Effects of rHuEPO treatment on red blood cell osmotic resistance

Red blood cell osmotic resistance (RBCOR) is defined as resistance to osmotic changes in cell integrity after their exposure to hypotonic saline solution. The investigation examined the effect of rHuEPO on RBCOR in hemodialysed patients. The study included 58 patients aged 49 +/- 14 years, treated by hemodialysis for 59 +/- 43 months on average. Half of the patients received rHuEPO for anemia correction. RBCOR was determined in all patients as 3 values: hemolysis start point (HSP), hemolysis end point (HEP) and middle osmotic resistance (MOR). The patients underwent laboratory checkup for parameters characteristically changed in the uremic syndrome. In the control group of healthy subjects (n = 16) RBCOR was only determined. No differences were found in the average values of HSP, HEP and MOR between the rHuEPO treated group of patinets and the untreated group. Compared to healthy individuals, the hemodialysed patients displayed significantly higher values of HSP, HEP and MOR. The only one significant correlation of RBCOR and routine laboratory features was found between MOR and predialytic serum concentrations of calcium (r = 0.28, p < 0.05) and hydrogen ions (r = 0.37, p < 0.05). Our results suggest that the administration of rHuEPO does not affect RBCOR in hemodialysed patients, that RBCOR is not always reduced in this population and that it correlates with a small number of laboratory parameters characteristic for the uremic syndrome.     

Modulation of cortisol metabolism during treatment of acromegaly is independent of body composition and insulin sensitivity

OBJECTIVES: The set point of cortisol-cortisone conversion is shifted in the direction of cortisone by the inhibition of the activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) during adult GH replacement and in active acromegaly. Additionally, both fat mass and insulin may modulate 11beta-HSD1 and are both influenced by changes in GH status. This study examined the relative direct contribution of GH/IGF1 in modulating cortisol metabolism. METHODS: Overall cortisol/cortisone conversion (ratio of urine 11-hydroxy-/11-oxo-cortisol metabolites; Fm/Em), insulin sensitivity (homeostatic model assessment; HOMA %S) and fat mass (DXA) were examined in parallel in 6 patients (mean age 53 years, range 42-76; 4 males, 2 females) with previously untreated active acromegaly during 6 months of therapy with Sandostatin LAR (20-30 mg i.m. 4 weekly). All but 1 patient had normal ACTH reserve. RESULTS: At baseline, Pearson correlation demonstrated an inverse relationship between serum GH (mean of a 5-point day curve) and Fm/Em (r = -0.83, p = 0.04) and a trend towards an inverse relationship between HOMA %S and Fm/Em (r = -0.79, p = 0.06) but no other patterns were evident. During the course of treatment, serum GH decreased from 9.9 +/- 6.4 (mean +/- SD) to 3.5 +/- 3.1 ng/ml (p < 0.01) and serum IGF-1 from 785 +/- 268 to 431 +/- 156 ng/ml (p < 0.005). Fm/Em increased from 0.52 +/- 0.1 to 0.75 +/- 0.08 (p < 0.03) consistent with increased 11beta-HSD1 activity. There were no significant changes in truncal fat percentage (33.0 +/- 9.0 vs. 33.0 +/- 8.2) or insulin sensitivity (HOMA %S: 37.1 +/- 8.6 vs. 52.8 +/- 33.7). CONCLUSIONS: Modulation of cortisol metabolism during treatment of active acromegaly is dependent on changes in GH/IGF-1 status and is not influenced by any individual change in body composition or insulin sensitivity.     

Pharmacological PPARgamma stimulation in contrast to beta cell stimulation results in an improvement in adiponectin and proinsulin intact levels and reduces intima media thickness in patients with type 2 diabetes.

