title: Parameters associated with residual insulin secretion during the first year of disease in children and adolescents with Type 1 diabetes mellitus.
abstract: Factors associated with residual insulin secretion and spontaneous remission in Type 1 diabetic patients are important in the evaluation of treatment aimed at modifying the natural history of Type 1 DM. We investigated the effect of parameters at onset on residual beta cell function in 215 Type 1 DM children and adolescents. Blood gas analysis, HLA, GAD and IA-2 antibodies before the start of insulin treatment were recorded for each patient. Residual C-peptide secretion was assessed by the glucagon test, and parameters of metabolic control (HbA1c and insulin dose U kg(-1) day(-1)) were examined at disease onset and after 3, 6, and 12 months. Residual C-peptide secretion throughout the first year of disease was significantly reduced in patients with disease onset before age 5. Multiple regression analysis showed that low pH at onset showed a significant and independent association with reduced C-peptide at 3 months (p = 0.02) and that the detection of GAD antibodies had a significant independent association with decreased C-peptide secretion at 6 months of follow-up (p = 0.02). Insulin requirement was higher in the youngest patients group and in patients with GAD antibodies. Spontaneous insulin remission (HbA1c <6% and insulin <0.3 U kg(-1) day(-1)) occurred in 22/192 (11%) patients at 3 months of follow-up, in 15/190 (8%) patients at 6 months and in 8/169 (5%) patient at 12 months. Remission was more prevalent in older patients (p = 0.01) and in patients without detectable GAD antibodies: (14/64 vs 8/128, p = 0.001). Sex, IA-2 antibodies and HLA DR were not independently associated with C-peptide secretion, insulin requirement or remission in the first year of Type 1 DM. This study confirms the association of young age, severe acidosis at disease onset, and GAD antibodies with decreased residual beta-cell function and spontaneous remission during the first year of insulin treatment. These factors should be considered in trials evaluating therapies to retain beta-cell function and induce remission at and after disease onset.
authors.affiliation: Department of Paediatrics, Scientific Institute H San Raffaele, University of Milan, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Bonfanti
authors.forename: E
authors.initials: E
authors.lastname: Bazzigaluppi
authors.forename: G
authors.initials: G
authors.lastname: Calori
authors.forename: M C
authors.initials: MC
authors.lastname: Riva
authors.forename: M
authors.initials: M
authors.lastname: Viscardi
authors.forename: E
authors.initials: E
authors.lastname: Bognetti
authors.forename: F
authors.initials: F
authors.lastname: Meschi
authors.forename: E
authors.initials: E
authors.lastname: Bosi
authors.forename: G
authors.initials: G
authors.lastname: Chiumello
authors.forename: E
authors.initials: E
authors.lastname: Bonifacio
mesh_terms: D000293:Adolescent; D000328:Adult; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007223:Infant; D007328:Insulin / Q000276:immunology / Q000378:metabolism* / Q000627:therapeutic use; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008565:Membrane Proteins; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases / Q000276:immunology; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D012075:Remission, Spontaneous; D012189:Retrospective Studies
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D002097:C-Reactive Protein; D005968:Glutamate Decarboxylase; D006442:Glycated Hemoglobin; D006684:HLA-DR Antigens; D007004:Hypoglycemic Agents; D007328:Insulin; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; C102889:PTPRN2 protein, human