Population-based incidence of diabetes in Australian youth aged 10-18 yr: increase in type 1 diabetes but not type 2 diabetes.

BACKGROUND: Global incidence of childhood type 2 diabetes has increased, with a greater rise amongst certain ethnic groups. OBJECTIVES: To examine the change in the incidence of type 1 and type 2 diabetes in Australian youth, aged 10-18 yr, in New South Wales, Australia. METHODS: Prospective population-based incidence study (2001-2008). Primary case ascertainment was from the Australasian Paediatric Endocrine Group Diabetes Register, secondary independent ascertainment from the National Diabetes Register. RESULTS: There were 202 incident cases of type 2 diabetes (96 boys, 48%). The mean age at diagnosis (±SD) was 14.6 ± 2.5 yr; 93% were overweight (International Obesity Taskforce Grade ≥1). Mean HbA1c was 8.8 ± 2.8%. Ethnicity was Caucasian 31%, Indigenous Australian 20%, Southeast Asian 11%, North African/Middle Eastern 9%, and NewZealander/Melanesian/Polynesian 8%. The mean annual incidence of type 2 diabetes was 3.0 per 100 000 per year (95% confidence interval (CI): 2.6-3.4) and did not change over time. The mean annual incidence of type 1 diabetes was 22.0 per 100 000 per year (95% CI: 20.8-23.1), and increased by 3.8% per year [incidence rate ratio IRR: 1.04, 95% CI: 1.02-1.06, p = 0.001]. Incidence was higher in Indigenous vs. non-Indigenous youth, IRR: 6.9 (95% CI: 4.7-10.2, p < 0.001). CONCLUSION: In 10-18 yr old youth, in Australia, the incidence of type 2 diabetes has remained steady during the last decade; however, the incidence of type 1 diabetes continues to rise. Most common diabetes in Australian youth is type 1 diabetes.

A diabetes awareness campaign prevents diabetic ketoacidosis in children at their initial presentation with type 1 diabetes.

OBJECTIVE: To evaluate the effect of a diabetes awareness campaign on the incidence of diabetic ketoacidosis (DKA) at the first presentation of type 1 diabetes in children (0-18 yr). METHODS: This study was a controlled population intervention study with a 2-yr baseline period and a 2-yr intervention period. Data were collected on all children presenting with their initial diagnosis of type 1 diabetes [pH, bicarbonate, base excess, blood glucose level (BGL), urea, and creatinine] at Gosford, Newcastle, and Sydney (Sydney Children's Hospital and Royal North Shore Hospital). During the intervention period, diabetes education occurred in the intervention region (Gosford). Child care centers, schools, and doctor's offices were offered education and posters about the symptoms of type 1 diabetes. Doctor's offices were given glucose and ketone testing equipment. The control regions (Newcastle and Sydney) did not receive any educational intervention or test equipment. DKA was defined as pH < 7.3 or bicarbonate < 15 mmol/L. RESULTS: In Gosford, the proportion of children presenting in DKA decreased from 37.5% (15/40) during the 2-yr baseline period to 13.8% (4/29) during the 2-yr intervention (p < 0.03). There was no significant change in the control regions during the same time periods, 37.4% (46/123) and 38.6% (49/127), respectively. In Gosford, the average BGL at presentation was 27.5 mmol/L during the baseline and 21.2 mmol/L during the intervention (p < 0.01). CONCLUSION: During the diabetes awareness campaign, the rate of DKA at initial diagnosis of type 1 diabetes in children decreased by 64%.

Children with islet autoimmunity and enterovirus infection demonstrate a distinct cytokine profile.

