Israel Medical Association Journal

Background: Patients with type 2 diabetes mellitus (T2DM) have a high rate of cardiovascular disease (CVD). The Mediterranean diet is preferred for CVD prevention. Endothelial dysfunction is demonstrated early in T2DM.

Objectives: To study the effects of dietary intervention of T2DM patients without known CVD on endothelial function and vascular inflammation.

Methods: A prospective study enrolled 22 patients with T2DM. Patients were divided randomly into two groups: an intervention group with 12 patients (55 ± 7 years old, 6 women) and a control group with 10 patients (59 ± 10 years old, 5 women). Clinical evaluation included body mass index (BMI) and endothelial function measured by the flow mediated percent change (FMD%). Fasting blood was drawn on entry to the study and 3 months later, measuring C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), total cholesterol, triglycerides, and glycosylated hemoglobin (HbA1C%). The intervention was based on weekly telephone calls by a clinical dietitian for 3 months.

Results: In the intervention group CRP and ICAM-1 were reduced (from 4.2 ± 3.3 mg/dl to 0.4 ± 0.5 mg/dl, P = 0.01 and from 258.6 ± 98.3 ng/ml to 171.6 ± 47.7 ng/ml, P = 0.004). Endothelial function (FMD%) was improved (from 0.5 ± 8.0% to 9.5 ± 11.5%, P = 0.014). No change was observed in BMI, HbA1C%, total cholesterol, and triglycerides levels in either group.

Conclusions: Patients with T2DM on the Mediterranean diet who received a weekly telephone call for 3 months improved their endothelial function with reduction of markers of inflammation.

Background: The sonographic assessment of estimated fetal weight (EFW) is essential for identification of fetuses in weight extremes and aids in peripartum management. However, there are inconsistent reports regarding EFW accuracy.

Objective: To examine maternal and fetal determinants associated with unreliable EFW.

Methods: A retrospective case-control study was conducted at a single, tertiary medical center between 2011 and 2019. All term, singleton deliveries with a sonographic EFW within 2 weeks of delivery were included. Unreliable EFW was defined as > 500 grams discordance between it and the actual birth weight. We allocated the study cohort into two groups: unreliable EFW (cases) and accurate EFW (controls).

Results: Overall, 41,261 deliveries met inclusion criteria. Of these, 1721 (4.17%) had unreliable EFW. The factors positively associated with unreliable EFW included body mass index > 30 kg/m², weight gain > 20 kg, higher amniotic fluid index, pregestational diabetes, gestational age > 41^0/7, and birth weight ≥ 4000 grams. On multiple regression analysis, pregestational diabetes (odds ratio [OR] 2.22, 95% confidence interval [95%CI] 1.56–3.17, P < 0.001) and a higher birth weight (OR 1.91, 95%CI 1.79–2.04, P < 0.001) were independently associated with unreliable EFW. On analysis of different weight categories, pregestational diabetes was associated with unreliable EFW only among birth weights ≥ 3500 grams (OR 3.28, 95%CI 1.98–5.44, P< 0.001) and ≥ 4000 grams (OR 4.27, 95%CI 2.31–7.90, P < 0.001).

Conclusion: Pregestational diabetes and increased birth weight are independent risk factors for unreliable EFW and should be considered when planning delivery management.

Background: The incidence of gestational diabetes mellitus (GDM) is increasing in parallel to the worldwide obesity and type 2 diabetes pandemic. Both GDM and pre-gestational diabetes mellitus (PGDM) are associated with short- and long-term consequences in the offspring. There are few recent studies addressing outcomes of newborns born to women diagnosed with GDM and PGDM in Israel.

Objectives: To assess perinatal complications in offspring of women with GDM and PGDM.

Methods: The authors conducted a single-center retrospective case-control study of outcomes of all newborns whose mothers had been diagnosed with diabetes in pregnancy compared to randomly assigned controls born on the same date, whose mothers had no diabetes.

Results: In the study period 2015–2017, 526 mothers diagnosed with GDM or PGDM and their newborn infants were identified. The authors randomly assigned 526 control infants. The rate of women with diabetes in pregnancy was 5.0%. Mothers with GDM and PGDM had higher rates of pre-eclampsia, multiple pregnancies, and preterm deliveries. Mothers with PGDM had significantly higher rates of intrauterine fetal demise (4.3%), congenital anomalies (12.8%), and small-for-gestational-age neonates (10.6%) compared to controls (0%, 3.2%, and 4.2%, respectively, P < 0.001). The risks for preterm or cesarean delivery, large-for-gestational-age neonate, respiratory morbidity, hypoglycemia, and polycythemia were increased in offspring of mothers with diabetes, especially PGDM.

Conclusions: Despite all the advancements in prenatal care, diabetes in pregnancy, both PGDM and GDM, is still associated with significant morbidities and complications in offspring. Better preconception and inter-pregnancy care might reduce these risks

Background: Pregestational diabetes mellitus (PGDM) carries a significantly elevated risk of adverse maternal and fetal outcomes. There is evidence that certain interventions reduce the risk for adverse outcomes. Studies have shown that a multi-disciplinary approach improves pregnancy outcomes in women with PGDM.

Objectives: To determine pregnancy outcomes in women with PGDM using a multi-disciplinary approach.

Methods: We retrospectively reviewed consecutive women with pregestational type 1 and type 2 diabetes who were monitored at a high-risk pregnancy clinic at the Sheba Medical Center. Clinical data were obtained from the medical records. All data related to maternal glucose control and insulin pump function were prospectively recorded on Medtronic CareLink® pro software (Medtronic MiniMed, Northridge, CA).

