Beneficial effects of intensive therapy of diabetes during adolescence: outcomes after the conclusion of the Diabetes Control and Complications Trial (DCCT).

OBJECTIVE: The Diabetes Control and Complications Trial (DCCT) demonstrated that intensive therapy of type 1 diabetes mellitus reduces the risk of development and progression of microvascular complications. The Epidemiology of Diabetes Interventions and Complications (EDIC) study assessed whether these benefits persisted after the end of DCCT. Results for the adolescent DCCT cohort are reported here. STUDY DESIGN: Of the DCCT adolescent cohort (n = 195), 175 participated in EDIC, 151 had fundus photography, and 156 had albumin excretion rate measured at year 3 or 4. The odds of progression of retinopathy and albuminuria from closeout of the DCCT until EDIC year 4 were assessed. RESULTS: In contrast to the 7.4 years of the DCCT, during which mean hemoglobin A(1c) levels were significantly lower with intensive therapy than conventional therapy (8.06% vs 9.76%; P <.0001), the subsequent first 4 years of EDIC had mean hemoglobin A(1c) levels that were similar between the former intensive and the former conventional groups (8.38% vs 8.45%). However, the prevalence of worsening of 3 steps or more in retinopathy and of progression to proliferative or severe nonproliferative retinopathy were reduced by 74% (P <.001) and 78% (P <.007), respectively, in the former intensive therapy group compared with the former conventional group. CONCLUSIONS: These findings provide further support for the DCCT recommendation that most adolescents with type 1 diabetes receive intensive therapy aimed at achieving glycemic control as close to normal as possible to reduce the risk of microvascular complications.

First-phase insulin release during the intravenous glucose tolerance test as a risk factor for type 1 diabetes.

OBJECTIVE: To determine the relationship between first-phase (1 minute + 3 minutes) insulin production during the intravenous glucose tolerance test (IV-GTT) and risk factors for developing type 1 diabetes. STUDY DESIGN: Relatives of persons with type 1 diabetes (n = 59,600) were screened for islet cell antibodies (ICAs). Subjects who had positive screening results underwent IV-GTT (> or =2 times), repeat ICA screening, insulin autoantibody (IAA) screening twice, and an oral glucose tolerance test. RESULTS: Of the 59,600 subjects in the study, 2199 (3.69%) had positive findings on initial ICA test. IV-GTTs were performed in 1622 subjects, with children <8 years having the lowest first-phase insulin release (FPIR) and subjects 8 to 20 years of age having the highest FPIR. The FPIR was lower for subjects with a confirmed positive ICA test result or a positive IAA test result, subjects with higher titers of ICA or IAA, and subjects who had an abnormal (impaired or diabetic) oral glucose tolerance test result. CONCLUSION: FPIR in the IV-GTT correlates strongly with risk factors for development of type 1 diabetes.

Prevalence and consequences of nocturnal hypoglycemia among conventionally treated children with diabetes mellitus.

