Search

Objective To evaluate the impact of the Diabetes Coach Program (DCP) on glycated hemoglobin (A1C) levels in youth with type 1 diabetes. The youth were referred to and participated in the DCP between October 2011 and May 2016. Methods The Diabetes Coach visited families in their homes every 1 to 2 weeks and updated patients' diabetes teams regularly. A1C levels before the DCP were compared with A1C levels during and after discharge from the DCP. Six participating families completed satisfaction surveys via telephone. Results The DCP included 23 participants (43% male; median age, 11 years; range, 8.8 to 14.5 years); median duration of type 1 diabetes, 1.7 years (range, 0.1 to 6.3 years); median time in the DCP, 1.5 years (range, 0.2 to 2.5 years). During involvement in the program, median A1C levels decreased from baselines of 11.1% (range, 8.9% to 15.3%) to 10.2% (range, 7.6% to 12.4%) (p=0.0028). For 11 of 13 patients discharged from the DCP, the most recent median A1C levels, 11.2% (range, 9.1% to 13.6%), an average of 2.4 years later, were not different from the initial A1C levels (p=0.85). Family feedback was overwhelmingly positive. Conclusions Participation in the DCP decreased A1C values in pediatric patients; however, the levels were not sustained after visits stopped. Pediatric health coaches may play an important role in the management of type 1 diabetes, but further research is needed to explore their benefits and how positive effects can be sustained.

Objectives In a contemporary cohort of youth with type 1 diabetes, we examined the interval between episodes of severe hypoglycemia (SH) as a risk factor for recurrent SH or hypoglycemic coma (HC). Methods This was a large longitudinal observational study. Using the DPV Diabetes Prospective follow-up data, we analyzed frequency and timing of recurrent SH (defined as requiring assistance from another person) and HC (loss of consciousness or seizures) in 14 177 youths with type 1 diabetes aged Results Among 14 177 patients with type 1 diabetes, 72% (90%) had no, 14% (6.8%) had 1 and 14% (3.2%) >1 SH (HC). SH or HC in the last year of observation was highest with SH in the previous year (odds ratio [OR] 4.7 [CI 4.0-5.5]/4.6 [CI 3.6-6.0]), but remained elevated even 4 years after an episode (OR 2.0 [CI 1.6-2.7]/2.2 [CI 1.5-3.1]). The proportion of patients who experienced SH or HC during the last year of observation was highest with SH/HC recorded during the previous year (23% for SH and 13% for HC) and lowest in those with no event (4.6% for SH and 2% for HC) in the initial 4 years of observation. Conclusions Even 4 years after an episode of SH/HC, risk for SH/HC remains higher compared to children who never experienced SH/HC. Clinicians should continue to regularly track hypoglycemia history at every visit, adjust diabetes education and therapy in order to avoid recurrences.

Congenital adrenal hyperplasia (CAH) is often considered a pediatric endocrinology condition, but we present two cases of young adults who presented with hypertension. An 18-year-old woman was found to have hypertension and hypokalemia when she presented for gonadectomy for 46, XY gonadal dysgenesis. She was subsequently found to have low cortisol, elevated progesterone, and elevated aldosterone. Genetic testing confirmed 17-alpha hydroxylase deficiency (17OHD). Her case was unique in that 17OHD usually presents with hypoaldosteronism. We also present the case of a 15-year-old man (46, XX) with resistant hypertension due to 11-beta hydroxylase deficiency (11OHD) who underwent bilateral adrenalectomy for control of hypertension. The relevant literature is reviewed including the pathophysiology, clinical presentation, and treatment of the hypertensive variants of congenital adrenal hyperplasia. We also review the unique areas of hyperaldosteronism in 17OHD and the use of bilateral adrenalectomy for control of hypertension in CAH.

