Evidence of a plateau in the incidence of type 1 diabetes in children 0-4 years of age from a regional pediatric diabetes center; Auckland, New Zealand: 1977-2019.

OBJECTIVE: To determine the incidence of new onset type 1 diabetes in children aged 0-14 years from 1977 to 2019 in Auckland, New Zealand. RESEARCH DESIGN AND METHODS: A cohort study of children with type 1 diabetes aged 0-14 years (n = 1688; 50.4% male) managed by the regional diabetes service between 1977 and 2019. Incidence rates were estimated using census data. RESULTS: The incidence of type 1 diabetes increased by 2.9%/year from 1977 to 2006 (95% confidence interval [CI] 2.13% - 3.48%). Although there was no significant change from 2006 to 2019 (-0.3%/year, 95% CI -1.62% - 1.08%), there was a dramatic fall from 1976 to 2018 in the proportion of New Zealand Europeans, from 69.9 to 33.9%. New Zealand Europeans had the highest incidence (23.3/100,000, 95% CI 20.6-26.1) compared to Maori (8.3/100,000, 95% CI 6.3-10.2), Pasifika (8.6/100,000, 95% CI 6.9-10.4) and other (6.4/100,000, 95% CI 4.7-8.0). All groups showed an overall increase in incidence over time, Maori 4.4%/year, Pasifika 3.7%, compared to New Zealand European 2.7%, and other 2.1%. Incidence increased consistently in 5-9 and 10-14 year olds (2.0% and 2.2%/year, respectively). By contrast, whereas 0-4 year olds showed an increase of 4.6%/year from 1977 to 2003 (p < 0.01), there was no change from 2003 to 2019 (p = 0.2). CONCLUSION: There has been a plateau in the incidence of type 1 diabetes in children 0-4 years of age in the Auckland region since 2003, but not older children. The apparent plateau in the overall incidence of new onset type 1 diabetes in children 0-14 years since 2006 was mediated by substantial changes in the ethnic makeup of the Auckland region.

Children and adolescents with type 1 diabetes in Australasia: An online survey of model of care, workforce and outcomes.

AIM: To survey the model of care and workforce that manages children and adolescents with type 1 diabetes (T1D) in Australasia along with glycaemic outcomes. METHODS: Tertiary and regional paediatric clinics in Australia and New Zealand (NZ) caring for children and adolescents with diabetes were invited to complete an online survey assessing health-care professional (HCP) workforce numbers and available clinical data for the 2016 calendar year. RESULTS: A total of 38 sites responded - 25 Australian (10 tertiary, 15 regional), 13 NZ (4 tertiary, 8 regional) - representing 9715 children with T1D. HCP resourcing varied across sites, with overall HCP/100 patient ratios of: doctors: 0.36 (0.08-1.07), nurses: 0.72 (0-1.8), dieticians: 0.19 (0-0.49) and psychologist/social workers: 0.13 (0-0.36). Overall, 39% of patients used insulin pump therapy (CSII) (29.5% NZ, 40.8% Australia). Databases were being used locally by 26 sites. Thirty-two sites reported the mean clinic HbA1c, mean HbA1c 66 mmol/mol (8.2%) (NZ = 69 mmol/mol (8.5%), Australia = 66 mmol/mol (8.2%)), with 29% of patients attaining the recommended HbA1c target of <58 mmol/mol (7.5%) (NZ = 28%, Australia = 29%). CONCLUSIONS: This is the largest Australasian paediatric T1D workforce survey to date. HCP to patient ratios remain well below international recommendations and have not changed over the last 5-7 years. Glycaemic outcomes in this population were below recommended levels in the majority of patients. There is an urgent need to reform models of care and workforce and to institute systematic benchmarking in both countries in order to prevent acute and chronic complications of T1D.

Increasing incidence of type 2 diabetes in New Zealand children <15 years of age in a regional-based diabetes service, Auckland, New Zealand.

