Biomedical subjects

W S Cutfield

Publications and source records attributed to W S Cutfield.

At least 19 recordsLinked to original sources

PubMed2006

Combination therapy with acipimox enhances the effect of growth hormone treatment on linear body growth in the normal and small-for-gestational-age rat.

Growth hormone (GH) therapy is often associated with adverse side effects, including impaired insulin sensitivity. GH treatment of children with idiopathic short stature does not lead to an optimized final adult height. It has been demonstrated that FFA reduction induced by pharmacological antilipolysis can stimulate GH secretion per se in both normal subjects and those with GH deficiency. However, to date, no investigation has been undertaken to establish efficacy of combination treatment with GH and FFA regulators on linear body growth. Using a model of maternal undernutrition in the rat to induce growth-restricted offspring, we investigated the hypothesis that combination treatment with GH and FFA regulators can enhance linear body growth above that of GH alone. At postnatal day 28, male offspring of normally nourished mothers (controls) and offspring born with low birth weight [small for gestational age (SGA)] were treated with saline, GH, or GH (5 mg.kg(-1).day(-1)) in combination with acipimox (GH + acipimox, 20 mg.kg(-1).day(-1)) or fenofibrate (GH + fenofibrate, 30 mg.kg(-1).day(-1)) for 40 days. GH plus acipimox treatment significantly enhanced linear body growth in the control and SGA animals above that of GH, as quantified by tibial and total body length. Treatment with GH significantly increased fasting plasma insulin, insulin-to-glucose ratio, and plasma volumes in control and SGA animals but was not significantly different between saline and GH-plus-acipimox-treated animals. GH-induced lipolysis was blocked by GH plus acipimox treatment in both control and SGA animals, concomitant with a significant reduction in fasting plasma FFA and insulin concentrations. This is the first study to show that GH plus acipimox combination therapy, via pharmacological blocking of lipolysis during GH exposure, can significantly enhance the efficacy of GH in linear growth promotion and ameliorate unwanted metabolic side effects.

Animals↗

PubMed2006

Prematurity--another example of perinatal metabolic programming?

Low birth weight is associated with both later adult diseases such as type 2 diabetes mellitus and a number of metabolic abnormalities, the foremost of which is insulin resistance. Indeed the link between an adverse perinatal environment, manifested by low birth weight, and adult life pathology may be an early, permanent reduction in insulin sensitivity. A reduction in insulin sensitivity has been demonstrated in small for gestational age (SGA), term subjects from childhood through to adulthood. Less is known about children born premature into an adverse neonatal environment. We present data demonstrating that premature infants also have metabolic abnormalities similar to those observed in term, SGA children and that these occur irrespective of whether they are SGA or appropriate for gestational age (AGA).

Adipose Tissue↗

PubMed2006

Safety of growth hormone treatment in children born small for gestational age: the US trial and KIGS analysis.