Congenital adrenal hyperplasia (CAH), resulting from mutations in CYP11B1, a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11β-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of CYP11B1 revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11β-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clinical, genetic, hormonal, and structural effects of CYP11B1 gene mutations in the largest international cohort of 108 patients with steroid 11β-hydroxylase deficiency CAH. Fil: Khattab, Ahmed. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Haider, Shozeb. University College London; Estados Unidos Fil: Kumar, Ameet. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Dhawan, Samarth. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Alam, Dauood. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Romero, Raquel. University College London; Estados Unidos Fil: Burns, James. University College London; Estados Unidos Fil: Li, Di. University College London; Estados Unidos Fil: Estatico, Jessica. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Rahi, Simran. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Fatima, Saleel. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Alzahrani, Ali. King Faisal Specialist Hospital And Research Centre; Arabia Saudita Fil: Hafez, Mona. Cairo University; Egipto Fil: Musa, Noha. Cairo University; Egipto Fil: Azar, Maryam Razzghy. Iran University Of Medical Sciences; Irán Fil: Khaloul, Najoua. Hopital Farhat Hached Sousse; Túnez Fil: Gribaa, Moez. Hopital Farhat Hached Sousse; Túnez Fil: Saad, Ali. Hopital Farhat Hached Sousse; Túnez Fil: Charfeddine, Ilhem Ben. Hopital Farhat Hached Sousse; Túnez Fil: De Mendonça, Berenice Bilharinho. Universidade de Sao Paulo; Brasil Fil: Belgorosky, Alicia. Hospital de Pediatria Samic Prof. Dr. Juan P. Garrahan; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Dumic, Katja. University Of Zagreb. School Of Medicine; Croacia Fil: Dumic, Miroslav. University Of Zagreb. School Of Medicine; Croacia Fil: Aisenberg, Javier. Hackensack University Medical Center; Estados Unidos Fil: Kandemir, Nurgun. Hacettepe Universitesi; Turquía Fil: Alikasifoglu, Ayfer. Hacettepe Universitesi; Turquía Fil: Ozon, Alev. Hacettepe Universitesi; Turquía Fil: Gonc, Nazli. Hacettepe Universitesi; Turquía Fil: Cheng, Tina. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Kuhnle Krahl, Ursula. University of Munich; Alemania Fil: Cappa, Marco. Ospedale Pediatrico Bambino Gesu; Italia Fil: Holterhus, Paul-Martin. Universitatsklinikum Schleswig-Holstein; Alemania Fil: Nour, Munier A.. University of Saskatchewan; Canadá Fil: Pacaud, Daniele. University of Calgary; Canadá Fil: Holtzman, Assaf. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Li, Sun. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Zaidi, Mone. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: Yuen, Tony. Icahn School Of Medicine At Mount Sinai; Estados Unidos Fil: New, Maria I.. Icahn School Of Medicine At Mount Sinai; Estados Unidos

Introduction: We studied the potential for motor unit number estimation (MUNE) to detect subclinical changes in motor unit numbers in children with type 1 diabetes mellitus (DM). Methods: Blinded observers performed clinical assessment, electrophysiology, and multipoint MUNE of the extensor digitorum brevis muscle in children with DM for ≥5 years and age-matched healthy controls. Results: For 51 DM subjects, the disease duration was 9.1 ± 2.6 years. Subjects with DM and healthy controls (n = 21) had similar demographics. There were no clinical symptoms or signs of peripheral neuropathy in any subject, nor differences in standard electrophysiology between cohorts. Estimated motor unit numbers were decreased significantly in children with DM (224 ± 87 vs. 274 ± 101, P = 0.036). Conclusion: Despite the absence of clinical or standard electrophysiological differences from normal control subjects, MUNE can detect a small significant difference in children with DM, suggesting that motor unit loss begins early and subclinically in the disease. Muscle Nerve 50: 593–598, 2014

Kearns-Sayre syndrome (KSS), resulting from a mitochondrial DNA deletion, is a rare cause of diabetes in children. We report 2 pediatric cases of KSS associated with diabetes that presented with hyperosmolar hyperglycemia with minimal ketosis. Both patients were treated initially with isotonic fluid resuscitation followed by intravenous insulin infusion. The first case was a boy of Blackfoot Aboriginal ancestry who presented with failure to thrive, developmental delay and Fanconi syndrome and was diagnosed with KSS at 3 years of age. At 4 years he presented with a cough and left upper lobe lung infiltrate as well as a hyperosmolar hyperglycemic episode. He subsequently required multiple daily insulin injections. This patient developed cardiomyopathy and died at the age of 10 years. The second case was a 6-year-old boy of Asian ancestry who presented with ataxia exacerbated by intercurrent illnesses, decreased exercise tolerance, gross motor and fine motor delays, anorexia and recurrent episodes of vomiting associated with dehydration, and he was subsequently diagnosed with KSS. At 11 years of age, the patient developed hyperosmolar hyperglycemia, and after treatment for it, he required multiple daily insulin injections. He died of end stage congestive heart failure secondary to cardiomyopathy at 13 years of age. These 2 cases are presented to describe the possible pathophysiology of mitochondrial diabetes and to emphasize the need to monitor for the development of diabetes in patients with known mitochondrial disease and also to be aware of possible mitochondrial disease in pediatric patients who present with hyperglycemia in the context of multisystem involvement.

