Therapeutic Management Of Diabetes Mellitus Research Articles

Deciphering the ameliorative effect of Aloe vera (L.) burm. F. extract on histopathological alterations in Streptozotocin-induced WNIN/GR-ob rats

Ethnopharmacological relevanceNatural products have emerged as a novel source in the management of non-communicable diseases, more so in diabetes mellitus and its comorbidities. Aloe vera is widely recognized for its anti-hyperglycemic and anti-hyperlipidemic properties and numerous researchers have identified component (s) from Aloe vera attributing to these therapeutic effects. Aim of the studyThe current work was undertaken to gain insight into the protective effect of Aloe vera (L.) Burm. f. extract to study the cytoarchitecture/histopathological alterations in the target organs in mutant Obese WNIN/GR-Ob rats that were made frank diabetic with streptozotocin. Materials and methodsRats were divided into five groups. 1)WNIN-GR-Ob/control group 2)WNIN-GR-Ob treated with STZ 3)WNIN-GR-Ob + STZ + Sitagliptin 4)WNIN-GR-Ob + STZ + Aloe vera 5)WNIN-GR-Ob/control group + Aloe vera. Histopathological analysis of the pancreas, kidney, liver, and adipocytes was done after 4 weeks of treatment. ResultsThe histopathological examination of STZ-induced diabetic rats revealed significant changes in all the vital organs including cell infiltration, degeneration, and necrosis. Treatment with A. vera negated most of the histopathological changes seen in STZ induced rats. Sitagliptin—which served as a positive control in the present study—reversed the alterations seen in streptozotocin rats. ConclusionConsidering the hypoglycaemic and hypolipidemic activities of Aloe vera that have been previously demonstrated by us, the present study further re-instates the therapeutic efficacy of Aloe vera towards vital organs. It was able to restore islet cells and reduce β-cell damage. In addition, it was also able to aid in kidney tubular regeneration and reverse the degenerative changes brought on by streptozotocin on liver. Further, Aloe vera treated group exhibited moderate hyperplasia with decreased size of adipocytes and reduced macrophage infiltration. Thus, our findings advocate its application as an important nutraceutical in the therapeutic management of diabetes mellitus and associated complications.

A smart device for smart self-monitoring of glycemia in patients with diabetes

A smart device for smart self-monitoring of glycemia in patients with diabetes

Comparative evaluation of efficacy and safety of A Unani coded drug UNIM-221 and Metformin in cases of Diabetes mellitus type-II: A preliminary study

Diabetes mellitus is a major public health problem affecting millions of people worldwide. Available synthetic medicines have serious side effects, therefore, medicines of herbal origin have been widely used in therapeutic management of diabetes mellitus for a long time, and have received renewed attention of scientists globally. The present study envisages to evaluate the comparative efficacy and safety of a Unani coded drug UNIM-221 with an allopathic drug Metformin in diabetes mellitus type II cases. The data presented is a part of multicentric, randomized and open level clinical trials conducted on 32 UNIM-221and 44 cases on Metformin at Regional Research Institute of Unani Medicine, Aligarh, during 2013-2018. The statistical analysis of data presented was done by using one-way analysis of variance (ANOVA) followed by Dennett’s’ test and, p value of ≤0.05 was considered significant. The results were compared with baseline to different follow-up of two groups of diabetes patients treated with Unani and allopathic drug, namely, UNIM-221 and Metformin. We conclude that UNIM-221 has shown a significant and better relief in various symptoms of diabetes mellitus patients viz; polydipsia, polyuria, polyphagia, nocturia, fatigue, loss of weight, burning sensation in palm and soles and giddiness as compared to allopathic drug Metformin. Thus, whereas both the drugs do possess antidiabetc activity and reduce blood glucose level and HbA1c level, respectively, yet the Unani drug UNIM-221 has shown comparatively better rate of efficacy and safety and, therefore, recommended for long time use in diabetes mellitus type II cases without any side effects. Further studies are suggested on a larger group.

Pharmacokinetic and pharmacodynamic interactions of Tinospora cordifolia aqueous extract and hypoglycemic drugs in streptozotocin-induced diabetes in rats

