Prevention and early detection of type 2 diabetes in children and adolescents.

Type 2 ("adult-onset") diabetes in young adults and children has become increasingly common over the last 10 years, and has been described as an "emerging epidemic." The financial and societal ramifications of such a development are substantial and demand a prompt and aggressive public health response. Emphasis must be placed upon preventive behaviors and early detection, and creation of new public policy to address the related societal issues. Recommendations for prevention and screening of high-risk children and adolescents are provided.

Body mass index (BMI) in Turner Syndrome before and during growth hormone (GH) therapy.

OBJECTIVE: To study whether body mass index (BMI) is different in girls with Turner syndrome (TS) compared to normal girls, and whether BMI in TS is affected by growth hormone (GH) treatment. DESIGN: A retrospective cross-sectional study. SUBJECTS: 2468 girls with TS enrolled in the National Cooperative Group Study (NCGS), a collaborative surveillance study for assessing GH-treated children. MEASUREMENTS: BMI and BMI standard deviation score (BMI SDS) at baseline and during GH treatment were computed from height and weight data. RESULTS: BMI in TS patients increases with age as expected. However, BMI SDS increased starting at about age 9 y. A similar pattern of increase in BMI SDS was observed after each year of GH treatment for up to 4 y, but GH treatment did not change the magnitude of increase. BMI and BMI SDS curves before and during GH treatment were essentially superimposable. CONCLUSION: These findings suggest that mechanisms specific for TS are responsible for the age-related increase in BMI SDS. This increase was unaffected by GH treatment.

Effect of newborn screening for congenital adrenal hyperplasia.

OBJECTIVE: To compare the incidence of diagnosis and morbidity in newborns who were screened with newborns who were not screened for congenital adrenal hyperplasia (CAH). DESIGN: A retrospective cohort study. SETTING: Arkansas, Oklahoma, and Texas. PATIENTS: An unscreened population in Arkansas and Oklahoma (n = 400118) was compared with a screened population in Texas (n = 1613378) during a 5-year period. Simultaneous data were collected on the incidence of diagnosis and associated morbidity in patients with CAH. MAIN OUTCOME MEASURES: Diagnosis of CAH, age (in days) at diagnosis, and frequency and length of initial hospitalization. RESULTS: The incidence of diagnosis of classic CAH per 100000 newborns in the unscreened cohort (5.75) and in the screened cohort (6.26) was similar (relative risk, 0.92; 95% confidence interval, 0.58-1.44). The unscreened group had 0.73 fewer male newborns with salt-wasting CAH diagnosed per 100000 newborns (relative risk, 0.73; 95% confidence interval, 0.35-1.56). The median age at diagnosis was 26 days for male newborns with salt-wasting CAH in the unscreened cohort vs 12 days in the screened cohort (z = 2.49; P = .01). Male newborns with simple-virilizing CAH and newborns with nonclassic CAH were detected only in the screened cohort. CONCLUSIONS: There was not a statistically significant (P = .73) increase in the diagnosis of salt-wasting CAH in the screened cohort. Male newborns benefited as a result of significantly (P = .01) earlier diagnosis, reduced morbidity, and shorter lengths of hospitalization. Large collaborative studies or meta-analyses are needed to determine the life-saving benefits of screening.

Lipoprotein changes in relation to body mass index in Native American adolescents.

In view of their known high incidence of noninsulin dependent diabetes (NIDDM), we sought to determine whether Native American (Plains Indian) children and adolescents show evidence of risk factors for both NIDDM and cardiovascular disease. Children and adolescents between the ages of 4 and 19 y were recruited, and field days were organized for data collection, which included height, weight [to compute body mass index (BMI)], waist and hip circumference, family histories, quantum of Native American ancestry, and blood sampling for fasting lipids, apolipoproteins, insulin, and glucose. BMI increased with age in boys and girls and tended to be higher than in Caucasian children. The difference was significant in 5-9-y-old (p < 0.05) and 10-14-y-old (p < 0.05) boys and 10-14-y-old girls (p < 0.001). Ten- to 14-y-old girls in the highest quartile for BMI had higher triglyceride levels (p < 0.05) and lower HDL cholesterol (p < 0.001) when compared with those in the lower quartiles. In contrast, 15-19 y olds in the highest quartile for BMI had higher cholesterol, LDL cholesterol, and apolipoprotein B (p < 0.001). The mean fasting insulin levels were not related to BMI. The data suggest that, within this Plains Indian population, obesity associated with elevated lipid levels tends to begin at an early age in Native American children. Insulin levels do not appear to be related to BMI, a putative index of adiposity, in this population of children known to be prone to NIDDM in adult life.

