Factors Influence Diabetes Mellitus Control at a Primary Health Care Facility in Durban, South Africa

Background: Type-2 diabetes mellitus, a non-communicable disease contributes significantly to morbidity and mortality in South Africa. It is considered a silent epidemic in certain countries in the world with the incidence expected to rapidly escalate due to ageing of the population. Little is known about the treatment outcome from Primary Health Care facilities in SA. The study estimated control and determinants of diabetes control among rural black patients attended a PHC facility. Method: A cross-sectional prospective design was adopted. Chi-square test was carried out to find significant association between dependent and independent variables. Forward stepwise logistic regression was performed to determine the significant predictor for diabetes control. Two-sided statistical tests were performed at 0.05 level of significance. Result: A total of 240 DM patients were recruited and (68.7%) of them had HbA1c level measured) and only 49 (29.7%) were found with glycaemic control. Logistic regression analysis showed that patients those read newspaper daily or almost daily were almost three times (OR=2.6) more likely to have control. Patients those measured the blood sugar at home were 4.4 times more likely to have their diabetes controlled. It was found that knowing normal blood sugar had four times more chances of controlling their diabetes than those did not know. Duration of DM treatment (5-9 years) was 60% less likely to have DM control that those had 10 or more years of DM treatment (p<0.05). Conclusion: Glycaemic control of DM was poor and identified several factors towards diabetes control among DM patient. Training and education to healthcare workers and DM patients may lead to improve DM control.

Exogenous Hydrogen Sulfide Alleviated Left Ventricular Fibrosis Via Enhancing Cardiac Autophagy and Decreasing Cardiomyocyte Apoptosis in StreptozotocinInduced Diabetic Rats: From Network Pharmacology to Experimental Pharmacology

Streptozotocin (STZ)-induced diabetes mellitus (DM) model shows the signal of cardiac dysfunction, which is manifested as myocardial fibrosis and hypertrophy. This study was designed to predict targets of sodium hydrosulfide (NaHS) for diabetic cardiomyopathy and its corresponding triggered pathways by network pharmacology analysis and test the effects of NaHS as well as its mechanism as possible modulators of left ventricular remodeling in diabetic rats. The drug-target networks were constructed via approaches of network pharmacology, and the predicted targets and pathways were validated by in vivo experiments. Rats were randomly divided into 3 groups (n=6/group): STZ-induced DM group (STZDM); STZ-induced DM treated with H2S group (STZ-NaHS); control group. The control group was treated with daily saline (i.p.); the diabetic model was induced by intraperitoneal (i.p.) injections of 40 mg/kg/day STZ. After 12 weeks, the rat cardiac function was determined, and the pathological morphology of the heart was analysed by Masson trichrome staining in each group. The expression level of matrix metalloproteinase 9 (AGEs), CSE, CBS and several autophagy associated proteins were detected by the ELISA analysis. Results from the PPI network implied that 27 targets were key regulators. The AGE-RAGE signaling pathway in diabetic complications and the apoptotic signaling pathway was discovered to be the key to anti-diabetic cardiomyopathy of NaHS upon the GO enrichment analyses and KEGG pathway. In the in vivo experiment, compared with the control group, cardiac fibrosis and attenuated left ventricular function were observed. Furthermore, compared with the control group, the expression level of CSE, CBS and autophagy associated proteins Atg5 was significantly decreased, while that of AGEs, autophagy associated proteins p62 and p-ERK1/2 was significantly increased in the STZDM group (P<0.05). In the STZ-NaHS group, cardiac fibrosis and ventricular dysfunction were ameliorated, the expression level of CSE, CBS and autophagy associated proteins Atg5 was increased, and the expression level of AGEs, autophagy associated proteins p62 and p-ERK1/2 was significantly decreased (P<0.05). In conclusion, H2S may alleviate cardiac fibrosis of the STZ-induced DM rat model by enhancing cardiac autophagy, inhibiting cardiomyocyte apoptosis and downregulating p-ERK1/2.

Diabetic Retinopathy: Complications Associated with Treatment and the Way Out

Objective: Elevation in blood sugar level damages the blood vessels of retina leading to a condition called diabetic retinopathy (DR). The treatment of DR is a critical factor as the condition is very difficult to target at early stage. Key Findings: Advancements in the field of drug delivery and introduction of nanotechnology have made way out to treat DR and to solve the problem associated with its treatment. The researchers have recommended that there is need of new treatments which are based on the proper understanding of the mechanism of the disease and its pathophysiology. Summary: The condition of diabetic retinopathy leads to blurred vision and ultimately loss of vision. The treatment involves control of blood sugar levels, surgery and medications like anti-VEGF. The Nano technological systems are so tiny and can cross the barriers of eye thus improving the bioavailability and permeability of drugs. Researches have been done in the field of nanotechnology and the advancements have suggested that it can be used in the treatment of DR.