The role of intact proinsulin and adiponectin in endothelial dysfunction and insulin resistance has been receiving increasing attention. This study investigates the effect of PPARgamma stimulation or beta-cell stimulation on metabolic and vascular parameters in patients with type 2 diabetes. In our study, 173 type 2 diabetic patients were recruited and randomly assigned to pioglitazone 45 mg or glimepiride 1 - 6 mg treatment. Intima media thickness of the carotid artery, glycemic control, insulin resistance, adiponectin and intact proinsulin levels were assessed at baseline and after six months of treatment. Despite similar improvements in metabolic control (HbA (1c) after 24 weeks: - 0.8 +/- 0.9% [pioglitazone] vs. - 0.6 +/- 0.8% [glimepiride]; mean +/- SD; p < 0.0001, respectively), improvements in intima media thickness (- 0.033 +/- 0.052 mm; p < 0.0001), proinsulin intact (- 5.92 +/- 10.04 pmol/l; p < 0.0001), adiponectin (10.9 +/- 6.3 microg/ml; p < 0.0001) and HOMA score (- 2.21 +/- 3.40; p < 0.0001) were observed by pioglitazone but not glimepiride treatment. Reduction in intima media thickness was correlated with improved insulin sensitivity (r = 0.29; p = 0.0003), and proinsulin intact levels (r = 0.22; p = 0.006), while an inverse correlation was found with adiponectin levels (r = - 0.37; p < 0.0001). Measurement of adiponectin and intact proinsulin enables characterization of the metabolic situation and an estimation of atherosclerotic risk in patients with type 2 diabetes.     

Plasma adiponectin concentrations in patients with chronic renal failure: relationship with metabolic risk factors and ischemic heart disease.

AIMS: To compare plasma adiponectin levels between healthy controls and patients with chronic renal failure and to examine for a relationship between plasma adiponectin levels and ischemic heart disease as well as aortic distensibility which is an early marker of atherosclerosis. METHODS: We included 89 patients with CRF (45 on and 44 not on hemodialysis) and 70 controls in a cross-sectional study. Plasma adiponectin levels were measured by radioimmunoassay. Aortic distensibility was assessed by high-resolution ultrasonography. RESULTS: Plasma adiponectin levels were significantly almost twice as high in patients with renal failure compared to controls (9.7 +/- 1.1 vs. 5.4 +/- 0.6 microg/ml, p < 0.0001). No significant differences were found between renal patients on hemodialysis and not on hemodialysis (p = 0.71). Multivariate linear regression analysis in the renal patient group demonstrated a significant negative relationship between plasma adiponectin levels and ischemic heart disease (p = 0.02). The same analysis in the control subjects group showed a significant, negative relationship between plasma adiponectin levels and body mass index (p = 0.02) and a highly significant positive relationship with the high density lipoprotein cholesterol (p < 0.0001). In the total study population, glomerular filtration rate was the only independent predictor of plasma adiponectin concentrations. Aortic distensibility was lower in renal patients than in controls at a high level of significance (p < 0.0001). However, no significant relationship could be found between plasma adiponectin and aortic distensibility in either the controls or the renal patients. CONCLUSIONS: Plasma adiponectin levels are almost twice as high in patients with chronic renal failure in comparison with healthy controls, but not different between renal patients on and those not on hemodialysis. In addition, low plasma adiponectin levels are strongly associated with ischemic heart disease, but not with aortic distensibility in chronic renal failure.     

Antioxidant status and lipid peroxidation in hemodialysis patients undergoing erythropoietin and erythropoietin-vitamin E combined therapy.

In this study, plasma and red blood cell (RBC) antioxidant status and plasma lipid peroxidation were investigated in 46 hemodialysis patients. In addition, the effect of erythropoietin (EPO) and EPO-vitamin E combination therapy on plasma and RBC antioxidant status, and plasma lipid peroxidation were examined. There were 10 healthy subjects in the control group and 10 hemodialysis patients in the untreated group. The third group included 36 hemodialysis patients that were given EPO (100 U/kg) for 3 months, 3 times per week. The fourth group included 36 hemodialysis-patients from the EPO group that were given EPO at a 50% decreased dose + vitamin E (300 mg/day) for 3 months. MDA levels in the untreated group, the EPO group and the EPO + vitamin E groups were found to be higher than the control group (p < 0.001, in both). Furthermore, MDA levels in both of the treatment groups were lower when compared to the untreated group (p < 0.001, in both). Plasma vitamin E levels in the untreated, the EPO group and EPO + vitamin E groups were lower than the control group (p < 0. 001). In contrast, plasma vitamin E levels in the treatment groups were higher in comparison with the control group (p < 0.05). SOD activities in the untreated, the EPO group and the EPO + vitamin E groups were found to be lower than the control group (p < 0.001). SOD activities in the treatment groups were higher than the control group (p<0.001). The SOD activities in the EPO+vitamin E group increased when compared to the EPO group (p < 0.001). CAT activities in the untreated, the EPO group and the EPO + vitamin E groups were found to be lower than the control group (p < 0.001 in untreated and EPO groups, p <0.01 in EPO+ vitamin E group). CAT activities in EPO and EPO+ vitamin E groups were increased when compared to the untreated group (p < 0.01). In conclusion, our findings have shown that antioxidant status decreased and lipid peroxidation increased in hemodialysis patients. EPO has an antioxidant effect on the RBC and plasma antioxidant status, and plasma lipid peroxidation. These effects were moderately increased by the combination of vitamin E and EPO.     