Cytokines are upregulated in prediabetes, but their relationship with Enterovirus (EV) infection and development of islet autoimmunity is unknown. Cytokines (n = 65) were measured using Luminex xMAP technology in a nested case-control study of 67 children with a first-degree relative with type 1 diabetes: 27 with islet autoantibodies (Ab(+)) and 40 age-matched persistently autoantibody negative (Ab(-)) control subjects. Of 74 samples, 37 (50%) were EV-PCR(+) in plasma and/or stool (EV(+)) and the remainder were negative for EV and other viruses (EV(-)). Fifteen cytokines, chemokines, and growth factors were elevated (P ≤ 0.01) in Ab(+) versus Ab(-) children (interleukin [IL]-1ß, IL-5, IL-7, IL-12(p70), IL-16, IL-17, IL-20, IL-21, IL-28A, tumor necrosis factor-α, chemokine C-C motif ligand [CCL]13, CCL26, chemokine C-X-C motif ligand 5, granulocyte-macrophage colony-stimulating factor, and thrombopoietin); most have proinflammatory effects. In EV(+) versus EV(-) children, IL-10 was higher (P = 0.005), while IL-21 was lower (P = 0.008). Cytokine levels did not differ between Ab(+)EV(+) and Ab(+)EV(-) children. Heat maps demonstrated clustering of some proinflammatory cytokines in Ab(+) children, suggesting they are coordinately regulated. In conclusion, children with islet autoimmunity demonstrate higher levels of multiple cytokines, consistent with an active inflammatory process in the prediabetic state, which is unrelated to coincident EV infection. Apart from differences in IL-10 and IL-21, EV infection was not associated with a specific cytokine profile.

Case report: consumptive hypothyroidism consequent to multiple infantile hepatic haemangiomas.

A 10-month-old infant with multiple infantile hepatic hemangiomas and developmental delay is reported. He was found to be profoundly hypothyroid. Evaluation and management issues are discussed. This case emphasizes the importance of screening for hypothyroidism in patients with hemangiomas and the potential therapeutic benefit of prednisolone therapy in this condition.

Type 2 diabetes in Indigenous and non-Indigenous children and adolescents in New South Wales.

OBJECTIVE: To determine the incidence of type 2 diabetes mellitus (T2DM) in 2001-2006 in young people < 19 years and the characteristics of T2DM in the Indigenous group. DESIGN AND SETTING: Prospective population-based incidence study, New South Wales. PARTICIPANTS: Primary ascertainment was from the Australasian Paediatric Endocrine Group NSW Diabetes Register, with secondary ascertainment from the National Diabetes Register (Australian Institute of Health and Welfare). MAIN OUTCOME MEASURES: Incidence of T2DM in young people in NSW; incidence of T1DM and T2DM in Indigenous young people; characteristics at diagnosis. RESULTS: There were 128 incident cases of T2DM (62 boys, 66 girls) in the study period. The median age at diagnosis was 14.5 years (interquartile range, 13.0-16.4), and 90% were overweight or obese (body mass index > 85th percentile for age). Mean annual incidence was 2.5/100,000 person-years (95% CI, 2.1-3.0) in 10-18-year-olds. Of the ethnic groups represented, white Australian comprised 29%, Indigenous 22%, Asian 22%, North African/Middle Eastern 12% and Maori/Polynesian/Melanesian 10%. The incidence of T2DM was significantly higher in the Indigenous than the non-Indigenous group (incidence rate ratio, 6.1; 95% CI, 3.9-9.7; P<0.001), but incidence rates of T1DM were similar (15.5 v 21.4/100,000, respectively). CONCLUSIONS: T2DM accounts for 11% of incident cases of diabetes in 10-18-year-olds, and the majority are overweight or obese. The high rate among Indigenous Australian children supports screening for T2DM in this population.

Autonomic nerve testing predicts the development of complications: a 12-year follow-up study.

