Pediatric Endocrine and Diabetes Unit

H̱olon, Israel

Pediatric Endocrine and Diabetes Unit

H̱olon, Israel
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von Laer Tschudin L.,University of Lausanne | Schwitzgebel V.M.,Pediatric Endocrine and Diabetes Unit | von Scheven-Gete A.,Rhumatologie Pediatrique Romande | Hofer M.,Rhumatologie Pediatrique Romande | And 4 more authors.
Pediatric Diabetes | Year: 2015

Type 1 diabetes (T1D) is rarely a component of primary immune dysregulation disorders. We report two cases in which T1D was associated with thrombocytopenia. The first patient, a 13-year-old boy, presented with immune thrombocytopenia (ITP), thyroiditis, and, 3 wk later, T1D. Because of severe thrombocytopenia resistant to immunoglobulins, high-dose steroids, and cyclosporine treatment, anti-cluster of differentiation (CD20) therapy was introduced, with consequent normalization of thrombocytes and weaning off of steroids. Three and 5 months after anti-CD20 therapy, levothyroxin and insulin therapy, respectively, were stopped. Ten months after stopping insulin treatment, normal C-peptide and hemoglobin A1c (HbA1c) levels and markedly reduced anti-glutamic acid decarboxylase (GAD) antibodies were measured. A second anti-CD20 trial for relapse of ITP was initiated 2 yr after the first trial. Anti-GAD antibody levels decreased again, but HbA1c stayed elevated and glucose monitoring showed elevated postprandial glycemia, demanding insulin therapy. To our knowledge, this is the first case in which insulin treatment could be interrupted for 28 months after anti-CD20 treatment. In patient two, thrombocytopenia followed a diagnosis of T1D 6 yr previously. Treatment with anti-CD20 led to normalization of thrombocytes, but no effect on T1D was observed. Concerning the origin of the boys' conditions, several primary immune dysregulation disorders were considered. Thrombocytopenia associated with T1D is unusual and could represent a new entity. The diabetes manifestation in patient one was probably triggered by corticosteroid treatment; regardless, anti-CD20 therapy appeared to be efficacious early in the course of T1D, but not long after the initial diagnosis of T1D, as shown for patient two. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Sadeh M.,Wolfson Medical Center | Glazer B.,Hadassah University Hospital | Landau Z.,Pediatric Endocrine and Diabetes Unit | Wainstein J.,Diabetes Unit | And 5 more authors.
The Israel Medical Association journal : IMAJ | Year: 2013

BACKGROUND: Type 1 diabetes in humans is an autoimmune disease in which Tcells target pancreatic islets of Langerhans, leading to the progressive destruction of the insulin-producing beta cells. Both genetic and environmental factors contribute to the development of autoimmune diabetes. The non-obese diabetic (NOD) mouse model of human type 1 diabetes demonstrates two missense mutations in the transient receptor potentialvanilloid receptor-1 (TRPVi) gene.OBJECTIVES: To investigate whether polymorphism in the TRPV1 gene may play a role in the predisposition to human type 1 diabetes.METHODS: We genotyped 146 Ashkenazi Jewish type 1 diabetic patients and 205 Ashkenazi Jewish healthy controls for the rs222747 (M3151), rs224534 (T4691) and rs8065080 (1585V) variants of the TRPV1 gene.RESULTS: There was a significant increase in the rs222747 (M3151) variant of the TRPV1 gene in the type 1 diabetes cohort compared to the control: rs222747 (M3151) homozygous: (61% vs. 48.3%, P = 0.02). Logistic regression analysis revealed that type 1 diabetes was significantly associated with rs222747 (M3151), such that having diabetes increased the odds of rs222747 homozygosity (M3151) by 67.2%, odds ratio 1.6, 95% confidence interval 1.08-2.57, P < 0.02. No difference was found in the rs224534 (T4691) and rs8065080 (1585V) allelic variants. There was no difference in any of the TRPV1 variants by gender, age when type 1 diabetes was diagnosed, body mass index, glycemic control, blood pressure, positive autoantibodies (ICA, GAD, IAA), and other autoimmune diseases.CONCLUSIONS: Our study demonstrates that TRPV1 may be a susceptible gene for type 1 diabetes in an Ashkenazi Jewish population. These results should be replicated in the same ethnic group and in other ethnic groups.


