Effect of CLA supplementation on factors related to vascular dysfunction in arteries of orchidectomized rats.

The vascular endothelium is a monolayer of flat epithelial cells located between the circulating blood and the underlying connective tissue. It conveys key functions that when impaired, lead to endothelial dysfunction. This condition is responsible for the pathogenesis of vascular diseases. The cardioprotective effect of sex hormones is widely known; hence, a murine orchidectomized model has been employed to study the effects caused by their deficiency. In the search for approaches to maintain vascular health, the effect of dietary fatty acids as CLA on cardiovascular diseases has been studied. Some proven beneficial properties of CLA are antioxidant, antiatherogenic and anti-inflammatory. Our objective was to evaluate the effect of a diet supplemented with 1.8 % (w/w) of CLA, administered during eight weeks, on the amount of cholesterol oxidation products (COPs) produced by orchidectomy and on factors related to vascular dysfunction in the aorta and the mesenteric arteries. The diet with CLA prevented the increase in prostanoids formation and maintained the normal physiological conditions of NO and antioxidant activity. In addition, it prevented the increase in cholesterol and COPs at the vascular wall. CLA-supplemented diet prevented the orchidectomy-induced alterations on prostanoids, NO and COPs and also improved the antioxidant activity. These findings could contribute to understand the mechanisms of actions of CLA involved in the prevention of cardiovascular diseases.

Regular insulin added to total parenteral nutrition vs subcutaneous glargine in non-critically ill diabetic inpatients, a multicenter randomized clinical trial: INSUPAR trial.

BACKGROUND: There is no established insulin regimen in T2DM patients receiving parenteral nutrition. AIMS: To compare the effectiveness (metabolic control) and safety of two insulin regimens in patients with diabetes receiving TPN. DESIGN: Prospective, open-label, multicenter, clinical trial on adult inpatients with type 2 diabetes on a non-critical setting with indication for TPN. Patients were randomized on one of these two regimens: 100% of RI on TPN or 50% of Regular insulin added to TPN bag and 50% subcutaneous GI. Data were analyzed according to intention-to-treat principle. RESULTS: 81 patients were on RI and 80 on GI. No differences were observed in neither average total daily dose of insulin, programmed or correction, nor in capillary mean blood glucose during TPN infusion (165.3 ± 35.4 in RI vs 172.5 ± 43.6 mg/dL in GI; p = 0.25). Mean capillary glucose was significantly lower in the GI group within two days after TPN interruption (160.3 ± 45.1 in RI vs 141.7 ± 43.8 mg/dL in GI; p = 0.024). The percentage of capillary glucose above 180 mg/dL was similar in both groups. The rate of capillary glucose ≤70 mg/dL, the number of hypoglycemic episodes per 100 days of TPN, and the percentage of patients with non-severe hypoglycemia were significantly higher on GI group. No severe hypoglycemia was detected. No differences were observed in length of stay, infectious complications, or hospital mortality. CONCLUSION: Effectiveness of both regimens was similar. GI group achieved better metabolic control after TPN interruption but non-severe hypoglycemia rate was higher in the GI group. CLINICAL TRIAL REGISTRY: This trial is registered at clinicaltrials.gov as NCT02706119.

Dietary docosahexaenoic acid supplementation prevents the formation of cholesterol oxidation products in arteries from orchidectomized rats.

Testosterone deficiency has been correlated with increased cardiovascular diseases, which in turn has been associated with increased oxidative stress. Several studies have considered cholesterol oxidation products (COPs) as oxidative stress biomarkers, since some of them play pro-oxidant and pro-inflammatory roles. We have previously described the cardioprotective effects of a dosahexaenoic acid (DHA) supplemented diet on the aortic and mesenteric artery function of orchidectomized rats. The aim of this study was to investigate whether impaired gonadal function alters the formation of COPs, as well as the potential preventive role of a DHA-supplemented diet on that effect. For this purpose, aortic and mesenteric artery segments obtained from control and orchidectomized rats, fed with a standard or supplemented with DHA, were used. The content of the following COPs: 7α-hydroxycholesterol, 7ß-hydroxycholesterol, 7-ketocholesterol, 5,6α-epoxycholesterol, 5,6ß-epoxycholesterol, cholestanetriol and 25-hydroxycholesterol, were analyzed by gas chromatography. The results showed that orchidectomy increased the formation of COPs in arteries from orchidectomized rats, which may participate in the orchidectomy-induced structural and functional vascular alterations already reported. The fact that the DHA-supplemented diet prevented the orchidectomy-induced COPs increase confirms the cardiovascular protective actions of DHA, which could be of special relevance in mesenteric arterial bed, since it importantly controls the systemic vascular resistance.

Docosahexaenoic Acid Supplemented Diet Influences the Orchidectomy-Induced Vascular Dysfunction in Rat Mesenteric Arteries.