BACKGROUND: Recently, growth hormone (GH) therapy for children with short stature born small for gestational age (SGA) has been approved in the USA and Europe. There have been few reports examining adverse events during GH treatment of these children. AIMS: (i) To examine glucose tolerance and insulin sensitivity during GH treatment of children born SGA in a US trial. (ii) To determine and compare adverse events reported in children born SGA with those reported in children with idiopathic short stature (ISS) enrolled in KIGS - Pfizer International Growth Database. METHODS: In the US SGA trial, an oral glucose tolerance test was performed and fasting plasma glucose, insulin and glycosylated haemoglobin (HbA(1C)) concentrations were measured at baseline and after 12 months of GH therapy. Insulin sensitivity was calculated using the homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI). In the KIGS analysis, a retrospective audit of spontaneously logged cumulative adverse events in children born SGA and those with ISS was undertaken. Adverse events are reported per 1,000 patients. Values are expressed as mean with 10th-90th percentiles. RESULTS: In the US trial, 84 patients had complete data sets for analysis. Median birth weight was 1.78 kg (SDS, -2.5) and birth length 43 cm (SDS, -2.2) at a median gestational age of 36.5 weeks; 79% were Caucasian. At entry, median age of the patients analysed was 6.6 years, and 65% were male. Median height was 104.3 cm (SDS, -2.97), median weight 15.95 kg (SDS, -2.21) and body mass index 14.66 kg/m(2) (SDS, -0.67). No patients developed impaired glucose tolerance or overt diabetes mellitus. The 0-min glucose concentration was 81 mg/dl at baseline and 86 mg/dl at 1 year, while the 120-min glucose concentration was 90 mg/dl at baseline and 96 mg/dl at 1 year. The 0-min insulin concentrations were 2.9 mU/l at baseline and 5.3 mU/l at 1 year, while the 120-min insulin levels were 7.7 mU/l at baseline and 11 mU/l at 1 year. The proportions of HbA(1C) were 5.2 and 5.4% at baseline and 1 year, respectively. HOMA and QUICKI values were 0.59 and 0.42, respectively, at baseline, and 1.13 and 0.38 at 1 year. In KIGS, there were 1909 children born SGA aged 9.1 (3.9-13.3) years with a birth weight SDS of -2.6 (-4.0 to -1.5), birth length SDS of -2.7 (-4.3 to -1.3) and height SDS of -2.71 (-3.9 to -1.8) prior to treatment. GH doses ranged from 0.032 to 0.037 in the USA and from 0.022 to 0.023 mg/kg/day in the remaining countries in KIGS. Neither total (187 vs. 183) nor serious (14 vs. 10) adverse events occurred more commonly in the SGA group than in the ISS group. Although respiratory adverse events occurred more commonly in children born SGA (34.3 vs. 16.8; p < 0.05), endocrine (12.0 vs. 2.7; p < 0.05) and hepatobiliary (6.2 vs. 1.1; p < 0.05) adverse events occurred more commonly in children with ISS. CONCLUSIONS: As expected, a reduction in insulin sensitivity occurred during GH treatment of children born SGA; however, glucose tolerance remained normal. No adverse events were reported more commonly in children born SGA than in those with ISS. Minor differences in adverse events reporting within organ systems between children born SGA and those with ISS are probably due to variable under-reporting of adverse events. GH appears to be a safe drug to use at current doses as a growth-promoting agent in short children born SGA.

Adolescent↗

PubMed2006

Insulin sensitivity in people born pre-term, with low or very low birth weight and small for gestational age.

Evidence has accumulated that small for gestational age (SGA) children have long-term adult health consequences including obesity, Type 2 diabetes mellitus, hypertension, coronary artery disease and stroke. This increased risk of later adult disease is likely a consequence of an early, persistent reduction in insulin sensitivity. The SGA children and adults studied were predominantly at term gestation, and it appears that prematurity also leads to insulin resistance with possibly similar health consequences for later life. Both term SGA and premature children have an abnormal early environment: one in utero and one post-natally. Parallels are made among those born SGA at term or premature to show the potential importance of maternal factors, the intrauterine milieu, including nutrient supply and intake in fetal and early newborn life. It is possible that manipulation of these factors during early neonatal life in premature babies could lead to normalisation of insulin sensitivity. To confirm this hypothesis, further studies are needed to better understand the pathophysiological mechanisms leading to reduced insulin sensitivity and confirm that prematurity is linked with similar long-term health consequences as being born SGA.

Adult↗

PubMed2005

Neonatal leptin treatment reverses developmental programming.

An adverse prenatal environment may induce long-term metabolic consequences, in particular obesity and insulin resistance. Although the mechanisms are unclear, this programming has generally been considered an irreversible change in developmental trajectory. Adult offspring of rats subjected to undernutrition during pregnancy develop obesity, hyperinsulinemia, and hyperleptinemia, especially in the presence of a high-fat diet. Reduced locomotor activity and hyperphagia contribute to the increased fat mass. Using this model of maternal undernutrition, we investigated the effects of neonatal leptin treatment on the metabolic phenotype of adult female offspring. Leptin treatment (rec-rat leptin, 2.5 microg/g.d, sc) from postnatal d 3-13 resulted in a transient slowing of neonatal weight gain, particularly in programmed offspring, and normalized caloric intake, locomotor activity, body weight, fat mass, and fasting plasma glucose, insulin, and leptin concentrations in programmed offspring in adult life in contrast to saline-treated offspring of undernourished mothers who developed all these features on a high-fat diet. Neonatal leptin had no demonstrable effects on the adult offspring of normally fed mothers. This study suggests that developmental metabolic programming is potentially reversible by an intervention late in the phase of developmental plasticity. The complete normalization of the programmed phenotype by neonatal leptin treatment implies that leptin has effects that reverse the prenatal adaptations resulting from relative fetal undernutrition.