Results: This study comprised 121 neonates from 116 pregnancies of 94 women. In 83% of the pregnancies continuous glucose monitoring (CGM) sensors were applied during a part or all of the pregnancy. Pregnancy outcomes among women who were followed by a multi-disciplinary team before and during pregnancy, and during labor and puerperium resulted in better glucose control (hemoglobin A1c 6.4% vs. 7.8%), lower risk for pregnancy induced hypertension/preeclampsia (7.7% vs. 15.6%), lower birth weight (3212 g vs. 3684 g), and lower rate of large size for gestational age and macrosomia (23.1% vs. 54.2% and 3.3% vs. 28.4%, respectively), compared to data from European cohorts.

Conclusions: The multi-disciplinary approach for treating women with PGDM practiced in the high-risk pregnancy clinic at the Sheba Medical Center resulted in lower rates of macrosomia, LGA, and pregnancy induced hypertension compared to rates reported in the literature.

The Bedouins living in southern Israel are a Muslim-Arab population that is transitioning from a nomadic lifestyle to life in permanent settlements. The population has unique characteristics that could affect hemoglobin A1c (HbA1c) measurements. The objective of this study was to describe the socio-demographic and unique morbidity characteristics of this community and their effect on HbA1c measurements. Consanguinity, especially among cousins in the Bedouin population, results in a high prevalence of autosomal recessive genetic diseases such as thalassemia (underestimate of HbA1c), hemoglobinopathies (underestimate and overestimate), Gilbert’s disease, and glucose-6-phosphate dehydrogenase deficiency, an X-linked disorder, which can cause hyperbilirubinemia with an overestimate of HbA1c. Furthermore, nutritional deficiencies, autosomal recessive diseases, high birth rates, parasitic infections, and poverty can all cause high rates of anemia (iron and vitamin B12 deficiencies) that can raise HbA1c levels. Congenital dyserythropoietic anemia is found among Bedouin tribes in the Negev region and can lead to an underestimation of HbA1c levels. Pregnancy can also affect HbA1c levels. Medical teams working in the Bedouin community and in other Muslim populations with similar morbidity characteristics throughout the world should identify patients with medical conditions that can affect HbA1c measurements and be aware of possible measurement alternatives such as fructosamine and glycated albumin.

Background: Basal-bolus (BB) insulin treatment is increasingly used in poorly controlled diabetes patients during hospitalization and is commonly recommended at discharge; however, the extent of adherence with this recommendation is unknown.

Objectives: To determine short-term adherence of type 2 diabetes mellitus (T2DM) patients discharged from internal medicine wards with recommendation for BB insulin treatment.

Methods: Prescription (primary physician adherence) and purchase (patient adherence) of long-acting and short-acting insulins during the first month following discharge from internal medicine wards was determined in 153 T2DM patients. Adherence was defined as full if prescription/purchase of both basal (long-acting) and bolus (short-acting) insulin was completed, and as partial if only one kind of insulin (basal or bolus) was prescribed/purchased. Association between demographic and clinical parameters and adherence was determined.

Results: Full adherence with discharge instructions was higher for primary physicians than for patients )79.1% vs. 69.3%, respectively, P = 0.0182). Pre-hospitalization hemoglobin A1C was significantly associated with adherence by both patients and primary physicians (full-adherence group 9.04% ± 2.04%; no-adherence group 7.51% ± 1.35%, P = 0.002). Age was negatively associated with adherence of both primary physicians and patients; however, this association did not reach statistical significance. Patients with certain background diseases such as atrial fibrillation, coronary heart disease, and chronic heart failure had significantly worse adherence (P < 0.05). When the sole cause of admission was diabetes, full adherence (100%) of both primary physicians and patients was found.

Conclusions: Short-term adherence with discharge recommendation for BB insulin treatment is associated with pre-hospitalization patient characteristics.

Background: The salutary effects of statin therapy in patients with cardiovascular disease (CVD) are well established. Although generally considered safe, statin therapy has been reported to contribute to induction of diabetes mellitus (DM).

Objectives: To assess the risk-benefit of statin therapy, prescribed for the prevention of CVD, in the development of DM.

Methods: In a population-based real-life study, the incidence of DM and CVD were assessed retrospectively among 265,414 subjects aged 40–70 years, 17.9% of whom were treated with statins. Outcomes were evaluated according to retrospectively determined baseline 10 year cardiovascular (CV) mortality risks as defined by the European Systematic COronary Risk Evaluation, statin dose-intensity regimen, and level of drug adherence.

Results: From 2010 to 2014, 5157 (1.9%) new cases of CVD and 11,637 (4.4%) of DM were observed. Low-intensity statin therapy with over 50% adherence was associated with increased DM incidence in patients at low or intermediate baseline CV risk, but not in patients at high CV risk. In patients at low CV risk, no CV protective benefit was obtained. The number needed to harm (NNH; incident DM) for low-intensity dose regimens with above 50% adherence was 40. In patients at intermediate and high CV risk, the number needed to treat was 125 and 29; NNH was 50 and 200, respectively.

Conclusions: Prescribing low-dose statins for primary prevention of CVD is beneficial in patients at high risk and may be detrimental in patients at low CV risk. In patients with intermediate CV risk, our data support current recommendations of individualizing treatment decisions.

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.