Comparative Retinopathy Risk in People with Type 2 Diabetes Treated with Post Metformin Second-line Incretin Therapies: Study Based on US Electronic Medical Records

Studies have reported conflicting results of the association of incretin-based treatment with the risk of diabetic retinopathy (DR), while the risk of DR in people treated with different antidiabetic drugs (ADD) in the context of glycaemic control in real-world settings is limited. This study aimed to evaluate (1) the risk of developing DR in metformin-treated patients with type 2 diabetes (T2DM) who initiated secondline ADD and (2) if glycaemic control over one-year post-therapy initiation is associated with DR risk during follow-up . From US Electronic Medical Records (EMR), those who received second line DPP-4 inhibitor (DPP-4i), GLP-1 receptor agonist (GLP-1RA), sulfonylurea, thiazolidinedione, or insulin for ≥3 months post-2004 were analysed. Based on 237,133 people with an average of 3.2 years follow-up, compared to people who initiated second-line with sulfonylurea, those with DPP-4i/GLP1RA/thiazolidinedione had 30%/31%/15% significantly lower adjusted risk of developing DR; insulin users had 84% increased risk (all p< 0.01), with significantly better sustainable HbA1c control over one year in incretin groups. This population representative EMR based study suggests that DR risk is not higher in people treated with incretins, versus other ADD, with the benefit of better glycaemic control.

Enteric Leaks from Simultaneous Pancreas Kidney Transplantation at a Single Centre: Risk Factors and Management Over a 20-Year Period

Background: Simultaneous pancreas-kidney transplantation (SPK) remains the gold standard treatment for patients with type I diabetes mellitus and end-stage renal failure. Enteric drainage is utilised to handle exocrine secretions from the graft, with enteric leaks being the most challenging of complications. There remains a lack of published research regarding risk factors for enteric leaks. Methods: As such we undertook a retrospective cohort study of SPK transplants performed at Westmead Hospital over twenty years (between 1998-2017, n=425) to identify the occurrence of enteric leaks as well as donor, recipient and transplantation procedure risk factors. Descriptive statistics were generated using SPSS version 22.0 (IBM SPSS Statistics for Windows, Armonk, NY, USA). The student’s t-test and/or Mann-Whitney U test was used to detect significance. All tests were two tailed and any statistically significant difference was considered at the P <0.05 level. Results: Of the 425 patients, 16 (3.5%) experienced an enteric leak. Of these, 12 (80%) had significant vascular disease, defined as coronary artery disease, cerebrovascular disease, retinopathy, peripheral neuropathy or peripheral vascular disease requiring surgical intervention. The risk of an enteric leak increased in recipients with significant vascular disease. Conclusion: The rates at Westmead Hospital were lower than those published in the literature. We demonstrated that the presence of significant vascular disease predisposed recipients to enteric leak. These findings highlight the importance of careful donor and recipient selection to optimise patient outcomes.

Obesity and Metabolic Associated Fatty Liver Disease (MAFLD) as Risk Factors for COVID-19 Severity

In December 2019 Coronavirus disease 2019 (COVID-19) emerged in Wuhan, China and rapidly spread to other areas and has been declared a pandemic in 2020. Until now there are about half million deaths. Of note the highest fatality rate was found for cardiovascular disease, diabetes mellitus followed by chronic respiratory diseases, hypertension and cancer. Remarkably early data have reported higher BMI is associated with a higher risk of developing severe symptoms and complications of COVID-19 disease. Patients with metabolic associated fatty liver disease (MAFLD) are often obese and have additional metabolic risk factors which may increase risk of respiratory diseases. Identification of risk factors of COVID-19 severity is crucial to provide additional medical care; in this review we shed light on the association between MAFLD and COVID-19 severity.

CAC: An Under-Utilized Tool for Screening of ASCVD in Diabetes

Diabetes Mellitus is the silent killer of the 21st century affecting 425 million people all over the world. The situation is worse in south east Asia particularly India where the prevalence is increasing at a rapid pace. The overall prevalence of diabetes in all 15 states of India was 7.3%. Coronary artery disease (CAD) contributes the highest in morbidity, mortality and financial burden of diabetes. Observational studies and RCTs report the prevalence of silent myocardial ischaemia in asymptomatic DM as 22%. There are many ways to estimate cardiovascular risk in asymptomatic diabetes people like clinical risk score, various biomarkers and other modalities like exercise stress test, echocardiography, Ankle Brachial Index (ABI), Carotid Intima Media Thickness (CIMT), Coronary Artery Calcium Score (CAC), CT angiography, Cardiac MRI, Nuclear Imaging etc. In this article we tried to review various modalities and their usefulness in screening asymptomatic ASCVD. Out of all available modalities CAC score is found to be very cost effectiveness and sensitive way to predict ASCVD. Still CAC is an underutilized modality to screen asymptomatic ASCVD in diabetes people.

