Objective: Traditional denoising algorithms perform less due Limited Directional Selectivity problem and do not adequately capture directional information in pixels. Traditional algorithms' edge representation and texture details are insufficient for the earlier detection of DH. Limited Directional Selectivity leads to inaccurate diagnosis and classification of Disc Herniation (DH) stages. The DH stages are (i) Degeneration (ii) Prolapse (iii) Extrusion and (iv) Sequestration. Moreover, detection of DH size below 2mm using MR image is the major problem.

Methods: To solve the above problem, spinal cord MR images fed to the proposed Parrot optimization tuned Denoising Convolutional Neural Network (Po- DnCNN) algorithm for perspective enhancement of nucleus pulposus region in the spinal cord, vertebrae. The perspective enhancement of Spinal cord image led to the accurate classification of stages and earlier detection of DH by using the proposed Hippopotamus optimization- Fast Hybrid Vision Transformer (Ho–FastViT) algorithm. For this study, spinal cord MR images are obtained from the Grand Challenge website – SPIDER dataset.

Results: The proposed Po-DnCNN method and Ho-FastViT results are analysed quantitatively and qualitatively based on the edge, contrast, classification of the stage, and enhancement of the projected nucleus pulposus region in the spinal cord and vertebrae. The predicted DH results using the proposed method are compared with the manual Pfirrman Grade value of the spinal card method.

Conclusion: Proposed method is better than traditional methods for earlier detection of DH. Po-DnCNN and Ho-FastViat methods give high accuracy of about 98% and 97% compared to traditional methods.

Objectives: The purpose of this article is to provide a narrative review on the management of DKA.

Methods: A PubMed search was performed with clinical queries using the key term “diabetic ketoacidosis”. The search strategy included randomized controlled trials, clinical trials, meta-analyses, observational studies, guidelines, and reviews. The search was restricted to English literature and the age range of 18 years and younger. Moreover, we reviewed and compared major guidelines.

Results: Selected international guidelines for DKA, namely International Society for Pediatric and Adolescent Diabetes (ISPAD), National Institute for Health and Care Excellence (NICE), British Society for Paediatric Endocrinology and Diabetes (BSPED), and South Thames Retrieval Service (STRS) were reviewed. There are considerable differences in the management approaches for DKA between different countries. One of the main areas of differences between guidelines is the administration of fluid, with most guidelines adopting a restrictive approach. This is based on the concern over cerebral oedema, a lethal sequela allegedly to be caused by excessive fluid administration. However, recent new clinical studies suggest that there is no causal relationship between intravenous fluid therapy and DKA-related cerebral injury. The British Society of Paediatric Endocrinology updated its guideline in 2020 to adopt a more permissive approach to fluid administration, which has sparked controversy among some paediatricians.

Conclusion: The management of DKA involves early recognition, accurate diagnosis, meticulous fluid and insulin treatment with close monitoring of blood glucose, ketones, electrolytes, renal function, and neurological status. There is still limited clinical evidence to support either a restrictive or permissive approach in the fluid management of paediatric DKA patients. Clinicians should exercise caution when applying different guidelines in their clinical practice, considering the specific circumstances of individual paediatric patients.

Purpose: To investigate the feasibility of muscle CT radiomics in evaluating muscle changes in diabetes.

Materials and Methods: 60 diabetics and 60 health controls (HC) were assessed with the method of muscle CT radiomics. 93 CT images of radiomics features of the pectoralis major muscle (PMM) were obtained by using the software 3D Slicer and were then compared between diabetics and HC cases. The least absolute shrinkage and selection operator (LASSO) regression method was used to establish a prediction model. The receiver operating characteristic (ROC) curve was used to determine the performance of the model.

Results: Diabetics and HC cases differed in 19 radiomics features (P<0.05). By using the LASSO method, 6 features were finally selected. The AUC of the model in the discrimination of diabetics and HC were 0.92 and 0.90, respectively, for the training cohort and validation cohort.

Conclusion: Muscle CT radiomics is feasible in evaluating muscle changes in diabetes.

Objective: To create a systematic correlation between the disease and locate the exact mechanism and receptors responsible for it. So, this article covers a proper way to resolve the conditions and their manifestation through literacy and diagrammatic.

Conclusion: Hence, this will be an insight for many scholars to understand the exact mechanism involved in the process.

Objective: The objective of the study was to combine the 3-amino-4-(2,4,5- trifluorophenyl) butyric acid and menthol to develop a new candidate drug molecule that can be used as a hypoglycemic drug in type II diabetes.

Methods: In this study, the molecular structure of 3-amino-4-(2,4,5-trifluorophenyl) butyric acid in sitagliptin was modified by replacing pyrazine imidazole with menthol. The structure of the target compound was characterized by nuclear magnetic resonance (NMR). The anti-diabetic activity of BHF in N000180 BKS.Cg-Dock7m+/ +Leprdb/Nju mice with spontaneous diabetes was preliminarily studied.

Results: A potential multi-target drug molecule, 3-amino-4-(2,4,5-trifluorophenyl) butyrate (BHF), was synthesized by combining 3-amino-4-(2,4,5-trifluorophenyl) butyric acid and menthol. BHF is suitable for hyperglycemic mice and has a significant hypoglycemic effect; the low dose of 10 mg/kg-1 started to be effective, and the high dose of 40 mg/kg-1 was more effective than the positive drug metformin.

Conclusion: In this study, BHF has been synthesized and presented significant antidiabetic activities.

Methods: The systematic review was conducted on PubMed, Lilacs, and Embase, according to PRISMA. For this purpose, three groups of descriptors were used: Adults with T1DM, anaerobic physical exercise, and glycemic control. The search filter was set to human beings older than 18 years of age, longitudinal and cross-sectional studies, with studies published from 2000 to 2023 in English, Spanish, or Portuguese. Titles and abstracts were read independently by two reviewers, and then the articles were selected for this review. The Kappa coefficient was measured to evaluate the selection.

Results: A total of 738 articles were identified, and five were selected to be part of the review after applying the steps of the procedure. Some benefits were observed in fatigue reduction, absence of diabetic ketoacidosis requiring hospitalization, and enhancement of glucose monitoring during exercise. In the anaerobic workouts of the groups with T1DM, glycemic mean values ranged from 124.5-185.0 mg/dl, and glycated hemoglobin records ranged from 6.7-8.1%.

Conclusion: Anaerobic exercise improved the biomarkers of T1DM, especially glycemic control, and the reduction of symptomatic hypoglycemic episodes. Anaerobic exercise can be performed by individuals with T1DM, suggesting an individualized training prescription and encouraging its practice associated with aerobic exercise.

Objective: This review aims to provide a comprehensive overview of the chemistry, pharmacology, and toxicology of empagliflozin, synthesizing the available literature to present a concise summary of its properties and implications for clinical practice.

Methods: A systematic search of relevant databases was conducted to identify studies and articles related to the chemistry, pharmacology, and toxicology of empagliflozin. Data from preclinical and clinical studies, as well as post-marketing surveillance reports, were reviewed to provide a comprehensive understanding of the topic.

Results: Empagliflozin is a selective SGLT2 inhibitor that works by constraining glucose reabsorption in the kidneys, causing increased urinary glucose elimination. Its unique mechanism of action provides glycemic control, weight reduction, and blood pressure reduction. The drug's chemistry is characterized by its chemical structure, solubility, and stability. Pharmacologically, empagliflozin exhibits favorable pharmacokinetic properties with rapid absorption, extensive protein binding, and renal elimination. Clinical studies have demonstrated its efficacy in improving glycemic control, reducing cardiovascular risks, and preserving renal function. However, adverse effects, for instance, urinary tract infections, genital infections, and diabetic ketoacidosis have been reported. Toxicological studies indicate low potential for organ toxicity, mutagenicity, or carcinogenicity.

Conclusion: Empagliflozin is a promising SGLT2 inhibitor that offers an innovative approach to the treatment of type 2 diabetes mellitus. Its unique action mechanism and favorable pharmacokinetic profile contribute to its efficacy in improving glycemic control and reducing cardiovascular risks. While the drug's safety profile is generally favorable, clinicians should be aware of potential adverse effects and monitor patients closely. More study is required to determine the longterm safety and explore potential benefits in other patient populations. Overall, empagliflozin represents a valuable addition to the armamentarium of antidiabetic medications, offering significant benefits to patients suffering from type 2 diabetes mellitus. This study covers all aspects of empagliflozin, including its history, chemistry, pharmacology, and various clinical studies, case reports, and case series.

