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: Initiating oral antidiabetic therapy, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors, is generally not recommended during hospitalization. However, guidelines since 2021 have supported their use in heart failure with reduced ejection fraction (HFrEF), and since 2023 in preserved ejection fraction (HFpEF).

Objectives: To assess the safety and outcomes of initiating SGLT2 inhibitors during hospitalization for acute heart failure (HF).

Methods: We conducted a historical cohort study of 307 patients admitted with acute HF between October 2018 and April 2022. Patients were grouped as chronic SGLT2i users, new initiators during hospitalization, or controls who did not receive SGLT2i.

Results: Among the 307 patients, 50.4% had HFrEF, 30.8% HFpEF, and 18.8% HF with mildly reduced ejection fraction. In-hospital mortality was 3.6% (11 patients); 2-year mortality was 37.7% (116 patients). New SGLT2i initiators had the lowest 2-year mortality (22.2%) compared to controls (43.9%) and chronic users (41.8%) (P = 0.008). They also had the lowest 1-year rehospitalization rates (18.3% vs. 35.5% vs. 32.8%; P = 0.025). Multivariable analysis identified older age and co-morbidities as independent predictors of mortality. SGLT2i initiation was associated with reduced rehospitalization. Adverse effects occurred in 15.6% of SGLT2i users, mainly acute kidney injury.

Conclusions: In-hospital SGLT2 inhibitor initiation in patients with HF appears safe and is associated with reduced post-discharge mortality and readmission rates.

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: Congestive heart failure (CHF) with reduced ejection fraction (HFrEF) or with preserved ejection fraction (HFpEF) is a common diagnosis in patients hospitalized in the department of internal medicine. Recently, the therapeutic regimens were updated, as the sodium-glucose cotransporter-2 (SGLT2) inhibitors became an integral part of the therapeutic regimen for either HFrEF or HFpEF.

Objectives: To define the demographic and clinical characteristics of CHF patients hospitalized in the department of medicine.

Methods: We conducted a retrospective cohort study that included all patients hospitalized in the departments of medicine at the Rabin Medical Center, Israel, between 2016 and 2019. Demographic and clinical background, in-hospital procedures, discharge regimens, and outcome parameters were evaluated according to HFrEF/HFpEF.

Results: The cohort included 4458 patients. The majority (97%) presented with a preexisting diagnosis, whereas HF was an active condition in only half of them. The rates of HFrEF/HFpEF were equal. In most cases, the trigger of the exacerbation could not be determined; however, infection was the most common cause. There were basic differences in the demography, clinical aspects, and therapeutic regimens at discharge between HFrEF and HFpEF. Both conditions were associated with high in hospital mortality (8%) and re-admissions rates (30 days [20%], 90 days [35%]) without any difference between them.

Conclusions: HFrEF/HFpEF patients differed by demographics and co-morbidities. They were equally represented among patients admitted to medical wards and had similar prognosis. For both diagnoses, hospitalization should be considered for updating therapeutic regimens, especially with SGLT2 inhibitors.

Background: The coronavirus disease 2019 (COVID-19) pandemic has severe consequences in terms of mortality and morbidity. Knowledge of factors that impact COVID-19 may be useful in the search for treatments.

Objectives: To determine the effect of glucose-6-phosphate dehydrogenase (G6PD) deficiency on morbidly and mortality associated with COVID-19.

Methods: All patients admitted to Hadassah Hebrew University Medical Center between 01 March 2020 and 03 May 2021 with a diagnosis of COVID-19 were included. We retrospectively retrieved demographic, clinical, and laboratory data from the hospital’s electronic medical records. The main outcomes were mortality, intensive care unit (ICU) admission, and severity of COVID-19.

Results: The presence of G6PD deficiency emerged as an independent protective predictor for ICU admission (odds ratio [OR] 0.258, 95% confidence interval [95%CI] 0.077–0.619, P = 0.003) and the development of critical illness (OR 0.121, 95%CI 0.005–0.545, P = 0.006). Moreover, patients with G6PD deficiency had a trend toward lower mortality rates that did not reach statistical significance (OR 0.541, 95%CI 0.225–1.088, P = 0.10).

Conclusions: Patients with G6PD deficiency were less likely to have a severe disease, had lower rates of ICU admission, and trended toward lower mortality rates.

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.

Background: Stress hyperglycemia (SH) is a common finding in patients in pediatric emergency departments (PED) and has been related to increased morbidity and mortality.

Objectives: To assess the incidence of SH among children visiting the PED. To identify which diseases predispose patients to SH and whether they indicate a worse outcome.

Methods: Data were collected retrospectively from the medical records of all children aged 0–18 years who visited the PED during the years 2010–2014 and who had a glucose level of ≥ 150 mg/dl. Data collected included age, gender, weight, blood glucose level, presence or absence of a pre-existing or a new diagnosis of diabetes mellitus, and previous treatment with medications affecting blood glucose levels or with intravenous fluids containing dextrose. Data were collected regarding hospitalization, duration of hospitalization, discharge diagnosis, and survival status.

