Congenital disorder of glycosylation type Ia: heterogeneity in the clinical presentation from multivisceral failure to hyperinsulinaemic hypoglycaemia as leading symptoms in three infants with phosphomannomutase deficiency.

We describe three patients with congenital disorder of glycosylation (CDG) type Ia, all of whom had persistent hyperinsulinaemic hypoglycaemia responding to diazoxide therapy as a common feature. The first patient, an infant girl, presented with recurrent vomiting, failure to thrive, liver impairment, hypothyroidism and a pericardial effusion. The second patient, also female, had a milder disease with single organ involvement, presenting as isolated hyperinsulinaemic hypoglycaemia, not associated with any cognitive impairment. The third patient, a boy presented with multi-organ manifestations including congenital hypothyroidism, persistent hyperinsulinaemic hypoglycaemia, coagulopathy, olivopontocerebellar hypoplasia and recurrent pancreatitis. All three patients had a type 1 serum transferrin isoform pattern, and were subsequently found to have low phosphomannomutase activity, confirming the diagnosis of CDG type Ia. Our findings emphasize that CDG should be considered as a differential diagnosis in patients with persistent hyperinsulinaemic hypoglycaemia and that it may even occasionally be the leading symptom in CDG Ia.

Prevalence of diabetes complications 6 years after diagnosis in an incident cohort of childhood diabetes.

AIMS: To examine the prevalence of early diabetes complications 6 years after diagnosis of diabetes. The hypothesis that initial contact with a multidisciplinary team would be associated with a reduced risk of microvascular complications was tested in this cohort. METHODS: Participants were recruited from an incident cohort of children aged < 15 years diagnosed between 1990 and 1992 in NSW, Australia. Initial management at a teaching hospital was documented at case notification. At 6 years, health care questionnaires and complications were assessed: retinopathy by 7-field stereoscopic retinal photography and elevated albumin excretion rate (AER) defined as the median of three overnight urine collections > or = 7.5 microg/min. Case attainment was 58% (209/361) with participants younger than non-participants and more likely living in an urban than rural location. RESULTS: Retinopathy was present in 24%, median AER > or = 7.5 microg/min in 18%, and median AER > or = 20 microg/min in 2%. In multivariate analysis, initial management at a teaching hospital or consultation with all three allied health professionals combined with pubertal staging and cholesterol or HbA1c were all determinants of risk for retinopathy. CONCLUSIONS: Early retinopathy and elevated AER are common in children 6 years after diagnosis. Initial allied health contact and management at a teaching hospital were associated with a reduced risk of microvascular complications in this cohort.

The rising incidence of childhood type 1 diabetes in New South Wales, Australia.

OBJECTIVES: 1. To determine the incidence of type 1 (insulin dependent) diabetes in children aged 0-14 years who were resident in the state of New South Wales, Australia over the period 1992-1996. 2. To analyse the trends in incidence over the period 1990-1996. METHODS: Primary ascertainment of patients was performed using a prospective incidence register established in 1990. The secondary source of ascertainment was the National Diabetes Supply Scheme, a government subsidised scheme for diabetic supplies. RESULTS: There were 1,230 patients identified over the five-year period. Using the capture-recapture method, ascertainment was estimated to be 99% complete. The lowest incidence occurred in 1992 (16.9 per 10(5) person years) and the highest incidence was in 1995 (21.7 per 10(5)). The crude incidence of IDDM from 1990-1996 was 17.8 per 10(5) and there was a statistically significant rise in the incidence of type 1 diabetes over this period (p=0.0003). The annual incidence has increased on average by 3.2% per year since 1990. CONCLUSION: The incidence of childhood type 1 diabetes in NSW has increased significantly since 1990.

Insulin lispro versus regular insulin in children with type 1 diabetes on twice daily insulin.

