Epidemiology of diabetes mellitus in children in Hong Kong: the Hong Kong childhood diabetes register

OBJECTIVES: To establish a registry for Chinese children with onset of type 1 (insulin dependent) diabetes mellitus before 15 years of age and to determine the incidence of childhood onset type 1 diabetes mellitus in Chinese children in Hong Kong. RESEARCH DESIGN AND METHODS: A registry was established in 1997 to collect childhood diabetes cases retrospectively from all districts in Hong Kong. The study included all newly diagnosed cases of diabetes with onset < 15 yr of age from 1st January 1984 to 31 December 1996. Primary ascertainment was based on review of medical records at all regional public hospitals in Hong Kong and survey of all the registered practitioners in Hong Kong. The secondary source of validation was made impractical, if not impossible, because of the recent implementation of the Personal Data Privacy Ordinance in Hong Kong. RESULTS: A total of 255 diabetic cases were identified, 227 type 1 diabetes mellitus (218 were Chinese), 18 type 2 diabetes mellitus and 11 secondary diabetes. 246 patients were Chinese and 9 non-Chinese. The age-standardized incidence of type 1 and type 2 diabetes mellitus in southern Chinese children in Hong Kong was 1.4/100,000/yr and 0.1/100,000/yr respectively for children < 15 yr of age during the study period. The incidence rates for type 1 diabetes were 0.9, 1.5 and 1.7 per 100,000/yr for 0-4 years, 5 to 9 years and 10 to 14 years age-groups respectively. The incidence for males was 1.2/100,000/yr and for females 1.7/100,000/yr. A significant increase in the incidence was demonstrated during the study period by simple linear regression (slope 0.14/100,000/year, r2 = 0.73, p = 0.0002) CONCLUSIONS: A diabetic registry is established in Hong Kong. This study documents a very low incidence rate of childhood type 1 diabetes mellitus in southern Chinese children in Hong Kong and we have seen an increasing incidence of the disease in the past 13 years.     

Incidence, prevalence, and mortality of insulin-dependent (type 1) diabetes mellitus in Lithuanian children during 1983-98

Abstract: Aims/hypothesis: Our purpose is to analyze interrelations of the incidence, prevalence and mortality of childhood‐onset insulin‐dependent diabetes mellitus (type 1) in Lithuania. Methods: Incidence and prevalence rates were based on the national type 1 diabetes register during 1983–98. The cohort study was performed to evaluate the standardized mortality ratios. Results: The average incidence of type 1 diabetes during the 16‐yr study period was 7.36 per 100 000/yr. For both males and females the highest incidence of type 1 diabetes was recorded in the 10–14 yr age group. The regression‐based linear trends of the increase in incidence in various age groups and the annual percentage change for both genders was 2.05 (p = 0.0039) and the greatest regression slope is observed for both genders in the 10–14 yr age group. Regression‐based linear trends in type 1 diabetes prevalence indicate an even growth in all age groups (3.47; p = 0.001), although the annual percentage change is most prominent in the 5–9 yr age group for girls (4.95%/yr) and in the 10–14 yr age group for boys (4.06%/yr). The standardized mortality ratio of all‐cause mortality in people with diabetes is higher than in the common population 7.71 (p < 0.0001). The standard mortality ratio for all causes increases with longer diabetes duration. Conclusion/interpretation: The significant increasing trend of incidence and prevalence during 1983–98 is observed. The annual percentage change is similar. The young patients with type 1 diabetes have a higher mortality risk.     

Polymorphism in the transmembrane region of the MICA gene and type 1 diabetes

Although MHC class II genes have a stronger association with type 1 diabetes than MHC class I genes, studies have shown that MHC class I molecules play an independent role in the etiology of type 1 diabetes, and the existence of susceptibility genes within a segment of MHC between the HLA-B and TNF genes has been predicted, where MHC class I chain-related gene A (MICA) resides. MICA has a triplet repeat polymorphism in the transmembrane region consisting of five alleles. We analyzed this polymorphism in 162 unrelated children (82 boys) with type 1 diabetes (age at diagnosis 7.01 +/- 3.76 yr) and 154 randomly selected unrelated children (87 boys), age 2.81 +/- 2.12 yr. Phenotype frequency of allele A9 in children with type 1 diabetes was significantly higher than in controls (RR = 2.42, 95% CI = 1.52-3.85, p = 0.000162, pc = 0.00081). Gene frequency of allele A9 was also significantly higher in children with type 1 diabetes when compared with control children (RR = 2.73, 95% CI = 1.85-4.03, p = 2.62 x 10(-7), pc = 1.31 x 10(-6)). This study demonstrates that MICA allele A9 confers risk of type 1 diabetes.     

