Current Diabetes Reviews - Volume 15, Issue 4, 2019

Substantial terms have been recognized on the associated risk elements, comorbidities as well as, putative pathophysiological processes of Alzheimer disease and related dementias (ADRDs) as well as, type 2 diabetes mellitus (T2DM), a few from greatest important disease from the moments. Very much is considered regarding the biology and chemistry of each predicament, nevertheless T2DM and ADRDs are an actually similar pattern developing from the similar origins of maturing or synergistic conditions connected by aggressive patho-corporeal terms and continues to be ambiguous. In this depth-critique article, we aimed to investigate all possibilities and represented a novel and applicable approach from the Medicinal Chemistry concepts.

Introduction: Sodium-glucose cotransporter 2(SGLT2)-inhibitors are new antihyperglycemic agents that have shown a reduction in cardiovascular events in type 2 diabetes mellitus. Recent warnings have been developed about an increased risk of euglycemic and moderate hyperglycemic diabetic ketoacidosis with the use of SGLT2 inhibitors, but its real incidence is not available yet. 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.

Background: The association of polymorphisms in the renin-angiotensin-aldosterone system candidate genes, namely Angiotensin-Converting Enzyme (ACE) Insertion/Deletion (I/D), Angiotensinogen (AGT) M235T and Angiotensin II Receptor Type 1 (AGTR1) A1166C with Diabetic Nephropathy (DN) has been studied for decades. Objective: This meta-analysis aimed to assess the updated pooled effects of these polymorphisms with DN among Asian populations with type 2 diabetes mellitus. Methods: The PubMed electronic database was searched without duration filter until August 2017 and the reference list of eligible studies was screened. The association of each polymorphism with DN was examined using odds ratio and its 95% confidence interval based on dominant, recessive and allele models. Subgroup analyses were conducted based on region, DN definition and DM duration. Results: In the main analysis, the ACE I/D (all models) and AGTR1 A1166C (dominant model) showed a significant association with DN. The main analysis of the AGT M235T polymorphism did not yield significant findings. There were significant subgroup differences and indication of significantly higher odds for DN in terms of DM duration (≥10 years) for ACE I/D (all models), AGT M235T (recessive and allele models) and AGTR1 A1166C (recessive model). Significant subgroup differences were also observed for DN definition (advanced DN group) and region (South Asia) for AGTR1 A1166C (recessive model). Conclusion: In the Asian populations, ACE I/D and AGTR1 A1166C may contribute to DN susceptibility in patients with T2DM by different genetic models. However, the role of AGT M235T needs to be further evaluated.

Background: Previous studies suggested that the single nucleotide polymorphisms of Pro12Ala located within the PPARG gene were significantly associated with the T2DM. Recently, the genetic studies on Pro12Ala were conducted in the different ethnic groups and the results of each study were shown to be inconsistent. Moreover, the systematic review has not been updated since 2000. Objective: To further validate the risk of Pro12Ala for T2DM disease based on the genetic data. Methods: The genetic studies on the Pro12Ala in the T2DM were searched in the PubMed and PMC database from January 2000 to October 2017. The meta-analysis was conducted with the CMA software. Results: The meta-analysis collected 14 studies including 20702 cases and 36227 controls. The combined analysis of all studies found that Pro12Ala was shown to be significantly associated with T2DM and the Ala allele played the increasing risks for the disease. Nevertheless, publication bias was detected in the combined analysis. The subgroup analysis indicated that Pro12Ala was found to be significant in the Caucasian and Chinese population. There was no heterogeneity and publication bias in these two groups. Conclusion: The meta-analysis confirmed the evidence that the Pro12Ala was the susceptible variant for the decreasing risks for the T2DM.

Background: Diabetes is a metabolic disorder, whose incidences are increasing day by day. Various classes of anti-diabetic drugs are clinically approved by the Food and Drug Administration (FDA) for the treatment of diabetes mellitus, but unfortunately, none of them is able to treat this condition. Thus, the exploration of novel mechanistic pathways of existing molecules may help to develop more safe and effective anti-diabetic agents. Sodium orthovanadate is a well known common laboratory agent used to preserve the protein tyrosyl phosphorylation state of the protein. Methods: The data related to sodium orthovanadate and diabetes mellitus has been collected from Pubmed. Results: Various reports have indicated the potential of sodium orthovanadate as Protein Tyrosine Phosphatase (PTP1B) inhibitors which play an important role in the pathogenesis of diabetes. However, safety of Sodium orthovanadate is still questionable. Conclusion: The sodium orthovanadate could be developed as an anti-diabetic agent. However, further studies are required to confirm its safety profile in the treatment of diabetes mellitus before starting a clinical trial.