OBJECTIVE: The aim of this study was to compare the clinical efficacy and safety of insulin lispro with regular insulin in 5- to 10-yr-old prepubertal children on twice daily insulin. RESEARCH DESIGN AND METHODS: Thirty-five children (16 M, 19 F) completed an open-label randomised crossover study, with each child receiving insulin lispro for 3 months and regular insulin for 3 months in addition to their intermediate-acting insulin. Families were instructed to give regular insulin 30 min before meals and insulin lispro immediately before meals. Glycaemic control was monitored by eight-point blood glucose profiles and six weekly hemoglobin A1cs (HbA1cs) and the frequency and severity of hypoglycaemia was documented. RESULTS: The endpoint HbA1c after 3 months on insulin lispro (8.33%, SD+/-0.89) was not significantly different to that on regular insulin (8.14%, SD+/-0.77). No significant differences were found in blood glucose levels before or after meals, 2-h postprandial glucose excursions or in blood glucose levels before bed between the treatments. However, blood glucose levels at 3 am were significantly lower on regular insulin than on insulin lispro (mean difference -2.35 mmol/L (95%CI: -3.98, -0.72, p=0.01). There was no significant difference in the frequency of hypoglycaemic episodes between the groups. CONCLUSIONS: The main advantage of insulin lispro in children on twice daily insulin was found to be its greater convenience, this being achieved without a deterioration in glycaemic control. The higher 3 am blood glucose levels in those on insulin lispro could translate to reduced nocturnal hypoglycaemia in some individuals.

Diabetes complication screening in 937 children and adolescents.

Results are presented of diabetes complication screening in children and adolescents aged 6-20 years. Their diabetes duration was 0.02-18.4 yr and median HbA1c over the preceding 36 months was 8.4% [IQR 7.8-9.3]. Gradable retinal photographs were obtained in 937: 110 less than 11 years (< 11 yr Gp). Albumin excretion rate (AER) was obtained from 3 timed overnight urine collections in 691: 100 in < 11 yr Gp. Early retinopathy was found in 27% (9% in < 11 yr Gp). Microalbuminuria (AER > or = 20 micrograms/min) was found in 4%. Significant individual risk factors for both complications were higher blood pressure, cholesterol, HbA1c, pubertal staging, older age and longer diabetes duration. Using multiple logistic regression, significant risk factors for retinopathy were longer duration and older age and in addition higher HbA1c. Diabetes complication screening detected early subclinical disease in children and adolescents who may benefit from lowering blood pressure and improving metabolic control. Screening should commence after five years of duration in young children, and after two years of duration in adolescents.

Limited joint mobility in the hands and feet of adolescents with Type 1 diabetes mellitus.

AIMS: Limited joint mobility (LJM) in the foot has not been assessed in adolescents with Type 1 diabetes mellitus (DM) but is associated with neuropathic ulceration in adults. This study was designed to determine the presence of LJM in adolescents with Type 1 DM and its association with microvascular disease. METHODS: The hands, feet and hips were examined in 302 diabetic adolescents and 51 nondiabetic controls (aged 11.5-20 years). LJM was defined as less than the fifth percent reference for controls. RESULTS: Reduced motion was found in 35% of diabetic adolescents at the subtalar (ST) joint, 18% at the first metatarsophalangeal (MTP) joint, 26% at the fifth metacarpophalangeal (MCP) joint and 13% had limited passive extension of the interphalangeal (IP) joints of the hands. Limited passive IP joint extension of the hands was not present in the controls. Limited active IP joint extension, a positive 'prayer sign', occurred in 35% of diabetic adolescents and 14% of controls. Diabetic adolescents showing LJM in any of these areas, except the prayer sign, were more likely to have retinopathy (odds ratio 2.53, CI: 1.53-4.18). Those with LJM in the foot were more likely to have albumin excretion rates >7.5 microg/min (OR 2.06, CI: 1.16-3.68). CONCLUSION: LJM in the feet of adolescents with Type 1 DM is associated with microvascular disease and is a useful routine clinical measure.

Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand.

