Current Diabetes Reviews - Volume 18, Issue 3, 2022

The risk of type 2 diabetes mellitus (T2DM) is increasing abundantly due to lifestyle-related obesity and associated cardiovascular problems. Presently, Glycogen synthase kinase-3 (GSK-3) has gained considerable attention from biomedical scientists to treat diabetes. Phosphorylation of GSK-3 permits a number of cellular activities like regulation of cell signaling, cellular metabolism, cell proliferation and cellular transport. Inhibiting GSK-3 activity by pharmacological intervention has become an important strategy for the management of T2DM. This review focuses on the schematic representation of fundamental GSK-3 enzymology and encompasses the GSK-3 inhibitors as a future therapeutic lead target for the management of T2DM that may significantly regulate insulin sensitivity to insulin receptor, glycogen synthesis and glucose metabolism. The various signaling mechanisms of inhibiting the GSK-3 by describing insulin signaling through Insulin Receptor Substrate (IRS-1), Phosphatidylinositol-3 Kinase (PI3K) and Protein Kinase B (PKB/ AKT) pathways that may hopefully facilitate the pharmacologist to design for antidiabetic drug evaluation model in near future have also been highlighted.

There is emerging evidence that several oral diseases and conditions can be associated with DM. Dental caries, hyposalivation, fungal diseases and endodontics lesions may represent potential oral complications that can be aggravated by chronic hyperglycemia. Individuals with DM have a low perception of oral diseases which can lead to clinically important oral and systemic complications. This review aims to provide data on the most common oral signs and symptoms related to DM and to explore the mechanisms that might explain associations between DM and oral diseases in order to clarify the risks posed by poor oral health in DM. Since the linkage between oral diseases and DM is part of multifactorial aspects related to chronic hyperglycemic status and several common conditions affecting the whole body, both require rigorous self-control from patients and attention from medical and dental professionals.

Background: Diabetes mellitus (DM) is among the most frequently reported comorbidities in patients tainted with the pandemic coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With a high pervasiveness of diabetes mellitus, there is an urgency to understand the special aspects of COVID-19 in hyperglycemic patients. Diabetic patients are at higher risk than the general population of viral or bacterial infections, thus require special attention since diabetes is linked with severe, critical, and lethal modes of COVID-19. Objective: The objective of this study was to focus on epidemiology, pathophysiology, mechanism, and management of DM with COVID-19. Methods: The search was carried out on databases portals such as Pubmed, EMBASE, Google Scholar, and CINAHL with the keywords, i.e., COVID-19, coronavirus, SARS-CoV-2, diabetes, covid-19, etc. Result: DM and COVID-19 disease conditions can impact each other in terms of clinical progression and outcome. Available laboratory/clinical observations suggest that hyperglycemia-induced immune dysfunction, inflated lactate grades, and cytokines storm may play critical roles in the seriousness of COVID-19 in patients with diabetes; however, the exact mechanisms linking diabetes and COVID-19 remain to be further clarified. Conclusion: Standards to constrain the disease spread at the individual and community level are the key to extenuate the speedily rising pandemic, while definitive treatment, like plasma therapy, chemoprophylaxis, or vaccine for COVID-19, has yet to be discovered.

The most common cause of mortality among people with type 1 diabetes is cardiovascular diseases. Arterial stiffness allows predicting cardiovascular complications, cardiovascular mortality, and all-cause mortality. There are different ways to measure arterial stiffness; the gold standard is pulse wave velocity. Arterial stiffness is increased in people with type 1 diabetes compared to healthy controls. It increases with age and duration of type 1 diabetes. Arterial stiffness among people with type 1 diabetes positively correlates with systolic blood pressure, obesity, glycated hemoglobin, waist circumference, and waist to hip ratio. It has a negative correlation with the estimated glomerular filtration rate, high-density lipoprotein, and the absence of carotid plaques. The increased arterial stiffness could result from insulin resistance, collagen increase due to inadequate enzymatic glycation, and endothelial and autonomic dysfunction. The insulin-induced decrease in arterial stiffness is impaired in type 1 diabetes. There are not enough proofs to use pharmacotherapy in the prevention of arterial stiffness, but some of the medicaments got promising results in single studies, for example, renin-angiotensin-aldosterone system inhibitors, statins, and SGLT2 inhibitors. The main strategy of prevention of arterial stiffness progression remains glycemic control and a healthy lifestyle.