Sadeh M.,Wolfson Medical Center | Sadeh M.,Tel Aviv University | Glazer B.,Hadassah University Hospital | Landau Z.,Pediatric Endocrine and Diabetes Unit | And 11 more authors.
Israel Medical Association Journal | Year: 2013

Background: Type 1 diabetes in humans is an autoimmune disease in which T cells target pancreatic islets of Langerhans, leading to the progressive destruction of the insulinproducing beta cells. Both genetic and environmental factors contribute to the development of autoimmune diabetes. The non-obese diabetic (NOD) mouse model of human type 1 diabetes demonstrates two missense mutations in the transient receptor potential vanilloid receptor-1 (TRPV1) gene. Objectives: To investigate whether polymorphism in the TRPV1 gene may play a role in the predisposition to human type 1 diabetes. Methods: We genotyped 146 Ashkenazi Jewish type 1 diabetic patients and 205 Ashkenazi Jewish healthy controls for the rs222747 (M315I), rs224534 (T469I) and rs8065080 (I585V) variants of the TRPV1 gene. Results: There was a significant increase in the rs222747 (M315I) variant of the TRPV1 gene in the type 1 diabetes cohort compared to the control: rs222747 (M315I) homozygous: (61% vs. 48.3%, P = 0.02). Logistic regression analysis revealed that type 1 diabetes was significantly associated with rs222747 (M315I), such that having diabetes increased the odds of rs222747 homozygosity (M315I) by 67.2%, odds ratio 1.6, 95% confidence interval 1.08-2.57, P < 0.02. No difference was found in the rs224534 (T469I) and rs8065080 (I585V) allelic variants. There was no difference in any of the TRPV1 variants by gender, age when type 1 diabetes was diagnosed, body mass index, glycemic control, blood pressure, positive autoantibodies (ICA, GAD, IAA), and other autoimmune diseases. Conclusions: Our study demonstrates that TRPV1 may be a susceptible gene for type 1 diabetes in an Ashkenazi Jewish population. These results should be replicated in the same ethnic group and in other ethnic groups.


Rachmiel M.,Tel Aviv University | Strauss P.,Kamada Ltd Ness Ziona Israel | Dror N.,The Jesse Z And Sara Lea Shafer Institute For Endocrinology And Diabetes | Benzaquen H.,The Jesse Z And Sara Lea Shafer Institute For Endocrinology And Diabetes | And 10 more authors.
Pediatric Diabetes | Year: 2015

Background and objectives: Alpha-1 antitrypsin (AAT) has been shown to reduce pro-inflammatory markers and protect pancreatic islets from autoimmune responses in recent studies. Our aim was to evaluate its safety and tolerability in three different doses, in a pediatric population with recent onset type 1 diabetes mellitus (T1DM). Methods: A 37-wk prospective, open-label, phase I/II interventional trial, comprised of 24 recently diagnosed subjects (12 males; age 12.9±2.4yr), who received 18 infusions of 40, 60, or 80mg/kg/dose high-purity, liquid, ready to use AAT over 28 wk (Glassia®; Kamada Ltd., Ness Ziona, Israel). Primary outcomes: safety and tolerability; secondary outcomes: glycemic control, C-peptide reserve, and autoantibody levels. Possible responders were defined as individuals with peak C-peptide that declined less than 7.5% below baseline. Results: No serious adverse events, diabetic ketoacidosis (DKA), or severe hypoglycemic episodes were reported. Adverse events were dose-independent and transient. Glycemic control parameters improved during the study in all groups, independent of dosage. Hemoglobin A1c (HbA1c) decreased from 8.43 to 7.09% (mean, p<0.001). At the end of the study, 18 subjects (75%) had a peak C-peptide ≥0.2pmol/mL. Eight subjects (33.3%) were considered possible responders and were characterized by shorter duration of T1DM at screening (54.5±34.3 vs. 95.9±45.7d, p=0.036) and greater decrease in their HbA1c during the study period (-2.94±1.55 vs.-0.95±1.83%, p=0.016). Conclusions: AAT treatment was safe and well tolerated in pediatric subjects with recently diagnosed autoimmune diabetes. Placebo-controlled studies with larger cohorts and dose range are warranted in order to assess efficacy in maintaining pancreatic beta cell reserve and glycemic control. © 2015 John Wiley & Sons A/S.


