COVID-19 associated mucormycosis – An emerging threat

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly become a global threaten since its emergence in the end of 2019. Moreover, SARS-CoV-2 infection could also present with co-infection or secondary infection by other virus, bacteria, or fungi. Among them, mucormycosis is a rare but aggressive fungal disease and it mainly affects patients particularly with poorly controlled diabetes mellitus with diabetic ketoacidosis (DKA). We here did a comprehensive review of literature reporting COVID-19 associated with mucormycosis (CAM) cases, which have been reported worldwide. The prevalence is higher in India, Iran, and Egypt than other countries, particularly highest in the states of Gujarat and Maharashtra in India. Poor diabetic control and the administration of systemic corticosteroids are the common precipitating factors causing mucormycosis in the severe and critical COVID-19 patients. In addition, COVID-19 itself may affect the immune system resulting in vulnerability of the patients to mucormycosis. Appropriate treatments of CAM include strict glycemic control, extensive surgical debridement, and antifungal therapy with amphotericin B formulations.     

Diabetes and bone health

The increasing prevalence of diabetes especially type 2 diabetes worldwide is indisputable. Diabetics suffer increased morbidity and mortality, compared to their non-diabetic counterparts, not only because of vascular complications, but also because of an increased fracture incidence. Both types 1 and 2 diabetes and some medications used to treat it are associated with osteoporotic fractures. The responsible mechanisms remain incompletely elucidated. In this review, we evaluate the role of glycemic control in bone health, and the effect of anti-diabetic medications such as thiazolidinediones, sulfonylureas, DPP-4 inhibitors, and GLP-1 agonists. In addition, we examine the possible role of insulin and metformin as anabolic agents for bone. Lastly, we identify the current and future screening tools that help evaluate bone health in diabetics and their limitations. In this way we can offer individualized treatment, to the at-risk diabetic population.     

Dipeptidyl peptidase-4(DPP-4) inhibitors: promising new agents for autoimmune diabetes

Dipeptidyl peptidase-4 (DPP-4) inhibitors constitute a novel class of anti-diabetic agents confirmed to improve glycemic control and preserve β-cell function in type 2 diabetes. Three major large-scale studies, EXAMINE, SAVOR-TIMI 53, and TECOS, have confirmed the cardiovascular safety profile of DPP-4 inhibitors. Based on these results, DPP-4 inhibitors have gained widespread use in type 2 diabetes treatment. It is currently unknown, however, whether DPP-4 inhibitors have similar therapeutic efficacy against autoimmune diabetes. Several in vitro and in vivo studies have addressed this issue, but the results remain controversial. In this review, we summarize experimental findings and preliminary clinical trial results, and identify potentially effective immune modulation targets of DPP-4 inhibitors for autoimmune diabetes.     

Novel appearance of hyperglycemia/diabetes,associated with COVID-19

In a recent meta-analysis the prevalence of coronavirus disease 2019 (COVID-19)-associated hyperglycemia was 25%, and that of COVID-19-associated new-onset diabetes was 19%. An association between hyperglycemia or new-onset diabetes and COVID-19 has been suggested. In a recent relevant study of critically and non-critically ill patients with COVID-19, we found that indeed beta-cell function was compromised in critically ill patients with COVID-19 and that these patients showed a high glycemic gap. Nevertheless, one quarter of critically ill patients with no history of diabetes have stress hyperglycemia, a finding which could obscure the prevalence of hyperglycemia or new-onset diabetes that could be attributed to COVID-19 per se.     