Over the past few decades, the cardiovascular benefits of a high dietary intake of long-chain polyunsaturated fatty acids (PUFAs), like docosahexaenoic acid (DHA), have been extensively studied. However, many of the molecular mechanisms and effects exerted by PUFAs have yet to be well explained. The lack of sex hormones alters vascular tone, and we have described that a DHA-supplemented diet to orchidectomized rats improve vascular function of the aorta. Based on these data and since the mesenteric artery importantly controls the systemic vascular resistance, the objective of this study was to analyze the effect of a DHA-supplemented diet on the mesenteric vascular function from orchidectomized rats. For this purpose mesenteric artery segments obtained from control, orchidectomized or orchidectomized plus DHA-supplemented diet were utilized to analyze: (1) the release of prostanoids, (2) formation of NO and ROS, (3) the vasodilator response to acetylcholine (ACh), as well as the involvement of prostanoids and NO in this response, and (4) the vasoconstrictor response to electrical field stimulation (EFS), analyzing also the effect of exogenous noradrenaline (NA), and the NO donor, sodium nitroprusside (SNP). The results demonstrate beneficial effects of DHA on the vascular function in orchidectomized rats, which include a decrease in the prostanoids release and superoxide formation that were previously augmented by orchidectomy. Additionally, there was an increase in endothelial NO formation and the response to ACh, in which NO involvement and the participation of vasodilator prostanoids were increased. DHA also reversed the decrease in EFS-induced response caused by orchidectomy. All of these findings suggest beneficial effects of DHA on vascular function by reversing the neurogenic response and the endothelial dysfunction caused by orchidectomy.

Effect of Dietary Docosahexaenoic Acid Supplementation on the Participation of Vasodilator Factors in Aorta from Orchidectomized Rats.

Benefits of n-3 polyunsaturated fatty acids (PUFAs) against cardiovascular diseases have been reported. Vascular tone regulation is largely mediated by endothelial factors whose release is modulated by sex hormones. Since the incidence of cardiovascular pathologies has been correlated with decreased levels of sex hormones, the aim of this study was to analyze whether a diet supplemented with the specific PUFA docosahexaenoic acid (DHA) could prevent vascular changes induced by an impaired gonadal function. For this purpose, control and orchidectomized rats were fed with a standard diet supplemented with 5% (w/w) sunflower oil or with 3% (w/w) sunflower oil plus 2% (w/w) DHA. The lipid profile, the blood pressure, the production of prostanoids and nitric oxide (NO), and the redox status of biological samples from control and orchidectomized rats, fed control or DHA-supplemented diet, were analyzed. The vasodilator response and the contribution of NO, prostanoids and hyperpolarizing mechanisms were also studied. The results showed that orchidectomy negatively affected the lipid profile, increased the production of prostanoids and reactive oxygen species (ROS), and decreased NO production and the antioxidant capacity, as well as the participation of hyperpolarizing mechanisms in the vasodilator responses. The DHA-supplemented diet of the orchidectomized rats decreased the release of prostanoids and ROS, while increasing NO production and the antioxidant capacity, and it also improved the lipid profile. Additionally, it restored the participation of hyperpolarizing mechanisms by activating potassium. Since the modifications induced by the DHA-supplemented diet were observed in the orchidectomized, but not in the healthy group, DHA seems to exert cardioprotective effects in physiopathological situations in which vascular dysfunction exists.

Prevalence of diabetes, prediabetes, and stress hyperglycemia: insulin therapy and metabolic control in patients on total parenteral nutrition (prospective multicenter study).

OBJECTIVE: The prevalence of carbohydrate metabolism disorders in patients who receive total parenteral nutrition (TPN) is not well known. These disorders can affect the treatment, metabolic control, and prognosis of affected patients. The aims of this study were to determine the prevalence in noncritically ill patients on TPN of diabetes, prediabetes, and stress hyperglycemia; the factors affecting hyperglycemia during TPN; and the insulin therapy provided and the metabolic control achieved. METHODS: We undertook a prospective multicenter study involving 19 Spanish hospitals. Noncritically ill patients who were prescribed TPN were included, and data were collected on demographic, clinical, and laboratory variables (glycated hemoglobin, C-reactive protein [CRP], capillary blood glucose) as well as insulin treatment. RESULTS: The study included 605 patients. Before initiation of TPN, the prevalence of known diabetes was 17.4%, unknown diabetes 4.3%, stress hyperglycemia 7.1%, and prediabetes 27.8%. During TPN therapy, 50.9% of patients had at least one capillary blood glucose of >180 mg/dL. Predisposing factors were age, levels of CRP and glycated hemoglobin, the presence of diabetes, infectious complications, the number of grams of carbohydrates infused, and the administration of glucose-elevating drugs. Most (71.6%) patients were treated with insulin. The mean capillary blood glucose levels during TPN were: known diabetes (178.6 ± 46.5 mg/dL), unknown diabetes (173.9 ± 51.9), prediabetes (136.0 ± 25.4), stress hyperglycemia (146.0 ± 29.3), and normal (123.2 ± 19.9) (P<.001). CONCLUSION: The prevalence of carbohydrate metabolism disorders is very high in noncritically ill patients on TPN. These disorders affect insulin treatment and the degree of metabolic control achieved.