PubMed | Epidemiology and Research Unit, Diabetes Unit, Hadassah University Hospital, Wolfson Medical Center and Pediatric Endocrine and Diabetes Unit
Type: Journal Article | Journal: The Israel Medical Association journal : IMAJ | Year: 2013

Type 1 diabetes in humans is an autoimmune disease in which Tcells target pancreatic islets of Langerhans, leading to the progressive destruction of the insulin-producing beta cells. Both genetic and environmental factors contribute to the development of autoimmune diabetes. The non-obese diabetic (NOD) mouse model of human type 1 diabetes demonstrates two missense mutations in the transient receptor potentialvanilloid receptor-1 (TRPVi) gene.To investigate whether polymorphism in the TRPV1 gene may play a role in the predisposition to human type 1 diabetes.We genotyped 146 Ashkenazi Jewish type 1 diabetic patients and 205 Ashkenazi Jewish healthy controls for the rs222747 (M3151), rs224534 (T4691) and rs8065080 (1585V) variants of the TRPV1 gene.There was a significant increase in the rs222747 (M3151) variant of the TRPV1 gene in the type 1 diabetes cohort compared to the control: rs222747 (M3151) homozygous: (61% vs. 48.3%, P = 0.02). Logistic regression analysis revealed that type 1 diabetes was significantly associated with rs222747 (M3151), such that having diabetes increased the odds of rs222747 homozygosity (M3151) by 67.2%, odds ratio 1.6, 95% confidence interval 1.08-2.57, P < 0.02. No difference was found in the rs224534 (T4691) and rs8065080 (1585V) allelic variants. There was no difference in any of the TRPV1 variants by gender, age when type 1 diabetes was diagnosed, body mass index, glycemic control, blood pressure, positive autoantibodies (ICA, GAD, IAA), and other autoimmune diseases.Our study demonstrates that TRPV1 may be a susceptible gene for type 1 diabetes in an Ashkenazi Jewish population. These results should be replicated in the same ethnic group and in other ethnic groups.


Goldberg-Stern H.,Epilepsy Service | Goldberg-Stern H.,Tel Aviv University | Itzhaki T.,Hadassah University Hospital | Itzhaki T.,Tel Aviv University | And 4 more authors.
Hormone Research in Paediatrics | Year: 2015

Background/Aims: To prospectively evaluate the long-term impact of valproate (VPA) versus carbamazepine (CBZ) on anthropometric, hormonal, and metabolic parameters in young male patients treated for epilepsy. Methods: Of 61 boys with newly diagnosed epilepsy followed up, 24 were excluded from analysis (17 were lost to follow-up and 7 changed therapy within <1 year). Findings were compared by time, treatment (VPA or CBZ), and epilepsy type (generalized or partial) as well as against a matched control group with adequately treated hypothyroidism. Results: Twenty-four boys were treated with VPA and 13 with CBZ. The weight-standard deviation score (SDS) significantly increased during the first 6 months of treatment (p < 0.001), irrespective of the drug type, but decreased between the first and the last visit (p = 0.01). In patients with generalized epilepsy, there was a slight decrease in height-and weight-SDS between the first and the last visit (p = 0.04 and p = 0.01, respectively). The height-SDS at the last visit was comparable to the parental height-SDS. The mean age at puberty onset was 11.2 and 11.4 years in the study and the control group, respectively (p = 0.08). There were no significant differences in the other parameters by treatment or epilepsy type. Conclusions: Long-term therapy with VPA or CBZ has no significant endocrinological or metabolic adverse effect on male children and adolescents with epilepsy. © 2015 S. Karger AG, Basel.