FH Tulsa-1 and -2: two unique alleles for familial hypercholesterolemia presenting in an affected two-year-old African-American male.

A two-year-old African American boy presented with cutaneous xanthomata and extreme hypercholesterolemia. Subsequent studies revealed that the LDL-cholesterol was 1,001 mg/dl and apoB 507 mg/dl. LDL-receptor activity was almost undetectable, which is compatible with the finding of two newly described defective alleles on exon 4 of the LDL-receptor gene coding for part of the ligand-binding domain. One allele contained a 21 base-pair insertion from codon 200 to 207 whereas the other had a point mutation at codon 207. The rarity of genes for FH reported in individuals of African ancestry is discussed.

A microcalorimetric investigation of the interaction of surfactants with crystalline and partially crystalline salbutamol sulphate in a model inhalation aerosol system.

PURPOSE: The purpose of the work is to study the adsorption of Oleic acid and Span 85 (materials frequently used in aerosols as surfactants) onto partially amorphous and essentially crystalline salbutamol sulphate, attempting to understand the behaviour of metered dose inhalers (MDIs) and observing whether there were any differences in adsorption behaviour and if this could be related to the surface properties of the powder. METHODS: Isothermal titration microcalorimetry was the principal technique used to measure the adsorption behaviour of surfactants to salbutamol sulphate. A Malvern particle size analyzer was also employed to provide size data on the interactions between the surfactant and powder suspensions. RESULTS: The calorimetric data revealed that surfactant adsorption to the crystalline micronised powder (78% RH and aged dry sample) produced significant exotherms, whereas adsorption to the partially amorphous micronised powder resulted in small heat responses. The differences in adsorption behaviour to the partially crystalline and crystalline surfaces resulted in changes in aggregation behaviour. CONCLUSIONS: The stability of MDIs varies depending on the water content, crystallinity and surface composition of the powder. The advantages of using isothermal titration microcalorimetry to evaluate this surface behaviour in such difficult systems was demonstrated.

Child and maternal adaptation to cystic fibrosis and insulin-dependent diabetes mellitus: differential patterns across disease states.

Investigated the relationship between maternal and child emotional adaptation both across and within samples of children with cystic fibrosis (CF) and insulin-dependent diabetes mellitus (IDDM). Higher levels of maternal depression were associated with increased depression in children with IDDM. In addition, increased illness severity and greater length of time since diagnosis were related to increased depression in children with IDDM. Whereas maternal depression was related to decreased trait anxiety for children in the CF group, neither maternal anxiety or depression were associated with child depression or state anxiety. Empirical and clinical implications of a disease-specific approach to studying chronic disease in children are discussed.

Lipids and apolipoproteins in growth hormone-deficient children during treatment.

The role of growth hormone (GH) in regulating the transport of plasma lipoproteins has not been clearly defined, but past studies suggest that GH may influence cholesterol levels. This protocol was designed to evaluate possible changes in lipid and apolipoprotein status in GH-deficient children and children with neurosecretory dysfunction (NS) before GH therapy and at intervals after GH therapy was started. Twenty children with classic GH deficiency were evaluated, and 28% were hyperlipidemic at the onset of the study. Seven children were evaluated in the NS group, and only one (14%) showed an elevated total cholesterol (TC) greater than 200 mg/dL. The mean TC for all the GH-deficient children was elevated above the normal range, but not for the NS group. The mean apolipoprotein (apo) C-III level and its heparin-precipitated fraction (HP) were also elevated in the GH-deficient group, but only the apo C-III HP was elevated in the NS group. A standard replacement dose of recombinant methionyl GH was used, and therapy had no significant effect on TC or triglyceride (TG) levels. Apo C-III HP, a marker of hypertriglyceridemia, increased after the start of therapy, but no other lipoprotein levels changed significantly in the GH-deficient group. No changes were seen with treatment in the NS group. The longitudinal design of this study allowed demonstration of the later changes in the apolipoproteins and the presence of a distinct subset of patients with both GH deficiency and hypercholesterolemia. This study supports the role of GH in modulating lipid metabolism.

Thyroxine and triiodothyronine autoantibodies in Hashimoto's thyroiditis with severe hormone-resistant hypothyroidism.