Background: Stigma in chronic disease involves unwarranted rejection, judgement, or exclusion by others based on the chronic disease itself. Objective: We aim to determine the prevalence of stigma among youth and young adults with type 1 diabetes in Canada, to assess associations between stigma and glycemic control, and to explore ways to address stigma related to type 1 diabetes. Methods: The study includes 3 distinct phases: (1) refinement of survey questions, (2) assessment of test-retest reliability, and (3) a data collection and analysis phase (online survey and mailed-in capillary blood sample to assess hemoglobin A1c). A total of 380 youth and young adults (14 to 24 years old) with type 1 diabetes are being recruited through social media and clinic posters. Results: Phases 1 and 2 are complete, and phase 3 is in progress. Thirty participants completed phase 2. The survey includes the Barriers to Diabetes Adherence in adolescent scale (intraclass correlation [ICC]=0.967, 95% CI 0.931-0.984), the Self-Efficacy for Diabetes Self-Management measure (ICC=0.952, 95% CI 0.899-0.977), the World Health Organization-5 Well-Being Index (ICC=0.860, 95% CI 0.705-0.933), 12 closed-ended questions, and an additional 5 open-ended questions to explore challenges and solutions developed by the team of experts, including a patient representative. Conclusions: This will be the first large-scale survey to estimate the prevalence of stigma in young people with type 1 diabetes. The results of this study will allow for an appreciation of the magnitude of the problem and the need for developing and implementing solutions. This work is intended to provide an initial understanding of youth perspectives on the challenges of living with type 1 diabetes and will serve as a foundation for future research and action to help youth improve their experience of living with diabetes. Trial Registration: ClinicalTrials.gov NCT02796248, https://clinicaltrials.gov/ct2/show/NCT02796248 (Archived at http://www.webcitation.org/6mhenww3o). [JMIR Res Protoc 2016;5(4):e242]

BACKGROUND: Although type 1 diabetes (T1D) remains the most frequent form of diabetes in individuals aged less than 20 years at onset, other forms of diabetes are being increasingly recognized.OBJECTIVES: To describe the population of children with other forms of diabetes (non-type 1) included in the multinational SWEET (Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) database for children with diabetes.METHODS: Cases entered in the SWEET database are identified by their physician as T1D, type 2 diabetes (T2D) and other types of diabetes according to the ISPAD classification. Etiologic subgroups are provided for other types of diabetes. Descriptive analyses were tabulated for age at onset, gender, daily insulin doses, and hemoglobin A1c (A1C) for each type and subtype of diabetes and when possible, values were compared.RESULTS: Of the 27 104 patients included in this report, 95.5% have T1D, 1.3% T2D, and 3.2% other forms of diabetes. The two most frequent etiologies for other forms of diabetes were maturity onset diabetes of the young (MODY) (n = 351) and cystic fibrosis-related diabetes (CFRD) (n = 193). The cause was unknown or unreported in 10% of other forms of diabetes. Compared with T1D, children with T2D and CFRD were diagnosed at an older age, took less insulin and had lower A1C (all P < .0001).CONCLUSION: In centers included in SWEET, forms of diabetes other than type 1 remain rare and at times difficult to characterize. Sharing clinical information and outcome between SWEET centers on those rare forms of diabetes has the potential to improve management and outcome.

Diabetes affects many children living in developing countries. Through an informal survey, five SWEET (Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) centers from developing countries (Mali, Costa Rica, Argentina and two from India) share their perspective on caring for children with diabetes. Each center provides a description of the population of children with diabetes they serve, the organization of care, and the challenges encountered on a daily basis in the provision of this care. In the second part, we summarize the anticipated benefits and challenges associated with participation in SWEET. This resulting article is a testimony of the reality of managing diabetes by dynamic teams striving to achieve recommended standards of care for pediatric diabetes in an environment with limited resources.

Background eHealth systems are being rapidly diffused and used by health organizations, healthcare providers and patients for diabetes educational purposes because of perceived cost savings, convenience and access from remote locations. Objective To compare the use of 3 education systems that varied media (face-to-face vs. electronic), communication (e.g. synchronous and asynchronous) and information processing functionality (e.g. Internet searching, view laboratory blood test results) for education of newly diagnosed patients with type 2 diabetes mellitus. Design/Methods In a randomized controlled trial, changes in glycated hemoglobin (A1C), self-efficacy and diabetes knowledge were compared between 3 models of education and communication support in newly diagnosed patients with type 2 diabetes: controls (face-to-face education, synchronous and asynchronous communication), Web Static (electronic education and virtual appointments using asynchronous communication) and Web Interactive (electronic education and virtual appointments using both synchronous and asynchronous communication). Results In an intent-to-treat analysis, all 3 groups had similar improvement in diabetes knowledge, self-efficacy and diabetes self-care activities. Independent of which group subjects were randomized to, findings were significant when examining correlation between website usage and outcomes: a higher total use was associated with a higher diabetes knowledge score (r=0.265, p=0.029), a higher total diabetes self-efficacy by final study visit (r=0.317, p=0.008) and a lower A1C by final study visit (r=−0.271, p=0.026) by the last visit. Conclusions Initial diabetes education can be delivered successfully through electronic media. Higher adoption of electronic media is associated with improved clinical outcomes.

