Lynne L. Levitsky

ESPE/LWPES consensus statement on diabetic ketoacidosis in children and adolescents

Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (TIDM). Mortality is predominantly related to the occurrence of cerebral oedema; only a minority of deaths in DKA are attributed to other causes. Cerebral oedema occurs in about 0.3–1% of all episodes of DKA, and its aetiology, pathophysiology, and ideal method of treatment are poorly understood. There is debate as to whether physicians treating DKA can prevent or predict the occurrence of cerebral oedema, and the appropriate site(s) for children with DKA to be managed. There is agreement that prevention of DKA and reduction of its incidence should be a goal in managing children with diabetes.

Energy expenditure and body composition in Prader-Willi syndrome☆

Abstract Patients with Prader-Willi syndrome are frequently obese. To determine if obesity is partially explained by a low energy expenditure, we compared total daily energy expenditure, basal metabolic rate, and body composition in Prader-Willi patients with obese controls. Total energy expenditure was measured by doubly labeled water, basal metabolic rate was measured by respiratory gas analysis using an open-system canopy design, and body composition was calculated from total body water determinations using 18 O labeled water. In six Prader-Willi subjects, basal metabolic rates were normal when compared on the basis of fat free mass, but not body surface area or height, weight, and age. Ten Prader-Willi subjects (8 to 24 years-old) had a total daily energy expenditure (± SD) of 1,980 ± 580 kcal/d, which was 47% less than their obese controls (3,700 ± 820 kcal/d). When normalized for their smaller fat free mass and body mass, however, the difference was only 14% ( P

Preserving adult height potential in girls with idiopathic true precocious puberty

We designed a prospective study of height potential in girls with idiopathic precocious puberty, comparing the presenting features of girls with and without evidence of reduced adult height potential. The 14 girls with impaired adult height prognoses (group 1) were reexamined after treatment with a gonadotropin releasing hormone agonist, nafarelin. The seven girls with the prognosis of unimpaired height (group 2) were followed without therapy. We found that the group could be distinguished at initial examination by the greater bone age/height age ratio of group 1 (mean +/- SEM: 1.4 +/- 0.06 vs 1.0 +/- 0.05; p less than 0.005) and by the greater difference between predicted height and target height in group 1. The mean predicted height in group 1 was significantly less than the mean target height (150.7 +/- 2.1 vs 165.4 +/- 3.0 cm; p less than 0.005), whereas the mean predicted and target heights in group 2 were similar (165.4 +/- 3.0 vs 164.3 +/- 2.1 cm). Initial estradiol levels were also greater in group 1 than in group 2 (21.6 vs 10.6 pg/ml; p less than 0.05), although this difference was not sustained during follow-up. In group 1, nafarelin therapy suppressed the pituitary-gonadal axis, and although there was a transient reduction in height potential in girls with the youngest bone ages during the first 6 months of therapy, 2 years of treatment slightly improved predicted heights from 150.7 +/- 2.1 to 152.7 +/- 2.0 cm (p less than 0.05). Height predictions also increased without therapy during the 2-year observation period in group 2, from 165.4 +/- 3.0 to 168.7 +/- 4.1 cm (p less than 0.05). Our data indicate that gonadotropin releasing hormone agonist therapy preserves height potential in girls with an initially impaired height prognosis, and that height potential is preserved without therapy in those with a good initial height prognosis.

Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children

Recommendations from the Pediatric Endocrine Society for Evaluation and Management of Persistent Hypoglycemia in Neonates, Infants, and Children Paul S. Thornton, MB, BCh, Charles A. Stanley, MD, Diva D. De Leon, MD, MSCE, Deborah Harris, PhD, Morey W. Haymond, MD, Khalid Hussain, MD, MPH, Lynne L. Levitsky, MD, Mohammad H. Murad, MD, MPH, Paul J. Rozance, MD, Rebecca A. Simmons, MD, Mark A. Sperling, MBBS, David A. Weinstein, MD, MMSc, Neil H. White, MD, and Joseph I. Wolfsdorf, MB, BCh