Severe hypothyroidism in an 8 year-old girl was associated with a paradoxically high free thyroxine (T4), a high TSH level and antimicrosomal antibodies suggestive of Hashimoto's thyroiditis. Low radiolabelled T3 binding to resin in the standard T3 resin uptake test suggested thyroid hormone binding which was subsequently found to be due to antibodies to T4. T4 by equilibrium dialysis was very low confirming that conventional free T4 and total T4 assays overestimated the true values. Subsequent normalization of free T4 by dialysis coincided with a decline in the T4 autoantibody titer allowing a change in treatment from Cytomel (triiodothyronine) to Synthroid (L-thyroxine) while maintaining therapeutic efficacy.

Hyperlipidemia in children.

Advances toward improving cardiovascular health of tomorrow's adults lie both in acknowledging that the pathogenesis of atherosclerosis begins in childhood and in considering the influence of environmental factors on genetic endowment of risk. Based on current understanding of lipoprotein transport processes, an array of genetic disorders with various degrees of atherogenicity can be classified according to the predominant lipoprotein density class, as represented by a standard lipid profile, and then further defined by assaying apolipoproteins and their receptors, lipoprotein transport enzymes, or the respective variant genes. Alternatively, a simple and potentially cost-effective representation of multifactorial influences on lipid transport is provided by an assessment of apolipoprotein particle composition using serial immunologic precipitation of apolipoproteins while on their intact plasma lipoproteins. A comprehensive intervention strategy can be based on identification of inherited risk and the effects of nongenetic factors, which include dietary excess, inactivity, disease states, and medications.

Composition of plasma ApoA-I-containing lipoprotein particles in children and adults.

The purpose of this study was to examine sex- and age-related differences in the concentration and composition of lipoprotein particles containing apoA-I (LP-A-I) and those containing apoA-I and apoA-II (LP-I:A-II), the main HDL as defined by their apolipoprotein composition. Lipoproteins were isolated by immunoaffinity chromatography of whole plasma from 16 normal prepubertal children and 15 normal male and female adults using "pan"-MAb to apoA-I and apoA-II. Although there was no difference between children and adults in the concentration of LP-A-I:A-II, adult females had significantly higher levels of LP-A-I than either children or adult males. Main differences between children and adults as well as between adult males and females were in the apolipoprotein composition of the lipoprotein particles; children had the highest content of minor apolipoproteins (apoC and apoE) in LP-A-I but the lowest in LP-A-I:A-II. The lipid/apolipoprotein ratios of LP-A-I and LP-A-I:A-II were significantly higher in children and women than in men. The LP-A-I and LP-A-I:A-II contained 75% of the total plasma apoC and apoE in women and children but only 50% in men. However, in all three groups, 70-90% of the minor HDL apolipoproteins were associated with LP-A-I:A-II. The nonmolar ratios of minor apolipoproteins in LP-A-I and LP-A-I:A-II and the sex- and age-related differences in apoA-I/apoA-II ratios of LP-A-I:A-II suggest that both lipoproteins may consist of a spectrum of lipoprotein subfamilies differing in their apolipoprotein composition.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetic ketoacidosis at the Children's Hospital of Oklahoma: a review on presentation and management.

Examination of 394 cases of diabetic ketoacidosis presenting at the Children's Hospital of Oklahoma from 1975 to 1987 has indicated a higher frequency of very young patients with low insulin requirements and frequent presentation in the winter months. The severity of the preceding hyperglycemia varies widely as indicated by the range of glycosylated hemoglobin values at the time of diagnosis. In addition we have identified measures to prevent the main hazards occurring during therapy which are related to potassium replacement and correction of dehydration without causing cerebral edema. The general principles of management are reviewed and we have selected certain aspects for emphasis and discussion based on past experience.

C-terminal domain of apolipoprotein CII as both activator and competitive inhibitor of lipoprotein lipase.

In this study we have prepared peptides of the C-terminal domain of apolipoprotein CII (ApoCII) by a solid-peptide-synthesis technique and demonstrated that the C-terminal tetrapeptide, Lys-Gly-Glu-Glu, represents an inhibitor of lipoprotein lipase. The tetrapeptide not only inhibits the basal activity of lipoprotein lipase, but also blocks the activation effect of native ApoCII. The lengthening of this tetrapeptide resulted in a corresponding increase in affinity for lipoprotein lipase. This suggested that amino acids other than those of the C-terminal tetrapeptide also contribute to the binding affinity of ApoCII for lipoprotein lipase. On the basis of an essential requirement of the ApoCII terminal domain for binding to lipoprotein lipase, we suggest that the initial interaction of ApoCII, mediated via the C-terminal tetrapeptide, promotes the proper alignment of ApoCII with lipoprotein lipase, followed by the weak interaction of the ApoCII activator domain with the lipoprotein lipase activator site, enhancing the lipolysis process.

