Protective Effect Of Diabetes Research Articles

Tirzepatide alleviates oxidative stress and inflammation in diabetic nephropathy via IL-17 signaling pathway.

Oxidative stress (OS) and inflammation play essential roles in the development of diabetic nephropathy (DN). Tirzepatide (TZP) has a protective effect in diabetes. However, its underlying mechanism in DN remains unclear. DN model mice were induced by intraperitoneal injection of streptozotocin (STZ; 60mg/kg), followed by administration of different doses of TZP (3 and 10nmol/kg) via intraperitoneal injection for 8weeks. The effects of TZP on DN were evaluated by detecting DN-related biochemical indicators, kidney histopathology, apoptosis, OS, and inflammation levels. Additionally, to further reveal the potential mechanism, we investigated the role of TZP in modulating the IL-17 pathway. TZP reduced serum creatinine (sCR), blood urea nitrogen (BUN), and advanced glycosylation end products (AGEs) levels, while simultaneously promoting insulin secretion in diabetic mice. Additionally, TZP attenuated tubular and glomerular injury and reduced renal apoptosis levels. Further studies found that TZP increased the levels of SOD and CAT, and decreased MDA. Meanwhile, TZP also reduced the expression of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in both mouse serum and kidney homogenates. TZP effectively inhibited the IL-17 pathway, and subsequent intervention with an IL-17 pathway agonist (IL-17A) reversed the suppressive effects of TZP on OS and inflammation. TZP can improve DN by inhibiting OS and inflammation through the suppression of the IL-17 pathway.

Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization

BackgroundIn observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization.Materials and methodsWe performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately.ResultsThe IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836–0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12–44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607–0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta.ConclusionMendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.Graphical abstract

The Effects of 1,1-Dimethylbiguanide Hydrochloride (Metformin) on Detrusor Muscle Contractile Response in Ovariectomized Female Rats

Aim: Menopause is defined as the depletion of the ovarian follicular reserve followed by the cessation of menstrual cycles. It has been
 reported that gonadal steroid hormones play an important role in bladder function in women. Changes in urine pattern including
 overactive bladder, stress incontinence and recurrent urinary tract infections occur as a result of menopause. 1,1-dimethylbiguanide
 hydrochloride, metformin, (MET) is an oral anti-diabetic drug used to reduce hepatic glucose production and peripheral insulin
 resistance. Recent studies have revealed that MET has a protective effects in diabetes induced bladder dysfunction. The aim of this
 study was to test the therapeutic potential of MET in detrusor contractile function of ovariectomized (OVX) female rats.
 Material and Methods: Bilateral ovariectomy was performed to eliminate endogenous gonadal steroids secretion. Four groups are
 designed with 8 animals in each group: Control, MET-administered control, OVX, and MET-administered OVX groups. MET (25 mg/
 kg) was administered daily by oral gavage for 14 days. Contractile activity of isolated bladder muscle strips were evaluated in vitro organ
 bath. The contractile responses of detrusor strips were determined using different doses of carbachol (10-8-10-2M) and purinergic
 agonist ATP. The relaxation response of strips were determined by isoproterenol
 Results: The contractile responses of detrusor muscle strips to carbachol at doses 10-5-10-2 M were decreased in the OVX group
 compared to control and MET treated control groups. MET treatment partially reversed the reduction in OVX-induced contractile
 responses at 10-2 and 10 -3 M carbachol doses. There were no statistically significant difference in relaxation response between the
 experimental groups.
 Conclusion: Our findings suggest that treatment with MET could be the new potential therapeutic agent against bladder dyfunction
 in postmenopausal women. Further studies are needed for the therapeutic potential of MET in detrusor dysfunction induced by
 menopause.

