METABOLIC AND IMMUNE PARAMETERS AT CLINICAL ONSET OF INSULIN-DEPENDENT DIABETES - A POPULATION-BASED STUDY

The age at diagnosis of insulin-dependent diabetes mellitus (type I DM ) varies between childhood and adulthood. The aim of this study was to define the immunologic and metabolic characteristics of the disease a ccording to the age at which it is diagnosed. We evaluated the residua l beta-cell function (basal and stimulated C-peptide) and frequency of two major islet cell-related autoantibodies, glutamic acid decarboxyl ase (GAD) and tyrosine phosphatase-like molecule (IA-2ic), at the onse t of type I DM. A population-based study was performed with 235 consec utive cases of recent-onset (<4 weeks) type I DM (ages 5 to 45 years) diagnosed in the Lazio region of central Italy. Five age groups were c onsidered: patients diagnosed between ages 5 and 7 years (n = 10), 7 a nd 10 years (n = 38), 10 and 17 years (n = 94), 17 and 20 years (n = 1 7), and 20 and 45 years (n = 76). Patients diagnosed before puberty ha d significantly reduced C-peptide secretion compared with patients dia gnosed at a later age (P < .02). Glycosylated hemoglobin (HbA(1c)) did not differ at diagnosis between the different age groups. Patients di agnosed at puberty or after required significantly less insulin compar ed with younger patients (P < .04). GAD antibodies were found in 65% a nd IA-2ic antibodies in 59% of patients. GAD antibodies tended to be m ore frequent in patients diagnosed after age 17 compared with younger patients (P = .05), while IA-2ic antibodies were not age-related. Thes e data suggest that (1) the extent of beta-cell damage differs between patients diagnosed before and after puberty, the process being more d estructive in children less than 7 years of age, when C-peptide levels are the lowest; and (2) residual beta-cell function at diagnosis is n ot influenced by the presence or absence of islet cell-related antibod ies. These findings have implications for trials in type I DM diagnosi s aimed at protecting P cells from end-stage destruction and in attemp ts to prevent the disease in susceptible individuals. Copyright (C) 19 98 by W,B. Saunders Company.