AIM: It is important to understand whether type 2 diabetes mellitus (T2DM) is increasing in childhood for health-care planning and clinical management. The aim of this study is to examine the incidence of T2DM in New Zealand children, aged <15 years from a paediatric diabetes centre, Auckland, New Zealand. METHODS: Retrospective analysis of prospectively collected data from a population-based referral cohort from 1995 to 2015. RESULTS: Hundred and four children presented with T2DM over the 21-year period. The female:male ratio was 1.8:1, at mean (standard deviation) age 12.9 (1.9) years, body mass index standard deviation score +2.3 (0.5), blood sugar 15.3 (8.5) mmol/L, HbA1c 76 (28) mmol/mol. At diagnosis, 90% had acanthosis nigricans and 48% were symptomatic. In all, 33% were Maori, 46% Pacific Island, 15% Asian/Middle Eastern and 6% European. There was a progressive secular increase of 5% year on year in incidence. The overall annual incidence of T2DM <15 years of age was 1.5/100 000 (1.2-1.9) (95% confidence interval), with higher rates in Pacific Island (5.9/100 000) and Maori (4.1/100 000). CONCLUSIONS: The incidence of T2DM in children <15 years of age in New Zealand has increased progressively at 5%/year over the last 21 years. The risk was disproportionately associated with girls and children from high-risk ethnic groups.

Angiotensin-converting enzyme-inhibitor therapy in adolescents with type 1 diabetes in a regional cohort: Auckland, New Zealand from 2006 to 2016.

AIM: To review indications and use of angiotensin-converting enzyme-inhibitor (ACEI) therapy for the treatment of persistent microalbuminuria (MA) and/or hypertension (HTN) in adolescents with type 1 diabetes mellitus (T1DM). METHODS: Retrospective chart review of adolescent patients with T1DM seen within the paediatric diabetes service in Auckland, New Zealand, from 2006 to 2016. MA, HTN, patient demographic characteristics and ACEI prescribing and monitoring indices were examined. RESULTS: Five hundred adolescents with T1DM were included. There were 26 patients (5%) with MA and/or HTN. MA alone was present in 16, HTN alone in 3 and both HTN and MA in 7. The 5-year MA/HTN-free rate was 98%, and the 10-year MA/HTN-free rate was 93%. Longer disease duration and earlier diagnosis were predictors of MA/HTN. There was no significant difference in standard clinical indices between study patients and others. ACEI was prescribed for 17 of 26 patients for either HTN or MA. Within 6 weeks of ACEI commencement, less than half of the subjects had repeat serum creatinine and MA screens and no record of repeat blood pressure measurement. Despite this, all patients had 3-monthly reviews within outpatient clinics where adjustments of ACEI doses were made. CONCLUSION: In our regional adolescent population with T1DM, there were low rates of both MA and/or HTN. In those who required treatment with ACEI, clinical monitoring post-commencement of therapy was inconsistent. Local consensus guidelines for the management of persistent MA in children and adolescents with diabetes mellitus were developed in response to this study.

Anthropometry, glucose homeostasis, and lipid profile in prepubertal children born early, full, or late term.

To examine differences in growth and metabolism in prepubertal children born early term, full term, and late term. We retrospectively studied 294 prepubertal children aged 7.3 years (range 3.0-12.1 years). Children were separated into those born early term (37 0/7-38 6/7 weeks of gestation; n = 68), full term (39 0/7-40 6/7 weeks; n = 179), and late term (41 0/7-41 6/7 weeks; n = 47). Clinical assessments included anthropometry, DXA-derived body composition, fasting lipids, and glucose homeostasis. Statistical models accounted for important confounding factors, such as gender, age, birth weight SDS, birth order, and parental variables. When birth weight was adjusted for sex and gestational age (birth weight SDS), late terms were heavier than both early (p = 0.034) and full (p = 0.020) terms. Early term children were shorter than both full (p = 0.010) and late (p = 0.049) term children, but differences in height disappeared following correction for parents' heights. There were no differences in glucose homeostasis, BMI SDS, adiposity, or fat distribution between groups. Lipid profiles were also similar. When important confounding factors were accounted for, there were no meaningful differences in anthropometry, glucose homeostasis, and lipid profile among children born early term, full term, or late term.

Increasing paternal age at childbirth is associated with taller stature and less favourable lipid profiles in their children.

