Gokhan Erdem

Plasma Apelin and ADMA Levels in Patients with Essential Hypertension

Both apelin and asymetric dymethyl arginine (ADMA) regulate blood pressures. Low apelin and high ADMA levels have been reported in several cardiometabolic disorders. However, there is no data about ADMA and apelin levels in essential hypertension and any relationship between them. We investigated a group of newly diagnosed and untreated 30 young hypertensive men and 30 healthy controls. Apelin levels were significantly lower and the ADMA levels were significantly higher in the patients (p = 0.04 for both). Both ADMA and apelin were related to the systolic blood pressures (SBP) (beta = −0.393, p = 0.003; beta = 0.285, p = 0.03, respectively). Future studies are necessary in order to clearly define the role of ADMA and apelin in the pathogenesis of essential hypertension.

Effect of a hypocaloric diet on serum visfatin in obese non-diabetic patients

OBJECTIVE Obesity and insulin resistance are associated with classic and new cardiovascular risk factors, such as inflammatory markers and adipocytokines. The aim of this study was to examine whether weight reduction could change visfatin serum concentrations in obese patients. METHODS This was an interventional longitudinal study analyzing a population of 80 obese non-diabetic outpatients. Weight, blood pressure, fasting serum glucose, C-reactive protein, plasma insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triacylglycerols, and insulin resistance (homeostatic model assessment) were measured before and after 3 mo on a hypocaloric diet. RESULTS Eighty patients were enrolled. The mean age was 46.7 +/- 16.7 y, the mean body mass index was 34.1 +/- 4.8 kg/m(2), with 20 men (25%) and 60 women (75%). After 3 mo on a hypocaloric diet, body mass index, fat mass, waist circumference, systolic blood pressure, fasting serum glucose, total cholesterol, and low-density lipoprotein cholesterol decreased. The serum concentration of visfatin decreased with weight loss (112.14 +/- 70.2 versus 99.4 +/- 58.1 ng/mL, P < 0.05). In the multivariate analysis of visfatin concentration before and after treatment, as a dependent variable, only age remained an independent predictor in the model (F = 12.5, P < 0.02), with an inverse correlation: visfatin decreased 4.1 g/mL (F = 12.5, P < 0.05) and 3.7 g/mL (95% confidence interval 1.2-6.1), respectively, for each year of age. CONCLUSION Weight reduction after a 3-mo period of a hypocaloric diet is associated with a significant decrease in circulating serum concentrations of the novel adipokine visfatin in obese subjects. Visfatin is inversely correlated with age.

LDL-cholesterol lowering increases plasma apelin in isolated hypercholesterolemia

Apelin, a relatively newer adipokine with various actions in cardiovascular system, was recently reported to decrease in dyslipidemia. The present study addresses whether plasma apelin increases after hypolipidemic intervention either through therapeutic life style change (TLC) or statin treatment. A total of 134 patients were subjected to treatment with a TLC intervention for 12 weeks. Of these, 116 successfully completed the period, and LDL-cholesterol level decreased to target level (<160 mg/dL) in 54 (46.5%) individuals. The remaining 62 patients were treated with rosuvastatin for 12 weeks, and 56 of them finished the study. Circulating apelin, adiponectin, leptin, TNF-alpha, hsCRP and insulin levels were determined both at baseline and after TLC intervention and statin treatment. There was no significant change in plasma apelin concentration in patients unresponsive to TLC (p=0.110). LDL-cholesterol lowering either through TLC or statin treatment was accompanied by an increase in plasma apelin (p=0.000, p=0.020) and adiponectin (p=0.001, p=0.011). Serum leptin decreased after successful TLC (p=0.042/male, p=0.023/female) but not after statin treatment (p=0.959/male, p=0.134/female). Serum TNF-alpha (p=0.902) and plasma hsCRP (p=0.135) levels remained unchanged after TLC intervention but decreased after statin treatment (p=0.000, p=0.023, respectively). Plasma insulin and homeostasis model assessment scores decreased after TLC (p=0.000 for both) but not rosuvastatin treatment (p=0.865, p=0.722, respectively). In conclusion, independent of the type of treatment, reduction in LDL-cholesterol levels in otherwise healthy people with isolated dyslipidemia results in an increase in plasma apelin concentration. More experiments may show a substantial role for this peptide in the mechanism of atherosclerosis.

