Serum Levels of Oxidative Stress Markers in Patients with Type 2 Diabetes Mellitus and Non-alcoholic Steatohepatitis.

INTRODUCTION: Oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. The aim of this study was to evaluate the serum levels of oxidative stress markers in patients with type 2 diabetes mellitus (DMT2) and non-alcoholic steatohepatitis (NASH) and test their relationships with clinical and biochemical patient characteristics, compared to patients with DMT2 without non-alcoholic fatty liver disease (NAFLD), and controls. MATERIALS AND METHODS: In all, 60 consecutive patients with DMT2 and NASH, 55 with DMT2 without NAFLD, and 50 age-and-gender-matched healthy subjects participated in the study. The serum levels of protein carbonyls and 8-isoprostane were determined by ELISA methods, while the serum levels of malondialdehyde (MDA) were detected by means of the spectrophotometric method. Clinical, demographic, and laboratory parameters were examined for all the subjects included in the study. Multivariate logistic regression was used to test the independent predictive factors in the relationships investigated here. RESULTS: Patients with DMT2 and NASH displayed significantly higher serum levels of protein carbonyls (1.112 ± 0.42 nmol/dL), MDA (6.181 ± 1.81 ng/mL), and 8-isoprostane (338.6 ± 98.5 pg/mL) compared to patients with DMT2 without NAFLD, and controls. Results of multivariate logistic regression analyses indicate that in patients with DMT2 and NASH, the serum levels of oxidative stress markers were independently and positively associated with: HbA1c, duration of diabetes, the UKPDS cardiovascular risk score (for protein carbonyls); age, LDL-cholesterol (for 8-isoprostane); and triglycerides serum levels (for MDA). CONCLUSIONS: Our findings indicate that the process of oxidative stress tends to increase in patients with DMT2 and NASH, compared to patients with DMT2 without NAFLD, and controls. This evidence suggests that an antioxidant therapy might prove useful in the treatment of patients with DMT2 and NASH.

Two different types of diabetes mellitus in pancreatic cancer population. Comparative study between new onset and long standing diabetes mellitus on 76 patients with pancreatic cancer.

BACKGROUND: There are some studies which have reported a higher diagnosis probability for PC if the DM occurred within the past 2-3 years. Information on the clinical profile of pancreatic cancer (PC) associated with diabetes mellitus (DM) is limited. The aim of the study was to compare clinic-morphological features in patients with new onset DM and PC and long lasting DM and PC, in order to detect new factors or markers which can help in early diagnosis of PC. METHODS: This study included 76 patients with pancreatic cancer admitted between 2000-2009 in the 4th Medical Clinic Cluj-Napoca; in group A 56 patients with PC and new onset of DM (< 24 months duration) were included and in group B 20 patients with PC and long standing diabetes (> 60 months duration) were included. We compared the demographic, clinical, biochemical and morphological characteristics of new onset or long lasting DM and pancreatic cancer. RESULTS: New onset DM was more prevalent (74% vs. 26%, p < .05) than long lasting DM among patients with PC. The patients with long lasting DM had a greater frequency of urban environment (100% vs. 55.6% p = .02), a higher body mass index (BMI)(32.1 SD 8.4 vs. 29.9 SD 6.7 kg/m2, p = .05), higher fasting blood glucose levels (182 mg/dL vs. 134 mg/dL, p = .008) and urinary ketone bodies (60% vs. 10.7%, p = .002) compared with those with new-onset DM and PC. There was no statistical difference regarding gender, median age, blood group, location and staging of tumours, long and hard alcohol and cigarettes consumption, between group A and B. CONCLUSIONS: New onset DM was more significantly frequent than long lasting DM in patients with PC. New onset diabetes DM associated with PC is frequent, mild and non-decompensated. In patients with PC and long lasting DM, the metabolic status and diabetes are imbalanced.

Nonalcoholic fatty liver disease--a risk factor for microalbuminuria in type 2 diabetic patients.