FC 121: The Combination of Empagliflozin and Atrasentan on Top of RAS Blockade Ameliorates Cardiorenal Injury in a Type 2 Diabetic Mouse Model

Abstract BACKGROUND AND AIMS sodium-glucose 2 cotransporter inhibitors (SGLT2i) prevent cardiovascular events in diabetic patients. Moreover, their diuretic effect could attenuate the adverse events of endothelin receptor antagonists (ERA), which have also shown kidney protective effects in diabetes. The present study aimed to evaluate the beneficial cardiorenal impact of the combination of SGLT2i, ERA and ramipril versus treatment with ramipril alone in experimental diabetes. METHOD Twelve-week-old db/db mice were treated for 8 weeks with different combinations of an SGLT2i (empagliflozin, 10 mg/Kg/day), an ERA (atrasentan, 7 mg/Kg/day) and an RAS blocker (ramipril, 8 mg/Kg/day). Vehicle-treated diabetic and nondiabetic mice were included as controls. During the experiment, blood pressure (BP), glomerular filtration rate (GFR) and echocardiographic parameters were measured. Kidney and heart were collected at the end for histological studies. RESULTS The triple therapy with empagliflozin, atrasentan and ramipril was superior to ramipril alone in reducing BP (mean BP 61.0 mmHg versus 67.10 mmHg in the ramipril group), preventing diabetic hyperfiltration (214.3 μL/100 g/min GFR decrease versus 34.7 μL/100 g/min decrease in the ramipril group) (Figure 1), and improving echocardiographic parameters of diastolic dysfunction, including left atrium diameter and isovolumetric relaxation time. Moreover, the combined therapy offered protection against diabetic injury in kidney and heart by a reduction of mesangial matrix expansion (46.0% of glomerular mesangial matrix versus 46.9% in the ramipril group), as well as left ventricle cardiomyocyte hypertrophy (mean cardiomyocyte area 125 μm2 versus 131 μm2 in the ramipril group) and heart collagen deposition (Figure 1). CONCLUSION In experimental diabetes, combined therapy of ramipril, empagliflozin and atrasentan promotes both heart and kidney protective effects that outweigh the beneficial effects of ramipril alone.

Effects of aerobic exercise on lipopolysaccharide-induced experimental acute lung injury in the animal model of type 1 diabetes mellitus.

What is the central question of this study? We evaluated the effects of diabetes and exercise on lipopolysaccharide-induced acute lung injury. By providing a comprehensive analysis of redox status, blood gases and histological parameters, we aimed to contribute to the ongoing debate in the literature. What are the main findings and its importance? We demonstrated the preventive effect of exercise, but diabetes did not alter the severity of acute lung injury. Acute lung injury (ALI) is a life-threatening respiratory condition. Diabetes (DM) is a metabolic disease characterized by hyperglycaemia. There is an ongoing debate concerning whether there is a protective effect of diabetes in ALI. Exercise is a special type of physical activity that has numerous beneficial effects. The aim of our study was to investigate the effects of diabetes and exercise on the prognosis of ALI. Male Wistar albino rats were divided into two groups (sedentary and exercise). Both groups were divided into four subgroups: Control, ALI, DM, DM+ALI (n=6 each). Diabetes was induced by injection of streptozotocin (50mg/kg i.p.). The maximal exercise capacity was determined with the incremental load test. Animals were exercised on a treadmill for 45min at 70% of maximal exercise capacity, 5days a week for 12weeks. Acute lung injury was induced by intratracheal injection of lipopolysaccharide (100μg/100g body weight) 24h before the end of the experiment. We performed arterial blood gas analysis. Redox status was measured in both plasma and lung tissue. Malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels were measured in lung tissue. Lung tissue was evaluated histologically. Acute lung injury caused significant damage in the lung tissue, which was verified histologically, with an increase in oxidative stress parameters. Exercise prevented the lung damage induced by ALI and reduced oxidative stress in the lung tissue. Diabetes did not alter the magnitude of damage done by ALI. Exercise showed a protective effect against DM and ALI in rats. The effect of DM was insignificant for the prognosis of ALI.

ACE2, Metformin, and COVID-19.