The effects of pioglitazone and metformin on plasma visfatin levels in patients with treatment naive type 2 diabetes mellitus

AIMS Circulating visfatin levels are altered in insulin resistant states. We evaluated the effects of two insulin-sensitizing hypoglycemic agents on plasma visfatin and adiponectin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus (T2DM). METHODS Forty-four patients with T2DM were randomized to treatment either with pioglitazone (15-45mg/day) or metformin (1000-2000mg/day). Plasma visfatin and adiponectin levels and homeostasis model assessment of insulin resistance (HOMA-IR) scores were determined at baseline and at 12th week of treatment. RESULTS By the end of the 12th week, fasting plasma glucose, HbA1c, HOMA-IR scores and waist circumferences improved equally in both treatment arms. HDL cholesterol and adiponectin levels increased only in the pioglitazone group (p=0.01 and p=0.003, respectively). On the other hand, metformin treatment had additional regulatory effects on BMI, blood pressure and total and LDL-cholesterol levels (p=0.002, p=0.01, p=0.004, p=0.001 and p<0.001, respectively). Neither pioglitazone nor metformin displayed a significant effect on circulating visfatin concentration. CONCLUSIONS Despite improvements in insulin sensitivity and glycemic regulation, either pioglitazone or metformin treatment did not result in any effect on blood visfatin levels in patients with treatment naïve T2DM.

The plasma levels of soluble P-selectin in subjects with prediabetes

Prediabetes has been associated with an increased risk of cardiovascular disease and mortality. Soluble P‐selectin (sP‐selectin) is an index of platelet activation and also a risk factor for future vascular events. sP‐selectin levels were investigated in prediabetic subjects who had no confounding factors such as hypertension, obesity or dyslipidaemia. sP‐selectin, hsCRP levels and HOMA‐IR indexes were measured in 40 prediabetic subjects (n = 24 for IFG and n = 16 for IGT) and age‐, sex‐ and BMI‐matched 40 healthy controls. sP‐selectin levels in prediabetic subjects were not significantly different compared with those in controls (p = 0.12). Prediabetic group had similar hsCRP (p = 0.29), higher HOMA‐IR indexes (p < 0.001) and lower HDL cholesterol levels (p = 0.001) when compared with healthy controls. The power of the study was 0.93 for sP‐selectin, 0.7 for hsCRP and 1.0 for HOMA. Our data suggest that sP‐selectin may not contribute to the prothrombotic state as well as the accelerated atherogenesis associated with prediabetes.

Soluble CD40 ligand, soluble P-selectin and von Willebrand factor levels in subjects with prediabetes: the impact of metabolic syndrome.

OBJECTIVES The data regarding circulating levels of markers of platelet activation and endothelial function in people with prediabetes are scant. The aim of the present study was to search blood levels of soluble CD40 ligand (sCD40L), soluble P-selectin (sP-sel) and von Willebrand Factor (vWF) in subjects with prediabetes, along with the effects of the metabolic syndrome (MetS) on these markers. DESIGN AND METHODS A total of 77 prediabetic individuals and 81 age, sex and body mass index matched healthy subjects with normal glucose tolerance (NGT) were prospectively analyzed. Anthropometric parameters, fasting plasma glucose, blood d lipid profiles and insulin resistance indexes were determined. Plasma sCD40L, sP-sel and vWF levels were measured by ELISA. RESULTS sCD40L, sP-sel and vWF levels in the prediabetic group were similar to those in the controls. However, prediabetic subjects with the MetS had significantly higher level of sCD40L compared to those without MetS. Moreover, sCD40L level correlated significantly with waist circumference, systolic blood pressure and HDL-cholesterol level in the patient group. CONCLUSION These data imply that MetS may contribute, at least in part, to the mechanism of platelet activation and endothelial dysfunction in people with prediabetes.

Soluble CD40 ligand levels in otherwise healthy subjects with impaired fasting glucose.