Absorptiometry, Photon↗

PubMed2005

Reduced insulin sensitivity and the presence of cardiovascular risk factors in short prepubertal children born small for gestational age (SGA).

BACKGROUND: Epidemiological studies have shown that the metabolic syndrome, a combination of type 2 diabetes mellitus, hypertension, dyslipidaemia and a high body mass index (BMI), occurs more frequently among adults who were born with a low birth weight. Because insulin is thought to play a key role in the pathogenesis of this syndrome we investigated insulin sensitivity and risk factors for cardiovascular disease in short prepubertal children born small for gestational age (SGA). PATIENTS AND METHODS: Frequently sampled intravenous glucose tolerance tests (FSIGT) were performed in 28 short prepubertal children born SGA. Short stature was defined as a height < -2SD. SGA was defined as a birth length and/or a birth weight for gestational age < -2SD. Twelve short children born appropriate for gestational age (AGA) were used as controls for the FSIGT's results only. AGA was defined as a birth weight and/or birth length for gestational age > -2SD. In short SGA children, blood pressure (BP), fasting levels of serum free fatty acids (FFA), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) were measured and compared to reference values. RESULTS: Mean insulin sensitivity (Si) level in short SGA children was significantly reduced to 38% of the mean Si level measured in short AGA controls (P = 0.004). Mean acute insulin response (AIR) was significantly higher in SGA children compared to short AGA controls (P < 0.001). Differences in Si and AIR between the two groups remained significant after adjusting for age and BMI (P < 0.001 and P = 0.003, respectively). The mean (SD) systolic BP SDS was 1.3 (1,1), being significantly higher than zero. Mean fasting serum levels of FFA, TC, TG, HDL and LDL were all within the normal range. However, 6 of the 28 SGA children had serum FFA levels above the normal range. Cardiovascular risk factors could statistically be represented in two clusters. Both clusters played a significant role in the development of insulin insensitivity (1/Si). CONCLUSION: Although the metabolic syndrome has been described in adulthood, our study showed that risk factors for the development of type 2 diabetes mellitus and cardiovascular disease are already present during childhood in short prepubertal children born SGA, suggesting a pretype 2 diabetes mellitus phenotype.

Cardiovascular Diseases↗

PubMed2004

The metabolic consequences of prematurity.

An association between low birth weight, commonly a reflection of an adverse in utero environment, and the subsequent development of diseases such as type 2 diabetes and hypertension in later life is now generally accepted - as is an association between an adverse perinatal environment and a permanent reduction in insulin sensitivity. This and other metabolic abnormalities have been demonstrated from childhood through to adulthood in subjects who were born full-term but small for gestational age (SGA). Less is known about children born prematurely into an adverse neonatal environment. We present data demonstrating that premature infants also have metabolic abnormalities similar to those observed in full-term, SGA children, and that these occur irrespective of whether the premature infants are SGA or appropriate for gestational age (AGA).

Child↗

PubMed2004

Increasing prevalence of type 2 diabetes in adolescents.

