Current Diabetes Reviews - Volume 17, Issue 5, 2021

Background: Numerous studies have shown a significant association between Type 2 Diabetes Mellitus (T2D) and Alzheimer's Disease (AD), two pathologies affecting millions of people worldwide. Chronic inflammation and oxidative stress are two conditions common to these diseases, also affecting the activity of the serpin Alpha-1-antichymotrypsin (ACT), but a possible common role for this serpin in T2D and AD remains unclear. Objective: To explore the possible regulatory networks linking ACT to T2D and AD. Materials and Methods: A bibliographic search was carried out in PubMed, Medline, Open-i, ScienceDirect, Scopus, and SpringerLink for data indicating or suggesting association among T2D, AD, and ACT. Searched terms like “alpha-1-antichymotrypsin”, “type 2 diabetes”, “Alzheimer's disease”, “oxidative stress”, “pro-inflammatory mediators” among others were used. Moreover, common therapeutic strategies between T2D and AD as well as the use of ACT as a therapeutic target for both diseases were included. Results: ACT has been linked with the development and maintenance of T2D and AD and studies suggest their participation through the activation of inflammatory pathways and oxidative stress, mechanisms also associated with both diseases. Likewise, evidences indicate that diverse therapeutic approaches are common to both diseases. Conclusion: Inflammatory and oxidative stresses constitute a crossroad for T2D and AD, where ACT could play an important role. In-depth research on ACT involvement in these two dysfunctions could generate new therapeutic strategies for T2D and AD.

It is evident that COVID-19 and diabetes have a significant influence on population health across the world, including the Middle East and North Africa (MENA) region. COVID-19 patients with diabetes have been observed to be more prone to developing severe infections and higher risk of mortality compared to non-diabetics. As diabetes is one of the major health issues, widely prevalent in the MENA countries, the current review focused on understanding the epidemiology of COVID-19 in people with diabetes, and the interventions implemented by the governments to minimize the impact of it. Considering the importance and need, the MENA countries have enforced several prevention and control measures to mitigate the impact of the pandemic. Though there has been a considerable amount of research on COVID-19, only a few countries from the MENA region focused on the epidemiology of COVID-19 among patients with diabetes and its effects. Hence, we emphasize the need for intensive research which is an urgent need to have a clear understanding of COVID-19 and its association with diabetes to develop and implement evidence- based programs and policies in the MENA region.

The circadian rhythms have been controlled with the aid of a circadian clock in the hypothalamus region, which is known as the suprachiasmatic nucleus. Chronotherapeutics, a branch of pharmacotherapeutics, plays a mandatory role in the treatment of various disorders, such as delivering the drug in the correct schedule, correct site, and correct extent and provides benefit to the patients. The chronopharmacological aspects are very much important in the treatment of diabetes mellitus during daytime as the patients’ timing of daily activities of body and medicine treatment has an impact on the increase in the glucose levels in the blood. This leads to the fact that the increased risk of obesity and diabetes gets worse, ultimately increasing the rates of cardiovascular diseases and deaths. According to a medical saviour who works on the problems related to diabetes, the level of glucose in plasma changes independently as regard to eating habits and use of insulin and medicines. People suffering from dawn phenomenon are difficult to manage, hence, the basic aim is to detect the functioning of the biological clock of human body and its chronotherapeutic effect on human beings that increases the therapeutic effects and reduces side effects. Keeping these points in mind, an attempt has been made in the present review to discuss the role of chronotherapy in the management of diabetes, various techniques used in formulation and design of chronotherapeutic drug delivery systems and regulatory issues related to chronotherapeutics.

