Serum adipokine levels in patients with type 1 diabetes are associated with degree of obesity but only resistin is independently associated with atherosclerosis markers.

PURPOSE: The role of adipokines in causing inflammation and insulin resistance in normal weight and obese patients is generally well studied. However, there are often conflicting results regarding their levels in type 1 diabetes mellitus (T1DM) patients and their relationship to micro- and macrovascular disease. We therefore investigated which serum adipokine levels are independently associated with markers of early atherosclerosis and microvascular complications in patients with T1DM. METHODS: A cross-sectional study was performed in the Diabetes Outpatient Clinic of Hippokrateion General Hospital, Thessaloniki, Greece. Sixty T1DM patients (30 females, mean age 38.8 ± 10.6 years, mean diabetes duration 17.4 ± 9.9 years) were included. Plasma adiponectin, leptin, and resistin, carotid artery intima media thickness (cIMT), and arterial stiffness (pulse wave velocity, PWV/SpygmoCor CP System and Mobil-O-Graph 24 h PWA) were assessed. RESULTS: Leptin and resistin levels were significantly higher in overweight and obese patients (p = 0.002 and p = 0.039, respectively). Adiponectin was the only adipokine negatively correlated with BMI (rs = - 0.41, p = 0.001). We report a bivariate association between serum adiponectin levels and retinopathy (p = 0.007). Resistin was the only adipokine that showed significant correlation with systolic (rs = 0.42, p = 0.001) and diastolic (rs = 0.29, p = 0.024) hypertension and PWV (p = 0.035). CONCLUSIONS: Serum adipokine levels demonstrate similar bivariate associations with anthropometric variables in patients with T1DM to those in normal weight subjects. Although microvascular complications are associated with serum adipokine levels by bivariate analysis, only resistin, an inflammatory marker, is independently associated with arterial stiffness in patients with T1DM.

Microcirculatory function deteriorates with advancing stages of chronic kidney disease independently of arterial stiffness and atherosclerosis.

Cardiovascular disease is the main cause of mortality in chronic kidney disease (CKD). Endothelial dysfunction and capillary rarefaction are established cardiovascular risk factors. Nailfold video capillaroscopy provides a thorough assessment of capillary density and functional reserve. This study aimed to examine possible differences in structural and functional capillary density in CKD stages 2-4 with nailfold video capillaroscopy. Ninety-six CKD patients, divided into four equally sized groups according to CKD stage (2, 3a, 3b, 4), underwent nailfold video capillaroscopy, during which capillary density was measured at baseline, after 4-min arterial occlusion and after 2-min venous occlusion. Arterial stiffness and wave parameters were measured with applanation tonometry and common carotid intima-media thickness (ccIMT) with ultrasound. Baseline capillary density showed a progressive reduction with advancing CKD stages (stage 2: 32.6 ± 2.8, stage 3a: 31.2 ± 3.8, stage 3b: 32.5 ± 3.3, stage 4: 28.5 ± 3.1, p = 0.011). Similar reductions were observed during postocclusive hyperemia (39.4 ± 3.0, 37.6 ± 4.2, 38.4 ± 3.8, and 33.8 ± 3.3, respectively; p = 0.021) and after venous congestion (41.1 ± 3.1, 39.0 ± 4.4, 39.9 ± 3.5, and 35.2 ± 3.4; p = 0.032). Office PWV and ccIMT showed nonsignificant increasing trends with advancing CKD. In multivariate analysis, eGFR showed a positive association (per ml/min increase; ß: 0.053, 95% CI: 0.004-0.101), whereas diabetes (ß: -1.706, 95% CI: -3.176 to -0.236) and parathyroid hormone (PTH) (per pg/ml increase; ß: -0.022, 95% CI: -0.036 to -0.008) had negative associations with postocclusive capillary density. Both structural and functional capillary density progressively decrease with advancing CKD stages. Apart from reduced eGFR, diabetes and increased PTH levels are independently associated with this reduction. This capillary rarefaction may largely contribute to the increased cardiovascular risk of CKD patients.