Pathophysiology and treatment of patients with type 2 diabetes exhibiting failure to oral drugs

It is generally accepted that a poor glycaemic control increases the risk for development of vascular complications in diabetic patients. This advocates for early introduction of insulin treatment in patients with type 2 diabetes exhibiting a secondary failure to oral treatment. This strategy is facilitated by introduction of long-acting insulin glargine and biphasic insulin aspart 70/30. The introduction of Glucagon-like peptide-1 (GLP-1) mimetics and dipeptidyl peptidase 4 (DPP-4) inhibitors in treatment of type 2 diabetes will however, to a large extent, influence therapeutic policy. Thus we suggest that DPP-4 inhibitors or long-acting GLP-1 mimetics will be used as either first-line therapy or as an early addition to metformin. The already generated results in animal and clinical studies suggest that these two classes of antidiabetic drugs may in addition to improving glycaemic control protect islet beta-cell mass and thereby postpone development of a secondary failure. When patients treated with metformin, sulfonylurea (SU), tiazolidinediones or a combination of these drugs fail, the GLP-1 mimectics may be preferred to insulin treatment. First, the risk of hypoglycaemia is less if not combined with SU. Secondly, the body weight is usually decreased while insulin treatment increases weight. Patients not responding to GLP-1 mimetics or experiencing significant side effects will be treated with insulin. Irrespective of the policy used for the drug treatment of type 2 diabetes, exercise and proper diet will remain important for optimization of metabolic control.     

CCR2 and DPP9 expression in the peripheral blood of COVID-19 patients: Influences of the disease severity and gender

IntroductionHyper-inflammatory reactions play a crucial role in the pathogenesis of the severe forms of COVID-19. However, clarification of the molecular basis of the inflammatory-related factors needs more consideration. The aim was to evaluate the gene expression of two fundamental molecules contributing to the induction of inflammatory like CCR2 and DPP9 in cells from peripheral blood samples from patients with various patterns of COVID-19.MethodsPeripheral blood samples were collected from 470 patients (235 male and 235 female) with RT-qPCR-confirmed COVID-19 test exhibiting moderate, severe, and critical symptoms based on WHO criteria. 100 healthy subjects (50 male and 50 female) were also enrolled in the study as a control group. The gene expression of DPP-9 and CCR-2 was assessed in the blood samples using real-time PCR method.ResultsThe COVID-19 patients in severe stage expressed higher levels of CCR2 and DPP9 compared with healthy controls. In male and female patients, the levels of CCR2 and DDP9 expression significantly differed between moderate, severe, and critical patterns (p < 0.0001) as well as between each COVID-19 form and control group (p < 0.0001). The male patients with severe COVID-19 expressed greater levels of CCR2 and DPP-9 than female with same disease form. The female patients with moderate and critical COVID-19 expressed greater levels of CCR2 and DPP-9 than male patients with same disease stage.ConclusionWe demonstrated that the expression of DPP-9 and CCR-2 was substantially increased in COVID-19 patients with different forms of disease. Considerable differences were also demonstrated between male and female with different patterns of disease. Therefore, we suggest to consider the gender of patients and disease severity for management of COVID-19.     

Achieving recommended goals for blood-glucose and blood-pressure control in diabetic patients: a multi-center cross-sectional evaluation in the Niigata prefecture

Hypertension in patients with diabetes mellitus can contribute to a deterioration of the patient's status as much as most diabetes mellitus-related complications. Previous interventional trials have found that to prevent the onset and progression of diabetic microangiopathy, the optimal glycemic threshold is an HbA1c of less than 6.5% and the optimal blood pressure is less than 130/85 mmHg. The present study investigated the prevalence of achieving these recommended goals for glycemic and blood pressure control in type 2 diabetic patients in the Niigata prefecture. A questionnaire was administered in this multi-center study to 3573 patients from 92 participating Niigata Diabetic Complication Study hospitals. Patients aged 63.5 +/- 11 years with type 2 diabetes were evaluated. Only 46.8% of patients achieved the recommended glycemic control level, and only 41.4% of patients achieved the BP target. Moreover, only 20.5% of all patients achieved both target levels for blood glucose and blood pressure. This demonstrates the difficulty in clinical practice of achieving concurrent glucose and blood pressure control in diabetic patients.     

COVID-19-associated mucormycosis in India: Why such an outbreak?

