Frequency, Immunogenetics, and Clinical Characteristics of Latent Autoimmune Diabetes in China (LADA China Study)

Author:

Zhou Zhiguang1,Xiang Yufei1,Ji Linong2,Jia Weiping3,Ning Guang4,Huang Gan1,Yang Lin1,Lin Jian1,Liu Zhenqi5,Hagopian William A.6,Leslie R. David7,

Affiliation:

1. Diabetes Center, Institute of Metabolism and Endocrinology, The Second Xiangya Hospital and Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, Changsha, China

2. Department of Endocrinology and Metabolism, Peking University People’s Hospital, Beijing, China

3. Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

4. Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Ruijin Hospital, Shanghai, China

5. Department of Internal Medicine, Division of Endocrinology and Metabolism, University of Virginia Health System, Charlottesville, Virginia

6. Pacific Northwest Diabetes Research Institute, Seattle, Washington

7. Department of Diabetes and Metabolic Medicine, Blizard Institute, London, U.K.

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.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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