Implementation of recommended treatment for children in weight management programs: Lessons from the stay in treatment study sites.

OBJECTIVES: Pediatric obesity remains a public health crisis in the United States, exacerbated by the COVID-19 pandemic. There are recommended guidelines for multidisciplinary care, but they remain challenging to implement, even in tertiary care weight management programs. The aim of this analysis is to describe the implementation of these recommendations among four pediatric weight management programs in the United States. METHODS: This report capitalizes on a convenience sample of programs participating in the Stay In Treatment (SIT) Study, a multicenter study to address attrition among pediatric weight management programs in tertiary care, academic institutions in diverse geographic locations. The programs were compared regarding structure, program offerings, and funding support. RESULTS: The four programs were interdisciplinary, offered individual and group treatment options, and were family-based. A range of clinicians provided interventions with nutrition, physical activity, behavioral and psychosocial components. Anti-obesity pharmacotherapy and bariatric surgery were offered, when appropriate. None of the programs were self-sustaining; they required institutional and philanthropic support to provide recommended, comprehensive treatment. CONCLUSIONS: Ongoing state and national advocacy are needed in the US to create consistent coverage for private and public insurance plans, so that high-risk children can have access to recommended treatment.

Diazoxide choline extended-release tablet in people with Prader-Willi syndrome: results from long-term open-label study.

OBJECTIVE: This study assessed the effect of 1-year administration of diazoxide choline extended-release tablet (DCCR) on hyperphagia and other complications of Prader-Willi syndrome (PWS). METHODS: The authors studied 125 participants with PWS, age ≥ 4 years, who were enrolled in the DESTINY PWS Phase 3 study and who received DCCR for up to 52 weeks in DESTINY PWS and/or its open-label extension. The primary efficacy endpoint was Hyperphagia Questionnaire for Clinical Trials (HQ-CT) score. Other endpoints included behavioral assessments, body composition, hormonal measures, and safety. RESULTS: DCCR administration resulted in significant improvements in HQ-CT (mean [SE] -9.9 [0.77], p < 0.0001) and greater improvements in those with more severe baseline hyperphagia (HQ-CT > 22). Improvements were seen in aggression, anxiety, and compulsivity (all p < 0.0001). There were reductions in leptin, insulin, and insulin resistance, as well as a significant increase in adiponectin (all p < 0.004). Lean body mass was increased (p < 0.0001). Disease severity was reduced as assessed by clinician and caregiver (both p < 0.0001). Common treatment-emergent adverse events included hypertrichosis, peripheral edema, and hyperglycemia. Adverse events infrequently resulted in discontinuation (7.2%). CONCLUSIONS: DCCR administration to people with PWS was well tolerated and associated with broad-ranging improvements in the syndrome. Sustained administration of DCCR has the potential to reduce disease severity and the burden of care for families.

How much did it cost to develop and implement an eHealth intervention for a minority children population that overlapped with the COVID-19 pandemic?

BACKGROUND: eHealth interventions using active video games (AVGs) offer an alternative method to help children exercise, especially during a pandemic where options are limited. There is limited data on costs associated with developing and implementing such interventions. OBJECTIVES: We quantified the costs of delivering an eHealth RCT intervention among minority children during COVID-19. METHODS: We categorized the total trial cost into five subcategories: intervention material development, advertising and recruitment, intervention delivery, personnel salaries, and COVID-19-related equipment costs. RESULTS: The total RCT cost was $1,927,807 (Direct: $1,227,903; Indirect: $699,904) with three visits required for each participant. The average cost per participant completing the RCT (79 participants/237 visits) was $24,403 (Direct: $15,543; Indirect: $8860). Due to no-shows and cancellations (198 visits) and dropouts before study completion (61 visits; 56 participants), 496 visits had to be scheduled to ensure complete data collection on 79 participants. If all 496 visits were from participants completing the three-visit protocol, that would correspond to 165 participants, bringing the average cost per participant down to $11,684 (Direct: $7442; Indirect: $4242). Of the subcategories, intervention material development accounted for the largest portion, followed by personnel salaries. While the direct COVID-19-specific cost constituted <1% of the entire budget, the indirect effects were much larger and significantly impacted the trial. CONCLUSION: RCTs typically involve significant resources, even more so during a pandemic. Future eHealth intervention investigators should budget and plan accordingly to prepare for unexpected costs such as recruitment challenges to increase flexibility while maximizing the intervention efficacy.