SummaryCOVID-19 is becoming a leading cause of mortality throughout the world, and few effective therapies are currently available. Angiotensin converting enzyme 2 (ACE2) is essential to COVID-19 pathogenesis, as the binding of SARS-CoV-2 spike protein (S protein) is required for viral entry and development of COVID-19. ACE2 regulates the protective arm of the renin-angiotensin-aldosterone system (RAAS) that endows anti-hypertensive and anti-inflammatory effects in the cardiovascular and pulmonary systems. Preclinical data suggest ACE2 might be downregulated after SARS-CoV-2 binding, and treatments that increase ACE2 may prevent cardiopulmonary injury. Development, testing, and mass production of novel ACE2 therapies may take years, whereas more effective treatments for COVID-19 are needed urgently. Metformin is a widely available anti-diabetic agent that has an excellent safety profile, and clinical and preclinical data suggest metformin may offer cardiopulmonary protection in COVID-19 via enhanced ACE2 expression.

Educational inequalities in the prevalence and outcomes of diabetes in the Emilian Longitudinal Study

Background and aimStudies carried out in Italy in the last decades reported an effect modification in the association between socioeconomic position and diabetes outcomes, and the disease integrated care approach has been suggested as an explanatory factor. Whether this is true in Emilia-Romagna region in recent years is unknown and the aim of this study is to describe the role of educational level both on diabetes prevalence and health outcomes among the adult population with and without diabetes enrolled in the Emilian Longitudinal Study. Methods and resultsInequalities in diabetes prevalence were evaluated through standardised estimates and prevalence ratios by educational level and inequalities in outcomes through standardised hospitalisation and mortality ratios and rate ratios by educational level. The lower the education the greater the diabetes prevalence; such differences were larger among women and younger age groups. Diabetes conferred a higher risk of hospitalisation and mortality; those outcomes also presented a social gradient with the less educated bearing the higher risk. However, educational differences were slightly stronger among the disease-free subjects, especially in the case of mortality. In both genders, inequalities tended to disappear with age. ConclusionThis study confirms that diabetes increases the risk of unfavourable outcomes, but does not increase social inequalities in outcomes as might be expected. Similarly to what has been previously shown, it is likely that the protective effect of diabetes on the negative health effects of the low social position is attributable to the disease integrated care approach.

Changes in the Protective Effect of Diabetes on Abdominal Aortic Aneurysms: Results of Two Large National Screening Studies and a Meta-analysis of Population-based Screening Studies

Changes in the Protective Effect of Diabetes on Abdominal Aortic Aneurysms: Results of Two Large National Screening Studies and a Meta-analysis of Population-based Screening Studies

Potential therapeutic effect of Moroccan propolis in hyperglycemia, dyslipidemia, and hepatorenal dysfunction in diabetic rats.

Objective(s):The effect of propolis collected in Morocco on blood glucose, lipid profile, liver enzymes, and kidney function was investigated in control and diabetic rats. Materials and Methods:Antioxidant activity of propolis was evaluated with the use of DPPH, 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS•+), ferric reducing power and total antioxidant activity assay. To study its effect in streptozotocin (STZ)-induced diabetes, the rats were divided into eight groups; four control and four diabetics. The animals received distilled water, glibenclamide, or propolis extract, 50 mg/kg/BW) or 100 mg/kg/b.wt, daily for 15 days. Blood glucose, triglyceride, lactic acid dehydrogenase, liver enzymes, creatinine, blood urea, lipid profile, and body weight were measured on day 15 after commencement of the treatment. Results:Propolis has a strong antioxidant activity and high total flavonoids and polyphenols content. Glibenclamide and propolis have no significant effect on lipid parameters, and renal and hepatic function in non-diabetic rats. However, propolis or glibenclamide caused a significant lowering of blood glucose after a single administration and at day 15 after daily administration in diabetic rats (P<0.05). Both interventions significantly lowered lactic acid dehydrogenase, increased body weight, and ameliorated dyslipidemia and abnormal liver and kidney function caused by diabetes. The effect of propolis was dose-dependent and in a high dose it was more potent than glibenclamide. Conclusion:Propolis exhibited strong antihyperglycemic, antihyperlipidemic, and hepato-renal protective effects in diabetes, and significantly lowered the elevated lactic acid dehydrogenase. The study demonstrated for the first-time the effect of Moroccan propolis in diabetes and it will pave the way for clinical investigations.