Benign intracranial hypertension (BIH) is reported in three children from Australia and one from New Zealand, who were being treated with recombinant human growth hormone (rhGH). Three males and one female, aged between 10.5 and 14.2 y, developed intracranial hypertension within 2 weeks to 3 months of starting treatment. A national database, OZGROW, has been prospectively collecting data on all 3332 children treated with rhGH in Australia and New Zealand from January 1986 to 1996. The incidence of BIH in children treated with growth hormone (GH) is small, 1.2 per 1000 cases overall, but appears to be greater with biochemical GHD (<10 IU ml(-1)), i.e. 6.5/1000 (3 in 465 cases), relative risk 18.4, 95% confidence interval 1.9-176.1, than in all other children on the database. The incidence in patients with Turner's syndrome was 2.3/1000 (1 in 428 cases). No cases in patients with partial GHD (10-20 IU ml(-1)) or chronic renal failure were identified. Possible causative mechanisms are discussed. The authors' practice is now to start GH replacement at less than the usual recommended dose of 14 IU m(-2) week(-1) in those children considered to be at high risk of developing BIH. Ophthalmological evaluation is recommended for children before and during the first few months following commencement of rhGH therapy and is mandatory in the event of peripheral or facial oedema, persistent headaches, vomiting or visual symptoms. The absence of papilloedema does not exclude the diagnosis.

The effect of prepubertal diabetes duration on diabetes. Microvascular complications in early and late adolescence.

OBJECTIVE: To define the significance of prepubertal diabetes duration in the development of diabetic microvascular complications in adolescents. RESEARCH DESIGN AND METHODS: Study A compares complications in 38 prepubertal (PreP) and 140 pubertal (Pub) subjects of the same age (10-14 years) and diabetes duration (3-12 years) to determine if the absence of puberty itself confers a lower risk of complications. Study B examines the importance of prepubertal and pubertal diabetes duration in 193 older adolescents (ages 15-22 years) with prepubertal onset of diabetes. Retinopathy status was assessed using stereoscopic fundus photography of seven fields per eye. Albumin excretion rate (AER) was assessed by three consecutive overnight urine collections, using a polyclonal radioimmunoassay. RESULTS: In study A, there were no significant differences between the PreP and Pub groups for retinopathy (27 vs. 29%, P = 0.8) or differences in elevated AER (17 vs. 31%, P = 0.1). In study B, longer prepubertal diabetes duration improved the prediction for retinopathy over postpubertal duration alone (P < 0.0005). No relationship with duration was found for elevated AER (> 7.5, > 15, and > 30 micrograms/min). CONCLUSIONS: Prepubertal subjects with diabetes did not have less retinopathy or elevated albumin excretion compared with pubertal subjects of the same age. Prepubertal diabetes duration is significantly related to the presence of retinopathy in adolescents.

Diabetes microvascular complications in prepubertal children.

These are the baseline findings of a group of 68 prepubertal children enrolled in a longitudinal study of the development of early diabetes microvascular complications prior to gonadarche. The median age of the children was 9.8 years, the median diabetes duration 3.6 years and the mean HbA1c 8.4%. Mild nonproliferative retinopathy was present in 6 of 67 (9%) children, assessed by 7-field stereoscopic fundus photography. Those with retinopathy had higher total cholesterol (p < 0.05) and lower DHEAS (p < 0.01). Albumin excretion rate (AER) was calculated as the mean of three overnight consecutive urine collections. AER > 7.5 micrograms/min was present in 5 of 64 (8%), and one boy had a mean AER > 15 micrograms/min. Those with AER > 7.5 micrograms/min had higher diastolic blood pressure and diastolic blood pressure percentiles (p < 0.05). Longitudinal study of this cohort will establish which factors in the prepubertal years are important for the development of diabetes microvascular complications.

Prospective assessment of autonomic and peripheral nerve function in adolescents with diabetes.