BACKGROUND: Paternal age at childbirth has been increasing worldwide, and we assessed whether this increase affects growth, body composition and metabolism in their children. METHODS: We studied 277 children (aged 3-12 years) born to fathers aged 19·8-51·8 years. Clinical assessments were height and weight adjusted for parental measurements, DEXA-derived body composition, fasting lipids, glucose homoeostasis and hormonal profiles. RESULTS: Children born to fathers aged 31-35 (P = 0·009) and >35 years (P = 0·021) were 2 cm taller than those of fathers aged ≤30 years. Children of fathers aged >35 years at childbirth had a lower body mass index (BMI) (-0·32 SDS) than offspring of fathers aged 31-35 (-0·01 SDS; P = 0·043) and ≤30 (0·22 SDS; P = 0·019). There were marked effects of paternal age at childbirth on childhood blood lipids. LDL-C concentrations in children born to fathers aged >35 years were 11% and 21% higher than in children of fathers aged 31-35 and ≤30 years, respectively (P < 0·01). Total cholesterol to HDL-C ratio was also higher among the children of fathers aged 31-35 (12%; P = 0·014) and >35 (16%; P = 0·004) years at childbirth compared with the ≤30 group. In addition, HOMA-IR in girls (but not boys) born of fathers aged 31-35 (0·99) and >35 years (1·11) indicated better insulin sensitivity compared with offspring in the ≤30 group (1·63; P < 0·05). CONCLUSIONS: Increasing paternal age at childbirth is associated with a more favourable phenotype in their children (taller and slimmer, with better insulin sensitivity in girls) but with a less favourable lipid profile.

Increasing maternal age is associated with taller stature and reduced abdominal fat in their children.

BACKGROUND: Maternal age at childbirth continues to increase worldwide. We aimed to assess whether increasing maternal age is associated with changes in childhood height, body composition, and metabolism. METHODS: 277 healthy pre-pubertal children, born 37-41 weeks gestation were studied. Assessments included: height and weight corrected for parental measurements, DEXA-derived body composition, fasting lipids, glucose, insulin, and hormonal profiles. Subjects were separated according to maternal age at childbirth: <30, 30-35, and >35 years. RESULTS: Our cohort consisted of 126 girls and 151 boys, aged 7.4 ± 2.2 years (range 3-10); maternal age at childbirth was 33.3 ± 4.7 years (range 19-44). Children of mothers aged >35 and 30-35 years at childbirth were taller than children of mothers aged <30 years by 0.26 (p = 0.002) and 0.23 (p = 0.042) SDS, respectively. There was a reduction in childhood BMISDS with increasing maternal age at childbirth, and children of mothers aged >35 years at childbirth were 0.61 SDS slimmer than those of mothers <30 years (p = 0.049). Children of mothers aged 30-35 (p = 0.022) and >35 (p = 0.036) years at childbirth had abdominal adiposity reduced by 10% and 13%, respectively, compared to those in the <30 group. Children of mothers aged 30-35 years at childbirth displayed a 19% increase in IGF-I concentrations compared to offspring in <30 group (p = 0.042). Conversely, IGF-II concentrations were lower among the children born to mothers aged 30-35 (6.5%; p = 0.004) and >35 (8.1%; p = 0.005) compared to those of mothers aged <30 years. Girls of mothers aged 30-35 years at childbirth also displayed improved HOMA-IR insulin sensitivity (p = 0.010) compared to girls born to mothers aged <30 years. CONCLUSIONS: Increasing maternal age at childbirth is associated with a more favourable phenotype (taller stature and reduced abdominal fat) in their children, as well as improved insulin sensitivity in girls.

Phenotypic differences in children conceived from fresh and thawed embryos in in vitro fertilization compared with naturally conceived children.

OBJECTIVE: To determine whether anthropometric and biochemical features differ in in vitro fertilization (IVF) children conceived via fresh (IVFF) or thawed (IVFT) embryo transfer compared with naturally conceived controls. DESIGN: A cross-sectional controlled study. SETTING: University clinical research unit. PATIENT(S): Healthy prepubertal children (3.5-11.0 years), singletons, born at term (>37 weeks), who were either naturally conceived (controls; n = 94) or IVF children conceived via the transfer of a fresh (IVFF; n = 72) or thawed (IVFT; n = 43) embryo. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Assessments of anthropometry (adjusted for parental variables), dual-energy X-ray absorptiometry-derived body composition, fasting plasma growth factors, lipids, and parameters of glucose regulation. RESULT(S): The IVFF but not the IVFT children weighed less at birth than the control children. The IVFF children were taller than both the controls and IVFT children. Sex-specific analyses showed height differences among girls, with IVFF girls being taller than their control and IVFT counterparts. Taller stature in IVFF children was associated with increased insulin-like growth factor I (IGF-I) concentrations compared with controls, whereas the IVFT children displayed increased IGF-II and decreased insulin-like growth factor binding protein 3 (IGFBP-3) concentrations compared with the controls. More favorable lipid profiles were also evident in IVFF but not IVFT children compared with the control children. CONCLUSION(S): These preliminary findings highlight that the transfer of a fresh versus a thawed IVF embryo affects height, plasma growth factor, and lipid profiles in childhood. Therefore, embryo derivation should be considered when assessing physical and biochemical phenotype of IVF children.