An unprecedented mucormycosis outbreak occurred in India during the second COVID-19 wave in spring 2021. COVID-19-associated mucormycosis (CAM) was observed, mainly rhino-orbito-cerebral mucormycosis (ROCM), in patients with poorly controlled diabetes and treated with inappropriate doses of glucocorticoids. The aim of this mini-review was to compare the characteristics of the CAM epidemic in India with (i) mucormycosis cases before the COVID-19 pandemic and (ii) CAM in the rest of the world (particularly in France) in order to identify the reasons for this outbreak. In India, the major mucormycosis epidemiologic change during the COVID-19 pandemic was an increase in the percentage of patients treated with corticosteroids who developed CAM. Compared with the rest of the world, India reported a higher mucormycosis incidence even before the COVID-19 pandemic. Moreover, in India, patients with CAM were more likely to have diabetes mellitus and ROCM; conversely, mortality rates were lower. The reasons for such a localized epidemic in India have remained unclear, but some hypotheses can be put forward, particularly the combination of high prevalence of uncontrolled diabetes mellitus and frequent indiscriminate corticosteroid utilization in a country that already had a high mucormycosis burden before the COVID-19 pandemic.     

Ethnic disparities in type 2 diabetes: pathophysiology and implications for prevention and management

Based on 2000 census data, ethnic minorities constitute approximately 25% of the overall population of the United States, and the population of minority groups has been increasing at a faster rate than the general U.S. population. Compared with caucasians, persons from minority ethnic groups suffer disproportionately from type 2 diabetes and its long-term complications. Acute complications of diabetes occur with varying frequencies in the different demographic groups, but there are indications that the rate of hospitalization for diabetic ketoacidosis and nonketotic coma may be higher among certain minority populations. Genetic and lifestyle factors likely account for the increased prevalence of type 2 diabetes among ethnic minorities. However, the increase in morbidity and mortality from diabetes may be the result, in part, of socioeconomic factors. Pathophysiologically, several studies have documented a higher prevalence of insulin resistance in minority groups, even after correction for obesity and lifestyle factors. These findings underscore the need for a more aggressive approach to diabetes management in high-risk populations. Behavioral and pharmacologic interventions that reduce insulin resistance have profound beneficial effects in African-American patients and subjects with diabetes from other ethnic groups. Indeed, much of the ethnic difference in morbidity from diabetic complications disappears when caucasians and non-caucasians are treated to identical degrees of glycemic control.     

Enhanced superoxide release and elevated protein kinase C activity in neutrophils from diabetic patients: association with periodontitis

Inflammation and oxidative stress are important factors in the pathogenesis of diabetes and contribute to the pathogenesis of diabetic complications. Periodontitis is an inflammatory disease that is characterized by increased oxidative stress, and the risk for periodontitis is increased significantly in diabetic subjects. In this study, we examined the superoxide (O(2)(-))-generating reduced nicotinamide adenine dinucleotide phosphate-oxidase complex and protein kinase C (PKC) activity in neutrophils. Fifty diabetic patients were grouped according to glycemic control and the severity of periodontitis. Neutrophils from diabetic patients with moderate [amount of glycated hemoglobin (HbA(1c)) between 7.0% and 8.0%] or poor (HbA(1c) >8.0%) glycemic control released significantly more O(2)(-) than neutrophils from diabetic patients with good glycemic control (HbA(1c) <7.0%) and neutrophils from nondiabetic, healthy individuals upon stimulation with 4beta-phorbol 12-myristate 13-acetate or N-formyl-Met-Leu-Phe. Depending on glycemic status, neutrophils from these patients also exhibited increased activity of the soluble- and membrane-bound forms of PKC, elevated amounts of diglyceride, and enhanced phosphorylation of p47-phox during cell stimulation. In addition, we report a significant correlation between glycemic control (HbA(1c) levels) and the severity of periodontitis in diabetic patients, suggesting that enhanced oxidative stress and increased inflammation exacerbate both diseases. Thus, hyperglycemia can lead to a novel form of neutrophil priming, where elevated PKC activity results in increased phosphorylation of p47-phox and O(2)(-) release.     

Can fasting plasma glucose and glycated hemoglobin levels predict oral complications following invasive dental procedures in patients with type 2 diabetes mellitus? A preliminary case-control study

OBJECTIVE:

To evaluate the effects of the levels of glycemic control on the frequency of clinical complications following invasive dental treatments in type 2 diabetic patients and suggest appropriate levels of fasting blood glucose and glycated hemoglobin considered to be safe to avoid these complications.

