Short-term therapy with rosiglitatzone, a PPAR-¿ agonist improves metabolic profile and vascular function in non-obese lean wistar rats

A number of preclinical and clinical studies have reported blood-pressure-lowering benefits of thiazolidinediones in diabetic subjects and animal models of diabetes. This study was designed to further elucidate vascular effects of rosiglitazone, on healthy nonobese, lean animals. Adult male Wistar rats were randomized and assigned to control and rosiglitazone-treated groups and were dosed daily with either vehicle or rosiglitazone (10 mg kg(−1) day(−1)) by oral gavage for 5 days. Compared with control group, rosiglitazone treatment significantly reduced plasma levels of triglycerides (>240%) and nonesterified free fatty acids (>268%) (both, P < 0.001). There were no changes in vascular contractility to KCl or noradrenaline between two groups. However, rosiglitazone therapy improved carbamylcholine-induced vasorelaxation (93 ± 3 % versus control 78 ± 2, P < 0.01) an effect which was abolished by L-NAME. There was no difference in sodium nitroprusside-induced vasorelaxation between the control and rosiglitazone-treated animals. These results indicate that short-term rosiglitazone therapy improves both metabolic profile and vascular function in lean rats. The vascular effect of rosiglitazone appears to be mediated by alteration in NO production possibly by activation of endothelial PPARγ. This increased NO production together with improved lipid profile may explain mechanism(s) of blood-pressure-lowering effects of thiazolidinediones on both human and experimental animals

Effect of diet-induced obesity on protein expression in insulin signalling pathways of skeletal muscle in male Wistar rats

BACKGROUND: The prevalence of diet-induced obesity is increasing globally, and posing significant health problems for millions of people worldwide. Diet-induced obesity is a major contributor to the global pandemic of type 2 diabetes mellitus. The reduced ability of muscle tissue to regulate glucose homeostasis plays a major role in the development and prognosis of type 2 diabetes. In this study, an animal model of diet-induced obesity was used to elucidate changes in skeletal muscle insulin signaling in obesity-induced diabetes. METHODS: Adult male Wistar rats were randomized and assigned to either a control group or to a test group. Controls were fed a standard laboratory pellet diet (chow-fed), while the test group had free access to a highly palatable diet (diet-fed). After 8 weeks, the diet-fed animals were subdivided into three subgroups and their diets were altered as follows: diet-to-chow, diet-fed with addition of fenofibrate given by oral gavage for a further 7 weeks, or diet-fed with vehicle given by oral gavage for a further 7 weeks, respectively. RESULTS: Untreated diet-fed animals had a significantly higher body weight and metabolic profile than the control chow-fed animals. Intramuscular triacylglyceride levels in the untreated obese animals were significantly higher than those in the control chow-fed group. Expression of protein kinase C beta, phosphatidylinositol 3, Shc, insulin receptor substrate 1, ERK1/2, and endothelial nitric oxide synthase was significantly increased by dietary obesity, while that of insulin receptor beta, insulin receptor substrate 1, and protein kinase B (Akt) were not affected by obesity. CONCLUSION: These data suggest that diet-induced obesity affects insulin signaling mechanisms, leading to insulin resistance in muscle

Sociodemographic and clinical predictors of self-management among people with poorly controlled Type 1 and Type 2 Diabetes: the role of illness perceptions and self-efficacy

Self-management is critical if people with diabetes are to minimise their risk of macrovascular and microvascular complications, yet adherence to self-management recommendations is suboptimal. Understanding the predictors of optimal diabetes self-management in specific populations is needed to inform effective interventions. This study investigated the role of demographic and clinical characteristics, illness perceptions, and self-efficacy in explaining adherence to self-management recommendations among people with poorly controlled diabetes in North West of England. Illness perceptions and self-efficacy data were collected using validated questionnaires and clinical data were obtained from hospital records. Correlations were used to investigate bivariate relationships between independent variables and self-management, and multiple regression techniques were used to determine demographic and psychosocial predictors of self-management. Various demographic and clinical characteristics were associated with adherence to self-management recommendations. In particular, employment status explained 11% of the variation in adherence to foot care whilst diabetes treatment category explained 9% of exercise and 21% of the variations in SMBG recommendations. Also, 22% and 8% of the variations in overall self-management were explained by illness perceptions and self-efficacy beliefs, respectively. Illness perceptions and self-efficacy beliefs of people with poorly controlled diabetes are important predictors of their self-management behaviours and could potentially guide effective interventions

The effects of 8-weeks concurrent training on necdin levels and insulin resistance index in obese middle-aged men.

