Tatjána Ábel

Receptor polymorphisms and diseases

The aim of our review is to summarize common genetic variations of some receptors associated with clinical consequences, which were not outlined in the previous special issue of this journal. Because of the multiple pathomechanisms of diseases, a set of genetic variation can play a role in the development of pathological conditions. From the data available three articles would merit a greater interest. In systemic lupus erythematosus the associations related to some polymorphisms of Fc-, tumor necrosis factor (TNF) alpha- and interferon receptor may explore new autoimmunological and inflammatorical pathomechanisms. In the endocrinology, the androgen receptor repeat polymorphism will exert significant aspects in the development of prostate cancer. The pleoitropic responsibility of vitamin D3 receptor polymorphism in the pathogenesis of immunological disorders (primary biliary cirrhosis, inflammatory bowel disease, type 1 diabetes mellitus) and of malignancies (malignant melanoma, breast cancer) shed light on the importance of common nuclear receptors. Nevertheless, in the future studies a more consistent approach minimizing requirement bias in the selection of patients will approve our understanding the role of genetic influence on the pathogenesis of diseases.

Non-alcoholic fatty liver disease and cardiovascular risk

Non-alcoholic fatty liver disease is present in 15-25% of the general population. The fundamental derangement in non-alcoholic fatty liver disease is insulin resistance, a key component of the metabolic syndrome, which includes type 2 diabetes mellitus, dyslipidemia, hypertension, and obesity. The natural history of non-alcoholic fatty liver disease is not always benign, and causality for chronic liver disease and cirrhosis is well known in clinical practice and sometimes it is accompanied by hepatocellular carcinoma. Non-alcoholic fatty liver disease is likely to be associated with increased cardiovascular disease risk, and it raises the possibility that non-alcoholic fatty liver disease may be not only a marker but also an early mediator of atherosclerosis. Therapy is currently directed at treating components of the metabolic syndrome which may be beneficial also for the liver.

The effect of ciprofibrate on flow-mediated dilation and inflammatory markers in patients with combined hyperlipidemia

Impairment of flow-mediated dilation (FMD) has been shown to be associated with hypercholesterolemia and hypertriglyceridemia and reduction of cholesterol and/or triglyceride levels can improve FMD. In hyperlipidemia the role of inflammatory substances on endothelial function requires further clarification. In patients with combined hyperlipidemia (n = 29), the capacity of FMD was weaker whereas the levels of interleukin (IL)-lalpha, tumor necrosis factor alpha (TNFalpha), soluble intercellular adhesion molecule (sICAM), and fibrinogen were higher compared to normolipemic controls with normal FMD adjusted for age and sex. Patients were randomized to a diet-only or to a ciprofibrate treatment group. After 8 weeks FMD levels rose significantly both in the diet-only (10.2%) and the ciprofibrate treatment (79.4%) groups. In the diet-only group improvement of FMD was significantly associated with the reduction of triglyceride (by 15.9%) and cholesterol (6.9%) levels. The much larger improvement of FMD due to ciprofibrate therapy was accompanied by significant reductions of cholesterol (by 14.4%), fibrinogen, IL-1alpha, and sICAM levels and by significant increase of high-density lipoprotein (HDL) cholesterol concentration, but the change in FMD correlated only with the reduction of the cholesterol level. In line with previous data the authors emphasize that improvement of FMD in patients with combined hyperlipidemia treated with diet and/or ciprofibrate is linked directly to the reduction of cholesterol and triglyceride concentrations rather than to changes in the level of the investigated inflammatory markers.

[Efficacy and safety of ezetimibe/simvastatin combination therapy in patients with type 2 diabetes and nonalcoholic fatty liver disease].

UNLABELLED Nonalcoholic fatty liver disease is commonly associated with type 2 diabetes, dyslipidemia and obesity all of which are components of the metabolic syndrome. AIM To determine the efficacy and safety of ezetimibe/simvastatin 10/20mg combination therapy on patients with type 2 diabetes and nonalcoholic fatty liver disease. METHODS We studied nineteen patients with type 2 diabetes and nonalcoholic fatty liver disease diagnosed and treated between 2005 and 2008 at Health Center of Budaörs. After six months of ezetimibe/simvastatin (10/20mg/day) combination treatment, all patients were assessed for changes serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and triglycerides. RESULTS Six months of ezetimibe/simvastatin administration reduced significantly the serum levels of ALT (63.78+/-5.12 vs 32.57+/-3.92 U/L; p < 0.0001), AST (50.79+/-3.66 vs 23.68+/-3.42 U/L; p < 0.0001), cholesterol (6.26+/-0.46 vs 4.02+/-0.31 mmol/L; p < 0.0001) and LDL-cholesterol (4.24+/-0.37 vs 2.22+/-0,1 mmol/L; p < 0.0001). Combination therapy reduced significantly serum triglyceride level (2.62+0.48 vs 1.33+0.20 mmol/L; p < 0.0001) and increased the level of HDL-cholesterol (1.02+/-0.12 vs 1.18+/-0.07 mmol/L; p < 0.0001). CONCLUSIONS These findings indicate that ezetimibe/simvastatin combination therapy is safe and effective in patients with type 2 diabetes and nonalcoholic fatty liver disease.

