Incidence of IDDM in Western Australia in children aged 0-14 yr from 1985 to 1989.

OBJECTIVE: To document the incidence of insulin-dependent diabetes mellitus (IDDM) in Western Australia in children aged 0-14 yr between 1985 and 1989 and to test for differences in incidence by year of diagnosis, age of diagnosis, and sex. RESEARCH DESIGN AND METHODS: A population-based register that used a primary source of case ascertainment (diabetes clinics at teaching hospitals and direct approach to general practitioners and general physicians) and a secondary source (Western Australian Hospital Morbidity Data System) established numerator data. Denominator data were obtained from the Australian Bureau of Statistics. RESULTS: From 1985 to 1989 inclusive, 235 children in the 0- to 14-yr age-group were diagnosed with IDDM in Western Australia. Case ascertainment was estimated at 99% complete. The mean age-adjusted (developed-world population) annual incidence of IDDM was 13.2 per 100,000 person-yr and there was no evidence of an increasing incidence over the 5 yr. However, girls were more likely than boys to be diagnosed with IDDM in this period (P = 0.006). CONCLUSIONS: The incidence of IDDM in Western Australia is in the middle range of IDDM incidence in countries throughout the world. The unexpected finding of an increased incidence of IDDM in girls compared with boys needs to be confirmed in a future study.

The use of biothesiometry to detect neuropathy in children and adolescents with IDDM.

OBJECTIVE: To develop clinically useful reference ranges for vibration perception thresholds (VPTs), using biothesiometry in children and adolescents and to assess the reliability of the technique to identify subclinical neuropathy in subjects with IDDM at this age and to examine a large population-based sample of pediatric patients. RESEARCH DESIGN AND METHODS: VPTs were measured using a handheld biothesiometer at the medial malleolus and hallux in 232 nondiabetic children and adolescents aged 7-18 years (12.9 +/- 4.2 years) and a population-based sample of 307 young IDDM patients (13.3 +/- 4.6 years of age). The mean of three readings at each site was correlated with height, pubertal status, and age for all subjects and, in addition for the IDDM sample, with the duration of IDDM, ambient blood glucose, and mean HbA1c from diagnosis. Those IDDM subjects found to have elevated VPTs (> 97th percentile), and a control group of patients with IDDM underwent nerve conduction studies to determine the sensitivity and specificity of biothesiometry to detect abnormal neural function in children. Interoperator reliability was assessed in a separate trial in which two operators measured VPTs independently in the same 11 children. RESULTS: In the nondiabetic control subjects, height demonstrated the best correlation with VPT measures, and a reference range was thus established with percentile charts, using mean VPT and height. VPTs were higher in the diabetic sample, compared with the nondiabetic sample (P < 0.05). Of the children, 28 (9.1%) had VPT values > 97th percentile developed from studies of the nondiabetic subjects; of these, 11 were younger than 11 years and 8 were prepubertal. Nerve conduction studies confirmed reduced conduction velocity and prolonged distal latencies in those with abnormal VPTs, compared with normal control subjects and IDDM patients with normal VPTs. Sensitivity of biothesiometry to reflect abnormal nerve function was estimated as 82% and specificity as 75% at this age. Interoperator variation was small (7.25% of total variance). CONCLUSIONS: Biothesiometry is a useful noninvasive tool for the detection of subclinical neuropathy in children and adolescents. The use of height-related reference ranges may make screening for neuropathy more feasible in younger patients and allow large-scale longitudiral analysis of its development.

Hypoglycemia: incidence and clinical predictors in a large population-based sample of children and adolescents with IDDM.