Internet Usage May Improve Quality of Life (QoL) in Type 1 Diabetes Mellitus Patients

Objective: To delineate the effect of self-gained information through internet on glycemic control and overall QoL in type 1 diabetes patient. Methodology: 35 type 1 diabetes patients, who had reasonably good glycemic control were classified by a single clinician into net- savvy and ordinary based on their behaviour towards use of internet to gather information regarding health queries and their glycemic control and QoL analysed.WHO-5 questionnaire which is used in clinical practise was applied. Result: Of net savvy group (n=18), 14 (82%) had WHO-5 score greater than 13 while among ordinary (n=17) only 7 had WHO5 of same range. Thus, those who surfed internet were in general likely to have better QoL. Among net savvy group all had individual smart phones and used google as search engine. Among ordinary, 40% (9/17) had smart phones. The mean HbA1c of net savvy group was 7.2 which was lower than that of ordinary group mean HbA1c of 7.6. Those of net savvy group were more likely to agree to increase in number of s.c. insulin injections (12/18) as compared to ordinary group (4/17). The self-reported hypoglycemia episodes were also more in net savvy group (6/ person-week) as compared to ordinary (2/ person- week). Conclusion: Use of smart search engines like google (with strong in-built Artificial Intelligence (AI) systems), even if unsupervised, should be encouraged as part of DSME in type 1 Diabetes patients for optimizing glycemic control and detecting hypoglycemic episodes.

Low Glucose Enhances the Cytoprotective Effect of Metformin Against Doxorubicin Induced Cytotoxicity in Normal Cells

The anti-diabetic drug, metformin, has been reported to be beneficial for the cardiovascular system and may facilitate the extension of a healthier lifespan. Doxorubicin is a leading chemotherapeutic drug used to treat a variety of cancers, yet it can cause significant adverse effects with cardiac toxicity and longterm damage. To test the hypothesis that the hypoglycaemic agent, metformin, may protect normal cells during chemotherapy treatment with liposomal doxorubicin, C2C12 myoblast cells were used to study cellular bioenergetics, variations in gene expressions and biochemical alterations induced by metformin and pegylated liposomal doxorubicin (L-Doxo) under low glucose conditions (2.7 mM or 50 mg/dL). Using confocal microscopy, we noted that treatment of C2C12 cells with 30 µg/mL L-Doxo under low glucose conditions induced a number of cellular defects. L-Doxo treatment dysregulated the expression of mitochondrial fission and fusion genes, which may influence transformation of the network’s connectivity. L-Doxo significantly reduced mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). However, pre-treatment of cells with 100 nM metformin provided protection against L-Doxo-induced damage and increased cell viability and ATP levels in cells even under low glucose conditions. In addition, metformin increased and restored the decreased OCR and ECAR. Our data provide a mechanism by which low dose metformin exerts protective effects against L-Doxo via involvement of AMPKα under low glucose conditions. Taken together, our results demonstrate that metformin protects normal cells from L-Doxo damage even under low glucose conditions.

Vitamin D Deficiency is Associated with Metabolic Syndrome

Background: Metabolic syndrome (MetS), insulin resistance (IR) and diabetes mellitus (DM) are highly interrelated abnormalities seeking multidisciplinary public health interventions. Vitamin D has recently gained attention as a protective factor for MetS, IR, DM and cardiovascular diseases (CVD). However, there is no clearly defined mechanism of action, and supplementation guidelines on vitamin D (VD) in either prevention or treatment against MetS, IR, DM and CVD. The purpose of this study is to determine the strength of association between VD and MetS, IR, and DM in the general U.S. population. Methods: The study was done using the National Health and Nutrition Examination Survey (NHANES) 2005-2006 data. NHANES data represent the civilian, non-institutionalized US population. Subject recruitment was based on a multistage, stratified sampling method. Regression models were used to determine the relationship of vitamin D with DM, MetS and IR. Results: We found a consistent observation in which VD deficiency was significantly associated with DM (OR=2.16), MetS (OR=2.09) and IR (OR=1.83). Female gender, older age, and overweight - all positively associated with DM, MetS or IR. Conclusion: The inverse relationship of VD status with MetS, IR and DM indicates a strong support of increasing vitamin D intake as an inexpensive intervention strategy in the national endeavor to reduce the burden of MetS, IR, DM, and its complications.