Non-obese adult onset diabetes with oral hypoglycemic agent failure: islet cell autoantibodies or reversible beta cell refractoriness?
Pancreatic beta cell function and insulin sensitivity, analyzed by the homeostasis model assessment, before and after 24 weeks of insulin therapy were studied and correlated with the presence of autoantibodies against beta cells (islet cell and anti-glutamic acid decarboxylase antibodies), in a group of 18 Brazilian lean adult non-insulin-dependent diabetes mellitus (NIDDM) patients with oral hypoglycemic agent failure (OHAF). Median fasting plasma glucose before and after insulin treatment was 19.1 and 8.5 mmol/l, respectively (P < 0.001); median HbA1c was 11.7% before vs 7.2% after insulin treatment (P < 0.001). Forty-four percent of the patients were positive (Ab+) to at least one autoantibody. Fasting C-peptide levels were lower in Ab+ than Ab- patients, both before (Ab+: 0.16+/-0.09 vs Ab-: 0.41+/-0.35 nmol/l, P < 0.003) and after insulin treatment (Ab+: 0.22+/-0.13 vs Ab-: 0.44+/-0.24 nmol/l, P < 0.03). Improvement of H was seen in Ab- (median before: 7.3 vs after insulin therapy: 33.4%, P = 0.003) but not in Ab+ patients (median before: 6.6 vs after insulin therapy: 20.9%). These results show that the OHAF observed in the 18 NIDDM patients studied was due mainly to two major causes: autoantibodies and beta cell desensitization. Autoantibodies against beta cells could account for 44% of OHAF, but Ab- patients may still present beta cell function recovery, mainly after a period of beta cell rest with insulin therapy. However, the effects of beta cell function recovery on the restoration of the response to oral hypoglycemic agents need to be determined.
D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000276:immunology / Q000627:therapeutic use*; D007328:Insulin / Q000276:immunology / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000276:immunology* / Q000502:physiology; D008297:Male; D017211:Treatment Failure
D001323:Autoantibodies; D007004:Hypoglycemic Agents; D007328:Insulin; C024211:islet cell antibody