The use of complementary and alternative medicine (CAM) has undergone exponential growth in recent years (1–3) and has evolved into a multibillion dollar industry (2,3) whose influence in modern medicine has become a force to be reckoned with. While the definition of CAM is somewhat vague and ill-defined (4), the National Institutes of Health (USA) has defined CAM as a “group of diverse medical and health care systems, practices, and products that are not generally considered to be part of conventional medicine” (5). The current health care system is witnessing an increasing interest in the use of CAM, and this has been well documented in the United States (6–8), Canada (9,10) and Europe (11). Although children and adolescents are not exempt from its use, CAM prevalence in the paediatric population varied greatly from 11% to 68% (12). CAM is used most often by individuals who have serious, chronic or recurrent illness, sometimes for symptom control and sometimes to combat the primary disease (13). Therefore, we were not surprised to see a growing body of literature regarding the use of CAM, particularly reports demonstrating increased use of CAM in many paediatric chronic disease populations (13). Type 1 diabetes mellitus (T1DM) is the most common paediatric endocrine disease, and one of the most common chronic conditions in children and adolescents (14). Insulin therapy is the mainstay of the medical management of T1DM. Contrary to other paediatric chronic conditions, there are very few reports in the literature of CAM use in children and adolescents. In 2002, one report from Italy described three patients with T1DM who experienced an unexpected worsening of their glycemic control due to a reduction in their insulin dosage in favour of some ‘alternative’ treatments using herbs, vitamins, alternative diets and trace elements prescribed by nonmedical professionals (15). Still, two recent large studies (16,17) – one in Germany and the other in the United States – showed that 18.4% and 36.4% of children with T1DM use CAM. However, there is a paucity of information on the frequency of serious side effects associated with most of the alternative therapies (18). The aim of our study was to quantitatively describe the patterns and determinants of CAM use in children and adolescents with T1DM receiving care at the Alberta Children’s Hospital Diabetes Clinic in Calgary, Alberta.

SUMMARY Severe hypoglycemia (lost of consciousness or convulsion) has been reported in up to 40% of pregnancies complicated by Type 1 diabetes and in up to 22% of cases there is more than one episode reported during pregnancy. This article reviews relevant literature and explores the potential impact of severe hypoglycemia during pregnancy on the neurocognitive development of children. As no human research has specifically examined this issue, we will first review research that has used animal models followed by a review of studies that have investigated the impact of maternal diabetes on the neurocognitive outcome of the offspring. Research on the impact of severe hypoglycemia on young children’s neurocognitive outcomes will also be examined. Finally, the direction and need for further research in this field will be discussed.

BACKGROUND Starting subcutaneous insulin doses in children with newly diagnosed type 1 diabetes vary widely from 0.2 units/kg/day to 0.8 units/kg/day. AIM To determine whether there are correlations between starting insulin dose and diabetes-related outcomes. METHODS By reviewing the charts of children newly diagnosed with type 1 diabetes, the prevalence of hypoglycemia in the first 48 h was compared between those who received low (0.5 units/kg/day or less) and those who received high (greater than 0.5 units/kg/day) starting insulin doses. RESULTS Forty-two children were initially prescribed a low dose of insulin, and 55 children were given a high dose. Approximately one-third of children (36.4%) younger than six years of age who received a high starting dose of insulin had mild hypoglycemia within 48 h of subcutaneous insulin initiation, compared with 16.0% of children six to 10 years of age and 5.3% of children older than 10 years of age. CONCLUSIONS Hypoglycemia was not more frequent among children given high-insulin starting doses. However, children younger than six years of age remained at increased risk for hypoglycemia.

OBJECTIVE: To assess the prevalence of secondary diabetes seen in pediatric tertiary care centres in Canadian children with acute lymphoblastic leukemia (ALL), cystic fibrosis (CF), thalassemia major, or heart, liver or renal transplant. A secondary objective was to determine risk factors associated with the development of secondary diabetes in these populations. METHODS: A multicentre, retrospective descriptive study of pediatric patients RESULTS: The prevalence of reported secondary diabetes was 1.8% in ALL, 2.9% in CF, 0% in thalassemia major, 3.4% in heart transplant, 2.6% in liver transplant and 1.5% in renal transplant. An odds ratio of 15.0 (95% CI 1.2-747.4) was found for developing secondary diabetes in children > 12 years of age with ALL compared to those ≤ 12 years of age with ALL; 50% of cases of secondary diabetes with ALL had a body mass index greater than the 95th percentile, compared to 0% of control patients with ALL (p=0.005). No other significant risk factors were found to be associated with the development of secondary diabetes. CONCLUSIONS: This is the first study examining the prevalence of secondary diabetes in children seen in pediatric tertiary care centres from multiple at-risk populations. The prevalence of secondary diabetes was lower than that previously reported in predominantly young adult populations. Assessment for associated risk factors was limited by the small number of cases and controls available.