Insulin resistance in nonobese patients with polycystic ovary syndrome

OBJECTIVES: Most patients with polycystic ovary syndrome (PCOS) are obese and known to have insulin resistance. Obesity per se is a cause of insulin resistance. This study was performed to determine whether insulin resistance occurs in patients with PCOS in the absence of obesity and acanthosis nigricans. METHOD: For this purpose, an euglycemic hyperinsulinemic clamp study was performed in 12 nonobese patients with PCOS and in 10 healthy control subjects matched for age and weight. RESULTS: The mean serum testosterone and luteinizing hormone (LH) levels were significantly elevated (4.09 +/- 1.32 vs. 1.18 +/- 0.53 pg/ml, p < 0.001, and 11.63 +/- 5.37 vs. 4.98 +/- 2.73 mIU/ml, p < 0.001, respectively), and the serum sex hormone binding globulin level was significantly reduced (40.96 +/- 14.94 vs. 73.98 +/- 30.40 nmol/l, p < 0.001) in patients with PCOS as compared with the values in control subjects. The mean serum insulin level was also elevated in patients with PCOS as compared with control subjects (32.33 +/- 4.98 vs. 19.56 +/- 2.21 microU/ml, p < 0.05). The insulin sensitivity was lower in patients with PCOS as compared with the control subjects (200 +/- 27.8 vs. 427.8 +/- 88.9 micromol x kg(-1) x min(-1), p < 0.001). In patients with PCOS, the serum levels of free testosterone (r = -0.89, p < 0.001) and LH were inversely correlated with the insulin sensitivity (r = -0.63, p < 0.05). Serum follicle-stimulating hormone, prolactin, and dehydroepiandrosterone sulfate levels were similar in both groups. CONCLUSIONS: These results indicate that a significant degree of insulin resistance exists in nonobese patients with PCOS and that this insulin resistance is significantly related to serum LH and free testosterone levels. Thus, measures to decrease insulin resistance may have to be considered earlier to decrease the potential risks of developing diabetes mellitus and coronary artery disease at later ages of life in these patients.     

Serum leptin and adiponectin concentrations in patients infected with human immunodeficiency virus type 1 (HIV-1) on antiretroviral therapy

The lipodystrophy syndrome with dyslipidaemia and insulin resistance is side-effect of combined antiretroviral therapy (CART). Aim of the study: to describe the influence of CART on leptin and adiponectin concentration in connection with lipids levels in HIV-infected patients on antiretroviral therapy. BMI, serum leptin, adiponectin, triglycerides, total cholesterol, HDL- and LDL-cholesterol concentrations were measured in 56 HIV(+) patients before and on CART; average of treatment duration 38.4 +/-13.2 months. Significant increase of BMI (p=0.0268) of (22.6 +/- 3.3 before and 23.5 +/- 3.4 kg/m2 on therapy, respectively) and all analyzed lipids were found. Mean adiponectin concentration in treated patients was significantly (7.256 +/- 3.551 microg/ml) lower than mean value before treatment (8.395 +/- 3.568 microg/ml; p=0.0011). Mean values of leptin concentrations did not differ significantly (before therapy 3.721 +/- 0.347 log10; on therapy 3.1737 +/- 0.353 log10). Significant positive correlation between BMI and leptin concentrations was found before, as well as during CART (r=0.5333; p<0.0001), but negative correlation between adiponectin and leptin concentrations (r=-0.2677; p=0.042). Leptin and adiponectin concentrations did not revealed significant correlation with lipids levels before therapy. The decrease of adiponectin concentration on CART correlated negatively with total (r=-0.2912; p=0.0310) and LDL-cholesterol (r=-0.310; p=0.0225). CART lasting longer than 2 years resulted in the decrease of adiponectin concentration, with lack of influence on leptin concentration in analyzed group. The increase of total cholesterol and LDL-cholesterol in correlation with the decrease of adiponectin concentration confirms that CART induces metabolic disturbances related to higher risk of atherosclerosis and its sequel.     