Stay in treatment: Predicting dropout from pediatric weight management study protocol.

INTRODUCTION: Childhood obesity is a serious public health concern. Multidisciplinary pediatric weight management programs have been deemed effective. However, effectiveness of these programs is impacted by attrition, limiting health benefits to children, and inefficiently utilizing scarce resources. METHODS: We have developed a model (the Outcomes Forecasting System, OFS) that isolates variables associated with attrition from pediatric weight management, with the potential to forecast participant dropout. In Aim 1, we will increase the power and precision of the OFS and then validate the model through the consistent acquisition of key patient, family, and treatment data, from three different weight management sites. In Aim 2, external validity will be established through the application of the OFS at a fourth pediatric weight management program. Aim 3 will be a pilot clinical trial, incorporating an intervention built on the results of Aims 1 and 2 and utilizing the OFS to reduce attrition. DISCUSSION: A greater understanding of the patient, family, and disease-specific factors that predict dropout from pediatric weight management can be utilized to prevent attrition. The goal of the current study is to refine the OFS to a level of precision and efficiency to be a valuable tool to any weight management program. By identifying the most pertinent factors driving attrition across weight management sites, new avenues for treatment will be identified. This study will result in a valuable forecasting tool that will be applicable for diverse programs and populations, decrease program costs, and improve patient retention, adherence, and outcomes. CLINICALTRIALSGOV IDENTIFIER: NCT04364282.

The impact of narratives and active video games on long-term moderate-to-vigorous physical activity: A randomized controlled trial protocol.

BACKGROUND: Although physical activity (PA) has been shown in helping prevent and treat obesity, current PA interventions are still not effective in ameliorating the obesity epidemic. Additional forms of PA need to be investigated to improve PA engagement and outcomes. We hypothesize that pairing a narrative (i.e., story) with an active video game (AVG), a less traditional form of PA, will increase participant engagement in PA. This paper presents the rationale, implementation, and pilot results of a study assessing the effect of narrative's impact on PA and a series of other health outcomes. OBJECTIVE: This paper presents the rationale, implementation, and pilot results of a study assessing the effect of narrative's impact on PA and a series of other health outcomes. METHODS/DESIGN: The Active Video Game Study is a six-month randomized controlled single-blind trial projected to include 210 participants. The intervention strategy will pair a narrative to an active video game (AVG). Participants will be randomized into 3 groups: condition A [Narrative + AVG], condition B [AVG Only], and condition C [Control]. Participants will undergo three in-person data collection visits over the course of six months. Inclusion criteria are that children are between the ages of 8-12 and have a BMI ≥ 85%. The primary outcome is change in moderate to vigorous physical activity (MVPA). Secondary outcome measures include change in BMI percentile, fasting insulin and glucose, lipid panel, C-reactive protein, and cognitive function. A pilot trial of n = 6 was conducted to help develop procedures and address problems that could arise in the main trial. DISCUSSION: Successful completion of this study will provide the empirical basis for novel intervention and design strategies to enhance the impact of AVGs on long-term MVPA.

Trends in pediatric obesity management, a survey from the Pediatric Endocrine Society Obesity Committee.