Context: Tinospora cordifolia (Willd.) Miers is an antidiabetic herb globally marketed as a single or polyherbal formulation. The pharmacological activities of T. cordifolia suggest its potential to be co-administered with commonly prescribed oral hypoglycemic drugs in the therapeutic management of diabetes mellitus. Aims: The aim of this study was to evaluate the potential pharmacokinetic (PK) and pharmacodynamic (PD) interactions of the aqueous extract of T. cordifolia (TCE) with metformin (MET), sitagliptin (SITA), and glibenclamide (GLI) in streptozotocin (STZ)-induced diabetes in rats. Settings and Design: The aqueous TCE (400 mg/kg, p.o.) was co-administered with MET (90 mg/kg, p. o.), SITA (10 mg/kg, p. o.), and GLI (1 mg/kg, p. o.) for 28 days in STZ-induced diabetes in rats. Materials and Methods: The PK parameters of the three drugs were calculated using Phoenix WinNonlin®, and PD activity was determined by estimating fasting blood glucose, liver and kidney function tests, and lipid parameters. Further, histopathological examination of pancreatic cells and estimation of pancreatic antioxidant enzymes was carried out. Statistical Analysis Used: The pharmacokinetic parameters were estimated using pharmacokinetic program WinNonlin® version 3.0 (Pharmasight corporation, Mountain view, CA). The pharmacodynamic parameters were analysed using Graph Pad prism Version 6.00 applying one-way ANOVA followed by the Tukey–Kramer post test. Results: No significant PK interaction was observed between TCE and the three oral hypoglycemics. However, a significant improvement was observed in glycemic control and the conditions associated with diabetes mellitus. In addition, no incidences of hypoglycemia were observed. Conclusion: The co-administration of TCE with MET, SITA, and GLI helped in better management of diabetes and associated comorbidities than their individual administrations. There were no significant PK interactions observed. Our findings provide insights into the safety and efficacy of the combination therapy of TCE with MET, SITA, and GLI in the management of diabetes and associated conditions.

Evaluation and Validation of Utility of BD Glucose Vacutainer for Glycosylated Hemoglobin Assay for Timely Therapeutic Management of Diabetes Mellitus

Evaluation and Validation of Utility of BD Glucose Vacutainer for Glycosylated Hemoglobin Assay for Timely Therapeutic Management of Diabetes Mellitus

Opening of liver mitochondrial permeability transition pore in streptozotocin-induced diabetic rats and its inhibition by methanol fraction of Ficus mucoso (Welw) root bark

ObjectiveSeveral pathologies arise from the inappropriate opening of the mitochondrial permeability transition (mPT) pore. In this regard, inhibition of mPT pore represents a cytoprotective approach to preserve mitochondrial function for treatment of diseases characterized by excessive tissue wastage such as diabetes mellitus. The aim of this study, therefore, was to study the effects of fractions of Ficus mucoso, a medicinal plant used in the traditional treatment of diabetes, on mPT pore in normal and streptozotocin (STZ)-induced diabetic rat liver. MethodsDifferent solvent fractions of the crude methanol extract of F. mucoso were obtained by vacuum liquid chromatography and were tested on the mPT pore. Of all the fractions tested, methanol fraction of F. mucoso (MFFM) was the most potent and was used for in vivo studies. Diabetes mellitus was induced by a single intraperitoneal injection of 60 mg/kg STZ, while treatment lasted for 14 d. In vivo, 30 male Wistar rats were divided into five groups: A, normo-glycemic control (distilled water); B, STZ (65 mg/kg; diabetic control); C, STZ + MFFM (25 mg/kg); D, STZ + MFFM (50 mg/kg); E, STZ + glibenclamide (5 mg/kg). The mPT, mitochondrial ATPase activity, lipid peroxidation and cytochrome c release were assessed spectrophotometrically while blood glucose levels were monitored using glucometer. ResultsIn vitro, the solvent fractions of F. mucoso, at all concentrations tested, had no effect on the mPT pore, in the absence of calcium, with no significant release of cytochrome c. Interestingly, calcium-dependent pore opening was inhibited by all solvent fractions of F. mucoso, with the MFFM having the highest inhibitory effect of 83% at 3 mg/mL. Induction of opening of the mPT pore, significant (P < 0.001) enhancement of mitochondrial ATPase activity and elevated malondialdehyde (MDA) levels in STZ-induced diabetes were significantly (P < 0.001) reversed by MFFM and were comparable with the effects of glibenclamide, a standard antidiabetic drug. Also, treatment with MFFM at different doses significantly (P < 0.001) reduced high serum blood glucose compared to the diabetic control. ConclusionF. mucoso could be useful in therapeutic management of diabetes mellitus given its ability to prevent excessive tissue wastage via inhibition of pore opening, and reduction in levels of MDA and serum blood glucose.