Background: Diabetes mellitus is an endocrine metabolic disorder, which affects the major organs in human and comorbid with others. Besides, diabetic patients are more prone to various infectious diseases as well as COVID-19 sporadic infection which is a high risk for patients with diabetes mellitus. To combat these infections and comorbid situations, an integrated balanced nutritional supportive could help in maintaining sound health and increase immunity for prevention and management of such type of viral infections. Objectives: While information regarding nutritional supports in COVID-19 pandemic in diabetic patients is not available, this review aimed to accumulate the evidence from previous publications where studied about nutrition-based supports or interventions for viral diseases with special emphasis on respiratory infections. Methods: For reviewing, searches are done for getting journal articles into Google Scholar, Pub Med/Medline, Database of Open Access Journal and Science Direct for relevant data and information. Results: Integrated nutritional supports of both macronutrients and micronutrients guidelines, including home-based physical exercise schedule, is summarized in this comprehensive review for possible prevention and management of diabetic patients in COVID-19 infections. The immuneboosting benefits of some vitamins, trace elements, nutraceuticals and probiotics in viral infections of diabetic patients are also included. Conclusion: There is an urgent need for a healthy diet and integrated nutritional supports with home-based physical activities for diabetic patients during the self-isolation period of COVID-19 Infection.

Background: Diabetes is a major metabolic aggressive disease that has exponentially increased around the globe, including both developed and developing countries. The significant change in the lifestyle of people, attributed to the fast-paced living style and dietary conditions, are a few of the core reasons behind the disease. Multiple studies conducted in various developing countries conclude that patient education, along with adhered practices and attitudinal outlook, can significantly help in deterring the ill effects of diabetes mellitus. Objective: The review aimed at understanding the impact of KAP on the management of diabetes mellitus in emerging economies. Methods: Multi-central analytical cross-sectional and prospective studies were conducted for research in multiple countries with median per capita income of ~$4,000 (developing countries - Ethiopia, Bangladesh, Iraq, Iran, Nigeria, etc.), wherein significant difference was witnessed in the outlook of patients and related stakeholders, who had a decent score of KAP relative to ones with lower scores, towards type 2 diabetes mellitus. Results: Among all the three variables that are capable of managing diabetes - knowledge, attitude and practice (KAP) - knowledge attained a high degree of importance as it served as the initial step to control DM. In developing countries, the ratio of people with knowledge - relating to disease - is significantly dependent on age, socio-economic status and education. As per the previous studies and their corresponding results, educational awareness is of utmost importance in order to eradicate myths and wrong information around the same. Conclusion: The review concludes the importance of patient counseling to modify their KAP towards the disease will be highly effective in countries like India, where the count of diabetes mellitus patients is increasing aggressively. Investment in patient counselling to improve their KAP score will significantly help in palliating the effect of this disease.

Background: Diabetic foot ulcers (DFUs) are a major complication of diabetes mellitus and a leading cause of lower limb amputation. Interventions to reduce psychological stress may have the potential to improve self-care and greatly reduce the morbidity and mortality associated with DFU. This review is focused on the consequences of psychological stress in wound healing and reflects on the effects of currently used psychological stress-reducing interventions in patients with DFU, proposing new applications for currently used stress-reduction interventions. Results: Stress is a natural and fundamental survival mechanism that becomes harmful when chronic. DFU is associated with high levels of anxiety and chronic psychological stress. Chronic stressinduced cortisol and adrenaline release impair wound healing, independently of the stressor. Psychological stress-reducing interventions, such as relaxation with guided imagery, biofeedback-assisted relaxation, mindfulness-based strategies, and hypnosis, can lead to a reduction in perceived stress and improve wound healing by reducing wound inflammation and pain while improving glycemic control. All stress reduction interventions also lead to pain relief and improved patient’s quality of life. Conclusion: Psychological stress-reducing interventions are promising adjuvant therapies for DFU. Their clinical application can improve self-care by tackling patient’s expectations, anxieties, and fears. They can also help patients manage stress and pain while reducing wound inflammation and improving wound healing.

Diabetes mellitus has been identified as a major risk factor for developing severe COVID 19 complications. In this review article, the efforts were directed to provide insights and the possible extent to which some diabetic pharmacological interventions may exacerbate COVID 19 or may not be idyllic options for COVID 19 patients. Articles reviewed were identified using the Google scholar database, and search was done using the English language. Anti-hyperglycemic is associated with undesirable effects including episodes of hypoglycemia, diarrhea, lactic acidosis, and increased risks of cardiovascular and hepatic hazards. These undesirable effects associated with the anti-hyperglycemic agents possess a threat of developing severe COVID19 complications Therefore, this calls for more studies to understand the extent of the risks these agents possess in diabetic COVID 19 patients. Almost all the anti-hyperglycemic agents have the potential to worsen COVID 19, despite their class. COVID 19 may limit the options in terms of available anti-hyperglycemic agents which may not heighten the risk of developing severe COVID 19 complications. The research towards the discovery and development of new compounds and also new therapeutic targets for hyperglycemia should be encouraged and welcome.