PubMed | Hadassah University Hospital, Tel Aviv University and Pediatric Endocrine and Diabetes Unit
Type: Review | Journal: Diabetes/metabolism research and reviews | Year: 2016

Many patients with type 2 diabetes fail to achieve adequate glucose control despite escalation of treatment and combinations of multiple therapies including insulin. Patients with long-standing type 2 diabetes often suffer from the combination of severe insulin deficiency in addition to insulin resistance, thereby requiring high doses of insulin delivered in multiple injections to attain adequate glycemic control. Insulin-pump therapy was first introduced in the 1970s as an approach to mimic physiological insulin delivery and attain normal glucose in patients with type 1 diabetes. The recent years have seen an increase in the use of this technology for patients with type 2 diabetes. This article summarizes the clinical studies evaluating insulin pump use in patients with type 2 diabetes and discusses the benefits and shortcomings of pump therapy in this population. Copyright 2016 John Wiley & Sons, Ltd.


Landau Z.,Maccabi National Juvenile Diabetes Center | Landau Z.,Tel Aviv University | Landau Z.,Pediatric Endocrine and Diabetes Unit | Mazor-Aronovitch K.,Maccabi National Juvenile Diabetes Center | And 9 more authors.
Pediatric Diabetes | Year: 2012

Objective: To determine whether the use of an Internet-based blood glucose monitoring system could improve glycemic control in adolescents with type 1 diabetes mellitus (T1DM). Methods: In a randomized, controlled clinical trial, a total of 70 adolescent subjects with T1DM were recruited. Subjects randomized to the intervention group (n = 36) were instructed to submit their blood glucose levels weekly by Internet to the Diabetes Care Team during a period of 6 months. Subjects randomized to the control group (n = 34) did not submit results but were under routine follow-up. Results: At baseline, patients were 15.1 ± 2.6 years of age with mean HbA1c of 8.3 ± 1.3%. At the 6-month follow-up period, no by-group differences in change from baseline to end of treatment HbA1c levels were detected. In the intervention group, 12/36 did not submit blood glucose levels and were classified as non-compliant. In a secondary exploratory analysis in which non-compliant patients were omitted, HbA1c values in the compliant intervention group declined from 8.5 ± 1.7% at baseline to 8.2 ± 1.2% at 6 months, while in the control group HbA1c values increased from 8.2 ± 1.1 to 8.4 ± 1.1%, this difference did not reach statistical significance. Conclusions: An Internet-based blood glucose monitoring system was not associated with improved glycemic control in adolescents with T1DM. Identification of a sub-group of compliant subjects who may improve metabolic control by using this tool is needed. © 2011 John Wiley & Sons A/S.


Pinhas-Hamiel O.,Pediatric Endocrine and Diabetes Unit | Pinhas-Hamiel O.,Tel Aviv University | Levy-Shraga Y.,Pediatric Endocrine and Diabetes Unit | Levy-Shraga Y.,Tel Aviv University
Current Diabetes Reports | Year: 2013

Diabetes is associated with increased risk for eating disorders; with different types of eating disorders associating with different types of diabetes. Binge eating disorders show increased prevalence among individuals with type 2 diabetes (T2DM). Intentional omission of insulin for the purpose of inducing weight loss presents among individuals with type 1 (T1DM). Similarly, some individuals with T2DM intentionally omit oral hypoglycemic drugs, resulting in poor glycemic control, and weight loss. Common dominators for the development of eating disorders in T1DM and T2DM are female gender, increased body weight, body dissatisfaction, a history of dieting, and a history of depression. Patients tend to deny the existence of the problem. Clinical signs that should raise suspicion are: poor glycemic control, missed clinical appointments, recurrent episodes of diabetes ketoacidosis, recurrent hypoglycemia secondary to intentional overdose, poor self-esteem, and dietary manipulation. Eating disorders are associated with poorer glycemic control, and therefore increased risk of diabetes associated comorbidities. © 2012 Springer Science+Business Media New York.

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