Diabetes Mellitus (DM) is a chronic disease, and the complications may be life-threatening; however, with proper treatment and control measures, it can be very well-managed. Self-management training and education of diabetes are critical in diabetes care and management. It is essential that patients with diabetes must have a comprehensive understanding of the nature of the disease, risk factors, complications, and possible treatment modalities to attenuate the complications. Over the last few years, DM in Saudi Arabia has been rapidly growing at an alarming rate. It has affected around one-fifth of the adult population, and by 2030, the numbers are predicted to rise further and exceed more than double the present number. An estimated tenfold increase has been reported over the past three decades in Saudi Arabia. However, there has not been much research focusing on understanding the knowledge and awareness of DM in Saudi Arabia as compared to developed nations. This review aims to present an overview of the current knowledge and awareness level of DM among the population of Saudi Arabia through an extensive review of the currently available literature. The review findings could be of immense assistance to the government, healthcare systems, educational institutions, and researchers to develop evidence-based programs, policies, and guidelines towards increasing the knowledge and awareness about diabetes and its management, so that early detection and management can be ensured to control the escalating burden of diabetes in Saudi Arabia.

The scarcity of human cadaver islets for transplantation in patients with Diabetes Mellitus (DM) has necessitated the search for alternative islet sources. With advancing islet biology research, Islet-Like Clusters (ILCs) derived from stem cells have demonstrated potential for treating DM and in novel drug discovery programs for drug and cytotoxicity testing. In vitro differentiation of ILCs from stem cells also provides an opportunity to mimic the in vivo islet developmental pathways. In vitro derived ILCs are often considered immature as they do not respond to glucose challenges efficiently. However, the in vitro and in vivo performance of ILCs can be improved by pharmacological preconditioning. In this review, we discuss how ILCs generated from human postnatal tissues can be utilized as an in-vitro model to study cytotoxicity, drug screening and enhancement of transplantation efficacy. The use of human cadaver islets is not permitted for research purposes in India. Under these restrictions, the application of ILCs in drug screening and their role in complementing, reducing, and replacing animal testing will evolve as a reliable platform for in vitro screening as well as for stem cell-based treatment in DM.

Background: COVID-19 is a world disaster. The relationship between COVID-19 and Diabetes Mellitus (DM) is double-faced because DM is considered one of the COVID-19 key risk factors causing an increase in COVID-19 related conditions and death rates; at the same time, high stress in patients with COVID-19 can lead to the occurrence of DM. This relationship adversely affects immune functions. Relaxation techniques have been demonstrated to positively affect immune functions, glycemic control, and stress levels. Methods: A search in Scopus, Web of Science, Medline databases, and EBSCO has been made. The search included clinical trials and systematic and literature reviews on the effects of relaxation techniques on immune functions, glycemic control, and stress levels. Results: This review found that relaxation techniques produce short-term effects on decreasing stress levels through autonomic regulation, controlling glycemic control through decreasing hyperglycemia, and increasing immune functions through increasing immune cells and immunoglobins A. Conclusion: This review summarizes the important role of performing regular relaxation techniques in COVID-19 patients with DM. Relaxation techniques benefit diabetic patients with COVID-19 through decreasing stress levels, better controlling of glycemic control, and increasing immune functions.

Glucolipotoxicity-induced oxidative stress and mitochondrial dysfunction of pancreatic β-cells are some of the mechanisms that have been related to the low insulin secretion and cell death during diabetes development. In early or non-chronic stages, the pancreatic β-cells respond to hyperglycemia or hyperlipidemia, stimulating insulin secretion. However, the chronic effect of both leads to glucolipotoxicity, which induces constant overstimulation of pancreatic β-cells, a condition that leads to cell death by apoptosis. The mechanism described, at this moment, is the accelerated mitochondrial dysfunction triggered by the high production of reactive oxygen species (ROS) due to excess nutrients. At first, mitochondria respond to over-nutrition accelerating oxygen consumption and consequently increasing the ATP synthesis. A permanent increase of ATP/ADP ratio leads to a constant inhibition of K⁺ATP-channel and, therefore, a continuous insulin secretion accompanied by an increase in ROS. Finally, ROS accumulation compromises mitochondrial function due to the uncontrolled oxidation of proteins, lipids, and DNA generating functional alterations such as a drop of membrane potential, deregulation of mitochondrial dynamics, low rate of ATP synthesis and consequently the cell death. This review aims to describe the effect of glucolipotoxicity- induced oxidative stress and its relationship with mitochondrial dysfunction in β-cell during type 2 diabetes development.