Incidence data of childhood-onset type I diabetes in France during 1988-1997: the case for a shift toward younger age at onset

The objective was to test whether the pattern of increase in incidence of type I diabetes in children under 20 y of age varies with age at onset in France during 1988-1997. The French register of insulin-dependent diabetes was based on the direct identification of new cases by a prospective registration in children under the age of 20 y. Data from the French Social Security were used as a secondary independent source of cases. The rate of ascertainment was >/=95% over the 10-y period studied. Data were analyzed using linear regression; departure from a linear trend was tested in each age group. A total of 1,867 children under 20 y of age at the time of diagnosis were included. The incidence rate of type I diabetes in children rose significantly between 1988 and 1997, from 7.41 per 100,000 per year (95% confidence interval: 6.55-8.27) to 9.58 per 100,000 per year (95% confidence interval: 8.64-10.52) with p = 0.0001. The percentage increase was greater in the 0-4 y age group, with a significant departure from linear trend (p = 0.036), reflecting an acceleration of the increase. Incidence rates rose linearly in 5-9 y (average increase 0.43 per 100,000 per year, p = 0.011) and 10-14 y (average increase 0.40 per 100,000 per year, p = 0.002) age groups, whereas it remained stable in the 15-19 y age group (p = 0.77). The incidence rate was significantly higher in boys than in girls (p = 0.005), but the rise in incidence did not differ between the two genders. The rise in incidence of type I diabetes in France was of the same magnitude as observed in the rest of Europe over 10 y. A specific pattern was observed in children under 5 y of age, contrasting with stable rates over 15 y. These data suggest a shift toward a younger age at onset of type I diabetes in childhood, contributing, at least in part, to the observed increase in incidence of type I diabetes in children.     

Ketoacidosis at onset of type 1 diabetes mellitus in children--frequency and clinical presentation

Abstract: Background: Since 1987, patients with newly diagnosed diabetes mellitus type 1 under 15 yr of age have been registered in Baden‐Wuerttemberg (BW), Germany. Aim: Our aim was to describe the frequency and the clinical presentation of diabetic ketoacidosis (DKA) at onset of type 1 diabetes mellitus in children. Methods: All 31 pediatric departments in BW and one diabetes center participated in this study. Hospital records of 2121 children below 15 yr of age were examined retrospectively. DKA was defined as glucose > 250 mg/dL, pH < 7.30 or bicarbonate < 15 mmol/L and ketonuria. Statistical analysis was done after logarithmic transformation. Results: 26.3% (n = 558) of all patients presented with DKA. The mean age of these patients was 7.9 yr. The frequency of DKA is higher in girls than in boys (28.9 vs. 23.8%; p = 0.0079). Those aged 0–4 yr suffered most frequently (p < 0.0001) from ketoacidosis (36.0%). The percentage of DKA in newly diagnosed cases was constant over 10 yr. 23.3% of all patients with DKA presented with an altered level of consciousness; 10.9% of these had clinical signs of coma. No deaths occurred. The proportion of ketoacidosis does not increase concurrently with the number of diabetes manifestations in winter. Conclusion: The proportion of DKA in children with newly diagnosed diabetes mellitus is significant. In particular, children < 5 yr and girls face an increased risk. DKA may be the result of a particularly aggressive subtype of diabetes.     

Short-term changes in lower leg length in children treated for acute lymphoblastic leukaemia.

