Exploring the Correlation and Protective Role of Diabetes Mellitus in Aortic Aneurysm Disease

Introduction: Diabetes mellitus is recognised as a significant risk factor for cardiovascular and peripheral vascular disease, as the abnormal metabolic state increases the risk for atherosclerosis, occlusive arterial disease and vascular dysfunction. There have been reports of potential association across the literature that illustrates a link between diabetes mellitus and aortic aneurysm, with the former having a protective role on the development of the latter.Methods: A thorough literature search was performed through electronic databases, to provide a comprehensive review of the study's reporting on the association of diabetes mellitus and aortic aneurysm, discussing the mechanisms that have been reported; furthemore, we reviewed the reports of the impact of oral hypoglycameic agents on aortic aneurysms.Results: Various proposed mechanisms are involved in this protective process including endothelial dysfunction, chronic hyperglycemia and insulin resistance. The evidence suggests a negative association between these disease process, with prevelance of diabetes mellitus resulting in lower rates of aortic aneurysm, via its protective mechanistic action. The increase in advanced glycation end products, increased arterial stiffness and vascular remodelling seen in diabetes, was found to have a profound impact on aneurysm development, its slow progression and lower rupture rate in these individuals. This review has also highlighted the role of oral hypoglycaemic agents having a protective effect against AA disease.Conclusion: A decrease in development, progression and mortality from aortic aneurysms as well as reduced rates of dissection, have been observed in those with diabetes. This review has provided a comprehensive insight on the effect of diabetes and its physiological processes, and elements of its con-committant treatment, having a protective role against these aortic diseases.

The ADDition of DAPAgliflozin to angiotensin receptor blocker-neprilysin inhibitors non-responders in patient with refractory HFrEF

Objectives We evaluated the efficacy and safety of dapagliflozin, a SGLT2i along with ARNI in refractory HFrEF irrespective of their diabetic status. Methods We performed a prospective, open-label study of symptomatic patients of HFrEF despite of optimal medical management with ARNI between January–June 2020. Despite the maximum tolerated dose of ARNI and other medications in patients the symptoms of heart failure persisted. The initial dose of 5 mg was started and after 4 weeks irrespective of their glycemic control, then the dose was escalated to 10 mg. They were followed for the 6-months after the combination of ARNI and SGLT2i. Results The 104 patients who had HFrEF despite of optical medical management were added dapagliflozin on top of ARNI. The primary endpoint of mean change in Left Ventricular ejection fraction (LVEF) +9.00±0.62 with a significant p value of <0.001. The Mean difference in NYHA class was −2.9±0.057. A study of 104 patients at 6-months follow-up found that 92.6% of patients were in NYHA class I and 7.4% were in NYHA class II. They also reached the HbA1C goal of <7% in the diabetic subgroup. None of them had either symptomatic hypotension, dyselectrolytemia, and elevation of serum creatinine. The drug was well received by most patients (Picture 1). Conclusions Dapagliflozin are not only oral hypoglycaemic agents but can be used in refractory HFrEF despite the use of ARNI. The combination of the ARNI and SGLT2i is well tolerated but we need large, randomized trials to prove this hypothesis (Picture 2). FUNDunding Acknowledgement Type of funding sources: None. Picture 1. Screening and outcomes of patients Picture 2. Graphical abstract

Effectiveness of Buerger Allen exercise on Lower extremity perfusion among patients with type 2 Diabetes mellitus admitted at selected Hospitals of City

Background: Health is a dynamic condition resulting from a body's adjustment and adaptation in response to changes in the environment and stress for maintaining an equilibrium. Diabetes mellitus (DM), commonly referred to as diabetes, is a group of metabolic disorders in which there is high blood sugar level over a prolonged period. Type 2 Diabetes Mellitus begins with insulin resistance, a condition in which cells fail to respond to insulin properly. Type 2 diabetes is the most common form of diabetes. Type 2 diabetes mellitus is first treated with diet and exercise, then oral hypoglycaemic agents are needed. Objectives: 1) To assess the lower extremity perfusion before Buerger Allen Exercise among Patients with type 2 Diabetes Mellitus admitted at selected hospitals of City. 2) To assess the level of pain before Buerger Allen Exercise among Patients with type 2 Diabetes Mellitus admitted at selected hospitals of City. 3) To determine the effectiveness of Buerger Allen Exercise on Lower Extremity Perfusion among Patients with type 2 Diabetes Mellitus admitted at selected hospitals of city. 4) To determine the effectiveness of Buerger Allen Exercise on Level of pain among Patients with type 2 Diabetes Mellitus admitted at selected hospitals of city. 5) To find association of post intervention findings with selected demographic variables. Research question: Is Buerger Allen Exercise effective on lower extremity perfusion among patients with type 2 Diabetes Mellitus admitted at selected hospitals of city? Setting: The study was conducted in selected hospitals of city. Samples: 60 samples with type 2 Diabetes Mellitus were selected for the study. Result: Since the null hypothesis was rejected. All the p-values were large (greater than 0.05), none of the demographic variables was found to have significant association with the lower extremity perfusion among patients with type 2 diabetes mellitus. Buerger Allen Exercise is significantly effective on Lower Extremity Perfusion among Patients with type 2 Diabetes Mellitus admitted at selected hospitals of city.

