Carlos Morillas

Rapid Onset of Wernicke's Encephalopathy following Gastric Restrictive Surgery

A patient with severe vomiting following gastric banding developed Wernickes encephalopathy. All neurological disorders disappeared with thiamine treatment. This complication may be prevented by keen awareness, early diagnosis and treatment, in patients with persistent vomiting. Vitamin and mineral supplementation must be taken in patients following bariatric surgery.

Effect of Thyroid Hormone Replacement on Lipoprotein(a), Lipids, and Apolipoproteins in Subjects With Hypothyroidism

OBJECTIVE To study the effect of thyroid hormone replacement on total cholesterol, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-I and B-100, and lipoprotein(a) [Lp(a)] in subjects with hypothyroidism. MATERIAL AND METHODS In 17 patients with clinical primary hypothyroidism, studies were done before and after thyroid hormone replacement therapy. Free thyroxine and thyrotropin were determined by chemiluminescent assay. Total cholesterol and triglycerides were measured by enzymatic methods, and HDL-C was measured after dextran sulfate-MgCl2 precipitation. Apolipoprotein A-I and B-100 were assayed by immunonephelometry. For measurement of Lp(a), we used a sequential sandwich enzyme-linked immunosorbent assay. RESULTS After levothyroxine treatment, the mean concentration of thyrotropin decreased from 91.4 to 3.7 microIU/mL, and free thyroxine increased from 0.5 to 1.2 ng/ dL. Total cholesterol, triglycerides, HDL-C, low-density lipoprotein cholesterol, and apolipoprotein A-I and B-100 decreased after thyroid hormone replacement therapy. Lp(a) levels also decreased significantly (P<0.05) after treatment, from a mean of 33.4 to 25.6 mg/dL. CONCLUSION Hypothyroidism is associated with an increase in total cholesterol, triglycerides, HDL-C, apolipoprotein A-I and B-100, and Lp(a). A reduction in lipid and lipoprotein levels after thyroid hormone replacement in our study cohort resulted in a less atherogenic profile.

Effects of phytosterol ester-enriched low-fat milk on serum lipoprotein profile in mildly hypercholesterolaemic patients are not related to dietary cholesterol or saturated fat intake.

Phytosterols (PS) are recommended to reduce LDL-cholesterol. However, the influence of cholesterol and fat intake on the lipid-lowering effect of PS in mildly hypercholesterolaemia is unclear. Thus, the aim of the present study was to evaluate whether the efficacy of PS is related to the composition of saturated fat and dietary cholesterol intake. Additionally, serum carotenoid content was analysed to evaluate to what extent it was undermined by PS. This was a 3-month randomised, parallel trial with a three-arm design. Patients were divided into three groups: healthy diet (n 24), healthy diet+PS (n 31) and free diet+PS (n 29), receiving 2 g/d of PS. Healthy and free diets were characterised by a daily ingestion of 6.8 % of saturated fat and 194.4 mg of cholesterol and 12.7 % of saturated fat and 268.1 mg of cholesterol, respectively. After PS therapy, patients receiving the healthy diet+PS or a free diet+PS exhibited a similar reduction in total cholesterol (6.7 and 5.5 %), LDL-cholesterol (9.6 and 7.0 %), non-HDL-cholesterol (12.2 and 8.9 %) and apo B-100/apo A-I ratio (11.5 and 11.6 %), respectively. In patients following the healthy diet, (β-carotene concentration rose by 26.9 %, whereas the β-carotene and lycopene levels dropped by 21.0 and 22.8 % in the group receiving the free diet+PS, respectively. No change was observed in carotenoid levels in healthy diet+PS group. In conclusion, the efficacy of PS in relation to lipoprotein profile is not influenced by saturated fat or dietary cholesterol intake, which confirms the positive effect of healthy diet therapy in improving the negative effects that PS exert on carotenoid levels.

Cardiovascular autonomic neuropathy in Type 1 diabetic patients with and without peripheral neuropathy

One hundred Type 1 diabetic patients (54 men, 46 women) mean age 28.9+/-8.4 years, were selected from among individuals referred to our hospital, with no previous diagnosis of diabetic chronic complications including diabetic neuropathy. After clinical and physical examinations, subjects were divided into two groups: with (n = 37) and without (n = 63) peripheral neuropathy. The percentage of subjects with cardiovascular autonomic neuropathy (AN), diagnosed by positive results to at least two of the five cardiovascular tests (Valsalva ratio, EI ratio, 30/15 ratio, blood-pressure response to standing up and handgrip test), was 40%: 72.9% in the group with peripheral neuropathy and 20.6% in the group without peripheral neuropathy (P < 0.0001). The prevalence of cardiovascular AN was related to the duration of the diabetes (P < 0.0001) and to HbA1c (P < 0.02). The presence of microalbuminuria and the existence of retinopathy were higher (P < 0.01 ) in group 1 (with peripheral neuropathy). Logistic regression analysis showed that only the presence of higher excretion of albumin is independently related to the presence of peripheral neuropathy. In conclusion, cardiovascular AN is frequent in Type 1 diabetes; furthermore, prevalence increases with the existence of peripheral neuropathy and with duration of the diabetes.

Management of diabetic ketoacidosis in a teaching hospital

The aim of our study was to evaluate clinical management of diabetic ketoacidosis (DKA) in a teaching hospital. We followed all the patients hospitalised for DKA over six years (1995–2000), and we recorded clinical data, laboratory finding at entrance and clinical management. We compared the data to the standards set in guidelines. Our study showed an important delay of initiation of intravenous fluid (70% of cases), an under-replacement with intravenous fluid (69% of cases) and with potassium therapy (80% of cases), and an excessive use of alkali therapy. In conclusion, suboptimal management of DKA occurred in a large percentage of patients.