Background In the United States, 18.5% of children are obese. Dietary and lifestyle modifications are key, but often ineffective. There are limited approved pediatric pharmacotherapies. The objective of this study was to evaluate current treatment practices for pediatric obesity among members of the Pediatric Endocrine Society (PES, n = 1300) and the Pediatric Obesity Weight Evaluation Registry (POWER, n = 42) consortium. Methods A 10-question online survey on treatment of children with obesity in clinical practice was conducted. Results The response rates were 19% for PES and 20% for POWER members. The majority were female (65%) and board certified in pediatric endocrinology (81%). Most practitioners saw 5-10 patients with obesity/week and 19% prescribed weight-loss medications. POWER participants were more likely to prescribe weight-loss medications than PES participants (46% vs. 18%, p = 0.02). Metformin was the most commonly prescribed medication. Response to medication was poor. Use of dietary non-pharmacological treatment options was uncommon. Over half of the respondents (56%) referred patients for bariatric surgery and 53% had local access to pediatric bariatric surgery. Conclusions Metformin was the most common drug prescribed among respondents, but successful weight-loss responses were uncommon. Among practitioners who are using pharmacological interventions, therapeutic strategies vary widely. Targeted research in pharmacologic and surgical treatment for pediatric obesity is urgently needed.

Skeletal muscle mitochondrial function is associated with longitudinal growth velocity in children and adolescents.

CONTEXT: Periods of rapid growth require an increase in energy use and substrate formation. Mitochondrial function contributes to each of these and therefore may play a role in longitudinal growth. METHODS: Twenty-nine children and adolescents of ages 8-15 yr were enrolled in a comprehensive longitudinal assessment of glucose homeostasis and mitochondrial function. Fasting laboratory studies and an estimate of mitochondrial function (as assessed by the time to recovery of phosphocreatine (PCr) concentration after submaximal quadriceps extension/flexion exercise using (31)P magnetic resonance spectroscopy) were obtained at baseline and annually for 2 yr. RESULTS: Data were complete for 23 subjects. Subjects were 11.3 ± 1.9 (sd) yr old at the beginning of the study; 61% were male. Average annualized growth velocity at 1 yr for boys was 7.1 ± 1.5 cm/yr and for girls 6.5 ± 1.7 cm/yr. More rapid recovery of PCr concentration, suggestive of greater skeletal muscle oxidative phosphorylation capacity at baseline, was associated with faster growth velocity in the subsequent year (r(2) = 0.29; P = 0.008). In multivariate modeling, baseline mitochondrial function remained significantly and independently associated with growth (R(2) for model = 0.51; P = 0.05 for effect of phosphocreatine recovery time constant), controlling for age, gender, Tanner stage, body mass index Z-score, and height Z-score. CONCLUSIONS: We report a novel association between time to recovery of PCr concentration after submaximal exercise and faster annual linear growth in healthy children. Future studies are needed to determine the physiological mechanisms and clinical consequences of this observation.

Recombinant human prolactin for the treatment of lactation insufficiency.

CONTEXT: Lactation insufficiency has many aetiologies including complete or relative prolactin deficiency. Exogenous prolactin may increase breast milk volume in this subset. We hypothesized that recombinant human prolactin (r-hPRL) would increase milk volume in mothers with prolactin deficiency and mothers of preterm infants with lactation insufficiency. DESIGN: Study 1: R-hPRL was administered in an open-label trial to mothers with prolactin deficiency. Study 2: R-hPRL was administered in a randomized, double-blind, placebo-controlled trial to mothers with lactation insufficiency that developed while pumping breast milk for their preterm infants. PATIENTS: Study 1: Mothers with prolactin deficiency (n = 5). Study 2: Mothers of premature infants exclusively pumping breast milk (n = 11). DESIGN: Study 1: R-hPRL (60 µg/kg) was administered subcutaneously every 12 h for 28 days. Study 2: Mothers of preterm infants were randomized to receive r-hPRL (60 µg/kg), placebo or r-hPRL alternating with placebo every 12 h for 7 days. MEASUREMENTS: Change in milk volume. RESULTS: Study 1: Peak prolactin (27·9 ± 17·3 to 194·6 ± 19·5 µg/l; P < 0·003) and milk volume (3·4 ± 1·6 to 66·1 ± 8·3 ml/day; P < 0·001) increased with r-hPRL administration. Study 2: Peak prolactin increased in mothers treated with r-hPRL every 12 h (n = 3; 79·3 ± 55·4 to 271·3 ± 36·7 µg/l; P < 0·05) and daily (101·4 ± 61·5 vs 178·9 ± 45·9 µg/l; P < 0·04), but milk volume increased only in the group treated with r-hPRL every 12 h (53·5 ± 48·5 to 235·0 ± 135·7 ml/day; P < 0·02). CONCLUSION: Twice daily r-hPRL increases milk volume in mothers with prolactin deficiency and in preterm mothers with lactation insufficiency.