Effects of first-line diabetes therapy with biguanides, sulphonylurea and thiazolidinediones on the differentiation, proliferation and apoptosis of islet cell populations

Aims Metformin, rosiglitazone and sulfonylureas enhance either insulin action or secretion and thus have been used extensively as early stage anti-diabetic medication, independently of the aetiology of the disease. When administered to newly diagnosed diabetes patients, these drugs produce variable results. Here, we examined the effects of the three early stage oral hypoglycaemic agents in mice with diabetes induced by multiple low doses of streptozotocin, focusing specifically on the developmental biology of pancreatic islets. Methods Streptozotocin-treated diabetic mice expressing a fluorescent reporter specifically in pancreatic islet α-cells were administered the biguanide metformin (100 mg/kg), thiazolidinedione rosiglitazone (10 mg/kg), or sulfonylurea tolbutamide (20 mg/kg) for 10 days. We assessed the impact of the treatment on metabolic status of the animals as well as on the morphology, proliferative potential and transdifferentiation of pancreatic islet cells, using immunofluorescence. Results The effect of the therapy on the islet cells varied depending on the drug and included enhanced pancreatic islet β-cell proliferation, in case of metformin and rosiglitazone; de-differentiation of α-cells and β-cell apoptosis with tolbutamide; increased relative number of β-cells and bi-hormonal insulin + glucagon + cells with metformin. These effects were accompanied by normalisation of food and fluid intake with only minor effects on glycaemia at the low doses of the agents employed. Conclusions Our data suggest that metformin and rosiglitazone attenuate the depletion of the β-cell pool in the streptozotocin-induced diabetes, whereas tolbutamide exacerbates the β-cell apoptosis, but is likely to protect β-cells from chronic hyperglycaemia by directly elevating insulin secretion.

Analysis of continuous glucose tracking data in people with Type 1 Diabetes (T1DM) after Covid-19 Vaccination reveals unexpected link between immune and metabolic response, augmented by adjunctive oral medication

Introduction The COVID-19 vaccination programme is under way. Anecdotal evidence is increasing that some people with Type 1 Diabetes Mellitus (T1DM) experience temporary instability of blood glucose (BG) levels post-vaccination which normally settles within 2-3 days. We report an analysis of BG profiles of 20 individuals before and after vaccination. Methods We examined the BG profile of 20 consecutive adults (18 years of age or more) with T1DM using the FreeStyle® Libre flash glucose monitor in the period immediately before and after COVID-19 vaccination. The primary outcome measure was percentage(%) BG readings in the designated target range 3.9-10mmmol/L as reported on the LibreView portal for 7 days prior to the vaccination (week -1) and the 7 days after the vaccination (week +1). Results There was a significant decrease in the %BG on target following the COVID-vaccination for the 7 days following vaccination (mean 45.2% ±se 4.2%) vs pre-COVID-19 vaccination (mean 52.6% ±se 4.5%). This was mirrored by an increase in the proportion of readings in other BG categories 10.1-13.9%/ ≥14%. There was no significant change in BG variability in the 7days post COVID-19 vaccination. This change in BG proportion on target in the week following vaccination was most pronounced for people taking Metformin/Dapagliflozin+basal bolus insulin (-23%) vs no oral hypoglycaemic agents (-4%), and median age <53 vs ≥53 years (greater reduction in %BG in target for older individuals (-18% vs -9%)). Conclusion In T1DM, we have shown that COVID-19 vaccination can cause temporary perturbation of BG, with this effect more pronounced in patients talking oral hypoglycaemic medication plus insulin, and in older individuals. This may have consequences for patients with T2DM who are currently not supported by flash glucose monitoring.