Introduction: DN has become one of the most prevalent complications of clinical hyperglycemia, with individual-specific variations in the disease spectrum that leads to fatal consequences. Diverse etiologies involving oxidative and nitrosative stress, activation of polyol pathway, inflammasome formation, Extracellular Matrix (ECM) modifications, fibrosis, and change in dynamics of podocyte functional and mesangial cell proliferation adds up to the clinical complexity of DN. Current synthetic therapeutics lacks target-specific approach, and is associated with the development of inevitable residual toxicity and drug resistance. Phytocompounds provides a vast diversity of novel compounds that can become an alternative therapeutic approach to combat the DN.

Methods: Relevant publications were searched and screened from research databases like GOOGLE SCHOLAR, PUBMED and SCISEARCH. Out of 4895 publications, the most relevant publications were selected and included in this article.

Result: This study critically reviews over 60 most promising phytochemical and provides with their molecular targets, that can be of pharmacological significance in context to current treatment and concomitant research in DN.

Conclusion: This review highlights those most promising phytocompounds that have the potential of becoming new safer naturally-sourced therapeutic candidates and demands further attention at clinical level.

Objective: The present review discusses the functional interdependence between COVID-19 and Mucormycosis and summarizes the possible synergic links between COVID and Mucormycosis.

Conclusion: The receptors and metabolic pathways affected by COVID-19 result in severe physiological conditions- hyperglycemia, DKA, anemia, iron overload, immunosuppression, and hypoxia. All these conditions not only increase the expression of GRP-78, the major receptor for entry of fungi but also play a crucial role in providing quality media for Mucormycosis fungus to establish and grow. Hence explains the fungal epidemic observed in India during the second wave of COVID-19 in India.

Case Presentation: Here we report an interesting case of middle-aged African woman, newly diagnosed with KPD, presenting with DKA hematemesis. The patient was first treated at Intensive Care Unit for the ketoacidosis with intravenous fluids combined with continuous insulin infusion, and then switched to subcutaneous regimen. At the same time, esophagogastroduodenoscopy (EGD) was performed to diagnose acute esophageal necrosis, which was promptly managed with proton pump inhibitors infusion, fasting, and parenteral nutrition. After the correct clinical evaluation, the patient was switched to oral antidiabetic and basal insulin at discharge and an EGD follow-up was scheduled.

Conclusions: KPD remains an under-recognized and under-diagnosed type of diabetes which can present as DKA. Since DKA could be a possible trigger of AEN, a rare but potentially lifethreatening condition, that clinicians should be aware of, in patients presenting with upper gastrointestinal bleeding and ketoacidosis. The prompt management and classification of DKA, combined with the EGD execution for early AEN diagnosis and follow-up, is essential.

Objective: In this work, we aimed to summarize the interesting results from preclinical and clinical studies that assessed the effects of natural alkaloids (berberine, nigelladine A, piperine, trigonelline, capsaicin, nuciferine, evodiamine, mahanine, and magnoflorine) on impaired insulin sensitivity and worsened insulin resistance, which play a pivotal role in the pathogenesis of type 2 diabetes.

Methods: In the current review, PubMed, ScienceDirect, Springer, and Google Scholar databases were used. The inclusion criteria were based on the following keywords and phrases: insulin sensitivity, insulin resistance, alkaloids and insulin resistance, alkaloids and type 2 diabetes, mechanisms of action, and alkaloids.

Results: The outcomes reported in this review demonstrated that the selected alkaloids increased insulin sensitivity and reduced insulin resistance in vitro and in vivo evidence, as well as in clinical trials, through improving insulin-signaling transduction mainly in hepatocytes, myocytes, and adipocytes, both at cellular and molecular levels. Insulin signaling components (InsR, IRS-1, PI3K, Akt, etc.), protein kinases and phosphatases, receptors, ion channels, cytokines, adipokines, and microRNAs, are influenced by alkaloids at transcriptional and translational levels, also in terms of function (activity and/or phosphorylation). Multiple perturbations associated with insulin resistance, such as ectopic lipid accumulation, inflammation, ER stress, oxidative stress, mitochondrial dysfunction, gut microbiota dysbiosis, and β-cell failure, are reversed after treatment with alkaloids. Furthermore, various indices and tests are employed to assess insulin resistance, including the Matsuda index, insulin sensitivity index (ISI), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT), which are all enhanced by alkaloids. These improvements extend to fasting blood glucose, fasting insulin, and HbA1c levels as well. Additionally, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the Homeostasis Model Assessment of β-cell function (HOMA-β) are recognized as robust markers of insulin sensitivity and β-cell function, and it is noteworthy that alkaloids also lead to improvements in these two markers.

Conclusion: Based on the findings of the current review, alkaloids may serve as both preventive and curative agents for metabolic disorders, specifically type 2 diabetes. Nonetheless, there is an urgent need for additional clinical trials to explore the potential benefits of alkaloids in both healthy individuals and those with type 2 diabetes. Additionally, it is crucial to assess any possible side effects and interactions with antidiabetic drugs.

Methods: We categorized patients into four groups based on their BMI utilizing data from our hospital's medical record system from 2018 to 2020 in the Department of Endocrinology: obese DK or DKA patients (OB+DK/DKA, n = 41), non-obese DK or DKA patients (DK/DKA, n = 201), obese type 2 diabetes patients without DK or DKA (OB+T2D, n = 93), and patients with type 2 diabetes only (T2D only, n = 304). The comparisons were made on glycosylated hemoglobin (HbA1c), body mass index (BMI), fasting plasma C-peptide (FPCP), and plasma lipids, in addition to bone metabolism indicators such as total 25-OH-VitD3 (25-OH-VitD3), N-terminal middle molecular fragment of osteocalcin (NMID), -C terminal cross-linking telopeptide of type 1 collagen (-CTX), parathyroid hormone (PTH), and blood calcium (Ca²⁺).

Results: The OB+DK/DKA group had a lower average age (p < 0.05) than the DK/DKA group, while the DK/DKA group had a significantly lower FPCP (p < 0.05). The 25-OH-VitD3 levels of DK/DKA patients were considerably lower than those of the T2D-only group (p < 0.05). In contrast, NMID and Ca²⁺ levels were significantly lower than those of non-ketosis or acidosis patients (p < 0.05), and PTH levels in the DK/DKA group were significantly lower than those of OB+ T2D patients (p < 0.05). In contrast, the β-CTX of the DK or DKA group (OB+DK/DKA and DK+DKA) was significantly greater than that of the non-DK or DKA group (p < 0.05), although there was no significant difference in blood phosphorus between OB+DK/DKA and DK/ DKA (p > 0.05). The levels of thyroid-stimulating hormone (TSH) and free T4 (FT4) did not differ significantly among the four groups (p > 0.05); however, the levels of total T3 (TT3), T4 (TT4), and free T3 (FT3) were significantly lower in the DK/DKA group (p < 0.05); the ratio of TT3 to TT4 (TT3/TT4) was significantly decreased in the DK/DKA group, whereas the ratio of FT3/FT4 was significantly lower (p < 0.05).

Conclusion: Obese patients with DK or DKA have a younger onset age, superior pancreatic function, and better blood glucose management than non-obese patients with DK/DKA. Despite having higher bone absorption signals than non-DK/DKA patients, OB+DK/DKA patients have stronger bone formation markers than non-obese DK/DKA patients, according to a recent study. Changes in markers of bone metabolism may be linked to non-thyroidal illness syndrome in cases of DK or DKA.

Case Presentation: Here we report two peculiar cases of young African patients, affected by KPD and hypergonadotropic hypogonadism, respectively Klinefelter’s syndrome and primary ovarian failure. Both patients were treated promptly for the ketoacidosis with intravenous fluids combined with continuous insulin infusion, and then switched to subcutaneous regimen. After the correct clinical evaluation, oral antidiabetic drugs were added.

