Antidiabetic activity of aqueous root extract of Merremia tridentata (L.) Hall. f. in streptozotocin-induced-diabetic rats

ObjectiveTo investigate the antidiabetic effect of aqueous extract of Merremia tridentata (M. tridentata) root (MTRAE) in normal, glucose-loaded hyperglycemic and streptozotocin (STZ)-induced diabetic rats.MethodsOral administration of MTRAE at the doses of 50, 100 and 150 mg/kg was studied in normal, glucose-loaded and STZ-diabetic rats. The three doses caused significant reduction in blood glucose levels in all the models.ResultsThe effect was more pronounced in 100 and 150 mg/kg than 50 mg/kg. MTRAE also showed significant increase in serum insulin, body weight and glycogen content in liver and skeletal muscle of STZ-induced diabetic rats while there was significant reduction in the levels of serum triglyceride and total cholesterol. MTRAE also showed significant antilipidperoxidative effect in the pancreas of STZ-induced diabetic rats. The antidiabetic effect of M. tridentata was compared with glibenclamide, a well known hypoglycemic drug.ConclusionsThe results indicate that aqueous extract of M. tridentata root possesses significant antidiabetic activity.     

Hypoglycemic effect of Octomeles sumatrana aqueous extract in streptozotocin–induced diabetic rats and its molecular mechanisms

ObjectiveTo investigate the hypoglycemic effect of the aqueous extract of Octomeles sumatrana (O. sumatrana) (OS) in streptozotocin-induced diabetic rats (STZ) and its molecular mechanisms.MethodsDiabetes was induced by intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg) in to male Sprague-Dawley rats. Rats were divided into six different groups; normal control rats were not induced with STZ and served as reference, STZ diabetic control rats were given normal saline. Three groups were treated with OS aqueous extract at 0.2, 0.3 and 0.5 g/kg, orally twice daily continuously for 21 d. The fifth group was treated with glibenclamide (6 mg/kg) in aqueous solution orally continuously for 21 d. After completion of the treatment period, biochemical parameters and expression levels of glucose transporter 2 (Slc2a2), glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PCK1) were determined in liver by quantitative real time PCR.ResultsAdministration of OS at different doses to STZ induced diabetic rats, resulted in significant decrease (P<0.05) in blood glucose level in a dose dependent manner by 36%, 48%, and 64% at doses of 0.2, 0.3 and 0.5 g/kg, respectively, in comparison to the STZ control values. Treatment with OS elicited an increase in the expression level of Slc2a2 gene but reduced the expression of G6Pase and PCK1 genes. Morefore, OS treated rats, showed significantly lower levels of serum alanine transaminase (ALT), aspartate aminotransferase (AST) and urea levels compared to STZ untreated rats. The extract at different doses elicited signs of recovery in body weight gain when compared to STZ diabetic controls although food and water consumption were significantly lower in treated groups compared to STZ diabetic control group.ConclusionsO. sumatrana aqueous extract is beneficial for improvement of hyperglycemia by increasing gene expression of liver Slc2a2 and reducing expression of G6Pase and PCK1 genes in streptozotocin-induced diabetic rats.     

Role of asymmetric-dimethyl-l-arginine (ADMA) and nitrite/nitrate (NOx) in the pathogenesis of oxidative stress in female subjects with uncomplicated type 1 diabetes mellitus

AimsTo explore the role of asymmetric-dimethyl-l-arginine (ADMA), an endogenous nitric oxide synthetases (NOS) inhibitor, and nitrite/nitrate (NOx) in the pathogenesis of oxidative stress in early stages of type 1 diabetes mellitus.MethodsWe measured in 99 female subjects with uncomplicated type 1 diabetes (duration disease <10 years) and in 44 sex-matched controls (comparable for age, smoking habit, diet and physical activity) plasma levels of NOx, glycosylated haemoglobin (HbA1c), glucose, uric acid, total cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides and serum ADMA.ResultsType 1 diabetic subjects have higher levels of glycemia, HbA1c, LDL cholesterol and NOx, but lower ADMA and serum uric acid (UA), compared with the control group; no further differences were found. A significant linear and inverse correlation was found between NOx and ADMA levels (R² = 0.237, p < 0.001).ConclusionsThis study suggests a reduced ADMA inhibition of NOS as possible mechanism involved in the pathogenesis of oxidative stress in female subjects with a short duration and uncomplicated type 1 diabetes.     

