Metabolic Characteristics of Recently Diagnosed Adult-Onset Autoimmune Diabetes Mellitus

J Clin Endocrinol Metab. 2018 Feb 1;103(2):429-437. doi: 10.1210/jc.2017-01706.


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.

Trial registration: NCT01055093.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Autoantibodies / blood
  • Case-Control Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Diabetes Mellitus, Type 1 / metabolism*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diagnostic Errors
  • Female
  • Humans
  • Insulin / metabolism
  • Insulin Resistance
  • Insulin Secretion
  • Islets of Langerhans / physiopathology
  • Male
  • Middle Aged


  • Autoantibodies
  • Insulin

Associated data