Background: The purpose of this study is to determine the impact of depressive symptoms on the quality of life of type 2 diabetic patients (T2DM). Methods: A cross-sectional study of 332 T2DM patients aged ≥18 years living in Jazan region of Saudi Arabia was conducted. Validated questionnaire was used for demographic and disease characteristics. Depressive symptoms of the participants were assessed using the Patient Health Questionnaire (PHQ-9). The Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) was utilized to assess the degree of life enjoyment and satisfaction. Results: Depressive symptoms were observed in 34.7% (112) of the total participants. The overall sense of wellbeing (mean 3.23, P. value 0.000), physical (mean 3.37, P. value 0.003), psychosocial (mean 2.99 P. value 0.000) and social domains (mean 3.53, P. value 0.000) of quality of life were significantly reduced in T2DM patients with depressive symptoms. Conclusion: The impact of depressive symptoms on quality of life of T2DM patients was more significant than the impact of diabetes alone. Symptoms of depression reduce the individual coping and hence reduce functioning. This study emphasizes the vital importance of an integrated holistic approach that addresses both the practical and emotional issues in diabetes care.

Background: People from Latin America (LA) and the Hispanic/Latino community living in the United States (LUS) exhibit a high prevalence of diabetes (DM) and obesity (OB). The Gut Microbiome (GM) is capable of altering energy regulation and glucose metabolism, but for the expression of these diseases a combination of multiple factors such as ethnicity, genetic and nutritional factors are required. A systematic research was conducted to understand if the prevalence of OB and/or DM has an interaction with the GM in LA and LUS. Methods: Research was conducted in PubMed, Web of Science, Scielo, Embase and Google Scholar for articles between 1990 and 2017. It was restricted to human studies published in English, Spanish, or Portuguese that applied genetic techniques to study the GM in LA or LUS and discussed the association with OB and/or DM. Results: Different gut Firmicutes/Bacteroidetes relationships in several populations from LA influenced by geography, diet and lifestyles interacted with OB. Healthy people from the Mexico and US border had the same imbalance between Firmicutes and Bacteroidetes found in OB or Type 2 DM. High levels of Bacteroides and a reduced proportion of Prevotella, Megamonas, and Acidaminococcus were found in newly diagnosed type 1 DM. Once the patient was treated with insulin, an increase of Prevotella levels was seen. Inverse Firmicutes/Bacteroidetes relationship was reported before the development of Type 1 DM. Conclusion: An important relation between GM and OB and/or DM exists in LA and LUS. Further elucidation of pathophysiologic mechanisms is required.

Exercise is essential for managing type 2 diabetes, however approximately only 40% of people with the condition meet guidelines. The aim of this review is to examine the evidence regarding the use self-report measures of affect to understand and predict exercise adherence. Self-reported affect has been successfully used to regulate exercise intensity, monitor training load, prevent injury, and predict future physical activity participation in otherwise healthy and some clinical populations. Specific recommendations are provided for research to explore the utility of self-report measures of affect to promote exercise adherence in people with type 2 diabetes.

Aptamers have several positive advantages that made them eminent as a potential factor in diagnosing and treating diseases such as their application in prevention and treatment of diabetes. In this opinion-based mini-review article, we aimed to investigate the DNA and RNA-based hybrid molecules specifically aptamers and had a logical conclusion as a promising future perspective in early diagnosis and treatment of diabetes.