METHOD:

Type 2 diabetic patients and non-diabetic patients were selected and divided into three groups. Group I consisted of 13 type 2 diabetic patients with adequate glycemic control (fasting blood glucose levels <140 mg/dl and glycated hemoglobin (HbA1c) levels <7%). Group II consisted of 15 type 2 diabetic patients with inadequate glycemic control (fasting blood glucose levels >140 mg/dl and HbA1c levels >7%). Group III consisted of 18 non-diabetic patients (no symptoms and fasting blood glucose levels <100 mg/dl). The levels of fasting blood glucose, glycated HbA1c, and fingerstick capillary glycemia were evaluated in diabetic patients prior to performing dental procedures. Seven days after the dental procedure, the frequency of clinical complications (surgery site infections and systemic infections) was examined and compared between the three study groups. In addition, correlations between the occurrence of these outcomes and the glycemic control of diabetes mellitus were evaluated.

RESULTS:

The frequency of clinical outcomes was low (4/43; 8.6%), and no significant differences between the outcome frequencies of the various study groups were observed (p>0.05). However, a significant association was observed between clinical complications and dental extractions (p = 0.02).

CONCLUSIONS:

Because of the low frequency of clinical outcomes, it was not possible to determine whether fasting blood glucose or glycated HbA1c levels are important for these clinical outcomes.     

Preventing diabetes-related morbidity and mortality in the primary care setting

Diabetes is the leading cause of blindness, end-stage renal failure, non-traumatic limb amputations, and cardiovascular morbidity and mortality. The vast majority of patients with diabetes receive routine care from primary care providers who are not endocrinologists. Primary care providers, including internists, family practice physicians, and physician extenders with advanced skills, face the important task of implementing standards of care recommendations for persons with diabetes. These recommendations draw upon an emerging body of compelling evidence regarding the prevention and management diabetes and its complications. The challenge of diabetes must be tackled on three fronts: Primary prevention, secondary prevention (of diabetes complications), and tertiary prevention (of morbidity and mortality from established complications). There is now abundant evidence that type 2 diabetes, which accounts for greater than 90% of diabetes world-wide, is preventable. Moreover, the complications of diabetes are preventable by a policy of tight glycemic control and comprehensive risk reduction. Even after complications have set in, intensive glucose control dramatically reduces the risk of progression of complications. The challenge, therefore, is the identification of strategies that enable translation of existing scientific data to pragmatic benefits. This article proposes 10 strategies for preventing or reducing diabetes-related morbidity and mortality at the primary care level. These strategies include provider education; patient empowerment through promotion of lifestyle and self-care practices; surveillance for microvascular complications; cardiovascular risk reduction; efficient use of medications; goal setting; and stratification of patients and triaging of those with poor glycemic control for more intensive management.     

Renal microvascular injury in diabetes: RAGE and redox signaling

Diabetic nephropathy remains a major cause of morbidity and mortality in the diabetic population and is the leading cause of end-stage renal failure in the Western World. Despite current therapeutics including intensified glycemic control and blood pressure lowering agents, renal disease continues to progress relentlessly in diabetic patients, albeit at a lower rate. It is well recognized that metabolic and hemodynamic factors play a central role in accelerating renal disease in diabetes. However, recent experimental studies have suggested that increased generation of reactive oxygen species (ROS) as a result of the diabetic milieu may play a central role in the progression of diabetic microvascular complications. These ROS appear to be generated primarily from mitochondrial sources and via the enzyme, NADPH oxidase. This review focuses on how ROS play a deleterious role in the diabetic kidney and how they are involved in crosstalk among various signaling pathways, ultimately leading to renal dysfunction and structural injury.     