OBJECTIVE: Cardiac autonomic nerve tests have predicted increased mortality in adults with diabetes, predominantly due to nephropathy, cardiac disease, and hypoglycemia. The significance of subclinical autonomic nerve test abnormalities has not been systematically studied in adolescents. We aimed to reassess an adolescent cohort, whose autonomic nervous system had been tested 12 years earlier by both pupillometry and cardiovascular tests. RESEARCH DESIGN AND METHODS: From 1990 to 1993, adolescents with type 1 diabetes (n = 335) were assessed for autonomic neuropathy (median age 14.7 years [interquartile range 13.0-16.8], duration of diabetes 6.3 years [4.0-9.6], and A1C 8.3% [7.5-9.4]). Between 2003 and 2005, contact was made with 59% of the original group. Individual assessment 12 years later included completion of a validated hypoglycemia unawareness questionnaire (n = 123) and urinary albumin-to-creatinine ratio (n = 99) and retinal (n = 102) screening, as well as analysis of reports from external doctors (n = 35). RESULTS: At baseline, there was no difference in age, duration of diabetes, or complications between those who participated in the follow-up phase (n = 137) and those who did not participate (n = 196). However, baseline A1C was lower in the follow-up participants (8.2 vs. 8.5% for participants vs. nonparticipants, respectively, P = 0.031). At 12 years of follow-up, 93% were aware and 7% were unaware that they had hypoglycemia; 32 (31%) had no retinopathy, but 10% required laser therapy, and 80 (81%) had no microalbuminuria. Small pupil size at baseline was independently associated with the development of microalbuminuria (odds ratio 4.36 [95% CI 1.32-14.42], P = 0.016) and retinopathy (4.83 [1.3-17.98], P = 0.019) but not with the development of hypoglycemia unawareness. There was no association with baseline cardiovascular tests and the development of complications 12 years later. CONCLUSIONS: In this study, we found an association between baseline pupillometry tests and the presence of microalbuminuria and retinopathy at 12 years of follow-up. This suggests that pupillometry abnormalities may be early indicators of patients who are at high risk of future microvascular disease.

Prevalence of diabetes complications in adolescents with type 2 compared with type 1 diabetes.

OBJECTIVE: To compare the prevalence of diabetes complications and their risk factors in youth with type 1 versus type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed a comparative clinic-based study of 1,433 patients with type 1 diabetes and 68 patients with type 2 diabetes aged <18 years from New South Wales, Australia. Retinopathy was assessed by seven-field stereoscopic retinal photography; albumin excretion rate from three consecutive, timed, overnight urine collections; peripheral neuropathy by thermal and vibration threshold; and autonomic neuropathy by pupillometry. HbA(1c) (A1C) and lipids were measured in all patients and C-peptide in patients with type 2 diabetes. RESULTS: In patients with type 1 versus type 2 diabetes, median (interquartile range) age was 15.7 years (13.9-17.0) and 15.3 years (13.6-16.4), respectively (P = 0.2), whereas median diabetes duration was 6.8 years (4.7-9.6) and 1.3 years (0.6-3.1), respectively (P < 0.0001). Retinopathy was significantly more common in patients with type 1 diabetes (20 vs. 4%, P = 0.04), while microalbuminuria and hypertension were significantly less common (6 and 16% in type 1 diabetes vs. 28 and 36% in type 2 diabetes). Rates of peripheral and autonomic neuropathy were similar (27 and 61% in type 1 diabetes vs. 21 and 57% in type 2 diabetes). In multivariate analyses, microalbuminuria was significantly associated with older age (odds ratio 1.3 [95% CI 1.2-1.5], P < 0.001) and systolic hypertension (3.63 [2.0-6.3], P < 0.001) in type 1 diabetes, while only higher A1C (1.7 [1.3-2.9], P = 0.002) was significant in patients with type 2 diabetes. CONCLUSIONS: Youth with type 2 diabetes have significantly higher rates of microalbuminuria and hypertension than their peers with type 1 diabetes, despite shorter diabetes duration and lower A1C. The results of this study support recommendations for early complications screening and aggressive targeting of glycemic control in patients with type 2 diabetes.

The rising incidence of childhood type 1 diabetes in New South Wales, 1990-2002.