Umbelliferone ameliorates renal function in diabetic nephropathy rats through regulating inflammation and TLR/NF-κB pathway.

Diabetic nephropathy (DN) is a leading cause of renal failure, contributing to severe morbidity and mortality in diabetic patients. Umbelliferae (Umb) has been well characterized to exert protective effects in diabetes. However, the action and mechanism of Umb in DN remains unclear. In this work, we studied the effect of Umb in a streptozotocin (STZ)-induced DN rat model and explore its underlying mechanism. DN rats were treated withUmb (20, 40 mg·kg-1) orirbesartan (15 mg·kg-1) for 4 weeks. Levels of serum glucose, insulin, blood uric acid, creatinine, triglycerides (TG) and total cholesterol (TC) were measured bycommercial assay kits, respectively. Histopathological changes andinflammatory cytokine levels including IL-6, IL-1β and TNF-α in the kidney were also evaluated. Alterations in the expression of podocin, CD2AP and TLR/NF-κB were assessed by western blotting. Our results showed that Umb reduced renal injury in DN rat model, as evidenced by the decrease in blood glucose, 24 h urinary protein, serum creatinine, and blood uric acid. Umb also significantly ameliorated the renal histopathological alteration, and down-regulated the expression of epithelial-to-mesenchymal transition-related molecular markers podocin and CD2AP. Moreover, Umb inhibited TLR2, TLR4, MyD88 expressions, NF-κB activation and considerably reduced levels of other downstream inflammatory molecules (TNF-α, IL-6, IL-1β). These findings indicated that Umb improved renal function through regulating inflammation and TLR/NF-κB pathway, suggesting the potential efficacy of Umb in DN treatment.

Characterization of claudin‐5, ‐2, occludin and PPAR alpha in a model of early diabetic nephropathy

The WHO estimates that there are more than 422 million people with diabetes in the world, of whom 90% are diagnosed as type 2. Hyperglycemia plays an important role in renal damage, thus diabetic nephropathy is the most common complication of this pathology. Claudins are components of paracellular transport which are determinants to the ion balance in the kidney. Any alteration in the tight junctions carry a pathophysiological renal consequences that have not yet described in diabetic type 2 model. PPARs are nuclear receptors ligand‐dependent and their alpha isoform is activated by fibrates. Pharmacological therapy with fibrates in diabetes had showed to prevent cardiovascular risk, if they have renal protective effects in diabetes and if they are involved in paracellular ion transport, is not well understood. Those actions, could be useful as a target to identify, prevent and treat diabetic nephropathy may contribute to a better understanding of this disease. Type 2 diabetes model that we used was induced to neonatal rats by the intraperitoneal administration of streptozotocin, a chemical that selectively destroys the β cells of the pancreas, diabetics rats showed moderate hyperglycemia since 4th week and at 14‐week, had a decrease in body weight gain, glucose intolerance, lower insulin secretion and an increase in renal mass. We evaluated renal function in this model and we observed that proteinuria was associated with a decrease in claudin‐5 expression in the glomerulus and the increased fractional excretion of Na+ and K+ was related with a decrease of claudin‐2 and occludin in the proximal tubule. In addition, we observed a loss of renal expression of peroxisome proliferator‐activated receptor alpha (PPAR‐α) in both segments of the nephron. The present work provides evidence that type 2 diabetes alters the renal expression of tight junctions proteins such as claudin‐5, claudin‐2 and occludin, as well as PPAR‐α. This is related to the loss of renal function, suggesting that the loss of these proteins is a fundamental part of the early stages of type 2 diabetic nephropathy.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Abstract P2-13-02: Risk Factors for high risk breast density patterns in Hispanic/Latinas living in the Northeast, US

