Peter M. Wolfgram

Long-term effects of recombinant human growth hormone therapy in children with Prader-Willi syndrome.

Purpose of review Recombinant human growth hormone (hGH) therapy in children with Prader–Willi syndrome (PWS) improves linear growth, body composition, physical strength and agility, and other metabolic parameters. These benefits must be weighed against potential adverse effects, including rare occurrences of sudden death. This review summarizes recent evidence important to a benefit–risk analysis of hGH use in children with PWS. Recent findings Studies consistently show that hGH improves stature, body composition, fat percentage and distribution, and other metabolic markers in children with PWS. Preliminary reports of improved cognitive development during hGH have also emerged. Scoliosis progression is influenced by growth rate, but frequency of occurrence and severity are not increased by hGH exposure. PWS genotype does not appear to affect response to hGH. Concerns about hGH-associated sudden death persist, but recent studies show either absence of change in sleep-disordered breathing or improved sleep cardiovascular function during hGH therapy. Summary Recent studies confirm and expand reported benefits of hGH therapy in children with PWS, including a possible salutary role in cognitive development. These findings support previous assertions that hGH can reduce morbidity and improve function in children with PWS, and suggest that potential risks of such treatment are favorably balanced by its benefits.

Is Waist Circumference a Better Predictor of Insulin Resistance Than Body Mass Index in U.S. Adolescents

PURPOSE To determine whether waist circumference (WC) is a better predictor of insulin resistance (IR) than body mass index (BMI) in U.S. adolescents aged 12-18 years. METHODS Using data from the National Health and Nutrition Examination Survey 1999-2002, we evaluated an ethnically diverse sample of 1,571 adolescents with regard to BMI, WC, and fasting glucose and insulin levels. Children were classified as having IR if they had a homeostasis model assessment of insulin resistance (insulin [U/mL] × glucose [mmol/L]/22.5) of greater than 4.39.We created receiver operating characteristic curves predicting IR across various thresholds of WC and BMI, and area under the curve was compared. RESULTS The prevalence rate of IR in the study population was 11.8%. Measures of test performance (sensitivity and specificity) for predicting IR were similar for abnormal BMI and WC thresholds; that is, thresholds of BMI 85th% and WC 75th% and thresholds of BMI 95th% and WC 90th% were quite similar. There were no significant differences in area under the curve for WC versus BMI (.85; 95% CI, .83-.88; p = .84) either for the overall population or for specific racial groups. CONCLUSIONS WC does not seem to provide a distinct advantage over BMI for identifying adolescents with IR.

Predicting Hepatic Steatosis in a Racially and Ethnically Diverse Cohort of Adolescent Girls

OBJECTIVE To develop a risk assessment model for early detection of hepatic steatosis using common anthropometric and metabolic markers. STUDY DESIGN This was a cross-sectional study of 134 adolescent and young adult females, age 11-22 years (mean 13.3±2 years) from a middle school and clinics in Madison, Wisconsin. The ethnic distribution was 27% Hispanic and 73% non-Hispanic; the racial distribution was 64% Caucasian, 31% African-American, and 5% Asian, Fasting glucose, fasting insulin, alanine aminotransferase (ALT), body mass index (BMI), waist circumference (WC), and other metabolic markers were assessed. Hepatic fat was quantified using magnetic resonance imaging proton density fat fraction (MR-PDFF). Hepatic steatosis was defined as MR-PDFF>5.5%. Outcome measures were sensitivity, specificity, and positive predictive value (PPV) of BMI, WC, ALT, fasting insulin, and ethnicity as predictors of hepatic steatosis, individually and combined, in a risk assessment model. Classification and regression tree methodology was used to construct a decision tree for predicting hepatic steatosis. RESULTS MR-PDFF revealed hepatic steatosis in 16% of subjects (27% overweight, 3% nonoverweight). Hispanic ethnicity conferred an OR of 4.26 (95% CI, 1.65-11.04; P=.003) for hepatic steatosis. BMI and ALT did not independently predict hepatic steatosis. A BMI>85% combined with ALT>65 U/L had 9% sensitivity, 100% specificity, and 100% PPV. Lowering the ALT value to 24 U/L increased the sensitivity to 68%, but reduced the PPV to 47%. A risk assessment model incorporating fasting insulin, total cholesterol, WC, and ethnicity increased sensitivity to 64%, specificity to 99% and PPV to 93%. CONCLUSION A risk assessment model can increase specificity, sensitivity, and PPV for identifying the risk of hepatic steatosis and guide the efficient use of biopsy or imaging for early detection and intervention.

Ethnic differences in the effects of hepatic fat deposition on insulin resistance in nonobese middle school girls

In nonobese youth, to investigate whether hepatic fat deposition and its metabolic consequences vary between ethnic groups.