Skeletal muscle phosphocreatine recovery after submaximal exercise in children and young and middle-aged adults.

CONTEXT: Elderly subjects have reduced mitochondrial function. However, it remains unclear whether the decline in mitochondrial function begins earlier in the life span. OBJECTIVE: The objective of the study was to determine skeletal muscle mitochondrial oxidative phosphorylation by (31)phosphorous-magnetic resonance spectroscopy (MRS) across a variety of age groups. DESIGN: This was a cross-sectional study of 121 healthy normal-weight and overweight individuals from age 8 to 55 yr. SETTING: The study was conducted at a single university medical center in Boston, MA. PARTICIPANTS: Participants included 68 children and 53 adults from the Boston community. INTERVENTIONS AND MAIN OUTCOME MEASURES: Phosphocreatine (PCr) recovery was evaluated by (31)phosphorous-MRS after submaximal exercise. Subjects were also evaluated with anthropometric measurements, metabolic profiles, and measures of physical activity. RESULTS: PCr recovery determined by (31)phosphorous-MRS is positively associated with age in univariate analysis in a cohort of individuals aged 8-55 yr (r = +0.55, P < 0.0001). Stratification of subjects into four age groups (prepubertal and early pubertal children, pubertal and postpubertal children < 18 yr, young adults aged 18-39 yr, and middle aged adults aged 40-55 yr) demonstrates prolongation of PCr recovery with increasing age across the four groups (P < 0.0001 by ANOVA). The relationship between PCr recovery and age remains strong when controlling for gender; race; ethnicity; body mass index; measures of physical activity and inactivity; and anthropometric, nutritional, and metabolic parameters (P < 0.004). CONCLUSIONS: Skeletal muscle PCr recovery measured by (31)phosphorous-MRS is prolonged with age, even in children and young adults.

Insulin enhances glucose-stimulated insulin secretion in healthy humans.

Islet beta-cells express both insulin receptors and insulin-signaling proteins. Recent evidence from rodents in vivo and from islets isolated from rodents or humans suggests that the insulin signaling pathway is physiologically important for glucose sensing. We evaluated whether insulin regulates beta-cell function in healthy humans in vivo. Glucose-induced insulin secretion was assessed in healthy humans following 4-h saline (low insulin/sham clamp) or isoglycemic-hyperinsulinemic (high insulin) clamps using B28-Asp insulin that could be immunologically distinguished from endogenous insulin. Insulin and C-peptide clearance were evaluated to understand the impact of hyperinsulinemia on estimates of beta-cell function. Preexposure to exogenous insulin increased the endogenous insulin secretory response to glucose by approximately 40%. C-peptide response also increased, although not to the level predicted by insulin. Insulin clearance was not saturated at hyperinsulinemia, but metabolic clearance of C-peptide, assessed by infusion of stable isotope-labeled C-peptide, increased modestly during hyperinsulinemic clamp. These studies demonstrate that insulin potentiates glucose-stimulated insulin secretion in vivo in healthy humans. In addition, hyperinsulinemia increases C-peptide clearance, which may lead to modest underestimation of beta-cell secretory response when using these methods during prolonged dynamic testing.