Abstract Introduction: Breast densities are the non-fat (epithelial and stromal) breast tissue observable on screening mammograms. Known to be associated with a 4 to 6 fold increase in breast cancer risk, dense breast patterns complicate the reading of screening mammograms resulting in lowered sensitivity. Little is currently known about the prevalence and/or predictors of breast density in Hispanic/Latino women living in the Northeast, US. Objective: The goal of this prospective study is to identify risk factors for high risk breast density patterns among a large cohort of Hispanic/Latino women with ancestral ties primarily to the Eastern Caribbean (Puerto Rico and the Dominican Republic) as well as Central and South America. Because the hormonal milieu is somewhat different in Hispanic/Latinas compared with White women, and likely also differs from that of Hispanic/Latinas living in other parts of the US, we explored the role of reproductive and physiological factors in high risk breast density patterns. Methods: We analyzed breast density predictors in an established cohort of 1,600 Hispanic/Latino women recruited from primary care clinics in 4 cities with the largest enclaves of Hispanic/Latinos in Connecticut. Hour-long telephone interviews provided baseline data on biological, medical care, and sociodemographic factors. We retrieved radiology records on 1570 (98.7%) consenting women. For this analysis, we report predictors of breast density among the 1,040 (65.4%) women who received at least one screening mammogram during 2 to 4 years of follow-up. Breast density classification was based on radiologist assigned BI-RADS classification. Associations between predictors and high risk breast density patterns were examined using chi square tests. Multivariate analyses were conducted using logistic regression; odds ratios (OR) and 95% confidence intervals (CI) are reported. Results: Of the 1,040 women who received at least one screening mammogram during the follow-up period, 280 (27%) women were identified as having high risk dense breasts (extremely or heterogeneously dense, i.e., greater than 50% of the breast composed of fibroglandular densities), while 760 women (73%) were classified as having nondense breasts (fatty or scattered fibroglandular densities), suggesting a lower prevalence of high risk breast density patterns in this population. In multivariate analysis, breast density predictors were similar to those reported for the general population (mostly White) women, and are similar to known risk factors for breast cancer. However, we found that Hispanic/Latinas with diabetes to be at significantly reduced odds of high risk breast density patterns. There was also evidence that the relationship between age at menarche and density was modified by BMI, with early age at menarche a risk factor among normal and underweight women only. Conclusion: Our findings suggest that Hispanic/Latino women may differ in breast density prevalence relative to the general population. However, we observed a protective effect of diabetes and a potential interaction between age at menarche and BMI. This investigation enhances our understanding of breast density in a subset of the Hispanic/Latino population and provides the basis for further research. Citation Format: Jones BA, Claye E, Philpotts L, Hooley R, Silber A, Epstein L. Risk Factors for high risk breast density patterns in Hispanic/Latinas living in the Northeast, US [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-13-02.

Salvianolic acid B improves vascular endothelial function in diabetic rats with blood glucose fluctuations via suppression of endothelial cell apoptosis

Vascular endothelial cell injury is an initial event in atherosclerosis. Salvianolic acid B (Sal B), a main bioactive component in the root of Salvia miltiorrhiza, has vascular protective effect in diabetes, but the underlying mechanisms remain unclear. The present study investigated the effect of Sal B on vascular endothelial function in diabetic rats with blood glucose fluctuations and the possible mechanisms implicated. The results showed that diabetic rats developed marked endothelial dysfunction as exhibited by impaired acetylcholine induced vasodilation. Supplementation with Sal B resulted in an evident improvement of endothelial function. Phosphorylation (Ser 1177) of endothelial nitric oxide synthase (eNOS) was significantly restored in Sal B treated diabetic rats, accompanied by an evident recovery of NO metabolites. Sal B effectively reduced vascular endothelial cell apoptosis, with Bcl-2 protein up-regulated and Bax protein down-regulated markedly. Treatment with Sal B led to an evident amelioration of oxidative stress in diabetic rats as manifested by enhanced antioxidant capacity and decreased contents of malondialdehyde in aortas. Protein levels of NOX2 and NOX4, two main isoforms of NADPH oxidase known as the major source of reactive oxygen species in the vasculature, were markedly decreased in Sal B treated groups. In addition, treatment with Sal B led to an evident decrease of serum lipids. Taken together, this study indicates that Sal B is capable of improving endothelial function in diabetic rats with blood glucose fluctuations, of which the underlying mechanisms might be related to suppression of endothelial cell apoptosis and stimulation of eNOS phosphorylation (Ser 1177).

