Nondiabetic relatives of probands with IDDM who are in the first two decades of life, are members of multiplex pedigrees, and have increased titers of islet-cell antibodies are the most likely to contract IDDM themselves.
A period of early, intensive insulin treatment is thought to improve subsequent beta-cell function in insulin-dependent diabetes mellitus (IDDM). To study this hypothesis, we randomly assigned adolescents with newly diagnosed IDDM to receive either conventional treatment (n = 14) (NPH insulin, 1 U per kilogram of body weight per day, in two divided doses) or an experimental treatment (n = 12) (a two-week hospitalization with maintenance of blood glucose levels between 3.3 and 4.4 mmol per liter by continuous insulin infusion delivered by an external artificial pancreas [Biostator]). During the two-week intervention, the experimental-therapy group received four times more insulin than the conventionally treated group, and their endogenous insulin secretion was more completely suppressed, as evidenced by a urinary C-peptide excretion rate one seventh that of the conventionally treated group. After the first two weeks, both groups were treated similarly and received similar amounts of insulin. At one year, the mean (+/- SEM) plasma level of C peptide was significantly higher after mixed-meal stimulation in the experimental-therapy group than in the conventionally treated group (0.51 +/- 0.07 vs. 0.27 +/- 0.06; P less than 0.01). The experimental-therapy group also had better metabolic control, as evidenced by lower glycohemoglobin values (7.2 +/- 0.7 vs. 10.8 +/- 1.2 percent; P less than 0.01). We conclude that suppression of endogenous insulin by intensive, continuous insulin treatment during the first two weeks after the diagnosis of IDDM may improve beta-cell function during the subsequent year.
Anti-BSA antibodies may reflect a general defect in the process of immunologic tolerance associated with a predisposition to autoimmunity rather than immunity specific to beta cells. The absence of cellular immunity to BSA and ABBOS in IDDM does not support a role for this antigen in the pathogenesis of the disorder.
IntroductionIslet cell antibodies (ICA) in the sera of nondiabetic relatives of patients with insulin-dependent diabetes (IDD) are predictive of the disease, a finding that permits the design of intervention strategies to prevent it. However, 85% or more of patients with new onset IDD have no affected relative. We therefore screened 9,696 schoolchildren between the ages of 5 and 18 yr (mean age 10.7 yr) in Pasco County, Florida for ICA in three surveys during 1984/5, 1987/8, and 1990/1 and have followed them prospectively. Approximately 4,000 of these children have been followed for nearly 8 yr. ICA titers 2 10 Juvenile Diabetes Foundation units on replicate tests were detected in 57 of the children (0.59%). 10 children have developed diabetes so far, and all had ICA detected beforehand. The likelihood of developing IDD among the ICA-positive children was compared with 2,959 age-matched nondiabetic first degree relatives of IDD probands who were screened for ICA by our laboratory during the same time period and also followed prospectively. Of 103 (3.5%) ICA-positive relatives, 31 have developed IDD. Life table analysis reveals no statistically significant differences in the probability of developing IDD between the ICApositive schoolchildren and ICA-positive first degree relatives (P = 0.3). The estimated risk of developing IDD by 7 yr in the ICA-positive schoolchildren was 45% (95% confidence interval 15-74%) compared with 43% (confidence interval 22-63%) in the relatives. We conclude that ICA appear to be as predictive of IDD in low-risk schoolchildren as they are in high-risk relatives. These data suggest that it is feasible to predict IDD by screening a general population of schoolchildren for ICA and that those found to be positive could be considered, in addition to relatives, for intervention protocols to prevent the disease.
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