Unlike diabetes mellitus and impaired glucose tolerance, it is not clear whether the subjects with impaired fasting glucose (IFG) are at increased risk of atherosclerosis and cardiovascular diseases. The CD40-CD40 ligand interaction is involved in the mechanism of atherosclerosis. We investigated whether soluble CD40L (sCD40L) as well as high sensitive C-reactive protein (hsCRP) levels are increased in subjects with IFG having no confounding factors for inflammation or atherosclerosis. Twenty four IFG subjects with no additional disorders and 40 appropriate healthy controls were studied. sCD40L and hsCRP levels in the IFG and control groups were similar. Blood pressures, total and LDL-cholesterol, and triglyceride levels were also similar, whereas HDL-cholesterol was lower and HOMA-IR indexes were higher in the IFG group. Though the sample size was small, the present data show that sCD40L seems not to alter in subjects with IFG suggesting that it might not be an independent risk factor for atherosclerosis.

Metabolic Syndrome is Related to Nonalcoholic Steatohepatitis in Severely Obese Subjects

To the Editor: Huang et al. reported some interesting data regarding a relation between metabolic syndrome (MetS) and nonalcoholic steatohepatitis (NASH) in severely obese subjects [1]. Although most clinicians believe that an association is already present, the study is important because it provides scientific information on this clinically relevant condition. However, we think that some points should be discussed. First, as stated in the text and shown in Table 1, some of the subjects with and without NASH have overt diabetes. However, no information about the glucose tolerance of other subjects can be seen. Although both diabetes mellitus (DM) and impaired glucose tolerance (IGT) are among the components of MetS [2], plasma insulin and adipokine levels differ according to the degree of glucose dysregulation [3, 4]. The same is true for hypertension or elevated blood pressure and dyslipidemia [5, 6]. Lastly, circulating adipokines and measures of insulin sensitivity are easily affected from the medications started for the underlying conditions [7, 8]. The authors state in their article that the participants were accepted as having MetS according to predefined criteria [2]. The diagnostic criteria can be used clinically with success; however, while designing clinical studies to display mechanistic associations, we have to give ultimate effort to exclude possible confounders that might interfere with the results. Finally, we would like to ask the authors whether they can present some additional data by categorizing their patients with MetS and NASH according to metabolic confounders such as DM, IGT, blood pressure, lipid profile, and medication. This would certainly provide the readers clearer information about the association between MetS and NASH.

Rosiglitazone for Nonalcoholic Steatohepatitis

ear Sir: In a recent issue of GASTROENTEROLOGY, Ratziu et al1 eported the efficacy and safety of rosiglitazone, an insuin-sensitizing agent, in patients with nonalcoholic stetohepatitis (NASH). The study is important because it rovides scientific information on this clinically relevant ondition. However, we think that some points should be iscussed. First, as shown in Table 1 of the article, most of the atients with NASH are overweight or obese. In addition, n important portion of the study participants have ther metabolic disturbances (high blood pressure, dysipidemia, etc) alone or in combination. It is well known hat all components that constitute the metabolic synrome are risk factors for type 2 diabetes mellitus as well s prediabetes, namely, impaired fasting glucose and/or mpaired glucose tolerance.2 Although both type 2 diaetes and impaired glucose tolerance are among the comonents of the metabolic syndrome,3 plasma insulin and dipokine levels differ according to the degree of glucose ysregulation.4,5 The same is also true for hypertension r elevated blood pressure and dyslipidemia.6,7 Second, part from the metformin and sulfonamides, no inforation about the drug use of the subjects could be seen n the text. We know that circulating adipokines and easures of insulin sensitivity are easily affected by medcations started for the metabolic problems mentioned bove.8 –10 Collectively, all these points raise several quesions warranting discussion. Therefore, we would like to ask the authors whether hey can present some new results by categorizing the atients with NASH according to metabolic confounders uch as type 2 diabetes, impaired glucose tolerance, blood ressure, and lipid profile. This may provide the readers learer information regarding the relationship between dipokines and NASH.

Successful but Cautious Use of FDG-PET Scan in the Evaluation of Fever of Unknown Origin: A Case Report

Fever of unknown origin (FUO) is a challenging condition in the practice of internal medicine. It frequently requires use of complicated tests and applications in the diagnostic workup. We here report a patient presented with FUO who was diagnosed with osteomyelitis by biopsy after a positive Fludeoxyglicose Positron Emission tomography (FDG-PET) scan.