Protective effects of Quercetin and chronic moderate exercise (training) against oxidative stress in the liver tissue of streptozotocin-induced diabetic rats.

Background To investigate the protective effects of Quercetin administration associated with chronic moderate exercise (training) on oxidative stress in the liver in streptozotocin-induced diabetic rats. Methods Diabetic rats that performed exercise training were subjected to a swimming training program (1 hour/day, 5 days/week, 4 weeks). The diabetic rats received natural antioxidant, Quercetin (20 mg/kg body weight/day) for 4 weeks. At the end of the study, all animals were sacrificed and liver samples were collected for estimation: some oxidative stress markers (malondialdehyde, MDA and protein carbonyls groups, PC), the activity of antioxidant enzymes (superoxide dismutase, SOD and catalase, CAT), reduced glutathione (GSH) level and reduced (GSH) and oxidized (GSSG) glutathione ratio. Results Diabetic rats submitted to exercise training showed significantly increased the oxidative stress markers (MDA and PC) and a reduction of antioxidant enzyme (SOD and CAT) activity, GSH level and GSH/ GSSG ratio in hepatic tissues. A decrease in the levels of oxidative stress markers associated with elevated activity of antioxidant enzymes, the GSH level and GSH/GSSG ratio in the hepatic tissue were observed in Quercetin-treated diabetic trained rats. Conclusions These findings suggest that Quercetin administration in association with chronic moderate exercise exerts a protective effect in diabetes by attenuating hyperglycemia-mediated oxidative stress in hepatic tissue.

Effects of Low Intensity Exercise Against Apoptosis and Oxidative Stress in Streptozotocin-induced Diabetic Rat Heart.

Background The aim of this study was to investigate the effects of low intensity exercise on heart of streptozotocin (STZ)-induced diabetic rats. Materials and Methods The rats were randomly divided into 3 experimental groups: A (control), B (diabetic untreated), and C (diabetic treated with low intensity exercise); each group contains 8 animals. B and C groups received STZ. Diabetes was induced in 2 groups by a single intraperitoneal (i.p) injection of STZ (40 mg/kg, freshly dissolved in 0,1 M citrate buffer, pH 4.2). 2 days after STZ treatment, diabetes in 2 experimental groups was confirmed by measuring blood glucose levels. Rats with blood glucose levels of 250 mg/dl or higher were considered to be diabetic. Animals in the exercise group were made to run the treadmill once a day for 4 consecutive weeks. Exercise started 3 days prior to STZ administration. Results After induction of diabetes, histological abnormalities were observed, including myofibrillar loss, vacuolization of cytoplasm and irregularity of myofibrils. These alterations were attenuated by low intensity exercise. Our data indicates a significant reduction of oxidative stress and apoptosis in cardiomyocytes after exercise. Treatment of diabetic animals with low intensity exercise, decreased the elevated tissue malondialdehyde (MDA) levels and increased the reduced activities of the enzymatic antioxidants superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in cardiac tissue. Conclusion These findings suggest that low intensity exercise has a therapeutic protective effect in diabetes by decreasing oxidative stress and apoptosis, and by preservation of myocardial integrity.

