Random Blood Glucose Concentration Research Articles

The Effect of HIV on the Association of Hyperglycaemia and Active Tuberculosis in Zambia, a Case-Control Study.

To determine if HIV modifies the association between hyperglycaemia and active tuberculosis in Lusaka, Zambia. A case-control study among newly-diagnosed adult tuberculosis cases and population controls in three areas of Lusaka. Hyperglycaemia is determined by random blood glucose (RBG) concentration measured at the time of recruitment; active tuberculosis disease by clinical diagnosis, and HIV status by serological result. Multivariable logistic regression is used to explore the primary association and effect modification by HIV. The prevalence of RBG concentration ≥ 11.1mmol/L among 3843 tuberculosis cases was 1.4% and among 6977 controls was 1.5%. Overall, the adjusted odds ratio of active tuberculosis was 1.60 (95% CI 0.91-2.82) comparing those with RBG concentration ≥ 11.1- < 11.1mmol/L. The corresponding adjusted odds ratio among those with and without HIV was 5.47 (95% CI 1.29-23.21) and 1.17 (95% CI 0.61-2.27) respectively; p-value for effect modification by HIV = 0.042. On subgroup analysis, the adjusted odds ratio of smear/Xpert-positive tuberculosis was 2.97 (95% CI 1.49-5.90) comparing RBG concentration ≥ 11.1- < 11.1mmol/L. Overall, no evidence of association between hyperglycaemia and active tuberculosis was found, though among those with HIV and/or smear/Xpert-positive tuberculosis there was evidence of association. Differentiation of hyperglycaemia caused by diabetes mellitus and stress-induced hyperglycaemia secondary to tuberculosis infection is important for a better understanding of these findings.

The association of admission random blood glucose concentration and body-mass index with mortality in COVID-19 patients.

This study aimed to investigate the association between hyperglycemia and body mass index (BMI), along with other associated comorbidities in hospitalized COVID-19 patients among the Indonesian population. This was a retrospective study conducted at Hasan Sadikin Hospital, Bandung between March 1, 2020, and August 30, 2020. Data were analyzed using the chi-square test for categorical data and unpaired t-test and Mann-Whitney alternative test for numerical data using SPSS version 24.0 (IBM SPSS Statistics for Windows, Version 24.0. IBM, Armonk, NY, USA) and GraphPad Prism version 7.0 for Windows. A total of 142 hospitalized COVID-19 patients were documented between March and August 2020 at the Hasan Sadikin Hospital. Among the 142 patients, 116 (81.7%) survived, while 26 (18.3%) died. Sex, age, BMI, number of comorbidities, heart rate, respiratory rate, peripheral oxygen saturation, platelet count, random blood glucose (RBG), and length of stay (LOS) were significantly associated with mortality. Multivariate analyses demonstrated that admission RBG levels > 140 mg/dl were independently associated with an increased risk of mortality in COVID-19 patients (OR 4.3, 95% CI 1.1-17.5, p = 0.043), while BMI > 25 kg/m2 was significantly associated with reduced mortality (OR, 0.22; 95% CI 0.05-0.88, p = 0.033). Admission hyperglycemia, indicated by an increase in RBG levels >140 mg/dL, is independently associated with an increased risk of mortality in hospitalized COVID-19 patients, while obesity (BMI >25 kg/m2) might have protective properties against the risk of death.

Advanced glycation end products as predictors of renal function in youth with type 1 diabetes

To examine if skin autofluorescence (sAF) differed in early adulthood between individuals with type 1 diabetes and age-matched controls and to ascertain if sAF aligned with risk for kidney disease. Young adults with type 1 diabetes (N = 100; 20.0 ± 2.8 years; M:F 54:46; FBG-11.6 ± 4.9 mmol/mol; diabetes duration 10.7 ± 5.2 years; BMI 24.5(5.3) kg/m2) and healthy controls (N = 299; 20.3 ± 1.8 years; M:F-83:116; FBG 5.2 ± 0.8 mmol/L; BMI 22.5(3.3) kg/m2) were recruited. Skin autofluorescence (sAF) and circulating AGEs were measured. In a subset of both groups, kidney function was estimated by GFRCKD-EPI CysC and uACR, and DKD risk defined by uACR tertiles. Youth with type 1 diabetes had higher sAF and BMI, and were taller than controls. For sAF, 13.6% of variance was explained by diabetes duration, height and BMI (Pmodel = 1.5 × 10–12). In the sub-set examining kidney function, eGFR and sAF were higher in type 1 diabetes versus controls. eGFR and sAF predicted 24.5% of variance in DKD risk (Pmodel = 2.2 × 10–9), which increased with diabetes duration (51%; Pmodel < 2.2 × 10–16) and random blood glucose concentrations (56%; Pmodel < 2.2 × 10–16). HbA1C and circulating fructosamine albumin were higher in individuals with type 1 diabetes at high versus low DKD risk. eGFR was independently associated with DKD risk in all models. Higher eGFR and longer diabetes duration are associated with DKD risk in youth with type 1 diabetes. sAF, circulating AGEs, and urinary AGEs were not independent predictors of DKD risk. Changes in eGFR should be monitored early, in addition to uACR, for determining DKD risk in type 1 diabetes.

