139 IMPAIRED GLUCAGON COUNTERREGULATION IN CHILDREN WITH INSULIN-DEPENDENT DIABETES (IDD)

Abstract

Intravenous insulin (0.3-0.5 u/kg) was given over 2 mins to 36 pts with IDD, duration 1.7-16.7 yrs (x 8.2±4.2) aged 10.9-18.4 yrs (x 15.8±1.8). Plasma glucagon (IRG) responses were compared to those of 6 endocrinologically normal children with short stature (C) aged 13.2±3.2 yrs. Antibodies to IRG were found in 3 IDD pts who had relatively poor recovery from hypoglycemia. Increments from baseline (Δ) & peak IRG in the other 33 IDD pts were markedly lower than in C (80±67 vs 354±79 pg/ml, p=<.001, 211±97 vs 407±87, p < .001, resp). IRG response did not correlate with age, duration of IDD, free insulin (FI) levels (n=25), or % insulin antibody binding (IAb) (n=10). Also Δ IRG did not correlate with plasma glucose (G), nadir, % drop, or G recovery from nadir. This G recovery was impaired compared to C (P < .001) & did not correlate with FI levels or % IAb. 10 pts were studied after both insulin withdrawal & 3 days of intensive insulin Rx with no significant difference in IRG response. During intensive Rx there was a +ve correlation between IRG Δ, & G recovery from hypoglycemia (P < .001). Adequate IRG reserve was demonstrated during insulin withdrawal by a greater IRG response to a mixed meal than insulin (Δ 156±80 vs 55±57 pg/ml; P < .001); however, there was a +ve correlation between the IRG peaks after these 2 stimuli (r=.93, P < .001) suggesting some impairment of α cell function. The significance of this must be related to multiple other counterregulatory abnormalities, but IRG deficit appears to be a primary factor during intensive Rx.