c-peptide and Thrombocytopenia

It has been shown that danazol (14-ethinyltestosterone) induces hyperglucagonaemia. To investigate the effect of chronic glucagon excess on carbohydrate metabolism, we studied six patients before and after treatment with danazol for immunothrombopenia. Glucose tolerance and insulin, C-peptide and glucagon secretion during an oral glucose tolerance test (oGTT) as well as peripheral and hepatic insulin sensitivity were determined by means of euglycaemic clamp technique (40 mU m-2 min-1) before and after 3 months of danazol therapy. Overall glucose turnover (Rd) was assessed radioisotopically. (1) Plasma glucagon levels rose significantly from 88 +/- 16 pg mL-1 before to 683 +/- 148 pg mL-1 after therapy (P < 0.01). (2) Glucose levels during an oGTT were not significantly different before and after therapy. Glucose-stimulated insulin secretion at 60 and 120 min and the area under the curve (AUC) for insulin during the oGTT, were significantly increased after danazol treatment compared with pre-treatment values (P < 0.05), whereas glucagon secretion showed a similar decrease at both time points of investigation (NS). (3) Rd during steady state showed a significant decrease during the entire period of euglycaemic clamp following therapy (after 240 min, 3.8 +/- 0.6 vs. 5.3 +/- 0.7 mg kg-1 min-1, P < 0.05). The decline in glucagon during the clamp was similar during steady state before and after therapy. (4) Basal hepatic glucose output did not differ significantly before and after therapy (1.74 +/- 0.41 vs. 1.45 +/- 0.22 mg kg-1, NS), whereas hepatic glucose output during the clamp was significantly less suppressed after danazol therapy. The authors conclude that chronic glucagon excess leads to a decrease in peripheral and hepatic insulin action which is accompanied by an increase in insulin secretion.

Topics: Adult; Aged; Blood Glucose; C-Peptide; Danazol; Female; Glucagon; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Liver; Male; Middle Aged; Thrombocytopenia

A 43-year-old woman with spontaneous episodes of neuroglycopenic hypoglycemia was found to have immune-mediated thrombocytopenic purpura and primary biliary cirrhosis. Hypoglycemia along with hyperinsulinemia suggested insulinoma. Serum c-peptide levels were disproportionately low, raising the possibility of factitious hypoglycemia. The patient's plasma contained circulating insulin receptor autoantibodies, thought to cause hypoglycemia by their insulin-like actions. With prednisone therapy, her other autoimmune features improved, and the hypoglycemia eventually resolved. Hypoglycemia mediated by insulin receptor autoantibodies should be considered in patients with fasting hypoglycemia and features suggesting an underlying autoimmune disorder before pursuing more invasive procedures. High-dose steroids may be life-saving in this disorder.

Topics: Adult; Autoantibodies; Autoimmune Diseases; C-Peptide; Diagnosis, Differential; Fasting; Female; Humans; Hypoglycemia; Insulin; Liver Cirrhosis, Biliary; Prednisone; Receptor, Insulin; Syndrome; Thrombocytopenia

Increasing evidence that Type 1 (insulin dependent) diabetes mellitus is an autoimmune disease, together with successful cure/prevention in animal models of this disease (e.g. BB/W rat) has led to several trials of immunotherapy in recent onset Type 1 diabetes of man. In this communication we report our experience with short courses of prednisone and antithymocyte globulin (ATGAM) plus prednisone. Prednisone characteristically suppressed Ia positive T lymphocytes into the normal range, but had no long-lasting effect on T-cell phenotype. ATGAM plus prednisone markedly decreased the ratio of T4/T8 ("helper"/"suppressor-cytotoxic") positive T lymphocytes, and this remained suppressed for months. ATGAM treated patients had lower HbA1c on a lower dose of insulin 100 or more days following immune therapy (with 4 out of 5 patients requiring less than 0.2 U/Kg insulin/day). Two patients in the ATGAM treated group did not require insulin for more than 8 months; during remission they had normal fasting blood glucose values, but with abnormal glucose tolerance on oral glucose tolerance testing. Severe, though transient, thrombocytopenia was observed in 2 patients on ATGAM therapy which outweighed its clinical effects.

Topics: Adolescent; Adult; Antilymphocyte Serum; C-Peptide; Child; Child, Preschool; Diabetes Mellitus, Type 1; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Immunotherapy; Male; Prednisone; T-Lymphocytes; Thrombocytopenia; Time Factors