Evaluation of fish oils in amelioration of diabetes-induced tissue dam-ages in mice (Mus musculus)

Prolonged diabetes leads to multi-organ damages due to oxidative stress. Fish oil rich in omega-3 poly unsaturated fatty acid is known to reduce the oxidative stress. The present study has been aimed to evaluate the ameliorative effect of two fish oils extracted from Sardinella longiceps and Rastrelliger kanagurta, in diabetes-induced tissue damages in liver, kidney and heart tissues of mice, Mus musculus. Diabetes was induced by repetitive intra-peritoneal injection of alloxan (100mg/kg BW). The diabetic mice were fed the commercial pellet diet supplemented with 10% laboratory extracted fish oil of S.longiceps and R.kanagurta, for period of one month. Concentra-tion of various parameters viz.,Thiobutaric acid reactive substance, Vitamin C, Vitamin E and reduced glutathione along with activities of Aspartate aminotransferase, Alanine aminotransferase, Gamma glutamyltranspeptidase, Lactate dehydrogenase, Superoxide dismutase and Catalase were monitored in these tissues. Altered level of tissue biochemical composition and enzyme activities due to diabetes-induced damages was nearly brought down to nor-mal levels with the supplementation of 10% fish oil. Histological studies of liver, heart and kidney confirms the protective effect of dietary fish oil from diabetes induced tissue damages. Fish oil from S.longiceps brought maximum changes in concentration of TBARS, Vitamin C and in the activities of AST, LDH and Catalase in diabetic mice in comparison with the fish oil of R.kanagurta. Fish oil from S.longiceps offers better protective effect in diabe-tes induced mice in comparison to R. kanagurta oil.

Role of Diabetes in the Development of Acute Respiratory Distress Syndrome*

Diabetes has been associated with decreased development of acute respiratory distress syndrome in some, but not all, previous studies. Therefore, we examined the relationship between diabetes and development of acute respiratory distress syndrome and whether this association was modified by type of diabetes, etiology of acute respiratory distress syndrome, diabetes medications, or other potential confounders. Observational prospective multicenter study. Four adult ICUs at two tertiary academic medical centers. Three thousand eight hundred sixty critically ill patients at risk for acute respiratory distress syndrome from sepsis, pneumonia, trauma, aspiration, or massive transfusion. None. Diabetes history was present in 25.8% of patients. Diabetes was associated with lower rates of developing acute respiratory distress syndrome on univariate (odds ratio, 0.79; 95% CI, 0.66-0.94) and multivariate analysis (adjusted odds ratio, 0.76; 95% CI, 0.61-0.95). After including diabetes medications into the model, diabetes remained protective (adjusted odds ratio, 0.75; 95% CI, 0.59-0.94). Diabetes was associated with decreased development of acute respiratory distress syndrome both in the subgroup of patients with sepsis (adjusted odds ratio, 0.77; 95% CI, 0.61-0.97) and patients with noninfectious etiologies (adjusted odds ratio, 0.30; 95% CI, 0.10-0.90). The protective effect of diabetes on acute respiratory distress syndrome development is not clearly restricted to either type 1 (adjusted odds ratio, 0.50; 95% CI, 0.26-0.99; p = 0.046) or type 2 (adjusted odds ratio, 0.77; 95% CI, 0.60-1.00; p = 0.050) diabetes. Among patients in whom acute respiratory distress syndrome developed, diabetes was not associated with 60-day mortality on univariate (odds ratio, 1.11; 95% CI, 0.80-1.52) or multivariate analysis (adjusted odds ratio, 0.81; 95% CI, 0.56-1.18). Diabetes is associated with a lower rate of acute respiratory distress syndrome development, and this relationship remained after adjusting for clinical differences between diabetics and nondiabetics, such as obesity, acute hyperglycemia, and diabetes-associated medications. In addition, this association was present for type 1 and 2 diabetics and in all subgroups of at-risk patients.