Autonomic and peripheral nerve function were studied prospectively in 102 adolescents with Type 1 diabetes over a 5-year period. All adolescents were assessed three times; 54 were assessed four times. The median age at baseline was 14.5 (range 10.4-18.0) yr. The median diabetes duration at baseline was 6.8 (range 1.3-15.2) yr. Autonomic nerve function was assessed by measuring heart rate variation during deep breathing, valsalva manoeuvre, standing from a lying position (30/15 ratio), and the postural change in systolic blood pressure. Peripheral nerve function was assessed by determining the thermal threshold for heat and cold at the wrist and foot and the vibration threshold at the great toe and medial malleolus. At baseline, 29.5% adolescents had at least one abnormal autonomic nerve test and 28.4% had at least one abnormal peripheral nerve test. There was no significant increase in the number of abnormalities over the study period. Persisting abnormalities were present in only six individuals. Abnormalities were not related to age, diabetes duration or glycaemic control. In summary, a low rate of neurological abnormalities was found, suggesting that more than 3 years of follow-up is required to detect evolving neuropathy in this age group.

Vascular responses by transcutaneous oximetry in adolescents with and without diabetes.

The vascular response of the skin was evaluated by transcutaneous oximetry (TcPO2) in the forearm in 119 adolescents with type I diabetes aged 10.4-19.8 (median 15.3) years, with a duration of diabetes 0.7 to 18.3 (median 7.8) years, and 49 nondiabetic adolescents aged 11.3-18.8 (median 15.5) years. Two different vascular stimuli were used: heating of the probe to 43 degrees C and 5 min of ischemia. Baseline TcPO2 after 13 min of equilibration at a probe temperature of 43 degrees C, postischemic maximum TcPO2, and the postischemic TcPO2 increase were significantly lower in the diabetic group compared to the control group (p = 0.0001, p < 0.0001, and p = 0.0001, respectively). In both the diabetic and the control groups, gender differences were found for baseline TcPO2 (p = 0.0001 and p = 0.0009, respectively) and postischemic maximum TcPO2 (p = 0.0001 and p = 0.005, respectively), the girls having consistently higher values. After controlling for gender by multiple linear regression analysis, duration of diabetes showed a significant effect on postischemic maximum TcPO2 (R2 = 22%, p = 0.02). The postischemic TcPO2 increase was not affected by gender. Lower values for the postischemic TcPO2 increase were related to higher GHb values (R2 = 4%, p = 0.03). Abnormal values for oximetry were associated only with some autonomic nerve function abnormalities. Differences in the vascular response to heat and ischemia as measured by transcutaneous oximetry can be demonstrated between adolescents with type I diabetes and nondiabetic controls, as well as between girls and boys. Lower values in diabetic subjects are weakly associated with diabetes duration and metabolic control, independent of gender.

Development and progression of diabetic retinopathy: adolescents at risk.

The aims of this study were to evaluate short-term changes in retinopathy in adolescents, and to examine the relationship of these changes to risk factors. Two-hundred and three adolescents, with a median age of 14.5 (range 10.4 to 20.6) yr and a median duration of diabetes of 6.6 (1.1 to 16.3) yr, were included in the study. Retinopathy was assessed on two occasions, using stereoscopic fundus photography; the median time between assessment was 1.3 (0.5 to 3.0) yr. At baseline, 41% of the adolescents had background retinopathy. When patients were stratified according to the median diabetes duration (DD) (6.6 yr) and glycaemic control over the 12 months prior to assessment (HbA1C) (8.4%), the percentage of retinopathy in each group was: lowDD/lowHbA1C 13%; lowDD/highHbA1C 40%; highDD/lowHbA1C 42%; and highDD/highHbA1C 72%. Using a 2-step criteria for stability or change in retinopathy, 11% of the 203 adolescents showed progression of retinopathy, 41% had stable retinopathy, 5% showed regression, and 43% had no retinopathy at either assessment. Change in retinopathy was related to age at baseline assessment (borderline significance, p = 0.06), diabetes duration (p < 0.001), glycaemic control (p < 0.001) and total cholesterol (p = 0.04), and was also related to DD/HbA1C group membership (chi 2, p < 0.001). This study highlights the combined adverse effect of long diabetes duration and poor glycaemic control on the development and progression of retinopathy during adolescence, and identifies a group that is likely to show progression over a relatively short period.

