolution of type 2 diabetes, new research suggests.

Impaired fasting glucose (IFG) refers to a mildly elevated glucose level immediately after an oral glucose tolerance test (OGTT), whereas impaired glucose tolerance (IGT) indicates a mildly elevated plasma glucose levels 2 hours later. In the United States, detection of diabetes relies on measurement of fasting plasma glucose levels alone, and it is assumed that the value is predictive of impaired glucose tolerance and ultimately type 2 diabetes. This assumption has not been validated in longitudinal studies, however.

James B. Meigs, MD, MPH, with the Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues studied this progression using biennial oral glucose tolerance tests and survival analysis to assess progression from normal glucose tolerance (NGT) to abnormal fasting plasma glucose (FPG; > 6.1 mmol/L); abnormal 2-h plasma glucose (2hPG; >7.8 mmol/L); impaired fasting glucose (IFG) (FPG 6.1-6.9 mmol/L, 2hPG <7.8 mmol/L); and IGT (FPG <6.1 mmol/L, 2hPG 7.8-11.0 mmol/L). It was also used to assess progression from IFG-IGT to diabetes (FPG >7.0 mmol/L or 2hPG >11.1 mmol/L).

At baseline, 815 subjects of the Baltimore Longitudinal Study of Aging had a mean age of 57 years, 35% were women, and 60% (n=488) had NGT. Of those, over half were followed for at least 10 years.

By 10 years, 14% had progressed to abnormal FPG, and 48% had progressed to abnormal 2hPG, the researchers report. Of the 267 subjects who progressed to IFG-IGT, 216 were followed for an additional 10 years. During that time, 8% of them progressed to diabetes by FPG whereas 27% progressed by 2hPG. However, of the subjects developing abnormal FPG, 42% did not develop abnormal 2hPG, and vice versa.

"These data suggest that abnormal FPG and 2hPG levels are not necessarily part of a continuum in the evolution of hyperglycaemia," the researchers conclude.

Dr. Meigs and colleagues note that detection programs "relying solely on elevated FPG levels using current diagnostic thresholds may only detect the more uncommon IFG phenotype, and miss a substantial number of subjects at risk for diabetes on the basis of abnormal 2hPG levels."

They also point out that specifying a lower "abnormal" FPG level (in the 5.55-5.7 mmol/l range), using the OGTT, or identifying clusters of insulin resistance-related traits may be required to maximize identification of subjects at risk for developing type 2 diabetes.