T-Cell Expression and Release of Kidney Injury Molecule-1 in Response to Glucose Variations Initiates Kidney Injury in Early Diabetes.

Half of the mortality in diabetes is seen in individuals <50 years of age and commonly predicted by the early onset of diabetic kidney disease (DKD). In type 1 diabetes, increased urinary albumin-to-creatinine ratio (uACR) during adolescence defines this risk, but the pathological factors responsible remain unknown. We postulated that early in diabetes, glucose variations contribute to kidney injury molecule-1 (KIM-1) release from circulating T cells, elevating uACR and DKD risk. DKD risk was assigned in youth with type 1 diabetes (n = 100; 20.0 ± 2.8 years; males/females, 54:46; HbA1c 66.1 [12.3] mmol/mol; diabetes duration 10.7 ± 5.2 years; and BMI 24.5 [5.3] kg/m2) and 10-year historical uACR, HbA1c, and random blood glucose concentrations collected retrospectively. Glucose fluctuations in the absence of diabetes were also compared with streptozotocin diabetes in apolipoprotein E -/- mice. Kidney biopsies were used to examine infiltration of KIM-1-expressing T cells in DKD and compared with other chronic kidney disease. Individuals at high risk for DKD had persistent elevations in uACR defined by area under the curve (AUC; uACRAUC0-10yrs, 29.7 ± 8.8 vs. 4.5 ± 0.5; P < 0.01 vs. low risk) and early kidney dysfunction, including ∼8.3 mL/min/1.73 m2 higher estimated glomerular filtration rates (modified Schwartz equation; Padj < 0.031 vs. low risk) and plasma KIM-1 concentrations (∼15% higher vs. low risk; P < 0.034). High-risk individuals had greater glycemic variability and increased peripheral blood T-cell KIM-1 expression, particularly on CD8+ T cells. These findings were confirmed in a murine model of glycemic variability both in the presence and absence of diabetes. KIM-1+ T cells were also infiltrating kidney biopsies from individuals with DKD. Healthy primary human proximal tubule epithelial cells exposed to plasma from high-risk youth with diabetes showed elevated collagen IV and sodium-glucose cotransporter 2 expression, alleviated with KIM-1 blockade. Taken together, these studies suggest that glycemic variations confer risk for DKD in diabetes via increased CD8+ T-cell production of KIM-1.

Effect of probucol on autophagy and apoptosis in the penile tissue of streptozotocin-induced diabetic rats.

Autophagy and apoptosis have been regarded as important processes in the development of diabetic erectile dysfunction (DMED). Probucol is considered to have anti-apoptotic effects, but its relationship with autophagy has not been reported. The aim of this study was to investigate the effects and mechanisms of probucol on erectile function. Thirty Sprague–Dawley (SD) male rats (12 weeks old) were fasted for 12 h. Twenty SD rats were injected with a single intraperitoneal injection of 60 mg kg−1 streptozotocin (STZ). Ten rats were given vehicle only and used as a sham group. After 72 h, 20 STZ-treated rats with random blood glucose concentrations consistently greater than 16.7 mmol l−1 were used as successfully established diabetic rats. The diabetic rats were divided randomly into two groups and treated with a daily gavage of probucol at a dose of 0 or 500 mg kg−1 for 12 weeks. After treatment, the intracavernous pressure (ICP) was used to measure erectile function upon electrical stimulation of the cavernous nerve. After euthanasia, penile tissue was examined using immunohistochemistry and Western blot to assess the protein levels of B-cell lymphoma-2 (Bcl-2), BCL2-associated X (Bax), microtubule-associated protein light chain 3-II (LC3-II), mammalian target of rapamycin (mTOR), and sequestosome 1 (P62). Caspase-3 activity was measured to determine apoptosis using a caspase-3 assay kit. After 12 weeks of treatment, the erectile function of the probucol group was significantly better than that of the DM group (P < 0.05). Bax and LC3-II protein expression and caspase-3 activity were significantly lower in the probucol group than those in the DM group (all P < 0.05), while Bcl-2, mTOR, and P62 protein expression levels were significantly higher than those in the DM group (all P < 0.05). We demonstrated that probucol inhibited apoptosis and autophagy in STZ-induced diabetic rats.

Random Blood Glucose Concentrations and their Association with Body Mass Index in Indian School Children.