Carica papaya L. Leaf: A Systematic Scoping Review on Biological Safety and Herb-Drug Interactions

Introduction. The Carica papaya L. leaf is gaining interest as a potential therapeutic agent for alleviating dengue- and non-dengue-associated thrombocytopaenia. In that regard, safety considerations are as important as efficacy potential. The safety evaluation of botanical products for human use is complicated by variable formulations, complex phytochemical composition, and extrinsic toxicants. This review aimed to systematically collate related safety clinical and preclinical data, as well as reports on herb-drug interactions of C. papaya leaf consumption. Methods. A systematic search using predetermined keywords on electronic databases (MEDLINE, Cochrane Library Central, LILACS, and Web of Science) and grey literature was conducted. Relevant clinical and preclinical studies were identified, screened, and analysed to present an overall safety profile of C. papaya leaf consumption. Results. A total of 41 articles were included (23 clinical, 5 ongoing trials, and 13 preclinical) for descriptive analysis on study characteristics, adverse reactions, toxicity findings, and herb-drug interactions, from which 13 randomised controlled and quasiexperimental trials were further assessed for risk of bias and reporting quality. Overall, C. papaya leaf consumption (in the form of juice and standardised aqueous extract) was well tolerated by adult humans for short durations (<five days) while one randomised controlled trial reported safe consumption of C. papaya leaf standardised aqueous extract in children (aged 1–12 years). Minor gastrointestinal side effects were most commonly reported. There are concerns about hepatotoxicity and reproductive toxicity in long-term use, supported by animal studies. Unfavourable herb-drug interactions with metformin, glimepiride, digoxin, ciprofloxacin, and artemisinin were accounted. Conclusion. C. papaya leaf consumption in adults is generally safe for short-term use though cautioned in pregnancy and people with liver impairment. It has potential herb-drug interactions with oral hypoglycaemic agents, p-glycoprotein substrates, and antibiotics with cation chelating properties.

Comparing Quality of Life in Type 2 Diabetic Patients Using Dulaglutide and Liraglutide

Background and Aims: WHO has defined quality of life as individuals perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. The quality of life evaluation is seen as an important aspect of care of diabetes mellitus 1. In this context it is imperative to study how new agents will affect the quality of life. In this study we have compared the quality of life of patients using dulaglutide and liraglutide. Deign and Method: We have used a simple self-administered patient centered quality of life (PCQoL) measure that is based on general and diabetes related life. This tool has shown to strongly correlate with the established reference scorings system, diabetes related quality of life (DQoL) score, developed for the Diabetes Control and Complications Trial 2,3. Sixty eligible patients on oral hypoglycaemic agents and Dulaglutide (N:30) or Liraglutide (N:30) formed the study group. All study subjects were on steady dose of GLP 1 RA for at least six months before they took two part quality of life (general and diabetes related) questionnaire during their hospital visit. In each part, subjects nominated five facets of life, judged to be important to them for quality of life (most important rated 5). Each aspect was then weighted by the patient for their current level of satisfaction on a five-point Likert scale (5, completely satisfied; 1, not at all satisfied), and a total score was calculated. Groups were matched for for age, sex, diabetes duration, comorbidities and HbA1C. The means were compared with Student’s t test. Results: The quality of life scores were better for dulaglutide than for liraglutide treated subjects (mean [SD] PCQoL: 66 [61–70] vs 56 [52 - 60], p &lt; 0.05). Discussion: In the diabetes management strategy, a primary therapeutic goal is to address and better the quality of life. In this study we have established that once weekly Dulaglutide offers better quality of life than daily injections of Liraglutide. PCQoL is a patient centered quality of life measurement is quick, simple, repeatable, sensitive, and valid in type 2 diabetes mellitus. References: 1.Rubin R, Peyrot M. Quality of life and diabetes. Diab Metab Res Rev. 1999;15(3):205–18. 2.Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes. N Engl J Med. 1993;329(14):977–86. 3.John C. Pickup, Anna Harris. Assessing Quality of Life for New Diabetes Treatments and Technologies: A Simple Patient-Centered Score. Journal of Diabetes Science and Technology. 2007;1(3):394–99.

