Metabolic characteristics of recently diagnosed adult-onset autoimmune diabetes mellitus

Abstract

Context and Objective: Among patients diagnosed with type 2 diabetes, autoimmune diabetes often remains undetected. Metabolic features of these patients are insufficiently characterized at present. Design, Setting, and Patients: This study compared age-And sex-matched adult (aged 41 to 62 years) humans with recent-onset diabetes: patients positive for antibodies against glutamic acid decarboxylase (GAD) and/or cytoplasmic islet-cell antigen with an insulin-free period of .6 months [antibody positive/insulin negative (ab+/ins2); previously termed latent autoimmune diabetes of adults], type 1 diabetes [antibody positive/insulin positive (ab+/ins+)], and type 2 diabetes [antibody negative/insulin negative (ab2/ins2)], as well as glucose-Tolerant humans (controls) of the German Diabetes Study (n = 41/group). b-Cell function was assessed from glucagon tests and intravenous glucose tolerance tests (IVGTTs), and insulin sensitivity was determined from hyperinsulinemic-euglycemic clamps. Results: Of the ab+/ins2 patients, 33 (81%) were initially diagnosed as having type 2 diabetes. In ab+/ins2, bodymass index (BMI) was higher than in ab+/ins+ (27.865.3 kg/m2 vs 25.063.5 kg/m2, P,0.05), lower than in ab2/ins2(31.965.8 kg/m2, P,0.05), and similar to controls (29.466.6 kg/ m2). In ab+/ins2, GAD antibody titers correlated negativelywith BMI (r =20.40, P,0.05) andwith C-peptide secretion in glucagon stimulation tests (r = 20.33, P , 0.05). b-Cell function from IVGTT was 228% higher in ab+/ins2 than in ab+/ins+ but 35% lower than in ab2/ins2 and 61% lower than in controls (all P , 0.05). Insulin sensitivity in ab+/ins2 was comparable to ab+/ins+ and controls but 41% higher than in ab2/ins2 (P , 0.05) after adjustment for BMI and fasting blood glucose or hemoglobin A1c. Conclusion: Even shortly after diagnosis, ab+/ins2 patients feature partly preserved b-cell function and chronic hyperglycemia, which possibly contributes to the observed impairment of whole-body insulin sensitivity.