Sustained Normoglycemia in Newly Diagnosed Type I Diabetic Subjects: Short-Term Effects and One-year Follow-up

The impact on remission of normalizing blood glucose levels immediately after diagnosis of type I diabetes was studied in 14 adolescents. Accordingly, in this randomized prospective primary intervention study, 7 of the subjects (i.v. group) received insulin by continuous intravenous (i.v.) infusion via a portable preprogrammed system for 28–62 days and 7 (s.c. group) received conventional subcutaneous (s.c.) therapy. Before therapy, the two groups did not differ significantly with respect to glycosylated hemoglobin, fasting plasma C-peptide, or 24-h urinary C-peptide excretion. During the infusion period, the overall mean fasting plasma glucose (FPG) concentration for the i.v. group was 84 mg/dl with a mean coefficient of variation of 18 ± 4% (mean ± SD). During the comparable period for the s.c. group, the mean FPG was 253 mg/dl with a coefficient of variation of 30 ± 20%. Twenty-four-hour urinary glucose excretions for the two groups were 0.29 ± 0.06 (mean ± SEM) and 59 ± 11 g/day, respectively. Daily insulin requirements in the i.v. group decreased from 1.47 ± 0.19 U/kg body wt/day at the start to 0.47 ± 0.10 U/kg/day at the end of the infusion period. Notably, 10–25 days after the infusion period, 5 of 7 subjects experienced a further decrease to a low of 0.27 ± 0.01 U/kg/day. The mean peak and low requirements in the s.c. group were 0.71 ± 0.15 and 0.33 ± 0.13 U/kg/day, respectively, with the only peak requirements being significantly different (P < 0.01). No patient was able to discontinue insulin therapy. The fasting plasma C-peptide level rose significantly (P < 0.05) by 1 mo in the i.v. group, but only achieved similar levels by 4 mo in the s.c. group. In the i.v. group, 24-h urinary C-peptide excretion decreased during the first week of therapy, rose through the infusion period, and finally peaked at 60 ± 14 μg day 3–30 days later. In the s.c group, the urinary C-peptide excretion gradually increased reaching a significantly lower peak (P < 0.05) of 36 ± 8 μg day at 113 ± 38 days. Glycosylated hemoglobin levels declined significantly only in the i.v. group with 4 subjects achieving normal levels. At 1 mo after diagnosis, the i.v. group had significantly higher (P < 0.05) fasting plasma C-peptide levels and lower (P < 0.005) glycosylated hemoglobin levels than did the s.c. group. Inspite of the higher peak urinary C-peptide excretion for the i.v. group, 4 and 12 mo after diagnosis the groups did not differ in mean 24-h urinary C-peptide excretion, fasting plasma C-peptide, insulin requirements, or glycosylated hemoglobin. We conclude that sustained strict glycemie control within normal limits at diagnosis of type I diabetes does not of itself augment the remission phase.