Comparison of ambulatory central hemodynamics and arterial stiffness in patients with diabetic and non-diabetic CKD.

Increased arterial stiffness is independently associated with renal function decline in patients with diabetes mellitus (DM). Whether DM has additional deleterious effects on central hemodynamics and arterial stiffness in chronic kidney disease (CKD) patients is yet unknown. This study aimed to compare ambulatory central BP, arterial stiffness parameters, and trajectories between patients with diabetic and non-diabetic CKD. This study examined 48 diabetic and 48 non-diabetic adult patients (>18 years) with CKD (eGFR: <90 and ≥15 ml/min/1.73 m2 ), matched in a 1:1 ratio for age, sex, and eGFR within CKD stages (2, 3a, 3b and 4). All patients underwent 24-h ABPM with the Mobil-O-Graph device. Parameters of central hemodynamics [central systolic (cSBP) and diastolic blood pressure (cDBP), pulse pressure (PP)], wave reflection [augmentation index (AIx), and pressure (AP)] and pulse wave velocity (PWV) were estimated from the 24-h recordings. Diabetic CKD patients had higher 24-h cSBP (118.57 ± 10.05 vs. 111.59 ± 9.46, P = .001) and 24-h cPP (41.48 ± 6.80 vs. 35.25 ± 6.98, P < .001) but similar 24-h cDBP (77.09 ± 8.14 vs. 76.34 ± 6.75 mmHg, P = .625) levels compared to patients with non-diabetic CKD. During day- and nighttime periods, cSBP and cPP levels were higher in diabetics compared to non-diabetics. 24-h PWV (10.10 ± 1.62 vs. 9.61 ± 1.80 m/s, P = .165) was numerically higher in patients with DM, but no between-group differences were noted in augmentation pressure and index. In multivariate analysis, DM, female gender, and peripheral SBP were independently associated with higher cPP levels. Patients with diabetic CKD have higher ambulatory cSBP and increased arterial stiffness, as indicated by higher ambulatory cPP. These finding suggest that DM is a factor independently contributing to the adverse macrocirculatory profile of CKD patients.

Targeted Analysis of Three Hormonal Systems Identifies Molecules Associated with the Presence and Severity of NAFLD.

AIMS: To investigate circulating levels and liver gene expression of 3 hormonal pathways associated with obesity, insulin resistance, and inflammation to identify leads towards potential diagnostic markers and therapeutic targets in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: We compared circulating levels of (1) proglucagon-derived hormones (glucagon-like peptide [GLP]-1, GLP-2, glicentin, oxyntomodulin, glucagon, major proglucagon fragment [MPGF]), (2) follistatins-activins (follistatin-like [FSTL]3, activin B), (3) IGF axis (insulin-like growth factor [IGF]-1, total and intact IGF binding protein [IGFBP]-3 and IGFBP-4, and pregnancy-associated plasma protein [PAPP]-A) in 2 studies: (1) 18 individuals with early stage NAFLD versus 14 controls (study 1; early NAFLD study) and in (2) 31 individuals with biopsy proven NAFLD (15 with simple steatosis [SS] and 16 with nonalcoholic steatohepatitis [NASH]), vs 50 controls (24 lean and 26 obese) (study 2). Liver gene expression was assessed in 22 subjects (12 controls, 5 NASH, 5 NASH-related cirrhosis). RESULTS: Patients in early stages of NAFLD demonstrate higher fasting MPGF and lower incremental increase of glicentin during oral glucose tolerance test than controls. In more advanced stages, FSTL3 levels are higher in NASH than simple steatosis and, within NAFLD patients, in those with more severe lobular and portal inflammation. The IGF-1/intact IGFBP-3 ratio is lower in patients with liver fibrosis. Genes encoding follistatin, activin A, activin B, and the IGF-1 receptor are higher in NASH. CONCLUSION: MPGF and glicentin may be involved in early stages of NAFLD, whereas FSTL3 and IGF-1/intact IGFBP3 in the progression to NASH and liver fibrosis respectively, suggesting potential as diagnostic markers or therapeutic targets.

Renovascular Hypertension: Novel Insights.