The prospective assessment of autonomic nerve function by pupillometry in adolescents with type 1 diabetes mellitus.

The study aimed to compare the longitudinal assessment of automatic nerve function by computerized infrared pupillometry and standard cardiovascular tests in adolescents with diabetes. Adolescents (n = 150) were assessed at two time points (T1 and T2). The median time interval between assessments was 1.5 (range 0.9-3) years. At T1 the median age was 14.5 (range 8.3-19.5) years and the median duration was 6.5 (range 1.1-16) years. The pupillary variables assessed included the resting pupil diameter, the maximum constriction velocity, and the reflex amplitude of constriction. Heart rate reflexes were assessed in response to deep breathing, the Valsalva manoeuvre, and on standing from a lying position (30/15 ratio). Between visits there was a significant decrease in maximum constriction velocity (6.0 mm s-1 vs 6.3 mm s-1, p = 0.0001) and resting pupil diameter (6.2 mm vs 6.3 mm, p = 0.001). At reassessment pupillary abnormalities increased from 32 (21%) to 45 (30%), with 17 (54%) of the initial abnormalities persisting. Adolescents with abnormally slow maximum constriction velocity compared to those with normal maximum constriction velocity had a higher glycated haemoglobin (HbA1c%) at T2 (p = 0.02) and between assessments (p = 0.01). Cardiovascular test abnormalities did not increase between visits and the persistence of initial abnormalities was low (21%). In summary, pupillometry appears a more sensitive test of automatic nerve dysfunction in adolescents with diabetes than assessment of cardiovascular reflexes.

'Exaggerated adrenarche' in children presenting with premature adrenarche.

OBJECTIVE: Previous reports of endocrinological profiles in children presenting with premature adrenarche have not shown consistent abnormalities. We therefore aimed to review the clinical and biochemical aspects of a large number of patients presenting with premature adrenarche without virilization and determine the relation between clinical and biochemical characteristics and the frequency of adrenal steroid disorders. DESIGN AND PATIENTS: Eighty-eight patients presenting with adrenarche without virilization during 1985-1992 were retrospectively reviewed. There were 72 girls and 16 boys. All were normotensive and had either prepubertal breasts or testes < 4 ml. In patients with high adrenal androgen levels, adrenal tumours had been excluded by either adrenal ultrasound or CT scan. MEASUREMENT: We recorded clinical manifestations, auxological data, bone age, biochemical results including basal 17OH-progesterone (b17OHP), dehydroepiandrosterone sulphate (DHEAS), androstenedione (delta 4A), testosterone, cortisol and stimulated 17OHP and cortisol. ACTH stimulation tests (using soluble Synacthen 250 micrograms intramuscularly and collecting blood at 0, 30 and 60 minutes) were performed when clinically indicated. 17OH-Pregnenolone (17OHPreg) was also measured during ACTH stimulation tests in 13 individuals to look for abnormalities of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD). RESULTS: The age of onset ranged from 3 to 9.5 years (mean 6.8 +/- 1.3). There were no significant differences by sex for height SDS, weight SDS or % ideal body weight, but bone age advancement was greater in males (P < 0.02). The most common presenting clinical manifestation was premature appearance of pubic hair in 93.8%, the other 6.2% presenting with body odour, acne and/or hirsutism. Twelve patients had b17OHP > 6 nmol/l of whom 5 were diagnosed as having congenital adrenal hyperplasia (CAH) resulting from 21-hydroxylase deficiency after ACTH stimulation tests. A further 33 patients who had b17OHP < 6 nmol/l had normal 17OHP and cortisol responses to ACTH stimulation. Patients, after excluding those with CAH, were divided on the basis of their DHEAS levels into prepubertal (< 1.5 mumol/l), pubertal (1.5-6 mumol/l) and above pubertal range (> 6 mumol/l). The 8 patients with DHEAS values above the pubertal range were described as having 'exaggerated adrenarche'. There were no significant clinical differences between these 3 groups, but significant differences were found for bone age advancement and the steroids, b17OHP, delta 4A and testosterone. There was a strong correlation between DHEAS and delta 4A (r = 0.623, P < 0.001). The 'exaggerated adrenarche' group had higher 17 OHPreg/17OHP ratios at 60 minutes after stimulation but these were not diagnostic for 3 beta-HSD deficiency. CONCLUSION: The value of assessing basal steroids in children presenting with premature adrenarche is demonstrated in this series with 5.7% being diagnosed with 21-hydroxylase deficiency and 9.1% with 'exaggerated adrenarche'. No relation was found between adrenal steroids and clinical features except for the acceleration of bone age. The relation between 'exaggerated adrenarche' and future ovarian hyperandrogenism needs further evaluation.