Objective and Aims:Overweight/obese children are at risk of developing type 2 diabetes mellitus. Random glucose elevations provide early warning signs of glycemic dysregulation. To assess random blood glucose (RBG) concentrations and risk factors associated with prediabetes in children aged 3-18 years from six Indian regions.Method:Multicenter, cross sectional, observational school-based study; multi-stage stratified random sampling was carried out. Height and weight measured; body mass index (BMI) was computed. RBG measured using a glucometer. National sample survey was used for dietary patterns. Data were analyzed using SPSS 25.0 for Windows.Setting:Study centers were from Maharashtra, Gujarat, Chhattisgarh, Assam, Tamil Nadu and Punjab from 40 selected schools.Participant:Children aged 3-18 years were measured.Results:Data on 14339 subjects (7413 boys) were analyzed. Prevalence of obesity was 5.8% and overweight-10.6%. Overall, 1% had low (<3 mmol/L), 93.7% in reference range (3.9-7.2 mmol/L) and 5.3% had elevated RBG (>7.2 mmol/L). With increasing mean BMI, there was increase in RBG concentrations. Children from Tamil Nadu were more likely to have RBG outside reference range compared to other regions (P < 0.05). Assam and Punjab had highest prevalence of RBG and BMI within reference range. Energy intake partly explained regional variations. Multivariate analysis showed male gender, urban residency, age >10 yrs (girls) and 13 yrs (boys), and overweight or obesity were predictive of prediabetes.Conclusion:Increased prevalence of overweight, obesity and prediabetes in Indian children are a matter of concern. Regional differences suggest that strategies to prevent obesity and combat perturbations in blood sugar may have to be customized.

Probucol improves erectile function via Activation of Nrf2 and coordinates the HO-1 / DDAH / PPAR-γ/ eNOS pathways in streptozotocin-induced diabetic rats

BackgroundDiabetic erectile dysfunction (DMED) is mainly attributed to oxidative stress, and Nrf2 plays an important role in cellular antioxidation and regulates NO production in the vascular endothelium. Probucol maintains endothelial function through its antioxidant activity. This study investigated the efficacy and mechanism of probucol in improving erectile function in streptozotocin-induced diabetic rats. MethodsIn our study, thirty 12-week-old Sprague-Dawley male rats were fasted for 12 h. All rats received a 1-time injection of intraperitoneal streptozotocin(60 mg/kg) or vehicle. After 72 h, STZ-treated rats (with random blood glucose concentrations consistently greater than 16.7 mmol/L) were considered diabetic. The diabetic rats were randomly assigned into 2 groups and treated with daily gavage feedings of probucol at doses of 0 and 500 mg/kg for 12 weeks. A positive control group underwent intraperitoneal injection of normal saline followed by daily gavage of saline solution. Erectile function was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure measurement. After euthanasia, penile tissue was investigated using immunohistochemistry, Western blot, and ELISA to assess the proteins of Nrf2/HO-1/DDAH/PPAR-γ/eNOS pathways. ResultsAfter treatment, the rats in the probucol group presented significantly improved erectile function (P < 0.05) than that of the diabetic group without probucol treatment (DM). Also, protein expression of Nrf2, DDAH, PPAR-γ, HO-1 and eNOS was significantly higher than that of the DM group (P < 0.05). CGMP concentrations and SOD concentrations of probucol-treated rats were higher than those of DM group (P < 0.05). The MDA levels and ADMA levels were significantly lower than those of DM group rats (P < 0.05). ConclusionProbucol can improve erectile function via activation of Nrf2, which coordinates the HO-1/DDAH/PPAR-γ/eNOS pathways in streptozotocin-induced diabetic rats.

Cardiovascular Risk Factors in a Suburban Community in Nigeria.

The burden of hypertension, a silent killer, continues to increase in low- and middle-income countries. This study evaluated blood pressure (BP) in healthy adults to determine their risk of developing hypertension and to reduce associated morbidity of the disease. Overall, 182 subjects aged >16 years participated in the study. Systolic (SBP) and diastolic blood pressure (DBP) was measured after a resting period using mercury sphygmomanometer. Random blood glucose (RBG) concentration was also determined. Regression models were used to determine risk of high BP with p values < 0.05 indicating statistical difference. Prehypertension was present in 36.8% population and high BP in 31% individuals with hypertensive symptoms. DBP ≥ 90 mmHg was prevalent in the undiagnosed group, while diabetes comorbidity was detected in only 4 individuals. High BP or diabetes was not detected in those <20 year olds. Age > 35 years was an independent risk (likelihood ratio: 22.56, p < 0.0001); this increases to 26.48 (p < 0.0001) in the presence prediabetes and RBG > 100 mg/dl. Undiagnosed hypertension rate is high in the study area, and urgent interventions for large scale screening and management of the disease are required to reduce the burden of hypertension in Nigeria.