Husband AC, Crawford S, McCoy LA, Pacaud D. The effectiveness of glucose, sucrose, and fructose in treating hypoglycemia in children with type 1 diabetes. Objective: There is a lack of evidence regarding the most effective treatment option for managing naturally occurring hypoglycemia in children with type 1 diabetes. The objectives of this study were (i) to determine if sucrose and fructose are equally effective as glucose in the treatment of spontaneous hypoglycemia in children with type 1 diabetes; and (ii) to determine prestudy and poststudy hypoglycemia treatment preferences. Methods: Thirty-three subjects [aged 5.4–15.5 yr and average duration of type 1 diabetes of 3.1 yr (SD = 2.3)] participated in a randomized, crossover design. The main outcome was the effectiveness of treatment as defined by a blood glucose meter reading that was ≥ 4.0 mmol/L 15 min after treatment. Each subject treated five hypoglycemic events with each treatment type: glucose (BD Glucose Tablets™), sucrose (Skittles™), and fructose (Fruit to Go™). Results: There was a significant difference between the effectiveness of the three treatments [Wilk's Lambda F(2,28) = 8.64, p = 0.001]. No significant difference between treatment with glucose and treatment with sucrose was noted, but the treatment effectiveness for fructose was significantly lower than sucrose [F (1,29) = 16.09, p < 0.001] and glucose [F (1,29) = 15.64, p < 0.001]. The preferred treatment choices before the study were as follows: 36% glucose, 18% sucrose, and 33% fructose sources. Poststudy, 52% of children preferred the same treatment, which was effective (glucose or sucrose), followed by 35% who changed their preference to an effective treatment. Conclusion: Skittles™ are as effective in treating hypoglycemia as more expensive BD Glucose Tablets™ in children with type 1 diabetes.

ObjectiveGhrelin is secreted primarily by the stomach and circulates as both acylated and desacyl ghrelin. Acylated (but not desacyl) ghrelin stimulates appetite. Both concentrations are elevated in Prader–Willi syndrome (PWS), suggesting that ghrelin may contribute to hyperphagia and overweight in these subjects. We evaluated whether long-acting octreotide (Oct) decreases acylated and desacyl ghrelin concentrations, body mass, appetite and compulsive behaviour towards food in adolescents with PWS.DesignA 56-week prospective, randomized, cross-over trial.MethodsNine subjects with PWS (age 14.6 (10.8–18.9) years, body mass index (BMI) Z-score +1.9 (0.6–3.0)) received either Oct (30 mg) or saline i.m. every 4 weeks for 16 weeks and were switched over to the other treatment after a 24-week washout period.ResultsEight subjects completed the study. Oct caused a decrease in both acylated (−53%) and desacyl (−54%) fasting ghrelin concentrations (PConclusionsOct treatment caused a prolonged decrease in ghrelin concentrations in adolescents with PWS but did not improve body mass or appetite. Future intervention studies aiming at clarifying the role of ghrelin in PWS should focus on the administration of specific inhibitors of ghrelin secretion or ghrelin receptor activity that do not interfere with other appetite-regulating peptides.

Purpose Previous research suggests that having diabetes may complicate the passage from adolescence to adulthood. The aim of this study was to establish if young adults with Type 1 diabetes (T1DM) had delays in aspects of their psychosocial maturation compared with healthy controls (HC). Methods A cross-sectional study compared psychosocial maturation in individuals aged 18–25 years with T1DM to age-matched healthy controls. After obtaining consent, participants completed the following measures: Responsibility and Independence Scale for Adolescents (RISA; psychosocial maturity); Social Maturation Index (SMI, social maturity); Levenson's Locus of Control Scales (LOC, internal versus external locus of control) and the Social Density Grid (SDG, social network). Results In total, 160 subjects completed the study (97 T1DM, 63 HC). Participants included 101 females. No group differences were found on the RISA total score or the Responsibility or Independence Subscales of this measure. On the SMI, the proportion of subjects within each category (good, moderate or poor) was similar for each group. The overall number of social contacts identified on the SDG was similar for all groups; however, individuals with diabetes identified fewer friends within their social network that knew each other (F (2,160) = 3.28, p Conclusions Young adults with Type 1 diabetes did not show delayed psychosocial maturation when compared with healthy young adult controls.