Dominantly inherited childhood gigantism resembling Sotos' syndrome.

Excessive growth in infancy and onset of puberty at age four was observed in a boy with features resembling Sotos syndrome. Early development of secondary sexual characteristics and advanced osseous maturation were observed. The family history was significant; excessive weight gain tended to occur in female family members in association with rapid growth in infancy and childhood. A delayed insulin response to glucose was observed in both mother and sister, and diabetes developed during his mother's gestation. These observations suggest that undetermined factors associated with excessive growth may be inherited as a dominant trait with variable expression.

Plasma apolipoprotein C-III levels in children with type I diabetes.

The serum concentrations of apolipoproteins C-III, B, and A-I were determined in children with type I diabetes mellitus to establish whether they correlated with the level of glycosylated hemoglobin (Hb A1) and to determine whether these values differ between diabetic children and a population of normal children. Triglyceride (TG), total cholesterol (TC), and apolipoprotein (Apo) levels were studied in 95 children with type I diabetes; 51 of the children were attending a diabetes clinic and 44 were attending a diabetes summer camp. The level of Hb A1 correlated with Apo C-III (P less than .001) and TC (P less than .001) values in the clinic group, but not with Apo A-I or TG levels in either group. The Apo C-III level was higher in both groups of diabetic children (8.0 +/- 0.5 and 9.5 +/- 0.4 mg/dl) (P less than .01) than in normal subjects (6.1 +/- 0.2 mg/dl). We conclude that the Apo C-III level tends to be higher in diabetics than in normal subjects, even in the normotriglyceridemic camp group. The Apo C-III level correlated with both the TC level and Hb A1, suggesting that Apo C-III determinations in type I diabetic patients may permit early identification of atherosclerotic risk.

Child and Adolescent Athletes With Diabetes.

In brief: The common desire to participate in sports can be harnessed to encourage children and adolescents with type 1 diabetes to participate actively in controlling their disease. This is partly because the diabetic who successfully learns to control blood glucose during exercise by wise regulation of diet and insulin is rewarded with enhanced athletic performance. Age, duration of the diabetes, insulin dosage, hypoglycemia, seasonality, training, duration of training periods, and calorie intake must be considered in prescribing specific exercise regimens for diabetic youngsters. To participate in endurance sports, persons with diabetes must manage the effects of exogenous insulin on their normal triphasic metabolic fuel supply derived from muscle, liver, and adipose tissue. If educational guidelines are followed and potential risks due to complications are taken into account, the benefits of regular exercise early in the course of the disease outweigh potential disadvantages.

Plasma lipids and apolipoproteins in a 13-year-old boy with diabetic ketoacidosis and extreme hyperlipidemia.

A 13-year-old boy with untreated diabetes presented in severe ketoacidosis (DKA) for the first time with an initial triglyceride (TG) level of 14,461 mg/dl. Serial blood samples were drawn to determine the interrelationships of changes in lipids and apolipoproteins during treatment with insulin and intravenous fluids. The TG level declined to 122 mg/dl in 7 days concomitant with a lowering of apolipoproteins C-II, C-III, E, D, and F. Further observations suggested that the TG-rich lipoproteins underwent degradation associated with a decline in the levels of apolipoproteins associated with very low density lipoprotein (VLDL) in contrast to an increase in high density lipoprotein-cholesterol (HDL-C), ApoA-I and ApoA-II. ApoB and low density lipoprotein cholesterol (LDL-C) were increased transiently. Subsequent therapy with continuous subcutaneous insulin infusion (CSII) were effective in maintaining glucose homeostasis and normolipidemia for 6 months.

Increased levels of HDL-cholesterol and apolipoprotein A-I after intensified insulin therapy for diabetes.

Sixteen subjects with insulin-dependent diabetes mellitus were studied to determine whether changes in plasma lipids and apolipoproteins follow intensified control using preprandial doses of regular insulin with an additional dose of NPH insulin before bedtime. The mean total dialy dose of insulin was increased from 1.03 +/- 0.09 to 1.17 +/- 0.44 units/kg throughout the six-month period. Levels of HDL-cholesterol and apolipoprotein A-I increased without significant changes in hemoglobin A1 (HbA1), triglyceride, or cholesterol. These findings suggest that increases in HDL-cholesterol and apolipoprotein A-I were a result of the intensified insulin delivery.