OBJECTIVE: The rising prevalence of obesity in childhood and adolescence in North America has been paralleled by the emergence of type 2 diabetes in the adolescent age group. We have examined trends in the prevalence of type 2 diabetes in adolescents attending a diabetes clinic in Auckland, New Zealand. METHODS: Surveys of the prevalence of type 2 diabetes in attendees at the adolescent diabetes clinic at the Auckland Diabetes Centre were undertaken in 1996 and 2002. The proportion of type 2 diabetes in incident cases of diabetes diagnosed between these years was also calculated. RESULTS: The prevalence of type 2 diabetes was 1.8% (2/110) in 1996, and 11.0% (18/163) in 2002 (P = 0.008). Type 2 diabetes accounted for 12.5% (6/48) of incident cases of diabetes in the years 1997-1999, and 35.7% (10/28) of cases in the years 2000-2001, indicating a sharp rise in the incidence (P = 0.017) between the two periods. At diagnosis the mean age of the type 2 diabetes subjects was 15 years and the mean body mass index 34.6 kg/m2. Risk factors for cardiovascular disease were common in the subjects with type 2 diabetes: 85% had dyslipidaemia, 58% had increased albumin excretion rates and 28% had systolic hypertension. CONCLUSIONS: Obesity-related type 2 diabetes now accounts for a substantial proportion of newly recognized diabetes in the adolescent age group - and this proportion is escalating rapidly. Adverse cardiovascular risk factors are prevalent in this population. Public health measures to curtail the rise of obesity in childhood and adolescence are required urgently.

Adolescent↗

PubMed2001

The changing presentation of children with newly diagnosed type 1 diabetes mellitus.

Although it is known that the incidence of type 1 diabetes mellitus (DM) in childhood is progressively increasing, it is less clear whether the presentation of newly diagnosed DM is changing. The aim of this study was to establish whether any biochemical or clinical presentation parameters have altered over time. A retrospective study was performed comparing newly diagnosed children with DM in two 24 month time intervals, 8 yrs apart (1988-89 and 1995-96). Fifty-seven children were diagnosed with type 1 DM in 1988-89 and 70 children in 1995-96. At presentation, children born in the later cohort had a higher pH (p < 0.001) and lower serum glucose (p < 0.05). Although the frequency of diabetic ketoacidosis (DKA) was higher in the 1988/89 cohort (63% vs. 42% in 1995/96) the absolute number of children with DKA in each time interval was similar (33 subjects in 1988-89 vs. 30 subjects in 1995/96). Islet cell antibody (ICA) levels were very different between the two cohorts; higher antibody levels were found in the 1988/89 group (p < 0.01). DKA was also associated with higher ICA titres (p < 0.05). Hospital admission stay decreased from 6.5 DS to 3.4 DS over the 8-year period (p < 0.0001). At our institution, the presentation of children with type 1 DM is changing with many more children diagnosed before developing DKA. We speculate that a new environmental factor(s) may be responsible for the absolute increase in patients presenting without DKA, while older etiologies (both genetic and environmental) are responsible for the steady, unchanging number of patients with a more severe presentation. Greater awareness of diabetes in children is not the factor contributing to earlier diagnosis before DKA develops.

Journal Article↗

PubMed2001

Foot-to-foot bioelectrical impedance analysis: a valuable tool for the measurement of body composition in children.

OBJECTIVE: To determine the accuracy of foot-to-foot bioelectrical impedance analysis (BIA) and anthropometric indices as measures of body composition in children. DESIGN: Comparison of foot-to-foot BIA and anthropometry to dual-energy X-ray absorptiometry (DEXA)-derived body composition in a multi-ethnic group of children. SUBJECTS: : Eighty-two European, NZ Maori and Pacific Island children aged 4.9-10.9 y. MEASUREMENTS: DEXA body composition, foot-to-foot bioelectrical impedance, height, weight, hip and waist measurements. RESULTS: Using a BIA prediction equation derived from our study population we found a high correlation between DEXA and BIA in the estimation of fat-free mass (FFM), fat mass (FM) and percentage body fat (PBF) (r=0.98, 0.98 and 0.94, respectively). BIA-FFM underestimated DEXA-FFM by a mean of 0.75 kg, BIA-FM overestimated DEXA-FM by a mean of 1.02 kg and BIA-PBF overestimated DEXA-PBF by a mean of 2.53%. The correlation between six anthropometric indices (body mass index (BMI), ponderal index, Chinn's weight-for-height index, BMI standard deviation score, weight-for-length index and Cole's weight-for-height index) and DEXA were also examined. The correlation of these indices with PBF was remarkably similar (r=0.85-0.87), more variable with FM (r=0.77-0.94) and poor with FFM (r=0.41-0.75). CONCLUSIONS: BIA correlated better than anthropometric indices in the estimation of FFM, FM and PBF. Foot-to-foot BIA is an accurate technique in the measurement of body composition.