PURPOSE To assess the image and patient level interrater agreement and repeatability within 1 month for corneal nerve fiber length (CNFL) measured using in vivo corneal confocal microscopy (IVCCM) in children. METHODS Seventy-one subjects (mean [SD] age 14.3 [2.6] years, range 8-18 years; 44 with type 1 diabetes and 27 controls; 36 males and 35 females) were included. 547 images (∼6 images per subject) were analyzed manually by two independent and masked observers. One-month repeat visit images were analyzed by a single masked observer in 21 patients. Automated image analysis was then performed using a specialized computerized software (ACCMetrics). RESULTS For CNFL, the ICC (95% CI) were 0.94 (0.93-0.95) for image-level, 0.86 (0.78-0.91) for patient-level, and 0.88 (0.72-0.95) for the 1-month repeat assessment, and the Bland-Altman plots showed minimal bias between observers. Although there was excellent agreement between manual and automated analysis according to an ICC 0.89 (0.82-0.93), the Bland-Altman plot showed a consistent bias with manual measurements providing higher readings. CONCLUSIONS In vivo corneal confocal microscopy image analysis shows good reproducibility with excellent intraindividual and interindividual variability in pediatric subjects. Since the image-level reproducibility is stronger than the patient-level reproducibility, refinement of the method for image selection will likely further increase the robustness of this novel, rapid, and noninvasive approach to detect early neuropathy in children with diabetes. Further studies on the use of IVCCM to identify early subclinical neuropathy in children are indicated.

Context 11β-hydroxylase deficiency is the second most common form of congenital adrenal hyperplasia. Untreated, this enzyme deficiency leads to virilization, hypertension, and significant height impairment. Patient We describe a patient from abroad who first presented to us at age 7 years for follow-up of ambiguous genitalia. He had been investigated and treated in Pakistan at 3-years-of-age following presentation for bilateral cryptorchidism. He was found to have 46, XX karyotype, elevated 17-OH progesterone and was diagnosed with congenital adrenal hyperplasia. In Pakistan, the patient had abdominal hysterectomy, bilateral salpingoophrectomy, and was started on corticosteroid replacement. At 7 years, shortly after immigrating to Canada, height was 138 cm and BMI 19.3 kg/m2 (+2.9 SDS and +1.7 SDS, respectively, male growth chart) and blood pressure was greater than the 99th percentile for age and height. The patient had Prader stage III - IV genital anatomy. Bone age was significantly advanced, yielding a severely compromised predicted final adult height. Biochemical evaluation was consistent with 11β-hydroxylase deficiency congenital adrenal hyperplasia. Intervention and outcome In an attempt to improve final height, in addition to glucocorticoid replacement, this patient was treated with recombinant growth hormone and a third generation aromatase inhibitor (Letrozole) with an improvement in final height attained as compared with predicted height. Conclusions This case of a 46,XX patient raised as male with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency highlights a number of unique and difficult treatment challenges; specifically, the role of new therapeutic options for optimization of growth in the context of prior suboptimal disease management.

Background: Neuropathy is an important complication and contributes to the morbidity of diabetes mellitus. The availability of simple and non-invasive tests for screening of early diabetic neuropathy (DN) in children with diabetes may prevent further progression of this complication. The purpose of this study was to compare conventional nerve conduction studies (NCS) with non-invasive techniques, including vibration perception thresholds (VPT) and tactile perception thresholds (TPT) for the detection of DN in children and adolescents with type 1 diabetes. Methods: Children from the Alberta Children’s Hospital Diabetes Clinic with at least 5 yr duration of type 1 diabetes underwent detailed evaluations, including neurologic exam, NCS, VPT, and TPT testing. Information on duration of diabetes, height, and mean glycosylated hemoglobin (A1C) were also collected. Descriptive statistics, including Student’s t-test and chi-squared test, were used for analysis. Results: Seventy-three children (mean age of 13.7 ± 2.6 yr) completed the study. The mean duration of diabetes was 8.1 ± 2.6 yr, and the mean A1C was 9.0 ± 1.0%. Forty-two (57%) children had DN based on NCS. Using NCS as a gold standard, the sensitivity and specificity of VPT were 62 and 65%, while the sensitivity and specificity of TPT were 19 and 64%, respectively. Conclusions: Subclinical DN is common among children and adolescents with type 1 diabetes, and there is a need for better metabolic control in this population. VPT and TPT may not be adequate screening tools for the detection of DN in children.

OBJECTIVE To determine the accuracy and reliability of reporting of selfmonitoring of blood glucose results by adults with types 1 and 2 diabetes during 2 different periods. METHODS Sixty adults (15 with type 1 diabetes on intensive management and 45 with type 2 diabetes on conventional management) who were part of separate clinical trials participated. Logbooks were compared with meter-downloaded results from the first 2 months (period 1) and last 2 months (period 2) of each trial. Reported values were categorized as clinically accurate (≤ 15% difference between logbook and meter), modified (> 15% difference), phantom (absent in meter) or omission (absent in logbook). RESULTS Only 53% of type 1 and 59% of type 2 patients were very reliable (> 90% of values clinically accurate) in their reporting by period 2. Inaccuracies consisted of phantom and omitted values but did not represent an attempt to improve the clinical profile. Individuals who were very reliable had optimal glycemic control; were more satisfied and less worried (quality of life); and were more confident (self-efficacy) in their diabetes self-management. CONCLUSIONS Relying solely on logbooks for self-management data can be misleading. Therefore, we recommend that clinicians also use meter-downloaded data to inform decision-making in the clinical care of patients with diabetes.