Mitochondrial function and insulin resistance in overweight and normal-weight children.

BACKGROUND: Obesity has become an epidemic in children, associated with an increase in insulin resistance and metabolic dysfunction. Mitochondrial function is known to be an important determinant of glucose metabolism in adults. However, little is known about the relationship between mitochondrial function and obesity, insulin resistance, energy expenditure, and pubertal development in children. METHODS: Seventy-four participants, 37 overweight (> or = 85th percentile body mass index for age and sex) and 37 normal-weight (< 85th percentile) without personal or family history of diabetes mellitus were enrolled. Subjects were evaluated with an oral glucose tolerance test, metabolic markers, resting energy expenditure, Tanner staging, and (31)P magnetic resonance spectroscopy of skeletal muscle for mitochondrial function. RESULTS: Overweight and normal-weight children showed no difference in muscle ATP synthesis [phosphocreatine (PCr) recovery after exercise] (32.4 +/- 2.3 vs. 34.1 +/- 2.1, P = 0.58). However, insulin-resistant children had significantly prolonged PCr recovery when compared with insulin-sensitive children, by homeostasis model assessment for insulin resistance quartile (ANOVA, P = 0.04). Similarly, insulin-resistant overweight children had PCr recovery that was prolonged compared with insulin-sensitive overweight children (P = 0.01). PCr recovery was negatively correlated with resting energy expenditure in multivariate modeling (P = 0.03). Mitochondrial function worsened during mid-puberty in association with insulin resistance. CONCLUSION: Reduced skeletal muscle mitochondrial oxidative phosphorylation, assessed by PCr recovery, is associated with insulin resistance and an altered metabolic phenotype in children. Normal mitochondrial function may be associated with a healthier metabolic phenotype in overweight children. Further studies are needed to investigate the long-term physiological consequences and potential treatment strategies targeting children with reduced mitochondrial function.

Management of obesity, insulin resistance and type 2 diabetes in children: consensus and controversy.

Childhood obesity has become a national and international epidemic. The prevalence and incidence of type 2 diabetes in youth have been increasing, and type 2 diabetes is one of the most challenging complications of obesity in childhood. Comprehensive lifestyle interventions that include attention to dietary change, increased physical activity and behavior change appear to be required for the successful treatment of pediatric obesity. In particular, aspects of behavioral interventions that have been identified as contributing to effectiveness have included intensity, parent/family participation, addressing healthy dietary change, promoting physical activity, and involving behavioral management principles such as goal setting. A multidisciplinary team approach is required for successful management of type 2 diabetes in youth as well. As with many therapies in pediatrics, clinical trials and support for treatments of obesity and type 2 diabetes in youth lag behind adult data. Pediatric recommendations may be extrapolated from adult data and are often based on consensus guidelines. Type 2 diabetes in children is most commonly managed with lifestyle modification and medications, metformin and/or insulin, the only medications currently approved for use in children. However, many opportunities exist for ongoing research to clarify optimal management for obesity and type 2 diabetes in youth.

Salsalate improves glycemia and inflammatory parameters in obese young adults.

OBJECTIVE: Sedentary lifestyle and a western diet promote subacute-chronic inflammation, obesity, and subsequently dysglycemia. The aim of the current study was to evaluate the efficacy of the anti-inflammatory drug salsalate to improve glycemia by reducing systemic inflammation in obese adults at risk for the development of type 2 diabetes. RESEARCH DESIGN AND METHODS: In a double-masked, placebo controlled trial, we evaluated 20 obese nondiabetic adults at baseline and after 1 month of salsalate or placebo. RESULTS: Compared with placebo, salsalate reduced fasting glucose 13% (P < 0.002), glycemic response after an oral glucose challenge 20% (P < 0.004), and glycated albumin 17% (P < 0.0003). Although insulin levels were unchanged, fasting and oral glucose tolerance test C-peptide levels decreased in the salsalate-treated subjects compared with placebo (P < 0.03), consistent with improved insulin sensitivity and a known effect of salicylates to inhibit insulin clearance. Adiponectin increased 57% after salsalate compared with placebo (P < 0.003). Additionally, within the group of salsalate-treated subjects, circulating levels of C-reactive protein were reduced by 34% (P < 0.05). CONCLUSIONS: This proof-of-principle study demonstrates that salsalate reduces glycemia and may improve inflammatory cardiovascular risk indexes in overweight individuals. These data support the hypothesis that subacute-chronic inflammation contributes to the pathogenesis of obesity-related dysglycemia and that targeting inflammation may provide a therapeutic route for diabetes prevention.