OBJECTIVE: To determine the frequency of moderate and severe hypoglycemia and to identify clinical predictors associated with its occurrence in a large population-based sample of children and adolescents with IDDM. RESEARCH DESIGN AND METHODS: A total of 657 patients (age: 12.1 +/- 4.4 years, mean +/- SD) were included in the study, yielding 1,449 patient-years of data. A prospective assessment of severe hypoglycemia (an event resulting in a seizure or coma) and moderate hypoglycemia (an event requiring assistance of another, excluding severe episodes) was made over a 3-year period. Patients and caregivers detailed episodes of significant hypoglycemia (moderate and severe events) and these were recorded at each 3-month clinic visit along with HbA1c. Data were analyzed using generalized estimating equation models fitted with the exchange correlation structure. RESULTS: The overall incidence of severe events was 4.8/100 patient-years and of moderate events was 13.1/100 patient-years. Over 3 years, severe events occurred in 8.5% of children and moderate events occurred in 26.9%. Significant hypoglycemia was rare in the first 12 months after diagnosis. Rates of hypoglycemia were increased in children < 6 years of age versus > 6 years of age (40.9 vs. 16.6/100 patient-years, age < or = 6 years vs. age > 6 years, P < 0.001). Rates of hypoglycemia doubled when HbA1c fell below 8%, and children with HbA1c < 7% had a threefold increase in both moderate and severe hypoglycemia (e.g., severe episodes 14.9 vs. 4.1/100 patient-years, HbA1c < or = 7% vs. HbA1c > 7%, P < 0.001). Most severe events were seizures, and 75% of them occurred at night. The majority of events were related to missed meals or increased activity. However, in 38% no predisposing factor was evident. CONCLUSIONS: Newly diagnosed children appear to be protected from severe hypoglycemia. Rates increase with lower glycated hemoglobin, especially when mean HbA1c is < 8.0%. Younger children, who may be more susceptible to the adverse effects of neuroglycopenia, are at a particular risk of significant hypoglycemia.

Steroid inhibitory effects upon human adrenal 3 beta-hydroxysteroid dehydrogenase activity.

The inhibitory effects of varying concentrations of steroids upon 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) kinetics were studied in human adrenal microsomes. Each enzyme assay was conducted in triplicate at five different concentrations of three substrates (dehydroepiandrosterone, pregnenolone, and 17OH-pregnenolone), using microsomes from at least three donors. Each steroid was screened for possible inhibition at concentrations of 10(-8) and 10(-6) M and then studied in more detail at five different concentrations. The type of inhibition and the inhibition constant (Ki) were determined by analysis of Lineweaver-Burk and Dixon plots, together with replots of the slopes from the Dixon plots. The mean Km (Michaelis-Menten constant) for the three substrates was 0.42 +/- 0.04 (SE) mumol/liter (n = 73). Each steroid tested, including delta 5-3 beta-hydroxysteroids, estrogens, and several delta 4-3-ketosteroids, with the exception of cortisol, caused significant inhibition of 3 beta-HSD activity, and in each case the steroid appeared to behave as a competitive inhibitor. In most cases the Ki value was approximately 10(-7) M. At micromolar concentrations several steroids, notably estrone and estradiol, caused almost total inhibition of adrenal 3 beta-HSD activity. Comparison of the calculated Ki values with available data concerning changes in intra-adrenal steroid concentrations during childhood suggests that these changes would be sufficient to cause a relative decline in 3 beta-HSD activity during adrenarche. Although postnatal circulating steroid concentrations would appear to be insufficient to influence adrenal steroidogenesis, the high serum levels of placental steroids during fetal life would be expected to cause marked 3 beta-HSD inhibition.

Kinetic analysis of adrenal 3 beta-hydroxysteroid dehydrogenase activity during human development.

Kinetic analyses of microsomal 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity in adrenal glands from 11 individuals, aged 1-60 yr, were carried out to determine whether changes in substrate or cofactor affinity (Km) or cellular content, as reflected in maximal velocity, could explain the changes in adrenal delta 5-3 beta-hydroxysteroid secretion that occur in late childhood and puberty. The Km values for the cofactor NAD+ were similar regardless which substrate, dehydroepiandrosterone (DHA), pregnenolone, or 17-hydroxypregnenolone (17OH-delta 5P), was used. The Km values for DHA (0.3 microM), pregnenolone (0.4 microM), and 17OH-delta 5P (0.3 microM) were similar and within the intraadrenal concentration ranges for DHA and 17OH-delta 5P previously reported. Each substrate was a competitive inhibitor for the others, with close similarity between affinity and inhibition constants. These observations point to the presence of a single 3 beta-HSD, rather than several substrate-specific variants. There was no change in substrate Km with age; the maximal velocity was lower (0.1-0.6 nmol/mg X min) in a single 1-yr-old infant than in later life, but there was no significant change (mean, 2.9-4.6 nmol/mg X min for the three substrates) between values at 12 and 60 yr. This suggests that ACTH-mediated induction of 3 beta-HSD may be low in infancy and higher in adults, while in vivo studies point to a reduction in actual 3 beta-HSD activity during this period. The likely explanation for this paradox between enzyme levels and final activity is that 3 beta-HSD is progressively inhibited during late childhood and puberty by rising intraadrenal concentrations of various delta 4-3-ketosteroids.