The worldwide burden of diabetes and its complications in children continues to increase due to the rise in type 1 and type 2 diabetes. Although overt diabetic neuropathy is rarely present in children and adolescents with diabetes, subclinical diabetic neuropathy has been estimated to occur in approximately half of all children with type 1 diabetes with a duration of 5 years or longer and up to 25% of pediatric patients with newly diagnosed diabetes have abnormal findings on nerve conduction studies. The present review on the state of pediatric diabetic neuropathy covers the definition, prevalence, pathogenesis, diagnosis, risk factors, and possible treatment approaches specific to children and adolescents with diabetes. It also highlights the many unknowns in this field. Nonetheless, new emerging interventions that can either prevent or delay the progression of diabetic microvascular and macrovascular complications may become available in the near future. Until specific interventions for diabetic neuropathy are available for use in children, it will be hard to justify screening for neuropathy other than through clinical assessment. Meanwhile, the search for quicker, easily administered, and quantifiable tests for diabetic neuropathy and efforts to establish valid pediatric norms for well-established measures used in adults will need to continue.

To compare the characteristics of symptoms of hypoglycemia in children and in adults with type 1 diabetes.Adults with diabetes and parents of children with diabetes who were participants were asked to call a phone system to report episodes of hypoglycemia (presence of symptoms and a blood glucose4.0 mmol/L). For each episode, blood glucose reading and a scoring of 28 symptoms on a 7-point scale (1 = not present, 7 = very intense) were collected.Sixty six children (49.2% males, mean age = 12.1±2.4 years, mean age at diagnosis = 7.5±2.9 years) and 53 adults (41.2% males, mean age 38.7±14.5 years, mean age at diagnosis = 17.5±12.9 years) with type 1 diabetes participated. The most common symptoms in adults were hunger, sweating, trembling and weakness. The most common symptoms in children were weakness, trembling and hunger. The 2 most discriminating variables between children and adults were sleepiness and tiredness, which were more common in children (p0.01). In a comparative factor analysis, 3 factors emerged: factor 1, autonomic and neuroglycopenic; factor 2, behavioural; and factor 3, general malaise. Factors 2 and 3 were significantly more common or intense in children than in adults; MANOVA: F(1, 113) = 6.72, p0.05 and F(1, 113) = 4.64, p0.05, respectively.Symptoms relating to behaviour and general malaise are more common in children than in adults with type 1 diabetes. The results of this study may assist providers in educating caregivers of children and patients with diabetes how to better recognize episodes of hypoglycemia.

The worldwide burden of diabetes and its complications in children continues to increase due to the rise in type 1 and type 2 diabetes. Although overt diabetic neuropathy is rarely present in children and adolescents with diabetes, subclinical diabetic neuropathy has been estimated to occur in approximately half of all children with type 1 diabetes with a duration of 5 years or longer and up to 25% of pediatric patients with newly diagnosed diabetes have abnormal findings on nerve conduction studies. The present review on the state of pediatric diabetic neuropathy covers the definition, prevalence, pathogenesis, diagnosis, risk factors, and possible treatment approaches specific to children and adolescents with diabetes. It also highlights the many unknowns in this field. Nonetheless, new emerging interventions that can either prevent or delay the progression of diabetic microvascular and macrovascular complications may become available in the near future. Until specific interventions for diabetic neuropathy are available for use in children, it will be hard to justify screening for neuropathy other than through clinical assessment. Meanwhile, the search for quicker, easily administered, and quantifiable tests for diabetic neuropathy and efforts to establish valid pediatric norms for well-established measures used in adults will need to continue.

Androgen replacement therapy for male hypogonadism may be prescribed utilizing intramuscular, oral or more recently, topical formulations. With topical formulations, there is a risk of person-to-person transmission if appropriate precautions are not taken. We describe two cases of virilization in pre-pubertal children following passive transfer of paternal topical testosterone. A 21 month old male was referred with a 6 week history of pubic hair, phallic growth, and linear growth spurt. Genital examination revealed Tanner stage 2 pubic hair and Tanner stage 3 phallic development, which was discordant with the pre-pubertal testicular size (2 mL bilaterally). A 3 year 8 month old girl was referred for a 2 month history of increasing pubic hair development. Examination revealed Tanner stage 2 pubic hair and Tanner stage 1 breast development. Both of these patients had fathers who had been diagnosed with hypogonadism and were being treated with topical androgen gel therapy, which they applied to their arms and chest before bed. In addition, both patients often slept with their parents resulting in skin-to-skin contact. Investigations were consistent with gonadotropin independent virilization with both patients demonstrating elevated testosterone levels. Testosterone levels returned to normal pre-pubertal levels with no further development of secondary sexual characteristics following discontinuation of exposure to topical testosterone. Precautions must be taken to prevent person-to-person transfer of topical steroids. With the increasing popularity of topical steroids for the treatment of low testosterone, it is imperative that these therapies be prescribed and utilized judiciously to prevent harm, specifically gonadotropin-independent virilization.