Conclusion: KPD remains an under-recognized and under-diagnosed type of diabetes. As hypogonadism is strongly linked to dysmetabolic disorders, the evaluation of sex hormones should be performed at the onset of diabetes. Further studies should investigate the hypothalamic-pituitary-gonadal axis and its role in the development of KDP and its manifestations and complications.

Methods: Based on predetermined criteria, a bibliographical search was performed on May 31, 2022, by searching the following databases: ISI Web of Science, Embase, PubMed, and the Cochrane Library. Statistical analysis was conducted to assess renal protection and safety of SGLT2i by using Cochrane Review Manager Version 5.3.

Results: Thirty randomised controlled trials fulfilled the inclusion criteria and were eligible for this meta-analysis. Our study found that the SGLT2i can sustainably reduce the urine albumin/creatinine ratio (UACR) at different time points and prevent the progression to macroalbuminuria. Before 24 weeks, SGLT2i can decrease the estimated glomerular filtration rate (eGFR) compared to the control group. Interestingly, after 24 weeks, SGLT2i can continuously maintain the increase in eGFR when compared with the control group. Furthermore, SGLT2i can reduce the event rates of incident or worsening nephropathy, a decline in estimated eGFR of ≥ 50%, doubling of serum creatinine level, acute renal failure and renal failure. Interestingly, the renoprotective effects of SGLT2i are independent of its glycemic effects. SGLT2i can reduce the morbidity rate of any related adverse events, any related severe adverse events and SGLT2i have not increased the event rates of urinary tract infection, bone fractures, amputation, and acute pancreatitis when compared with the control group.

Conclusion: SGLT2i can protect renal function and are safe drug for CKD. SGLT2i are promising therapeutic agents for CKD patients.

Methods: The present retrospective cross-sectional study aims to describe the experience on the clinical profile, morbidity profile, and comorbidities of Type1 DM in children below 15 years of age admitted to the SAQR and Fujairah hospitals in the Northern part of United Arab Emirates (UAE) from 1st January 2017 to 31st December 2019. The study material was the digital medical records of children below 15 years who got admitted to emergency and pediatric wards with type 1 Diabetes mellitus (T1DM) in SAQR and Fujairah hospitals.

Results: Total admissions during the study period were 98. At the time of diagnosis, 12.2% of children were below five years of age, whereas 87.75% were more than five years. All 98 children were UAE nationals, of which 52% were males and 48% were females. 50% of our study population has a strong family history of either type 1 or type 2 diabetes mellitus, of which 12.2% of siblings of the study population had T1DM. The first symptoms in 58% and 57% of children were polyuria and polydipsia. Among 90% of children under follow-up for three years, one child developed microalbuminuria, three developed systolic hypertension, and 8% were lost to follow-up.

Conclusion: The present study highlights the need for future prospective studies in the UAE to know the actual burden of the disease with an emphasis on early screening.

Introduction: The overarching goal of diabetic research and treatment has always been to restore insulin independence and an average blood glucose level. Chemotherapeutic antidiabetic agents can manage diabetes but often show toxicity and drug resistance. Natural phytomedicines may be useful along with stem cell therapy for diabetes management. Even if the whole pancreatic organ and islet transplantation, are becoming benchmark techniques for diabetes management and control, a considerable scarcity of eligible donors of pancreatic tissues and organs severely limits their use. Stem cell treatment provides a bunch of possibilities for treating people with diabetes.

Methods: For this purpose, comprehensive article searching was conducted, with relevant material obtained using search engines such as Scopus, PubMed, MEDLINE, Google, and others, using appropriate keywords.

Results: Stem cell therapies, including induced pluripotent stem cells and mesenchymal stem cells, are now becoming a popular area of investigation. Recent advancements in stem cell therapy might provide a feasible treatment option. Furthermore, in recent years, some novel bioactive compounds derived from plants have demonstrated antidiabetic action with higher potency than oral hypoglycaemic medications. Recent regenerative medicine and stem cell treatment advancements might subsequently provide a feasible diabetic management option. On the other hand, medicinal herbs have been considered a better choice for the extensive treatment of diabetes.

Conclusion: If proper attention is not given to control diabetes by antidiabetic chemotherapeutic agents, natural phytomedicine, and sophisticated treatment like stem cell therapy, then the lifespan of patients will be decreased, and some associated secondary problems will also arise. So, the present review attempts to discuss naturopathy as an alternative resource in combination with stem cell therapy for the progressive management of diabetes and associated disorders.

Case Presentation: Herein we present the case of a 57-year-old woman referred to our clinic due to poor glycemic control (HbA1c 80 mmol/mol, therapeutic target <53 mmol/mol), class III obesity (BMI 41 kg/m2; normal value <25 kg/m²), and high cardiovascular risk misdiagnosed with T2D several years before. C-peptide measurement (0.3 ng/dL; reference range 1.1 – 4.4 ng/mL) confirmed the diagnosis of an insulinopenic form of diabetes, and the islet autoimmunity was consequently measured (GADA 2,000 UA/mL, reference range <5 UA/mL; IA2 17.1 UA/mL, reference range <7.5 UA/mL) and defined the diagnosis of an autoimmune form of diabetes.

Discussion: Deprescribing insulin therapy in T2D patients in favor of other antihyperglycemic medications has become a growing therapeutic opportunity to provide adequate glucose control, promote weight loss, improve insulin sensitivity, and ameliorate cardiovascular and renal outcomes. However, a blunted insulin reserve poses significant restriction on the prescription of non-insulin agents (e.g., diabetic ketoacidosis due to gliflozins). According to our experience, the routine testing of insulin reserve provides detailed information on diabetes pathophysiology with positive implications for the appropriateness of pharmacological prescriptions.

Conclusion: As part of our routine evaluation of diabetic patients, C-peptide measurement is a valuable and inexpensive tool to reclassify diabetes types and provide more appropriate disease management.

Methods: Diabetic ketoacidosis is more common in type 1 diabetic patients, although it can also be fall in type 2 diabetic patients. DKA occurs when the body lacks enough insulin to allow blood sugar to enter the cells and is used for energy. Instead, the liver breaks down fat for fuel-producing chemicals known as ketones.

Results: When too many ketones are created too quickly, they can reach dangerously high levels in the body. Mucormycosis is a rare but serious infectious disease that requires medication or surgical removal.

Conclusion: The confluence of diabetes and COVID-19 makes managing mucormycosis a serious and dead issue. Although the effectiveness of prophylactic antifungal therapy has yet to be demonstrated, hyperglycemia control appears to be the most important step in managing mucormycosis in DKA patients.

Case Presentation: A 23-year-old gravida 3, para 2 woman sustained a forearm laceration at 18 weeks of gestation. Her hemoglobin dropped to 7.9 mg/dL. A surgical laceration repair was completed, and she was transfused with blood. At the OB visit the following week, her fetal US showed abnormal brain, evident by the increased size of the lateral ventricles. A follow-up MRI at 30 weeks of gestation confirmed fetal encephalomalacia. A complete investigation, including free cell maternal DNA for chromosomal anomalies, TORCH infection, and Covid PCR, all were negative. Conclusion:

We concluded from the case that any history of significant acute maternal blood loss that required blood transfusion should necessitate a fetal ultrasound to look for fetal well-being, especially for any brain structural changes in the developing brain.]]> https://www.benthamscience.comarticle/121996 https://www.benthamscience.comarticle/118744Background: The growing numbers of patients with diabetes mellitus in Africa and the Middle East on antidiabetic therapies necessitate an understanding of adverse event (AE) reporting in these regions.

Objective: The aim of the study was to provide an AE reporting overview in patients using insulin in Africa and the Middle East by characterizing and comparing individual case safety reports (ICSRs) features.

Methods: The cross-sectional study analyzed ICSR data from a global pharmaceutical company’s pharmacovigilance database for January to December 2018 to describe and compare patient demographics, report sources, reporter types, ICSR seriousness, suspect products, indication for insulin use and AE preferred terms, by country.