Environmental factors in childhood IDDM. A population-based, case-control study.

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.

Anti-glutamate decarboxylase and other antibodies at the onset of childhood IDDM: a population-based study.

Sera obtained at diagnosis from 273 children (0-14 years) with insulin-dependent diabetes mellitus (IDDM) were studied to compare different autoantibody levels. The subjects comprise 75% of all incident cases in New South Wales, Australia, for a 2-year period (ascertainment > 99% complete). Antibodies against glutamate decarboxylase were measured by radioimmunoprecipitation, insulin autoantibodies (on 176 sera collected within 4 days of initiation of insulin therapy) by radioimmunoassay, thyroid peroxidase and antigliadin IgA antibodies by enzyme-linked immunoassay, and anti-endomysial IgA and islet cell antibodies by indirect immunofluorescence. Reference ranges for anti-glutamate decarboxylase and insulin autoantibodies were determined in a group of non-diabetic children. Of the sera 69% were positive for anti-glutamate decarboxylase, 65% for insulin autoantibodies, 71% for islet cell antibodies (> or = 20 Juvenile Diabetes Foundation units), 10% for anti-thyroid peroxidase, 2.6% for antigliadin and 3.0% for anti-endomysial antibodies. Islet cell antibodies and insulin autoantibodies were both negative in 13.7% of the sera, while only 5.8% were negative for all three of islet cell antibodies, insulin autoantibodies and anti-glutamate decarboxylase. There was a higher frequency of anti-glutamate decarboxylase among girls than boys (75% vs 63%, p = 0.03) and a negative correlation between the level of insulin autoantibodies and age at diagnosis (r = -0.41, p < 0.0001). A higher frequency of antithyroid peroxidase was found with increasing age (p = 0.05). Higher titres of islet cell antibodies were associated with a higher frequency of both anti-glutamate decarboxylase (p < 0.0001) and insulin autoantibodies (p = 0.003).(ABSTRACT TRUNCATED AT 250 WORDS)

The incidence of childhood IDDM in New South Wales, Australia.

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.

Prevalence and risk factors for retinopathy in adolescents with type 1 diabetes.

OBJECTIVES: To establish the prevalence of, and risk factors associated with, diabetic retinopathy in an Australian adolescent diabetes clinic population. DESIGN: A prospective longitudinal study; baseline findings. PATIENTS: Two hundred and fifty-five patients with Type 1 (insulin-dependent) diabetes mellitus assessed by our service were studied. Entry criteria were: age 11.0-19.9 years; diabetes duration of at least two years; and gradable fundus photographs of at least one eye. MAIN OUTCOME MEASURES: The presence and severity of retinopathy, as assessed by the grading of stereoscopic fundus photographs. Possible risk factors assessed were age, sex, diabetes duration, pubertal stage, blood pressure, glycaemic control and total cholesterol level. RESULTS: The prevalence of retinopathy was 42%; all of those affected had mild background retinopathy. Highly significant associations were found with glycaemic control and both total and prepubertal duration of diabetes. No associations were found with age, sex, pubertal stage, blood pressure or total cholesterol level. CONCLUSIONS: The high prevalence of early diabetic retinopathy in this group of Australian adolescents is comparable to recent reports from other centres. The significant associations with glycaemic control and duration of diabetes provide further strong evidence for the benefit of optimal glycaemic control during adolescence. Our finding that the prepubertal years of diabetes contribute to the development of retinopathy suggests that glycaemic control before puberty should also be optimised. The planned follow-up of this cohort will establish the risk of progression to vision-threatening retinopathy and allow risk factors to be further evaluated.