Birth order progressively affects childhood height.

BACKGROUND: There is evidence suggesting that first-born children and adults are anthropometrically different to later-borns. Thus, we aimed to assess whether birth order was associated with changes in growth and metabolism in childhood. METHODS: We studied 312 healthy prepubertal children: 157 first-borns and 155 later-borns. Children were aged 3-10 years, born 37-41 weeks gestation, and of birth weight appropriate-for-gestational-age. Clinical assessments included measurement of children's height, weight, fasting lipid and hormonal profiles and DEXA-derived body composition. RESULTS: First-borns were taller than later-borns (P < 0·0001), even when adjusted for parents' heights (0·31 vs 0·03 SDS; P = 0·001). There was an incremental height decrease with increasing birth order, so that first-borns were taller than second-borns (P < 0·001), who were in turn taller than third-borns (P = 0·007). Further, among sibling pairs both height SDS (P = 0·009) and adjusted height SDS (P < 0·0001) were lower in second- vs first-born children. Consistent with differences in stature, first- (P = 0·043) and second-borns (P = 0·003) had higher IGF-I concentrations than third-borns. Both first- (P < 0·001) and second-borns (P = 0·004) also had reduced abdominal adiposity (lower android fat to gynoid fat ratio) when compared with third-borns. Other parameters of adiposity and blood lipids were unaffected by birth order. CONCLUSIONS: First-borns were taller than later-born children, with an incremental height reduction from first to third birth order. These differences were present after correction for genetic height, and associated to some extent with alterations in plasma IGF-I. Our findings strengthen the evidence that birth order is associated with phenotypic changes in childhood.

Missed congenital hypothyroidism in an identical twin.

Newborn screening for congenital hypothyroidism has been remarkably effective, although rare cases of false negative screening have been reported in same sex twins, presumptively due to fetal blood exchange. We report a case in which the diagnosis of congenital hypothyroidism due to thyroid ectopia in a monozygotic twin was delayed by 8 months, with a normal newborn screening TSH level of 11 mIU/L blood (normal < 15 mIU/L) at 2 days of life. This is the first such case since the national New Zealand newborn screening programme introduced screening for congenital hypothyroidism in 1981 (30 years ago). Repeating thyroid studies at 14 days of age in same-sex twins has been advocated to avoid delayed diagnosis, but given the low risk, may not be cost effective. It is important to maintain a high index of suspicion in same-sex twin pregnancies of potential congenital hypothyroidism.

Ovarian stimulation leads to shorter stature in childhood.

