Current Diabetes Reviews - Volume 16, Issue 7, 2020

Background: Diabetes is a metabolic disorder associated with abnormally high levels of glucose in the blood due to inadequate production of insulin or inadequate sensitivity of cells to the action of insulin. Diabetes has become an increasing challenge in the world. The predicted diabetic population according to the World Health Organization is 8.7% between the age group 20-70 years. There are many complications linked to prolonged high blood glucose levels, such as microvascular complications and macrovascular complications. Vitamins play an important role in glucose metabolism and the potential utility of supplementation is relevant for the prevention and/or management of diabetes mellitus and its complications. 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.

Background: The increasing prevalence of reported cases of diabetes has evidently become a major global public health concern. Although diabetes management is possible by the administration of synthetic anti-diabetic agents, there are profound side-effects associated with their long-term usage. Hence there is a demand for safer alternatives which could be possibly formulated using specific yet common phytonutrients. Objectives: The main objective of this review is to describe the cellular mechanisms of phytonutrients as an alternative to commercially available synthetic anti-diabetic agents in the management of diabetes and related complications. Furthermore, the clinical evidence that supports this view is also highlighted. Methodology: An in-depth review of published literature was carried out to identify the most promising phytonutrients in the management of diabetes and related complications. Results: A number of phytonutrients are reported to be potential anti-diabetic agents. Few examples include biguanides, resveratrol, lycopene, thymoquinone and quercetin. However, suitable formulations using these phytonutrients and their clinical trials are still underway. Most of the reported findings focus on one aspect of several biochemical processes e.g. enhancement of glucose utilization, antioxidation, induction of insulin production, antiglycation, etc. An in-depth study of phytonutrients with respect to functional, immunological as well as biochemical factors suggesting their efficacy, as well as safety in the management of diabetes, is rarely reported. Conclusion: Our study thus highlights the abundance of clinical evidence of the efficiency of phytonutrients, and at the same time, the scarcity of clinically approved and marketed phytonutrients, as drugs, for the management of diabetes and related complications.

This article presents a scoping review and synthesis of research findings investigating the toxic cellular accumulation of dysregulated inorganic phosphate—phosphate toxicity—as a pathophysiological determinant of diabetes and diabetic complications. Phosphorus, an essential micronutrient, is closely linked to the cellular metabolism of glucose for energy production, and serum inorganic phosphate is often transported into cells along with glucose during insulin therapy. Mitochondrial dysfunction and apoptosis, endoplasmic reticulum stress, neuronal degeneration, and pancreatic cancer are associated with dysregulated levels of phosphate in diabetes. Ectopic calcification involving deposition of calcium-phosphate crystals is prevalent throughout diabetic complications, including vascular calcification, nephropathy, retinopathy, and bone disorders. A low-glycemic, low-phosphate dietary intervention is proposed for further investigations in the treatment and prevention of diabetes and related diabetic pathologies.

Background: Diabetes and its related complications are now a global health problem without an effective therapeutic approach. There are many herbal medicines which have attracted much attention as potential therapeutic agents in the prevention and treatment of diabetic complications due to their multiple targets. Aim: The aim of this study is to review available knowledge of mangiferin focusing on its mode of action. Methods: Mangiferin was extensively reviewed for its antidiabetic activity using online database like Scopus, PubMed, and Google Scholar as well as some offline textbooks. A critical discussion based on the mechanism of action and the future perspectives is also given in the present manuscript. Results: Mangiferin is a natural C-glucoside and mainly obtained from its primary source, the leaves of mango tree (Mangifera indica L.). Therapeutic and preventive properties of mangiferin include antimicrobial, anti-inflammatory, antioxidative, antiallergic, neuroprotective, and cognition-enhancing effects. It dissolves well in water, so it can be easily extracted into infusions and decoctions and hence, a number of researches have been made on the therapeutic effect of this molecule. Recently, mangiferin has been proved to be an effective remedy in diabetes and diabetes-related complications. It is a beneficial natural compound for type 2 diabetes mellitus as it improves insulin sensitivity, modulates lipid profile and reverts adipokine levels to normal. Conclusion: This study concludes that mangiferin has the potential to treat diabetes and it can be developed as a therapeutic agent for diabetes and the complications caused by diabetes.

Background: Prediabetes is defined as a state of glucose metabolism between normal glucose tolerance and type 2 diabetes. Continuous β-cell failure and death are the reasons for the evolution from normal glucose tolerance to prediabetes and finally type 2 diabetes. Introduction: The necessity of new therapeutic approaches in order to prevent or delay the development of type 2 diabetes is obligatory. Liraglutide, a long-acting GLP-1 receptor agonist, has 97% homology for native GLP-1. Identification of the trophic and antiapoptotic properties of liraglutide in preclinical studies, together with evidence of sustained β-cell function longevity during its administration in type 2 diabetes individuals, indicated its earliest possible administration during this disease, or even before its development, so as to postpone or delay its onset. Methods: Pubmed and Google databases have been thoroughly searched and relevant studies were selected. Results: This paper explores the current evidence of liraglutide administration both in humans and animal models with prediabetes. Also, it investigates the safety profile of liraglutide treatment and its future role to postpone or delay the evolution of type 2 diabetes. Conclusion: Liralgutide remains a valuable tool in our therapeutic armamentarium for individuals who are overweight or obese and have prediabetes. Future well designed studies will give valuable information that will help clinicians to stratify individuals who will derive the most benefit from this agent, achieving targeted therapeutic strategies.

