Israel Medical Association Journal

Pre-Ramadan fasting planning before the month of Ramadan represents a golden opportunity for better glucose control during the month of Ramadan among patients with type 2 diabetes mellitus (T2DM). Pre-Ramadan begins 1–2 months earlier and represents a crucial period when healthcare practitioners can provide medical instructions, risk assessment, and stratification to minimize the associated risks such as postprandial hyperglycemia and hypoglycemia during Ramadan fasting. This review focuses on two important classes of drugs that are widely used in Israel incretin-based therapy, particularly the glucagon-like peptide-1 receptor (GLP-1Rc) agonists class and the sodium-glucose cotransporter-2 inhibitors (SGLT-2i) class. In addition, we provide data regarding specific populations such as elderly patients and Bedouins living in the Negev area who require specific recommendations for safe Ramadan fasting. Our data are based on previously published guidelines, consensus statements, and our experience.

Background: The Iron Swords war created stressful circumstances that could negatively impact glycemic control in individuals with type 1 diabetes (T1D).

Objectives: To evaluate changes in continuous glucose monitoring (CGM) metrics in pediatric T1D patients during the war.

Methods: This retrospective study included T1D patients monitored by CGM. Metrics from three selected 2-week periods were compared (before the war, after the war outbreak, and 4 months later). Study variables included time-in-range (70–180 mg/dl; 3.9–10 mmol/L), time-in-tight-range (70–140 mg/dl; 3.9–7.8 mmol/L), time-in-marked-hypoglycemia (< 54 mg/dl; < 3 mmol/liter), and time-in-severe-hyperglycemia (> 250 mg/dl; >13.3 mmol/liter). Patients were treated with either a multiple daily insulin (MDI) regimen or insulin pump, with or without an open-source automated insulin delivery (OS-AID) system.

Results: Data of 99 patients were analyzed (mean age 12.2 ± 4.0 years, mean diabetes duration 4.6 ± 3.9 years, 52.5% males). No significant changes in CGM metrics were observed across the entire cohort at any time point. Patients with higher socioeconomic position (SEP; cluster > 7) had better CGM metrics, with an increase in time-in-tight-range in the lower SEP group and in time-in-severe-hyperglycemia in the higher SEP group (P = 0.003). OS-AID users (n=20) had superior pre-war CGM metrics and maintained stable glycemia during the war, MDI users showed increased time-in-severe-hyperglycemia post-outbreak (P = 0.05).

Conclusions: Throughout the war, children and adolescents with T1D treated with insulin pumps maintained relatively stable glycemic control. Susceptibility to change following the onset of war was influenced by SEP and mode of insulin therapy.

Background: Molybdenum cofactor deficiency (MoCD) is a group of three autosomal recessive disorders caused by deficiency of the de novo metabolic synthesis of molybdenum cofactor. Most patients present within the first weeks of life with intractable seizures and progressive encephalopathy. Type A is the most common form caused by pathogenic variants in MOCS1 gene that result in deficiency of the first enzyme, cyclic pyranopterin monophosphate synthase.

Objectives: To characterize MoCD type A clinical features, disease course, neuroradiology, and genetic features in Northern Israel.

Methods: In this retrospective study, we collected the clinical, brain imaging, and genetic data of confirmed MoCD type A patients in Northern Israel.

Results: The study included 10 confirmed MoCD type A patients (6 males, 4 females), all deceased. The patients were of consanguineous families. Nine patients were of Arab Muslim ethnicity and one was of Druze origin. A total of four different homozygous genotypes were identified. All patients presented initially between 1–4 days of life. Three died within the first month of life, five within the first year of life, and only two died after the age of 7 years. All patients who survived beyond the first month developed profound global developmental delays, had poorly controlled epilepsy, and developed severe microcephaly.

Conclusions: Although MoCD type A is an ultra-rare disease worldwide, it is relatively common in northern Israel due to several founder mutations and high consanguinity. All the patients presented the severe neonatal form of the disease with significant neurological deterioration and early lethality within infancy and childhood.

Anorexia nervosa (AN) is a common psychiatric disorder primarily affecting adolescents and young adults. It is characterized by extreme restriction of food intake, distorted body image, and weight-gain anxiety. We report a case with rapid progression and severe metabolic changes in a young restrictive-type AN patient, highlighting unique aspects of this presentation and discussing pathophysiology.

An 11-year-old girl presented with a significant 29% weight loss over 4 months, leading to a body mass index (BMI) of 11.7 (< 1st BMI percentile for her sex and age). She presented with severe bradycardia and metabolic abnormalities including hypoglycemia, hypercholesterolemia, and hypothyroidism. Following diagnosis with restrictive type AN based on the DSM-5 [1] criteria and stabilization at our department, she was transferred to a specialized unit. The hypercholesterolemia our patient presented with is more typical of binge-eating/purging subtype AN, yet it was markedly elevated in this restrictive-type case.