Absorptiometry, Photon↗

PubMed2001

Obesity in Auckland school children: a comparison of the body mass index and percentage body fat as the diagnostic criterion.

OBJECTIVES: First, to determine obesity rates in Auckland school children according to their ethnic group using two different criteria: the body mass index (BMI) and percentage body fat (PBF) derived from bioelectrical impedance analysis (BIA). Second to examine the relationship between BMI and body composition across ethnic groups to determine if BMI references from European children accurately reflect obesity in other ethnic groups. DESIGN: A total of 2273 Auckland school children, aged 5-10.9 y had their height, weight and bioelectrical impedance measured. Using these measurements, each child's BMI, fat free mass, fat mass and PBF were derived. RESULTS: In all 14.3% of children were obese using the recommended definition of obesity (BMI) greater than the 95th percentile). There was no clinically significant difference in the relationship between BMI and body composition in different ethnic groups. Obesity rates varied with ethnicity (P<0.0001) and were higher in Pacific Island (24.1%) and Maori (15.8%) than in European children (8.6%). Obesity rates also varied with age (P<0.03), with the highest rates in older children. PBF levels were higher in females than males (P<0.0001). Using a definition of obesity based on percentage body fat (PBF>30%), obesity rates were higher in all ethnic groups. CONCLUSIONS: Obesity rates are high in Auckland school children and there are clear differences in obesity rates in different ethnic groups. If BMI criteria are used to define obesity in our population, we recommend the same standards be used for children of all ethnicities.

Age Factors↗

PubMed2000

Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment.

BACKGROUND: Growth hormone (GH) contributes to insulin resistance, but whether children treated with GH are at increased risk of diabetes has not been established. We undertook a retrospective analysis of data from an international pharmacoepidemiological survey of children treated with GH to find out the incidence of impaired glucose tolerance and types 1 and 2 diabetes mellitus. METHODS: Reports to the survey of abnormal glucose metabolism were investigated and classified. The incidence and age-distribution of type 1 diabetes were compared with values from a model of reference data. The incidence of type 2 diabetes was compared with data from two reports of children not treated with GH. FINDINGS: 85 (0.36%) of 23333 children were reported with abnormal glucose metabolism. After investigation, 43 had confirmed glucose disorders (11 with type 1 diabetes, 18 with type 2 diabetes, and 14 with impaired glucose tolerance). The incidence and age at diagnosis of type 1 diabetes in children treated with GH did not differ from expected values. The incidence of type 2 diabetes was 34.4 cases per 100000 years of GH treatment which was six-fold higher than reported in children not treated with GH. Type 2 diabetes did not resolve after GH therapy was stopped. INTERPRETATION: GH treatment did not affect the incidence of type 1 diabetes mellitus in any age group. We postulate that the higher than expected incidence of type 2 diabetes mellitus with GH treatment may be an acceleration of the disorder in predisposed individuals.

Adolescent↗

PubMed2000

Limitations of first-phase insulin response to evaluate insulin secretion in children.

UNLABELLED: The first-phase insulin response (FPIR) is a widely used method to evaluate beta-cell function during the prediabetic phase of evolving type 1 diabetes mellitus (DM). The aim of the present study was to evaluate the influence of clinical and methodological variables on FPIR in normal children and adolescents. Children and adolescents who were first-degree relatives of those with type 1 DM and healthy young adults were studied. All subjects were islet cell antibody-negative. A FPIR test was performed on all subjects while fasting. Insulin samples were drawn at 0, 1, 2, 3, 4, 5, 6, 8, and 10 min after 0.3 g/kg of dextrose. FPIR(1-10) was calculated as the area under the FPIR curve corrected for baseline. Eighty-five subjects aged 4-22 yr were studied, 43 of whom were pre-pubertal, 24 pubertal, and 18 post-pubertal. FPIR(1-10) values were lower in the pre-pubertal group when compared to either the pubertal and post-pubertal groups (415 [179-965, 2SD], 756 [256-2 223] and 684 [235-1 180] mU/L, respectively; p<0.05). Obese subjects had a higher FPIR than non-obese subjects (856 vs. 520 mU/L; p<0.005). Despite correcting for the influence of puberty and obesity, there remained considerable unaccounted variability in FPIR(1-10) (R=0.46). Further variables found to influence FPIR(1-10) were: fasting insulin level (r(2)=0.49); weight for length index (r(2)=0.38); peak blood glucose level (r(2)=0.38, all p<0.001); and pre-pubertal age (r(2)=0.20, p<0.05). CONCLUSION: FPIR exhibited wide inter-subject variability and was influenced by a number of clinical and methodological factors that make interpretation more difficult without more specifically defined standards.