Efficacy of sitagliptin for the hospital management of general medicine and surgery patients with type 2 diabetes (Sita-Hospital): a multicentre, prospective, open-label, non-inferiority randomised trial

The role of incretin-based drugs in the treatment of patients with type 2 diabetes admitted to hospital has not been extensively assessed. In this study, we compared the safety and efficacy of a dipeptidyl peptidase-4 inhibitor (sitagliptin) plus basal insulin with a basal-bolus insulin regimen for the management of patients with type 2 diabetes in general medicine and surgery in hospitals. We did a multicentre, prospective, open-label, non-inferiority randomised clinical trial (Sita-Hospital) in five hospitals in the USA, enrolling patients aged 18-80 years with type 2 diabetes and a random blood glucose concentration of 7·8-22·2 mmol/L who were being treated with diet or oral antidiabetic drugs or had a total daily insulin dose of 0·6 units per kg or less, admitted to general medicine and surgery services. We randomly assigned patients (1:1) to receive either sitagliptin plus basal glargine once daily (the sitagliptin-basal group) or a basal-bolus regimen with glargine once daily and rapid-acting insulin lispro or aspart before meals (the basal-bolus group) during the hospital stay. All other antidiabetic drugs were discontinued on admission. The randomisation was achieved by computer-generated tables with block stratification according to randomisation blood glucose concentrations (ie, higher or lower than 11·1 mmol/L). The primary endpoint of the trial was non-inferiority in mean differences between groups in their daily blood glucose concentrations during the first 10 days of therapy (point-of-care measurements; non-inferiority was deemed a difference <1 mmol/L). The safety endpoints included hypoglycaemia and uncontrolled hyperglycaemia leading to treatment failure. All participants who received at least one dose of study drug were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT01845831. Between Aug 23, 2013, and July 27, 2015, we recruited 279 patients, and randomly assigned 277 to treatment; 138 to sitagliptin-basal and 139 to basal-bolus. The length of stay in hospital was similar for both groups (median 4 days [IQR 3-8] vs 4 [3-8] days, p=0·54). The mean daily blood glucose concentration in the sitagliptin-basal group (9·5 mmol/L [SD 2·7]) was not inferior to that in the basal-bolus group 9·4 mmol/L [2·7]) with a mean blood glucose difference of 0·1 mmol/L (95% CI -0·6 to 0·7). No deaths occurred in this trial. Treatment failure occurred in 22 patients (16%) in the sitagliptin-basal group versus 26 (19%) in the basal-bolus group (p=0·54). Hypoglycaemia occurred in 13 patients (9%) in the sitagliptin-basal group and in 17 (12%) in the basal-bolus group (p=0·45). No differences in hospital complications were noted between groups. Seven patients (5%) developed acute kidney injury in the sitagliptin-basal group and six (4%) in the basal-bolus group. One patient (0·7%) developed acute pancreatitis (in the basal-bolus group). The trial met the non-inferiority threshold for the primary endpoint, because there was no significant difference between groups in mean daily blood glucose concentrations. Treatment with sitagliptin plus basal insulin is as effective and safe as, and a convenient alternative to, the labour-intensive basal-bolus insulin regimen for the management of hyperglycaemia in patients with type 2 diabetes admitted to general medicine and surgery services in hospital in the non-intensive-care setting. Merck.

The association of hyperglycaemia with prevalent tuberculosis: a population-based cross-sectional study.

BackgroundSystematic reviews suggest that the incidence of diagnosed tuberculosis is two- to- three times higher in those with diabetes mellitus than in those without. Few studies have previously reported the association between diabetes or hyperglycaemia and the prevalence of active tuberculosis and none in a population-based study with microbiologically-defined tuberculosis. Most have instead concentrated on cases of diagnosed tuberculosis that present to health facilities. We had the opportunity to measure glycaemia alongside prevalent tuberculosis. A focus on prevalent tuberculosis enables estimation of the contribution of hyperglycaemia to the population prevalence of tuberculosis.MethodsA population-based cross-sectional study was conducted among adults in 24 communities from Zambia and the Western Cape (WC) province of South Africa. Prevalent tuberculosis was defined by the presence of a respiratory sample that was culture positive for M. tuberculosis. Glycaemia was measured by random blood glucose (RBG) concentration. Association with prevalent tuberculosis was explored across the whole spectrum of glycaemia.ResultsAmong 27,800 Zambian and 11,367 Western Cape participants, 4,431 (15.9%) and 1,835 (16.1%) respectively had a RBG concentration ≥7.0 mmol/L, and 405 (1.5%) and 322 (2.8%) respectively had a RBG concentration ≥11.1 mmol/L. In Zambia, the prevalence of tuberculosis was 0 · 5% (142/27,395) among individuals with RBG concentration <11.1 mmol/L and also ≥11.1 mmol/L (2/405); corresponding figures for WC were 2 · 5% (272/11,045) and 4 · 0% (13/322). There was evidence for a positive linear association between hyperglycaemia and pulmonary prevalent tuberculosis. Taking a RBG cut-off 11.1 mmol/L, a combined analysis of data from Zambian and WC communities found evidence of association between hyperglycaemia and TB (adjusted odds ratio = 2 · 15, 95% CI [1 · 17–3 · 94]). The population attributable fraction of prevalent tuberculosis to hyperglycaemia for Zambia and WC combined was 0.99% (95% CI 0 · 12%–1.85%) for hyperglycaemia with a RBG cut-off of 11.1 mmol/L.ConclusionsThis study demonstrates an association between hyperglycaemia and prevalent tuberculosis in a large population-based survey in Zambia and Western Cape. However, assuming causation, this association contributes little to the prevalence of TB in these populations.