To determine the prevalence and predictors of, and the glucose responses after, nocturnal hypoglycemia, we studied 135 pediatric patients with insulin-dependent diabetes mellitus on 388 nights. The frequencies of blood glucose values less than 60, 50, and 40 mg/dl (3.3, 2.8, and 2.2 mmol/L) at 2 AM were 14.4%, 7.0%, and 2.1%, and at 6 AM were 6.7%, 2.6%, and 0.5%, respectively. Longer duration of diabetes, higher daily insulin doses, and lower glycosylated hemoglobin values were all significant but weak predictors of 2 AM hypoglycemia (glucose less than or equal to 60 mg/dl (less than or equal to 3.3 mmol/L). A 10 PM glucose concentration less than or equal to 100 mg/dl (less than or equal to 5.6 mmol/L) was present on 48% of nights with 2 AM glucose values less than or equal to 60 mg/dl (less than or equal to 3.3 mmol/L), but only 24% of nights with 10 PM blood glucose values less than or equal to 100 mg/dl (less than or equal to 5.6 mmol/L) were followed by 2 AM hypoglycemia. After treatment of 70 episodes of 2 AM glucose concentrations less than or equal to 60 mg/dl (less than or equal to 3.3 mmol/L), mean 6 AM glucose concentration was 95 +/- 6 mg/dl (5.7 +/- 0.3 mmol/L) and less than or equal to 100 mg/dl in 68.6%. In only 4.3% of these cases was the 6 AM glucose concentration greater than 200 mg/dl (greater than 11.1 mmol/L). Among patients who experienced 2 AM hypoglycemia, after-breakfast glucose values were not greater on days with 2 AM hypoglycemia than on days without it. These data indicate that 2 AM hypoglycemia is relatively common in patients with insulin-dependent diabetes mellitus, is frequently preceded by a 10 PM glucose value less than or equal to 5.6 mmol/L, and is less well predicted by other factors. Appropriate treatment of 2 AM hypoglycemia seldom results in either before-breakfast or after-breakfast blood glucose values greater than 200 mg/dl (greater than 11.1 mmol/L). Early-morning hypoglycemia is an uncommon cause of otherwise unexplained, prebreakfast hyperglycemia in children with insulin-dependent diabetes mellitus.

Acquisition of cytomegalovirus infection from birth to 10 years: a longitudinal serologic study.

We performed serial serologic tests for cytomegalovirus (CMV) antibody in 177 children born to low- and middle-income families in Houston from 1975 to 1983. Mean duration of participation in the study was 4.8 years (range 1 to 9.6 years). Most rapid acquisition of antibody occurred during the first and second years of life, 13.6% and 12%, respectively; thereafter, annual acquisition varied from 1.5% to 4.6%, up to 10 years. Overall, 59 (33%) of the group were known to seroconvert by age 10 years. This was a minimal figure because of loss to follow-up. Analysis by the Kaplan-Meier method indicated that the probability of remaining seronegative was 65% at age 6 years, and 58% at age 8 years. Variables positively related to seroconversion by multivariate analysis were order of birth, seroconversion in a family member, and breast-feeding. During the first year of life, acquisition of CMV antibody was related to the seroimmune status of the mother. The variables of socioeconomic status, race, age of the mother, and attendance in a day care center did not appear to be related to seroconversion in these children.

Roles of site and timing of the morning insulin injection in type 1 diabetes.

To investigate the effect of site and timing of insulin injection on post-breakfast plasma glucose concentration, 23 children with type 1 diabetes were given their usual mixture of short- and intermediate-acting insulin five minutes prior to breakfast on one day and between 15 and 60 minutes before breakfast on the alternate day, depending on their 7:00 AM fasting blood glucose concentration. Thirteen children received insulin in an extremity, and 10 in the abdominal wall. Plasma insulin and glucose patterns were similar for the two injection sites. The mean post-breakfast peak glucose increment was significantly lower and the mean increment in free insulin values during the first hour after breakfast was higher on the day when insulin preceded breakfast by 30 to 60 minutes. Thus, significant reductions in post-breakfast hyperglycemia can be achieved by increasing the interval between the injection and breakfast in proportion to the fasting capillary glucose concentration. The timing of the morning insulin injection may be more important than the injection site.

Reversal of neuropathic and gastrointestinal complications related to diabetes mellitus in adolescents with improved metabolic control.

Two adolescents with insulin-dependent diabetes mellitus developed unusually severe diabetic neuropathy which responded to intensive measures to achieve improved metabolic control. Employing home blood glucose monitoring and either frequent insulin injections or a portable insulin infusion pump, painful peripheral neuropathy and autonomic gastrointestinal neuropathy improved after five and 12 months of therapy, respectively. During this period of time, abnormal ocular fluorophotometry, an early change in the eye of diabetic patients, also returned to normal. These patients demonstrate the reversibility of unusually severe neuropathy and early ocular changes in adolescents with diabetes when treated with intensive measures designed to improve metabolic control.