Impact of prior statin use on clinical outcomes in COVID-19 patients: data from tertiary referral hospitals during COVID-19 pandemic in Italy

BackgroundEpidemiological evidence suggests that anti-inflammatory and immunomodulatory properties of statins may reduce the risk of infections and infection-related complications.ObjectiveWe aimed to assess the impact of prior statin use on coronavirus disease (COVID-19) severity and mortality.MethodsIn this observational multicenter study, consecutive patients hospitalized for COVID-19 were enrolled. In-hospital mortality and severity of COVID-19 assessed with National Early Warning Score (NEWS) were deemed primary and secondary outcomes, respectively. Propensity score (PS) matching was used to obtain balanced cohorts.ResultsAmong 842 patients enrolled, 179 (21%) were treated with statins before admission. Statin patients showed more comorbidities and more severe COVID-19 (NEWS 4 [IQR 2–6] vs 3 [IQR 2–5], p < 0.001). Despite having similar rates of intensive care unit admission, noninvasive ventilation, and mechanical ventilation, statin users appeared to show higher mortality rates. After balancing pre-existing relevant clinical conditions that could affect COVID-19 prognosis with PS matching, statin therapy confirmed its association with a more severe disease (NEWS ≥5 61% vs. 48%, p = 0.025) but not with in-hospital mortality (26% vs. 28%, p = 0.185). At univariate logistic regression analysis, statin use was confirmed not to be associated with mortality (OR 0.901; 95% CI: 0.537 to 1.51; p = 0.692) and to be associated with a more severe disease (NEWS≥5 OR 1.7; 95% CI 1.067–2.71; p = 0.026).ConclusionsOur results did not confirm the supposed favorable effects of statin therapy on COVID-19 outcomes. Conversely, they suggest that statin use should be considered as a proxy of underlying comorbidities, which indeed expose to increased risks of more severe COVID-19.     

New-onset diabetes in COVID-19 and clinical outcomes: A systematic review and meta-analysis

BACKGROUNDDiabetes mellitus (DM) is associated with adverse clinical outcomes and high mortality in patients with coronavirus disease 2019 (COVID-19). The relationship between diabetes and COVID-19 is known to be bidirectional.AIMTo analyze the rate of new-onset diabetes in COVID-19 patients and compare the clinical outcomes of new-onset diabetes, pre-existing diabetes, hyperglycemic, and non-diabetes among COVID-19 patients.METHODSWe used the Meta-analysis of Observational Studies in Epidemiology statement for the present meta-analysis. Online databases were searched for all peer-reviewed articles published until November 6, 2020. Articles were screened using Covidence and data extracted. Further analysis was done using comprehensive meta-analysis. Among the 128 studies detected after thorough database searching, seven were included in the quantitative analysis. The proportion was reported with 95% confidence interval (CI) and heterogeneity was assessed using I².RESULTSAnalysis showed that 19.70% (CI: 10.93-32.91) of COVID-19 patients had associated DM, and 25.23% (CI: 19.07-32.58) had associated hyperglycemia. The overall mortality rate was 15.36% (CI: 12.57-18.68) of all COVID-19 cases, irrespective of their DM status. The mortality rate was 9.26% among non-diabetic patients, 10.59% among patients with COVID-19 associated hyperglycemia, 16.03% among known DM patients, and 24.96% among COVID-19 associated DM patients. The overall occurrence of adverse events was 20.52% (CI: 14.21-28.70) among COVID-19 patients in the included studies, 15.29% among non-diabetic patients, 20.41% among patients with COVID-19 associated hyperglycemia, 20.69% among known DM patients, and 45.85% among new-onset DM. Meta-regression showed an increasing rate of mortality among new hyperglycemic patients, known diabetics, and new-onset DM patients in comparison to those without diabetes.CONCLUSIONA significantly higher rate of new onset DM and hyperglycemia was observed. Higher mortality rates and adverse events were seen in patients with new-onset DM and hyperglycemia than in the non-diabetic population.     