The lower leg length velocity (LLLV) of 14 children with a median age of 4.5 yr who were undergoing chemotherapy (CT) for acute lymphoblastic leukaemia (ALL) was studied for a median duration of 56 weeks (range 14-112). Nine children were studied over the first 6 months, six over the first year, four over the full 2-year course and nine children over the 3 months before and after the end of CT. Over the first month of CT, during induction, median LLLV was 0 mm/wk (P5, P95: -1.6, 0.11); during the fourth month of CT, at the end of CNS-directed therapy, there was a significant rise to 0.38 mm/wk (P5, P95: -0.04, 0.81; p = 0.01, WSR). In the children measured following the end of CT, median LLLV rose from 0.46 mm/wk (P5, P95: -0.02, 0.79) in month 23 to 0.84 mm/wk (P5, P95: 0.72, 1.12) (p = 0.03). There was a positive relationship between neutrophil count and LLLV during continuation chemotherapy (r = 0.4, p = 0.0002); median LLLV was 0.2 mm/ wk (P5, P95: -0.15, 0.5) when the neutrophil count was less than 1 x 10(9)/l and 0.65 mm/wk (P5, P95: 0.1, 1.0) (p = 0.01) when the count was above 1 x 10(9)/l. No significant differences in LLLV were observed between children randomised to different UKALLXI regimens. Intensive chemotherapy for ALL adversely affects lower leg growth. Growth was subnormal during the first few weeks of chemotherapy, but was comparable to healthy children during CNS directed and continuation therapy. There was a significant relationship between growth velocity and neutrophil count during continuation chemotherapy. On discontinuation of chemotherapy there was a further acceleration in lower leg length velocity to supranormal levels ("catch-up" growth).     

Significant urban/rural differences in the incidence of type 1 (insulin-dependent) diabetes mellitus among Bulgarian children (1982-1998)

The systematic registration of the incidence of childhood (0-14 yr) type 1 (insulin-dependent) diabetes mellitus in Bulgaria dates back to 1973, with an invariably present difference in the incidence according to the area of residence. The present study has been undertaken to assess the trends in the incidence of type 1 diabetes among children in eastern Bulgaria (1982-1998) with respect to area of residence at onset. The data were collected prospectively, with an ascertainment of the primary source of 95.8%. The mean annual incidence is 6.99/100,000 (95% CI = 6.45-7.54), varying between 5.09 and 11.54/100,000. The mean annual incidence in towns is higher than in villages: 7.89 vs. 5.26/100,000, p < 0.0001. A linear trend of increase in the incidence with time is revealed applying Poisson regression analysis, with the area of residence as a strong predictor of the risk (p < 0.001). According to the model, the age-adjusted incidence rose by 4.1% annually. The stratified analysis by age group has found a significant linear trend in those aged 5-9 (p < 0.001) and 10-14 yr (p = 0.002) for both sexes. In conclusion, the markedly increasing incidence of type 1 diabetes among children in this study is strongly dependent on area of residence at onset. We suggest that in conjunction with the pronounced seasonality at the onset of diabetes and its connection with population density, this phenomenon should be regarded as a reflection of environmental influence and further explored.     

Microvascular complications assessment in adolescents with 2- to 5-yr duration of type 1 diabetes from 1990 to 2006

Cho YH, Craig ME, Hing S, Gallego PH, Poon M, Chan A, Donaghue KC. Microvascular complications assessment in adolescents with 2‐ to 5‐yr duration of type 1 diabetes from 1990 to 2006. Objective: Microvascular complications occur in adolescents with type 1 diabetes, although guidelines vary as to when screening should commence and prevalence data for those with ≤5‐yr duration are limited. We therefore investigated trends in prevalence of early microvascular complications over 17 yr. Research design and methods: 819 adolescents (54% female) aged 11–17 yr with 2‐ to 5‐yr diabetes duration were assessed for complications at a tertiary pediatric diabetes clinic between 1990 and 2006. Early retinopathy was detected using seven‐field fundal photography, albumin excretion rate (AER) by timed overnight urine collections and peripheral nerve function by thermal/vibration threshold at the foot. Results were analyzed by age, time period of assessment, and duration. Results: Early retinopathy declined from 1990 to 2002 (16–7%, p < 0.01), then remained unchanged until 2006. Early elevation of AER (≥7.5 µg/min) and microalbuminuria (≥20 µg/min) did not change over time, whereas peripheral nerve abnormalities increased (14–28%, p < 0.01). Median hemoglobin A1c improved (8.7–8.2%, p < 0.01), in parallel with increased total daily insulin dose and injections per day (p < 0.01). Body mass index standard deviation score increased over time (0.55–0.79, p < 0.01). In multivariate logistic regression, early retinopathy was associated with earlier time period [odds ratio (OR) 0.68, confidence interval (CI) 0.55–0.85, p < 0.01] and older age (OR 1.19, CI 1.02–1.39, p = 0.03). AER ≥ 7.5 µg/min was associated with older age (1.19, 1.06–1.34, p < 0.01) and longer diabetes duration (OR 1.28, CI 1.02–1.62, p = 0.04) and height‐adjusted peripheral nerve abnormalities with later time period (OR 1.26, CI 1.05–1.50, p = 0.01). Conclusions: Early complications are not uncommon in adolescents with 2‐ to 5‐yr diabetes duration, despite more intensive management in recent years.     

