Lingjiao Liu1, Xia Li1, Yufei Xiang1, Gan Huang1, Jian Lin1, Lin Yang1, Yunjuan Zhao1, Zhifang Yang1, Can Hou1, Yijun Li1, Jie Liu2, Dalong Zhu3, R David Leslie4, Xiangbing Wang1, Zhiguang Zhou5. 1. Institute of Metabolism and Endocrinology, The Second Xiangya Hospital and the Diabetes Center, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China. 2. Department of Endocrinology and Metabolism, Shanxi Provincial People's Hospital, Taiyuan, China. 3. Department of Endocrinology and Metabolism, Nanjing University affiliated Nanjing Drum Tower Hospital, Nanjing, China. 4. Department of Diabetes and Metabolic Medicine, Blizard Institute, London, U.K. 5. Institute of Metabolism and Endocrinology, The Second Xiangya Hospital and the Diabetes Center, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Center for Metabolic Diseases, Changsha, Hunan, China zhouzg@hotmail.com.
Abstract
OBJECTIVE: This study investigated the relationship between GAD autoantibody (GADA) titers and changing of β-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 (HbA1c), 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 β-cell function (FCP >0.2 nmol/L) was detected in only 42% with an initial high GADA titer compared with 90% with a low GADA 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 β-cell function similar to type 2 diabetic patients.
OBJECTIVE: This study investigated the relationship between GAD autoantibody (GADA) titers and changing of β-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 diabeticpatients, the latter two groups as controls of similar age, sex, and BMI. Clinical characteristics were determined annually, including glycosylated hemoglobin (HbA1c), 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 β-cell function (FCP >0.2 nmol/L) was detected in only 42% with an initial high GADA titer compared with 90% with a low GADA 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 β-cell function similar to type 2 diabeticpatients.
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