糖尿病患者伴发抑郁症的临床对照研究

目的:评价帕罗西汀治疗糖尿病患者伴发抑郁症的疗效和对患者血糖的影响.方法:对48名伴发抑郁症的糖尿病患者,进行8周的随机对照研究,实验组、对照组各24例.帕罗西汀20-40mg/日,以Beck抑郁问卷(BDI)和汉密尔顿抑郁量表(HAMD)评定疗效.糖化血红蛋白(GHb)用于血糖控制的监测.结果:帕罗西汀组抑郁症状的减轻明显优于对照组(P<0.05～0.01),根据BDI评分,帕罗西汀组的显效率明显高于对照组(62.5%,33.3%,P<0.05).根据HAMD评分,帕罗西汀组的治愈率高于对照组(45.8%,25.0%,P<0.05),帕罗西汀组GHb降低的趋势比对照组更明显(-0.5%,-0.1% ).结论:帕罗西汀能有效减轻糖尿病患者的抑郁症状,这种治疗更有利于血糖的控制.     

Inhibition of EGF Signaling Protects the Diabetic Retina from Insulin-Induced Vascular Leakage

Diabetes mellitus is a disease with considerable morbidity and mortality worldwide. Breakdown of the blood–retinal barrier and leakage from the retinal vasculature leads to diabetic macular edema, an important cause of vision loss in patients with diabetes. Although epidemiologic studies and randomized clinical trials suggest that glycemic control plays a major role in the development of vascular complications of diabetes, insulin therapies for control of glucose metabolism cannot prevent long-term retinal complications. The phenomenon of temporary paradoxical worsening of diabetic macular edema after insulin treatment has been observed in a number of studies. In prospective studies on non–insulin-dependent (type 2) diabetes mellitus patients, a change in treatment from oral drugs to insulin was often associated with a significant increased risk of retinopathy progression and visual impairment. Although insulin therapies are critical for regulation of the metabolic disease, their role in the retina is controversial. In this study with diabetic mice, insulin treatment resulted in increased vascular leakage apparently mediated by betacellulin and signaling via the epidermal growth factor (EGF) receptor. In addition, treatment with EGF receptor inhibitors reduced retinal vascular leakage in diabetic mice on insulin. These findings provide unique insight into the role of insulin signaling in mediating retinal effects in diabetes and open new avenues for therapeutics to treat the retinal complications of diabetes mellitus.Diabetic maculopathy, an important cause of vision loss in patients with type 2 diabetes, is characterized by hyperpermeability of retinal blood vessels and subsequent formation of macular edema and hard exudates. Although the increase in retinal vascular permeability occurs both diffusely and in focal regions, the basic physiological defect that causes retinal vascular leakage is unknown. The blood–retinal barrier (BRB) isolates the retina from the bloodstream, establishing a favorable environmental milieu with the regulation of ionic balance, nutrient availability, and blockage of potentially toxic molecules that allows for optimal retinal function. The BRB consists of an inner BRB, formed by endothelial cells lining the retinal blood vessels and the outer BRB formed by the retinal pigment epithelium (RPE), a layer of epithelial cells between the retina and the non-neuronal choroid.^1,2 Disruption of the BRB is an important feature of diabetic retinopathy.Based on data from the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), a prospective population-based cohort study of patients with type 1 and 2 diabetes mellitus, the prevalence of clinically significant macular edema is 5.9% for type 1 and 7.5% for type 2 diabetes.³ Although epidemiologic studies and randomized clinical trials suggest that glycemic control plays a major role in the development of vascular complications of diabetes,⁴ insulin therapies for control of glucose metabolism may not prevent long-term complications.^5,6 Even though both laser photocoagulation and anti-VEGF therapies have shown significant promise in the treatment of proliferating vessels in proliferative diabetic retinopathy, diabetic macular edema (DME) appears to be more resistant to these treatment approaches, suggesting that other factors might contribute to this complication. We have recently reported the potential role of betacellulin (Btc) in inducing retinal vascular permeability in diabetes.⁷ Clinical trials and other studies have determined that initiation of acute intensive insulin therapy in patients with long-standing poor glycemic control results in a transient worsening of diabetic retinopathy.^8–13 A change in treatment from oral drugs to insulin in patients with non–insulin-dependent (type 2) diabetes mellitus was associated with a significantly increased risk of retinopathy progression and visual impairment.^14–16 In addition, it has been reported that patients who undergo total pancreatectomy for cancer develop severe diabetes because of the complete absence of insulin but rarely if ever develop proliferative diabetic retinopathy,¹⁷ even when they survive for more than one or two decades. These reports led us to model and evaluate the pathophysiological effects of insulin on the retinal vasculature and the potential crosstalk between insulin and Btc in the regulation of retinal vascular permeability.     