UNLABELLED: The aim of our study was to assess the presence of microalbuminuria in diabetic subjects with nonalcoholic fatty liver disease (NAFLD) compared with diabetic patients without NAFLD and to correlate this with inflammatory markers such as high sensitive C- reactive protein (hsCRP). MATERIAL AND METHODS: The study was conducted on 75 diabetic subjects with ultrasonographical NAFLD, in which alcohol consumption and other causes of chronic liver disease have been excluded. The exclusion criteria also included smoking, arterial hypertension, known renal disease. The control group consisted of 70 diabetic patients, matched for age and gender, without ultrasonographical evidence of NAFLD. In all subjects we measured height, weight, BMI, fasting glucose, HbA1c, total cholesterol, LDL and HDL cholesterol, triglycerides, serum transaminases, hsC-reactive protein and microalbuminuria. A p-value <0.05 was considered statistically significant. RESULTS: Microalbuminuria was significantly more frequent in subjects with NAFLD than in controls (12.7% vs 7.8%, p<0.05). Microalbuminuria was positively correlated with hsCRP levels. In conclusion NAFLD is positively correlated with microalbuminuria-marker of early stage CKD, in diabetic patients. This seems to be related to higher levels of proinflammatory factors released by the liver, such as hsCRP.

Endothelial dysfunction in metabolic syndrome.

Metabolic syndrome (MS) or insulin resistance syndrome is the result of multiple metabolic abnormalities associated with cardiovascular disease. Since 1988, when Reaven first described MS, many researches have been conducted in order to understand its pathophysiology, epidemiology, prognostic implications and therapeutic strategies. Numerous metabolic abnormalities found in the metabolic syndrome, including hyperglycemia, excessive fatty acids and insulin resistance, cause an endothelial cell dysfunction by affecting nitric oxide synthesis or degradation. Although the exact mechanism by which metabolic syndrome induces endothelial dysfunction remains to be clarified, there are many possibilities of vascular endothelial damage and increase in cardiovascular risk in these patients. The most frequent metabolic, hormonal, hemostatic abnormalities in patients with metabolic syndrome that may contribute to endothelial dysfunction are: hyperinsulinemia, hyperglycemia, increase in fatty acid levels, hypertriglyceridemia, decrease in HDL-cholesterol, increase in small dense LDL-cholesterol, increase in apolipoprotein B, increase in insulin-1 growth factor levels, increase in tissue angiotensin II levels, increase in plasminogen activator inhibitor-1, increase in C reactive protein, increase in oxidative stress.

The prognosis of glycoregulation disturbances and insulin secretion in alcoholic and C virus liver cirrhosis.

We studied 49 alcoholic and viral C liver cirrhosis, over a period of 5 years, we evaluated OGTT, HOMA-IR, HOMA-beta, child score, diabetes mellitus and liver cirrhosis complications and survival. Both insulin resistance and lower insulin secretion in liver cirrhosis are important determinants of the degree of oral glucose tolerance. There is a correlation between the bad prognosis in patients with cirrhosis and glycoregulation disturbances, especially in those with alcoholic etiology.

Anemia--a complication of antiviral treatment in chronic viral hepatitis C.

Anemia is an important and frequent secondary effect of the treatment with pegylated interferon and ribavirin in patients with chronic viral C hepatitis. Ribavirin produces more often hemolytic anemia, while pegylated interferon may determine medullary suppression. The level of hemoglobin beneath 10 g/dL is considered by most authors as being the reference level for anemia secondary to the antiviral treatment. Beneath this hemoglobin value it is recommended to reduce or to stop the treatment with ribavirin, to administer recombinant human erythropoietin or blood transfusion, based on the severity of the anemia. The growth rate of the serum erythropoietin in the first few weeks of treatment is correlated with the necessity of decreasing the doses or even to stop the treatment with ribavirin. The SVR (sustained viral response) rate of the patients is reduced when the ribavirin doses are reduced due to anemia.

Serological and histological correlations in celiac disease.