Autonomic and peripheral nerve function in adolescents with and without diabetes.

In this study reference ranges were established for autonomic and peripheral nerve tests in 122 non-diabetic adolescents. Regression analysis was used to evaluate the effect of age and gender on neurological function. Increasing age was associated with: less heart rate variability during deep breathing (p = 0.03), higher thermal threshold for cold at the wrist (p = 0.009), and higher vibration threshold at the toe (p = 0.001) and medial malleolus (p = 0.01). Male gender was associated with higher Valsalva ratio (p = 0.0004), higher thermal threshold for hot at the foot (p = 0.002), and higher vibration threshold at the malleolus (p = 0.03). The REFVAL programme was used to determine parametric or non-parametric reference limits: the 5% limits for autonomic and 95% limits for peripheral tests. One hundred and eighty-one adolescents with diabetes were studied under identical conditions and similar effects of age and gender were found. Twenty-eight percent of the group with diabetes had at least one abnormal autonomic test result out of four (expected 18.5%); 24% had at least one abnormal peripheral test result out of six (expected 26.5%). Glycaemic control was associated with autonomic (p = 0.04) but not peripheral abnormalities. Using multiple regression analysis and adjusting for age and gender, there was no effect of diabetes duration or glycaemic control on neurological function.

Pupillary abnormalities in type I diabetes occurring during adolescence. Comparisons with cardiovascular reflexes.

OBJECTIVE: To evaluate computerized infrared pupillometry for the assessment of autonomic neuropathy in adolescents with type I diabetes. RESEARCH DESIGN AND METHODS: We measured resting pupil diameters and pupillary light reflexes in 142 adolescents with type I diabetes (72 boys and 70 girls, 10.4-19.8 yr of age, duration of diabetes 0.7-18.3 yr) and in 75 nondiabetic control subjects (29 boys, 46 girls, 11.3-19.8 yr of age). All study participants were assessed using four standard cardiovascular tests: maximum-minimum heart rate during deep breathing (mean of three cycles); heart-rate change during a Valsalva maneuver (Valsalva ratio, mean of three maneuvers); lying-to-standing heart-rate change (30:15 ratio); and lying-to-standing BP change. RESULTS: Mean resting pupil diameters were significantly smaller in the diabetic group: 6.28 +/- 0.06 vs. 6.77 +/- 0.11 mm, P < 0.0001); and significantly smaller with greater duration of diabetes (r = -0.29, P = 0.0006) and higher levels of GHb (r = -0.24, P = 0.004). Patients with retinopathy grade 30 or more (Wisconsin 191 grading) had significantly smaller resting pupil diameters: 5.9 +/- 0.16 vs. 6.4 +/- 0.12 mm, P = 0.008). The phasic light reflex as determined by reflex amplitude and maximum constriction velocity was significantly reduced in the diabetic group: 2.27 +/- 0.03 vs. 2.44 +/- 0.04 mm, P = 0.0009; and 6.68 +/- 0.12 vs. 7.24 +/- 0.16 mm/s, P = 0.007). Reduced reflex amplitude was related to a longer postpubertal duration of diabetes (r = -0.18, P = 0.04). We found no association between pupillary and cardiovascular tests. CONCLUSIONS: Infrared computerized pupillometry demonstrates subclinical diabetic autonomic neuropathy as early as adolescence. Its presence seems to be related to longer duration of diabetes and unfavorable metabolic control.