“Heart failure in COVID-19 patients: Critical care experience”: A letter to the editor

Coronavirus disease 2019 (COVID-19) is associated with poor cardiovascular outcomes in patients with heart failure (HF) of all categories of ejection fraction (EF), but mainly in patients with HF with reduced EF. Moreover, cardiac transplant patients exhibit worse cardiovascular prognosis, high mortality, and more admissions to the intensive care unit. In general, COVID-19 seems to de-teriorate the clinical status of HF and favors the development of acute respiratory distress syndrome and multiorgan failure, especially in the presence of cardiovascular comorbidities such as diabetes mellitus, kidney dysfunction, and older age. COVID-19 may induce new-onset HF with complex mechanisms that involve myocardial injury. Indeed, myocardial injury comprises a large category of detrimental effects for the myocardium, such as myocardial infarction type 1 or type 2, Takotsubo cardiomyopathy, microvascular dysfunction and myocarditis, which are not easily distinguished by HF. The pathophysiologic mechanisms mainly involve direct myocardial damage by severe acute respiratory syndrome coronavirus 2, cytokine storm, hypercoagulation, inflammation, and endothelial dysfunction. The proper management of patients with COVID-19 involves careful patient evaluation and ongoing monitoring for complications such as HF.     

Potential use of bitter melon (Momordica charantia) derived compounds as antidiabetics: In silico and in vivo studies

Momordica charantia (bitter lemon) belongs to the cucurbitaceae family which has been extensively used in traditional medicines for the cure of various ailments such as cancer and diabetes. The underlying mechanism of M. charantia to maintain glycemic control was investigated. GLP-1 and DPP-4 gene modulation by M. charantia (5–20% inclusion in rats diet) was investigated in vivo by RT-PCR and possible compounds responsible for diabetic action predicted through in silico approach. Phytochemicalss previously characterized from M. charantia were docked into glucacon like peptide-1 receptor (GLP-1r), dipeptidyl peptidase (DPP4) and Takeda-G-protein-receptor-5 (TGR5) predicted using Autodock Vina. The results of the in silico suggests momordicosides D (ligand for TGR5), cucurbitacin (ligand for GLP-1r) and charantin (ligand for DPP-4) as the major antidiabetic compounds in bitter lemon leaf. M. charantia increased the expression of GLP-1 by about 295.7% with concomitant decreased in expression of DPP-4 by 87.2% with 20% inclusion in rat’s diet. This study suggests that the mechanism underlying the action of these compounds is through activation of TGR5 and GLP-1 receptor with concurrent inhibition of DPP4. This study confirmed the use of this plant in diabetes management and the possible bioactive compounds responsible for its antidiabetic property are charantin, cucurbitacin and momordicoside D and all belong to the class of saponins.     

Intensive glycemic control in diabetic pregnancy with intrauterine growth restriction is detrimental to fetus

Hyperglycemia during early pregnancy can lead to congenital malformations and/or spontaneous abortion while in the last few days of pregnancy it causes neonatal metabolic complications. Macrosomia is the most common complication and is due to maternal hyperglycemia in second and third trimester of pregnancy. In view of all these, intensive glycemic control of the mother is recommended throughout pregnancy. Intrauterine growth restriction (IUGR) is a well known complication of pre-gestational diabetic patients due to vasculopathy and is also seen in gestational diabetes mellitus (GDM) due to overinsulinisation. Hitherto there are no separate recommendations for glycemic targets in pregnant diabetic patients with IUGR. In presence of IUGR due placental vascular insufficiency, intensive glycemic control may deprive fetus of nutrition. Secondly frequent hypoglycemias which are inevitable complication of insulin treatment may further worsen the IUGR. In presence of IUGR, macrosomia is a rare possibility, and in such situation intensive glycemic control throughout pregnancy may not be justifiable and may actually be detrimental. Neonatal metabolic complications can be avoided by strict glycemic control during last two weeks of pregnancy.