Characteristics and management of diabetic patients hospitalized for myocardial infarction in France

AimThe objective of this study was to compare the management of diabetic and non-diabetic patients before, during and after hospitalization for myocardial infarction (MI).MethodsHospital admissions for MI in France from January to June 2006 were obtained from the national hospital-discharge database and merged with data on medications, 6 months before and after hospitalization of patients covered by the general health insurance scheme. Diabetic patients were identified by having at least two refunds for antidiabetic medications 6 months before the index hospitalization. Results comparing diabetic and non-diabetic patients were adjusted for age and gender.ResultsOf the 14,007 patients included in the study, 2545 were diabetic (18.2%). Before hospital admission, diabetic patients more frequently received secondary cardiovascular preventative medications (12.7% vs 4.2%; P < 0.0001) and stent implants (4.2% vs 2.2%; P < 0.0001) than did non-diabetic patients. During hospitalization and the following month, angioplasty (56.1% vs 61.7%; P = 0.0001) and stent implantation (53.3% vs 59.3%; P < 0.0001) were less frequently performed in diabetic patients and only coronary angiography was done in similar proportions of diabetic and non-diabetic patients (16.7% vs 15.2%). In addition, during the 6 months after hospitalization, diabetic vs non-diabetic patients had more admissions for cardiovascular reasons (36.9% vs 29.5%; P < 0.0001) and were prescribed more secondary preventative medications (65.9% vs 61.7%; P < 0.0001). They were also more frequently treated with insulin only (19.6% 6 months before vs 27.2% 6 months after) or oral antidiabetic drugs (14.6% vs 19.7%, respectively) than were non-diabetics.ConclusionFrench diabetic patients subsequent to MI undergo fewer angioplasty procedures than do non-diabetic patients. After the acute stage, secondary preventative medications are used more often, with a marked rise in the use of insulin.     

Low intensity resistance training improves systolic function and cardiovascular autonomic control in diabetic rats

AimsWe evaluated the effects of low intensity resistance training (RT) on left ventricular (LV) function, baroreflex sensitivity (BRS), and cardiovascular autonomic control of streptozotocin-induced diabetic rats.MethodsMale Wistar rats were divided into (n = 8 each group): sedentary control (SC), trained control (TC), sedentary diabetic (SD), and trained diabetic (TD). Trained groups underwent low intensity RT (40%–50% 1 repetition maximum) for 10 weeks. Echocardiographic evaluation, arterial pressure (AP), heart rate (HR), BRS, and autonomic measurements were performed.ResultsDiabetes induced an increase in glycemia and a reduction in body weight in diabetics when compared with control animals. Diabetic rats displayed cardiac dysfunction, reduced systolic AP and HR, impaired BRS and autonomic derangement when compared to control rats. RT improved ejection fraction (SD: 68% ± 1.3% vs. TD: 75% ± 3.0%) and velocity of circumferential fiber shortening (SD: 0.32 ± 0.02 vs. TD: 0.40 ± 0.01 circ/seg.10^− 4). Trained diabetic rats presented increased AP (+ 10.2%), HR (+ 10.4%), and BRS after RT protocol.ConclusionsLow intensity RT induced an increase in systolic function in diabetic rats. This may be due to positive LV remodeling and BRS improvement, which may have played an important role in the attenuation of hemodynamic impairment and cardiac autonomic neuropathy in streptozotocin-diabetic rats.     

Activities of cyclooxygenases,and levels of prostaglandins E2 And F2α, in fetopathy associated with experimental diabetic gestation