Diabetes mellitus in Zambia and the Western Cape province of South Africa: Prevalence, risk factors, diagnosis and management

AimsTo determine the prevalence of and risk factors for diabetes mellitus and examine its diagnosis and management in the study communities. MethodsThis is a population-based cross-sectional study among adults in 24 communities from Zambia and the Western Cape (WC) province of South Africa. Diabetes is defined as a random blood glucose concentration (RBG)⩾11.1mmol/L, or RBG<11.1mmol/L but with a self-reported prior diabetes diagnosis. For individuals with a prior diagnosis of diabetes, RBG<7.8mmol/L was considered to be an acceptable level of glycaemia. ResultsAmong 45,767 Zambian and 12,496 WC participants the age-standardised prevalence of diabetes was 3.5% and 7.2% respectively. The highest risk groups identified were those of older age and those with obesity. Of those identified to have diabetes, 34.5% in Zambia and 12.7% in WC were previously unaware of their diagnosis. Among Zambian participants with diabetes, this proportion was lower among individuals with better education or with higher household socio-economic position. Of all those with previously diagnosed diabetes, 66.0% in Zambia and 59.4% in WC were not on any diabetes treatment, and 34.4% in Zambia and 32.7% in WC had a RBG concentration beyond the recommended level, ⩾7.8mmol/L. ConclusionsThe diabetes risk factor profile for our study communities is similar to that seen in high-income populations. A high proportion of individuals with diabetes are not on diabetes treatment and of those on treatment a high proportion have high glycaemic concentrations. Such data may assist in healthcare planning to ensure timely diagnosis and management of diabetes.

DJ-1 Protects Pancreatic Beta Cells from Cytokine- and Streptozotocin-Mediated Cell Death.

A hallmark feature of type 1 and type 2 diabetes mellitus is the progressive dysfunction and loss of insulin-producing pancreatic beta cells, and inflammatory cytokines are known to trigger beta cell death. Here we asked whether the anti-oxidant protein DJ-1 encoded by the Parkinson’s disease gene PARK7 protects islet cells from cytokine- and streptozotocin-mediated cell death. Wild type and DJ-1 knockout mice (KO) were treated with multiple low doses of streptozotocin (MLDS) to induce inflammatory beta cell stress and cell death. Subsequently, glucose tolerance tests were performed, and plasma insulin as well as fasting and random blood glucose concentrations were monitored. Mitochondrial morphology and number of insulin granules were quantified in beta cells. Moreover, islet cell damage was determined in vitro after streptozotocin and cytokine treatment of isolated wild type and DJ-1 KO islets using calcein AM/ethidium homodimer-1 staining and TUNEL staining. Compared to wild type mice, DJ-1 KO mice became diabetic following MLDS treatment. Insulin concentrations were substantially reduced, and fasting blood glucose concentrations were significantly higher in MLDS-treated DJ-1 KO mice compared to equally treated wild type mice. Rates of beta cell apoptosis upon MLDS treatment were twofold higher in DJ-1 KO mice compared to wild type mice, and in vitro inflammatory cytokines led to twice as much beta cell death in pancreatic islets from DJ-1 KO mice versus those of wild type mice. In conclusion, this study identified the anti-oxidant protein DJ-1 as being capable of protecting pancreatic islet cells from cell death induced by an inflammatory and cytotoxic setting.

Hypoglycemic and hypolipidemic activities of aqueous extract of flowers from Nycantus arbor-tristis L. in male mice.