Abstract Background: Obesity per se is a major global health problem leading to an increase in morbidity and premature mortality however increasing physical activity often results in a marked weight loss. Necdin has been shown to be an important negative regulator of adipogenesis of the white adipose tissue. We hypothesized that exercise training would impact necdin synthesis inhibiting adipocity and ultimately reducing obesity. Thus, this study was conducted to determine the effects of 8-weeks concurrent training on plasma necdin levels in obese middle-aged men. Methods: Twenty three sedentary obese middle-aged men were randomly assigned to concurrent training group (CTG: n=12) or control group (CG: n=11). The subjects in concurrent training group performed endurance and resistance training on the same days, 3 days a week, 55-65 (mean: 60) min gradually was spent over 8 weeks Results: At the end of the study, there were significant decreases in total body weight (up to 3.5 kg), body mass index (BMI; 1.2 kg/m2), waist hip ratio (WHR; 0.02 unit) and the fasting plasma insulin levels (up to 58%) and insulin resistance (HOMA-IR; P<0.05) in CTG group compared with the CG group. However, there were no significant differences in the fasting plasma levels of glucose or necdin between the two groups at the end of the study. Conclusion: Concurrent training is a viable tool in reducing body weight. There seems to be no association between 8-weeks concurrent training-induced weight loss and the total plasma necdin levels in obese middle-aged men

The effects of diet-induced obesity on hepatocyte insulin signaling pathways and induction of non-alcoholic liver damage

The prevalence of diet-induced obesity is increasing amongst adults and children worldwide, predisposing millions of people to an array of health problems that include metabolic syndrome, non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. In this study we used experimental animals to investigate the effects of dietary obesity on markers of hepatic insulin signaling as well as structural changes in hepatocytes. Adult male Wistar rats were randomized and assigned to either a control group or a test group. Controls were fed standard laboratory pelleted diet (chow-fed), while the test group had free access to a highly-palatable diet (HPD). After eight weeks, the HPD-fed animals were subdivided into three subgroups and their diets altered as follows: HPD-to-chow, HPD with the addition of fenofibrate given by oral gavage for a further seven weeks, or HPD with vehicle (1% carboxymethylcellulose at 1 mL/kg body weight) given by oral gavage for a further seven weeks, respectively. Untreated diet-fed animals had significantly higher body weight, liver weight, and all measured metabolic profiles compared with chow-fed and treated diet-fed groups. Expression of kinases IRβ, IRS-1, AKt, eNOS, Shc and ERK1/2 were unaffected by obesity, while IRS-2 and P I3 kinase levels were significantly reduced in untreated HPD animals. Compared with chow-fed animals, steatosis and steatohepatitis were almost doubled in animals from untreated HPD, while removal of HPD and fenofibrate-treatment reduced steatosis by 40% and 80% respectively. These data suggest that diet-induced obesity affects intracellular insulin signaling mechanisms, namely IRS-2 and PI 3-kinase, leading to hepatic insulin resistance. Moreover, diet-induced obesity induces fatty liver, an effect which can be reversed by either removal of the source of obesity or treatment with fenofibrate, a peroxisome proliferator-activated receptor alpha agonist

Working conditions, neighbourhood deprivation and quality of life among people with diabetes: a cross-sectional study

Diabetes is a chronic metabolic disorder that requires constant management to maintain good health and quality of life. Poorly managed diabetes could lead to serious complications and early death. With the ageing demographic profile, there is growing recognition that older people, including those with diabetes, are increasingly becoming a significant proportion of the labour force leading to changes in pension and retirement-related policies. For people with diabetes, understanding how working conditions influence their health and wellbeing is an important step to addressing issues that could compromise their prolonged participation in the labour force. This study examined impact of job-strain on health-related quality of life among people with diabetes. A hundred and twenty-three eligible individuals with diabetes who attended two acute trusts, participated in the study. Diabetes specific quality of life, job characteristics and personal/disease characteristics were measured using questionnaires. Univariate and multivariate statistical analyses were undertaken using SPSS version-22. Over a sixth (17.4%) of participants reported poor quality of life. Marital/co-habitation status, type of diabetes and presence of other long-term conditions were associated with quality of life. High deprivation levels was associated with poor quality of life but there was no association between deprivation levels and participants’ perception of the impact of diabetes on their quality of life. High psychological job-demands and physical job-demands were each associated with poor quality of life. High physical and psychological job-demands are potentially detrimental to quality of life in people with diabetes. Adjustments in working conditions could prove crucial in improving quality of life of employees with diabetes

Differential vascular dysfunction in response to diets of differing macronutrient composition: a phenomenonological study