Liver transplantation for hereditary tyrosinemia type I: analysis of the UNOS database

Patients with HT-1 can develop progressive liver disease and have a high incidence of HCC. LT is indicated in patients with fulminant liver failure, HCC or decompensated chronic liver disease refractory to NTBC. To determine the need for LT and outcomes after LT in children with HT-1. Children with HT-1 who had LT between 10/1987 and 5/2008 were identified from the UNOS database. Of 11,467 children in the UNOS database, 125 (1.1%) required LT secondary to HT-1. Mean age at LT was two and half yr (s.d. ± 3.6 yr). Mean age at LT during the first 10 yr of the study (1.82, s.d. ± 2.86 yr) was significantly lower than in the last decade (3.70, s.d. ± 4.42 yr), p = 0.01. Nearly half of the patients (58, 46.4%) were transplanted between 1988 and 1992. Overall, one- and five-yr patient survival was 90.4% and 90.4%, respectively. LT is a valuable option for children with HT-1 with fulminant liver failure or when medical treatment fails. The rate of LT for children with HT-1 has decreased and age at transplant increased over the last decade most probably reflecting the effect of early diagnosis and treatment with NTBC.     

Twenty‐one years of prospective incidence of childhood type 1 diabetes in Hungary – the rising trend continues (or peaks and highlands?)

The aim of this study was to examine secular trends in the incidence of type 1 diabetes in children aged 0-14 yr in Hungary over the period 1989-2009. Newly diagnosed children with type 1 diabetes aged 0-14 yr in Hungary were prospectively registered from 1989 to 2009. Primary ascertainment of cases was by prospective registration using hospital notifications. Case ascertainment was over 96% complete using the capture-recapture method. Standardized incidence rates were calculated and secular trends estimated using Poisson regression analysis. In Hungary during 1989-2009 a total number of 3432 children were identified, giving a standardized incidence rate of 12.5 [95% confidence interval (CI) 12.1-12.9] per 100,000 person yr. The overall incidence rate has doubled from 7.7 (95% CI 6.4-9.15) per 100,000 per yr in 1989 to 18.2 (95% CI 15.7-20.9) per 100,000 per yr in 2009. A significant linear trend in incidence (p < 0.001) has been observed over time, with a mean annual increase of 4.4%. The increase in incidence was present in both genders and in all age groups, with the largest relative increase in the youngest age group (6.2%; p < 0.001). The incidence of type 1 diabetes in Hungarian children continues to increase, with the highest rate in the very young. Although it seems that transient periods of stabilization followed by increases in incidence are apparent, the long-term trend continues to be steadily upward. Incidence of childhood type 1 diabetes is a dynamic process, probably reflecting the changes of the environmental exposures and continued registration is necessary to recognize these trends.     

High incidence of childhood type 1 diabetes in Al-Madinah, North West Saudi Arabia (2004-2009)

Habeb AM, Al‐Magamsi MSF, Halabi S, Eid IM, Shalaby S, Bakoush O. High incidence of childhood type 1 diabetes in Al‐Madinah, North West Saudi Arabia (2004–2009). Background: There is a geographical variation in the incidence of childhood type 1 diabetes mellitus (T1DM) with a steady increase reported from some countries. However, data on the incidence of childhood T1DM in Kingdom of Saudi Arabia are limited. Objective: To identify the incidence rate (IR) and epidemiological trends of childhood T1DM in the largest city of northwest Saudi Arabia. Methods: All patients with newly diagnosed T1DM aged 0–12 yr living in the city between 2004 and 2009 were identified from different sources. The data were analyzed according to age, sex, and month of presentation. Results: In total, 419 patients (249 girls) were diagnosed between 2004 and 2009 inclusive. The mean age at diagnosis was 6.9 ± 3.5 yr. The mean annual age‐standardized IR was 29.0 (95% confidence interval 26.0–32.0). The incidence was significantly higher in the 10–12‐yr age group than in younger children (p < 0.001) and higher in girls than in boys (33.0 vs. 22.2 per 100 000; p < 0.001). There was no significant increase in the annual incidence during the 6‐yr period (p = 0.68) and more cases were diagnosed during autumn and winter months (p = 0.002). Conclusions: Al‐Madinah city has the highest reported incidence of childhood T1DM in the Middle East and North Africa region. Further studies to identify the reasons for this high incidence are needed.     