AimThe present study investigated the cyclooxygenase (COX) pathway to elucidate any changes that may be involved in the mechanism(s) underlying diabetic fetopathy.MethodsDiabetes was induced in female rats (n = 12) by two successive daily injections of 55 mg/kg streptozotocin, while control animals (n = 10) were injected with a buffer solution; hyperglycaemia was confirmed by blood glucose levels greater than 11 mmol/L. The study female rats were made pregnant and, on day 15 of gestation, the rats were sacrificed, and the fetuses, placentas and membranes dissected out of the uterine horns. Following morphological examination, the fetuses, placentas and membranes were homogenized, and used to measure COX activities and prostaglandin (PG) E₂ and PGF_2α levels.ResultsFetuses from diabetic mothers exhibited significantly (P < 0.05) shorter crown-to-rump lengths, lower body weights and heavier placental weights. The activity of COX-1 in the fetuses, placentas and membranes from diabetic mothers represented a small percentage of total COX activity compared with that of COX-2. The presence of a COX-1 inhibitor in the control and diabetic rats was investigated and found to be negative. The activity of COX-2 in malformed fetuses from diabetic mothers was significantly lower (P < 0.05) compared with non-malformed fetuses from control and diabetic mothers. The mean level of PGE₂ in fetuses from diabetic mothers was significantly (P < 0.05) lower than that in controls. In contrast, the biggest increases in PGF_2α were observed in the malformed diabetic fetuses, placentas and membranes.ConclusionThe increased production of PGF_2α probably proceeds, at least in part, independently of the COX pathway and via the isoprostane route. However, it is unclear whether the relatively high levels of PGF_2α are causally related to, or simply coincidental with, fetal malformation.     

Impact of budesonide on liver function tests and gut inflammation in patients with primary sclerosing cholangitis and ileal pouch anal anastomosis

Background and aimBudesonide has been studied in patients with primary sclerosing cholangitis (PSC). This study was designed to evaluate the efficacy of oral budesonide on liver function tests in patients with PSC and pouchitis associated with ileal pouch-anal anastomosis (IPAA).Materials and methodsThe study group consisted of 18 pouch patients with underlying ulcerative colitis (UC) and PSC who were treated with 9 mg daily of budesonide for their underlying pre-pouch ileitis and pouchitis for 1-3 months followed by 3-6 mg maintenance for another 9 months. Demographic and clinical variables were analyzed.ResultsThe mean age was 39.4 ± 12.4 years (range, 21–59 years). There was no significant change in aspartate aminotransferase (AST) [median (interquartile range) (IQR) 32 (25, 43.8) vs. 35.5 (25.5, 53), p = 0.35], alanine aminotransferase (ALT) [37.5 (25.5, 49.5) vs. 40 (30, 84.3), p = 0.29], alkaline phosphatase [142.5 (98.5, 264.5) vs. 126 (94.3, 189.5), p = 0.35], serum bilirubin [0.7 (0.4, 1.3) vs., 0.6 (0.4, 1.6), p = 0.13] or albumin levels [4.3 (3.9, 4.4) vs. 4.2 (3.8, 4.4), p = 0.22] at the end of the treatment period (1 year). The revised Mayo Risk Score did not change significantly and three patients required evaluation for liver transplantation during treatment. There was a significant improvement in the endoscopy subscores in the afferent limb and pouch after a year of budesonide treatment (p = 0.001).ConclusionsOral budesonide appears to have no impact on liver function tests in pouch patients with PSC. However it significantly improved afferent limb and pouch inflammation in IPAA patients.     

Biochemical and histological changes in the heart of post-partum rats exposed to Natron

BackgroundThe customary puerperal practice of Natron consumption has been identified as one of the predisposing factors in the etiology of peripartum cardiomyopathy (PPCM). This study was designed to investigate the effect of Natron in postpartum Wistar albino rats.MethodsA total of 30 postpartum Wistar rats were exposed to different doses (50 mg/kg, 100 mg/kg, 200 mg/kg and 300 mg/kg) of Natron for 28 days. After the treatment, we carried out biochemical analyses and histological evaluations of kidney, liver and heart.ResultsThe study revealed that the exposure of postpartum rats to 100 mg/kg of Natron and above significantly (p < 0.05) increase the cardiac markers; myoglobin, creatine kinase-MB, troponin I and T as compared with control. The result of liver function indicated no significant difference in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, albumin and total protein of the Natron treated groups as compared with control. However, at higher doses, the levels of total protein, globulin and alkaline phosphatase activity were significantly increased in comparison to the control. There was no significant difference in the kidney function markers of the treatment groups as compared with control. Histological examinations revealed no changes in the kidney of the treated groups. Mild portal triaditis was observed in the liver of the treated rats. The heart of the rats administered ≥100 mg/kg of Natron showed myocyte hypertrophy.ConclusionThe study demonstrated that the administration of Natron for 28 days caused changes in the heart of postpartum rats and thus may contribute to the pathogenesis of PPCM.     

