Craig Jefferies

Evaluation of HOMA and QUICKI as measures of insulin sensitivity in prepubertal children

Abstract:  Background: Simple fasting sample methods to measure insulin sensitivity (SI) such as homeostasis model assessment (HOMA) and quantitative insulin‐sensitivity check index (QUICKI) have been widely promoted in adult studies but have not been formally evaluated in children. The aim of this study was to compare HOMA and QUICKI to the minimal model as measures of SI in prepubertal children.

Definition, epidemiology, and classification of diabetes in children and adolescents: Definition, epidemiology, and classification of diabetes

Maria E Craiga,b, Craig Jefferiesc, Dana Dabelead, Naby Baldee, Anju Sethf and Kim C Donaghuea aInstitute of Endocrinology and Diabetes, The Children’s Hospital at Westmead and University of Sydney, Sydney, Australia; bSchool of Women’s and Children’s Health, University of New South Wales, Sydney, Australia; cPaediatric Endocrinology, Starship Children’s Hospital, Auckland, New Zealand; dDepartment of Epidemiology, Colorado School of Public Health, University of Colorado, Aurora, CO, USA; eDepartment of Endocrinology, University Hospital, Conakry, Guinea and fLady Hardinge Medical College, New Delhi, India

The Impact of Early Nutrition in Premature Infants on Later Childhood Insulin Sensitivity and Growth

OBJECTIVES. Children born prematurely have decreased insulin sensitivity. The etiology of this insulin resistance is unknown. The aim of this study was to evaluate infant nutrition and its influence on insulin sensitivity and postnatal growth in children born ≤32 weeks’ gestation. METHODS. A total of 56 healthy, developmentally normal, prepubertal children, aged 4 to 10 years were recruited. Thirty-seven were born ≤32 weeks’ gestation, and 19 were control subjects born at term with a birth weight >10th percentile. Insulin sensitivity (10−4 min−1 μU/mL) was calculated from a 90-minute frequently sampled intravenous glucose tolerance test. Perinatal, nutritional, and growth data were obtained retrospectively from both neonatal and early infancy records in the premature cohort. RESULTS. Children born prematurely had decreased insulin sensitivity when compared with those born at term (13.8 vs 30.6). Neonatal nutrition was not correlated with insulin sensitivity; however, all of the infants had inadequate protein in the first month followed by excessive fat intake thereafter. Premature children with greater weight gain had lower insulin sensitivity. Higher carbohydrate intake in the first month of life was associated with greater weight gain from birth. No relationship was seen between weight gain and either protein or lipid intake. CONCLUSIONS. Prematurely born children are insulin resistant and have suboptimal neonatal nutrition. Greater childhood weight gain magnifies this reduction in insulin sensitivity and seems to be associated with early nutrition. We speculate that a high carbohydrate neonatal diet may lead to greater weight gain and a greater reduction in insulin sensitivity in this group.

An angled insertion technique using 6-mm needles markedly reduces the risk of intramuscular injections in children and adolescents

Aims  The aims of this study were (i) to establish which children with Type 1 diabetes are at risk of intramuscular or intradermal insulin injections and (ii) to determine a needle length and technique that reliably administers insulin into subcutaneous fat.

Increased Adiposity in Adults Born Preterm and Their Children

Background Preterm birth is associated with abnormalities in growth, body composition, and metabolism during childhood, but adult data are scarce and none exist for their offspring. We therefore aimed to examine body composition and cardiovascular risk factors in adults born preterm and their children. Methods A cohort of 52 adults (aged 35.7 years, 54% female, 31 born preterm) and their term-born children (n=61, aged 8.0 years, 54% female, 60% from a preterm parent) were studied. Auxology and body composition (whole-body dual-energy X-ray absorptiometry) were measured, and fasting blood samples taken for metabolic and hormonal assessments. Results Adults born preterm had greater abdominal adiposity, displaying more truncal fat (p=0.006) and higher android to gynoid fat ratio (p=0.004). Although women born preterm and at term were of similar weight and BMI, men born preterm (n=8) were on average 20 kg heavier (p=0.010) and of greater BMI (34.2 vs 28.4 kg/m2; p=0.021) than men born at term (n=16). Adults born preterm also displayed a less favourable lipid profile, including lower HDL-C concentrations (p=0.007) and greater total cholesterol to HDL-C ratio (p=0.047). Children of parents born preterm tended to have more body fat than the children of parents born at term (21.3 vs 17.6%; p=0.055). Even after adjustment for mean parental BMI, children of parents born preterm had altered fat distribution, with more truncal fat (p=0.048) and greater android to gynoid fat ratio (p=0.009). Conclusions Adults born preterm, particularly men, have markedly increased fat mass and altered fat distribution. A similar increase in abdominal adiposity was observed in the term born offspring of parents born preterm, indicating that adverse outcomes associated with preterm birth may extend to the next generation.

Increasing incidence and age at diagnosis among children with type 1 diabetes mellitus over a 20-year period in Auckland (New Zealand).