Results: The study population included 1245 children with SH, which comprised 2.6% of all patients whose blood glucose level was measured in the PED during the study period. The mean age of children with SH was 49 months; 709 (56.9%) were male. The mean blood glucose level was 184 mg/dl. The rate of hospitalization was 57.8%. The mean duration of hospital stay was 5.6 days and mortality rate was 0.96%. The majority were diagnosed with a respiratory illness.

Conclusions: SH is a common phenomenon among children evaluated in the PED and is associated with a high incidence of hospitalization. It may serve as an additional clinical indicator of disease severity.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) (such as canagliflozin, empagliflozin, and dapagliflozin) are widely used to treat patients with type 2 diabetes mellitus (T2DM) to improve glycemic, cardiovascular and renal outcomes. However, based on post-marketing data, a warning label was added regarding possible occurrence of acute kidney injury (AKI).

Objectives: To describe the clinical presentation of T2DM patients treated with SGLT2i who were evaluated for AKI at our institution and to discuss the potential pathophysiologic mechanisms.

Methods: A retrospective study of a computerized database was conducted of patients with T2DM who were hospitalized or evaluated for AKI while receiving SGLT2i, including descriptions of clinical and laboratory characteristics, at our institution.

Results: We identified seven patients in whom AKI occurred 7–365 days after initiation of SGLT2i. In all cases, renin-angiotensin-aldosterone system blockers had also been prescribed. In five patients, another concomitant nephrotoxic agent (injection of contrast-product, use of nonsteroidal anti-inflammatory drugs or cox-2 inhibitors) or occurrence of an acute medical event potentially associated with AKI (diarrhea, sepsis) was identified. In two patients, only the initiation of SGLT2i was evident. The mechanisms by which AKI occurs under SGLT2i are discussed with regard to the associated potential triggers: altered trans-glomerular filtration or, alternatively, kidney medullary hypoxia.

Conclusions: SGLT2i are usually safe and provide multiple benefits for patients with T2DM. However, during particular medical circumstances, and in association with usual co-medications, particularly if baseline glomerular filtration rate is decreased, patients treated with SGLT2i may be at risk of AKI, thus warranting caution when prescribed.

Abstract

Parenteral nutrition (PN) must be initiated as soon as possible after delivery in very low birth weight (VLBW) preterm infants in order to prevent postnatal growth failure and improve neurodevelopmental outcome. When administered early, high levels of parenteral amino acids (AA) are well tolerated and prevent negative nitrogen balance. Although proteins are the driving force for growth, protein synthesis is energy demanding. Intravenous lipid emulsions (ILE) constitute a good energy source because of their high energy density and provide essential fatty acids (FA) along with their long-chain polyunsaturated fatty acid (LC-PUFA) derivatives necessary for central nervous system and retinal development. Early supply of ILE is not associated with increased morbidity. No significant differences were found between ILE based on soybean oil only and mixed ILE containing soybean oil in combination with other fat sources, except for a reduction in the incidence of sepsis with non-pure soybean ILE, and possibly less PN-associated liver disease with mixed ILE containing some fish oil. In preterm infants glucose homeostasis is still immature in the first days of life and abnormalities of glucose homeostasis are common. VLBW infants may not tolerate high levels of glucose infusion without hyperglycemia. Administering lower levels of glucose infusion as part of full early PN seems more successful than insulin at this stage. Postpartum there is a transition period when the water and electrolyte balance may be severely disturbed and should be closely monitored. Avoiding fluid overload is critical for preventing respiratory and other morbidities

Objectives: To investigate the effect of hypoxemia and nocturnal glucose homeosatsis in non-diabetic patients with sleep apnea.

Methods: Seven non-diabetic patients with moderate to severe sleep apnea were connected to a continuous glucose-monitoring sensor while undergoing overnight polysomnography. Mean SpO₂ and percentage of time spent at SpO₂ < 90% were recorded. The correlation between mean glucose levels, the difference between consecutive mean glucose measurements (glucose variability) and the corresponding oxygen saturation variables were determined in each patient during REM[1] and non-REM sleep.

Results: No consistent correlation was found for the individual patient between oxygen saturation variables and glucose levels during sleep. However, a lower mean SpO₂ correlated with decreased glucose variability during sleep (r = 0.79, P = 0.034). This effect was primarily evident during REM sleep in patients with significant, compared to those with mild, oxygen desaturations during sleep (> 30% vs. < 10% of sleeping time spent with SpO₂ < 90%) (P = 0.03).

Conclusions: Severe nocturnal hypoxemia in non-diabetic patients with moderate to severe sleep apnea might affect glucose regulation primarily during REM sleep.

Since the Surviving Sepsis Campaign Guideline (SSG) was published in 2004, critical care physicians can readily access the evidence and current recommendations regarding management of patients with severe sepsis and septic shock. However, several issues including a potential conflict of interest in developing the guidelines were disclosed. There have also been dramatic changes in the management of sepsis, supported by high levels of evidence. SSG[1] 2008 was developed to update the evidence using a new grading system. We reviewed select topics, routinely addressed by intensivists in the surgical intensive care unit, that have changed between SSG 2004 and SSG 2008: namely, glucose control, and administration of steroids, recombinant human activated protein C (rhAPC) and total parenteral nutrition.