Effects of insulin-like growth factor-I deficiency and replacement therapy on the hematopoietic system in patients with Laron syndrome (primary growth hormone insensitivity)

BACKGROUND: Primary insulin-like growth factor-I (IGF-I) deficiencies, such as in Laron syndrome (LS), are a unique model in man to study the consequences resulting from defects in growth hormone (GH) signal transmission. OBJECTIVE: To assess retrospectively the effect of IGF-I deficiency and its therapy on the various cells of the hematopoietic system as reflected by peripheral blood counts. PATIENTS AND METHODS: Two groups of patients were studied. The first group consisted of 11 untreated patients with LS, seven males and four females, who were followed from childhood into adult age. Average age at the time of data analysis was 45.4 +/- 9.6 years. The second group included ten children with LS, six males and four females, who received IGF-I replacement therapy for an average period of 6 years, ranging in age from 0.9-11 years. The mean age at initiation of therapy was 6.9 +/- 4.28 years. Only the seven children treated for 5 years or more were included in the analysis. Data on blood counts were collected from the patients' charts. Blood samples were drawn at baseline, weekly during the first month, once a month during the first year, and once every 3 months thereafter. Statistical analysis of the change over time was performed using repeated measures ANOVA. RESULTS: Children with LS had red cell indices in the lower normal range and an elevated monocyte count. A statistically significant rise in red blood cell (RBC) indices was seen in children during IGF-I therapy: RBC rose from 4.66 x 10(6)/ml to 4.93 x 10(6)/ml (p = 0.011); hemoglobin from 11.55 g/dl to 13.01 g/dl (p < 0.001); hematocrit from 34.94% to 38.52% (p = 0.007), and mean corpuscular volume from 72.27 fl to 79.93 fl (p < 0.001). The platelet count diminished significantly during IGF-I therapy from 316 x 10(3)/ml to 219 x 10(3)/ml (p = 0.02), and the monocyte count from 0.74 x 10(3)/ml to 0.49 x 10(3)/ml (p < 0.001). CONCLUSIONS: The present investigation, the first of its kind in this syndrome, confirms that IGF-I has a strong stimulatory effect on erythropoiesis. In addition, IGF-I therapy had a reducing effect on monocytes and platelets, an effect not previously described. The mechanism by which IGF-I mediates these effects needs further elucidation.     

Single photon emission tomography (SPECT) study of regional cerebral blood flow in normoalbuminuric children and adolescents with type 1 diabetes

Abstract: Cerebral damage in diabetes can be related to chronic hyperglycemia and recurrent severe hypoglycemia as well as due to the associated vasculopathy. The pattern of regional cerebral blood flow using cerebral single photon emission tomography (SPECT) was evaluated in normoalbuminuric type 1 diabetic children and adolescents and its relation to the metabolic control and cognitive functions. Thirty-one type 1 diabetics aged 10–18 yr (mean 14.7 ± 3.4) were included, 16 males and 15 females, divided into four groups: group I (n = 8) with history of recurrent severe hypoglycemia (≥ 3); group II (n = 8) with history of severe diabetic ketoacidosis (≥ 3); group III (n = 7) with recurrent minor hypoglycemia (≥ 3/week); and group IV (n = 8) with controlled diabetes. The control group (V) comprised seven healthy children, aged 10–18 yr (mean 14.2 ± 3.1). SPECT was done using technetium-99m hexamethyl propylene amine oxime. There was significant brain hypoperfusion in diabetics compared with controls, mainly in the basal ganglia (p < 0.01) and frontal regions (p < 0.01), with less changes in parietal and temporal regions. These changes were not related to the age, sex, diabetes duration, mean blood glucose or HbA1C. Basal ganglia hypoperfusion was significant in groups I (p < 0.01) and II (p < 0.01) compared with controlled diabetics. There was no correlation between cerebral SPECT changes and cognitive scores in type 1 diabetics.
Conclusion: Subclinical alterations in cerebral blood flow (hypoperfusion) are present in children and adolescents with type 1 diabetes mainly affecting the basal ganglia and frontal regions, usually not associated with measurable alterations of the cognitive functions     