Severe Hypertriglyceridemia Causing Acute Pancreatitis in a Child with New Onset Type I Diabetes Mellitus Presenting in Ketoacidosis

A 10 year old girl presented with severe diabetic ketoacidosis (DKA) and a hemoglobin A1C of 17.9%. On hospital day 2 after acidosis had improved it worsened and she developed excruciating abdominal pain. Her serum triglycerides and lipase levels were found to be extremely high and ultrasound analysis of the pancreas was consistent with acute pancreatitis. She was diagnosed with acute pancreatitis secondary to hypertriglyceridemia. The pancreatitis resolved completely and two months later her hemoglobin A1C was 8.2% and the serum triglycerides were normal. Severe hypertriglyceridemia from insulin deficiency causing pancreatitis in new onset type 1 diabetes mellitus is a rare but serious complication of DKA in children.

In Nonobese Girls, Waist Circumference as a Predictor of Insulin Resistance Is Comparable to MRI Fat Measures and Superior to BMI

Objective: The aim of this study was to investigate the degree to which waist circumference (WC), body mass index (BMI), and magnetic resonance imaging (MRI)-measured abdominal fat deposition predict insulin resistance (IR) in nonobese girls of diverse racial and ethnic backgrounds. Methods: Fifty-seven nonobese girls (12 African-American, 16 Hispanic White, and 29 non-Hispanic White girls) aged 11-14 years were assessed for WC, MRI hepatic proton density fat fraction, visceral and subcutaneous adipose tissue volume, BMI Z-score, fasting insulin, homeostasis model of assessment (HOMA)-IR, adiponectin, leptin, sex hormone-binding globulin, high-density lipoprotein cholesterol, and triglycerides. Results: Univariate and multivariate analyses adjusted for race and ethnicity indicated that only WC and visceral adipose tissue volume were independent predictors of fasting insulin and HOMA-IR, while hepatic proton density fat fraction, BMI Z-score, and subcutaneous adipose tissue volume were dependent predictors. Hispanic White girls showed significantly higher mean fasting insulin and HOMA-IR and lower sex hormone-binding globulin than non-Hispanic White girls (p < 0.01). Conclusions: In nonobese girls of diverse racial and ethnic backgrounds, WC, particularly when adjusted for race or ethnicity, is an independent predictor of IR comparable to MRI-derived measurements of fat and superior to the BMI Z-score.

Polyglandular autoimmune syndrome type I - a novel AIRE mutation in a North American patient.

Abstract Autoimmune polyglandular syndrome type 1 (APS-1), also referred to as autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED), is a rare autoimmune disease that results from autosomal recessive mutations of the human autoimmune regulatory (AIRE) gene. We present the case of a 17-year-old North American girl of primarily Norwegian descent with a novel AIRE gene mutation causing APS-1. In addition to the classic triad of chronic candidiasis, hypoparathyoidism and autoimmune adrenocortical insufficiency, she also has vitiligo, intestinal malabsorption, autoimmune hepatitis, autoimmune hypothyroidism, myositis, myalgias, chronic fatigue, and failure to thrive. Genetic testing revealed heterozygosity for c.20_115de196 and c.967_979del13 mutations in the AIRE gene. The AIRE gene c.20_115de196 mutation has not been previously reported.

998 Reducing unnecessary iv starts in children with diabetes presenting to the emergency department

Background Unnecessary medical interventions prolong emergency department (ED) stays and increase costs. We found that 83% of children with diabetes mellitus (DM) presenting to the ED not in diabetic ketoacidosis (DKA) underwent unnecessary IV placement. Objectives We aimed to decrease IV placements to 20% within 18 months for children presenting to the ED with known DM not meeting DKA criteria. Methods This QI project was conducted in a tertiary care paediatric ED and included children with known DM. Plan-do-study-act cycles included point-of-care (POC) testing, order panel use, and DKA clinical care and nursing guidelines. Outcome measures, analysed on statistical process control charts, included number of IV starts and time to first bicarbonate result. The percent of patients receiving unnecessary IV starts was analysed using the Chi-square test. Process measures included rate of POC testing and order panel utilisation. Results Between January 2015 and July 2017, 294 DM patients were evaluated for DKA. 168 patients (57%) did not meet DKA criteria. In those patients without DKA, the overall number of unnecessary IV starts decreased from 83% pre-interventions to 41% post-interventions (p<0.001; Fig 1). In the same 168 patients, mean time to first bicarbonate decreased from 78 to 29 min (62%) after implementation of all four interventions (Fig 2). Use of POC testing and order panels increased from zero to 92% and 75%, respectively. Conclusions Using QI methodology, we achieved a meaningful reduction in unnecessary IV starts and time to DKA determination in patients presenting with known DM found not to have DKA.Abstract 998 Figure 1 P Chart: proportion of patients with IV start (Pts. with DM without DKA)Abstract 998 Figure 2 X-bar chart: reduction in time to first HCO3 (All DM patients presenting with concern for DKA)

State-to-state variability in Title V coverage for children with diabetes

Title V programs are federally supported safety nets for children with chronic diseases. However, using the example of children with diabetes mellitus, Title V program eligibility and scope of coverage vary by state and may result in health coverage gaps for high-risk patients.