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy.

Pediatric bone marrow transplantation (BMT) for various diseases can lead to endocrine system dysfunction owing to preparative regimens involving chemotherapy and radiation therapy. We assessed the prevalence of post-BMT endocrine complications in children treated at the Alberta Children's Hospital (ACH) from 1991 to 2001. Time of onset of endocrine dysfunction, underlying disease processes, chemotherapy, radiation therapy and age at BMT were characterized. Subjects of

Bisphosphonate treatment for bone fragility has expanded beyond children with osteogenesis imperfecta (OI) to those with other causes of low bone mass. However, clinical efficacy and optimal dosing in non-OI patients has not been established. We conducted a retrospective descriptive study of patients with non-OI-related bone fragility to describe the effects of two different pamidronate treatment regimens on the bone mineral density (BMD) and fracture rate of these children. Between 2000 and 2009, 15 non-OI patients aged 8-16 years received pamidronate 1 mg/kg intravenously for 1 day every 3 months (4 mg/kg/year) or 1 mg/kg/day for 3 days every 4 months (9 mg/kg/year). After 1 year of pamidronate, the two groups had a comparable increase in adjusted BMD and reduction in fragility fractures. No serious adverse effects were observed. Since the long-term effects of bisphosphonate are unknown, large trials are needed to delineate the minimal effective dose in these patients.

Objective The relationships among hope, perceived maternal empathy, medical regimen adherence, and glycemic control in adolescents with type 1 diabetes were examined. Method Twenty-nine girls and 21 boys with type 1 diabetes completed measures of hope, perceived maternal empathy, and medical regimen adherence. Each participant's most recent hemoglobin A1c, a measure of glycemic control, was obtained from the diabetes clinic database. Results Significant correlations were found among hope, perceived maternal empathy, and medical regimen adherence. Significant correlations were also found among hope, perceived maternal empathy, and glycemic control. Adolescents' perceptions of maternal empathy were positively correlated with level of hope. Hope appeared to mediate the relationship between perceived maternal empathy and adherence, as well as between perceived maternal empathy and glycemic control. Conclusions The results of this study affirm the need for longitudinal research that examines the associations among hope, perceived maternal empathy, medical regimen adherence, and glycemic control.

Background: Information about the prevalence of obesity in children with type 1 diabetes mellitus (DM1) is inconsistent and limited. The burden of the concurrent problems of obesity and DM1 can have notable medical, psychological, and social implications for both patients and their families. Aims: To determine prevalences of overweight and obesity in children with DM1 compared to a control population. Methods: In a cross-sectional study, we compared the prevalence of overweight/obesity in 390 children with DM1 (males 54%) and 565 controls (CONT; males 60%) aged 6 to 16 years. Overweight and obesity were defined as body mass indices between the 85 th and 95 th percentiles, and greater than the 95 th percentile for age, respectively. Results: Overall, 29.5% DM1 and 18.1% CONT (p

Given the recent spate of reports of vitamin D deficiency, there is a need to reexamine our understanding of natural and other sources of vitamin D, as well as mechanisms whereby vitamin D synthesis and intake can be optimized. This stateof-the-art report from the Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society was aimed to perform this task and also reviews recommendations for sun exposure and vitamin D intake and possible caveats associated with these recommendations. Pediatrics 2008;122:398‐417

Case 1: A 2-year-old North African boy was brought to our hospital because of absent teeth development and failure to walk. The patient appeared to be well nourished and content. His body mass index was 19.1 kg/m2 (90th percentile), he was 86 cm long (25th percentile) and he weighed 13.6 kg (75th

Neurological deterioration in children with diabetic ketoacidosis (DKA) is commonly caused by cerebral edema. However, stroke should also be suspected when focal neurological deficits are apparent, because children with hyperglycemia and DKA are prone to thrombosis. We report three cases of pediatric stroke associated with new onset type 1 diabetes mellitus (T1DM). The first case presented with sinovenous thrombosis, and the other two cases presented in DKA and had a late diagnosis of ischemic stroke following neurological deterioration. Our recent experiences and review of the literature emphasize the importance of early diagnosis, investigation, and treatment for patients that present with new onset T1DM and stroke.