c-peptide and Drug-Hypersensitivity

Insulin administration causes various types of immune response to insulin. However, there have been no reports that insulin administration triggers pancreatic beta-cell destruction in diabetic patients. We evaluated three patients who had suffered from type 2 diabetes or impaired glucose tolerance for 5-30 years. After an episode of diabetic mononeuropathy or poor glycemic control, they started human insulin therapy. All the patients' serum or urinary C-peptide levels were preserved before insulin therapy, whereas within a few months they rapidly declined to below detection limits. A high titer of insulin antibody was detected at or after the development of insulin deficiency. Shortly after the initiation of insulin therapy, two of the patients developed an insulin allergy. Autoantibodies to GAD65 or IA-2 were negative throughout the clinical course in two cases, but transiently positive in one case. In a histological examination of pancreas tissue obtained by a pancreatic biopsy in one case, mononuclear cell infiltration into the islets was observed. They all had a type 1 diabetes high-risk HLA class II haplotype in Japanese, and class I alleles of the insulin gene VNTR. The above findings suggest that insulin administration may have triggered pancreatic beta-cell destruction in these patients.

Topics: Aged; Aged, 80 and over; C-Peptide; Diabetes Mellitus, Type 2; Drug Hypersensitivity; Humans; Hypoglycemic Agents; Insulin; Insulin-Secreting Cells; Male; Middle Aged

To test the sensitivity to insulin in recent-onset IDDM patients, its course according to treatment, and the advent of remissions.. The euglycemic hyperinsulinemic clamp was used in 54 recent-onset IDDM patients and 14 healthy control subjects. Patients were tested after 1,2, and 4 wk of treatment with either insulin or insulin plus cyclosporin A, during cyclosporin A-associated long-lasting remissions, and during relapses.. Insulin sensitivity was markedly decreased in all patients at onset. It was rapidly restored by insulin therapy, whether immunosuppression was associated with it or not. Insulin sensitivity was even higher than normal in the remission patients, who also were characterized by the reappearance of some endogenous insulin secretion and the sustained normalization of blood glucose profiles. During relapses, the deterioration of the blood glucose profiles was associated with some loss of insulin sensitivity.. Cyclosporin A-associated remissions represent an original situation that associates euglycemia with the persistence of low endogenous insulin secretion. Cyclosporin A by itself had no influence on sensitivity to insulin, but allowed the reappearance of some insulin secretory capacity that contributed, with the improvement of insulin sensitivity, to the development of the diabetes honeymoon. The secretion of endogenous insulin, although lower than normal, was sufficient to secure a high sensitivity to insulin and the maintenance of normal blood glucose profiles, presumably because of the fact that insulin was released directly into the portal vein in these conditions. This metabolic state was precarious: the optimal sensitivity to insulin disappeared in patients who relapsed. These results have important clinical consequences: the preservation of islet residual secretory capacity by the use of newer nontoxic immunosuppressive protocols, combined with a minimal supportive insulin therapy in remission patients, may prolong remissions and maintain an optimal insulin sensitivity.

Topics: Adult; Analysis of Variance; Autoantibodies; Blood Glucose; C-Peptide; Cyclosporine; Diabetes Mellitus, Type 1; Drug Hypersensitivity; Female; Glucose Clamp Technique; Glycated Hemoglobin; HLA-DQ Antigens; HLA-DR Antigens; Humans; Insulin; Insulin Antibodies; Islets of Langerhans; Male; Reference Values

Insulin allergy and antibody-mediated resistance may complicate therapy with animal insulins. We describe a 53-year-old man manifesting both resistance and persistent systemic allergy despite treatment with recombinant human insulin. Insulin resistance and symptoms of allergy appeared in this patient several months after initiating therapy with mixed beef-pork insulin, as is often the case. Symptoms initially improved, but persisted, and then worsened again, despite continuous human insulin therapy. Total insulin-binding capacity by Scatchard analysis, high plasma insulin-binding capacity, and specific anti-insulin antibody levels were consistent with an immunologic form of insulin resistance. Glucocorticoid therapy was required both to reduce allergic findings and to restore glycemic control. Although recently available human insulins may be less immunogenic than animal forms, immune responses to exogenous human insulin still may pose significant clinical problems.

Topics: Adult; C-Peptide; Diabetes Mellitus, Type 2; Drug Hypersensitivity; Drug Therapy, Combination; Enzyme-Linked Immunosorbent Assay; Glucocorticoids; Humans; Insulin; Insulin Antibodies; Insulin Resistance; Intradermal Tests; Male; Protein Binding; Recombinant Proteins