Frequency, immunogenetics, and clinical characteristics of latent autoimmune diabetes in China (LADA China study): a nationwide, multicenter, clinic-based cross-sectional study

Abstract

Adult non-insulin requiring diabetes includes latent autoimmune diabetes of adults (LADA), distinguished from type 2 diabetes by the presence of islet autoantibodies. LADA China determined the characteristics of Chinese LADA. This nationwide, multicenter, clinic-based cross-sectional study was conducted in 46 university-affiliated hospitals in 25 Chinese cities. All 4,880 ketosis-free diabetic patients (<1 year postdiagnosis, without insulin therapy for >6 months, aged ≥30 years) had GAD antibody (GADA) and HLA-DQ genotype measured centrally with clinical data collected locally. GADA-positive subjects were classified as LADA. Of the patients, 5.9% were GADA positive with LADA. LADA showed a north-south gradient. Compared with GADA-negative type 2 diabetes, LADA patients were leaner, with lower fasting C-peptide and less metabolic syndrome. Patients with high GADA titers are phenotypically different from those with low GADA titers, while only a higher HDL distinguished the latter from those with type 2 diabetes. HLA diabetes-susceptible haplotypes were more frequent in LADA, even in those with low-titer GADA. HLA diabetes-protective haplotypes were less frequent in LADA. Our study implicates universal immunogenetic effects, with some ethnic differences, in adult-onset autoimmune diabetes. Autoantibody positivity and titer could be important for LADA risk stratification and accurate therapeutic choice in clinical practice.

FIG. 1.

Flowchart of LADA China Study. OGTT, oral glucose tolerance test.

FIG. 2.

China map for LADA China Study. , cities from the northeastern part of China; , cities from the northern part of China; , cities from northwestern China; , cities from eastern China; , cities from central China; , cities from southern China; and , cities from southwestern China. LADA frequency was higher in northern than southern China after age, sex, and BMI adjustment (P < 0.040). (A high-quality color representation of this figure is available in the online issue.)

FIG. 3.

Bimodal GADA titer (log 10 transformed) in LADA patients. GADA positivity above or below 180 units/mL largely captured the two modes, with high GADA titer (≥180 units/mL) in 26.5% of patients (76 of 287) and a low GADA titer (<180 units/mL) in 73.5% (211 of 287).