Recurrent insulin-induced hypoglycemia induces AngII and COX2 leading to renal (pro)renin receptor expression and oxidative stress

Background: Recurrent insulin-induced hypoglycemia (RIIH) is an avoidable consequence in the therapeutic management of diabetes mellitus. RIIH has been implicated in causing hypertension through an increase in renal and systemic AngII production.Objective: The present study was performed to assess the hypothesis that chronic insulin treatment enhances AngII and COX2 formation which in turn increases (pro) renin receptor (PRR) expression and NADPH oxidase-mediated oxidative stress, leading to renal and cardiac injury.Methods: The present studies were conducted in Male Sprague Dawley rats treated with daily subcutaneous injections of 7u/kg insulin or saline for 14 days. On the 14th day, surgery was performed for treatment infusion (captopril 12mg/kg, NS398 0.3mg/kg or vehicle), and renal interstitial fluid sample and urine collections for biomarker measurements. At the end of the experiments, kidneys and hearts were harvested to evaluate PRR and NOX2 (NADPH oxidase subunit) expression and oxidative stress.Results: We found that RIIH enhanced AngII and COX2 activity, leading to renal PRR expression and NADPH oxidase-induced oxidative stress in the heart and kidney. 8-isoprostane was evaluated as a renal biomarker of oxidative stress, which was induced in insulin treated animals and modulated by captopril and NS398. In addition, there was a slight increase in NGAL, a urinary biomarker of acute kidney injury (AKI), in insulin treated animals when compared to control.Conclusion: These results demonstrate that RIIH induces renal PRR expression and oxidative stress through increasing AngII and COX2 in the heart and kidney, leading to end-organ damage.

Management of Diabetes in Liver Cirrhosis

Diabetes mellitus (DM) is common in patients with liver cirrhosis, indicating a bidirectional relationship between DM and liver cirrhosis. Type 2 DM is a risk factor for development and progression of chronic liver disease including liver cirrhosis, and DM may occur as a complication of liver cirrhosis. Hyperglycemia and hyperinsulinemia have profibrogenic properties on hepatic stellate cells, and contribute to liver damage by promoting inflammation and fibrosis through an increase in mitochodrial oxidative stress mediated by adipokines. The presence of DM in patients with liver cirrhosis is not only related to the poor survival rate but also associated with major complications of cirrhosis. This suggests that optimal management of DM could be beneficial in patients with liver cirrhosis. However, the management of DM in patients with liver cirrhosis is complex because of impaired liver function and of the potential hepatotoxicity of oral hypoglycemic agents. We review the clinical implications and the therapeutic management of DM in patients with liver cirrhosis.

Tight glycemic control in the management of diabetic patients: what has changed since the '90s in the clinical approach?

Tight glycemic control represents one of the major goals of the therapeutic management of diabetes mellitus. However, several clinical studies have reported that an intensive glucose-lowering treatment, especially when insulin or sulfonylureas are used, is associated with an increased risk of hypoglycemia and may exert negative effects on the cardiovascular risk. Hypoglycemia is the major side effect of antidiabetic therapy and it has also been associated with adverse cardiovascular events. The surge of sympathetic activity during hypoglycemic episodes may induce cardiac and cerebral ischemia and promote potentially fatal arrhythmias. In addition, hypoglycemic episodes have a negative effect on patient compliance to the antidiabetic treatment and consequently may worsen glycemic control, thus increasing the risk of micro- and macroangiopathic complications of diabetes. Therefore, in order to counteract the cardiovascular risk it is necessary achieving a good glycemic control through therapeutic strategies associated with a lower risk of hypoglycemia. Unlike treatment with sulfonylureas, glucagon-like peptide-1 analogs and dipeptidyl peptidase-4 inhibitors have been demonstrated to improve metabolic control without inducing hypoglycemia and, therefore, represent a new therapeutic option for type 2 diabetes, which offer the advantage of combining glucose-lowering activity with a low risk of hypoglycemia, thus providing a greater cardiovascular protection.

Extract of Moringa oleifera leaves ameliorates streptozotocin-induced Diabetes mellitus in adult rats

Medicinal plants attract growing interest in the therapeutic management of Diabetes mellitus. Moringa oleifera is a remarkably nutritious vegetable with several antioxidant properties. The present study assessed the possible antioxidant and antidiabetic effects of an aqueous extract of M. oleifera leaves in treating streptozotocin-induced diabetic albino rats. The antidiabetic effects of aqueous extract of M. oleifera leaves were assessed histomorphometrically, ultrastructurally and biochemically. Fasting plasma glucose (FPG) was monitored and morphometric measurements of β-cells of islets of Langerhans (modified Gomori's stain) and collagen fibers (Mallory's trichrome stain) were performed. The antioxidant effects of M. oleifera leaves were determined by measuring the reduced glutathione and lipid peroxidation product, malondialdehyde, in pancreatic tissue. M. oleifera treatment significantly ameliorated the altered FPG (from 380% to 145%), reduced glutathione (from 22% to 73%) and malondialdehyde (from 385% to 186%) compared to control levels. The histopathological damage of islet cells was also markedly reversed. Morphometrically, M. oleifera significantly increased the areas of positive purple modified Gomori stained β-cells (from 60% to 91%) and decreased the area percentage of collagen fibers (from 199% to 120%) compared to control values. Experimental findings clearly indicate the potential benefits of using the aqueous extract of M. oleifera leaves as a potent antidiabetic treatment.