Renovascular hypertension (RVH) remains among the most prevalent and important, but also potentially reversible, causes of secondary hypertension. The predominant causes of renal artery stenosis (RAS) are atherosclerotic renovascular arterial stenosis (ARAS) and renal fibromuscular dysplasia. This condition can lead to progressive renal injury, cardiovascular complications and 'flash pulmonary edema'. Duplex Doppler ultrasonography, computed tomographic angiography and magnetic resonance angiography are the most commonly used diagnostic methods. There are three therapeutic options available: medical therapy including renin-angiotensin-aldosterone system antagonists, lipid-lowering agents, and antiplatelet therapy, percutaneous angioplasty with or without stent placement and surgical revascularization. Three large trials failed to demonstrate the superiority of renal artery revascularization over pharmaceutical therapy in controlling blood pressure and preserving renal function. For this reason, today revascularization is only recommended for patients with progressive worsening of renal function, recurrent 'flash pulmonary edema' and rapid increase in antihypertensive requirement in patients with previously well-controlled hypertension. However, more properly designed trials are needed in order to identify which patient populations would probably benefit from renal revascularization.

Fulminant cryptococcal meningoencephalitis after successful treatment of primary cutaneous cryptococcosis.

INTRODUCTION: Cryptococcal meningoencephalitis is a life-threatening disease affecting mainly immunocompromised hosts. CASE REPORT: We present a case of a 64-year-old immunocompetent patient, who initially developed a traumatic scalp skin infection due to Cryptococcus neoformans. The patient received oral fluconazole and subsequently liposomal amphotericin B due to the development of resistance with resolution of the infection. Two years later, during chemotherapy for newly diagnosed gastric and lung cancer, he developed fulminant cryptococcal meningoencephalitis, which did not respond to liposomal amphotericin B and flucytosine. CONCLUSIONS: To our knowledge, this is the first case of fulminant cryptococcal meningoencephalitis following long latency after adequately treated primary cutaneous infection.

Free Cortisol Is a More Accurate Marker for Adrenal Function and Does Not Correlate with Renal Function in Cirrhosis.

BACKGROUND: The accuracy of diagnosis and clinical implications of the hepatoadrenal syndrome, as currently diagnosed using total cortisol, remain to be validated. AIM: The aim of this study was to assess adrenal function using free cortisol in stable cirrhosis and study the potential implications of any abnormalities for renal and/or cardiac function. METHODS: Sixty-one stable consecutively enrolled patients with cirrhosis underwent assessment of adrenal function using the low-dose short Synacthen test, renal function by 51Cr-EDTA glomerular filtration rate (GFR), and cardiac function by two-dimensional echocardiography. RESULTS: Eleven patients (18%) had total peak cortisol (PC) < 500 nmol/L, but no patient had free PC < 33 nmol/L indicating that diagnosis of AI using total cortisol is not confirmed using free cortisol. Free cortisol did not correlate with GFR or parameters of cardiac function. Patients with higher Child-Pugh class had progressively lower free cortisol. Patients with low GFR < 60 mL/min (N = 22) had more frequently grade II-III diastolic dysfunction (66.7% vs. 17.6%; p = 0.005) and had higher Child-Pugh and MELD score compared to those with normal GFR. CONCLUSIONS: Diagnosis of AI using total cortisol is not confirmed using free cortisol and is thus considered unreliable in cirrhosis. Free cortisol is not associated with renal or cardiac dysfunction. Lower free cortisol in more advanced stages of liver disease might be secondary to decreased synthesis due to lower cholesterol levels. Irrespective of free cortisol, parameters of cardiac dysfunction are associated with renal impairment supporting the cardio-renal hypothesis.

Multimodal Treatment of Homozygous Familial Hypercholesterolemia.