OBJECTIVES: To determine the incidence of childhood type 1 diabetes mellitus (T1DM) in New South Wales from 1997 to 2002; to compare with previously published rates (1990-1996); and to analyse trends in incidence from 1990 to 2002. DESIGN, SETTING AND PARTICIPANTS: Prospective population-based incidence study. Primary ascertainment of incident cases aged < 15 years was from the Australasian Paediatric Endocrine Group NSW children's diabetes register. Secondary ascertainment was from the National Diabetes Supply Scheme until 1999 and from the Australian Institute of Health and Welfare thereafter. Childhood population data were obtained from the Australian Bureau of Statistics. MAIN OUTCOME MEASURES: Age-standardised incidence; trends in incidence by calendar year, and sex and age at diagnosis. RESULTS: There were 3260 incident cases (1629 boys, 1631 girls) in the 13 years. Case ascertainment was 99.7% complete using the capture-recapture method. Mean age-standardised incidence per 100 000 person-years was 20.9 (95% CI, 19.9 to 21.9) from 1997 to 2002 compared with 17.8 (95% CI, 17.0 to 18.7) from 1990 to 1996; there was a plateau in incidence between 1997 and 2002. Overall, the incidence increased on average by 2.8% per year (95% CI, 1.9% to 3.8%, P < 0.001) and increased with age, being 12.2 (95% CI, 11.3 to 13.1) in 0-4 year olds; 18.9 (95% CI, 17.8 to 20.0) in 5-9 year olds and 26.7 (95% CI, 25.4 to 28.1) in 10-14 year olds. The increase per year in 0-4 year olds (3.9%) was not significantly higher than in older children. The mean incidence of T1DM was 19.8 (95% CI, 18.8 to 20.7) in girls and 18.8 (95% CI, 17.9 to 19.7) in boys (P = 0.02). CONCLUSIONS: The incidence of childhood-onset T1DM has increased significantly in all age groups in NSW since 1990. Resource planning in the management of childhood diabetes in NSW should take these findings into account.

Discordant trends in microvascular complications in adolescents with type 1 diabetes from 1990 to 2002.

OBJECTIVE: Since the Diabetes Control and Complications Trial, diabetes management goals have changed. The aims of the present study were to assess complication rates, including nerve abnormalities, in adolescents from 1990 to 2002 and to investigate associated risk factors. RESEARCH DESIGN AND METHODS: Cross-sectional analysis of complications was assessed in three study periods (1990-1994 [T1], 1995-1998 [T2], and 1999-2002 [T3]) in adolescents matched for age and diabetes duration (n = 878, median age 14.6 years, median duration 7.5 years). Retinopathy was assessed by seven-field stereoscopic fundal photography, albumin excretion rate (AER) from three consecutive timed overnight urine collections, peripheral nerve function by thermal and vibration thresholds, and autonomic nerve function by cardiovascular reflexes. RESULTS: Retinopathy declined significantly (T1, 49%; T2, 31%; and T3, 24%; P < 0.0001), early elevation of AER (> or = 7.5 microg/min) declined (38, 30, and 25%, respectively, P = 0.022), and microalbuminuria (AER > or = 20 microg/min) declined (7, 3, and 3%, respectively; P = 0.017, T1 vs. T2 and T3). Autonomic nerve abnormalities were unchanged (18, 21, and 18%, respectively; P = 0.60), but peripheral nerve abnormalities increased (12, 19, and 24%, respectively; P = 0.0017). More patients were treated with three or more injections per day (12, 46, and 67%, respectively; P < 0.0001) and insulin dose increased (1.08, 1.17, and 1.22 units x kg(-1) x day(-1), respectively; P < 0.0001), but median HbA(1c) (A1C) was unchanged (8.5, 8.5, and 8.4%, respectively). BMI and height SD score increased: BMI 0.46, 0.67, and 0.79, respectively (P < 0.0001), and height -0.09, 0.05, and 0.27, respectively (P < 0.0001). CONCLUSIONS: Retinopathy and microalbuminuria declined over time in this cohort, but the increased rate of peripheral nerve abnormalities is of concern. Despite intensified management (higher insulin dose and more injections), A1C has not changed and remains well above the recommended targets for adolescents.

Intramyocellular lipid, adiposity, and muscle oxygen supply in prepubertal type 1 diabetes.

