Simona Zampetti1, Giuseppe Campagna1, Claudio Tiberti1, Marco Songini1, Maria Luisa Arpi1, Giuseppina De Simone1, Efisio Cossu1, Lorenzo Cocco1, John Osborn1, Emanuele Bosi1, Francesco Giorgino1, Marialuisa Spoletini1, Raffaella Buzzetti2. 1. Department of Experimental Medicine'Sapienza' University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyDepartment of Internal MedicineS. Michele Hospital, Cagliari, ItalyEndocrinologyGaribaldi di Nesima Hospital, Catania University, Catania, ItalyDiabetologic CenterDistretto 54 ASL Napoli 3, Naples, ItalyEndocrinology and DiabetesDepartment of Medical Sciences, University of Cagliari, Cagliari, ItalyU.O.C. Diabetologia/Endocrinology'A. Cardarelli' Hospital, Campobasso, ItalyDepartment of Public Health Sciences and Infectious Diseases'Sapienza' University of Rome, Rome, ItalySan Raffaele Scientific InstituteDiabetes Research Institute, Milan, ItalySection of Internal MedicineEndocrinology, Andrology and Metabolic Disease, Department of Emergency and Organ Transplantation, University of Bari, School of Medicine, Bari, Italy. 2. Department of Experimental Medicine'Sapienza' University of Rome, Viale Regina Elena 324, 00161 Rome, ItalyDepartment of Internal MedicineS. Michele Hospital, Cagliari, ItalyEndocrinologyGaribaldi di Nesima Hospital, Catania University, Catania, ItalyDiabetologic CenterDistretto 54 ASL Napoli 3, Naples, ItalyEndocrinology and DiabetesDepartment of Medical Sciences, University of Cagliari, Cagliari, ItalyU.O.C. Diabetologia/Endocrinology'A. Cardarelli' Hospital, Campobasso, ItalyDepartment of Public Health Sciences and Infectious Diseases'Sapienza' University of Rome, Rome, ItalySan Raffaele Scientific InstituteDiabetes Research Institute, Milan, ItalySection of Internal MedicineEndocrinology, Andrology and Metabolic Disease, Department of Emergency and Organ Transplantation, University of Bari, School of Medicine, Bari, Italy raffaella.buzzetti@uniroma1.it.
Abstract
OBJECTIVE: The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up. METHODS: This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression. RESULTS: During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes (P<0.0001 for both). A BMI of ≤25 kg/m2 and IA-2IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P<0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P<0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P<0.0001, OR=6.95). CONCLUSIONS: High GADA titer, BMI ≤ 25, ZnT8 and IA-2IC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients.
OBJECTIVE: The aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up. METHODS: This study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan-Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression. RESULTS: During the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan-Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes (P<0.0001 for both). A BMI of ≤25 kg/m2 and IA-2IC and zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P<0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P<0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P<0.0001, OR=6.95). CONCLUSIONS: High GADA titer, BMI ≤ 25, ZnT8 and IA-2IC positivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients.
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