Biomedical subjects
Publications and source records attributed to C F Verge.
We report the case of a 13-year-old boy with SHORT syndrome, including lipoatrophy and insulin resistance, who developed diabetes mellitus while receiving growth hormone therapy. The diabetes persisted after cessation of exogenous growth hormone but oral hypoglycaemic therapy was successful and could be discontinued eight months later.
OBJECTIVE: To identify environmental factors involved in the etiology of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: An estimated 90% of all incident cases of IDDM in patients 0-14 years of age in New South Wales, Australia, were ascertained over 18 months. For each IDDM patient, two age- and sex-matched control subjects were randomly selected from the population. Past environmental exposures were determined with a questionnaire completed by the parents. Response rates were 92% for the IDDM patients (217 of 235) and 55% for the control subjects (258 of 470). The relative risk associated with each exposure was estimated with the odds ratio (OR) adjusted for confounding factors using multiple logistic regression. RESULTS: The introduction of cow's milk-based infant formula into the diet before 3 months of age was associated with an increased risk (OR 1.52, 95% confidence interval [CI] 1.04-2.24). Exclusive breast-feeding for > or = 3 months was associated with a protective effect (OR 0.66, 95% CI 0.45-0.97). High dietary intake of cow's milk protein in the 12 months before the onset of diabetic symptoms was also associated with an increased risk (OR 1.84, 95% CI 1.12-3.00). A recent infection (during the 3 months before onset of diabetic symptoms) was more common in the patients than the control subjects (OR 2.92, 95% CI 1.96-4.35), as was day care attendance before the age of 3 (OR 1.73, 95% CI 1.00-3.00). When two age-groups, defined by the median age at onset of diabetes, were compared, the associations with early infant-feeding were stronger among the younger group (< 9.2 years), and associations with recent diet and recent infection were stronger among the older group (> or = 9.2 years). CONCLUSIONS: These results indicate an increased risk of IDDM associated with early dietary exposure to cow's milk-containing formula, short duration of exclusive breast-feeding, high intake of cow's milk protein in the recent diet, recent infection, and early attendance at day care.
OBJECTIVE: To determine the incidence of insulin-dependent diabetes mellitus (IDDM) in children 0-14 years of age in the state of New South Wales, Australia, which has a total population of 5.73 million. RESEARCH DESIGN AND METHODS: We established a prospective register, identifying 361 incident cases over a 2-year period (1990-1991) with two independent sources of case ascertainment. The primary source was the reporting of newly diagnosed patients by physicians and diabetes educators. The secondary source was a subsidized syringe scheme. RESULTS: Using the capture-recapture method, ascertainment was estimated to be 99.4% complete. The age-standardized incidence rate was 14.5 per 100,000 person-years (95% confidence interval: 13.0-16.0). No significant differences were found when comparing the first and second years of the register, boys and girls, geographical areas, or Aboriginal and non-Aboriginal children. There was seasonal variation in the onset (with more cases in winter), which was evident in the 10- to 14-year age-group (P = 0.01), but not in younger age-groups. A first-degree relative was already affected in 6.9% of the cases. No significant difference was noted in the age at onset when comparing cases with and without an affected first-degree relative. CONCLUSIONS: The incidence of childhood IDDM in New South Wales is similar to rates found in other predominantly Anglo-Saxon populations. IDDM occurs in Aboriginal children with a frequency comparable to that in the rest of the population.
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Currently, X-linked hypophosphataemic rickets (XLHR) is most commonly treated with a combination of phosphate and vitamin D, but there is conflicting evidence about the effects of this treatment on linear growth. In all, 25 patients with XLHR (current age range, 4.1-22.1 years; median, 8.2 years) were studied to determine whether there was any improvement in height SDS during treatment. The duration of therapy was 2.9-15.0 years (median, 5.7 years). Measurements before the age of 2 years or after the onset of puberty were excluded to remove the effects of measurement difficulties in small infants and of variation in pubertal timing. The growth of these patients was compared with a similar group of untreated historical controls. Patients treated with calcitriol and phosphate for at least 2 years before the onset of puberty (n = 22) had a significantly better mean height SDS than the historical controls (-1.23 compared with -2.05 for the historical controls; p = 0.02). Among patients treated with calcitriol and phosphate for at least 2 years (n = 21), the change in height SDS had a positive correlation with the duration of therapy (r = 0.51; p = 0.02). The growth of children with XLHR treated with combination therapy was thus significantly better than that of historical controls.