The effect of insulin treatment on HbA1c, body weight and lipids in type 2 diabetic patients with secondary-failure to sulfonylureas. A five year follow-up study.

No conclusive data are available about the long-term effect of insulin treatment in type 2 diabetic patients failing to maximal doses of sulfonylureas and caloric restriction. In total 160 non-obese type 2 diabetic patients with secondary failure were substituted with insulin using a diabetic teaching and care program. From these 160 patients 40 died within the observation period of five years; 102 patients had a complete five year follow-up, whereas the remaining 18 patients did not come to regular follow-up visits. Metabolic control parameters improved significantly in the 102 patients with the complete five year follow-up. Postprandial plasma glucose (16.0 mM vs 10.9 mM; p < 0.0001) and HbA1c values (8.7% vs 7.1%, p < 0.0001) decreased significantly from the state before to five years after insulin substitution. In addition, plasma lipid levels could be significantly lowered under insulin therapy (cholesterol 6.2 +/- 1.5 mM vs 5.4 +/- 3.6 mM, p < 0.0002; triglycerides 2.8 +/- 1.6 mM vs 2.4 +/- 2.1 mM, p < 0.01). However, we observed a significant weight gain (mean: 10.6 kg) associated with insulin application during the five year follow-up. Thus, the body-mass-index decreased from 28.9 at onset of type 2 diabetes to 24.5 (p < 0.0001) at time of secondary failure and increased again to 28.5 (p < 0.0001) at five years after onset of insulin treatment. Furthermore, small increases of plasma creatinine from 88.4 microM to 115 microM, as well as systolic (19.3 kPa to 20.7 kPa) and diastolic (10.7 kPa to 11.3 kPa) blood pressures were observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hyperinsulinemia and insulin insensitivity in women with nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency: the relationship between serum leptin levels and chronic hyperinsulinemia

BACKGROUND/AIM: Nonclassical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (NC-CAH) is associated with hyperandrogenemia, chronic anovulation, hirsutism, acne and adrenal hyperplasia. A few studies have shown hyperinsulinemia and insulin insensitivity in NC-CAH. Hyperinsulinemia can stimulate leptin secretion, and androgens can inhibit leptin secretion. Thus, we designed a study to investigate the insulin levels and insulin sensitivity and the effect of chronic endogenous hyperinsulinemia and androgens on leptin in patients with NC-CAH. METHODS: Eighteen women with untreated NC-CAH and 26 normally cycling control women with a similar body mass index (BMI) were studied. Basal hormones, fasted and fed insulin levels, leptin and stimulated 17-hydroxyprogesterone (17-OHP) concentrations were studied. Homeostasis model assessment was used to assess insulin sensitivity. RESULTS: The basal 17-OHP, the free testosterone (fT) and dehydroepiandrosterone sulfate (DHEA-S) were significantly different in the 2 groups (p < 0.05). Fasting and fed insulin levels of the NC-CAH group were higher than those of the control group (p < 0.05) and insulin sensitivity was lower in NC-CAH than in controls (p < 0.05). Insulin levels were correlated with fT and 17-OHP (p < 0.05). Serum leptin levels for NC-CAH (25.9 +/- 12.5 microg/l) did not differ from the controls (25.4 +/- 12.06 microg/l) and were positively correlated with BMI (r = 0.725) and percent body fat (r = 0.710) for both groups (both p < 0.001). Leptin levels were not correlated with estrogen or androgens, gonadotropins or insulin levels. CONCLUSION: Hyperinsulinemia and insulin insensitivity associated with hyperandrogenism were detected in untreated NC-CAH patients as in previous reports, whereas serum leptin levels did not differ from those of controls.     

Effect of doxazosin on insulin resistance in hypertensive patients with obesity.

