Pathophysiological study of the non-insulin-dependent phase of type I diabetes mellitus

The usual practice of considering type I diabetes synonymous with insulin-dependent diabetes has been criticized. Since type I diabetes can have a non-insulin-dependent phase (pre-type I diabetes and/or honeymoon) the differentiation of two main types of diabetes according to insulin-dependency is not absolute. We studied the insulin, C-peptide and glucagon responses to various tests (OGTT, IVGTT, glibenclamide test, mixed meal tolerance test and ITT) performed during the non-insulin-dependent phase of 3 young patients (range 8-18 years) who developed ketosis 12-24 months after the discovery of fasting hyperglycemia, and in 6 patients (age 15-23 years) who presented a remission phase 4-6 months after the sudden clinical onset of type I diabetes. An insignificant insulin and C-peptide increase following i.v. glucose was observed in all patients, whereas the B-cell response to both oral glucose and other secretagogues was preserved, although at a subnormal level. In the three hyperglycemic and preketoacidotic patients the basal levels of glucagon were low and no significant increase after secretagogues was seen. Sensitivity to exogenous insulin in all patients was good. Thus, B-cell response in our patients was reminiscent of the differential responsiveness to various stimulants in the early stage of type II (non-insulin-dependent) diabetes. These results suggest that type I and type II diabetes can be characterized by the same functional B-cell defect during a period of their natural history.