Thyroid hormone can favorably remodel the diabetic myocardium after acute myocardial infarction.

It has been previously shown that regulators of physiological growth such as thyroid hormone (TH) can favorably remodel the post ischaemic myocardium. Here, we further explored whether this effect can be preserved in the presence of co-morbidities such as diabetes which accelerates cardiac remodeling and increases mortality after myocardial infarction. Acute myocardial infarction (AMI) was induced by left coronary ligation in rats with type I diabetes (DM) induced by streptozotocin administration (STZ; 35 mg/kg; i.p.) while sham-operated animals served as controls (SHAM). AMI resulted in distinct changes in cardiac function and geometry; EF% was significantly decreased in DM-AMI [37.9 ± 2.0 vs. 74.5 ± 2.1 in DM-SHAM]. Systolic and diastolic chamber dimensions were increased without concomitant increase in wall thickness and thus, wall tension index [WTI, the ratio of (Left Ventricular Internal Diameter at diastole)/2*(Posterior Wall thickness)], an index of wall stress, was found to be significantly increased in DM-AMI; 2.27 ± 0.08 versus 1.70 ± 0.05. 2D-Strain echocardiographic analysis showed reduced systolic radial strain in all segments, indicating increased loss of cardiac myocytes in the infarct related area and less compensatory hypertrophy in the viable segments. This response was accompanied by a marked decrease in the expression of TRα1 and TRß1 receptors in the diabetic myocardium without changes in circulating T3 and T4. Accordingly, the expression of TH target genes related to cardiac contractility was altered; ß-MHC and PKCα were significantly increased. TH (L-T4 and L-T3) administration prevented these changes and resulted in increased EF%, normal wall stress and increased systolic radial strain in all myocardial segments. Acute myocardial infarction in diabetic rats results in TH receptor down-regulation with important physiological consequences. TH treatment prevents this response and improves cardiac hemodynamics.

Type II diabetes mellitus and cardiovascular risk factors: Current therapeutic approaches.

Worldwide, approximately 200 million people currently have type II diabetes mellitus (DM), a prevalence that has been predicted to increase to 366 million by 2030. Rates of cardiovascular disease (CVD) mortality and morbidity are particularly high in this population, representing a significant cost for health care systems. Type II DM patients generally carry a number of risk factors for CVD, including hyperglycemia, abnormal lipid profiles, alterations in inflammatory mediators and coagulation/thrombolytic parameters, as well as other 'nontraditional' risk factors, many of which may be closely associated with insulin resistance. Therefore, successful management of CVD associated with diabetes represents a major challenge to the clinicians. An effective way of tackling this problem is to detect the associated risk factors and to target treatment toward their improvement. Targeting hyperglycemia alone does not reduce the excess risk in diabetes, highlighting the need for aggressive treatment of other risk factors. Although the current use of statin therapy is effective at reducing low-density lipoprotein cholesterol, residual risk remains for other independent lipid and nonlipid factors. The peroxisome proliferator-activated receptor-gamma appears to be closely involved in regulating risk markers at multiple levels. A relatively new class of therapeutic agents that activate peroxisome proliferator-activated receptor-gamma, the thiazolidinedione insulin-sensitizing agents, is currently used to manage type II DM. These agents display a number of potential antiatherogenic properties, including effects on high-density lipoprotein cholesterol and triglycerides, as well as other beneficial nonlipid effects, such as regulating levels of mediators involved in inflammation and endothelial dysfunction. Research data suggest that simple strategies combining thiazolidinediones and statins could have complementary effects on CVD risk-factor profiles in diabetes, alongside the ability to control glycemia.

Inflammatory process in type 2 diabetes: The role of cytokines.