Several large clinical trials for the prevention of IDDM in islet cell antibody positive first-degree relatives are planned or underway. The design of these trials rests in part on assumptions about the natural history of autoimmunity during the prediabetic period and on the likely effectiveness of the intervention being tested. At this time, most of the factors that influence the required sample size can only be roughly estimated.
BACKGROUND: Patients with X-linked hypophosphatemic rickets, which is clinically manifested by growth failure and bowing of the legs, are usually treated with phosphate and a vitamin D preparation. However, the efficacy of this treatment has been disputed, and nephrocalcinosis is a recognized complication of therapy. METHODS: We studied 24 patients with X-linked hypophosphatemic rickets (9 boys and 15 girls) ranging in age from 1 to 16 years (median, 5.3). The duration of combination therapy ranged from 0.3 to 11.8 years (median, 3.0). We measured height as a standard-deviation (SD) score (the number of SDs from the mean height for chronologic age). Measurements made before the age of two years or after the onset of puberty were excluded. We compared the results with those reported in 1971 for 16 untreated prepubertal Australian patients. We also determined the severity of nephrocalcinosis (on a scale of 0 to 4, with 0 indicating no abnormalities and 4 stone formation) with renal ultrasonography and whether it could be related to the dosage of phosphate or vitamin D or to other factors. RESULTS: Patients treated for at least two years before the onset of puberty (n = 19) had a mean height SD score of -1.08, as compared with -2.05 in the untreated historical controls. The 13 patients who had been treated with calcitriol and phosphate for at least two years had an increase in the mean height SD score of 0.33, from -1.58 to -1.25 (95 percent confidence interval, 0 to 0.67; P = 0.05). Nineteen of the 24 patients (79 percent) had nephrocalcinosis detected on renal ultrasonography. The grade of nephrocalcinosis was significantly correlated with the mean phosphate dose (r = 0.60, P = 0.002), but not with the dose of vitamin D or the duration of therapy. All patients had normal serum creatinine concentrations. CONCLUSIONS: Therapy with calcitriol and phosphate may increase the growth of children with X-linked hypophosphatemic rickets. Nephrocalcinosis in these children represents a complication of therapy and is associated with the dose of phosphate received.
A novel microsatellite marker was found within 48.5 kb of the Fas gene. The observed heterozygosity in 160 healthy unrelated controls was 0.78. There was no evidence of linkage to type I diabetes mellitus in 120 diabetic children using the transmission disequilibrium test.
The recent cloning and recombinant expression of novel islet autoantigens [glutamic acid decarboxylase (GAD) 65 and islet-cell autoantibody 512 (ICA512)] has made possible the determination of whether the quantitative expression of autoantibodies to these molecules is correlated with age of diabetes onset and rate of progression to diabetes, similar to insulin autoantibodies (IAAs). We measured autoantibodies reacting with GAD65 (GAD65AA), ICA512 (ICA512AA), and insulin in patients who recently had received a diagnosis of diabetes and in first-degree relatives prospectively identified and then followed because of the expression of high titers of ICA. Levels of IAAs (but not GAD65AA or ICA512AA) correlated inversely with age at diagnosis of diabetes and directly with time to diabetes onset among the ICA-positive relatives. In multiple linear regression models, the level of IAAs remained a significant predictor of the time to diabetes after allowing for first-phase insulin secretion. The unique and dramatic association of IAAs with progression to diabetes suggests that IAAs contribute directly to disease pathogenesis or that levels of IAAs are influenced uniquely by the process, leading--at different rates in different prediabetic individuals--to type I diabetes. In addition, the linear regression model described (involving two variables, first-phase insulin secretion and levels of IAAs) aids in the prediction of time to diabetes among ICA-positive relatives.