title: High GADA titer increases the risk of insulin requirement in LADA patients: a 7-year follow-up (NIRAD study 7).
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.
authors.affiliation: 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.
authors.forename: Simona
authors.initials: S
authors.lastname: Zampetti
authors.affiliation: 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.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Campagna
authors.affiliation: 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.
authors.forename: Claudio
authors.initials: C
authors.lastname: Tiberti
authors.affiliation: 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.
authors.forename: Marco
authors.initials: M
authors.lastname: Songini
authors.affiliation: 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.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Arpi
authors.affiliation: 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.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: De Simone
authors.affiliation: 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.
authors.forename: Efisio
authors.initials: E
authors.lastname: Cossu
authors.affiliation: 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.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cocco
authors.affiliation: 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.
authors.forename: John
authors.initials: J
authors.lastname: Osborn
authors.affiliation: 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.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bosi
authors.affiliation: 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.
authors.forename: Francesco
authors.initials: F
authors.lastname: Giorgino
authors.affiliation: 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.
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Spoletini
authors.affiliation: 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.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Buzzetti
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012306:Risk; D017186:Titrimetry
chemical_list: D001323:Autoantibodies; D007004:Hypoglycemic Agents; D007328:Insulin; D005968:Glutamate Decarboxylase