UNLABELLED: The aim of this study was to compare the sensitivity of the serological markers in patients with non-treated celiac disease by determination of antiendomysium and anti-tissue-transglutaminase autoantibodies separately and together. At the same time we examined the correlation between the serum levels of the two antibodies and the severity of the histological lesions. MATERIAL AND METHODS: The research included 26 persons (19 females, 7 males, age range 18-56 years) in whom the small bowel biopsy confirmed the villous atrophy. The sera of these patients were investigated by the determination of antiendomysium antibodies (AEA) and antitissue-transglutaminase antibodies (ATTG). For the morphological disorders we used the Marsh modified criteria. ATTG were determined by a sandwich-ELISA technique and AEA were dosed by indirect immunofluorescence technique. RESULTS: 6 patients presented with partial villous atrophy (PVA), 7 with subtotal villous atrophy (SVA) and 13 with total villous atrophy (TVA). 23 persons were seropositive, having at least one of the two antibodies tested. The sensitivity of the serological investigation increased at 88% using both AEA and ATTG determinations. In patients with TVA, the sensitivity of ATTG was 100% and of AEA was 92%. In patients with SVA and PVA, the sensitivity of these antibodies was lower. Among the patients with SVA, 43% were negative for AEA and 50% for ATTG. The determination of AEA and ATTG together reduced the seronegativity at 15% in patients with SVA and at 34% in patients with PVA. CONCLUSIONS: Antitissue-transglutaminase antibodies testing in patients with non-treated celiac disease is more sensitive than antiendomysium antibodies. The efficiency of the serological diagnosis improves when both AEA and ATTG are determined. Serum antibodies levels correlated very well with the severe histological alterations (TVA), but the correlation is not so good with SVA and PVA. So, we can tell that high levels of AEA and/or ATTG are suggestive for severe histological disorders in celiac disease.

Glycoregulation disorders and alterations of C reactive protein in nonalcoholic fatty liver disease.

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological condition which ranges from simple steatosis and steatohepatitis to cryptogenetic cirrhosis. As insulinresistance plays a central pathogenetic role, NAFLD is regarded as the hepatic feature of the metabolic syndrome. Type 2 diabetes mellitus and obesity are the conditions most frequently associated with NAFLD. Subclinical inflammation has been suggested as a possible connective mechanism between glycoregulation disorders and NAFLD. The purpose of our study was to evaluate the prevalence and severity of glycoregulation disorders (impaired glucose tolerance and type 2 diabetes mellitus) in patients with ultrasonographical certified NAFLD, and to determine medium levels ofC reactive protein in these individuals. MATERIAL AND METHODS: The study was conducted on 104 patients with ultrasonographical certified steatosis, divided into two subgroups: simple steatosis and steatohepatitis, based on the elevation of hepatic enzymes. A control group of 100 subjects without ultrasonographical proof of hepatic steatosis had been used. Fasting glucose, oral glucose tolerance test and C reactive protein levels were performed for each patient. Statistical analysis was based on student t-test and Hi-square test. RESULTS: The prevalence of glycoregulation disorders was significantly higher in patients with NAFLD than in controls (p < 0.05). Patients with steatohepatitis had a significantly higher prevalence of type 2 diabetes mellitus than those with simple steatosis. Medium levels of C reactive protein were significantly higher in patients with NAFLD than in controls, respectively in subjects with steatohepatitis than in those with simple steatosis. CONCLUSIONS: NAFLD is at risk for developing glycoregulation disorders compared with controls; the severity of liver damage is correlated with an augmentation in the severity of glycoregulation disorders. Patients with NAFLD have higher levels of C reactive protein compared with controls, the medium levels C reactive protein increasing with an increase in hepatic damage.

The serum level of certain aminoacids in chronic liver diseases associated with impaired oral glucose tolerance.

We studied the plasma levels of some aminoacids and immunoreactive insulin in chronic liver diseases with impaired glucose tolerance during oral glucose tolerance test (OGTT). There are significant alterations of aminoacids levels and insulin in chronic hepatitis and liver cirrhosis, especially followed by impaired glucose tolerance.

The prognosis significance of insulin secretion in liver cirrhosis.