Új kezelési lehetoség a 2-es típusú diabetes terápiájában: DPP-4-gátlók (sitagliptin)

Type 2 diabetes is a very common worldwide disorder. A good glycemic control is reduce the rates of diabetes associated microvascular and possibly macrovascular complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors such as sitagliptin demonstrate an incretin based, glucose-dependent actions with low risk of hypoglycemia and no weight gain during the treatment of patients with type 2 diabetes.

Effect of moderate alcohol consumption on insulin sensitivity

Moderate alcohol consumption has been reported to be associated with lower risk for both cardiovascular disease and type 2 diabetes. An explanation for these epidemiologic observations is not entirely clear. Alcohol raises high-density lipoprotein (HDL) cholesterol levels. Other potential beneficial mechanisms have been proposed including anti-inflammatory and anti-thrombotic effects. The association between moderate alcohol consumption and insulin sensitivity is still under debate. Possible mechanisms include elevation of adiponectin level, reduction of C-reactive protein and suppression of free fatty acid release from adipose tissue.

Plasmapheresis in the treatment of hypertriglyceridemia

The authors present the case of a 38-year-old woman with severe hypertriglyceridemia-induced acute recurrent pancreatitis (triglyceride 16 761 mg/dl, 189.4 mmol/l). According to the knowledge of the authors, such a high triglyceride has not been previously reported in Hungarian and international scientific literature. The patient received conventional treatment (fluid replacement, analgesic, antibiotics, discontinuation of oral intake) and plasmapheresis too. After two sessions of plasmapheresis with one month interval the clinical and laboratory parameters greatly improved. Severe hypertriglyceridemia (triglyceride level more than 1000 mg/dl, ≈11.3 mmol/l) is an independent risk factor for acute pancreatitis. Plasmapheresis seems to be safe and effective to rapidly decrease triglyceride levels and to remove the causative agent for pancreatitis in a patient with severe hypertriglyceridemia.

Effect of Pintes white wine on metabolic parameters in patients with metabolic syndrome

UNLABELLED Moderate alcohol consumption has been associated with decreased cardiovascular mortality in the general population. Relatively few studies have been conducted to evaluate the effect of white wine on insulin sensitivity. AIMS The authors studied the impact of moderate Pintes white wine consumption on insulin sensitivity and other metabolic parameters. METHODS The prospective study involved 18 patients with metabolic syndrome. The patients consumed Pintes white wine for 4 weeks, and parameters were measured before and after consumption. RESULTS The HOMA-IR decreased significantly after white wine consumption (2.28±2.04 vs 1.08±0.6; p = 0.002). There were no changes in serum cholesterol, LDL-cholesterol, triglyceride and fasting plasma glucose levels. CONCLUSION White wine consumption improved insulin sensitivity in patients with metabolic syndrome.

Hyperlipidemia in pregnancy

Physiological changes in lipoprotein levels occur in normal pregnancy. Women with hyperlipoproteinemia are advised to discontinue statins, fibrates already when they consider pregnancy up to and including breast-feeding the newborn, because of the fear for teratogenic effects. Hypertriglyceridemia in pregnancy can rarely lead to acute pancreatitis. Management of acute pancreatitis in pregnant women is similar to that used in non-pregnant patients. Further large cohort studies are needed to estimate the consequence of supraphysiologic hyperlipoproteinemia or extreme hyperlipoproteinemia in pregnancy on the risk for cardiovascular disease later in life.

A new therapeutic class for the therapy of type 2 diabetes: DPP-4 inhibitors (sitagliptin)

Type 2 diabetes is a very common worldwide disorder. A good glycemic control is reduce the rates of diabetes associated microvascular and possibly macrovascular complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors such as sitagliptin demonstrate an incretin based, glucose-dependent actions with low risk of hypoglycemia and no weight gain during the treatment of patients with type 2 diabetes.