Background: The discovery of Sodium-Glucose co-transporter-2 (SGLT2) inhibitors had rewritten the treatment of diabetes mellitus with an impressive fall in the incidence of death and associated complications. 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.

Although novel pharmacological options for the treatment of type 2 diabetes mellitus (DM2) have been observed to modulate the functionality of several key organs in glucose homeostasis, successful regulation of insulin resistance (IR), body weight management, and pharmacological treatment of obesity remain notable problems in endocrinology. Leptin may be a pivotal player in this scenario, as an adipokine which centrally regulates appetite and energy balance. In obesity, excessive caloric intake promotes a low-grade inflammatory response, which leads to dysregulations in lipid storage and adipokine secretion. In turn, these entail alterations in leptin sensitivity, leptin transport across the blood-brain barrier and defects in post-receptor signaling. Furthermore, hypothalamic inflammation and endoplasmic reticulum stress may increase the expression of molecules which may disrupt leptin signaling. Abundant evidence has linked obesity and leptin resistance, which may precede or occur simultaneously to IR and DM2. Thus, leptin sensitivity may be a potential early therapeutic target that demands further preclinical and clinical research. Modulators of insulin sensitivity have been tested in animal models and small clinical trials with promising results, especially in combination with agents such as amylin and GLP-1 analogs, in particular, due to their central activity in the hypothalamus.

Introduction: Obesity shows a multifactorial disease and presents a serious public health problem, with an alarming epidemic character. According to NHANES (National Health and Nutrition Examination Survey) from 2015 to 2016, 39.6% of American adults and 18.5% of young people were obese and 7.7% of adults and 5.6% of young people had severe obesity. Brazil ranks fifth in the world ranking, with about 18 million people reaching up to 70 million overweight individuals. Despite shortterm weight loss with diet and exercise, weight regain continues to be a concern. Anti-obesity drugs, such as Sibutramine (SIB), Phentermine (PHEN), Fenproporex (FEN), Mazindol (MAZ), Amfepramone (AMFE) and Orlistat (ORL) may play a role in weight reduction in patients whose condition is refractory to non- and maintenance of weight loss. Objective: A systematic review followed by meta-analysis of randomized clinical trials over the past five years to explore the efficacy and safety of anorexigenic drugs for weight reduction and consequent treatment of obesity. Methods: The search strategy in MEDLINE / Pubmed, Web of Science, ScienceDirect Journals (Elsevier), Scopus (Elsevier), OneFile (Gale) is as follows : - search for mesh terms (Sibutramine, Phentermine, Fenproporex, Mazindol, Amfepramone , Orlistat, Weight loss, Safety), and the use of booleans "and" between mesh terms and "or" among historical findings. Results: It was observed that in the last five years of randomized studies no significant general complications were found, with only 5.7%. The mean overall weight loss was 6.18 (± 2.8) kg in the mean time of 12 months. The overall success rate among these drugs was 80.18%. The p-value values did not present a significant statistical difference, being p <0.05 within each drug group analyzed, for both weight and success rates. Conclusion: The scientific findings of randomized studies on the use of anorexigenic drugs to treat obesity have shown safety and efficiency in the last five years, with a reasonable weight loss and no significant complications.

Background: Restrictive lung pathology was reported in the previous meta-analysis among patients with Type 2 Diabetes mellitus (T2DM) which is date back to 2010. Objective: To see the effect of T2DM on pulmonary functions through updated systematic review and meta-analysis. Data source: PubMed. Study Eligibility Criteria: English language case-control or cross-sectional studies, published between 1 January 2010 to 31 August 2018. Participants and Intervention: T2DM and non-diabetic subjects were compared for at least one of the pulmonary function variables i.e. Forced expiratory volume in 1st second (FEV1), % FEV1, Forced vital capacity (FVC), % FVC and % FEV1/FVC. Study Appraisal and Synthesis Methods: Methodological quality of the study was assessed using Newcastle-Ottawa Quality Assessment Scale. Meta-analysis was done using Review Manager 5.3 (RevMan 5.3) and meta-regression was conducted using R statistical software. Results: We selected 22 articles that met our inclusion and exclusion criteria. Results reveal that among patients with T2DM all variables were reduced except %FEV1/FVC which shows statistically nonsignificant results with P=0.46. This confirms that T2DM patients have a restrictive type of lung pathology. Limitation: Only articles from the PubMed database were included. Conclusion and Implications of Key Findings: This review affirms the existing evidence of restrictive pathology among patients with T2DM. The future study could be conducted to see the effect of various rehabilitation protocols on pulmonary function among patients with T2DM.

Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disease whose etiology involves genetic predisposition as well as environmental factors. Polymorphisms of some genes are among the most important genetic factors that influence autoimmunity. Gender is another important factor affecting autoimmunity. Females are more susceptible to autoimmune diseases which may be due to the effect of sex hormones on the immune system activity. The metabolic effects of estrogen are mediated through its receptor – alpha. The exact mechanism is not well understood. A number of polymorphisms have been reported in the Estrogen Receptor- alpha (ER-alpha) IVS1 397 T>C gene which may be involved in the pathogenesis of diabetes. Objectives: To assess the influence of Estrogen Receptor- alpha gene [IVS1-397 T>C] polymorphism on vascular complications of type1 diabetes mellitus in pubertal females and on the glycemic control. Methods: This cross-sectional case-control study included 40 pubertal regularly menstruating girls less than 18 years with type 1 diabetes mellitus recruited from the Pediatric Diabetes Clinic, Children's Hospital, Ain-Shams University and 20 healthy age-and sex-matched controls. Estrogen receptor alpha genotypes were analyzed by Restriction Fragment Length PCR and correlated with both clinical and laboratory parameters in the studied cases. ER-alpha was chosen as it might play a role in diabetes pathogenesis. Results: The study revealed the TC genotype was the most prevalent genotype of the estrogen receptor. The TT genotype patients had a younger age of onset of T1DM. The prevalence of obesity was higher among TC and TT than in CC bearing patients. In addition, CC genotype patients had the least prevalence of microalbuminuria and had better glycemic control than other genotypes. Conclusion: Our findings suggest that Estrogen receptor- alpha gene may be affecting the age of onset of Type1 diabetes mellitus in pubertal girls as well as the glycemic control of these patients, where CC bearing girls had better glycemic control than other genotypes and less incidence of microalbuminuria.

Background: Type 1 diabetes mellitus is a common autoimmune disorder that often presents in children. In these patients, diabetic ketoacidosis is one of the most common and serious acute complications associated with significant morbidity and mortality. Nevertheless, limited studies are conducted in Ethiopia. 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.

İntroduction: Type 1 diabetes mellitus (DM) is characterized by selective autoimmune destruction of pancreatic b-cells, resulting in insulin deficiency and associated autoimmune disorders, such as celiac disease, autoimmune thyroiditis, and gastritis, which can coexist in patients with type 1 DM. These disorders are characterized by the presence of antibodies against tissue transglutaminase, thyroglobulin, and thyroid peroxidase (TPO), as well as against gastric parietal cells. Cross-sectional studies have reported that the risk of autoimmune thyroid diseases in patients with type-1 DM is two- to threefold higher than in the general population. However, there are a few studies in the literature that investigated the relationship between malignancy and type-1 DM, and it has been shown that type-1 DM does not increase thyroid cancer. Furthermore, there is a lot of controversy regarding the role of thyroid autoimmunity in the pathogenesis of thyroid cancer. Here, a type-1 DM patient diagnosed with papillary thyroid cancer is presented. Case Report: Herein, it was aimed to present a 20-year-old female patient diagnosed with type-1 DM and subsequently with papillary thyroid carcinoma (PTC). Thyroid ultrasound revealed a 10x12x18 mm hypoechoic irregular edges nodule with macrocalcification and microcalcification foci in the left lobe and pathological lymph nodes without echogenic hilus were detected at the fourth level of the left cervical chain. Fine needle aspiration biopsy of the nodule was consistent with papillary thyroid carcinoma. Total thyroidectomy, bilateral central lymph node dissection, and left neck dissection (level II to IV) were performed. Pathological examination revealed a 1.4x 0.9 cm diameter papillary carcinoma located in the left lobe of the thyroid gland with 13 lymph node metastases. Conclusion: Patients with type 1 DM should be examined for thyroid diseases, and patients with suspected thyroid disease should be evaluated with a thyroid ultrasound. Type 1 DM and PTC can coexist, albeit very rare. It should be known that type 1 diabetes can be observed together with thyroid cancer.

Aim: To present an insulinoma case with post-prandial hypoglycemic symptoms associated with glucose inducible endogenous hyperinsulinemia. Case: A 52-year-old female patient was evaluated for hypoglycemic symptoms especially those occuring within 3 hours after consuming sugary foods. These symptoms were persistent for a year and a half. She was diagnosed with reactive (post-prandial) syndrome and followed a recommended diet and was given acarbose but there was no improvement. The results suggested post-prandial endogenous hyperinsulinemia related hypoglycemia. Multiphasic computerized tomography revealed an 11x15x12 mm size mass lesion, anteriorly in the head and uncinate process of the pancreas and then the patients were treated surgically with pancreatic enucleation and cured. Conclusion: Distinguishing post-prandial syndrome by careful history and clinical evaluation in patients with postprandial symptoms is of great importance in terms of cost-effectivity. However, it should not be forgotten that although organic pathologies are mostly presented with fasting hypoglycemia, they may also cause post-prandial symptoms. Severity and progression of the symptoms that point to neuroglycopenia is important, and in this condition the most convenient clinical approach to the patient should be performed with careful and appropriate assessment steps.