Incidence and prevalence of type 1 diabetes in children aged <15 yr in Castilla-Leon (Spain)

OBJECTIVES: To determine the incidence and prevalence of type 1 diabetes in children younger than 15 yr in the Autonomous Community of Castilla-Leon (Spain). RESEARCH DESIGN AND METHODS: All type 1 diabetic cases with onset at <15 yr of age were recorded during 2003-2004. Identified case subjects were ascertained from several sources and the capture-recapture method was used to estimate the completeness of ascertainment. For prevalence, all patients younger than 15 yr with type 1 diabetes at the beginning and at the end of the study were identified. RESULTS: Over the study period, 130 children aged 0-14 yr were diagnosed with type 1 diabetes. The average observed incidence of type 1 diabetes in this population was 22.22/100 000/yr (95% CI 14.57-29.81). Age-standardized incidence was 22.01/100 000/yr (95% CI 18.18-25.83). The highest incidence was observed in the 5-9 yr age-group (32.45/100 000/yr, 95% CI 24.31-40.59). The prevalence at the beginning and at the end of the study was 1.01/1000 and 1.18/1000, respectively. CONCLUSION: Castilla-Leon appears to have one of the highest incidences of childhood type 1 diabetes in Spain, with recent incidence approaching those of some northern European countries.     

Role of exposure to air pollutants in the development of type 1 diabetes before and after 5 yr of age

Abstract: Objective: To assess the role of ambient air pollutants in type 1 diabetes in children. Design and methods: Prediagnosis exposure to five air pollutants was studied in two subgroups with onset of type 1 diabetes before and after 5 yr of age, and two matched subgroups of healthy children. Zip codes and dates of residence from birth to diagnosis were used to obtain geographic‐ and time‐specific air concentrations of SO₂, NO₂, ozone (O₃), SO₄, and particulate matter < 10 µm in diameter (PM₁₀). Prediagnosis time‐adjusted pollutant exposure levels were created by summing up zip code‐specific pollution data and dividing by months of exposure from birth to diagnosis. Two‐tailed t‐test and logistic regression were used to evaluate relative effects and test data between cases and controls. Results: Prediagnosis average O₃ exposure was significantly higher in children with type 1 diabetes than in healthy controls. Prediagnosis PM₁₀ exposure was significantly higher in children diagnosed before 5 yr of age, when compared with healthy controls. SO₂ exposure was significantly higher in children with later‐onset diabetes compared with those with early‐onset diabetes (EOD). NO₂, SO₂ and SO₄ exposure was significantly lower in children diagnosed after 5 yr of age, when compared with healthy controls. O₃, NO₂, SO₄ and PM₁₀ levels did not significantly differ between the two diabetic subgroups. Conclusion: Increased ozone exposure may be a contributory factor to the increased incidence of type 1 diabetes. PM₁₀ may be a specific contributory factor to the development of type 1 diabetes before 5 yr of age.     

Neonatal and infant beta cell hormone concentrations in relation to type 1 diabetes risk

Type 1 diabetes is preceded by the appearance of islet autoantibodies. Seroconversion to islet autoantibodies is greatest around 1 yr of age and is more frequent in children born to fathers with type 1 diabetes as compared to children born to mothers with type 1 diabetes. Here we asked whether changes in beta‐cell function in the neonate and infant reflect variations in the incidence of islet autoantibody seroconversion. Insulin, proinsulin, and c‐peptide concentrations were measured in sequential samples taken from birth to age 2 yr in 103 children who had a first degree relative with type 1 diabetes and who had been followed for islet autoantibody seroconversion. Serum insulin and proinsulin concentrations were highest at birth declining by age 3 months and stable thereafter until age 2 yr. C‐peptide concentrations, proinsulin/insulin, and proinsulin/c‐peptide ratios were stable from age 3 months. No differences were observed between children who developed islet autoantibodies and children who remained islet autoantibody negative. Children born to a mother with type 1 diabetes had higher birth concentrations of insulin (p = 0.005) and proinsulin (p = 0.014) as compared with children of non‐diabetic mothers. Increased insulin concentrations in children of type 1 diabetes mothers persisted until age 6 months. In conclusion, we could not relate excursions in beta‐cell hormones to autoantibody development, but suggest that the higher exposure to insulin and proinsulin in neonates born to mothers with type 1 diabetes may be linked to the relative protection against islet autoantibody seroconversion observed in these children.     