Background: Painful Diabetic Neuropathy (PDN) is a devastating condition affecting one in three people with diabetes. Introduction: Keeping in mind the unceasingly escalating prevalence of diabetes mellitus worldwide, the number of PDN patients is also expected to rise with a reduced quality of life in patients and a staggering increase in healthcare costs. Despite relentless efforts and continuous research, the commercially available medications for relieving diabetic neuropathy pain are only partially effective with substantial side effects. This is, in part, due to our partial awareness of the underlying complexities causing PDN. The pathogenesis of PDN remains elusive because of the difficulty in obtaining damaged nerve samples and the absence of non-invasive methods to investigate the pathogenesis at different stages of disease progression. The purpose of this review was to describe pathogenesis, clinical manifestations and treatment options for PDN. Methods: The keywords relevant to the scope of this paper were put in electronic databases (PubMed and Google Scholar) to fetch the relevant data. The data were then analyzed and compiled. Results: A simplified overview of PDN for researchers new to the field has been provided in an attempt to clarify common confusions. The changes in skin structure and functions in response to diabetes, diabetic neuropathy and painful diabetic neuropathy are also discussed. The unavailability of an efficacious pain reliever for PDN stresses on the need for identifying the microenvironmental factors that are altered in PDN and manipulate them to tailor targeted theranostics. Conclusion: In the end, we proposed to consider the altered skin structure, function and microenvironmental factors in the diabetic population for devising smart, targeted, stimuli-responsive treatment options to attain maximum pain relief with minimum side effects.

Introduction: Hepatic steatosis is a frequent condition that afflicts, especially, obese and insulin-resistant patients. Diagnosis is usually made through imaging tests. Despite the high prevalence and risk of complications, there is no specific treatment approved, though a vast number of medications have been tested. Objective: This study aimed to determine the efficacy of dipeptidyl peptidase IV inhibitors (i DPP- IV) in the treatment of NAFLD. Methods: We searched the electronic databases of the Cochrane Library, MEDLINE, EMBASE, and LILACS, as well as reference lists of the included studies and grey literature; 9 studies were selected for inclusion. Results: 7 studies were used for metanalysis for 3 outcomes. i DPP-IV showed an ALT-reducing power of MD -10.83 (95% CI 35.23 to 13.57) at 3 months and MD -9.27 (95% CI 10.92 to -7.62) at 6 months of intervention, as well as a reduction of hepatic steatosis via MRI of SMD 0.10 (95% CI 0.31 to 0.50); the overall incidence of adverse events was very low. The studies were considered of low and very low quality by the GRADE evaluation. Conclusion: Because of the overall poor quality of the studies and heterogeneity of the population analyzed, i DPP-IV did not show efficacy on inflammatory markers or fibrosis in patients with NAFLD.

Background: Individuals with diabetes mellitus (DM) are susceptible to balance, gait and cognitive impairments. Importantly, diabetes affects executive function, a set of cognitive processes critical to everyday cortical function and mobility. Reduced executive function is a risk factor for falls in people with DM. Dual-task testing, the completion of two tasks at once, enables the examination of the cognitive-mobility relationship. A synthesis of the literature on the effects of dual- task testing on the balance and gait of individuals with DM has not been performed. Objective: To systematically review the literature on the effect of dual-task testing on balance and gait in people with DM. Methods: Databases EMBASE, CINAHL, MEDLINE, PsycINFO, Scopus and Web of Science were searched (inception-April 2020). Inclusion criteria: participants were adults with a diagnosis of DM, instrumented dual-task balance and/or gait was assessed, and articles were published in English. Results: Ten articles met inclusion criteria- three examined dual-task balance and seven dual-task gait. In people with DM with or without peripheral neuropathy, dual-task resulted in larger sway velocities during standing tests. Individuals with DM and peripheral neuropathy had impaired dual-- task gait; specifically, and more consistently, reduced pace and rhythm compared to controls or people with DM without peripheral neuropathy. Conclusion: The findings support a compromise in the cognitive-mobility relationship of people with DM, and especially in those with peripheral neuropathy. Future research should continue to examine the cognitive-mobility relationship in order to understand the increased prevalence of falls in this population.