A new approach to facilitate diagnosis of nonalcoholic fatty liver disease through a galactose single point method in rats with fatty liver

BackgroundLiver biopsy reliably diagnoses nonalcoholic fatty liver disease, but its invasiveness and inter- and intra-observer errors limit its usefulness in monitoring.AimsUse a galactose single point method or combined biochemical parameters to improve assessments of nonalcoholic fatty liver disease in a rat model.MethodsThree nonalcoholic fatty liver disease severities were generated in 50 rats: a control group (n = 18) on a standard diet, and 2 study groups on a choline-deficient diet (n = 18), with and without treatment with silymarin (n = 14). At weeks 4, 8, and 18, a galactose solution (0.5 g/kg/body weight) was rapidly injected intravenously. Sixty minutes later, internal artery blood was taken for biochemical analyses, including galactose. The livers were then removed for haematoxylin–eosin staining and to measure the hepatic lipid content.ResultsAlkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, albumin, and total protein were each significantly correlated with nonalcoholic fatty liver disease severity. Regarding logistic regression, galactose single point method and total protein were significantly predictive. The optimal alanine aminotransferase cutoff point for nonalcoholic fatty liver disease prediction from the receiver-operating characteristic curve had 72.4% sensitivity and 52.4% specificity; galactose single point method alone had 82.8% and 72.4%, whereas galactose single point method + total protein showed 82.8% and 81.0%.ConclusionsBoth galactose single point method and galactose single point method + total protein had greater diagnostic sensitivity and specificity for nonalcoholic fatty liver disease than traditional biochemical tests.     

A quick,simple method for detecting circulating fluorescent advanced glycation end-products: Correlation with in vitro and in vivo non-enzymatic glycation

ObjectiveAdvanced glycation end-products (AGEs) constitute a highly heterogeneous family of compounds, relevant in the pathogenesis of diabetic complications, which could represent efficient biomarkers of disease progression and drug response. Unfortunately, due to their chemical heterogeneity, no method has been validated to faithfully monitor their levels in the course of the disease. In this study, we refine a procedure to quantitatively analyze fluorescent AGEs (fAGEs), a subset considered remarkably representative of the entire AGE family, and measure them in in vitro glycated BSA (gBSA) and in plasma and vitreous of diabetic rats, for testing its use to possibly quantify circulating AGEs in patients, as markers of metabolic control.MethodsfAGE levels were evaluated by spectrofluorimetric analysis in in vitro and in vivo experimental models. BSA was glycated in vitro with increasing D-glucose concentrations for a fixed time or with a fixed D-glucose concentration for increasing time. In in vivo experiments, streptozotocin-induced diabetic rats were studied at 1, 3, 6 and 12 weeks to analyze plasma and vitreous. To confirm the presence of AGEs in our models, non-diabetic rat retinal explants were exposed to high glucose (HG), to reproduce short-term effects, or in vitro gBSA, to reproduce long-term effects of elevated glucose concentrations. Rat retinal explants and diabetic retinal tissues were evaluated for the receptor for advanced glycation end-product (RAGE) by Western blot analysis.ResultsIn in vitro experiments, fluorescence emission showed glucose concentration- and time-dependent increase of fAGEs in gBSA (p ≤ 0.05). In streptozotocin-induced diabetic rats, fAGE in plasma and vitrei showed an increase at 6 (p ≤ 0.005) and 12 (p ≤ 0.05) weeks of diabetes, with respect to control. RAGE was time-dependently upregulated in retinas incubated with gBSA, but not with HG, and in diabetic retinal tissue, substantiating exposure to AGEs.ConclusionsApplying the proposed technique, we could show that fAGEs levels increase with glucose concentration and time of exposure in vitro. Furthermore, in diabetic rats, it showed that circulating fAGEs are similarly upregulated as those in vitreous, suggesting a correlation between circulating and tissue AGEs. These results support the use of this method as a simple and reliable test to measure circulating fAGEs and monitor diabetes progression.     

Aminotransferase activity in morbid and uncomplicated obesity: predictive role of fasting insulin