Results: Overall 7076 ICSRs were analyzed, 63.6% from the Middle East. Most ICSRs were nonserious (91.5%), from solicited sources (83.5%), and reported by consumers (70.7%). Patients from the Middle East were, on average, 34.2 years of age, had gestational diabetes mellitus as indication (64.3%), insulin detemir as suspect product (76.5%), and exposure during pregnancy as AE preferred term (89.1%). Patients from Africa were 48.1 years old on average, a higher proportion of type 2 diabetes mellitus was observed (52.2%), human insulin was the suspect product (51.6%), and blood glucose increased the AE preferred term (23.1%). Few macrovascular and microvascular complications were reported (< 1% in both regions). Associations between the region and patient age, gender, report sources, reporter types, indications for insulin use, suspect products, and AE preferred term were significant (p < 0.001).

Conclusion: ICSRs features were region-specific and dependent on patient age, gender, report sources, reporter types, suspect products, and AE preferred terms.

Conclusion: Our patient successfully managed with ascorbic acid and red blood cell transfusion. Clinicians should, therefore, be aware of the possibility of this uncommon association between diabetic ketoacidosis, G6PD deficiency, and methemoglobinemia which may be present in patients with G6PD deficiency and severe hemolysis.]]> https://www.benthamscience.comarticle/116389 https://www.benthamscience.comarticle/118109Background: Lipoprotein Lipase (LPL) is the rate-limiting enzyme catalyzing the hydrolysis of triglycerides and contributes to the amyloid-β formation, which shows promise as a pathological factor of cognitive decline in Type 2 Diabetes Mellitus (T2DM). This study aimed to investigate the pathogenetic roles of LPL and rs328 polymorphism in Mild Cognitive Impairment (MCI) in patients with T2DM.

Methods: Chinese patients with T2DM were recruited and divided into two groups based on the Montreal Cognitive Assessment score. Demographic data were collected, LPL was measured and neuropsychological test results were examined.

Results: Seventy-nine patients with diabetes and MCI had significantly decreased plasma LPL levels (p = 0.007) when compared with health-cognition controls (n = 91). Correlation analysis revealed that LPL was positively correlated with clock drawing test (r = 0.158, p = 0.043) and logical memory test (r = 0.162, p = 0.037), while lipoprotein a (r = -0.214, p = 0.006) was inversely associated with LPL. Logistic regression analysis further demonstrated that LPL concentration was an independent factor for diabetic MCI (p = 0.036). No significant differences were observed in the distributions of rs328 variants between patients with MCI and the controls. Moreover, no remarkable association was found among plasma LPL levels, cognitive performances, and lipid levels between the genotypic subgroups. The trail making test A was increased in the GC group when compared with the CC genotype in the control group.

Conclusion: Decreased plasma level of LPL could probably predict early cognitive deficits, especially verbal disfluency.

Recently, the Sodium Glucose Co-transporter type 2 inhibitors (SGLT2 inhibitors) used for the treatment of heart failure patients with or without diabetes has been a breakthrough in the field of medicine.

This review describes the established pathophysiology of diabetic cardiomyopathy and SGLT2 inhibitors, their mechanisms of action, and benefits in this group of patients.

Methods: A comprehensive literature search was carried out to identify eligible studies from MEDLINE/ PubMed, EMBASE, and SCIELO databases from 1970 to 2019 first semester.

Results: Pregnancy introduces changes in the pharmacodynamic and pharmacokinetic profile of some of the treatments used in MODY. MODY 3 (also known as HNF1-A MODY) is the most frequent MDF. MODY 3 patients are highly sensitive to Sulfonylureas (SU). This is also the case for MODY pregnant women. This high sensitivity to SU is also registered in patients with MODY 1 (HNF4-A MODY). Pharmacodynamic changes have been proposed to explain this behavior (Epac2 hyperactivity). However, changes in expression/activity of the metabolizing CYP2C9 cytochrome and/or alterations in the drug transporters oatp1 (Slc21a1), Lst-1 (Slc21a6), OATPD (SLC21A11), and oat2 may better explain, at least in part, this phenomenon by an increase in the concentration of the active drug.

Conclusion: The impact of changes in the pharmacological behavior of drugs like SU and other metabolized/transported by mechanisms altered in a pregnancy complicated by MODY is unknown. However, switching-to-insulin recommendation formulated for MODY 1 and 3 seems to be justified. Further research in this field is needed for a better understanding of changes in drug activity associated with this particular subset of patients with MFD.

Methods: An overview of DM pathogenesis and its associated micro- and macro-vascular complications is presented. Possible underlying mechanisms of herbal remedies in DM management are provided, highlighting some key therapeutic targets. The review also appraises the recent progress of herbal products in treating DM through regulating inflammation and gut microbiota. Finally, currently available pharmacological treatments are discussed.

Results: The results show that numerous plants have proven to be promising sources of insulin secreting agents, α-glucosidase and α-amylase inhibitors. Among the non- conventional targets, inhibition of key enzymes such as lipase, cholinesterases and angiotensin converting enzyme has been directly and/or indirectly linked to DM and DM complications. For instance, hypericin, pseudohypericin and I3,II8-biapigenin isolated from Hypericum perforatum L., and palmatine and columbamine isolated from Dichocarpum auriculatum (Franch.) W. T. Wang & P. K have been found to be powerful lipase and cholinesterase inhibitors, respectively. Moreover, a number of plant-derived compounds such as feruloylated oligosaccharides from maize bran, baicalein and berberine are reported to mediate anti-diabetic property via modulation of gut microbiota.

Conclusion: The information amassed in this review is anticipated to provide useful scientific baseline information to support advanced research in natural antidiabetic drug development.

Objective: This review aimed to describe the particularities of the RAS and the immune system profile of particular subgroups of patients.

Methods: This non-systematic review summarizes evidence on SARS-CoV-2 infection in specific subgroups of patients and possible relationships between immune system, RAS and the pathophysiology of COVID-19.

Results: The RAS and the immune system exert a role in the pathogenesis and prognosis of COVID-19, mainly in cases of hypertension, diabetes, obesity and other chronic diseases. The overactivation of the ACE/Ang II/AT1R axis and the enhancement of inflammation contribute to deleterious effects of COVID-19. Likewise, pregnant women and elderly patients usually display immune responses that are less effective in withstanding exposition to viruses, while children are relatively protected against severe complications of COVID-19. Women, conversely, exhibit stronger antiviral responses and are less sensitive to the effects of increased Ang II.

Future Perspectives: The recognition of vulnerable subgroups and risk factors for disease severity is essential to better understand the pandemic. Precision medicine tools, including proteomics and metabolomics approaches, identified metabolic patterns of the severe form of disease and might be the alternative to diagnose, evaluate and predict the prognosis and the efficiency of therapies.

Methods: A BPA was implemented on 9/15/2018. We conducted a retrospective review of patients admitted to the ICU with DKA a year before and after 9/15/2018. Adults (≥18 age) meeting DKA criteria on admission and treated with continuous insulin infusion (CII) were included. Pre-intervention group included patients admitted before BPA implementation and post-intervention group included patients admitted after. Summary and univariate analyses were performed.

Results: A total of 282 patients were included; 162 (57%) pre-intervention and 120 (43%) post-intervention. Mean (±SD) age of the patients was 44 (±17) years. There was no significant difference in baseline characteristics such as age, sex, race, BMI, HbA1c, initial blood glucose, anion gap or bicarbonate concentration between both the groups (p>0.05). Mean (±SD) total time on CII in hours was significantly lower in the post-intervention group {14.8 (±7.7) vs. 17.5 (±14.3) p=0.041, 95% CI: 0.11-5.3}. The incidence of hypoglycemia was lower in the post-intervention group {n=4 (3%) vs. 17 (10%), p=0.024}. There was no significant difference in hypokalemia, mortality, LOS or ICU stay between both the groups (p>0.05).

Conclusion: The BPA introduced in our DKA management algorithm successfully reduced the total time on insulin and the incidence of hypoglycemia.

Methods: Structured search of bibliographic databases from previously published peer-reviewed research papers was explored and data has been represented in terms of various approaches that are used for the treatment of DFU.

Results: About 148 papers, including both research and review articles, were included in this review to produce a comprehensive as well as a readily understandable article. A series of herbal and synthetic drugs have been discussed along with their current status of treatment in terms of dose and mechanism of action.