Acute hyperglycaemia impairs cognitive function in children with IDDM.

OBJECTIVE: The effects of acute hyperglycaemia on cognitive function in children remain controversial. This study was designed to investigate the suggestion that acute hyperglycaemia impairs cognition in IDDM children. DESIGN: To examine this question we studied 12 randomly selected children with IDDM (6 boys, 6 girls, mean age 12.4 years). Cognitive performance was assessed on two occasions at least six months apart (7.4 +/- 1.4 mths, range: 6.3-11.1 mths) under randomised conditions of hyperglycaemia (20-30 mmol/l) on one occasion and euglycaemia (5-10 mmol/l) on the other. Target glucose levels were achieved using a modified clamp technique with subjects and psychologist blinded to the glycaemic level. Cognitive tests chosen to assess performance skills were subtests from the Wechsler Intelligence Scale for Children-3rd Edition (WISC-111). RESULTS: No significant learning effect was present. However, there was a reduction in performance IQ at hyperglycaemia compared with euglycaemia (106 +/- 4.3 vs 112 +/- 4.5 IQ points respectively, p < 0.05). Under hyperglycaemic conditions the mean decrease in percentile score for performance IQ was 9.5%. Of the 12 children tested, 8 had a decrease in IQ when hyperglycaemic, which was independent of duration of diabetes and long term metabolic control assessed by HbA1c. CONCLUSION: Acute hyperglycaemia results in impairment of complex cognitive function in children with IDDM. This may have important implications for school performance.

Relationship between renal volume and increased albumin excretion rates in children and adolescents with type 1 diabetes mellitus.

OBJECTIVE: To compare renal volume in a group of prepubertal and pubertal children with type 1 diabetes mellitus (DM) and either borderline microalbuminuria (BM) or intermittent microalbuminuria (IM) with a matched group of normoalbuminuric (NA) controls with DM. RESEARCH DESIGN AND METHODS: Twenty-one patients with BM or IM were matched for age, gender and duration of DM with an NA control group. Total renal volume (RV), measured by ultrasound, was corrected for body surface area. Long-term diabetes control was assessed by glycosylated haemoglobin levels. RESULTS: There were no significant differences in age, duration of DM or glycosylated haemoglobin levels between the groups. Those with BM or IM had significantly increased total renal volume (303 +/- 8.4 ml/1.73 m2) compared to those with NA (276.3 +/- 10 ml/1.73 m2) (T40=2.04, P=0.05). Multivariate modelling suggested that this association was independent of potential confounding covariates. While not formally significant (chi2(1)=2.53, P=0.12), the frequency of nephromegaly (RV >300 ml/1.73 m2) was doubled in children with BM or IM (47.6%) compared to controls (23.8%). Nephromegaly was not found in prepubertal patients. CONCLUSIONS: This study suggests that nephromegaly is more common in patients with borderline increases in urinary albumin excretion rates (AER) than those with normoalbuminuria. Prospective follow-up of those with increased renal volume is needed to determine whether nephromegaly is an early marker of incipient nephropathy.

Red-back spider (Latrodectus mactans hasselti) envenomation in a neonate.

A case of red-back spider (Latrodectus mactans hasselti) envenomation in a neonate is presented. The signs of envenomation in a neonate are discussed, together with the dose of antivenom necessary for the successful treatment of envenomation. In episodes of untractable crying in neonates, the possibility that the baby has been bitten by a red-back spider should be considered.

Fludrocortisone induced heart failure in Addison's disease.

The first reported case of congestive cardiac failure in a child with Addison's disease secondary to fludrocortisone therapy is presented. A renal adaptation to compensate for chronic salt and water deprivation is suggested as a possible mechanism for the development of congestive cardiac failure in this patient.

Growth and growth hormone secretion after treatment for acute lymphoblastic leukemia in childhood. 18-Gy versus 24-Gy cranial irradiation.