Population-based studies have shown strong relationship between inflammatory markers and metabolic disturbances, obesity, and atherosclerosis, whereas inflammation has been considered as a "common soil" between these clinical entities and type 2 diabetes (T2D). The accumulation of macrophages in adipose tissue (AT), the common origin of macrophages and adipocytes, the prevalent presence of peripheral mononuclear cells, and apoptotic beta cells by themselves seem to be the sources of inflammation present in T2D, since they generate the mediators of the inflammatory processes, namely cytokines. The main cytokines involved in the pathogenesis of T2D are interleukin-1beta (IL-1beta), with an action similar to the one present in type 1 diabetes, tumor necrosis factor-alpha (TNF-alpha), and IL-6, considered as the main regulators of inflammation, leptin, more recently introduced, and several others, such as monocyte chemoattractant protein-1, resistin, adiponectin, with either deleterious or beneficial effects in diabetic pathogenesis. The characterization of these molecules targeted diabetes treatment beyond the classical interventions with lifestyle changes and pharmaceutical agents, and toward the determination of specific molecular pathways that lead to low grade chronic inflammatory state mainly due to an immune system's unbalance.

Differences in expression of cardiovascular risk factors among type 2 diabetes mellitus patients of different age.

Atherosclerotic coronary heart disease and other forms of cardiovascular disease (CVD) are the major cause of mortality in type II diabetes (T2DM) as well as a major contributor to morbidity and lifetime costs. The purpose of this article is the identification of the biochemical parameters in plasma, which may serve as predisposition factors to CVD in T2DM patients of different ages. The variability of hyperglycemia, dyslipidemia, and inflammation with age progression was also studied for comparison. Four different diabetic groups allocated on the basis of the subjects' age (Group A: 15-25 years old; Group B: 26-40 years old; Group C: 40-60 years old; Group D: 60-80 years old) and consisting of 10 patients each, in parallel with 10 healthy controls matched for age, sex, and ethnic origin were screened for glucose, insulin, lipid profile (total cholesterol, triglycerides, LDL, and HDL), and inflammatory mediators (CRP, IL-6, and TNF-alpha). Significant differences were observed among the expressions of biochemical markers among different age groups. Hyperglycemia showed no variability with age whereas dyslipidemia correlated positively with age progression, as well as obesity, low physical activity, and family history of heart disease or diabetes. Marked inflammation was prominent only in Groups C and D. This article indicates that different biochemical parameters may be used for the assessment of CVD risk in T2DM patients of variable age.

Interrelationship of hepatic function, thyroid activity and mood status in alcohol-dependent individuals.

BACKGROUND: Alcohol-induced changes in thyroid function may contribute to the development of mood disorders such as depression and anxiety that almost invariably coexist in alcohol-dependent individuals. The aim of the present study was to investigate the severity of liver dysfunction and thyroid activity in correlation with anxiety and depressive-like symptomatology before and after a detoxification period. PATIENTS AND METHODS: In a sample of 100 alcohol-abusing/dependent subjects treated on an in-patient basis according to a standard detoxification protocol, measurements of the serum levels of hepatic enzymes (ASAT, ALAT, gammaGT) and thyroid hormones (T3, T4, TSH) as well as measures of anxiety, depression and global functioning were obtained at baseline and at weekly intervals over the period of 4-5 weeks. RESULTS: After completion of the alcohol detoxification, most measurements returned to normal levels and correlations were observed between the levels of hepatic enzymes and thyroid hormones. Additionally, a significant correlation was obtained between the levels of thyroid hormones and the mood status scales. CONCLUSION: Our results indicated a dysfunction of the hypothalamic-pituitary-thyroid axis in alcohol dependence with possible implications in the diagnosis and treatment of mood disorders associated with alcohol abuse.

Evidence of reduced plasma HDL subfractions in patients with cutaneous discoid lupus erythematosus.