Bio-nanomechanical Detection of Diabetic Marker HbA1c

We report the development of an ultrasensitive immunosensor system for the detection of specific diabetic biomarker glycated hemoglobin (HbA1c) using specific antibody functionalized micromechanical cantilever chips. The biomolecules-induced deflection of the cantilever beam reflects the interplay between the strain energy increase of the cantilever and the free energy reduction of the interaction, providing a unique system for investigating the connection between the nanomechanics and the chemistry of antibody–antigen interaction at very low concentration. Cantilevers were functionalized with specific antibodies using site-directed antibody immobilization technique which was adopted to attach antibody on to the gold substrate. The antibody immobilized cantilevers were used to detect the level of the expressed biomarker in standard samples by adopting direct immunoassay format without using any labels. The assay exhibited an excellent sensitivity for HbA1c in the dynamic range from 0.147 to 1.47 pM. This label-free detection method could be used for fast, high-throughput screening of specific biomarkers for the therapeutic management of diabetes mellitus in clinical diagnostic at a very low cost.

Anti-diabetic activity of oryzanol and its relationship with the anti-oxidant property

Experimental evidence suggests that oxidative stress induced by streptozotocin (STZ) damage the pancreatic beta cells and produce hyperglycemia in rats. The current study was initiated to investigate the effects of oryzanol (OZ), a commercially-important bioactive phytochemical isolated from crude rice bran oil (cRBO) against experimental diabetes as well as the antioxidant potential of the drug. OZ was isolated by a two-step solvent crystallization process from cRBO, which was extracted from fresh rice bran by hexane mediated soxhlet extraction. Oral administration of OZ (50 and 100 mg/kg) reduced the blood glucose level in normal and in STZ (45 mg/kg, intravenous) diabetic rats in both single and multidose study. Oxidative stress produced by STZ was found to be significantly reduced by OZ when compared to control rats, as evident from a significant decrease in the extent of lipid peroxidation (LPO) and increased levels of enzymatic anti-oxidants such as superoxide dismutase (SOD) and reduced glutathione (GSH) in the liver. The findings indicate that OZ possesses the potential to effectively ameliorate the oxidative stress induced by STZ and produce a reduction in blood glucose levels. However, further experiments at the clinical level are warranted to confirm the utility of OZ in the therapeutic management of diabetes mellitus.

Natural Antidiabetic Compound for the Therapeutic Management of Diabetes Mellitus and Its Drug Delivery System

ABSTRACTA single tablet dosage form containing the freeze-dried aqueous leaf extract of Vernonia amygdalina (AD1), suitable for use in the therapeutic management of diabetes mellitus, has been developed. The compaction characteristics of the extract were studied using the Heckel equation. The mechanical properties as well as disintegration and dissolution profile of the compacts were also assessed. The results showed that AD1 exhibited very low densification due to dye filling and addition of filler–binders contributed significantly to their subsequent densification. The tablets produced had good mechanical properties. Of the three filler–binders tested, tablets containing Avicel had the shortest disintegration time of about 5 min, while tablets without any filler–binder had the longest disintegration time of 50 min. Dissolution results (T90%) showed that tablets containing Avicel released 100% of the extract in less than 15 min proving to be the most suitable in acute diabetes. The order of dissolution is Avicel > maize starch > lactose > extract. It is concluded that incorporation of Avicel as a filler–binder in AD1 preparation produced tablets of suitable compaction properties and ensured adequate drug release for the therapeutic management of diabetes mellitus.

Diabète chez le patient souffrant de schizophrénie et vieillissement

Patients with schizophrenia have a higher rate of diabetes mellitus compared to that of the general population. It seems that the frequency of diabetes mellitus is more important in older schizophrenic patients. Many factors can contribute to glycemic perturbation such as negative symptoms which are greater with time, unbalanced diets, toxic habits and consumption of neuroleptics. There are now consensuses for evaluation before any prescription of neuroleptics and surveillance of their potential complications such as diabetes mellitus. But this surveillance may be hard to apply to schizophrenic patients because their illness tends to isolate them from the society and the medical community. But schizophrenic patients who also suffer of diabetes mellitus have a higher risk of physical illness with a higher mortality rate. The association between schizophrenia and diabetes mellitus has to be underlined as well as screening and therapeutic management of diabetes mellitus in this population.