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The Normal Glucose Tolerance Continuum in Obese Youth: Evidence for Impairment in ß-Cell Function Independent of Insulin Resistance

Department of Pediatrics (C.W.Y., S.E.T., R.W., T.S.B., W.V.T., S.C.), The General Clinical Research Center (J.D.), and the Department of Internal Medicine (R.S.S.) of Yale University School of Medicine, New Haven, Connecticut 06520

Address all correspondence and requests for reprints to: Dr. Sonia Caprio, Yale University School of Medicine, Department of Pediatrics, P.O. Box 802064, New Haven, Connecticut 06520. E-mail: Sonia. Caprio{at}yale.edu.

Normal glucose tolerance is expressed over a wide range of glucose concentrations. Whether there is a continuum of risk for developing type 2 diabetes mellitus even when the 2-h plasma glucose is still within this normal range is uncertain. Oral glucose tolerance tests were performed in 407 obese normal glucose tolerance youth (4–20 yr) to examine the relationship between variations in 2-h plasma glucose levels and ß-cell responsiveness. Individuals were grouped by 2-h plasma glucose levels as follows: 1) less than 100 mg/dl, 2) 100–119 mg/dl, and 3) 120–139 mg/dl. Subsequent analysis stratified each 2-h plasma level by insulin sensitivity index. Increased 2-h glucose level was associated with a progressive increase in glucose between 0 and 30 min (P < 0.05). The (0–30 min) insulin did not vary significantly across levels, thus resulting in a decreased insulinogenic index (P < 0.02). This pattern was observed at every level of insulin sensitivity (P < 0.02). These data translated to an unfavorable (leftward) shift in the insulin feedback system for increasing 2-h glucose level (P < 0.005). Increased 2-h plasma glucose within the range of normal glucose tolerance in obese youth is associated with a specific impairment of ß-cell responsiveness distinct from the deterioration of insulin sensitivity.

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