Background We aimed to evaluate the incidence of type 1 diabetes mellitus in children <15 years of age (yr) in the Auckland region (New Zealand) over 20 years (1990–2009). Methods We performed a retrospective review of all patients <15 yr diagnosed with type 1 diabetes, from an unselected complete regional cohort. Results There were 884 new cases of type 1 diabetes, and age at diagnosis rose from 7.6 yr in 1990/1 to 8.9 yr in 2008/9 (r2 = 0.31, p = 0.009). There was a progressive increase in type 1 diabetes incidence among children <15 yr (p<0.0001), reaching 22.5 per 100,000 in 2009. However, the rise in incidence did not occur evenly among age groups, being 2.5-fold higher in older children (10–14 yr) than in the youngest group (0–4 yr). The incidence of new cases of type 1 diabetes was highest in New Zealand Europeans throughout the study period in all age groups (p<0.0001), but the rate of increase was similar in New Zealand Europeans and Non-Europeans. Type 1 diabetes incidence and average annual increase were similar in both sexes. There was no change in BMI SDS shortly after diagnosis, and no association between BMI SDS and age at diagnosis. Conclusions There has been a steady increase in type 1 diabetes incidence among children <15 yr in Auckland over 20 years. Contrary to other studies, age at diagnosis has increased and the greatest rise in incidence occurred in children 10–14 yr. There was little change in BMI SDS in this population, providing no support for the ‘accelerator hypothesis’.

Permanent Hypopituitarism Is Rare after Structural Traumatic Brain Injury in Early Childhood

BACKGROUND We sought to determine the incidence of permanent hypopituitarism in a potentially high-risk group: young children after structural traumatic brain injury (TBI). METHODS We conducted a cross-sectional study with longitudinal follow-up. Dynamic tests of pituitary function (GH and ACTH) were performed in all subjects and potential abnormalities critically evaluated. Puberty was clinically staged; baseline thyroid function, prolactin, IGF-I, serum sodium, and osmolality were compared with age-matched data. Diagnosis of GH deficiency was based on an integrated assessment of stimulated GH peak (<5 μg/liter suggestive of deficiency), IGF-I, and growth pattern. ACTH deficiency was diagnosed based on a subnormal response to two serial Synacthen tests (peak cortisol <500 nmol/liter) and a metyrapone test. RESULTS We studied 198 survivors of structural TBI sustained in early childhood (112 male, age at injury 1.7 ± 1.5 yr) 6.5 ± 3.2 yr after injury. Sixty-four of the injuries (33%) were inflicted and 134 (68%) accidental. Two participants had developed precocious puberty, which is within the expected background population rate. Peak stimulated GH was subnormal in 16 participants (8%), in the context of normal IGF-I and normal growth. Stimulated peak cortisol was low in 17 (8%), but all had normal ACTH function on follow-up. One participant had a transient low serum T(4). Therefore, no cases of hypopituitarism were recorded. CONCLUSION Permanent hypopituitarism is rare after both inflicted and accidental structural TBI in early childhood. Precocious puberty was the only pituitary hormone abnormality found, but the prevalence did not exceed that of the normal population.

Etiology of Increasing Incidence of Congenital Hypothyroidism in New Zealand from 1993–2010

BACKGROUND Recent reports suggest that the incidence of congenital hypothyroidism (CHT) is increasing in some countries. The etiology of this change is unclear, and it may relate to changes in screening thresholds. We aimed to determine whether the incidence of CHT in New Zealand has changed and whether ethnic-specific rates and the rates of CHT subtypes have also changed. METHODS The New Zealand neonatal TSH-based screening program has prospectively identified cases of CHT using the same assay and screening thresholds since 1993. Thyroid scintiscans are routinely recommended. We retrospectively identified all cases of CHT requiring levothyroxine treatment from 1993-2010 recorded by the national newborn screening program (>99.5% coverage). Among other parameters, ethnic and CHT subtype-specific incidence rates were calculated. RESULTS There were 330 new cases of CHT and 1,053,457 live births registered in New Zealand in the 18-yr period, and 86% of cases had a scintiscan, 67% of which had thyroid dysgenesis (female to male ratio 5.0:1.0) and 33% dyshormonogenesis (0.9:1.0). The overall incidence of CHT rose from 2.6 to 3.6 per 10,000 live births (P < 0.01). The incidence of dyshormonogenesis (P = 0.01) increased but not of dysgenesis (P = 0.13). This was mediated by a 2-fold increase in Asian births and 40% increase in Pacific Island births. Both ethnic groups displayed higher rates of dyshormonogenesis compared with New Zealand Europeans (odds ratio 3.3 and 2.6, respectively). There was no change in the ethnic-specific incidences of CHT. CONCLUSION Although the incidence of congenital hypothyroidism in New Zealand has increased, this is due to changes in the countrys ethnic composition.

A novel therapeutic paradigm to treat congenital hypothyroidism

Objective  To determine the effectiveness of a novel therapeutic paradigm to treat congenital hypothyroidism (CH) incorporating variable initial doses of L‐T4 based on the underlying aetiology and frequent monitoring, up to 2 years of age.

ISPAD Clinical Practice Consensus Guidelines 2018 Definition, epidemiology and classification of diabetes in children and adolescents

Diagnostic criteria for all types of diabetes in children and adolescents are based on laboratory measurement of plasma glucose levels (BGL) and the presence or absence of symptoms (E). Finger prick BGL testing should not be used to diagnose diabetes (E). A marked elevation of the BGL confirms the diagnosis of diabetes, including a random plasma glucose concentration ≥11.1 mmol/L (200 mg/dl) or fasting plasma glucose ≥7.0 mmol/l (≥126 mg/dl) in the presence of overt symptoms. This article is protected by copyright. All rights reserved.