BACKGROUND: In the non-diabetic population, intramyocellular lipid (IMCL) accumulation is associated with obesity and poor muscle oxygen supply. IMCL levels are increased in type 1 diabetes, but their significance is less clear. METHODS: We studied a group of 16 prepubertal boys (age 6.4-9.9 yr) with type 1 diabetes and a range of glycemic control [hemoglobin A1c (HbA1c) 6.4-10.2%]. Children's adiposity was assessed by anthropometry, muscle oxygen supply by near-infrared spectroscopy (NIRS), abdominal and IMCL content by magnetic resonance imaging (MRI), and magnetic resonance spectroscopy (MRS). RESULTS: IMCL content did not associate with muscle reoxygenation rate, abdominal adiposity, duration of diabetes, or recent glycemic control. Muscle reoxygenation rate correlated with percentage body fatness (r2 = 0.46, p = 0.004), visceral (r2 = 0.45, p = 0.007) and abdominal subcutaneous fat volume (r2 = 0.63, p = 0.0004), and dietary fat intake (r2 = 0.27, p = 0.03) but not with the duration of diabetes nor HbA1c. HbA1c was significantly related to dietary fat intake only (r2 = 0.28, p = 0.03). CONCLUSION: While causality cannot be inferred, interventions aimed at improving muscle oxygen supply, or preventing its deterioration, might reduce the development of adiposity in children with type 1 diabetes.

Reduced frequency of HLA DRB1*03-DQB1*02 in children with type 1 diabetes associated with enterovirus RNA.

Enteroviruses have been associated with type 1 diabetes mellitus (T1DM), but it is unclear whether there is a distinct disease subtype. Plasma and stool samples from 206 consecutively diagnosed children and 160 healthy control children were analyzed by reverse-transcription polymerase chain reaction for the RNA of 60 enteroviruses. More children with diabetes tested positive for enterovirus RNA (30% vs. 4%; odds ratio, 11.1; 95% confidence interval, 4.7-25.7; P<.001). Enterovirus 71 was detected in 25% of children; these were temporally associated with outbreaks in Southeast Asia and Australia. Fewer children with the diabetes-associated human leukocyte antigen DRB1*03-DQB1*02 genotype tested positive for enterovirus RNA (P=.02). More children presenting with severe diabetic ketoacidosis (pH, <7.1) tested positive for enterovirus RNA (P=.04). These results suggest that there is a subgroup of patients with T1DM, who are at low genetic risk, in whom enteroviruses contribute to diabetes onset.

Do all prepubertal years of diabetes duration contribute equally to diabetes complications?

OBJECTIVE: This study was designed to explore the timeline of protection against complications in prepubertal children with diabetes, in particular the effects of diabetes duration before age 5 years. RESEARCH DESIGN AND METHODS: In this study, 193 adolescents with prepubertal diabetes onset were followed longitudinally for retinopathy (early background and clinical) and microalbuminuria (albumin excretion rate >7.5 micro g/min and >20 micro g/min). Multiple logistic regression analysis was used to compare the effect of pre- and postpubertal diabetes duration on the risk of each complication in 90 subjects reassessed as young adults. For the entire cohort, Kaplan-Meier estimates were used to determine time free of each complication, and survival was compared in those diagnosed before and after age 5 years. Accelerated failure time modeling was used to estimate the effect of covariates, including diabetes duration before puberty, on the risk of complications. RESULTS: Prepubertal duration improved the prediction for retinopathy over postpubertal duration alone in the young adults. The survival-free period of retinopathy and microalbuminuria was significantly longer (2-4 years) for those diagnosed before age 5 years compared with those diagnosed after age 5 years. Time to onset of all complications increased progressively with longer diabetes duration before gonadarche. Higher HbA(1c) during adolescence had an independent effect on the risk of retinopathy and microalbuminuria. CONCLUSIONS: Prepubertal diabetes duration remains a significant predictor of retinopathy in young adults. The effect of time on the risk of retinopathy and microalbuminuria is nonuniform, with an increasing delay in the onset of complications in those with longer prepubertal duration. These findings are of major clinical importance when setting targets of glycemic control in young children who are at greatest risk of hypoglycemia.

Diagnosis of enterovirus infection by genus-specific PCR and enzyme-linked immunosorbent assays.

PCR for the diagnosis of enterovirus infections is resource intensive but is increasingly used due to wide availability. Enzyme-linked immunosorbent assays (ELISAs) that detect heterotypical antibodies against enterovirus immunoglobulin M (IgM), IgA, and IgG were compared with reverse transcription-PCR by using primers specific to the 5' untranslated regions of 60 enterovirus species. The ELISAs were less sensitive than the PCR, and only the ELISA for IgM was highly specific. When retrospective diagnosis is important or when specimens are unsuitable for PCR, the ELISA has a limited role if PCR is not available.