Background & Introduction: The advent of the sodium-glucose cotransporter-2 inhibitors [SGLT-2i] provides an additional tool to combat diabetes and complications. The use of SGLT-2i leads to effective and durable glycemic control with important reductions in body weight/fat and blood pressure. These agents may delay beta-cell deterioration and improve tissue insulin sensitivity, which might slow the progression of the disease. Methods & Results: In response to glycosuria, a compensatory rise in endogenous glucose production, sustained by a decrease in plasma insulin with an increase in glucagon has been described. Other possible mediators have been implicated and preliminary findings suggest that a sympathoadrenal discharge and/or rapid elevation in circulating substrates (i.e., fatty acids) or some yet unidentified humoral factors may have a role in a renal-hepatic inter-organ relationship. A possible contribution of enhanced renal gluconeogenesis to glucose entry into the systemic circulation has not yet been ruled out. Additionally, tissue glucose utilization decreases, whereas adipose tissue lipolysis is stimulated and, there is a switch to lipid oxidation with the formation of ketone bodies; the risk for keto-acidosis may limit the use of SGLT-2i. These metabolic adaptations are part of a counter-regulatory response to avoid hypoglycemia and, as a result, limit the SGLT-2i therapeutic efficacy. Recent trials revealed important cardiovascular [CV] beneficial effects of SGLT-2i drugs when used in T2DM patients with CV disease. Although the underlying mechanisms are not fully understood, there appears to be “class effect”. Changes in hemodynamics and electrolyte/body fluid distribution are likely involved, but there is no evidence for anti-atherosclerotic effects. Conclusion: It is anticipated that, by providing durable diabetes control and reducing CV morbidity and mortality, the SGLT-2i class of drugs is destined to become a priority choice in diabetes management.

Background: Both insulin deficiency and insulin resistance due to glucagon secretion cause fasting and postprandial hyperglycemia in patients with diabetes. Introduction: Metformin enhances insulin sensitivity, being used to prevent and treat diabetes, although its mechanism of action remains elusive. Results: Patients with diabetes fail to store glucose as hepatic glycogen via the direct pathway (glycogen synthesis from dietary glucose during the post-prandial period) and via the indirect pathway (glycogen synthesis from “de novo” synthesized glucose) owing to insulin deficiency and glucagoninduced insulin resistance. Depletion of the hepatic glycogen deposit activates gluconeogenesis to replenish the storage via the indirect pathway. Unlike healthy subjects, patients with diabetes experience glycogen cycling due to enhanced gluconeogenesis and failure to store glucose as glycogen. These defects raise hepatic glucose output causing both fasting and post-prandial hyperglycemia. Metformin reduces post-prandial plasma glucose, suggesting that the drug facilitates glucose storage as hepatic glycogen after meals. Replenishment of glycogen store attenuates the accelerated rate of gluconeogenesis and reduces both glycogen cycling and hepatic glucose output. Metformin also reduces fasting hyperglycemia due to declining hepatic glucose production. In addition, metformin reduces plasma insulin concentration in subjects with impaired glucose tolerance and diabetes and decreases the amount of insulin required for metabolic control in patients with diabetes, reflecting improvement of insulin activity. Accordingly, metformin preserves β-cell function in patients with type 2 diabetes. Conclusion: Several mechanisms have been proposed to explain the metabolic effects of metformin, but evidence is not conclusive and the molecular basis of metformin action remains unknown.

Diabetic polyneuropathy (DPN) is a complex and multifactorial entity in which various factors besides hyperglycemia play an important role. Symptoms of DPN are sensory, motor or autonomic. Intensive research proved that oxidative stress is the common denominator for the four major destructive pathways of hyperglycemia including increased hexosamine pathway flux, activation of Protein kinase-C (PKC) pathway, increased Advanced Glycated End-products (AGEs) formation, and increased Polyol Pathway flux. National data in Egypt confirms that more than 60% of Egyptian diabetic patients suffer from neuropathy. The most common complications of DPN are Cardiac Autonomic Neuropathy (CAN), diabetic foot and ulcers, neuromuscular disability, and anxiety. In addition, DPN affects the Quality of Life (QoL). According to common clinical practice, the common diagnostic tools are bed-side diagnosis and electrophysiological tests. Early diagnosis is critical to improve the prognosis of DPN and therapeutic intervention in the early phase. In this review, we provide a clear understanding of the pathogenesis, early diagnosis and the good management of DPN. Since the pathogenesis of DPN is multifactorial, its management is based on combination therapy of symptomatic; either pharmacological or non-pharmacological treatments, and pathogenic treatment. Alpha Lipoic Acid (ALA) is a potent anti-oxidant that has several advantages as a pathogenic treatment of DPN. So, in clinical practice, ALA may be prescribed for patients with early neuropathic deficits and symptoms. Patient education has an important role in the managemement of DPN.