Metabolic Characteristics of Recently Diagnosed Adult-Onset Autoimmune Diabetes Mellitus

• Published in: The journal of clinical endocrinology and metabolism 2018-02, Vol.103 (2), p.429-437
• Main Authors: Zaharia, Oana P, Bobrov, Pavel, Strassburger, Klaus, Bódis, Kálmán, Karusheva, Yanislava, Scholz, Michaela, Markgraf, Daniel F, Burkart, Volker, Schloot, Nanette C, Müssig, Karsten, Szendroedi, Julia, Roden, Michael
• Format: Article
• Language: English
• Subjects: Adult; Age of Onset; Autoantibodies - blood; Autoimmune diseases; Blood glucose; Body mass; Body mass index; Case-Control Studies; Clamps; Diabetes; Diabetes mellitus; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); 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; Glucagon; Glucose; Glucose tolerance; Glutamate decarboxylase; Glutamic acid; Hemoglobin; Humans; Hyperglycemia; Immunological tolerance; Insulin; Insulin - metabolism; Insulin Resistance; Insulin Secretion; Intravenous administration; Islets of Langerhans - physiopathology; Male; Metabolism; Middle Aged; Phenotypes; Secretion; Sensitivity; T cell receptors
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2017-01706

Among patients diagnosed with type 2 diabetes, autoimmune diabetes often remains undetected. Metabolic features of these patients are insufficiently characterized at present. 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. 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. 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.