BackgroundBoiled aqueous extract of flowers (AEF) from Nyctanthes arbor-tristis L. are used in Sri Lankan traditional Ayruvedic Medicine to manage diabetes mellitus. AEF has widely been used as a folk medicine for the treatment of various ailments due to its therapeutic activity. However, little is known concerning therapeutic activity of the extract as well as its underline mechanisms and safety. Diabetes is known to increase low-density cholesterol and decrease high-density cholesterol thus triggering coronary diseases. Hence, the primary objective of the present study is to investigate the hypoglycemic and hypolipidemic activities of the AEF.MethodsAEF was prepared and male mice (n = 9 group) were gavaged either with 250, 500 and 750 mg/kg of AEF or distilled water (DW). Subsequently, fasting and random blood glucose concentrations were determined. To investigate mechanisms of actions of AEF, animals were orally administered with 500 mg/kg or the vehicle (DW) and glucose tolerance was performed before and after glucose challenge. For further studies, in vitro alpha-amylase assay and glucose absorption from the gastrointestinal tract were performed using 500 mg/kg of the extract. Additionally, glycogen content in the liver and skeletal muscles, a complete lipid profile assay, and toxicological and biochemical parameters were conducted after a chronic study.ResultsFive hundred mg/kg and 750 mg/kg of AEF significantly (p < 0.01) reduced fasting blood glucose levels respectively by 49 and 39 % at 4 h post-treatment, while 500 mg/kg of AEF also decreased the random blood glucose level significantly (p <0.01) by 32 % at 4 h post-treatment. AEF significantly inhibited glucose absorption by 85 % from the intestine and increased diaphragm uptake of glucose by 64 %. The extract also exhibited inhibition (16.66 %) of alpha-amylase enzyme activity. It also decreased the level of total cholesterol (by 44.8 %), triglyceride (by 53 %) and increased (by 57 %) the high-density lipoprotein cholesterol. Treatment with AEF did not induce any overt signs of toxicity or hepatotoxicity.ConclusionResults the present study indicated that AEF possess hypoglycemic and hypolipdemic properties. Therefore, AEF could be used as an alternative medicine in management of diabetes mellitus.

Hypoglycaemic effect of the methanolic extract of Aporusa lindleyana leaves on rats

The Journal of the National Science Foundation of Sri Lanka publishes the results of research in all aspects of Science and Technology. The journal also has a website at http://www.nsf.gov.lk/. 2021 Impact Factor: 0.682The JNSF provides immediate open access to its content on the principle that making research freely available to the public supports a greater global exchange of knowledge.

Influence of chronic Cigarette Smoking on Serum Biochemical Profile among Sudanese smokers

Context: Cigarette smoking is a risk factor for wide range of diseases; however, still there are no laboratory screening tests for early detection of the possible biochemical derangements induced by smoking. Aim: to evaluate serum cholesterol, liver enzymes, uric acid and hemoglobin concentrations in smokers regardless of their present complain. Materials and Methods: the study involved a control group of apparently healthy non-smokers (N = 105) matched for age with a test group of smokers (N = 105). The age range of both groups was 25-63 years. Random blood glucose (RBG), serum cholesterol, uric acid, liver enzymes and haemoglobin concentrations were measured according to the standards. Appropriate statistical tests were used to assess significant difference in the means of the studied concentrations between smokers and the control group. Results: The smokers showed significantly higher RBG (M±SD = 143.7±27.0 mg/dl), aspartate transaminase (M±SD = 26.2±6.0 U/L), alanine transaminase (25.0±5.3 U/L) and haemoglobin (M±SD = 13.5±2.0 g/dl) levels compared to with non-smokers (M±SD = 127.9±26.4 mg/dl, 23.9±6.1 U/L, 22.6±10.1 U/L, 12.8±1.9 g/dl respectively, P < 0.05). In contrast, uric acid concentrations were less in smokers (M±SD = 4.9±0.8 mg/dl) compared with the control group (M±SD = 5.1±0.7 mg/dl and, P = 0.048). Cholesterol and alkaline phosphatase concentrations were not significantly different in the studied groups. Conclusion: the study added further evidences for the possible harmful consequences of smoking including augmented oxidative stress as indicated by low serum uric acid levels and high liver transaminases concentrations, hyperglycaemia and high haemoglobin concentrations.