Lipoprotein(a) levels in black and white children and adolescents with IDDM

Objective To examine the relationship between levels of lipoprotein(a) [Lp(a)], diabetes, and glycemic control in white and black nondiabetic control and insulindependent diabetic (IDDM) children and adolescents, fasting blood analyses were conducted on a subject sample drawn from referral-based diabetes and endocrine clinics and a primary-care general pediatric clinic. Research Design and Methods Thirty-six white and 16 black children with IDDM who volunteered to participate in this study were compared with 30 white and 42 black nondiabetic control children. Results Lp(a) protein levels were significantly higher (P < 0.05) in both groups of black children compared with whites (black vs. white nondiabetic children 6.8 ± 0.95 vs. 3.1 ± 0.68 mg/dl and black vs. white diabetic children 7.5 ± 1.52 vs. 3.0 ± 0.64 mg/dl). Lp(a) protein levels directly correlated with the level of glycosylated hemoglobin (r = 0.46, P < 0.01) in white diabetic children but not in black diabetic children. Well-controlled white diabetic children (n = 12, glycosylated hemoglobin <10%) had a mean Lp(a) protein level of 1.4 ± 0.3 mg/dl compared with poorly controlled white diabetic children (n = 10, glycosylated hemoglobin >13%) whose mean Lp(a) protein level was 5.7 ± 1 . 7 mg/dl (P < 0.01). Conclusions We conclude that circulating levels of Lp(a) protein are increased in hyperglycemia. A genetically determined elevated level of Lp(a) is a risk factor for atherosclerotic disease in white and Asian adults. Elevated Lp(a) should be investigated as an independent risk factor for atherosclerotic disease in IDDM. It could prove to be an additional mechanism for the development of diabetic complications in selected populations.

Plasma Aldosterone Concentration at Delivery and during the Newborn Period

Aldosterone concentrations in plasma of women on normal sodium intake undergoing cesarean section were 3.7+/-1.4 ng/100 ml (mean+/-1 SD). These values were significantly lower (P < 0.001) than those observed in mothers on normal sodium diet, delivered by the vaginal route (14.9+/-7.0 ng/100 ml). A significant elevation (P < 0.001) of the concentrations was found if the mothers had been on sodium restriction and/or diuretics (44.9+/-24.2 ng/100 ml). In supine position, adult nonpregnant subjects have aldosterone concentrations in plasma of 1.7+/-1.4 ng/100 ml on normal sodium intake and of 16.7+/-8.1 ng/100 ml on low sodium diet.Simultaneous determinations of aldosterone levels in cord blood showed that cord values were significantly higher than those of the corresponding mother (P < 0.01 by paired t test). However, values in cord blood of infants born to mothers on a normal sodium intake were significantly lower (P < 0.005) than those of infants whose mothers had required low sodium diet and/or diuretics during their pregnancy. Aldosterone concentrations in plasma of infants 1-72 hr of age and born to mothers on normal sodium intake were 25.9+/-11.7 ng/100 ml (mean +/-1 SD). These values were significantly lower (P < 0.005) than those of infants born to mothers on restricted sodium intake with or without diuretics (80.3+/-54.4 ng/100 ml). The concentrations at birth were not significantly different from those observed during the first 3 days of life (P > 0.6).

Echocardiographic evidence for impaired myocardial performance in children with type I diabetes mellitus

Thirty-three children with type I diabetes mellitus and 51 normal children underwent M-mode echocardiography. Abnormalities of myocardial performance were present in many of the diabetic children. The mean end-systolic volume of the left ventricle was greater in diabetics compared to control subjects. Mean ejection fraction, minor axis shortening, and velocity of circumferential fiber shortening were decreased in the diabetics. There was no evidence of increased myocardial mass in these diabetic children. There was no correlation between myocardial dysfunction, clinical assessment of control, or glycohemoglobin in the diabetic children.

Type 2 diabetes: an epidemic disease in childhood.

Type 2 diabetes mellitus in the pediatric population is now a public health problem. It represents 8 to 45% of all diabetes reported among children and adolescents. Concurrently, childhood obesity has become an epidemic in the United States. Epidemiologic risk factors and diagnostic criteria have largely been established: The incidence of type 2 diabetes increases with age and obesity. Children and adolescents diagnosed with type 2 diabetes usually have a first- or second-degree relative with the disorder. Familial clustering and twin studies have suggested a genetic component for type 2 diabetes. However, the molecular mechanisms that promote diabetes in susceptible individuals, the best treatment plans, and methods of prevention of this disorder are not yet established.

