Zohar Landau

Endocrine Effects of Valproate in Adolescent Girls with Epilepsy

Summary:  Purpose: To investigate the effect of epilepsy and/or valproate (VPA) monotherapy on physical growth, weight gain, pubertal development, and hormonal status in adolescent girls with epilepsy.

Clinical and genetic heterogeneity of congenital adrenal hypoplasia due to NR0B1 gene mutations.

Introduction  X‐linked adrenal hypoplasia congenita (AHC) is a rare disorder caused by mutations or complete deletion of the NR0B1 gene that encodes the DAX‐1 protein, an orphan member of the nuclear receptor superfamily. AHC is characterized by adrenal insufficiency in infancy and early childhood. Later, hypogonadotropic hypogonadism (HH) manifests as pubertal failure.

Fasting Until Noon Triggers Increased Postprandial Hyperglycemia and Impaired Insulin Response After Lunch and Dinner in Individuals With Type 2 Diabetes: A Randomized Clinical Trial

OBJECTIVE Skipping breakfast has been consistently associated with high HbA1c and postprandial hyperglycemia (PPHG) in patients with type 2 diabetes. Our aim was to explore the effect of skipping breakfast on glycemia after a subsequent isocaloric (700 kcal) lunch and dinner. RESEARCH DESIGN AND METHODS In a crossover design, 22 patients with diabetes with a mean diabetes duration of 8.4 ± 0.7 years, age 56.9 ± 1.0 years, BMI 28.2 ± 0.6 kg/m2, and HbA1c 7.7 ± 0.1% (61 ± 0.8 mmol/mol) were randomly assigned to two test days: one day with breakfast, lunch, and dinner (YesB) and another with lunch and dinner but no breakfast (NoB). Postprandial plasma glucose, insulin, C-peptide, free fatty acids (FFA), glucagon, and intact glucagon-like peptide-1 (iGLP-1) were assessed. RESULTS Compared with YesB, lunch area under the curves for 0–180 min (AUC0–180) for plasma glucose, FFA, and glucagon were 36.8, 41.1, and 14.8% higher, respectively, whereas the AUC0-180 for insulin and iGLP-1 were 17% and 19% lower, respectively, on the NoB day (P < 0.0001). Similarly, dinner AUC0-180 for glucose, FFA, and glucagon were 26.6, 29.6, and 11.5% higher, respectively, and AUC0-180 for insulin and iGLP-1 were 7.9% and 16.5% lower on the NoB day compared with the YesB day (P < 0.0001). Furthermore, insulin peak was delayed 30 min after lunch and dinner on the NoB day compared with the YesB day. CONCLUSIONS Skipping breakfast increases PPHG after lunch and dinner in association with lower iGLP-1 and impaired insulin response. This study shows a long-term influence of breakfast on glucose regulation that persists throughout the day. Breakfast consumption could be a successful strategy for reduction of PPHG in type 2 diabetes.

The effectiveness of Internet-based blood glucose monitoring system on improving diabetes control in adolescents with type 1 diabetes.

Landau Z, Mazor‐Aronovitch K, Boaz M, Blaychfeld‐Magnazi M, Graph‐Barel C, Levek‐Motola N, Pinhas‐Hamiel O. The effectiveness of Internet‐based blood glucose monitoring system on improving diabetes control in adolescents with type 1 diabetes.

Institutional blood glucose monitoring system for hospitalized patients: an integral component of the inpatient glucose control program.

Background: The ability to measure patient blood glucose levels at bedside in hospitalized patients and to transmit those values to a central database enables and facilitates glucose control and follow-up and is an integral component in the care of the hospitalized diabetic patient. Objective: The goal of this study was to evaluate the performance of an institutional glucometer employed in the framework of the Program for the Treatment of the Hospitalized Diabetic Patient (PTHDP) at E. Wolfson Medical Center, Holon, Israel. Methods: As part of the program to facilitate glucose control in hospitalized diabetic patients, an institutional glucometer was employed that permits uploading of data from stands located in each inpatient department and downloading of that data to a central hospital-wide database. Blood glucose values from hospitalized diabetic patients were collected from August 2007 to October 2008. The inpatient glucose control program was introduced gradually beginning January 2008. Results: During the follow-up period, more than 150,000 blood glucose measures were taken. Mean glucose was 195.7 ± 99.12 mg/dl during the follow-up period. Blood glucose values declined from 206 ± 105 prior to PTHDP (August 2007–December 2007) to 186 ± 92 after its inception (January 2008–October 2008). The decline was associated significantly with time (r = 0.11, p < 0.0001). The prevalence of blood glucose values lower than 60 mg/dl was 1.48% [95% confidence interval (CI) 0.36%] prior to vs 1.55% (95% CI 0.37%) following implementation of the PTHDP. Concomitantly, a significant increase in the proportion of blood glucose values between 80 and 200 mg/dl was observed, from 55.5% prior to program initiation vs 61.6% after program initiation (p < 0.0001). Conclusions: The present study was designed to observe changes in institution-wide glucose values following implementation of the PTHDP. Information was extracted from the glucometer system itself. Because the aforementioned study was not a clinical trial, we cannot rule out that factors other than introduction of the program could explain some of the variability observed. With these limitations in mind, it nevertheless appears that the PTHDP, of which the institutional glucometer is an integral, essential component, was associated with improved blood glucose values in the hospitalized diabetic patient.