Kidney-Targeted Transplantation of Mesenchymal Stem Cells by Ultrasound-Targeted Microbubble Destruction Promotes Kidney Repair in Diabetic Nephropathy Rats

We test the hypothesis that ultrasound-targeted microbubble destruction (UTMD) technique increases the renoprotective effect of kidney-targeted transplantation of bone-marrow-derived mesenchymal stem cells (BM-MSCs) in diabetic nephropathy (DN) rats. Diabetes was induced by streptozotocin injection (60 mg/Kg, intraperitoneally) in Sprague-Dawley rats. MSCs were administered alone or in combination with UTMD to DN rats at 4 weeks after diabetes onset. Random blood glucose concentrations were measured at 1, 2, 4, and 8 weeks, and plasma insulin levels, urinary albumin excretion rate (UAER) values, the structures of pancreas and kidney, the expressions of TGF-β1, synaptopodin, and IL-10 were assessed at 8 weeks after MSCs transplantation. MSCs transplantation decreased blood glucose concentrations and attenuated pancreatic islets/β cells damage. The permeability of renal interstitial capillaries and VCAM-1 expression increased after UTMD, which enhanced homing and retention of MSCs to kidneys. MSCs transplantation together with UTMD prevented renal damage and decreased UAER values by inhibiting TGF-β1 expression and upregulating synaptopodin and IL-10 expression. We conclude that MSCs transplantation reverts hyperglycemia; UTMD technique noninvasively increases the homing of MSCs to kidneys and promotes renal repair in DN rats. This noninvasive cell delivery method may be feasible and efficient as a novel approach for personal MSCs therapy to diabetic nephropathy.

Comparison of glycated albumin and hemoglobin A1c levels in diabetic subjects on hemodialysis

Glycated albumin is thought to more accurately reflect glycemic control in diabetic hemodialysis patients than hemoglobin A(1c) because of shortened red cell survival. To test this, glycated hemoglobin and albumin levels were measured in blood samples collected from 307 diabetic subjects of whom 258 were on hemodialysis and 49 were without overt renal disease. In diabetic subjects with renal disease, relative to those without, the mean serum glucose and glycated albumin concentrations were significantly higher while hemoglobin A(1c) tended to be lower. The glycated albumin to hemoglobin A(1c) ratio was significantly increased in dialysis patients compared with the controls. Hemoglobin A(1c) was positively associated with hemoglobin and negatively associated with the erythropoietin dose in hemodialysis patients, whereas these factors and serum albumin did not significantly impact glycated albumin levels. Using best-fit multivariate models, dialysis status significantly impacted hemoglobin A(1c) levels without a significant effect on glycated albumin. Our results show that in diabetic hemodialysis patients, hemoglobin A(1c) levels significantly underestimate glycemic control while those of glycated albumin more accurately reflect this control.

The Effect of Flutamide on Systemic and Renal Hemodynamics in Zucker Diabetic Rats: Paradoxic Renal Vasodilator Response to Endothelin-1 and TXA2 Receptor Activation in Female Sex

There is increasing evidence that endogenous sex hormones regulate vascular reactivity, and testosterone may contribute to the worse prognosis for renal disease in men. Male Zucker diabetic rats exhibit improved renal hemodynamic responses after castration. It is, however, unclear whether endogenous testosterone affects renal and systemic microcirculatory responses in the female sex, especially in type 2 diabetes. To test the hypothesis that endogenous testosterone in the female Zucker diabetic rat exerts a pathophysiologically relevant modulation of endothelial and renal microvascular function. Female Zucker diabetic rats (FZDR) aged 5-6 weeks and from the same litter were divided into 2 groups (n = 6-8 each). The experimental group received the androgen receptor blocker flutamide, dissolved in alcohol and added to their drinking water (500 mL) at 20 mg/rat/week. The control FZDR received only the alcohol vehicle added to the same volume of drinking water. Both FZDR groups were treated for 3 months before undergoing the hemodynamic studies. A sex comparison control group of male Zucker diabetic rats (MZDR), also aged 5-6 weeks, was studied, following same protocol. Mean arterial pressure (MAP) and renal cortical blood flow (RCF) response to phenylephrine, acetylcholine, TXA2-mimetic U46619, endothelin-1 (ET-1), angiotensin II, and L-NG-nitro arginine methyl ester were studied. Furthermore, the role of protein kinase C in the responses was assessed using phorbol-12,13 dibutyrate 10(-4) M. The impact of flutamide on body weights and blood glucose of the rats were also determined. Flutamide-treated FZDR had a significant reduction in body weight/adiposity to 432 +/- 44 g, compared to controls at 553 +/- 37 g (P = 0.045), and random blood glucose concentration of 185 +/- 44 g/dL, compared to the control FZDR at 475 +/- 34 g/dL (P = 0.002). Vehicle-treated FZDR (n = 6-8), exhibited little or no systemic or renal response to any of the agonists. By contrast, flutamide treatment of FZDR (n = 5-7) caused a normalization of the dose-dependent MAP and RCF pressor response to phenylephrine [P < 0.005, analysis of variance (ANOVA)] and the vasodilator response to acetylcholine (P <. 0.01, ANOVA). Flutamide-treated FZDR showed enhanced pressor response to U46619 (P = 0.024, ANOVA), ET-1, and angiotensin II (P < 0.03, ANOVA). Surprisingly, the augmented systemic pressor action of U46619 and ET-1 was accompanied by a renal vasodilator action, with paradoxic RCF increases to U46619 (P < 0.003, ANOVA) and to ET-1 (P < 0.001, ANOVA) only in flutamide-treated FZDR. By contrast, flutamide-treated MZDR exhibited no significant change in body weight and an attenuation of the vasoconstrictor responses and enhanced nitric oxide-mediated dilatation compared with male controls. However, no specific effect on ET-1 or TXA2 receptor-mediated renal perfusion was discernible. Both L-NG-nitro arginine methyl ester and the protein kinase C agonist phorbol-12,13 dibutyrate [10(-4)M] significantly increased MAP and reduced RCF (P < 0.03) in the experimental FZDR compared with their controls. Flutamide administration to FZDR resulted in the reversal of abnormal systemic and renal alpha-1-mediated vasoconstriction and enhanced nitric oxide-mediated vasodilation. Flutamide caused a paradoxic but specific increase in renal perfusion during ET-1 and TXA2 receptor activation, which could be renoprotective in females. The salutary effects of flutamide on vascular reactivity in the FZDR may be mediated by a protein kinase C-dependent mechanism. These results are compatible with the notion that endogenous testosterone may regulate systemic and renal microcirculation in the female sex and in the type 2 diabetic state.