Re-Evaluating "Transitional Neonatal Hypoglycemia": Mechanism and Implications for Management

A Committee of the Pediatric Endocrine Society was recently asked by xxx to develop guidelines for evaluation and management of hypoglycemia in neonates, infants, and children. To aid in formulating recommendations for neonates, in this review, we analyzed available data on the brief period of hypoglycemia which commonly is observed in normal newborns during the transition from fetal to extrauterine life, hereafter referred to as transitional neonatal hypoglycemia in normal newborns. The goal was to better understand the mechanism underlying this phenomenon in order to formulate recommendations for recognizing neonates requiring diagnosis and treatment during the first days of life for disorders causing severe and persistent hypoglycemia. It has long been known that plasma glucose concentrations are lower in the first 1–3 days of life in normal newborn infants than at later ages. Not until the 1960s was it appreciated that hypoglycemia in neonates could sometimes be symptomatic and, as in older infants and children, cause seizures or permanent brain damage (1, 2). Although studies in laboratory animals have demonstrated postnatal developmental changes in specific enzymes involved in hepatic gluconeogenesis and ketogenesis (3, 4), it is unclear that such changes adequately explain transitional neonatal hypoglycemia in human newborns or if other mechanisms may be involved (5, 6). A National Institutes of Health conference outlined many of the “gaps in knowledge” about neonatal hypoglycemia and lamented the lack of a rational basis for defining hypoglycemia in neonates (7). For this re-evaluation of transitional neonatal hypoglycemia in normal newborns, we used the strategy routinely employed by pediatric endocrinologists for evaluation of hypoglycemia in older infants and children. This strategy, based on an examination of the major metabolic fuel and hormone responses to hypoglycemia, makes it possible to discover the mechanism of hypoglycemia and to make a specific diagnosis of the underlying cause (Figure; available at www.jpeds.com) (8). We reviewed published data in normal newborns on metabolic fuel and hormone responses during the period of transitional neonatal hypoglycemia. We focused on mean responses as being most likely representative of normal newborns, recognizing the possibility of heterogeneity, particularly with regard to peri-partum stresses and feeding practices. We found that transitional neonatal hypoglycemia most closely resembles known genetic forms of congenital hyperinsulinism, which cause a lowering of the plasma glucose threshold for suppression of insulin secretion. This conclusion is based on strong evidence supported by two or more independent reports and provides a novel perspective on both the diagnosis and management of hypoglycemia in the first several days after birth. Figure Hypoglycemia diagnosis based on plasma metabolic fuel responses. Measurement of major fuels (lactate as a gluconeogenic substrate, FFA from adipose tissue lipolysis, and beta-hydroxybutyrate as the major ketone from hepatic ketogenesis) at a time of hypoglycemia ...

Effect of Body Mass Index on Peak Growth Hormone Response to Provocative Testing in Children with Short Stature

CONTEXT Obesity is associated with decreased spontaneous and stimulated GH secretion, but the effect of body mass index (BMI) on results of GH stimulation testing in children with short stature is not known. OBJECTIVE The aim of the study was to determine the impact of BMI on peak GH to provocative testing in children with short stature. DESIGN, SETTING, AND PARTICIPANTS This was a retrospective review of provocative GH testing performed in 116 children 2-18 yr old in the ambulatory clinic of the Pediatric Endocrinology Unit at the Massachusetts General Hospital from 2004-2008. MAIN OUTCOME MEASURES The main outcome measure was peak stimulated GH. Height, weight, IGF-I, and IGF-binding protein 3 were also measured. RESULTS In univariate regression analysis, BMI sd score (BMI SDS) was inversely associated with natural log (ln) peak GH to provocative testing (P = 0.002), whereas height SDS, ln IGF-I, and IGF-binding protein 3 were not significantly associated with ln peak GH. After controlling for age, gender, BMI, and pubertal status, BMI (P = 0.002) remained independently associated with ln peak GH. BMI SDS significantly influenced the likelihood of diagnosis of GH deficiency using peak GH cutoffs of 10, 7, and 5 microg/liter. CONCLUSION In children with short stature, BMI affects peak stimulated GH and should be considered when interpreting GH testing. Higher BMI SDS, even within the normal range, may lead to overdiagnosis of GH deficiency.