We determined the effect of alpha-adrenergic blocking agent doxazosin on insulin resistance in 19 hypertensive patients (blood pressure [BP] >160/90 mmHg) with obesity (mean body mass index [BMI]: 26.7 +/- 1.9 kg/m (2)). Patients received doxazosin 4 mg/day for 12 months. Systolic and diastolic BP decreased from 169 +/- 10.8 mmHg to 147 +/- 11.9 mmHg (p < 0.0001) and from 102 +/- 8.1 mmHg to 87 +/- 5.0 mmHg (p < 0.0001), respectively. Insulin resistance and fasting immunoreactive insulin (IRI) were lower at study end vs. baseline (HOMA-R = 1.29 +/- 0.38 vs. 3.58 +/- 2.23 [p = 0.022]; IRI = 6.00 +/- 1.88 microU/ml vs 13.74 +/- 8.51 microU/ml [p = 0.046]). Total cholesterol was significantly reduced following treatment. Circulating TNF-alpha and leptin levels decreased significantly within 3 months of treatment; leptin was independently associated with insulin resistance when adjusted for BMI. We conclude that doxazosin improves insulin resistance and improves dyslipidemia in obese hypertensive patients, and has a beneficial effect on adipose endocrine activity.     

Plasma tumor necrosis factor-alpha levels and insulin resistance in nondiabetic hypertensive subjects

OBJECTIVES: Tumor necrosis factor-alpha (TNF-alpha) is associated with insulin resistance in certain conditions. However, whether TNF-alpha is related to insulin resistance in hypertensive subjects is still controversial. The aim of this study was to determine the status of TNF-alpha and insulin resistance in hypertension. METHODS: Newly diagnosed nondiabetic 17 essentially hypertensive (6 men, 11 women) patients, and 11 control healthy subjects (5 men, 6 women) are involved in the study. Body mass index (BMI), insulin, fasting blood glucose, cholesterol, triglyceride, and TNF-alpha levels were measured. Insulin resistance is assessed according to homeostasis model of assessment (HOMA-IR). RESULTS: Serum insulin (8.4 +/- 2.7 vs. 6.1 +/- 1.4 mIU/ml; p < 0.01), triglyceride (245.0 +/- 39.9 vs. 193.0 +/- 22.8 mg/dl; p < 0.01), and TNF-alpha (4.2 +/- 0.7 vs. 3.0 +/- 0.6 pg/ml; p < 0.001) levels, and HOMA-IR (2.0 +/- 0.8 vs. 1.3 +/- 0.3; p < 0.001) were significantly higher in the hypertensive patients compared to the normotensive control group. There were positive correlations between TNF-alpha levels and body mass index (r = 0.64, p < 0.01), and triglyceride (r = 0.55 p = 0.02) levels in the whole study group. However, there was no correlation of either TNF-alpha or HOMA-IR. CONCLUSIONS: Our data revealed that hypertensive patients have insulin resistance and higher TNF-alpha levels, but there is no relation between TNF-alpha levels and insulin resistance.     

Abnormal fatty acid profile in chronic hemodialysis patients: possible deficiency of essential fatty acids

Plasma fatty acid profiles from maintenance hemodialysis patients (n = 9) were compared with those from healthy volunteers (n = 9). Hemodialysis patients had significantly higher levels of oleic acid, 15.3 +/- 1.1 vs. 8.9 +/- 0.6% (p less than 0.0001), and lower levels of arachidonic acid (6.0 +/- 0.5 vs. 8.4 +/- 0.3%, p less than 0.0009). Linolenic and linoleic acids, the essential fatty acid and precursors of arachidonic acid, were also significantly lower than normal in the dialysis group. These data show that dialysis patients have fatty acid abnormalities suggesting relative depletion of essential fatty acids. These observations are important because these abnormalities may play an important role in the pathogenesis of some common clinical conditions associated with uremia, such as a constellation of skin problems, fragility of erythrocytes, lipid anomalies and hormonal aberrations.     