BACKGROUND: Familial Hypercholesterolemia (FH) is an autosomal-dominant genetic disease, associated with premature atherosclerotic Cardiovascular Disease (CVD), especially in its homozygous type (HoFH). OBJECTIVE: The aim of this review is to discuss the safety and efficacy of combination treatments (procedures and drugs) for HoFH. RESULTS: Historically, liver transplantation was used first; however, it is currently considered only as a last resort for some patients. In the mid 70's, LDL aphaeresis was introduced and remains up today the treatment of choice for patients of any age, despite its significant cost. The use of Ezetimibe results in additive 15-20% reductions in LDL-C regardless of the therapeutic approach, while statins are modestly effective in patients with class 4 or 5 mutations, in which LDL Receptors (LDLR) are present. One of the novel drugs for HoFH is Lomitapide, which is a highly effective oral agent, but is also exceedingly expensive ($350, 000/year). Mipomersen is administered every week subcutaneously, is also effective but has been approved only in the US mainly due to injection site reactions up to 80%. Both Lomitapide (mainly) and Mipomersen have been found to promote fat accumulation in the liver, resulting in subsequent serum transaminases elevations. PCSK9 inhibitors are effective in those with partial LDLR presence and function by reducing frequency of LDL apheresis, improve cost effectiveness of treatment. CONCLUSION: Pediatric and adult HoFH treatment needs combination of procedures and drugs. The main treatment is LDL-C apheresis aided by ezetimibe and PCSK9 inhibitors. Lomitapide needs caution, and liver transplantation is an alternative as the last resort.

Primary aldosteronism in patients with adrenal incidentaloma: Is screening appropriate for everyone?

Primary aldosteronism (PA) is a common form of secondary hypertension. Several guidelines recommend that patients with adrenal incidentaloma have a high probability of suffering from PA. We conducted a prospective study of 269 consecutive adults with adrenal incidentaloma to investigate the prevalence and clinical characteristics of PA. In total, 9 participants were detected with PA, suggesting a prevalence of 3.35% among the study population. PA participants had a higher blood pressure level by 14/20.8 mm Hg and a lower serum potassium level by 0.8 mmol/L (P < .05). Importantly, all patients with PA presented with concurrent indications (hypertension with or without hypokalemia) for screening of the disease, but they have not undergone relative screening by the referring physician, thus casting doubts about the appropriate implementation of current guidelines in real-life practice. Intense efforts are needed to familiarize physicians with recommendations for PA to minimize undiagnosed cases and the detrimental sequelae of this endocrine form of hypertension.

Sexual Dysfunction, Cardiovascular Risk and Effects of Pharmacotherapy.

BACKGROUND: Sexual dysfunction affects millions of people with an increasing prevalence, worldwide. The pathophysiology of the disease shares several similarities with cardiovascular disease (CVD), including atherosclerosis, endothelial dysfunction, structural vascular damage and subclinical inflammation. Erectile dysfunction (ED) and female sexual dysfunction are common among patients with CVD and risk factors such as hypertension, diabetes, obesity and metabolic syndrome. Given the common pathogenesis of the diseases, ED is an independent prognostic factor of future ED events. Patients with overt ED or risk factors are usually treated with several drugs for the management of these conditions. Several of these drugs have been evaluated for their effect on sexual activity. RESULTS AND CONCLUSION: Among the antihypertensive drugs, diuretics and beta-blockers seem to exert a detrimental impact on sexual function, with nebivolol being the only beta-blocker with favorable properties through an increase in nitric oxide bioavailability. In contrast, renin-angiotensin system inhibitors and calcium-channel blockers have a neutral effect on sexual activity. Hypoglycemic drugs have been less evaluated in the ED setting, with metformin, pioglitazone and liraglutide presenting favorable results. Statins on the other hand have not provided consistent results with observational studies suggesting a detrimental role in sexual activity and a few randomized studies indicating a neutral or even beneficial effect on erectile function.

Is Nonalcoholic Fatty Liver Disease Indeed the Hepatic Manifestation of Metabolic Syndrome?