The relative risk of aortic aneurysm in patients with giant cell arteritis compared with the general population of the UK

To evaluate the risk of aortic aneurysm in patients with giant cell arteritis (GCA) compared with age-, gender- and location-matched controls. A UK General Practice Research Database (GPRD) parallel cohort study of 6999 patients with GCA and 41 994 controls, matched on location, age and gender, was carried out. A competing risk model using aortic aneurysm as the primary outcome and non-aortic-aneurysm-related death as the competing risk was used to determine the relative risk (subhazard ratio) between non-GCA and GCA subjects, after adjustment for cardiovascular risk factors. Comparing the GCA cohort with the non-GCA cohort, the adjusted subhazard ratio (95% CI) for aortic aneurysm was 1.92 (1.52 to 2.41). Significant predictors of aortic aneurysm were being an ex-smoker (2.64 (2.03 to 3.43)) or a current smoker (3.37 (2.61 to 4.37)), previously taking antihypertensive drugs (1.57 (1.23 to 2.01)) and a history of diabetes (0.32 (0.19 to 0.56)) or cardiovascular disease (1.98 (1.50 to 2.63)). In a multivariate model of the GCA cohort, male gender (2.10 (1.38 to 3.19)), ex-smoker (2.20 (1.22 to 3.98)), current smoker (3.79 (2.20 to 6.53)), previous antihypertensive drugs (1.62 (1.00 to 2.61)) and diabetes (0.19 (0.05 to 0.77)) were significant predictors of aortic aneurysm. Patients with GCA have a twofold increased risk of aortic aneurysm, and this should be considered within the range of other risk factors including male gender, age and smoking. A separate screening programme is not indicated. The protective effect of diabetes in the development of aortic aneurysms in patients with GCA is also demonstrated.

Does Diabetes Have a Protective Effect on Migraine?

Diabetes is associated with an increased risk of several other chronic diseases. In contrast, a previous study found an inverse relation between diabetes and migraine, whereas another large population-based study showed that the prevalence of migraine among patients with diabetes varied strongly depending on age. We aimed to investigate how the prevalence of medically treated migraine in patients with diabetes varied depending on diabetic drug treatment, sex, and age in the complete Norwegian population. Data on all persons in Norway being prescribed medication for diabetes (n =124,649) or migraine (n = 81,225) in 2006 were obtained from the National Register of Prescriptions and analyzed in a cross-sectional design. Persons using diabetic drugs had an overall reduced prevalence of medically treated migraine when compared with the nondiabetic population (odds ratio [OR] = 0.72 [95% confidence interval = 0.68-0.75]). The OR was strongly associated with age. Although young persons receiving oral diabetic medication had, in fact, an increased prevalence of medically treated migraine, the prevalence declined with increasing age to about the same reduced prevalence (OR = 0.4-0.6) for all types of diabetes treatment in patients 60 to 69 years of age. The prevalence was equally decreased between men and women. The results suggest a markedly reduced prevalence of migraine among older patients with diabetes, when compared with the general population. One may speculate that the seemingly protective effect of diabetes on migraine could be a result of neuropathy.

The Effects of the Human Germline Connexin40 Mutation A96S on Cardiac Physiology in the Intact Animal

myocytes of diabetic rabbits as indicated by increase in co-immunoprecipitation (co-ip) of p47phox with p22phox subunits of NADPH oxidase and in glutathionylation of endothelial nitric oxide synthase (eNOS) (58± 6%) known to uncouple eNOS. Diabetes reduced co-ip of 1 Na+-K+ pump subunit with glutaredoxin 1 (Grx1) that reverses glutathionylation of proteins. Consistent with this, glutathionylation of the 1 subunit was increased (52± 9%) and electrogenic Na+-K+ pump current measured in voltage-clamped myocytes was reduced (0.26± 0.04 vs 0.44± 0.04 pA/pF). Administration of CL (40 g/kg/h) had no effect on glucose or insulin levels but reduced lipid peroxidation. It also reduced p47phox/p22phox co-ip, reduced glutathionylation of eNOS (51± 1%) and 1 pump subunit (74± 13%), increased Grx1/ 1 pump subunit co-ip and increased Na+-K+ pump current (0.6± 0.1 vs 0.26± 0.04 pA/pF). Diabetes inducedmolecular remodelling in anoxidative pathway that is determinant of the functionally important oxidativemodification of Na+–K+ pump. Reversal of these changes by 3 AR stimulation suggests that 3 ARagonists may have cardiovascular protective effects in diabetes. http://dx.doi.org/10.1016/j.hlc.2013.05.239