Shlomit Shalitin

Use of continuous glucose monitoring in children and adolescents

Moshe Phillipa,b,c, Thomas Danned, Shlomit Shalitina,b,c, Bruce Buckinghame, Lori Laffelf, William Tamborlaneg, Tadej Battelinoh and for the Consensus Forum Participantsi aThe Jesse Z and Sara Lea Shafer Institute of Endocrinology and Diabetes, National Center for Childhood Diabetes, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel; bMolecular Endocrinology and Diabetes Laboratory, Felsenstein Medical Research Center, Petah Tikva, Israel; cSackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; dDiabetes Zentrum fur Kinder und Jugendliche, Kinderkrankenhaus auf der Bult, Hannover, Germany; ePediatric Endocrinology, Stanford University, Stanford, CA, USA; fPediatric, Adolescent and Young Adult Section, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA; gPediatric Endocrinology, Yale University School of Medicine, New Haven, CT, USA; hDepartment of Pediatric Endocrinology, Diabetes Metabolism, University Children’s Hospital, Ljubljana, Slovenia and iA complete list of participants in the forum can be found in the acknowledgments.

Serum ferritin level as a predictor of impaired growth and puberty in thalassemia major patients.

Abstract:  Objective: Previous studies suggested that in patients with thalassemia major, initiating deferoxamine (DFO) therapy before puberty can prevent iron‐induced failure of growth and puberty. However, early initiation of chelation has also been associated with DFO toxicity. The aim of this retrospective study was to determine the prevalence rates of endocrine complications and DFO bone toxicity in our thalassemia major patients and to correlate them with the degree of iron chelation. Methods: Thirty‐nine patients with thalassemia major were followed for a median of 16.3 yr (range 2–28). Individual mean serum ferritin level during the study period was calculated using repeated annual measurements. Bone DFO toxicity was assessed by wrist and spine radiographs; endocrine dysfunction by anthropometric measurements and pubertal stage; and hypogonadotropic hypogonadism by lack of luteinizing hormone response to gonadotropin‐releasing hormone. Results: Chelation therapy was initiated at median age 4.9 yr. Mean serum ferritin level during the study period was 2698 ± 1444 ng/mL. Hypogonadism was noted in 59% of the patients who reached pubertal age, and short stature was found in 36% of patients who reached final height. Mean ferritin level of 2500 ng/mL during puberty was the cut‐off for hypogonadism, and ferritin level of 3000 ng/mL during prepuberty was the cut‐off for final short stature. None of the patients who attained final height had signs of DFO bone toxicity. Conclusions: High serum ferritin levels during puberty are a risk factor for hypogonadism, and high serum ferritin levels during the first decade of life predict final short stature. It remains to be determined whether improving chelation by earlier initiation of DFO or by the combined use of DFO and deferiprone will lead to better growth and sexual development without DFO toxicity.

Effects of a twelve-week randomized intervention of exercise and/or diet on weight loss and weight maintenance, and other metabolic parameters in obese preadolescent children.

Aims: To compare the short- and long-term effects of intervention programs on body weight and cardiometabolic risk factors. Methods: 162 obese children (6–11 years) were randomly assigned to three 12-week interventions with a 9-month follow-up period: exercise (E): 90 min moderate exercise 3 days/week (n = 52); diet (D): balanced hypocaloric diet, weekly meetings with dietician (n = 55), and diet + exercise (D+E) (n = 55). Changes in anthropometric variables, cardiometabolic profile and psychological outcome were assessed. Results: At 12 weeks BMI-SDS, cardiometabolic profiles, and psychological score improved in all groups. The decrease in BMI-SDS was greater in D and D+E compared with E (p < 0.001), without a significant difference between the first two groups. Waist circumference and LDL cholesterol decreased more in D+E compared with E (p = 0.026 and p = 0.038, respectively). The increase in adiponectin was greater in D and D+E compared with E (p = 0.004). Anthropometric and cardiometabolic variables regressed without significant differences between groups after 9 months. However, BMI-SDS, body fat percentage and LDL cholesterol were lower compared to baseline. Conclusions: Diet alone or combined with exercise are the most effective short-term interventions for weight loss and improved cardiometabolic profiles, without a difference between them. In the long term, obese children need the long-term support of maintenance approaches.

Nonalcoholic fatty liver disease in overweight children and adolescents

Objective: To investigate the prevalence and characteristics of non‐alcoholic fatty liver disease (NAFLD) and identify predictors for NAFLD in an overweight paediatric population.