PURPOSE: Cranial irradiation (CI) given during the first phase of treatment of childhood acute lymphoblastic leukemia (ALL) has been associated with significant long-term morbidity. As a result, the dose of radiotherapy has been reduced from 24 to 18 Gy to reduce the severity of these late effects. To compare the effects of 24 and 18 Gy CI on growth, puberty, and growth hormone (GH) secretion, a cohort of survivors of childhood ALL were studied. PATIENTS AND METHODS: Of a total of 48 children, 28 (14 boys, 14 girls) had received 24 Gy and 20 (eight boys, 12 girls) had received 18 Gy. Similar chemotherapy regimens had been used in both groups, and age at diagnosis (5.2 +/- 2.7 vs. 5.1 +/- 2.8 years, 18 Gy vs. 24 Gy) and mean height at diagnosis [standard deviation score (SDS) 0.17 +/- 0.17 vs. 0.05 +/- 0.17, 18 Gy vs. 24 Gy] were comparable. RESULTS: Growth rates in both groups did not differ for the first 5 years after diagnosis. After this time, however, a significant height decrease was observed in children who had received 24 Gy but not in children who had received 18 Gy (at 8 years the change in SDS from diagnosis was -0.32 +/- 0.14 vs. -0.73 +/- 0.16, 18 Gy vs. 24 Gy, p < 0.05). Menarche occurred earlier in the girls in the 24-Gy group (at 12.9 +/- 0.3 vs. 11.7 +/- 0.4 years of age, 18 Gy vs. 24 Gy, p < 0.02). Overnight GH concentrations (12-h sampling every 20 min) were reduced in both groups compared with healthy age-matched control children but were even lower in the 24-Gy group (12.7 +/- 0.7 mU/L vs. 7.9 +/- 0.6 vs. 6.1 +/- 0.5 [6.4 +/- 0.4 ng/ml vs. 3.9-0.3 vs. 3.1 +/- 0.3]; control vs. 18 Gy and 24 Gy, p < 0.001; 18 Gy vs. 24 Gy, p < 0.025). CONCLUSIONS: Although both doses of CI impair GH secretion, 24 Gy has a greater impact on growth in the long term. This effect may be exaggerated by the induction of early puberty in some children.

Dramatic increase in incidence of insulin dependent diabetes mellitus in Western Australia.

OBJECTIVES: To document and suggest possible reasons for a dramatic increase in the incidence of insulin dependent diabetes mellitus (IDDM) in Western Australia in 1992. PATIENTS: Children aged 0-14 years with IDDM diagnosed in Western Australia from 1985 to 1992 inclusive. DESIGN: A population-based register in Western Australia, using name-identified data from two separate ascertainment sources, provided numerator data. Denominator data were estimated from census figures collected in 1986 and 1991 by the Australian Bureau of Statistics. The completeness of case ascertainment was estimated by the capture-recapture method. RESULTS: Case ascertainment for 1985-1992 was estimated as 99.6% complete. Between 1985 and 1991 the incidence of IDDM in the 0-14 year age group varied between 11.8 and 15.5 per 100,000 person-years without a significant increase. In 1992, however, based on the previous seven years, 52 cases would have been expected but 84 cases were observed, an incidence of 22.2 per 100,000 person-years. The increase in incidence occurred across all age groups and in both sexes. Place of residence at diagnosis, the prevalence of islet cell antibody positivity at diagnosis and the proportion of new cases with a first degree relative with IDDM were no different in 1992 than in preceding years. CONCLUSION: This is the first report of a significant increase in the incidence of IDDM in Australia. It appears to be a period, rather than a cohort, effect and provides further evidence for environmental antigens as disease triggers.

Impact of improved glycaemic control on rates of hypoglycaemia in insulin dependent diabetes mellitus.

Increased emphasis on strict glycaemic control of insulin dependent diabetes mellitus (IDDM) in young patients may be expected to cause increases in rates of significant hypoglycaemia. To evaluate whether this is the case for a large population based sample of IDDM children and adolescents rates of severe (coma, convulsion) and moderate (requiring assistance for treatment) hypoglycaemia were studied prospectively over a four year period. A total of 709 patients were studied yielding 2027 patient years of data (mean (SD) age: 12.3 (4.4); range 0-18 years, duration IDDM: 4.9 (3.8) years). Details of hypoglycaemia were recorded at clinic visits every three months when glycated haemoglobin (HbA1c) was also measured. Overall the incidence of severe hypoglycaemia was 7.8 and moderate was 15.4 episodes/100 patient years. Over the four years mean (SD) clinic HbA1c steadily fell from 10.2 (1.6)% in 1992 to 8.8 (1.5)% in 1995. In parallel with this there was a dramatic increase in the rate of hypoglycaemia, especially in the fourth year of the study, when severe hypoglycaemia increased from 4.8 to 15.6 episodes/100 patient years. This increase was particularly marked in younger children (< 6 years) in whom severe hypoglycaemia increased from 14.9 to 42.1 episodes/100 patient years in 1995. It is concluded that attempts to achieve improved metabolic control must be accompanied by efforts to minimise the effects of significant hypoglycaemia, particularly in the younger age group.