Conclusion: DFU has become one of the most common complications in patients having diabetes for more than ten years. Hence, understanding the root cause and its successful treatment is a big challenge because it depends upon multiple factors such as the judicious selection of drugs as well as proper control of blood sugar level. Most of the drugs that have been used so far either belong to the category of antibiotics, antihyperglycaemic or they have been repositioned. In clinical practice, much focus has been given to dressings that have been used to cover the ulcer. The complete treatment of DFU is still a farfetched dream to be achieved and it is expected that combination therapy of herbal and synthetic drugs with multiple treatment pathways could be able to offer better management of DFU.]]> https://www.benthamscience.comarticle/110814 https://www.benthamscience.comarticle/111137Background: Type 2 diabetes mellitus (DM) is associated with a considerable risk of cardiovascular and renal diseases, including heart failure. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have demonstrated unprecedented cardiorenal protective effects in large-scale clinical trials of patients with or without diabetes and either established cardiovascular disease (CV) or multiple CV risk factors.

Objective: Herein we aim to focus on the role of SGLT2 inhibitors regarding the improvement in heart failure outcomes and the proposed mechanisms of action by which these drugs confer their beneficial effect.

Methods: PubMed, Embase, and Google Scholar databases were searched to identify eligible articles that are comprehensively summarized and discussed in this study.

Results: The most commonly discussed mechanisms of action are diuresis and natriuresis, reduction in preload, afterload, and ventricular mass, as well as stimulation of erythropoietin production and improved myocardial energetics. SGLT2 inhibitors improve outcomes in patients with established heart failure (HF) and reduce the risk of death and HF admissions in patients with established chronic HF with reduced ejection fraction (HFrEF), either with or without diabetes.

Conclusion: Potential key mechanisms that may explain the notable cardioprotective benefits of SGLT2 inhibitors have been outlined. These agents have recently received class Ia recommendation in specific groups of people with DM to lower the risk of hospitalization for HF and risk of death, while these benefits may also extend to people without diabetes. It remains to be seen whether they will also emerge as treatment approaches in the acute phase of CV episodes.

Methods: The article is a narrative review based on recently published reviews and meta-analyses complemented with data from individual trials, when relevant.

Results and Discussion: Older data suggest a cardioprotective role of metformin (an inexpensive and safe drug); a role to date not convincingly challenged. The cardiovascular effects of thiazolidinediones, sulphonylurea, and glinides are debatable. Recent large-scale cardiovascular outcome trials suggest a neutral profile of dipeptidyl peptidase 4 inhibitors, yet provide compelling evidence of cardioprotective effects of glucagon-like 1 receptor antagonists and sodium-glucose transporter 2 inhibitors.

Conclusion: Metformin may have a role in primary and secondary prevention of cardiovascular disease; glucagon-like 1 receptor antagonists and sodium-glucose co-transporter 2 inhibitors play a role in secondary prevention of atherosclerotic cardiovascular disease. Sodium-glucose transporter 2 inhibitors have a role to play in both primary and secondary prevention of heart failure; yet, they carry a small risk of the potentially dangerous adverse effect, euglycemic diabetic ketoacidosis.]]> https://www.benthamscience.comarticle/109286 Objective: The aim of this study was to investigate the incidence and risk of DKA in connection with SGLT2i treatment in Denmark between 2013-2017.

Methods: A nationwide retrospective cohort of people with type 2 diabetes mellitus using SGLT2i or glucagon-like peptide-1 receptor agonists (GLP1-RA) was established and analysed using both Cox-proportional hazard regression and Kaplan-Meier survival analysis.

Results: The 37,058 individuals included in the cohort, were made up of SGLT2i (10,923), GLP1- RA (18,849), SGLT2i+insulin (2,069), and GLP1-RA+insulin (10,178) users. The incidence rate (IR) of DKA was 0.84 (95% CI 0.49-1.44) and 0.53 (95% CI 0.36-0.77) for the SGLT2i and GLP1-RA groups, respectively. There was no statistically significant increase in the risk for DKA with SGLT2i use (HR 1.02, 95% CI, 0.44-2.36). However, for the SGLT2i+insulin and GLP1- RA+insulin groups, IRs were 3.47 (95% CI 1.92-6.27) and 0.97 (95% CI 0.68-1.37) respectively, and the risk was statistically significantly higher (HR 5.42, 95% CI 2.16-13.56).

Conclusion: We observed no significant increase in the risk of DKA for SGLT2i users compared to GLP1-RA. However, a significantly higher IR of DKA was observed with concomitant insulin use, and the risk of DKA was considerably higher for the SGLT2 group using insulin.]]> https://www.benthamscience.comarticle/104082 Introduction: Primary studies have shown an association of glycemic dysregulation with increased length of hospital stay and mortality among overall patients, however, there is no systematic review of current evidence on the association between uncontrolled in-hospital glycemia in patients with diabetes and health outcomes. This study aimed to systematically review the current evidence on the association between uncontrolled in-hospital glycemia in patients with diabetes and health outcomes.

Methods: The association between glycemic dysregulation and health outcomes for inpatients with diabetes was systematically reviewed. PubMed, Embase, and LILACS databases were searched. Two independent reviewers were involved in each of the following steps: screening titles, abstracts, and fulltexts; assessing the methodological quality; and extracting data from included reviews. Descriptive analysis method was used.

Results: Seven cohort studies were included, and only two had a prospective design, consisting of 7,174 hospitalized patients with diabetes. In-hospital occurrence of hypoglycemia, hyperglycemia, and glycemic variability were assessed, and outcomes were mortality, infections, renal complications, and adverse events. Among the exposure and outcomes, an association was observed between severe hypoglycemia and mortality, hyperglycemia and infection, and hyperglycemia and adverse events.

Conclusion: In-hospital uncontrolled glycemia in patients with diabetes is associated with poor health outcomes. More studies should be conducted for proper investigation because diabetes is a complex condition. Effects of glycemic dysregulation should be investigated on the basis of overall health of a patient instead from only organ-target perspective, which makes the investigation difficult.]]> https://www.benthamscience.comarticle/106504Background and Introduction: Diabetes mellitus is a metabolic disorder that has emerged as a serious public health issue worldwide. According to the World Health Organization (WHO), without interventions, the number of diabetic incidences is expected to be at least 629 million by 2045. Uncontrolled diabetes gradually leads to progressive damage to eyes, heart, kidneys, blood vessels, and nerves.

Methods: The paper presents a critical review of existing statistical and Artificial Intelligence (AI) based machine learning techniques with respect to DM complications, mainly retinopathy, neuropathy, and nephropathy. The statistical and machine learning analytic techniques are used to structure the subsequent content review.

Results: It has been observed that statistical analysis can help only in inferential and descriptive analysis whereas, AI-based machine learning models can even provide actionable prediction models for faster and accurate diagnosis of complications associated with DM.

Conclusion: The integration of AI-based analytics techniques, like machine learning and deep learning in clinical medicine, will result in improved disease management through faster disease detection and cost reduction for the treatment.

Case Report: A 61-year-old man with a history of type 2 diabetes, taking an SGLT2 inhibitor empagliflozin 10 mg orally daily, presented to the emergency room with a 2-day history of nausea and chest pain. A week prior to presentation, he had started a ketogenic diet. He was initially admitted with a diagnosis of acute coronary syndrome. On initial assessment in the emergency room, his cardiac enzymes were normal and there were no ischemic changes in his ECG. As there was concern for unstable angina, he underwent cardiac catheterization, which showed a known total occlusion with collaterals and arteries with a non-obstructive disease without any evidence of acute plaque rupture. His baseline laboratory assessments revealed an elevated anion gap of 17, increased urinary and plasma ketones, and metabolic acidosis. His plasma glucose level was 84 mg/dL. The diagnosis of euDKA was made, and treatment with intravenous fluids and insulin was initiated. His chest pain and nausea subsequently resolved.

Conclusion: We present a case of euDKA triggered by a ketogenic diet while on SGLT2 inhibitor therapy presenting as chest pain. The recognition of euDKA is important in the context of increased SGLT2 use for the management of cardiovascular risk for patients with diabetes.