Prevalence of Thyroid Dysfunction in Obese Children and Adolescents before and after Weight Reduction and Its Relation to Other Metabolic Parameters

Aim: To establish the prevalence of elevated thyroid-stimulating hormone (TSH) levels in obese children and adolescents, and identify the relationship between changes in TSH levels and other metabolic and hormonal variables before and after weight reduction. Methods: 207 obese participants aged 5–18 years were evaluated for anthropometric, biochemical, metabolic and hormonal variables before and after a weight reduction. Results: At baseline, 46 participants (22.2%) had hyperthyrotropinemia (≥4.0 mIU/l). Free T4 levels were normal in all cases. Triglyceride levels were significantly higher in participants with hyperthyrotropinemia than in those with normal thyroid function (p = 0.011). Baseline TSH was significantly correlated with triglyceride levels (r = 0.261, p < 0.001), but not with age, anthropometric, or laboratory variables. Of the 142 participants who completed the intervention, 27 (19 %) had hyperthyrotropinemia. There was no significant relationship between changes in TSH level and changes in body mass index-standard deviation score. A significant correlation was found between the final TSH level and triglyceride level (r = 0.167, p = 0.045), and between the decrease in TSH level and the decrease in waist circumference (r = 0.291, p = 0.013). Conclusions: In obese children, hyperthyrotropinemia with normal free T4 levels appears to be frequent. The correlation of hyperthyrotropinemia with waist circumference and higher triglyceride levels raises the question of the necessity to treat the elevated TSH levels.

Homozygosity and linkage-disequilibrium mapping of the syndrome of congenital hypoparathyroidism, growth and mental retardation, and dysmorphism to a 1-cM interval on chromosome 1q42-43

The syndrome of hypoparathyroidism associated with growth retardation, developmental delay, and dysmorphism (HRD) is a newly described, autosomal recessive, congenital disorder with severe, often fatal consequences. Since the syndrome is very rare, with all parents of affected individuals being consanguineous, it is presumed to be caused by homozygous inheritance of a single recessive mutation from a common ancestor. To localize the HRD gene, we performed a genomewide screen using DNA pooling and homozygosity mapping for apparently unlinked kindreds. Analysis of a panel of 359 highly polymorphic markers revealed linkage to D1S235. The maximum LOD score obtained was 4.11 at a recombination fraction of 0. Analysis of three additional markers-GGAA6F06, D1S2678, and D1S179-in a 2-cM interval around D1S235 resulted in LOD scores >3. Analysis of additional chromosome 1 markers revealed evidence of genetic linkage disequilibrium and place the HRD locus within an approximately 1-cM interval defined by D1S1540 and D1S2678 on chromosome 1q42-43.

Factors associated with increased risk of insulin pump discontinuation in pediatric patients with type 1 diabetes.

de Vries L, Grushka Y, Lebenthal Y, Shalitin S, Phillip M. Factors associated with increased risk of insulin pump discontinuation in pediatric patients with type 1 diabetes.

Hypoglycemia in Type 1 Diabetes: A still unresolved problem in the era of insulin analogs and pump therapy

The Diabetes Control and Complications Trial demonstrated that in patients with type 1 diabetes, tight metabolic control achieved with intensive insulin therapy can reduce the risk of long-term microvascular complications. However, strict glycemic control carries an increased risk of severe hypoglycemia. Recurrent episodes of hypoglycemia, especially at young ages, can lead to hypoglycemia unawareness, exert adverse effects on neurocognitive function, and cause significant emotional morbidity in the child and parents. Although the introduction of the new insulin analogs in diabetes therapy and the use of continuous subcutaneous insulin infusion raised hopes for a solution to this problem, these modalities have not been associated with the expected reduction in hypoglycemic episodes. The findings suggest that the prevention of hypoglycemia in patients with type 1 diabetes lies in biologically controlled insulin secretion, as in islet transplantation, or the development of an autonomous closed-loop system that efficiently mimics the action of the pancreatic β-cells and maintains blood glucose levels within the desired range.

Low‐carbohydrate (low & high‐fat) versus high‐carbohydrate low‐fat diets in the treatment of obesity in adolescents

Aim: To compare the impact of low‐carbohydrate diets of different fat content to high‐carbohydrate low‐fat diet on weight and metabolic parameters in obese adolescents.

Predictors of glycaemic control in patients with Type 1 diabetes commencing continuous subcutaneous insulin infusion therapy

Diabet. Med. 27, 339–347 (2010)