Predictors of low bone density in young adolescent females with anorexia nervosa and other dieting disorders.

OBJECTIVE: To compare the bone density of adolescent patients with anorexia nervosa with adolescent patients with other dieting disorders and to evaluate risk factors for low bone density in these patients. METHOD: Sixty-nine consecutive female patients referred to an adolescent eating disorders clinic were studied by interview, blood sampling, body composition, and lumbar spine bone density measurement using dual energy X-ray absorptiometry. RESULTS: Although patients with anorexia nervosa were more malnourished, their bone density was similar to other dieting patients. Patients were divided into a low and normal bone density group irrespective of psychiatric diagnosis. Patients with low bone density had dieted for longer, had lower lean body mass, more often had not achieved menarche, and had longer duration of secondary amenorrhea and lower estrogen levels. DISCUSSION: Irrespective of clinical diagnosis, adolescents with dieting disorders have increased risk of low bone density when malnutrition commences early in puberty and is associated with reduced lean body mass and impaired ovarian function.

Luteinizing hormone-releasing hormone analogue (Buserelin) treatment for central precocious puberty: a multi-centre trial.

A multi-centre open trial of Buserelin, a luteinizing hormone-releasing hormone (LHRH) analogue, was conducted in 13 children with central precocious puberty. Eleven children (eight girls and three boys), aged 3.4-10.2 years at commencement, completed the required 12 month period of treatment. Initially all patients received the drug by intranasal spray in a dose of 1200 micrograms/day, but by the end of the 12 month period two were having daily subcutaneous injections and three were receiving an increased dose intranasally. The first month of treatment was associated in one boy with increased aggression and masturbation, and in the girls with an increase in the prevalence of vaginal bleeding. Thereafter, however, both behavioural abnormalities and menstruation were suppressed. Median bone age increased significantly during the study, but without any significant change in the ratio of height age to bone age. The median predicted adult height for the group therefore did not alter significantly over the twelve months of the study. Buserelin treatment caused a reduction in the peak luteinizing hormone and follicle-stimulating hormone (FSH) responses to LHRH, mostly to prepubertal levels, and also suppressed basal FSH. In the first weeks of treatment, the girls' serum oestradiol levels rose significantly and then fell to prepubertal or early pubertal levels. A similar pattern was seen for serum testosterone levels. Serum somatomedin-C levels, however, showed little fluctuation over the course of the study. Buserelin treatment was safe and well accepted, and offers the promise of improved linear growth potential in precocious puberty.

Diabetes in Western Australian children: descriptive epidemiology.

The prevalence and incidence of diabetes mellitus in the age group zero to 14 years in Western Australia were determined from a survey by means of Schools Health Services. Additional information from the State's computer-linked hospital records system, the State's only children's hospital, diabetic clinics and physicians enabled virtually complete ascertainment of cases of childhood diabetes. Only 60% of school-age diabetic children were known to school nurses before the survey, but the nurses were able to identify two-thirds of the remainder during the survey. Among non-Aboriginal children, the prevalence of diabetes in the age group zero to 14 years was 0.59 per 1000 children and the incidence was 12.3 per 100,000 children per year. These rates are somewhat lower than those that have been reported from the United Kingdom and North America, and substantially lower than the rates that were reported from Scandinavia. All but one of the diabetic children who were identified required insulin and were assumed to be insulin-dependent. An excess of boys was found. None of 8715 Aboriginal or part-Aboriginal children had insulin-dependent diabetes mellitus, which indicates that this racial group has a low prevalence of this condition. In case--control studies, which used questionnaires for parents, no significant trends were found in relation to the history of immunizations or of specific viral illnesses except for a past history of varicella which was less frequent in diabetic children. A past history of established breast-feeding (of more than one week) was less frequent in diabetic children, as was the ingestion of vitamin C supplements before the onset of diabetes. Some evidence for a seasonality of onset was obtained. The diabetic children were absent from school for more days and had more admissions to hospital than did non-diabetic children. The majority of diabetic children were prescribed insulin twice a day or more often (84%); performed home blood-glucose monitoring (74%); and attended hospital diabetic clinics (91%).