Methods: Research and online content related to diabetes online activity is reviewed. DKA is caused by a relative or absolute deficiency of insulin and elevated levels of counter-regulatory hormones.

Results: Goals of therapy are to correct dehydration, acidosis, and to reverse ketosis, gradually restoring blood glucose concentration to near normal.

Conclusion: It is essential to monitor potential complications of DKA and, if necessary, to treat them and any precipitating events.

In this mini-review, we will define diabetes, discuss the current status of diabetes treatments, review the current knowledge of the different hormones that participate in glucose homeostasis and the employment of different modulators of these hormones. As this issue deals with peptide therapeutics, special attention will be given to synthetic peptide analogs, peptide agonists as well as antagonists.

Objective: The anti-diabetic effects of β -glucan from Aureobasidium pullulans were assessed in a streptozotocin (STZ)-induced rat diabetes model at 62.5 and 125 mg/kg doses. In addition, the possibility of changes in the effects of β-glucan according to the severity of diabetes was also assessed at one dosage (62.5 mg/kg): severe, >360 mg/dL; slight, 130-200 mg/dL.

Methods: Test articles were administered orally to STZ-induced diabetic rats from 21 days after STZ dosing for 4 weeks. Each of five or six female rats per group was selected using blood glucose levels at 21 days after STZ dosing. Changes in body weight were recorded during the study, along with blood glucose, blood urea nitrogen, creatinine, and serum aspartate aminotransferase and alanine aminotransferase levels. On the day of sacrifice, livers and kidneys were weighed and observed microscopically for changes in the percentage of degenerative regions and numbers of degenerative tubules in the kidney.

Results: β-glucan showed no hypoglycemic effects in the STZ-induced diabetic rat model. However, it had favorable effects on decreasing diabetic complications related to diabetic nephropathy and hepatopathy.

Conclusion: Based on the results of this study, it was concluded that β-glucan showed favorable effects in decreasing diabetic complications in STZ-induced rat diabetes model.

Methods: Literature search was performed using various dataset like PUBMED, EBSCO, ProQuest, Scopus and selected websites like the National Institute of Health and the World Health Organization.

Result: Water-soluble vitamins have been thoroughly studied for their activity in diabetes and diabetic complications.

Conclusion: Water-soluble vitamins like B1, B3, B6, B7, B9 and B12 have notable effects in diabetes mellitus and its related complications like nephropathy, neuropathy, retinopathy and cardiomyopathy.

Objective: The aim of this study was to assess patient-related characteristics and outcomes of diabetic ketoacidosis, and their relative difference among children with newly diagnosed and previously known type-I diabetes mellitus.

Methods: This is a retrospective cross-sectional study of 63 type-1 diabetes patients admitted for ketoacidosis at Jimma university medical center, a tertiary hospital. Data was collected using a checklist, and entered into Epidata 4.2.0.0 and analyzed using STATA 13.0. Descriptive statistics was performed; Mann-Whitney and Chi-square test statistics were employed for comparison.

Result: Of the total, 39 were newly diagnosed type-I diabetes patients. Polydipsia and Polyuria (each in 74.6%) were the predominant symptoms at presentation. ketoacidosis precipitants were undocumented in the majority of the patients (53.97%). Mean (±SD) Random blood sugar was 434.05 (±117.62)mg/dl. Ketoacidosis was mild in severity in 63.49%. Family history of diabetes, unknown precipitants and the first episode of ketoacidosis were significantly different among the new and known type-I diabetes patients. No mortality was documented.

Conclusion: The observed patient characteristics are typical of those reported in many studies and standard resources. Despite no mortality was documented, the need for early diagnosis and management should not be overlooked. Further study, with large sample size, is recommended to point-out the real characteristics difference among new and known type-I diabetes mellitus patients admitted for ketoacidosis.

Introduction: The SGLT2 inhibitors by inhibiting the SGLT2 in the proximal nephron, helps in reducing the reabsorption of approximately 90% of the filtered glucose and increased urinary glucose excretion (UGE).

Methods: The literature related to SGLT2 inhibitors has been thoroughly explored from various available public domains and reviewed extensively for this article. Detailed and updated information related to SGLT2 inhibitors with a major focus on the recently approved Ertuglifolzin is structured in this review.

Result: The present review is an effort to understand the management of diabetes mellitus over the past few decades with a special focus on the role of SGLT2 receptor in the causes of therapeutic and preventive strategies for diabetes mellitus. Pragmatic placement of the currently available Canagliflozin, Dapagliflozin, and Empagliflozin as oral antidiabetic agents has been done. Well accommodated stereochemistry and a high docking score of Ertugliflozin in ligand-receptor simulation studies attribute to its high potency.

Conclusion: This review highlights the unique mechanism of SGLT2 Inhibitors coupled with pleiotropic benefits on weight and blood pressure, which make it an attractive choice of therapy to diabetic patients, not controlled by other medications.

Objective: This study aimed to explore the effect of mannitol on spinal cord edema after SCI in rats.

Methods: Seventy-eight adult female rats were assigned to three groups randomly: a sham control group (n = 18), a contusion and normal saline contrast group (n=30), and a contusion and mannitol treatment group (n=30). We used the open-field test to estimate the functional recovery of rats weekly. Spinal cord water content was measured to determine the spinal cord edema. The ultrastructure features of the injured dorsolateral spinal cord were determined on the 7th day after SCI by HE staining.

Results: The mannitol group had greatly improved Basso-Beattie-Bresnahan (BBB) scores when compared with the saline contrast group. The spinal cord water content was increased significantly after SCI, and there was no significant difference in the water content between the NaCl and mannitol groups 1 day after SCI. The water content at 3 and 7 days after SCI was significantly lower in the mannitol group than in the NaCl group (p < 0.05). Mannitol can reduce spinal cord edema by increasing the number of red blood cells in the injured spinal cord and decrease the ratio (dorsoventral diameter/ mediolateral diameter) of spinal cord 7 days post-SCI.

Conclusion: Mannitol increases recovery of motor function in rats, reduces spinal cord edema and increases the number of red blood cells in the injured spinal cord, decreasing the ratio of spinal cord to reduce pressure.

Case Report: A fifty-year-old Surinamese woman without any medical history was admitted for diabetic ketoacidosis. No specific anti-pancreatic autoimmunity was observed, and the C-peptide level was low, indicating atypical type-1 diabetes mellitus. DKA was associated with thyrotoxicosis in the context of thyroiditis and complicated by nonbacterial pericarditis and a Staphylococcus aureus subcutaneous abscess. The patient was infected with HTLV-1.

Conclusion: To our knowledge, this uncommon association is described for the first time. Few studies have analyzed the implications of HTLV-1 infection in thyroiditis and diabetes mellitus. We did not find any reports describing the association of pericarditis with HTLV-1 infection. Additional studies are necessary to understand the role of HTLV-1 in endocrine and cardiac disorders.

Methods: Single-institution retrospective review of patients admitted to the ICU with diabetic ketoacidosis between 4/1/2015 and 7/20/2018. Our institution introduced computer-based insulin infusion (Glucommander) to the intensive care unit on 3/28/2016. Patients were grouped into either paper-based group (preintervention) or a computer-based group (postintervention). Summary and univariate analyses were performed.

Results: A total of 620 patients (paper-based=247; computer-based=373) with a median (IQR) age of 40 (26-56) years were included; 46% were male. Patients in the computer-based group were significantly older (p=0.003); otherwise, there were no significant differences in gender, race, body mass index and HbA1c. The mean (±SD) time to diabetic ketoacidosis resolution in the computer-based group was significantly lower than the paper-based group (p=0.02). The number of patients in the paper-based group who developed severe hypoglycemia (<50 mg/dl) was significantly higher {8% vs 1%; p<0.0001}.

Conclusion: Our analyses demonstrate statistically significant decreases in time to DKA resolution and hypoglycemic events in DKA patients who were managed using a computer-based insulin infusion algorithm providing a more effective and safer option when compared to paper-based insulin infusion.

