Latent Autoimmune Diabetes in Adults With Low-Titer GAD Antibodies: Similar Disease Progression With Type 2 Diabetes A Nationwide, Multicenter Prospective Study (LADA China Study 3)

OBJECTIVE This study investigated the relationship between GAD autoantibody (GADA) titers and changing of beta-cell function in patients with latent autoimmune diabetes in adults (LADA). RESEARCH DESIGN AND METHODS This 3-year prospective study enrolled 95 subjects from 15 Chinese cities including 25 high-titer (GADA >= 180 units/mL) LADA patients, 42 low-titer (GADA <180 units/mL) LADA patients, and 28 type 2 diabetic patients, the latter two groups as controls of similar age, sex, and BMI. Clinical characteristics were determined annually, including glycosylated hemoglobin (HbA(1c)), fasting C-peptide (FCP), and 2-h postprandial C-peptide (PCP). RESULTS Despite similar initial FCP and PCP, FCP and PCP both decreased more in subjects with high GADA titer (FCP from mean 0.49 nmol/L at entry to 0.13 nmol/L at the third year; P < 0.05) than with low GADA titer (FCP from mean 0.48 to 0.38 nmol/L) and type 2 diabetes (FCP from mean 0.47 to 0.36 nmol/L); the latter two groups being similar. After 3 years, residual beta-cell function (FCP >0.2 nmol/L) was detected in only 42% with an initial high GADA titer compared with 90% with a lowGADA titer and 97% with type 2 diabetes (P < 0.01 for both). GADA positivity at the third year persisted more in subjects with initially high GADA (92%) than with low GADA (26%) titers (P < 0.01). CONCLUSIONS In selected LADA patients, initial GADA titers identified subjects with different degrees of persistent autoimmunity and disease progression. LADA patients with a low GADA titer had metabolic phenotypes and loss of beta-cell function similar to type 2 diabetic patients.