Studies on the Etiology of “Brittle Diabetes”: Relationship Between Diabetic Instability and Insulinogenic Reserve

Abstract

To clarify possible etiologie mechanisms for brittleness of diabetic control, a relationship between the degree of diabetic instability and insulinogenic reserve or insulin-binding capacity of plasma IgG was studied in 46 insulin-treated diabetics attending the outpatient clinic. Evaluation of insulinogenic reserve was based on elevations of plasma C-peptide immunoreactivity (CPR) during the oral glucose tolerance test (OGTT). The degree of instability was quantified by the standard deviations (S.D.) of 10 values of fasting blood glucose, which were determined for the last six months while subjects were attending a hospital as outpatients. An inverse correlation was evident between residual B-cell secretory capacity and blood glucose regulatory instability (r = −0.69, p < 0.005), but there was no consistent relationship of the insulin-binding capacity to the degree of diabetic instability (r = 0.15, p > 0.05). Furthermore, pancreatic A-cell functions were investigated in seven unstable and seven stable diabetics, classified according to their S.D. values. Although immunoreactive glucagon (IRG) responses to an infusion of arginine were observed, plasma IRG did not rise in unstable diabetics during insulin-induced hypoglycemia, in which condition IRG in stable diabetics rose significantly. In contrast, plasma cortisol responses to the insulin-induced hypoglycemia were demonstrated in both diabetic groups. Plasma CPR did not decrease in unstable but did in stable diabetics fol towing the insulin injection. The comparison of unstable diabetic patients with more stable ones on the basis of clinical data, such as means of age, duration of diabetes mellitus, duration of insulin therapy, and dose of insulin, revealed no significant difference. The total lack of insulinogenic reserve results inevitably in loss of the automatic regulation of circulating insulin levels, which seems to be one of the essential factors for causing the hyperla-biUty of diabetic control. The pancreatic A-cell dysfunction is also attributable in part to the metabolic variability in brittle diabetes.