Metabolic syndrome (MetS) is a cluster of central obesity, dyslipidaemia, insulin resistance and hypertension. MetS frequently co-exists with non-alcoholic fatty liver disease (NAFLD), which is characterized by fat accumulation in the liver in the absence of alcohol abuse, viral hepatitis and other causes of chronic liver diseases. Both MetS and NAFLD are associated with an increased risk for cardiovascular disease and type 2 diabetes mellitus. There are also other associations between MetS and NAFLD. In the present narrative review, we discuss the links between MetS and NAFLD in terms of prevalence, risk factors and treatment (both lifestyle interventions and drug therapy). Such associations highlight the common pathophysiological pathways of these metabolic disorders, although data for an independent association are not robust. Nevertheless, NAFLD may be regarded as a hepatic manifestation of MetS.

Statins: An Under-Appreciated Asset for the Prevention and the Treatment of NAFLD or NASH and the Related Cardiovascular Risk.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease (30% of the general population) and up to 40% of cases advance to the more severe form of the disease: nonalcoholic steatohepatitis (NASH), which is causally related to cirrhosis and cardiovascular disease (CVD). There is no generally accepted effective treatment for NAFLD/NASH. The joint guidelines of the European Association for the Study of the Liver (EASL), the European Association for the Study of Diabetes (EASD) and the European Association for the Study of Obesity (EASO) suggest the "off label" use of pioglitazone in patients without type 2 diabetes mellitus (T2DM) and pioglitazone in subjects with T2DM or vitamin E or their combination for the treatment of NASH; however pioglitazone has considerable limitations: weight gain, bone fractures in women, and heart failure. The aim of this narrative review is to assess the existing evidence supporting statin use for the treatment of NASH and the reduction of the high CVD risk of these patients. Animal data suggest that there is some benefit from statin use in liver histology in models of NASH. In humans, 3 post hoc analyses of randomised controlled trials (n=1,600, n=1,123, n=8,864) suggest that the use of atorvastatin (even in 80 mg/day) has a beneficial effect on NAFLD/NASH, in terms of liver enzyme reduction and ultrasonographic amelioration. Moreover, and most importantly, statin treatment halved CVD morbidity and mortality in statin-treated NAFLD/NASH patients compared with statin-treated participants with normal liver structure and function and reduced by 2/3rds CVD events in comparison with NAFLD/NASH patients that were not on a statin (90% of this population is not on statins because of the unjustified fear for liver damage). Three biopsy studies (n=20, n=107 and n=356) showed that statin treatment had a protective effect on steatosis, steatohepatitis and fibrosis. Data suggest that statin treatment in humans substantially improve or cure NAFLD/NASH, but above all substantially reduce CVD morbidity and mortality. Administration of potent statins appears safe and effective in saving lives in NAFLD/NASH patients.

Current and Potential Future Pharmacological Approaches for Non- Alcoholic Fatty Liver Disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects a large proportion of the general population. The disease ranges from simple steatosis, to non-alcoholic steatohepatitis (NASH), cirrhosis and even hepatocellular carcinoma. Several drugs are used in daily clinical practice to manage the disease. However, data on their efficacy in liver histology are not consistent. AIM: We discuss current treatment options for NAFLD and NASH and preliminary results from novel drugs under investigation. RESULTS: Among various drugs assessed for the management of NAFLD and NASH, only pioglitazone and vitamin E have provided consistent benefits on liver histology, and are recommended by the European and American guidelines. Statins were shown to produce clinically meaningful results in patients with NAFLD or NASH. Other drugs such as metformin and polyunsaturated fatty acids that are being used in clinical practice off-label have provided benefits on terms of hepatic biochemical and diabetesrelated markers; data on liver histology with these drugs are scarce and from small studies. Several new approaches to reduce inflammation, steatosis or fibrosis have shown promising results in experimental models of NAFLD or NASH lesions and are being evaluated in humans. CONCLUSION: Pioglitazone and vitamin E are the only drugs providing consistent benefits and are currently recommended for NASH. Various pathogenetic pathways are being targeted to reduce steatosis, inflammation and fibrosis and early data on several novel drugs are very promising. On-going human trials will unveil their true impact.

Nonalcoholic Fatty Liver Disease vs. Nonalcoholic Steatohepatitis: Pathological and Clinical Implications.