Prevalence of overweight, obesity and metabolic syndrome components in children, adolescents and young adults with type 1 diabetes mellitus

We aimed to determine the prevalence of overweight and obesity among children, adolescents and young adults with type 1 diabetes mellitus (T1DM), and to assess the prevalence of the metabolic syndrome and its components.

Alpha-1 antitrypsin therapy is safe and well tolerated in children and adolescents with recent onset type 1 diabetes mellitus†

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).

Influences of Breakfast on Clock Gene Expression and Postprandial Glycemia in Healthy Individuals and Individuals With Diabetes: A Randomized Clinical Trial

OBJECTIVE The circadian clock regulates glucose metabolism by mediating the activity of metabolic enzymes, hormones, and transport systems. Breakfast skipping and night eating have been associated with high HbA1c and postprandial hyperglycemia after lunch and dinner. Our aim was to explore the acute effect of breakfast consumption or omission on glucose homeostasis and clock gene expression in healthy individuals and individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS In a crossover design, 18 healthy volunteers and 18 volunteers with 14.5 ± 1.5 years diabetes, BMI 30.7 ± 1.1 kg/m2, and HbA1c 7.6 ± 0.1% (59.6 ± 0.8 mmol/mol) were randomly assigned to a test day with breakfast and lunch (YesB) and a test day with only lunch (NoB). Postprandial clock and clock-controlled gene expression, plasma glucose, insulin, intact glucagon-like peptide 1 (iGLP-1), and dipeptidyl peptidase IV (DPP-IV) plasma activity were assessed after breakfast and lunch. RESULTS In healthy individuals, the expression level of Per1, Cry1, Rorα, and Sirt1 was lower (P < 0.05) but Clock was higher (P < 0.05) after breakfast. In contrast, in individuals with type 2 diabetes, Per1, Per2, and Sirt1 only slightly, but significantly, decreased and Rorα increased (P < 0.05) after breakfast. In healthy individuals, the expression level of Bmal1, Rorα, and Sirt1 was higher (P < 0.05) after lunch on YesB day, whereas the other clock genes remained unchanged. In individuals with type 2 diabetes, Bmal1, Per1, Per2, Rev-erbα, and Ampk increased (P < 0.05) after lunch on the YesB day. Omission of breakfast altered clock and metabolic gene expression in both healthy and individuals with type 2 diabetes. CONCLUSIONS Breakfast consumption acutely affects clock and clock-controlled gene expression leading to normal oscillation. Breakfast skipping adversely affects clock and clock-controlled gene expression and is correlated with increased postprandial glycemic response in both healthy individuals and individuals with diabetes.

Improved pharmacokinetic and pharmacodynamic profiles of insulin analogues using InsuPatch, a local heating device

Previous studies have shown that heating the insulin injection site may accelerate insulin absorption. We investigated the pharmacological profile of insulin administered with InsuPatch, a local skin‐heating device.

Congenital Hyperreninemic Hypoaldosteronism in Israel: Sequence Analysis of CYP11B2 Gene

Background/Aims: Isolated aldosterone biosynthesis defect causing congenital hyperreninemic hypoaldosteronism with otherwise normal adrenal function usually results from aldosterone synthase deficiency. Patients present with manifestations of mineralocorticoid deficiency during the first weeks of life. The largest numbers of cases have been described in Iranian Jews, who carried concomitantly two homozygous missense mutations (R181W and V386A). In a few cases with presumed aldosterone synthase deficiency no mutations in CYP11B2 gene have been identified. We describe a molecular and endocrine evaluation of seven cases of congenital hyperreninemic hypoaldosteronism in Israel. Patients/Methods: Two of the six Jewish patients are of Iranian origin. The parents of five other patients originated from Yemen, Syria and Morocco. One patient is a Muslim-Arab. CYP11B2’s exons, exon–intron boundaries and promoter region were sequenced by multiple PCR amplifications. Gene size determination was performed either by long-range PCR or by Southern blot analysis. Results: Only two patients (Iranian Jews) carried a known homozygous R181W, V386A mutations, other two were compound heterozygotes for either the R181W or V386A and one additional novel amino acid substitution (A319V or D335G), and one patient was found to be a carrier of the two novel variations (A319V and D335G). We could not find a molecular defect in 2 patients: one was a carrier of the D335G mutation and the other had no detectable molecular change in the coding and promoter regions. Conclusion: The genetic and molecular basis of congenital hyperreninemic hypoaldosteronism is more heterogeneous than previously described. The significance of amino acid substitutions identified in this study remains to be determined.