Diabetes mellitus is a metabolic disorder caused by an increase in insulin resistance, a decrease in insulin production, or both of them, resulting in a high level of blood glucose or hyperglycemia. An uncontrolled state of DM may cause complications, namely skin disorder. One or more skin disorders are found amongst 74% of T2DM patients, with the highest percentage is dry skin (47%), followed by infection (10%), diabetic hand (5%), hair loss and diabetic dermopathy (each 4%). In DM, the state of hyperglycemia and production of advanced glycaemic end-products (AGEs) profoundly impact skin changes. In the pathological pathway, AGEs induce oxidative stress and inflammation. Nonetheless, AGEs level is higher in T2DM patients compared to non- T2DM people. This is caused by hyperglycemia and oxidative stress. Binding between AGEs and receptor of AGEs (RAGE) promotes pathway of oxidative stress and inflammation cascade via mitogen- activated protein kinases (MAPK), nuclear factor-k-light-chain-enhancer of activated β cells (NF-kβ), interleukin- 6 (IL-6), tumor necrosis factor-α (TNF-α), expression of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 2 (VCAM-2) pathway which furtherly effectuates DM complication including skin disorders.

Type 2 Diabetes Mellitus (DM) is the most common form of diabetes. The initial treatment of type 2 DM consists of the adoption of healthy lifestyle habits together with several classes of hypoglycemic agents. However, these medications are not always able to reduce the blood glucose levels in all patients. Therefore, creatine supplementation has emerged as a new putative candidate for type 2 DM treatment. This systematic review aimed to investigate the effects (benefits and harms) of creatine supplementation in patients with type 2 diabetes through a systematic review. The studies were searched in MEDLINE, EMBASE, LILACS, CENTRAL, SPORTDiscus, and CINAHL databases, without date or language restrictions. Methodological quality was assessed using the Cochrane risk-of-bias table. The certainty of the evidence was classified using the Grading of Recommendations Assessment, Development and Evaluation approach. Three randomized controlled trials (RCTs) were included (87 participants). Overall, the methodological quality was classified as unclear to a high risk of bias. Each trial compared creatine supplementation with a different control group (placebo, metformin, and glibenclamide). Creatine supplementation seems to be effective in decreasing glycemic levels and glycosylated hemoglobin concentrations compared to placebo. No difference was observed compared to metformin or glibenclamide with creatine, and all treatments were able to reduce blood glucose levels. No major adverse effects were observed. Based on the low certainty of evidence, creatine supplementation was shown to be a hypoglycemic intervention for patients with type 2 diabetes, without major adverse events reported. However, well- designed RCTs with larger sample sizes and long-term outcomes are needed to support this evidence.

Background: The novel coronavirus disease (COVID-19), declared a global pandemic by the World Health Organization (WHO) on March 11, 2020, and has constituted one of the most serious health challenges of the century, globally. The causative organism was initially named the 2019 novel coronavirus (2019 n CoV) but has subsequently been renamed Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The pandemic has so far infected several millions and killed about a million people worldwide. Diabetes mellitus (DM) is one of the leading causes of morbidity worldwide. Objectives: To examine the critical role diabetes plays in the pathogenesis and prognosis of COVID-19 and to assess the emerging therapies available to fight the pandemic. Methods: Authors conducted a systematic review of the literature to examine the role of diabetes as comorbidity in the pathogenesis and prognosis of COVID-19 by searching PubMed and Science Direct databases mainly for articles published since the outbreak of the pandemic. Results: Both experimental and observational data from early 2020 suggested that most people with COVID-19 have comorbidities, the most dominant of which are diabetes, cardiovascular disease, and hypertension. Empirical evidence indicates that diabetic patients infected with the COVID-19 disease had the worst outcomes concerning morbidity and mortality. Conclusion: A combination of underlying chronic conditions such as hypertension, obesity, and cardiovascular diseases together with altered ACE receptor expression, immune dysregulation via cytokine storm, alveolar and endothelial dysfunction, increased systemic coagulation may put individuals with diabetes at risk for COVID-19 severity. More studies are needed to elucidate how glucose- lowering drugs may modulate the host immune response in diabetic individuals, especially following the administration of potential COVID-19 vaccines.