Diabetes mellitus in dialysis and renal transplantation

Diabetes mellitus is the commonest cause of end-stage kidney failure worldwide and is a proven and significant risk factor for the development of cardiovascular disease. Renal impairment has a significant impact on the physiology of glucose homeostasis as it reduces tissue sensitivity to insulin and reduces insulin clearance. Renal replacement therapy itself affects glucose control: peritoneal dialysis may induce hyperglycaemia due to glucose-rich dialysate and haemodialysis often causes hypoglycaemia due to the relatively low concentration of glucose in the dialysate. Autonomic neuropathy which is common in chronic kidney disease (CKD) and diabetes increases the risk for asymptomatic hypoglycaemia. Pharmacological options for improving glycaemic control are limited due to alterations to drug metabolism. Impaired glucose tolerance and diabetes are also common in the post-kidney-transplant setting and increase the risk of graft failure and mortality. This review seeks to summarise the literature and tackle the intricacies of glycaemic management in patients with CKD who are either on maintenance haemodialysis or have received a kidney transplant. It outlines changes to glycaemic targets, monitoring of glycaemic control, the use of oral hypoglycaemic agents, the management of severe hyperglycaemia in dialysis and kidney transplantation patients.

AN OPEN LABELLED, RANDOMIZED, CONTROLLED, PROOF OF CONCEPT, COMPARATIVE STUDY TO ANALYZING THE EFFECT OF POLYHERBAL FORMULATIONS VIZ. MADHUNIL (DIABHAR), MADHUYOG (SUGARID) & DIABETOX TREATMENT PLAN FOR THE TREATMENT OF MADHUMEH – DIABETES TYPE 2

Background-Madhumeh – Diabetes Type 2 has a potential to cause a worldwide healthcare crisis hence finally being recognised as a global epidemic. Madhumeh – Diabetes Type 2 patients initially respond to all the measures including Oral Hypoglycaemic Agents, but some of the patients develop resistance to the drugs right from the beginning or in due course .To help society in this regard, there is an option for a Ho-listic treatment, which helps to balance the sugar levels without any side effects. Diabetes Type 2 matches with Madhumeh in Ayurveda, which is one of 20 types of Prameh. Virechan (detoxification) is one of the most Invigorating, Energizing and rejuvenating treatments that helps in Madhumeh. Material and Methods- Patients were randomly selected from the OPD of Ayushakti Ayurved Pvt Ltd, Malad, with classical signs and symptoms of Madhumeh. They received a Blood Test, Diabetox - Virechan karma, selected Herbal formulations and an adjusted Diet. This present study shows that when both tablets Madhunil (Diabhar) and Madhuyog (Sugarid) were administered in newly diagnosed Madhumeh – Diabetes Type 2 patients. Results-We were able to decrease the hyperglycaemic and hyperlipidaemic conditions significantly without any toxic - or side effects. We were also able to minimise the dose of OHA. When these polyherbal formu-lations were used alongside Diabetox - Virechan program (detoxification), we were able to reduce the complications. Conclusion-The above clinical trial reports the hypoglycaemic and hypolipidaemic effect of the polyherbal combinations Madhunil (Diabhar) and Madhuyog (Sugarid).

Evaluation of Pattern of Use of Prescribed Oral Hypoglycaemic Drugs in Newly Diagnosed Diabetic Nephropathy Patients Visiting a Tertiary Care Hospital of Southern Bihar

BACKGROUND Diabetes is the most important risk factor for chronic kidney disease. Because of this, clearance of many oral hypoglycaemic drugs from our body is hampered and time of exposure to these drugs increases. Therefore, patients of diabetes need to be assessed frequently for the development of diabetic nephropathy and the dosage of oral hypoglycaemic drugs should also be modified accordingly. So, the purpose of this study was to evaluate the doses of prescribed OHAs in newly diagnosed diabetic nephropathy patients. METHODS A hospital based observational study was conducted at Narayan Medical College and Hospital, Sasaram, Bihar, India. A total of 600 diagnosed patients of diabetic nephropathy of age more than 18 years visiting for the 1 st time in OPD of general medicine / nephrology department were included in the study after obtaining an informed consent. The results were expressed as a percentage of the assessed population. RESULTS Only about 38% of the total study population was taking doses of Oral Hypoglycaemic Agents (OHAs) according to their GFR status. 62% were taking wrong doses of OHAs with their respective renal function. CONCLUSIONS Treatment of diabetes in a CKD patient is more difficult than in non-CKD patient. GFR status should be monitored on regular basis in patients of diabetes with CKD. A significant number of these patients are still treated with wrong dosage of OHAs for their respective renal function. KEYWORDS Wrong Dose of OHA, Diabetic Nephropathy, Oral Hypoglycaemic Drugs