Background and aims.An elevation in liver enzymes and, most notably, high serum alanine aminotransferase (ALT) activity, has been correlated with metabolic syndrome and obesity. However, whether obesity per se or obesity-related co-morbidities affect aminotransferase activity is still unclear. In this study we sought to evaluate serum aminotransferase activity in morbid and uncomplicated obese subjectsMethods.In this cross-sectional study, serum aminotransferase activity, anthropometric and metabolic parameters were assessed in 290 morbid and 105 uncomplicated consecutive obese subjects matched for body mass index (BMI) (40.1 ± 6.8 vs. 39.9 ± 8.3 kg/m², respectively), age (35.9 ± 10 vs. 34.8 ± 9.6 years, respectively), sex distribution and duration of obesity.Results.Uncomplicated obese subjects showed significantly lower serum ALT activity (17.58 ± 6.3 (range 10–39) vs. 23.43 ± 16 (range 12–89) U/l, (p < 0.001)), and lower aspartate aminotransferase (AST), AST/ALT ratios and gamma-glutamyltranspeptidase (γGT) (p < 0.01 for all) than morbid obese subjects. Only 11% women and 19% men in the uncomplicated obese group showed high ALT levels, while ALT activity was high in 48% women and 51% men in the morbid obese group. Fasting insulin was the best correlate of ALT activity (R² = 0.21, p = 0.003).Conclusions.Our findings show that elevated ALT and AST activity are associated with increased fasting insulin and not with obesity per se, suggesting that the presence of insulin resistance, rather than BMI alone, plays a role in mediating the increased aminotransferase activity.     

The effect of pioglitazone as add-on therapy to metformin or sulphonylurea compared to a fixed-dose combination of metformin and glibenclamide on diabetic dyslipidaemia

Background and aimsDiabetic dyslipidaemia contributes to the increased risk of cardiovascular disease in patients with Type 2 diabetes. This paper examines the effectiveness of adding pioglitazone to metformin or a sulphonylurea (SU) compared with a fixed-dose combination of metformin and glibenclamide on diabetic dyslipidaemia in patients with Type 2 diabetes.Methods and resultsPatients (n = 250) treated with metformin (≤3 g/day) or an SU as monotherapy at a stable dose for ≥3 months were randomised to receive either pioglitazone (15–30 mg/day) in addition to their metformin or SU, or a fixed-dose combination tablet containing metformin (400 mg) and glibenclamide (2.5 mg) [up to 3 tablets daily] for 6 months. Addition of pioglitazone tended to increase plasma high-density lipoprotein-cholesterol (HDL-C) [0.04 mmol/L; P = 0.051] at 6 months and significantly reduced plasma triglycerides (−0.25 mmol/L; P = 0.013) compared with baseline. Patients treated with metformin/glibenclamide for 6 months had reduced HDL-C (−0.09 mmol/L; P < 0.01) and no change in plasma triglyceride levels (0.03 mmol/L; P = 0.733). Both treatment regimes resulted in a similar level of glycaemic control.ConclusionThe beneficial effects of pioglitazone on diabetic dyslipidaemia may help combat the increased cardiovascular morbidity and mortality observed in patients with Type 2 diabetes while providing stable glycaemic control.     

Impact of diabetes on uric acid and its relationship with the extent of coronary artery disease and platelet aggregation: A single-centre cohort study

BackgroundSerum uric acid (SUA) elevation has been associated with the main determinants of atherosclerosis and metabolic syndrome, although an independent relationship between SUA and coronary artery disease (CAD) has never been confirmed. Recent reports suggested a central role of SUA in diabetic patients, possibly being an early marker of impaired glucose metabolism and best predicting the risk of cardiovascular events in these patients. Aim of current study was to evaluate the relationship between diabetes and uric acid and its association with the extent of CAD and platelet aggregation among diabetics.MethodsIn diabetic patients undergoing coronary angiography, fasting samples were collected for uric acid levels assessment. Coronary disease was defined for at least 1 vessel stenosis > 50% as evaluated by QCA.ResultsDiabetes was observed in 1173 out of 3280 (35.7%) diabetes was related to age, hypercholesterolemia, hypertension, BMI, renal failure, previous MI or coronary revascularization (p < 0.001, respectively) and smoking (p = 0.001). Diabetics were more frequently treated with ACE-inhibitors, ARBs, b-blockers, calcium-antagonists, diuretics, statins (p < 0.001, respectively), and ASA (p = 0.004). Diabetics displayed higher glycemia and HbA1c (p < 0.001), higher creatinine and triglycerides (p < 0.001) but lower total and HDL cholesterol (p < 0.001) and haemoglobin (p < 0.001).No significant difference was found in SUA levels between diabetic and non diabetic patients (p = 0.09). In fact, we identified age, renal failure, hypertension, smoking, BMI, use of diuretics, statins, haemoglobin, triglycerides and HDL cholesterol levels as independent predictors of higher levels of uric acid (3rd tertile, ≥ 6.7 mg/dl or 0.39 mmol/l).Among diabetic patients, no relationship was found between uric acid and the extent of coronary artery disease (p = 0.27; adjusted OR [95%CI] = 0.93 [0.76-1.1], p = 0.48), or severe (LM-trivessel) CAD (P = 0.05; adjusted OR [95%CI] = 1.01 [0.86-1.18], p = 0.94). Furthermore, SUA levels did not influence platelet aggregation.ConclusionAgeing, BMI, renal failure, hypertension, smoking, use of statins and diuretics, haemoglobin, HDL cholesterol and tryglicerides levels but not diabetes or glycemic control are independent predictors of hyperuricemia. Among diabetic patients, higher SUA is not independently associated with the extent of CAD or with platelet aggregation.     