Background: The prognostic significance of diabetes mellitus (DM) on hospitalization outcomes of patients with acute decompensated heart failure (ADHF) remains inconclusive.

Objectives: To comprehensively assess the clinical outcomes of patients with and without DM hospitalized for ADHF.

Methods: This single center retrospective cohort study included consecutive hospitalized patients with a principal diagnosis of ADHF between 1 January 2010 and 31 December 2019. Patients were categorized into diabetic and non-diabetic groups. The primary outcomes assessed were in-hospital mortality, 1-year overall mortality, and readmission rate within a year of follow-up.

Results: The final analysis involved 787 ADHF patients, with 62% having a pre-existing diagnosis of DM. Despite a higher burden of co-morbidities in diabetic patients, there were no differences in clinical outcomes when compared to non-diabetic counterparts. Specifically, there were no differences in overall hospital mortality (10% vs. 10%, P = 0.675), 1-year mortality (22% vs. 25%, P = 0.389), and re-admissions (51% vs. 56%, P = 0.154). Notably, the 1-year mortality among diabetic patients was not influenced by HbA1c levels documented before or during admission.

Conclusions: The clinical outcomes of patients hospitalized with ADHF did not differ by the presence of diabetes. Instead, our findings emphasize the importance of early heart failure prevention and subsequent hospitalization. Considering the evolving landscape of disease-modifying therapies for heart failure, achieving this goal becomes increasingly feasible.

Letter 1: "Not type 2" by Moti Ravid 

Letter 2: "Hyponatremia, hyperkalemia, and acute kidney injury: clues for the diagnosis of uroperitoneum in patients with new-onset ascites" by Zvi Ackerman and Samuel N. Heyman, 

Letter 3: "Surgery in Mauthausen Concentration Camp" by George M. Weisz

Background: Diabetic ketoacidosis (DKA) poses a significant medical emergency in both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) patients. Recent attention has focused on the emergence of euglycemic DKA associated with sodium-glucose cotransporter-2 (SGLT2) inhibitors.

Objectives: To understand the epidemiology and outcomes of DKA, particularly in T2DM patients.

Methods: We conducted a retrospective cohort analysis of 204 patients admitted with DKA to Shamir Medical Center (2013–2021). We assessed demographics, clinical characteristics, and outcomes. Patients were stratified by diabetes type and SGLT2 inhibitor treatment status.

Results: Among the 204 patients with DKA, 38.2% had T2DM. Patients with T2DM exhibited older age, higher co-morbidity burden, and greater prevalence of microvascular complications compared to T1DM patients. Mortality rates were notably higher among T2DM patients, despite similar DKA severity at presentation, including in-hospital mortality rates of 6.4% vs. 0%, P < 0.05, and 90-day mortality rates of 7.7% vs. 0%, P < 0.05. T2DM was independently associated with adverse hospitalization outcomes, including a composite of rehospitalization, prolonged hospital stays, and mortality (odds ratio 2.68, 95% confidence interval 1.302–5.557). SGLT2 inhibitor treatment did not affect hospitalization outcomes of patients with T2DM.

Conclusions: Our findings underscore the importance of recognizing DKA as a substantial complication in diabetic patients, particularly those with T2DM. Vigilance in management, adherence to DKA guidelines, and awareness of triggers such as SGLT2 inhibitors are crucial for improving outcomes in this population.

Background: The use of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9 mAbs) is emerging for lowering low-density lipoprotein cholesterol (LDL-C). However, real-world data is lacking for their use among elderly patients.

Objective: To define the characteristics of elderly patients treated with PCSK9 mAbs and to evaluate the efficacy and tolerability compared with younger patients.

Methods: We conducted a retrospective cohort study of elderly patients (≥ 75 years at enrollment) treated with PCSK9 mAbs for primary and secondary cardiovascular prevention. Data were retrieved for demographic and clinical characteristics; indications for treatment; agents and dosages; concomitant lipid lowering treatment; LDL-C levels at baseline, 6, 12 months, and at the end of follow up. Data also included achieving LDL-C target levels and adverse effects.

Results: The cohort included 91 elderly patients and 92 younger patients, mean age 75.2 ± 3.76 and 58.9 ± 7.4 years (P < 0.0001). Most patients (82%, 80%) were in high/very high-risk categories. For almost all (98%, 99%), the indication was statin intolerance, with PCSK9 mAb monotherapy the most prevalent regimen. The average follow-up was 38.1 ± 20.5 and 30.9 ± 15.8 months (P = 0.0258). Within 6 months the LDL-C levels were reduced by 57% in the elderly group and by 59% in the control group (P = 0.2371). Only 53% and 57% reached their LDL-C target levels. No clinically significant side effects were documented.

Conclusion: PCSK9 mAbs have similar effects and are well tolerated among elderly patients as in younger patients.

