Shoichiro Tanaka1, Minoru Okubo2,3, Kaoru Nagasawa2,3, Soichi Takizawa1, Masashi Ichijo1, Sayaka Ichijo1, Masahiro Kaneshige1, Kaoru Aida1, Hiroki Shimura4, Yasumichi Mori2,3, Tetsuro Kobayashi1,3. 1. 1Third Department of Internal Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898 Japan. 2. 2Department of Endocrinology and Metabolism, Toranomon Hospital, 2-2-2, Minato, Tokyo, 105-8470 Japan. 3. 3Okinaka Memorial Institute for Medical Research, 2-2-2, Minato, Tokyo, 105-8470 Japan. 4. 4Department of Laboratory Medicine, Fukushima Medical University, 1 Hikarigaoka, Fukushima-shi, Fukushima 960-1295 Japan.
Abstract
AIMS: Whether the titer of glutamic acid decarboxylase antibodies (GADAs), especially a low titer, is a marker of progression of beta cell dysfunction in patients with slowly progressive insulin-dependent (type 1) diabetes (SPIDDM) is unclear. MATERIALS AND METHODS: Patients were subdivided as follows: patients with high GADA titers [≥10 U/ml (≥180 WHO U/ml): high GADA] (group 1, n = 37); those with low GADA titers [<10 U/ml (<180 WHO U/ml): low GADA] (group 2, n = 33); those without GADA and with islet cell antibodies (ICA) (group 3, n = 8); those without both GADA and ICA and with insulinoma-associated antigen 2 antibodies (IA-2A) (group 4, n = 6). We also allocated 198 type 2 diabetic patients without any GADA, ICA or IA-2A as group 5. Serum C-peptide responses to annual oral glucose tolerance tests (OGTTs) were followed up for a mean of 107 months from entry. RESULTS: The proportion of patients progressing to an insulin-dependent state in groups 1, 2, 3 and 4 was significantly higher than in group 5. C-peptide responses in OGTTs of patients in groups 1 and 2 were decreased at a significantly higher rate than in group 5. Multivariate Cox proportional hazard analysis revealed that factors including high GADA, low GADA, onset age <45 years, duration of diabetes <24 months, body mass index (BMI) <22.0 kg/m2, low degree of preserved beta cell function and ICA were independent risk factors for progression to an insulin-dependent state. CONCLUSIONS: SPIDDM patients with low GADA titers have a significantly higher risk of progression to an insulin-dependent state than type 2 diabetic patients, suggesting that the presence of GADA, irrespective of the titer, is a hallmark of beta cell failure. Other risk factors for further progression to an insulin-dependent state in SPIDDM patients were ICA, onset age, duration of diabetes, BMI and residual beta cell function.
AIMS: Whether the titer of glutamic acid decarboxylase antibodies (GADAs), especially a low titer, is a marker of progression of beta cell dysfunction in patients with slowly progressive insulin-dependent (type 1) diabetes (SPIDDM) is unclear. MATERIALS AND METHODS: Patients were subdivided as follows: patients with high GADA titers [≥10 U/ml (≥180 WHO U/ml): high GADA] (group 1, n = 37); those with low GADA titers [<10 U/ml (<180 WHO U/ml): low GADA] (group 2, n = 33); those without GADA and with islet cell antibodies (ICA) (group 3, n = 8); those without both GADA and ICA and with insulinoma-associated antigen 2 antibodies (IA-2A) (group 4, n = 6). We also allocated 198 type 2 diabetic patients without any GADA, ICA or IA-2A as group 5. Serum C-peptide responses to annual oral glucose tolerance tests (OGTTs) were followed up for a mean of 107 months from entry. RESULTS: The proportion of patients progressing to an insulin-dependent state in groups 1, 2, 3 and 4 was significantly higher than in group 5. C-peptide responses in OGTTs of patients in groups 1 and 2 were decreased at a significantly higher rate than in group 5. Multivariate Cox proportional hazard analysis revealed that factors including high GADA, low GADA, onset age <45 years, duration of diabetes <24 months, body mass index (BMI) <22.0 kg/m2, low degree of preserved beta cell function and ICA were independent risk factors for progression to an insulin-dependent state. CONCLUSIONS: SPIDDM patients with low GADA titers have a significantly higher risk of progression to an insulin-dependent state than type 2 diabetic patients, suggesting that the presence of GADA, irrespective of the titer, is a hallmark of beta cell failure. Other risk factors for further progression to an insulin-dependent state in SPIDDM patients were ICA, onset age, duration of diabetes, BMI and residual beta cell function.
Authors: Raffaella Buzzetti; Sergio Di Pietro; Andrea Giaccari; Antonio Petrone; Mattia Locatelli; Concetta Suraci; Marco Capizzi; Maria Luisa Arpi; Elena Bazzigaluppi; Francesco Dotta; Emanuele Bosi Journal: Diabetes Care Date: 2007-04 Impact factor: 19.112