Serum Uric Acid concentration is associated with insulin resistance and impaired insulin secretion in adults at risk for Type 2 Diabetes

AimsInsulin resistance (IR) predisposes to type 2 diabetes mellitus (T2DM). Although previous studies have associated serum uric acid concentration with IR in T2DM, its association with impaired insulin secretion and beta-cell dysfunction in subjects at risk for developing T2DM remains uncertain. Thus, we aimed to analyze the association of serum uric acid concentration with IR using surrogate insulin resistance/secretion and beta-cell function indices in subjects at risk for developing T2DM.MethodsThis is a cross-sectional study that included 354 subjects who underwent an oral glucose tolerance test who had at least two risk factors for T2DM without any chronic disease.ResultsParticipants were 51 ± 8 years old, 72.2% were women, had a mean body mass index of 29.9 ± 6.5 kg/m² and mean serum uric acid concentration of 5.7 ± 1.3 mg/dL. HOMA-IR, first-phase insulin secretion (S1Ph_OGTT), second-phase insulin secretion (S2Ph_OGTT), Matsuda and disposition indices were significantly correlated with serum uric acid concentrations (r = 0.239, r = 0.225, r = 0.201, r = ?0.287, r = ?0.208; respectively). After multiple linear regression analysis, serum uric acid concentration was independently associated with HOMA-IR (β = 0.283), HOMA-B (β = 0.185), S1Ph_OGTT (β = 0.203), S2Ph_OGTT (β = 0.186), and Matsuda Index (β = ?0.322). A serum uric acid concentration of 5.5 mg/dL had the best sensitivity/sensibility to identify subjects with IR (HOMA-IR ≥2.5).ConclusionsSerum uric acid concentration is significantly associated with IR and impaired insulin secretion, but not with beta-cell dysfunction, in subjects at risk for developing T2DM.     

Risk of coronary artery disease associated with initial sulphonylurea treatment of patients with type 2 diabetes: A matched case–control study

AimsThis study sought to assess the risk of developing coronary artery disease (CAD) associated with initial treatment of type 2 diabetes with different sulphonylureas.MethodsIn type 2 diabetic patients, cases who developed CAD were compared retrospectively with controls that did not. The 20-year risk of CAD at diagnosis of diabetes, using the UKPDS risk engine, was used to match cases with controls.ResultsThe 76 cases of CAD were compared with 152 controls. The hazard of developing CAD (95% CI) associated with initial treatment increased by 2.4-fold (1.3–4.3, P = 0.004) with glibenclamide; 2-fold (0.9–4.6, P = 0.099) with glipizide; 2.9-fold (1.6–5.1, P = 0.000) with either, and was unchanged with metformin. The hazard decreased 0.3-fold (0.7–1.7, P = 0.385) with glimepiride, 0.4-fold (0.7–1.3, P = 0.192) with gliclazide, and 0.4-fold (0.7–1.1, P = 0.09) with either.ConclusionsInitiating treatment of type 2 diabetes with glibenclamide or glipizide is associated with increased risk of CAD in comparison to gliclazide or glimepiride. If confirmed, this may be important because most Indian patients receive the cheaper older sulphonylureas, and present guidelines do not distinguish between individual agents.     

