ENDOCRINE-METABOLIC FUNCTION IN REMISSION-PHASE IDDM DURING ADMINISTRATION OF CYCLOSPORINE

We have studied the endocrine-metabolic status of patients in non-insulin-receiving (NIR) remission of insulin-dependent diabetes mellitus (IDDM) within 6-60 mo of diagnosis during administration of cyclosporine, in comparison with nondiabetic subjects. IDDM patients in NIR remission were recognized when target glycemic control (plasma glucose and mean capillary glood glucose levels < 7.8 mM before meals) was maintained without administration of insulin for at least 2 wk. In so-called isoglycemic tests, 50 g glucose was administered orally, and the glycemic curve was simulated in a subsequent study by programmed intravenous infusion of glucose. Under these conditions, the subjects with diabetes exhibited obvious glucose intolerance: acute beta-cell responses to intravenous glucose were virtually absent but significant, although subnormal responses were present after oral glucose. The responses of plasma immunoreactive gastric inhibitory polypeptide to oral glucose were normal. After bolus intravenous injections of glucose, the patients with diabetes again exhibited glucose intolerance; acute responses of immunoreactive insulin (IRI) and C-peptide were present, although grossly obtunded. On intravenous infusion of arginine (30 g in 30 min), the patients with diabetes showed substantial but subnormal increases in plasma IRI and C-peptide. Intravenous infusion of arginine elicited increments of plasma immunoreactive glucagon (IRGI) in both groups, and this response was slightly exaggerated in the patients with diabetes. On ingestion of a standard mixed meal (Sustacal) delivering 600 cal, there was a modest but significantly greater increase in plasma glucose levels in the diabetic subjects. This was associated with substantial increases in plasma IRI and C-peptide in both groups, whereas the responses of both hormones were significantly reduced in the patients with diabetes. Plasma IRGI did not change in response to Sustacal in nondiabetic or NIR subjects. Thus, patients in NIR remission of diabetes as defined exhibited grossly subnormal responses of the beta-cells to intravenous glucose, with relatively well-preserved responses to oral glucose, intravenous arginine, and a mixed meal. Evidence is cited that cyclosporine does not affect the endocrine-metabolic responses examined in this study. It appears that patients in this condition revert to a state similar to that in the interval shortly preceding manifestation of overt hyperglycemia.