Management of gestational diabetes mellitus and pharmacists' role in patient education.

The pathophysiology, diagnosis, complications, and management of gestational diabetes mellitus (GDM) are discussed, along with considerations in setting up a pharmacist-run GDM education service. GDM occurs when there is insufficient insulin secretion to counteract pregnancy-related decreases in insulin sensitivity. GDM can be diagnosed by using the same criteria used to diagnose types 1 and 2 diabetes mellitus (DM): a fasting blood glucose concentration of > 126 mg/dL on two separate occasions or a random blood glucose concentration of > 200 mg/dL on two separate occasions. Complications of GDM include maternal type 2 DM, maternal hypertension, macrosomia, shoulder dystocia, and neonatal hypoglycemia. GDM is managed with medical nutritional therapy (MNT), exercise, and therapy with human or synthetic insulin. The American Diabetes Association recommends starting insulin therapy when MNT fails to maintain plasma glucose concentrations at < or = 105 mg/dL during fasting, < or = 155 mg/dL one hour after eating, or < or = 130 mg/dL two hours after eating. A pharmacist interested in establishing a GDM education service must assess the feasibility of providing such education in his or her practice and whether such a program is needed. Other considerations are developing a curriculum, marketing the service, maintaining records, calculating costs, and obtaining reimbursement. GDM can have serious effects if not treated properly. A major part of managing GDM involves educating the patient about diet, exercise, blood glucose self-monitoring, and insulin self-administration. A successful pharmacist-run GDM education service must have a market and prices sufficient to generate profit.

1P-0023 Amount of thrombus at culprit lesion of acute myocardial infarction is dependent on angioscopically determined coronary atherosclerosis

Diabetic erectile dysfunction (DMED) is mainly attributed to oxidative stress, and Nrf2 plays an important role in cellular antioxidation and regulates NO production in the vascular endothelium. Probucol maintains endothelial function through its antioxidant activity. This study investigated the efficacy and mechanism of probucol in improving erectile function in streptozotocin-induced diabetic rats.In our study, thirty 12-week-old Sprague-Dawley male rats were fasted for 12 h. All rats received a 1-time injection of intraperitoneal streptozotocin(60 mg/kg) or vehicle. After 72 h, STZ-treated rats (with random blood glucose concentrations consistently greater than 16.7 mmol/L) were considered diabetic. The diabetic rats were randomly assigned into 2 groups and treated with daily gavage feedings of probucol at doses of 0 and 500 mg/kg for 12 weeks. A positive control group underwent intraperitoneal injection of normal saline followed by daily gavage of saline solution. Erectile function was assessed by electrical stimulation of the cavernous nerves with real-time intracavernous pressure measurement. After euthanasia, penile tissue was investigated using immunohistochemistry, Western blot, and ELISA to assess the proteins of Nrf2/HO-1/DDAH/PPAR-γ/eNOS pathways.After treatment, the rats in the probucol group presented significantly improved erectile function (P < 0.05) than that of the diabetic group without probucol treatment (DM). Also, protein expression of Nrf2, DDAH, PPAR-γ, HO-1 and eNOS was significantly higher than that of the DM group (P < 0.05). CGMP concentrations and SOD concentrations of probucol-treated rats were higher than those of DM group (P < 0.05). The MDA levels and ADMA levels were significantly lower than those of DM group rats (P < 0.05).Probucol can improve erectile function via activation of Nrf2, which coordinates the HO-1/DDAH/PPAR-γ/eNOS pathways in streptozotocin-induced diabetic rats.