BACKGROUND: We aimed to determine whether children conceived with ovarian stimulation alone (OS(A)) would differ phenotypically and biochemically from naturally conceived children of fertile and subfertile parents. METHODS: Healthy pre-pubertal children aged 3-10 years, born at term, after singleton pregnancies were recruited in Auckland (New Zealand) and were allocated into three groups: (i) children conceived following OS(A) and naturally conceived children of (ii) subfertile and (iii) fertile parents. Anthropometric, endocrine and metabolic parameters were recorded. Children's heights and body mass index (BMI) were expressed as standard deviation scores (SDS) and corrected for genetic potential (i.e. parental height or BMI). RESULTS: Three hundred fifty-two children were studied: 84 OS(A) subjects and 268 naturally conceived controls consisting of 54 children of subfertile parents and 214 children of fertile parents. Children of subfertile and fertile parents did not differ in measured outcomes. Overall, OS(A) children were shorter than children of both subfertile (SDS: -0.08 ± 0.09 versus 0.32 ± 0.07; P= 0.001) and fertile (SDS: -0.08 ± 0.09 versus 0.45 ± 0.10; P= 0.004) parents when corrected for genetic height potential. OS(A) boys were shorter than boys of subfertile (SDS:-0.18 ± 0.14 versus 0.42 ± 0.16; P= 0.03) and fertile (SDS: -0.18 ± 0.14 versus 0.35 ± 0.08; P= 0.01) parents. There was also a trend towards OS(A) girls being shorter than girls of subfertile parents (P= 0.06), but not significantly shorter than those of fertile parents (P= 0.17). OS(A) children also had a lower corrected BMISDS than children of subfertile (SDS-0.90 ± 0.15 versus -0.37 ± 0.17; P= 0.06) and fertile (-0.90 ± 0.15 versus -0.34 ± 0.10; P= 0.008) parents. Among metabolic parameters, fasting glucose was lower in OS(A) children than that in children of fertile parents (4.62 ± 0.07 versus 4.81 ± 0.04; P= 0.006). CONCLUSIONS: Conception after OS(A) was associated with shorter stature, particularly in boys, compared with naturally conceived children of fertile and subfertile parents.

The incidence, clinical features, and treatment of type 2 diabetes in children <15 yr in a population-based cohort from Auckland, New Zealand, 1995­2007.

BACKGROUND: The incidence of type 2 diabetes mellitus (T2DM) is increasing in adolescents in most western countries. The time-course of glycemic control and impact of early treatment remain poorly understood. OBJECTIVES: To determine the change in incidence of T2DM, and the time-course of glycemic control in a regional pediatric cohort with T2DM. METHODS: Retrospective analysis of prospectively collected data on 52 patients with T2DM from a population-based treatment referral cohort from 1 January 1995 to 31 December 2007. RESULTS: The annual incidence of new cases of T2DM in children <15 yr increased fivefold in the Auckland region of New Zealand from 1995 [0.5/100,000; 95% confidence interval (CI) 0.0­2.2] to 2007 (2.5/100,000; 95% CI 1.0­5.5). The average annual incidence per 100,000 over the entire period was 1.3 (95% CI 1.0­1.8) overall, 0.1 (0.0­0.4) in Europeans, and 3.4 in both Maori (2.0­5.3) and Pacifica (2.2­5.0). Fifty-seven percent of children were symptomatic at presentation. Fifty-eight percent of patients were treated with insulin from diagnosis, most of whom were symptomatic (p = 0.003). Follow-up data were available for 48 patients with a mean of 2.4 yr. Although insulin therapy was associated with a greater fall in HbA1c values in the first 12 months of treatment (to a nadir of 7.1 vs. 8.1%, p < 0.05), there was a rapid deterioration after 12 months, and subsequent mean HbA1c values were >9% in both groups. Therapy did not affect body mass index standard deviation score (BMI SDS). CONCLUSIONS: The incidence of T2DM in childhood or adolescence increased markedly over a 13-yr period in the Auckland region. Long-

Impact of insulin pumps on glycaemic control in a pump-naïve paediatric regional population.

AIM: To examine the clinical impact of insulin-pump therapy for children with type 1 diabetes mellitus (T1DM) in a regional paediatric service, Auckland, New Zealand. METHODS: Retrospective analysis of children with T1DM from the Starship paediatric diabetes database who started on insulin-pump therapy from 2002 to 2008 compared with the whole T1DM population and with an equal number of non-pump patients matched by age, sex, ethnicity and duration of diabetes. RESULTS: From 621 subjects with 6680 clinic visits, 75 children were treated with insulin-pump therapy for more than 12 months. Transitioning to insulin-pump treatment was associated with an improvement in HbA1c compared with baseline (-0.3%/year, P < 0.001) for up to 3 years. In contrast, despite similar deprivation scores, non-pump controls showed a continuing trend to higher HbA1C values (+0.2%/year, P < 0.01). The risk of severe hypoglycaemia fell after pump start (from 27 (0-223) to 5 (0-0.91) events/100 patient years) with no change in non-pump controls; the rate of diabetic ketoacidosis remained low in both groups. CONCLUSIONS: In a pump-naïve regional paediatric population, insulin-pump therapy for T1DM was safe and effective, and associated with sustained improvements in HbA1c and lower risk of hypoglycaemia.