Journal Article↗

PubMed2000

Impaired insulin-mediated glucose uptake in monocytes of short children with intrauterine growth retardation.

AIMS: To determine whether there was an impairment in insulin-mediated glucose uptake in monocytes from short children with intrauterine growth retardation (IUGR) when compared with control subjects. METHODS: Circulating monocytes were isolated by histopaque gradient separation followed by adherence. Monocytes were incubated with insulin at the following concentrations; 0, 0.1, 0.2, 0.6, 1, 2 and 6 nm. 2-deoxyglucose (2-DG) uptake was measured after incubation with [(3)H]2-DG and expressed as pmol/min/10(6) cells. Insulin-stimulated glucose uptake was determined in two ways: 6 nm insulin concentration minus baseline (6-0 nm) and the regression slope of glucose uptake over the range of log insulin concentrations (slope value). Insulin sensitivity was determined from a 90-min frequently sampled intravenous glucose tolerance test with the minimal model. RESULTS: Short children with IUGR (n = 16) had lower slope (4.6 +/- 1.1 vs. 9.5 +/- 2.0, p = 0.002) and 6-0 nm (8 +/- 2 vs. 15 +/- 3 pmol/min/10(6) cells, p = 0.048) glucose uptake values than normal children (n = 11). There was no difference in baseline glucose uptake between IUGR and normal children (36 +/- 5 vs. 48 +/- 7 pmol/min/10(6) cells). In the five subjects with IUGR that were evaluated, the in vivo insulin sensitivity index and glucose effectiveness were found to be positively correlated with insulin-mediated glucose uptake in monocytes (r = 0.54) and baseline glucose uptake in monocytes, respectively (r = 0.69). CONCLUSIONS: Short children with IUGR have impairment in insulin-mediated glucose uptake in monocytes when compared with normal children. Our hitherto limited data indicate that insulin-mediated glucose uptake in monocytes is correlated with in vivo assessment of insulin sensitivity in children with IUGR.

Journal Article↗

PubMed2000

Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition.

Environmental factors and diet are generally believed to be accelerators of obesity and hypertension, but they are not the underlying cause. Our animal model of obesity and hypertension is based on the observation that impaired fetal growth has long-term clinical consequences that are induced by fetal programming. Using fetal undernutrition throughout pregnancy, we investigated whether the effects of fetal programming on adult obesity and hypertension are mediated by changes in insulin and leptin action and whether increased appetite may be a behavioral trigger of adult disease. Virgin Wistar rats were time mated and randomly assigned to receive food either ad libitum (AD group) or at 30% of ad libitum intake, or undernutrition (UN group). Offspring from UN mothers were significantly smaller at birth than AD offspring. At weaning, offspring were assigned to one of two diets [a control diet or a hypercaloric (30% fat) diet]. Food intake in offspring from UN mothers was significantly elevated at an early postnatal age. It increased further with advancing age and was amplified by hypercaloric nutrition. UN offspring also showed elevated systolic blood pressure and markedly increased fasting plasma insulin and leptin concentrations. This study is the first to demonstrate that profound adult hyperphagia is a consequence of fetal programming and a key contributing factor in adult pathophysiology. We hypothesize that hyperinsulinism and hyperleptinemia play a key role in the etiology of hyperphagia, obesity, and hypertension as a consequence of altered fetal development.