The implications and prognosis of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH) are substantially different. The aim of the present review is to describe and compare the pathological and clinical implications of these two conditions. Patients with NASH have a higher risk of progressing to cirrhosis than patients with NAFL but without steatohepatitis, who tend to have a non-progressive disease and only a minority progresses to NASH. Patients with NASH also are at greater risk to develop hepatocellular cancer (HCC) and NASH is the third commonest cause of HCC. In contrast, only few cases of HCC have been reported in patients with isolated NAFL. Given that nonalcoholic fatty liver disease is the hepatic manifestation of metabolic syndrome, it is also strongly related to cardiovascular disease (CVD). Again, it appears that patients with NASH have higher cardiovascular risk than patients with NAFL. Finally, all-cause mortality is also higher in patients with NASH than in patients with NAFL; mortality rates in the latter patients do not differ from the general population. In conclusion, NAFL and NASH have different prognosis and therefore it is imperative to develop accurate, noninvasive methods that will identify the presence of steatohepatitis in this population.

The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement.

Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is characterized by accumulation of fat (>5% of the liver tissue), in the absence of alcohol abuse or other chronic liver diseases. It is closely related to the epidemic of obesity, metabolic syndrome or type 2 diabetes mellitus (T2DM). NAFLD can cause liver inflammation and progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis or hepatocellular cancer (HCC). Nevertheless, cardiovascular disease (CVD) is the most common cause of death in NAFLD/NASH patients. Current guidelines suggest the use of pioglitazone both in patients with T2DM and in those without. The use of statins, though considered safe by the guidelines, have very limited use; only 10% in high CVD risk patients are on statins by tertiary centers in the US. There are data from several animal studies, 5 post hoc analyses of prospective long-term survival studies, and 5 rather small biopsy proven NASH studies, one at baseline and on at the end of the study. All these studies provide data for biochemical and histological improvement of NAFLD/NASH with statins and in the clinical studies large reductions in CVD events in comparison with those also on statins and normal liver. Ezetimibe was also reported to improve NAFLD. Drugs currently in clinical trials seem to have potential for slowing down the evolution of NAFLD and for reducing liver- and CVD-related morbidity and mortality, but it will take time before they are ready to be used in everyday clinical practice. The suggestion of this Expert Panel is that, pending forthcoming randomized clinical trials, physicians should consider using a PPARgamma agonist, such as pioglitazone, or, statin use in those with NAFLD/NASH at high CVD or HCC risk, alone and/or preferably in combination with each other or with ezetimibe, for the primary or secondary prevention of CVD, and the avoidance of cirrhosis, liver transplantation or HCC, bearing in mind that CVD is the main cause of death in NAFLD/NASH patients.

Current challenges in antihypertensive treatment in the elderly.

Arterial hypertension affects more than 25% of the global population, and its prevalence is increasing with age. Arterial stiffening occurs with aging and results in a pattern of increased systolic and decreased diastolic blood pressure (BP). In the elderly population, elevated BP has been related with increased cardiovascular risk. Trials on this population have shown great benefits for morbidity and mortality from reducing systolic BP (SBP) levels to less than 150 mmHg. Most guidelines for the management of elderly hypertensive patients agree on BP reduction to less than 150/90 mmHg. However, there is still uncertainty whether further BP reduction could provide beneficial results. The recently published SPRINT trial demonstrated that reducing SBP to between 120 and 125 mmHg in patients over the age of 75 years is related with increased survival and is expected to affect future recommendations. On the contrary, the limited data that are available for octogenarians and frail nursing home patients create concerns for more aggressive BP strategies in these subgroups, and thus they should be treated more conservatively. Among the various antihypertensive classes of drugs, diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers were proved beneficial in the elderly and are favored as first choices for the management of elderly hypertensive individuals. Given the common coexistence of other comorbidities and polypharmacy, physicians should be careful when initiating or uptitrating treatments to avoid potential adverse events or interaction with other drugs or diseases.

Hypertrophic Mesenteric Adipose Tissue May Play a Role in Atherogenesis in Inflammatory Bowel Diseases.

