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 (HbA 1c and insulin dose U kg) 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 Cpeptide 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 (HbA 1c Ͻ6 % and insulin Ͻ0.3 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.

Age-Dependent Influences on the Origins of Autoimmune Diabetes

“…1A). Postdiagnosis, there is a decline in both fasting and stimulated C-peptide; however, persistent C-peptide secretion, implying less aggressive disease, is detected in more adults than adolescents and in more adolescents than prepubertal diabetic children (62)(63)(64).…”

Insulin Secretion in Type 1 Diabetes

“…Hence, measurement of insulin in the peripheral blood does not accurately reflect endogenous insulin secretion. Most studies have approximated insulin secretion with C-peptide levels measured when fasting, at random, or following provocation with mixed meals or glucagon (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). While glucagon produces a reliable insulin response, it does not simulate normal physiology while a mixed meal is physiological.…”

Preserved β-Cell Function in Type 1 Diabetes by Mesenchymal Stromal Cells

“…Retention of endogenous insulin secretion is an attractive goal, since it causes better glycemic control (2) and decreases the risk of microvascular complications and severe hypo-or hyperglycemia episodes (3,4).…”