We evaluate the prognostic significance of chronic liver diseases followed by diabetes mellitus in 40 patients by Child class, immunoreactive insulinemia (IRI), C peptide (CP) and pancreolaury-test (PLT) at 5 years. Death and hepatic insufficiency prevalence were significantly higher in cirrhotic diabetics, and in those diabetics with a lower insulin secretion (IRI, CP). Insulin hyposecretion (lower IRI, CP) was found in cirrhotic with abnormal PLT (below 20%). The onset of diabetes mellitus in liver cirrhosis has a bad prognosis when it is caused by decreased insulin secretion produced by chronic pancreatitis or pancreatic insufficiency.

The oxidative stress in the development of diabetes chronic complications in the elderly.

The diabetes mellitus occurs as an important disease at elderly people, to whom the micro- and macrovascular complications represent a major cause of morbidity and mortality. Experimental researches of the last years proved that the oxidative stress may be the common mechanisms that intervenes in the occurrence of the diabetes complications as well as in the aging process and is responsible for the increased prevalence of chronic complications at elderly diabetics. Starting from this information, we performed a comparative study where we followed the intensity of the oxidative stress at elderly diabetics as compared to adult diabetics and non-diabetic elderly people. At the same time, we have followed the involvement of oxidative stress in the occurrence of diabetic microangiopathy and atherosclerosis. 155 patients from the 4th Medical Clinic were studied during 2000-2003. These patients were divided into three lots: lot 1: elderly diabetics, lot 2: adult diabetics, lot 3: elderly non-diabetics. At these patients we have followed comparatively the intensity of the oxidant status by determining the plasma malondialdehyde (MDA) and the anti-oxidant status by determining the plasma ceruloplasmin, as well as the correlations of these two parameters with the chronic complications of diabetes. At elderly diabetics there is an increased oxidative stress underlined by an increased plasma level of MDA and ceruloplasmin as compared to the adult diabetics and non-diabetic elderly people and this increased oxidative stress is involved in the development of the chronic complications at this patients. In case of elderly diabetics, the age and the illness may induce the formation of oxygen-derived free radicals with synergic effect in injuring tissues and organs.

Rheological changes in diabetic microangiopathy.

OBJECTIVES: Evaluation of rheological changes in patients with diabetes mellitus. MATERIAL AND METHOD: Determination of plasma viscosity, erythrocyte deformability, erythrocyte adhesion, fibrinogen and hematocrit in a group of 56 patients with diabetes mellitus, of which 28 with diabetic microangiopathy. The group includes 20 patients with type 1 diabetes mellitus and 36 patients with type 2 diabetes mellitus. RESULTS: In patients with diabetes mellitus with microangiopathy, more important rheological changes are noted than in diabetes mellitus without microangiopathy; thrombocyte adhesion is increased in 25 patients with microangiopathy compared to those without microangiopathy (7), erythrocyte deformability is decreased in 23 patients with microangiopathy and only in 9 patients without microangiopathy, and increased plasma viscosity is found in 26 patients with microangiopathy compared to those without microangiopathy (3). CONCLUSIONS: In the study performed, a direct correlation is found between the decrease of erythrocyte deformability and the severity of diabetic microangiopathy; the decrease is more severe in patients with proliferative retinopathy or clinically manifest nephropathy. The increase of platelet adhesion in patients with diabetic microangiopathy suggests the hypothesis of the role of thrombocyte changes in the pathogenesis of microangiopathic complications of diabetes mellitus. Plasma viscosity contributes to the pathogenesis of diabetic nephropathy and diabetic polyneuropathy, its increase being noted in diabetic patients with microalbuminuria and peripheral neurological involvement.

Low insulin secretion in decompensated liver cirrhosis with diabetes mellitus.

The present study aimed to investigate the pathogenesis of altered glucose tolerance frequently observed in liver cirrhosis by means of oral glucose tolerance test (OGTT) and i.v. glucagon followed by determining the immunoreactive insulinemia and insulinogenic index (Seltzer). In these conditions of beta islet cells upper limit stimulation a low insulin secretion was found in decompensated liver cirrhosis with alteration of the glucose tolerance (DM or IGT) and a tendency toward hepatic resistance to i.v. glucagon.