Materials and Methods: This study featured children who were diagnosed with diabetic ketoacidosis and who were consecutively admitted to pediatric intensive care within one year of their diagnosis. Thiol/disulfide homeostasis was evaluated in 45 pediatric patients suffering from DKA, as well as 45 healthy controls of parallel gender and age. Thiol/disulfide homeostasis parameters were measured using a novel automated measurement method and the correlation between demographic data and parameters was measured.

Results: Pediatric patients were found to have low native thiols, total thiols and disulfide levels with type 1 diabetes after DKA (331.82±106.40, 362.71±113.31, 17.02±5.33 μmol/L, respectively) as compared to the control group (445.08±24.41, 481.21± 28.47, 18.06±5.12 μmol/L, respectively).

Conclusion: Thiol/disulfide homeostasis was distorted in pediatric patients with DKA. Furthermore, it was found that they are not likely to return to normal, immediately after treatment.

Materials and Methods: LHH was calculated from the number needed to treat (NNT) and number needed to harm (NNH) available from the absolute risk reductions reported with the outcomes of interest, in these two trials.

Results: In the CANVAS Program, LHH for major adverse cardiovascular events (MACE) points at a significant benefit with canagliflozin use in comparison to amputation (1.65), fractures (1.65) and euglycaemic diabetic ketoacidosis (euDKA) (16.67) risks. Only genital fungal infections were significant more in both sexes (0.21-M and 0.1-F) when LHH was matched against the positive outcomes. In contrast, the hHF benefits were outweighed by amputation (0.95) and fracture risks (0.95).

In CREDENCE trial, the LHH for Primary composite, Renal composite and MACE, all supported the benefits in comparison to any adverse events encountered in the trial.

The LHH from pooled data (CANVAS Program and CREDENCE trial) was in favour of all the benefits (hHF and renal composites) except for MACE matched against amputation (0.66).

Conclusion: The outcome benefits were in favour of canagliflozin in comparison to all reported adverse events, when hHF and renal composite were under consideration, in both the individual and pooled LHH analysis. However, the MACE benefits were overwhelmed by amputation risk in the pooled analysis.

Introduction: The current review discusses the various conventional drugs, herbal drugs, combination therapy and the use of nutraceuticals for the effective management of diabetes mellitus. The biotechnological aspects of various antidiabetic drugs are also discussed.

Methods: Structured search of bibliographic databases for previously published peer-reviewed research papers was explored and data was sorted in terms of various approaches that are used for the treatment of diabetes.

Results: More than 170 papers including both research and review articles, were included in this review in order to produce a comprehensive and easily understandable article. A series of herbal and synthetic drugs have been discussed along with their current status of treatment in terms of dose, mechanism of action and possible side effects. The article also focuses on combination therapies containing synthetic as well as herbal drugs to treat the disease. The role of pre and probiotics in the management of diabetes is also highlighted.

Conclusion: Oral antihyperglycemics which are used to treat diabetes can cause many adverse effects and if given in combination, can lead to drug-drug interactions. The combination of various phytochemicals with synthetic drugs can overcome the challenge faced by the synthetic drug treatment. Herbal and nutraceuticals therapy and the use of probiotics and prebiotics are a more holistic therapy due to their natural origin and traditional use.

Methods: We searched major databases and grey literature from their inception to October 2018, for RCTs with a duration ≥ 12 weeks, comparing liraglutide with placebo or any other comparator as adjunct to insulin in patients with T1D, investigating major efficacy and safety endpoints. This review is reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement.

Results: We included 5 trials with 2,445 randomized participants. Liraglutide provided modest reductions in HbA1c, with liraglutide 1.8 mg producing the greatest decrease (MD = -0.24%, 95% CI -0.32 to -0.16, I2=0%). Significant weight reduction, up to 4.87 kg with liraglutide 1.8 mg was also observed (95% CI -5.31 to -4.43, I2=0%). Decrease in total daily insulin dose, primarily driven by a decrease in bolus insulin requirements, was demonstrated. Liraglutide decreased non-significantly the odds for severe hypoglycemia (OR=0.80, 95% CI 0.57-1.14, I2=0%), while it increased significantly the odds for gastrointestinal adverse events (for nausea, OR=4.70, 95% CI 3.68-6.00, I2=37%, and for vomiting, OR=2.50, 95% CI 1.54-4.72, I2=27%). A significant increase in heart rate was also demonstrated. No association with diabetic ketoacidosis or malignancies was identified.

Conclusion: In patients with T1D, liraglutide might prove be an adjunct to insulin, improving glycemic control, inducing body weight loss and decreasing exogenous insulin requirements and severe hypoglycemia.

Objective: This study aimed to investigate the association between GV, hypoglycemia, and the 90-day mortality and length of hospital stay (LOS) among non-critically ill hospitalized elderly patients.

Methods: The medical records of 2,237 elderly patients admitted to the Zilda Arns Elderly Hospital over a 2.5-year period were reviewed. Hypoglycemia was defined as a glucose level <70 mg/dL (hypoglycemia alert value) and represented by the proportion of days in which the patient presented with this condition relative to the LOS. The Charlson comorbidity index was used to evaluate prognosis. Data were analyzed using multiple linear and logistic multivariate regression analyses.

Results: Adjusted analysis of 687 patients (305 men [44.4%] and 382 women [55.6%], mean age of 77.86±9.25 years) revealed that GV was associated with a longer LOS (p=0.048). Mortality was associated with hypoglycemia (p=0.005) and mean patient-day blood glucose level (p=0.036). Variables such as age (p<0.001), Charlson score (p<0.001), enteral diet (p<0.001), and corticosteroid use (p=0.007) were also independently associated with 90-day mortality.

Conclusion: Increased GV during hospitalization is independently associated with a longer LOS and hypoglycemia in non-critically ill elderly patients, while the mean patient-day blood glucose is associated with increased mortality.

Materials and Methods: Pediatric patients with Type I diabetes mellitus (T1DM) who were admitted to the pediatric intensive care unit with the diabetic ketoacidosis were assigned as the study group and healthy children who were admitted to the outpatient clinic and decided as healthy after clinic and laboratory evaluation were selected as the control group. IMA and adjusted IMA levels were evaluated in the blood samples from the control group and the study group when admitted first time to the intensive care unit during the acidosis period (DKA before treatment, DKA-BT), and after recovering from acidosis (DKA after treatment, DKA-AT).

Results: A total of 24 pediatric patients with diabetic ketoacidosis and 30 healthy control children matching age and sex were included in the current study. The albumin levels in pediatric patients with T1DM during DKA-BT were higher than the albumin levels after acidosis (4.101±0.373, 3.854±0.369 g/dL, respectively) (p<0.05). However, there was no significant difference when these values were compared to the control group. Mean values of IMA and Adj-IMA were statistically higher in DKAAT compared to the control group (0.748±0.150 vs 0.591±0.099, p< 0.001; 0.708±0.125 vs 0.607±0.824, p< 0.001, respectively). IMA and adjusted IMA levels measured after recovered from acidosis were significantly higher compared to the level of IMA during DKA (0.748±0.150 vs 0.606±0.105 as absorbance unit, p<0.001; 0.708±0.125 vs 0.625±0.100, p<0.05, respectively).

Conclusion: In children with T1DM, even though acidosis recovered following the treatment in diabetic ketoacidosis, which is an oxidative stress marker, the ischemia modified albumin levels and adjusted ischemia modified albumin levels were high.

Objective: The present study was aimed to analyze a possible association between the C1858T polymorphism in Egyptian children with T1DM.

Methods: This case-control study included 240 children divided evenly between T1DM patients and controls. The PTPN22 C1858T polymorphism was genotyped using polymerase chain reaction with Restriction Fragment Length Polymorphism (RFLP).

Results: Both the 1858CΤ and 1858ΤΤ genotypes and the 1858T allele were found more frequently in patients (32.5% and 18.7%, respectively) than in controls (10% and 5.0%, respectively), P=0.013 and P=0.007, respectively. Among females, the 1858T allele was more common in patients (18%) than in controls (2.6%), P=0.014.

Conclusion: These findings suggest that the PTPN22 1858T allele could be a T1DM susceptibility factor in the Egyptian population and that it might play a different role in susceptibility to T1DM according to gender in T1DM patients.