Introduction: A recent CDC report estimates that only 17.2% people with diabetes receive insulin. The aim of this study was to evaluate the knowledge, attitude and practice of patients with diabetes and their caregivers towards sharps waste disposal at home. Methods: A cross-sectional study was conducted from February to July 2019 at the two main diabetes specialist centers in Taif, Saudi Arabia. Data collected using an interviewer-administered questionnaire, which was designed after a thorough literature review, were used to assess knowledge, attitude and practice using a total of 36 items. Results: 406 patients comprised of mostly females and those who were unemployed, with a mean age of 53.2 +18.5 years and a mean DM duration of 13.6 +8.7 years were included. Approximately <10% reported sharing used insulin needles or lancets as well as accidental family member sticks by the used needle or lancet. More than half of the respondents answered, “I don’t know” regarding the knowledge of transmission of hepatitis B or C and HIV by sharing lancet or insulin needles. 52.5%, 51.7% and 47.0% of participants were considered to have high knowledge, high attitude and good practice levels, respectively. 78.8% of participants stated that they disposed of sharps waste in public household garbage bags, and one-third disagreed that they safely collected and brought their used sharps to a hospital. The highest score in the practice section was on optimal needle recap. A partial correlation adjusting to determine the relationship of practice levels with knowledge and attitude levels after controlling for baseline characteristics and duration of DM showed a statistically significant positive correlation between practice and knowledge levels (r = .172, P = .001) while a statistically significant negative correlation between practice and attitude levels (r = - .116, P = .021). Conclusion: Patients with type 1 diabetes exhibited a significantly higher mean score in practice only compared to patients with type 2 diabetes. A partial correlation showed a statistically significant positive correlation between practice and knowledge and a negative correlation between practice and attitude level.

Background: According to the Center for Disease Control and Prevention, diabetic ketoacidosis (DKA) hospitalization rates have been steadily increasing. Due to the increasing incidence and the economic impact associated with its morbidity and treatment, effective management is key. We aimed to streamline the management of DKA in our intensive care units (ICU) by implementing a Best-Practice Advisory (BPA) that notifies providers when DKA has resolved. 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.

Background: Type 2 diabetic patients often require insulin therapy for better glycaemic control. However, many of these patients do not receive insulin or do not receive it in a timely manner. Objective: The study was planned to assess the proportion of type 2 diabetic patients attaining treatment goals as per the ADA 2018 guidelines. In addition, patient’s perception of insulin therapy was assessed and compared between insulin naïve and insulin-initiated type 2 diabetic patients. Methods: The study was conducted in type 2 diabetic patients. Data on their demographics, medical history, duration of diabetes, history of diabetes related complications, the current anti-diabetic medication received, and the most recent glycaemic parameters were all noted. Patient’s perception of insulin initiation was recorded through a structured interview. Results: A total of 129 patients were included in the study. Around 76.7% patients achieved HbA1c target (<7%). The duration of the disease is much higher in patients who did not meet the HBA1c target. A good number of patients felt that insulin injection would be physically painful (56.5%). The majority of the patients also felt that insulin would make their life less flexible (64.8%). Many patients have the opinion that insulin is required for life long (73.2%). More number of patients on insulin agreed with the statement ‘Leads to good short-term outcomes as well as long-term benefits’ compared to insulin naïve patients. Conclusion: The results highlight that the proportion of patients achieving the recommended glycaemic target is not satisfactory. Many patients who are inadequately controlled with oral anti-diabetic drugs were reluctant to initiate insulin.