Antibodies to glutamic acid decarboxylase in Australian children with insulin-dependent diabetes mellitus and their first-degree relatives.

Antibodies to glutamic acid decarboxylase (GAD), previously known as the 64-kD pancreatic islet cell autoantigen, are an important serologic marker of insulin-dependent diabetes mellitus (IDDM). Antibodies to GAD (anti-GAD) were examined in sera from Australian children with newly diagnosed IDDM (within 1 mo of diagnosis), IDDM of longer duration (mean +/- SD, 4.8 +/- 3.3 y), and in first-degree relatives, using a radioimmuno-precipitation assay with purified porcine brain GAD as antigen. Antibodies to islet cell cytoplasmic antigens (ICAb) were tested concurrently. The frequency of anti-GAD was not significantly different in children with newly diagnosed IDDM (31 of 42, 74%) and with IDDM of longer duration (14 of 21, 67%), whereas ICAb were present more frequently in children with newly diagnosed IDDM (64%) than in those with longer duration IDDM (14%). In all, 90% of children with newly diagnosed IDDM had either anti-GAD or ICAb, whereas only 48% had both. For the 77 first-degree relatives, the frequency of anti-GAD was 2% (one of 44) in parents and 6% (two of 33) in siblings; ICAb were not detected in any of these relatives. The presence of anti-GAD in the majority of children with IDDM, irrespective of the duration of their disease, represents a useful diagnostic marker for IDDM, and should be of value in ascertaining individuals at risk for developing IDDM.

Late effects of childhood malignancies seen in Western Australia.

Eighty-nine pediatric oncology patients, in remission and off treatment for at least 4 years, were reviewed annually in the Late Effects Clinic of Princess Margaret Hospital for Children in Perth, Western Australia. Interval from time of diagnosis to follow-up ranged from 4 to 23 years (mean 10.8 years). Acute lymphoblastic leukemia (ALL) (40%) and Wilms' tumor (27%) were the most common primary malignancies in this group. Late sequelae included musculoskeletal abnormalities (23 children), growth hormone deficiency (11), second tumors (9), learning difficulties (7), puberty and fertility problems (4), and hypothyroidism (4). These complications were most often related to radiation therapy. The need for prolonged, regular follow-up of survivors of childhood malignancy for early detection of late sequelae and subsequent intervention is stressed.

Progression of borderline increases in albuminuria in adolescents with insulin-dependent diabetes mellitus.

We aimed to determine the natural history of borderline increases in albuminuria in adolescents with insulin-dependent (Type 1) diabetes mellitus (IDDM) and factors which are associated with progression to persistent microalbuminura. Fifty-five normotensive adolescents with IDDM and intermittent microalbuminura (overnight albumin excretion ratte of 20-200 micrograms min-1 on one of three consecutive timed collections, n = 29) or borderline albuminura (mean overnight albumin excretion rate of 7.2-20 micrograms min-1 on one of three consecutive timed collections, n = 30) were followed prospectively at 3 monthly intervals. The endpoint was persistent microalbuminuria defined as a minimum of three of four consecutive overnight albumin excretion rates of greater than 20 micrograms min-1. One hundred and forty-two adolescents with IDDM and normoalbuminura were also followed prospectively. Fifteen of the 59 patients (25.4%) with intermittent (9/29) or borderline (6/30) albuminura progressed to persistent microalbuminura (progressors) over 28 (15-50) months [median (range)] in comparison with two of the 142 patients with normoalbuminuria at entry (relative risk = 12.6; p = 0.001). Progressors to persistent microalbuminura were pubertal and had higher systolic (p = 0.02) and diastolic (p = 0.02) blood pressure, and HbA1c (p = 0.004) than non-progressors. All patients remained normotensive. Glomerular filtration rate, apolipoproteins, dietary phosphorus, protein and sodium intakes, and prevalence of smoking did not differ between progressors and non-progressors. Total renin was higher in the diabetic patients without a difference between progressors and non-progressors. In conclusion there is a relatively high rate of progression to persistent microalbuminuria in pubertal adolescents with borderline increases in albuminura and duration greater than 3 years. These patients require attention to minimize associated factors of poor metabolic control and higher blood pressure in the development of incipient nephropathy.