The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

Polyphenols are natural compounds widely spread in fruits and vegetables whose dietary intake has been considered inversely proportional to the incidence of DM and AD. So, it is believed that this group of phytochemicals may have preventive and therapeutic potential, not only by reducing the risk and delaying the development of these pathologies, but also by improving brain’s metabolic profile and cognitive function.

The aim of this review is to understand the extent to which DM and AD are related pathologies, the degree of similarity and the relationship between them, to detail the molecular mechanisms by which polyphenols may exert a protective effect, such as antioxidant and anti-inflammatory effects, and highlight possible advantages of their use as common preventive and therapeutic alternatives.

Case Report: We present a case of DKA with moderate hyperglycemia in a patient treated with metformin and empagliflozin.

Conclusion: DKA in patients treated with SGLT2 inhibitors can be presented as euglycemic and moderated hyperglycemia. This special presentation poses a physician’s challenge.

Materials and Methods: A total of 1,042 studies have been published from Nov. 2012-Nov. 2017 regarding SGLT2 inhibitors. After inclusion and exclusion criteria, 27 studies have been selected for the analysis of risk.

Results and Discussion: The emerging evidence indicates various adverse drug reactions such as foot and toe amputation, cancer, diabetic ketoacidosis, bone fracture risk and urinary as well as mycotic genital infection. The causality assessment has shown a correlation between SGLT2 inhibitors and diabetic ketoacidosis and urinary tract infection.

Conclusion: In conclusion, Marketing Authorization Holder (MAH) and Regulatory Authorities (RA) should monitor various adverse drug reactions such as diabetic ketoacidosis and urinary tract infection with the use of SGLT2 inhibitor.

Objectives: This study was done to assess risk factors, clinical features and management practices in T1D patients.

Methods: A review of records of 39 T1D cases admitted over the past five years in two hospitals was done.

Results: The mean age at diagnosis among males (n=21) was 19.9±10.3 years and among females (n=18) was 12.3±7.5 years (t=2.614, p=0.013). Mean age at diagnosis of patients who were underweight (n=7) was 9.9±4.4 years, compared to 17.8±10.1 years among patients (n=32) with normal or overweight status (t=2.028, p=0.05). The family history of T1D was present among 7(18.0%) cases. The most common symptoms among the cases were fatigue 22(56.4%), polyuria 19(48.7%) and polydipsia 18(46.1%). The most common sign was weight loss 27(69.2%). The most common complications were diabetic nephropathy and skin infections seen each among 10(25.6%) cases. Mean duration of T1D was significantly more among patients with diabetic nephropathy (p<0.001), compared to those without. Mean HbA1c value among patients was 12.9±2.7. It was significantly more among patients with Diabetic Ketoacidosis (DKA) (p=0.012). A short-acting insulin was used in the management of T1D among 59.5% cases. The outcome of the management showed a loss of one patient who developed DKA.

Conclusion: Routine growth monitoring and blood glucose analysis is required among T1D cases. The present study provides a database of risk factors, clinical features, and management practices among patients with T1D in this region and addresses several issues important to both patients and their care providers.]]> https://www.benthamscience.comarticle/95273 https://www.benthamscience.comarticle/92240

Methods: We conducted a comprehensive research of the relevant literature regarding the off-label use of SGLT-2 inhibitors in clinical practice, presenting the major benefits and the potential risks.

Results: SGLT-2 inhibitors are associated with improved glycemic control, reduction in body weight, and decrease in insulin dosage, along with their beneficial cardiovascular and renal effects. However, we cannot overlook the association with increased incidence of DKA events, in the presence of well known predisposing factors. Further investigation is required, in order to establish them as adjunctive treatment in those patients.

Conclusion: This novel class of antidiabetics seems to be a very attractive treatment option in patients with T1DM, due to their multiple beneficial effects, but the increased risk of DKA should be taken into account.]]> https://www.benthamscience.comarticle/89495

Introduction: Type 2 Diabetes Mellitus (T2DM) is increasing worldwide specifically in obese cases. Additionally, obesity worsens T2DM. Complications of each bariatric surgery method were assessed separately; but, a meta-analysis of these complications and comparison between procedures in T2DM patients have not been investigated previously. The result of this study will help surgeons to choose the most appropriate surgical technique, considering individual conditions for a diabetic patient.

Methods: We searched PubMed, Scopus, and ISI for original papers including bariatric surgical procedures for diabetic population and the reported consequences. Data analyses were done using Stata software.

Results: Mortality percentage between diabetic and non-diabetic patients was statistically nonsignificant (P = 0.987). Early and late complications were higher in diabetic group in comparison with non-diabetic (6.0% vs. 1.8%, P = 0.024 and 0.6% vs. 0.3%, P = 0.04, respectively). Most prevalent findings in malabsorptive (7.8%, P < 0.001) and restrictive procedures (80%, P < 0.001) were major complications and hypoglycemic episodes, respectively.

Conclusion: As our study showed, most of the complications are not necessarily higher in diabetic population but dependent on the method of surgery.]]> https://www.benthamscience.comarticle/89181

Aim: This review article is focused on the management of dysnatremias during hyperglycemic hyperosmolar state with the aim of providing clinicians a useful tool to early identify the sodium derangement in order to address properly its treatment.

Discussion: The plasma sodium concentration is modified by most of the therapeutic measures commonly required in such patients and the physician needs to consider these interactions when treating HHS. Moreover, an improper management of plasma sodium concentration (PNa+) and plasma osmolality during treatment has been associated with two rare potentially life-threatening complications (cerebral edema and osmotic demyelination syndrome). Identifying the correct composition of the fluids that need to be infused to restore volume losses is crucial to prevent complications.

Conclusion: A quantitative approach based on the comparison between the measured PNa+ (PNa+ M) and the PNa+ expected in the presence of an exclusive water shift (PNa+ G) may provide more thorough information about the true hydroelectrolytic status of the patient and may therefore, guide the physician in the initial management of HHS. On the basis of data derived from our previous studies, we propose a 7-step algorithm to compute an accurate estimate of PNa+ G.]]> https://www.benthamscience.comarticle/90619

Methods: The PubMed and CNKI databases were searched for “oral insulin, ” “drug delivery systems, ” and “pharmacokinetics, ” and 85 relevant articles were selected from the results as material for this review. These papers were authoritative and had a higher number of citations.

Results: Oral insulin would be highly advantageous but is poorly absorbed. The main reason for low absorptivity is the hydrolysis of insulin by enzymes in the gastrointestinal tract. Lack of active transport vectors that pass through the intestinal epithelium is also a non-negligible problem. Additional issues need to be considered to facilitate appropriate research, such as long-term efficacy and safety, clinical data, and toxicological characteristics.

Conclusion: This review summarized recent advances in oral insulin and the pharmacokinetic profile of the suitable delivery system, providing valuable reference material for future research.]]> https://www.benthamscience.comarticle/90163 Methods: We searched all published studies in Pubmed/Medline, and Cochrane library, using keywords: ‘stem cell’ AND ‘therapy’ AND ‘diabetes type 2’. Inclusion criteria: original articles on the use of stem cells in humans with T2DM. Exclusion criteria: articles in the non-English literature, studies on T2DM complications that did not assess both adverse events and any of the common diabetes study outcomes. Data collection: type of study, number of cases, and all data that were related to outcome and adverse events. Data were analyzed descriptively to conclude the possible cause of adverse reactions, and which protocols gave a satisfactory outcome.

Results: We collected 25 original articles, out of which 17 studies did not have controls and were classified as case reports, while there were 8 studies that were controlled clinical trials. Most studies used autologous bone marrow mononuclear cells (BM-MNCs) or autologous or allogeneic mesenchymal stem cells (MSCs) from various sources. Adverse events were mild and mostly intervention related. Efficacy of autologous BM-MNCs that were given via interventional route was comparable to Wharton jelly or umbilical cord MSCs that were given via intravenous (IV), Intra muscular (IM), or subcutaneous (SC) route.

Conclusion: Further controlled studies that compare BM-MNCs to BM-MSCs or WJ-MSCs or UCSCs are recommended to prove their comparable efficacy. In addition, studies that compare various routes of administration (IV, IM or SC) versus the more invasive interventional routes are needed.]]>