OBJECTIVES: The aim of the present study was to evaluate the dyslipidemic profile of patients with Cutaneous Discoid Lupus Erythematosus (DLE) with particular emphasis on the levels of High Density Lipoprotein (HDL) Cholesterol and its subfractions, HDL2 and HDL3. DESIGN AND METHOD: The study involved characterization of the lipid profile of 30 patients with diagnosed DLE (11 male and 19 female) and 34 age- and BMI-matched healthy individuals. RESULTS: Patients with DLE presented increased serum cholesterol, triglycerides and LDL-Cholesterol levels (P < 0.001, respectively) compared to the control group, while the levels of HDL-Cholesterol (P < 0.001), as well as its subfractions, HDL2 (P < 0.001) and HDL3 (P < 0.02) were markedly decreased. In addition, the ratio of CHOL/HDL was increased in patients with DLE (P < 0.001), whereas a reduction was observed in the ratio of HDL2/HDL3 (P < 0.001) in the same group. CONCLUSIONS: Our findings suggest that patients with cutaneous discoid lupus erythematosus have an increased risk of atherosclerosis due to the marked dyslipidemia associated with the disease. The reduced levels of HDL subfractions, HDL2 and HDL3, are believed to contribute to the dyslipidemic profile and further provide an important target for therapeutic intervention.

Effects of hormone replacement therapy on the main fatty acids of serum and phospholipids of postmenopausal women.

BACKGROUND: The anti-atherosclerotic effects of hormone replacement therapy (HRT) in postmenopausal women are partly mediated by improvement of the lipid and lipoprotein profiles. The present study aimed to investigate the effects of HRT on the main fatty acids of serum and phospholipids in postmenopausal women. PATIENTS AND METHODS: Serum samples of two groups of postmenopausal women, receiving either single oestrogen or in combination with progestogens, were analysed before and after a 6- month treatment period. RESULTS: Of the main serum fatty acids, there was a significant reduction in palmitic (p < 0.05) and arachidonic acids (p < 0.001), followed by an increase in oleic (p < 0.05) and linoleic acids (p < 0.05) in postmenopausal women receiving HRT compared to single oestrogen. The main fatty acids in phospholipids showed a similar pattern in those women. CONCLUSION: The above results demonstrate the beneficial effects of HRT in reducing the risk of cardiovascular disease through modification of the fatty acid profiles of postmenopausal women.

Comparison of the extent and severity of coronary artery disease in patients with acute myocardial infarction with and without microalbuminuria.

The extent and severity of coronary atherosclerosis were compared between 43 microalbuminuric and 87 normoalbuminuric nondiabetic patients with acute myocardial infarction. Patients with microalbuminuria had significantly greater scores of the severity (Gensini score) and extent (Hamsten score) of coronary artery disease (p <0.001).

The significance of serum HDL phospholipid levels in angiographically defined coronary artery disease.

OBJECTIVES: To evaluate discriminant serum lipid components associated with the presence and extent of coronary artery disease, with particular emphasis on the role of HDL phospholipids as an important predictor for disease severity. DESIGN AND METHODS: Total serum lipoprotein and phospholipids levels of 157 adult male patients (grouped based on degree of coronary artery occlusion) who underwent coronary angiography were analyzed. RESULTS: Patients showed elevated triglyceride (P < 0.001) and VLDL (P < 0.001) levels whereas a significant reduction was observed at LDL (P < 0.01), HDL (P < 0.01), and HDL-phospholipids (P < 0.001) concentrations. Correlation with disease progression (from one to three occluded vessels) showed significant rise in levels (P < 0.001) and markedly decreased HDL phospholipids (P < 0.001). CONCLUSIONS: Triglyceride levels and HDL phospholipids are better indicators of the presence and extent of coronary artery disease compared to the other lipoproteins studied. Furthermore, the HDL phospholipids/Total Cholesterol ratio is proposed as additional information of the degree of coronary artery occlusion.

Altered long chain fatty acids composition in Duchenne muscular dystrophy erythrocytes.