Acute or chronic aortic dissection is considered a rare emergency, with an estimated rate of 2.9 to 5 cases per 100,000 patients each year. This condition is most prevalent in males older than 65 years of age with a history of hypertension, atherosclerosis, and previous cardiac surgery [1,2]. To confirm the diagnosis, imaging is used, often by computed tomography angiography (CTA) of the chest. Although prompt treatment is required, patients often present with non-specific symptoms, such as abdominal pain or neurologic deficits, resulting in the early diagnosis of less than 20% and a high mortality rate [1].

Background: Type 2 diabetes mellitus (T2DM) is a known risk factor for cardiovascular disease and stroke. Metformin is an old, relatively safe, first line therapy for T2DM; however, it has been associated with stroke.

Objectives: To study the effects of metformin use and vitamin B12 deficiency on stroke rate among patients with T2DM.

Methods: We conducted a prospective study of patients admitted with ischemic stroke within 12 months (starting March 2020). We studied the clinical impact of metformin on vitamin B12 deficiency and stroke evolution. Student's t-test and ANOVA were used to compare the groups of patients and to determine whether there was any direct or indirect effect of metformin use on vitamin B12 deficiency and stroke.

Results: In total, 80 patients were admitted with ischemic stroke. Clinical status and biochemical data were collected and compared with healthy volunteers. There were 39 diabetic patients, 16 took metformin for at least 1 year. Among those who took metformin for at least 1 year, 9 had vitamin B12 level < 240 pg/ml (56.2%); 23 diabetic patients did not get metformin and only 4 had vitamin B12 level < 240 pg/ml (17.4%) (P = 0.014).

Conclusions: T2DM is a significant risk factor to the development of ischemic stroke. We found an association between metformin use and vitamin B12 deficiency and an association between vitamin B12 deficiency and stroke risk in patients with T2DM. Diabetic patients who are taking metformin should monitor their vitamin B12 level.

Background: Pediatric patients with newly diagnosed type 1 diabetes mellitus (T1DM) are commonly treated with daily multiple insulin injections or an insulin pump. They tend to have higher body mass index-standard deviation scores (BMI-SDS) than non-diabetic children.

Objectives: To identify patterns in the changes in BMI in the 3 years after T1DM diagnosis, and to discover factors that relate to excessive weight gain.

Methods: This retrospective study included clinical and laboratory data for 194 boys and girls aged 2–18 years at the time of diagnosis and at 1, 2, and 3 years after. Their BMI values were compared to non-diabetic children using BMI percentile and z-score (standard deviation) based on the U.S. Centers for Disease Control and Prevention (CDC) growth charts.

Results: Both males and females had low mean BMI-SDS at diagnosis (-0.4499 ± 1.38743 male, 0.3050 ± 1.29887 female) that increased after 1 year (-0.0449 ± 1.14772 male, 0.1451 ± 0.98893 female). Lower glycated hemoglobin (HbA1c) at 1 year correlated with higher BMI-SDS (r = -0.215, P = 0.011). No such correlation was found in the following 2 years. The daily dose of basal insulin correlated with higher BMI-SDS at 1 year (r = 0.183, P = 0.026) and 3 years (r = 0.297, P < 0.01). No association was found between the use of an insulin pump or continuous glucose monitoring and higher BMI-SDS.

Conclusions: BMI-SDS of children with T1DM was lower than average at the time of diagnosis and rose higher than average in the 3 years following. Higher BMI-SDS was not significantly associated with sex or ethnicity. The most prominent increase happened in the first year.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) are new antidiabetic drugs that are recommended by current guidelines as a class I novel glucose-lowering treatment that improves cardiovascular outcome in type 2 diabetes mellitus (T2DM), particularly in patients with cardiovascular disease.

Objectives: To evaluate adherence to the current guidelines for treatment with SGLT2i and GLP1-RA drugs in patients referred to ambulatory consultant cardiology clinics with pre-existing T2DM.

Methods: We studied consecutive new patients with a pre-existing diagnosis of T2DM who were referred to the Clalit Health Services ambulatory consultant cardiology clinic over a 6-month period. The recorded information included demographics, co-morbidities, and prescribed drugs at patient admission.

Results: During the study period, 1782 patients visited our outpatient cardiology clinic. At screening, T2DM was present in 428 patients (24%); 77 (18%) were being treated with SGLT2i, and 39 (9.1%) with GLP1-RA. Patients receiving SGLT2i and GLP1-RA were younger and had more coronary artery disease, lower mean left ventricular ejection fraction, and higher mean estimated glomerular filtration rates than those who were not receiving these drugs. HbA1C was > 7 in 205 (47.9%) patients and > 7.5 in 136 patients (31.8%). Body mass index was > 30 kg/m² in 231 (54%) patients.

Conclusions: GLP1-RA and SGLT2i drugs were found to be administered more frequently than previously reported, but they are not yet satisfactorily prescribed.