DIFFERENTIAL BETA-CELL RESPONSE TO GLUCOSE, GLUCAGON, AND ARGININE DURING PROGRESSION TO TYPE-I (INSULIN-DEPENDENT) DIABETES-MELLITUS

Acute insulin responses to glucose (AIRG), glucagon (AIRGln), and argi nine (AIRArg) were evaluated prospectively in nine subjects positive f or islet-cell antibodies (ICAs) who later progressed to type I diabete s or impaired glucose tolerance (IGT) (progressors), 64 ICA-positive s ubjects at risk who did not develop type I diabetes, 365 ICA-negative relatives of diabetic patients who also remained free of the disease, and 89 control subjects. Seven progressors already had a low AIRG at e ntry into the study, and the other two became low responders 3 to 9 mo nths before diabetes or IGT, with a progressive decline of AIRG over s erial intravenous (IV) glucose tolerance tests. At entry into the stud y, the group of progressors displayed lower AIRG, AIRGln, and AIRArg t han the other three groups (P < .001). However, AIRArg was less altere d than AIRG. During the course of the prediabetic phase, there was a p rogressive decline in AIRG and AIRGln analyzed as a function either of time (P < .006) or of basal glycemia (P < .05), ie, two different way s of estimating worsening of the disease process. Conversely, there wa s no significant decrease in AIRArg with time or with increasing basal glycemia, so that AIRArg was not totally blunted in these prediabetic subjects even a few months before the onset of diabetes. The persiste nce of a substantial response to arginine, ie, higher than the fifth c ontrol percentile, even at a late stage, was confirmed in five of nine diabetic patients tested either at onset of the disease or during non -insulin receiving remission. Whereas AIRG deteriorates during prediab etes, AIRArg appears to be less altered with time and increased basal glycemia, remaining substantial even at the onset of the disease. This reinforces the supposition that the prediabetic state may be associat ed with a glucose-specific beta-cell functional abnormality in additio n to a decreasing beta-cell mass. Copyright (C) 1996 by W.S. Saunders Company