Gender-specific differences in clinical and metabolic variables associated with NAFLD in a Mexican pediatric population

Introduction and ObjectivesNon-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children and it is more prevalent in Hispanic males. The gender differences can be explained by body fat distribution, lifestyle, or sex hormone metabolism. We evaluated anthropometric and metabolic differences by gender in children with and without NAFLD.MethodsWe included 194 participants (eutrophic, overweight, and individuals with obesity). The presence of NAFLD was determined using ultrasonography, and we evaluated the association between this disease with metabolic and anthropometric variables by gender.ResultsThe mean age was 10.64 ± 2.54 years. The frequency of NAFLD in boys was 24.51% and in girls was 11.96% (OR = 2.39; 95%CI = 1.10–5.19; p = 0.025). For girls, NAFLD was significantly associated with triglycerides (p = 0.012), homeostatic model assessment of insulin resistance (HOMA-IR) (p = 0.048), and the visceral adiposity index (VAI) (p = 0.024). The variables related to NAFLD in a gender-specific manner were body mass index (BMI) (p = 0.001), waist circumference (WC) (p < 0.001), HDL cholesterol (p = 0.021), alanine aminotransferase (ALT) (p < 0.001), and aspartate aminotransferase (AST) (p = 0.002).ConclusionsIn our study NAFLD is more frequent in boys, only ALT, and no other clinical or metabolic variables, were associated with NAFLD in these patients. HOMA-IR, VAI, triglyceride levels, and ALT were associated with NAFLD only in girls. The ALT cut-off points for the development of NAFLD in our study were 28.5 U/L in females and 27.5 U/L in males. Our findings showed that NAFLD should be intentionally screened in patients with obesity, particularly in boys.     

Prevalence of NAFLD in Guatemala following exposure to a protein-energy nutrition intervention in early life

Introduction and objectivesThe global prevalence of non-alcoholic fatty liver disease (NAFLD) is approximately 25%, with Hispanic populations at greatest risk. We describe the prevalence of NAFLD in a cohort of Guatemalan adults and examine whether exposure to a protein-energy supplement from conception to two years is associated with lower prevalence of NAFLD.Materials and methodsFrom 1969 to 1977, four villages in Guatemala were cluster-randomized to receive a protein-energy supplement (Atole) or a no-protein, low-energy beverage (Fresco). We conducted a follow-up of participants from 2015 to 2017. We assessed blood samples (n = 1093; 61.1% women; aged 37–53 years) for alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and estimated NAFLD prevalence using the liver fat score. We used generalized linear and logistic models to estimate the difference-in-difference effect of Atole from conception to two years on NAFLD.ResultsMedian ALT and AST were 19.7 U/L (interquartile range, IQR: 14.1, 27.4) and 26.0 U/L (IQR: 21.4, 32.8), respectively. The median NAFLD liver fat score was 0.2 (IQR: −1.2, 1.6) in women and −1.2 (IQR: −2.2, 0.5) in men (p < 0.0001). The prevalence of NAFLD was 67.4% among women and 39.5% among men (p < 0.0001). The association between Atole exposure from conception to two years and NAFLD was not significant (OR: 0.90, 95% CI: 0.50–1.63).ConclusionsNAFLD prevalence among Guatemalan adults exceeds the global average. Protein-energy supplementation in early life was not associated with later NAFLD. There is a need for further studies on the causes and onset of NAFLD throughout the life course.     

Is vitamin D status a predictor glycaemic regulation and cardiac complication in type 2 diabetes mellitus patients?

ObjectiveTo evaluate vitamin D as a predictor of glycaemic regulation in type 2 diabetes mellitus patients.Research design and methodsIn observational study 171 type 2 diabetic patients who are followed for median (range) of 10.15 (3–18) years. Mean ± SD age was 56 ± 10. Plasma 25-hydroxyvitamin D3 levels were determined by high-performance liquid chromatography/tandem mass spectrometry on baseline samples. Vitamin D deficiency was defined as a 25-OHD level of less than 20 ng/ml. Vitamin D levels between 20 and 30 ng/ml are termed ‘insufficient’. Vitamin D levels greater than 30 ng/ml are termed ‘optimal’.Results125 patients have vitamin D deficiency, 14 patients have insufficient and the others have optimal. Vitamin D levels were not associated with sex, age, BMI, HDL, LDL, kreatinin, hypertension and smoking. But vitamin D deficiency patients had more longer duration (p = 0.011), more higher uric acid (p = 0.021), fasting glucose (p = 0.037), postprandial glucose (p = 0.001) and HbA1c (p = 0.026).ConclusionsIn our study type 2 diabetic patients have 73% of vitamin D deficiency. Vitamin D deficiency predicts higher fasting and postprandial blood glucose and diabetes disregulation. Type 2 DM patients and low 25-OH vitamin D levels could increased cardiovascular disease directly or indirectly (low HDL and high uric acid in 25-OH vitamin D <20 ng/ml). Whether vitamin D substitution improves prognosis remains to be investigated.     