Bone mineral status in children with congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) is caused by a deficiency in an adrenal enzyme resulting in alterations in cortisol and aldosterone production. Bone status is affected by chronic glucocorticoid therapy and excess androgen exposure in children with CAH. This cross-sectional study enrolled participants with 21-hydroxylase deficiency from a pediatric referral center. Bone mineral density in the participants was normal when compared to age, gender and ethnicity adjusted standards, with respect to chronological age or bone age. Lean body mass was positively correlated with bone mineral content (BMC), independent of fat mass (p < 0.001). There was no significant correlation between glucocorticoid dose or serum androgen levels and skeletal endpoints. In conclusion, lean body mass appears to be an important correlate of BMC in patients with CAH. The normal bone status may be explained by the differential effects of glucocorticoids on growing bone, beneficial androgen effects, or other disease specific factors.

Normal ovarian structure and function with normal glucose tolerance in girls with early treatment of classic congenital adrenal hyperplasia.

UNLABELLED: Hyperandrogenism and hyperinsulinism have both been suggested as etiologic factors behind functional ovarian hyperandrogenism or polycystic ovary syndrome. Females with congenital adrenal hyperplasia provide a clinical model to evaluate the contribution of pre- and post-natal hyperandrogenism on ovarian structure and function. STUDY OBJECTIVE: To evaluate glucose tolerance, and structure and androgen production of the ovaries in young females with classic congenital adrenal hyperplasia. DESIGN, SETTING, PARTICIPANTS: Cross-sectional study, including the enrollment of participants, ages 8 to 20 years, recruited from the pediatric endocrinology clinical program of a tertiary pediatric referral center. INTERVENTIONS: Ten participants had oral glucose tolerance testing, adrenal and ovarian androgen measurements, and pelvic ultrasound studies performed. MAIN OUTCOME MEASURES: Presence of altered response to glucose challenge, ovarian hyperandrogenism, or presence of polycystic ovaries by ultrasound. RESULTS: Measurements of fasting blood glucose, post-challenge glucose, and insulin resistance were normal in this sample. There was no evidence of ovarian hyperandrogenism after adrenal suppression with dexamethasone. All participants had normal ovarian structure without evidence of polycystic ovaries. CONCLUSIONS: Females with classic congenital adrenal hyperplasia (21-hydroxylase deficiency) and normal glucose tolerance appear to have normal ovarian structure and function during the peripubertal period.

Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults.