Marked increase in type 1 diabetes mellitus incidence in children aged 0-14 yr in Victoria, Australia, from 1999 to 2002

OBJECTIVES: The objectives of the study were to (i) determine the incidence of type 1 diabetes mellitus (T1DM) in children aged <15 yr in Victoria, Australia, from 1999 to 2002 and (ii) to analyze trends in incidence over this period. METHODS: Prospective population-based incidence study. The primary source of case ascertainment was from the Australasian Paediatric Endocrine Group (APEG) Victorian diabetes register. The secondary source was the National Diabetes Register (NDR), which ascertains cases from the National Diabetes Service Scheme (NDSS), a Commonwealth government initiative, where patients register to receive diabetes supplies at a subsidized price. MAIN OUTCOME MEASURES: Age-standardized incidence, trends in incidence by age, sex and year, and variation in incidence by region, season, and socioeconomic status. RESULTS: Case ascertainment was 99.1% complete using the capture-recapture method. The mean annual age-standardized incidence was 19.3 per 100 000 person years from 1999 to 2002. On average, incidence increased by 9.3% per year, with a greater relative increase in the 0-4 yr age-group (p = 0.037). No gender bias in incidence was found, but the increase in females was statistically significant (13.6% per year, 95% confidence interval 3.7-24.3). Variation in geographical distribution and seasonal onset of incidence was not statistically significant. CONCLUSIONS: The marked increase in the incidence of T1DM in Victoria is greater than that recently described in other Australia states and developed nations. The etiology of this rise is unclear, while the increased caseload has major implications for diabetes health care providers for current and future resource allocation.     

Linear growth and height outcomes in children with early onset type 1 diabetes mellitus--a 10-yr longitudinal study

OBJECTIVE: To assess the linear growth and height outcomes and the influence of metabolic control on the near-final height in children with early onset type 1 diabetes mellitus (DM). STUDY DESIGN AND METHODS: Retrospective longitudinal evaluation of 99 children with prepubertal onset of type 1 DM before 8 yr of age, who were regularly assessed, clinically and metabolically, from 8 yr of age to 17.99 yr of age. RESULTS: The mean prepubertal height Z scores at 8 yr of age were -0.17 (standard deviation, SD = 0.99) for boys and -0.29 (1.19) for girls, respectively. There was normal linear growth in girls with their mean near-final height Z score being -0.13 (1.07). This was not statistically different from the mean at 8 yr (p = 0.13). The mean near-final height Z score in boys was -0.39 (0.98), which was 0.22 SD lower than their mean prepubertal height Z score (p = 0.03). There was no significant correlation between metabolic control and linear growth in either males or females. CONCLUSIONS: Linear growth and near-final height in children with type 1 DM compares favorably with the general population. Although there was some evidence of suboptimal peripubertal growth in boys, the actual extent of this height reduction was minimal and was not correlated with their metabolic control.     

Type 1 diabetes: increased height and weight gains in early childhood

Objective:  The accelerator/beta-cell stress hypothesis regards insulin resistance as one common basis for type 1 and type 2 diabetes and weight increase as an important trigger of type 1 diabetes. To test this hypothesis, we examined children's height and weight gain from birth to the time of diagnosis of type 1 diabetes.
Method:  Growth charts (n = 316) from children 0–16 yr old up to the time of diagnosis of type 1 diabetes were compared with growth charts from age- and sex-matched controls.
Results:  Compared with their controls, children who developed diabetes had experienced more pronounced gain in both weight and height. In the year of diagnosis, they were taller [0.5 vs. 0.36 standard deviation score (SDS), p < 0.03] and heavier (0.7 vs. 0.45 SDS, p < 0.01). Children who developed diabetes aged 5 yr or less gained more weight during the period between their third month and third year of life (p < 0.01). Children who were diagnosed between 6 and 10 yr of age had gained more in height before they were 5 yr old (p < 0.05). Regression analysis showed that a high weight or a high body mass index (BMI) at 5 yr of age indicated, more than the other measurements, a high risk for diabetes later during childhood, while height and weight at ages less than 5 yr did not add any further information on diabetes risk.
Conclusions:  Rapid growth before 7 yr of age and increased BMI in childhood are risk factors for later type 1 diabetes. These findings support the accelerator/beta-cell stress hypothesis.