BACKGROUND: Adipokines released by the adipose tissue are known to play a role in atherogenesis. The hypertrophic mesenteric fat in patients with inflammatory bowel diseases (IBD) also produces adipokines that are considered to play a role in intestinal inflammation. Whether they also contribute to accelerated atherosclerosis in IBD is unknown. The aim of this study was to assess the role of 2 adipokines, resistin and adiponectin, in IBD. METHODS: We previously published data on 3 markers of cardiovascular risk, carotid intima-media thickness, carotid-femoral pulse wave velocity, and lipoprotein-associated phospholipase A2, in 44 patients with IBD and 44 controls matched for established cardiovascular risk factors. In this study, we measured resistin and adiponectin levels, and assessed their correlations with carotid intima-media thickness, pulse wave velocity, and lipoprotein-associated phospholipase A2. RESULTS: Resistin levels were significantly higher in patients with IBD (13.7 versus 10 ng/mL; P = 0.022), but there was no difference in adiponectin levels. Resistin levels were significantly higher in patients with active disease compared with those in remission (18.9 versus 11.3 ng/mL; P = 0.014). Adiponectin levels were significantly lower in Crohn's disease compared with ulcerative colitis (6736.3 ± 3105 versus 10,476.1 ± 5575.7 ng/mL; P = 0.026). Adiponectin correlated inversely with pulse wave velocity (rho = -0.434; P < 0.0005) and carotid intima-media thickness (rho = -0.255; P = 0.021). CONCLUSIONS: This is the first study to suggest that adipokines produced by the hypertrophic mesenteric fat in IBD may play a role not only in intestinal inflammation but also in atherogenesis. Resistin has mainly pro-inflammatory properties, whereas adiponectin likely exerts an angioprotective effect.

Resolution of non-alcoholic steatohepatitis by rosuvastatin monotherapy in patients with metabolic syndrome.

AIM: To investigate the effect of rosuvastatin monotherapy on non-alcoholic steatohepatitis (NASH). At present there is no effective treatment for non-alcoholic fatty liver disease or its advanced form NASH. METHODS: This prospective study included 20 biopsy proven patients with NASH, metabolic syndrome (MetS) and dyslipidaemia. Biochemical parameters of the blood of the patients and an ultrasonography of the liver were performed at baseline. Then patients received lifestyle advice and were treated for a 12 mo period with rosuvastatin (10 mg/d) monotherapy. Patients were re-evaluated during the study at 3 mo intervals, during which biochemical parameters of the blood were measured including liver enzymes. A repeat biopsy and ultrasonography of the liver were performed at the end of the study in all 20 patients. Changes in liver enzymes, fasting plasma glucose, serum creatinine, serum uric acid (SUA), high sensitivity C reactive protein (hsCRP) and lipid profile were assessed every 3 mo. The primary endpoint was the resolution of NASH and the secondary endpoints were the changes in liver enzyme and lipid values. RESULTS: The repeat liver biopsy and ultrasonography showed complete resolution of NASH in 19 patients, while the 20(th), which had no improvement but no deterioration either, developed arterial hypertension and substantial rise in triglyceride levels during the study, probably due to changes in lifestyle including alcohol abuse. Serum alanine transaminase, aspartate transaminase, and γ-glutamyl transpeptidase were normalised by the 3(rd) treatment month (ANOVA P < 0.001), while alkaline phosphatase activities by the 6(th) treatment month (ANOVA, P = 0.01). Fasting plasma glucose and glycated haemoglobin were significantly reduced (P < 0.001). Lipid values were normalised by the 3(rd) treatment month. No patient had MetS by the 9(th) treatment month. Body mass index and waist circumference remained unchanged during the study. Thus, changes in liver pathology and function should be attributed solely to rosuvastatin treatment. A limitation of the study is the absence of a control group. CONCLUSION: These findings suggest that rosuvastatin monotherapy could ameliorate biopsy proven NASH and resolve MetS within 12 mo. These effects and the reduction of fasting plasma glucose and SUA levels may reduce the risk of vascular and liver morbidity and mortality in NASH patients. These findings need confirmation in larger studies.