Mitochondrial dysfunction may contribute to the development of insulin resistance and type 2 diabetes. Nucleoside reverse transcriptase inhibitors (NRTIs), specifically stavudine, are known to alter mitochondrial function in human immunodeficiency virus (HIV)-infected individuals, but the effects of stavudine on glucose disposal and mitochondrial function in muscle have not been prospectively evaluated. In this study, we investigated short-term stavudine administration among healthy control subjects to determine effects on insulin sensitivity. A secondary aim was to determine the effects of stavudine on mitochondrial DNA (mtDNA) and function. Sixteen participants without personal or family history of diabetes were enrolled. Subjects were randomized to receive stavudine, 30-40 mg, twice a day, or placebo for 1 mo. Insulin sensitivity determined by glucose infusion rate during the hyperinsulinemic euglycemic clamp was significantly reduced after 1-mo exposure in the stavudine-treated subjects compared with placebo (-0.8 +/- 0.5 vs. +0.7 +/- 0.3 mg.kg(-1).min(-1), P = 0.04, stavudine vs. placebo). In addition, muscle biopsy specimens in the stavudine-treated group showed significant reduction in mtDNA/nuclear DNA (-52%, P = 0.005), with no change in placebo-treated subjects (+8%, P = 0.9). (31)P magnetic resonance spectroscopy (MRS) studies of mitochondrial function correlated with insulin sensitivity measures (r2 = 0.5, P = 0.008). These findings demonstrate that stavudine administration has potent effects on insulin sensitivity among healthy subjects. Further studies are necessary to determine whether changes in mtDNA resulting from stavudine contribute to effects on insulin sensitivity.

Characteristics at diagnosis of type 1 diabetes in children younger than 6 years.

OBJECTIVE: To characterize the prodrome, presentation, family history, and biochemical status at diagnosis of type 1 diabetes mellitus (T1D) in children under age 6 years. STUDY DESIGN: This was a retrospective chart review of patients hospitalized at diagnosis with T1D from 1990 to 1999 in a children's hospital. RESULTS: A total of 247 children were hospitalized, 44% of whom presented in diabetic ketoacidosis (DKA). When stratified by 2-year age intervals, only total carbon dioxide (tCO(2)) was significantly lower in the youngest children (P = .02), and the duration of candidiasis was significantly longer in those children presenting in DKA (P = .004). Parents were more likely to recognize symptomatic hyperglycemia in children older than 2 years (P < .0001). Most parents sought care for their child suspecting that the child had diabetes; the other children were diagnosed when presenting with another concern. Only gender and tCO(2) were significantly correlated with hemoglobin A1c (HbA1c); age-adjusted HbA1c was 0.64% higher in girls compared with boys (P = .045), and each 1-mmol/L decrement in tCO(2) increased the age- and gender-adjusted HbA1c by 0.086% (P < .001). CONCLUSIONS: A high proportion of children under age 6 years present critically ill at the diagnosis of T1D. When any of the classic symptoms of diabetes or a yeast infection is present, a serum glucose level should be measured.

Diagnosis and treatment of polycystic ovarian syndrome and insulin resistance.

PCOS is a complex syndrome that includes clinical and biochemical evidence of hyperandrogenism and hyperinsulinism. Adolescents with PCOS are affected by the diagnosis with both short-term and long-term consequences. Adolescents with PCOS report lower self-esteem and quality of life, based on standard assessments, when compared with age matched peers. These young women also are concerned about future fertility, which may affect psychological well being and health behaviors. In addition, patients with PCOS are at an increased risk for development of insulin resistance, type 2 diabetes, metabolic syndrome, and cardiovascular disease. Therefore, this identified at-risk group requires rigorous evaluation, treatment and long-term counseling and management by healthcare providers.

Diencephalic syndrome: a cause of failure to thrive and a model of partial growth hormone resistance.

Diencephalic syndrome is a rare but potentially lethal cause of failure to thrive in infants and young children. The diencephalic syndrome includes clinical characteristics of severe emaciation, normal linear growth, and normal or precocious intellectual development in association with central nervous system tumors. Our group initially described a series of 9 patients with diencephalic syndrome and found a reduced prevalence of emesis, hyperalertness, or hyperactivity compared with previous reports. Also, the tumors were found to be larger, occur at a younger age, and behave more aggressively than similarly located tumors without diencephalic syndrome. We have been able to extend our follow-up of the original patients, as well as describe 2 additional cases. Because the mechanism of the growth and endocrinologic findings in diencephalic syndrome has not been explained, we report on these patients in light of current research on hypothalamic factors that affect growth and weight. This study emphasizes diencephalic syndrome as a model for additional study of growth hormone resistance and metabolic regulation of adiposity.