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+/ins−); previously termed latent autoimmune diabetes of adults], type 1 diabetes [antibody positive/insulin positive (ab+/ins+)], and type 2 diabetes [antibody negative/insulin negative (ab−/ins−)], as well as glucose-tolerant humans (controls) of the German Diabetes Study (n = 41/group). β-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+/ins− patients, 33 (81%) were initially diagnosed as having type 2 diabetes. In ab+/ins−, body mass index (BMI) was higher than in ab+/ins+ (27.8 ± 5.3 kg/m2 vs 25.0 ± 3.5 kg/m2, P < 0.05), lower than in ab−/ins− (31.9 ± 5.8 kg/m2, P < 0.05), and similar to controls (29.4 ± 6.6 kg/m2). In ab+/ins−, GAD antibody titers correlated negatively with BMI (r = −0.40, P < 0.05) and with C-peptide secretion in glucagon stimulation tests (r = −0.33, P < 0.05). β-Cell function from IVGTT was 228% higher in ab+/ins− than in ab+/ins+ but 35% lower than in ab−/ins− and 61% lower than in controls (all P < 0.05). Insulin sensitivity in ab+/ins− was comparable to ab+/ins+ and controls but 41% higher than in ab−/ins− (P < 0.05) after adjustment for BMI and fasting blood glucose or hemoglobin A1c.
Conclusion
Even shortly after diagnosis, ab+/ins− patients feature partly preserved β-cell function and chronic hyperglycemia, which possibly contributes to the observed impairment of whole-body insulin sensitivity.