Antioxidant,anti-diabetic and renal protective properties of Stevia rebaudiana

BackgroundStevia rebaudiana Bertoni has been used for the treatment of diabetes in, for example, Brazil, although a positive effect on antidiabetic and its complications has not been unequivocally demonstrated. This herb also has numerous therapeutic properties which have been proven safe and effective over hundreds of years. Streptozotocin is a potential source of oxidative stress that induces genotoxicity.ObjectiveWe studied the effects of stevia leaves and its extracted polyphenols and fiber on streptozotocin induced diabetic rats. We hypothesize that supplementation of polyphenols extract from stevia to the diet causes a reduction in diabetes and its complications.Design/MethodsEighty Wistar rats were randomly divided into 8 groups; a standard control diet was supplemented with either stevia whole leaves powder (4.0%) or polyphenols or fiber extracted from stevia separately and fed for one month. Streptozotocin (60 mg/kg body weight, i.p) was injected to the diabetic groups on the 31st day. Several indices were analyzed to assess the modulation of the streptozotocin induced oxidative stress, toxicity and blood glucose levels by stevia.ResultsThe results showed a reduction of blood glucose, ALT and AST, and increment of insulin level in the stevia whole leaves powder and extracted polyphenols fed rats compared to control diabetic group. Its feeding also reduced the MDA concentration in liver and improved its antioxidant status through antioxidant enzymes. Glucose tolerance and insulin sensitivity were improved by their feeding. Streptozotocin was also found to induce kidney damage as evidenced by decreased glomerular filtration rate; this change was however alleviated in the stevia leaves and extracted polyphenol fed groups.ConclusionThe results suggested that stevia leaves do have a significant role in alleviating liver and kidney damage in the STZ-diabetic rats besides its hypoglycemic effect. It might be adequate to conclude that stevia leaves could protect rats against streptozotocin induced diabetes, reduce the risk of oxidative stress and ameliorate liver and kidney damage.     

Evaluation of trace elements and Malondialdehyde levels in type II diabetes mellitus

BackgroundThere are so many factors contributing to the pathophysiology of type II DM, some of these factors are trace elements and Malondialdehyde (MDA). Their increase or decrease may affect control of diabetes and delay the complications.AimZinc (Zn), copper (Cu), magnesium (Mg), chromium (Cr), selenium (Se) and MDA were studied in this work to clarify their role in the pathogenesis and complications of type II DM aiming at preventing or delaying its complications.Materials and methodsThe present study was conducted on 50 patients with type II DM divided into 2 groups: group I (controlled diabetic patients), n = 20 and group II which comprised 30 uncontrolled diabetic patients complicated with diabetic nephropathy, neuropathy and retinopathy. Their results were compared to 15 age and sex matched healthy group. Patients and controls were subjected to full history taking, complete clinical examination and laboratory investigations which included measuring fasting serum glucose, cholesterol, triglycerides, HDL-c and LDL-c. HbA1c was measured by column chromatography. MDA was assayed using colorimetric technique. The trace elements were measured in blood by means of atomic absorption spectrometer.ResultsThe mean levels of Zn, Mg, Se were significantly lower in the diabetic groups than the control group (P < 0.001), while MDA was significantly higher in the diabetic groups (P < 0.001). MDA showed significant positive correlation with HbA1c (r = 0.301), cholesterol (r = 0.394), triglycerides (0.315) and LDL-c (r = 0.354) and negative correlation with HDL-c (r = ?0.315). Significant negative correlation was found between each of Zn, Mg and Se and each of HbA1c and cholesterol. Copper positively correlated with HbA1c, cholesterol and LDL-c. MDA positively correlated with copper (r = 0.307) and negatively correlated with Zn, Mg and Se (r = ?0.356, ?0.282, ?0.513, respectively).ConclusionTrace elements and MDA could have a role as cofactors in the pathogenesis of type II DM. They could be used as markers to evaluate the glycemic control as well as showing the lipid status of diabetic patients. Trace elements supplementations as zinc, magnesium and selenium might have utility in the treatment of the complex disorder in type II DM and may help in control of blood glucose and lipid levels, thus preventing or delaying serious clinical events in these patients.