<p>Abstract</p> <p>Background</p> <p>Vascular dysfunction can develop from consumption of an energy-rich diet, even prior to the onset of obesity. However, the roles played by different dietary components remain uncertain. While attempting to develop models of obesity in a separate study, we observed that two high-energy diets of differing macronutrient compositions affected vascular function differently in overweight rats.</p> <p>Methods</p> <p>Male Wistar rats (<it>n </it>= 6/group) were fed diets providing varying percentages of energy from fat and carbohydrate (CHO). For 10 weeks, they were fed either chow, as control diet (10% of energy from fat; 63% from CHO), chow supplemented with chocolate biscuit (30% fat; 56% CHO) or a high-fat diet (45% fat; 35% CHO). Blood concentrations of biochemical markers of obesity were measured, and epididymal fat pads weighed as a measure of adiposity. Mesenteric arteries were dissected and their contractile and relaxant properties analysed myographically. Data were tested by analysis of variance (ANOVA).</p> <p>Results</p> <p>Weight gain and plasma concentrations of glucose, insulin and leptin were similar in all groups. However, biscuit-fed animals showed increased food intake (+27%; <it>p </it>< 0.01) and elevated concentrations of TGs and NEFAs (+41% and +17%; both <it>p </it>< 0.05). High-fat-fed animals showed an increase only in NEFAs (+38%; <it>p </it>< 0.01). Arterial vasoconstriction in response to NA and KCl increased only in biscuit-fed rats (both <it>p </it>< 0.01), while vasorelaxation in response to CCh and SNP, but not histamine, was attenuated in both groups (both <it>p </it>< 0.01). Furthermore, whereas the effect of the high-fat diet was most pronounced in endothelium-dependent vasorelaxation, the biscuit diet had the greater effect on endothelium-independent vasorelaxation.</p> <p>Conclusion</p> <p>Vascular dysfunction resulting from consumption of a high-fat or combined relatively high-fat/high-CHO diet occurs through different physiological processes, which may be attributable to their differing macronutrient compositions. Combining potentially atherogenic macronutrients induces more extensive vascular impairment than that of high-fat alone, and may be attributable to the more marked dyslipidaemia observed with such a diet. Thus, these findings help clarify the role of dietary components in vascular impairment, which has implications for clinical approaches to preventing cardiovascular disease.</p

Effect of diabetes on caregiver burden in an observational study of individuals with Alzheimer’s disease

Background The burden on caregivers of patients with Alzheimer’s disease (AD) is associated with the patient’s functional status and may also be influenced by chronic comorbid medical conditions, such as diabetes. This post-hoc exploratory analysis assessed whether comorbid diabetes in patients with AD affects caregiver burden, and whether caregivers with diabetes experience greater burden than caregivers without diabetes. Caregiver and patient healthcare resource use (HCRU) were also assessed. Methods Baseline data from the GERAS observational study of patients with AD and their caregivers (both n = 1495) in France, Germany and the UK were analyzed. Caregiver burden was assessed using the Zarit Burden Interview (ZBI). Caregiver time on activities of daily living (ADL: basic ADL; instrumental ADL, iADL) and supervision (hours/month), and caregiver and patient HCRU (outpatient visits, emergency room visits, nights hospitalized) were assessed using the Resource Utilization in Dementia instrument for the month before the baseline visit. Regression analyses were adjusted for relevant covariates. Time on supervision and basic ADL was analyzed using zero-inflated negative binomial regression. Results Caregivers of patients with diabetes (n = 188) were younger and more likely to be female (both p < 0.05), compared with caregivers of patients without diabetes (n = 1307). Analyses showed caregivers of patients with diabetes spent significantly more time on iADL (+16 %; p = 0.03; increases were also observed for basic ADL and total caregiver time but did not reach statistical significance) and had a trend towards increased ZBI score. Patients with diabetes had a 63 % increase in the odds of requiring supervision versus those without diabetes (p = 0.01). Caregiver and patient HCRU did not differ according to patient diabetes. Caregivers with diabetes (n = 127) did not differ from those without diabetes (n = 1367) regarding burden/time, but caregivers with diabetes had a 91 % increase in the odds of having outpatient visits (p = 0.01). Conclusions This cross-sectional analysis found caregiver time on iADL and supervision was higher for caregivers of patients with AD and diabetes versus without diabetes, while HCRU was unaffected by patient diabetes. Longitudinal analyses assessing change in caregiver burden over time by patient diabetes status may help clarify the cumulative impact of diabetes and AD dementia on caregiver burden

Omega-3 fatty acid supplementation and cognitive function: are smaller dosages more beneficial?

Abdul-Razak Abubakari,1 Mohammad-Mahdi Naderali,2 Ebrahim K Naderali3 1School of Health and Life Sciences, Glasgow Caledonian University, London, UK; 2Blue Coat School, Liverpool, UK; 3School of Health Sciences, Liverpool Hope University, Hope Park Campus, Liverpool, UK Abstract: As longevity increases, so does the global prevalence of cognitive dysfunction. Numerous lifestyle and/or dietary interventions such as omega-3 fatty acids have been suggested to improve memory. Therefore, this study examined the consistency and strength of the impact of supplementation of omega-3 fatty acids on overall cognitive function using systematic reviews and meta-analytic methods. Of 905 studies retrieved from all searches, 12 randomized controlled trials were included in the meta-analysis. There were differences between studies reporting outcomes for single memory function parameters. Subgroup analysis of doses used (low versus high) indicated that subjects receiving low (&lt;1.73 g/day) doses of omega-3 fatty acids had a significant reduction in cognitive decline rate (-0.07, 95% confidence interval -0.01, -0.02) but there was no evidence for beneficial effects at higher doses (+0.04, 95% confidence interval -0.06, +0.14) compared with the placebo group. This study suggests that omega-3 fatty acids may be beneficial in preventing memory decline at lower doses. Keywords: cognitive impairment, Alzheimer&#39;s disease, dietary fatty acids, omega-3, docosahexaenoic aci