Association of serum retinol binding protein 4 with atherogenic dyslipidemia in morbid obese patients.

Retinol binding protein 4 (RBP4) is an adipokine that may contribute to the development of insulin resistance. However, how this adipokine is affected and its possible involvement in lipid metabolism in obese patients with varying degrees of insulin resistance is yet to be determined. A total of 299 middle-aged morbid obese patients (BMI>40 kg/m2) were divided in euglycemic, metabolic syndrome or type 2 diabetic. Anthropometric measurements, biochemical variables and systemic RBP4 levels were determined. RBP4 levels were significantly higher in patients with metabolic syndrome and type 2 diabetes than in euglycemic subjects (42.9±14.6; 42.3±17.0 and 37.4±11.7 µg/ml, respectively) and correlated with triglycerides but not with those of HOMA-IR in the whole population. The multivariate regression model revealed that triglycerides were the strongest predictor of systemic RBP4 levels. Analysis of lipoprotein subfractions in a subpopulation of 80 subjects showed an altered profile of insulin resistant states characterized by higher VLDL, sdLDL and small HDL percentages and lower large HDL percentage. Although RBP4 levels correlated significantly with LDL particle size and small HDL percentage, the latter parameter was independently associated only with RBP4. Our study reveals that systemic RBP4 levels could play an important role in lipid metabolism in morbid obesity, increasing triglyceride levels and contributing to the formation of small HDL.

Effect of weight loss on C3 and C4 components of complement in obese patients

Eur J Clin Invest 2012; 42 (5): 503–509

Evaluation of cardiovascular risk and oxidative stress parameters in hypercholesterolemic subjects on a standard healthy diet including low-fat milk enriched with plant sterols

A healthy diet and plant sterols (PS) are recommended for reducing low-density lipoprotein (LDL) cholesterol and, subsequently, the risk of premature cardiovascular disease. PS mediate a decrease in fat-soluble vitamin concentration, which can lead to a general impairment of antioxidative defenses and an increase in oxidative stress. Thus, we evaluated the effects of a healthy diet, including PS-enriched low-fat milk, on cardiovascular risk and oxidative stress parameters in hypercholesterolemic subjects. This was a randomized parallel trial employing 40 subjects and consisting of two 3-month intervention phases. After 3 months on a standard healthy diet, subjects were divided into two intervention groups: a diet group and a diet+PS group (2 g/day). Lipid profile, apolipoproteins, high-sensitivity C-reactive protein and oxidative stress parameters were analyzed. Diet significantly reduced total and LDL cholesterol (4.0% and 4.7%, respectively), produced an increase in the level of beta-carotene (23%) and improved the antioxidant capacity of LDL cholesterol particles (4.6%). PS induced a significant decrease in total cholesterol (6.4%), LDL (9.9%) and the apolipoprotein B100/apolipoprotein A1 ratio (4.9%), but led to a decrease in cryptoxanthin level (29%) without any change being observed in the antioxidant capacity of LDL cholesterol particles, total antioxidant status or lipid peroxidation. After 3 months, we observed the positive effect of including a PS supplement in dietary measures, as the lipoprotein-mediated risk of cardiovascular disease was reduced. Despite a decrease in the concentration of cryptoxanthin, no evidence of a global impairment of antioxidative defenses or an enhancement of oxidative stress parameters was found.

Is Glycemic Control Modulating Endoplasmic Reticulum Stress in Leukocytes of Type 2 Diabetic Patients

Oxidative and endoplasmic reticulum (ER) stress is related to type 2 diabetes (T2D), but the influence of glycemic control on these parameters and its relationship with leukocyte-endothelial interactions is not known. In our study population consisting of 164 diabetic patients, (102 with glycated hemoglobin [HbA1c] <7% and 62 with HbA1c >7%) and 84 nondiabetic controls, we have verified a common anthropometric and metabolic pattern of T2D with dyslipidemia. Inflammatory parameters (high-sensitive C-reactive protein [hs-CRP] and tumor necrosis factor alpha [TNFα]) and E-selectin levels were enhanced in the HbA1c >7% group with regard to controls. O2 consumption and mitochondrial membrane potential were lower in diabetic patients than in controls. Reactive oxygen species (ROS) production was enhanced in diabetic patients than in controls and positively correlated with HbA1c levels. GRP78 levels were higher in both diabetic groups. However, HbA1c <7% patients displayed higher levels of spliced X-box binding protein 1 (sXBP1), whereas HbA1c >7% patients exhibited preferentially enhanced levels of CHOP (CCAAT/enhancer binding protein [C/EBP] homologous protein) and activating transcription factor 6 (ATF6). Reduced leukocyte rolling velocity and increased rolling flux and adhesion were observed in diabetic patients. Our findings lead to the hypothesis of an association between poor glycemic control in T2D and increased leukocyte ROS production and chronic ER stress that could finally promote leukocyte-endothelial interactions, which, in turn, poses a risk of vascular complications for these patients.

Mitochondrial dysfunction and oxidative stress in insulin resistance.

Evidence is mounting of the involvement of mitochondrial dysfunction in insulin resistance, diabetes and associated complications. This review aims to provide an overview of the effects of insulin resistance on mitochondrial function in several tissues. We consider the pathogenesis of insulin resistance from a mitochondrial perspective and contemplate potential beneficial effects of strategies aimed at modulating mitochondrial function in insulin resistance, including insulin and insulin-sensitizing drugs, antioxidants, and selectively targeting antioxidants to mitochondria.