BACKGROUND: Biochemical abnormalities, increased efflux of soluble enzymes and muscle proteins, and altered permeability of muscle membranes imply the presence of a disorganized erythrocyte membrane in Duchenne muscular dystrophy (DMD). The purpose of the present study was to investigate this hypothesis of a generalized membrane defect. MATERIALS AND METHODS: Twenty-five patients with the disease were analyzed for their erythrocyte lipid composition and for alterations in their fatty acid content compared to twenty-five healthy subjects. RESULTS: DMD patients showed a decreased concentration of total phospholipids compared to healthy volunteers, with striking fluctuations in concentrations of erythrocyte long chain fatty acids. Specifically, the unsaturated fatty acids such as oleic, linoleic and arachidonic acids were significantly decreased in the disease, whereas the saturated fatty acid, palmitic acid was increased in DMD patients compared to healthy controls. CONCLUSION: Our findings suggest an abnormal fatty acid composition and disorganization of erythrocyte membrane in patients with DMD associated with possible functional alterations.

Correlation of liver dysfunction biological markers to the mood status of alcohol-dependent individuals.

OBJECTIVE: Alcohol intake is a major cause of liver cirrhosis as well as chronic liver disease, and commonly coexists with mood disorders such as depression and anxiety. The aim of the present study was to investigate the possible correlation between liver dysfunction related to alcohol intake with anxiety and depressive-like symptomatology prior to and after the detoxification period. METHODS: One hundred alcohol abusing/dependent subjects (81 males and 19 females) were treated on an inpatient basis according to a standard detoxification protocol and measurements of serum levels of hepatic enzymes (ASAT, ALAT, γGT), and measures of anxiety (HARS), depression (HDRS) and global functioning (GAS) were also obtained at baseline and at weekly intervals over a period of 4 weeks. RESULTS: Increased levels of hepatic enzymes were observed upon admission that were significantly reduced (P<0.001) following completion of the detoxification treatment. In addition, the psychopathological profile was improved at the end of the detoxification period and a significant correlation was obtained between the levels of hepatic enzymes and the global functioning of alcohol-dependent individuals. CONCLUSION: This observation further supports a relationship between the depressogenic action of alcohol and the disordered liver function observed in alcohol-dependent individuals, with possible implications in the diagnosis and treatment of mood disorders associated to alcohol abuse.

Comparison of raloxifene and atorvastatin effects on serum lipids composition of healthy post-menopausal women.

The aim of this study was to evaluate the effects of the selective oestrogen receptor modulator, raloxifene, and those of statin, atorvastatin, in reducing the cardiovascular risks associated with the post-menopausal status. A detailed study of serum lipid concentrations was performed in four groups of post-menopausal women receiving either placebo, raloxifene or atorvastatin alone or their combination for the period of three months. Group A (raloxifene) showed significant decrease in total cholesterol levels (P < 0.05) and an increase in phospholipids concentration (P < 0.05), followed by a marked reduction in low-density lipoprotein cholesterol (LDL-C) levels (P < 0.01) and ApoB amounts (P < 0.001). Additionally, ApoA-I concentration was significantly increased (P < 0.01). Group B (atorvastatin) presented decreased cholesterol (P < 0.05) and triglycerides levels (P < 0.01), followed by elevated high-density lipoprotein cholesterol (HDL-C) concentration (P < 0.05) and low LDL-C amounts (P < 0.001). ApoA-I was significantly increased (P < 0.001) whereas ApoB was reduced (P < 0.001). The combined treatment in Group C (raloxifene and atorvastatin) showed significant changes in the majority of serum lipids. In particular, total cholesterol was reduced (P < 0.001), as well as triglycerides (P < 0.001) levels. Phospholipids were raised (P < 0.01) whereas LDL-C was reduced (P < 0.001) as was ApoB (P < 0.001). Furthermore, ApoA-I was elevated (P < 0.001). A further attempt to evaluate each treatment group was performed and the significance of these results is discussed.