Animal Nutritional Physiological Phenomena↗

PubMed1997

Insulin resistance in short children with intrauterine growth retardation.

Epidemiological studies have demonstrated an association between intrauterine growth retardation and an increased risk of adult diseases that include essential hypertension, noninsulin-dependent diabetes mellitus, and ischemic heart disease. A common feature of these diseases is insulin resistance. To investigate whether abnormal insulin sensitivity was a characteristic of subjects with intrauterine growth retardation (IUGR), we compared two groups of short prepubertal children: a group with IUGR (birth weight less than the tenth percentile; n = 15) and a normal birth weight group (n = 12). Subjects underwent a modified frequently sampled iv glucose tolerance test that permitted calculation of the acute insulin response, insulin sensitivity index, and glucose effectiveness. A marked difference in the insulin sensitivity index was noted between groups, with the IUGR group being less insulin sensitive [6.9 vs. 16.9 10(-4)min-1.(microU/mL); P = 0.0048]. The acute insulin response was also significantly different between groups, with IUGR subjects having higher insulin levels (445 vs. 174 microU/mL; P = 0.005). There was no difference in glucose effectiveness between groups. Short prepubertal IUGR children have a specific impairment in insulin sensitivity compared to their normal birth weight peers. In short IUGR children, impaired insulin sensitivity is a potential marker for the early identification and intervention in the development of late adult-onset noninsulin-dependent diabetes mellitus.

Birth Weight↗

PubMed1996

High and low dose initial thyroxine therapy for congenital hypothyroidism.

OBJECTIVE: To assess factors influencing thyroxine (T4) levels 1 month after initiating replacement therapy for congenital primary hypothyroidism. METHODOLOGY: A retrospective review of 41 children with congenital hypothyroidism who received either high or low dose initial T4 therapy. Thyroid scintiscan was performed, and T4 levels determined before starting treatment and after 1 month. RESULTS: T4 levels at 1 month were correlated (r2 = 0.38, P < 0.001) with the pretreatment T4 level (r = 0.48), as well as with the T4 dose (r = 0.46). Suboptimal treated T4 levels (< 130 nmol/L) were seen with greater frequency in infants with thyroid agenesis (7/11) rather than ectopia (7/28, P < 0.03), despite receiving similar doses of thyroxine. Infants with suboptimal treated T4 levels had lower pretreatment T4 levels than those with optimal levels (21 +/- 7 vs 48 +/- 34 nmol/L, P < 0.02). Biochemical hyperthyroidism (T4 > 216 nmol/L) occurred in six patients; four of six had ectopia. CONCLUSIONS: These data suggest that infants with little residual thyroid function should receive higher initial T4 doses than those with significant ectopia.

Congenital Hypothyroidism↗

PubMed1995

Newborn screening for congenital adrenal hyperplasia in New Zealand.

OBJECTIVE: To evaluate the efficacy and efficiency of newborn screening for classic congenital adrenal hyperplasia (CAH) in New Zealand. DESIGN: All infants younger than 6 weeks of age identified by newborn screening between December 1984 and December 1993 were included. RESULTS: 23 cases of classic CAH (20 salt-losers) were identified. The incidence of classic CAH was 1 in 23,344. Screening identified 3 of 9 virilized female infants whose disease had not been detected clinically. Screening alone identified all 11 male infants. Notification of cases occurred at 11 +/- 3 days of age. There was a delay in treatment of the group identified by screening alone (n = 14) until 13 days of age (range, 4 to 35 days); at that time 11 infants had hyponatremia and 10 had hyperkalemia. Symptoms of vomiting, poor feeding, and shock were common after 10 days of age (2/10, < 10 days, and 8/8, 11 to 16 days of age). CONCLUSIONS: Newborn CAH screening is the only method of identifying male infants with classic CAH without a family history of CAH before symptoms develop, as well as a significant portion of overlooked virilized female infants. So that clinical or significant biochemical deterioration can be avoided, pediatrician notification of screening results and treatment should be started before 10 days of age.

Adrenal Hyperplasia, Congenital↗