PARAMETERS ASSOCIATED WITH RESIDUAL INSULIN-SECRETION DURING THE FIRST-YEAR OF DISEASE IN CHILDREN AND ADOLESCENTS WITH TYPE-1 DIABETES-MELLITUS

Factors associated with residual insulin secretion and spontaneous rem ission in Type 1 diabetic patients are important in the evaluation of treatment aimed at modifying the natural history of Type 1 DM. We inve stigated the effect of parameters at onset on residual beta cell funct ion in 215 Type 1 DM children and adolescents. Blood gas analysis, HLA , CAD and IA-2 antibodies before the start of insulin treatment were r ecorded for each patient. Residual C-peptide secretion was assessed by the glucagon test, and parameters of metabolic control (HbA(1c) and i nsulin dose U kg(-1) day(-1)) were examined at disease onset and after 3, 6, and 12 months. Residual C-peptide secretion throughout the firs t year of disease was significantly reduced in patients with disease o nset 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 CAD antibodie s had a significant independent association with decreased C-peptide s ecretion at 6 months of follow-up (p = 0.02). Insulin requirement was higher in the youngest patients group and in patients with CAD antibod ies. Spontaneous insulin remission (HbA(1c) <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 a t 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 asso ciated with C-peptide secretion, insulin requirement or remission in t he first year of Type 1 DM. This study confirms the association of you ng age, severe acidosis at disease onset, and CAD antibodies with decr eased residual beta-cell function and spontaneous remission during the first year of insulin treatment. These factors should be considered i n trials evaluating therapies to retain beta-cell function and induce remission at and after disease onset. (C) 1998 John Wiley & Sons, Ltd.