Erythrocyte insulin receptor and glucose tolerance test in children treated with prednisolone

Insulin receptors of erythrocytes and oral glucose tolerance test (O-GTT) were investigated in sixteen children treated with prednisolone for various diseases. Ten patients (Group 1) received low doses of prednisolone (0.2-0.5 mg/kg body weight/day) and six patients (Group 2) received higher doses of prednisolone (1.5-2.0 mg/kg body weight/day). Compared to the values for controls, the sums of blood glucose (sigma BS) at O-GTT in both group 1 and group 2 patients were significantly elevated. (422 +/- 75 mg/dl, p less than 0.01 Group 1; 419 +/- 39 mg/dl, p less than 0.01 Group 2; 338 +/- 41 mg/dl controls) Significant differences were not observed in the sums of insulin concentration at O-GTT, fasting blood concentration and basal insulin levels among these two groups and the controls. There was a significant increase in the maximum insulin binding in group 2 (9.13 +/- 0.68% in group 2, 7.97 +/- 1.06% in controls, p less than 0.05), but not in group 1 (8.59 +/- 1.82%). There is no significant difference in binding affinity or the number of receptors between any of these two patients' groups and the controls. When patients in group 1 and group 2 were combined, sigma IRI levels were significantly elevated in the patients (p less than 0.05). These results suggested that prednisolone treatment with a smaller dosage as well as with the higher dosage resulted in a carbohydrate intolerance, the main cause of which is located in a postreceptor step (or steps) of insulin action.     

Diagnostic value of serum IGF-I and IGFBP-3 in growth hormone disorders in adults

OBJECTIVE: To investigate the diagnostic value of serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) measurements in adult patients with acromegaly and GH deficiency (GHD). METHODS: Serum IGF-I and IGFBP-3 levels were measured in 39 active acromegalic patients, 34 adult patients with GHD and 150 healthy adults. Disease activity in patients with acromegaly was confirmed by nadir GH levels during an oral glucose tolerance test (OGTT). Among patients with acromegaly, 15 had not been treated previously and 24 had been treated but not cured. GHD in adults was diagnosed by an insulin tolerance test (ITT). Among patients with GHD, 15 were aged 20-40 years (9 men and 6 women) and 19 were aged over 40 years (9 men and 10 women). One hundred and fifty healthy subjects were recruited as a control group. To compare the individual serum IGF-I and IGFBP-3 levels of patients with the results of the gold standard, we calculated age- and sex-corrected standard deviation scores (SDS) for individual IGF-I and IGFBP-3 levels. The sensitivities of serum IGF-I and IGFBP-3 measurements for the disease diagnosis were analyzed using the mean +/- 2 SD of the values of healthy control subjects as a diagnostic cutoff, defining 95% specificity. RESULTS: The mean IGF-I and IGFBP-3 SDS levels were significantly higher in active acromegalic patients, both untreated and treated but not cured, than in the control subjects (p < 0.05). The sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of acromegaly were 97.4 and 81.8%, respectively. In untreated patients with acromegaly, the sensitivities of serum IGF-I and IGFBP-3 measurements for the diagnosis of disease were 100 and 100%, while these were 95.8 and 72.7% in treated patients with acromegaly. In adult patients with GHD, the mean IGF-I and IGFBP-3 SDS were significantly lower than those of the control subjects (IGF-I, -2.2 +/- 0.8 vs. 0.0 +/- 1.0 SDS, p < 0.0001); IGFBP-3, -1.7 +/- 1.2 vs. 0.0 +/- 1.0 SDS, p < 0.0001), but there was a considerable overlap between GHD in adults and the controls. In all patients with GHD, the sensitivities of serum IGF-I and IGFBP-3 measurements were 64.7 and 52.9%, respectively. In the group of women aged 20-40 years, the sensitivity of IGF-I measurement for the diagnosis of GHD was 100%, although the number of patients was only 6. CONCLUSION: Both serum IGF-I and IGFBP-3 measurements are comparable to an oral glucose tolerance test in patients with untreated acromegaly, but in acromegalic patients that have undergone surgery and/or radiotherapy, serum IGF-I is more valuable for determining disease activity than serum IGFBP-3. Serum IGF-I and IGFBP-3 measurements are not valuable for the diagnosis of GHD in adults, but in women aged 20-40 years serum IGF-I measurement appears to be useful in the diagnosis of GHD.     

The relationship between insulin sensitivity and serum adiponectin levels in three population groups.

Reduced plasma adiponectin levels are associated with insulin resistance. Black South Africans, like African Americans, are more insulin-resistant than BMI-matched white subjects, as are Asian Indians. We investigated whether this interethnic variation in insulin resistance is due to differences in plasma adiponectin levels. Blood and anthropometric measurements were taken from black, white and Asian-Indian subjects. Serum adiponectin, lipids, glucose and insulin were measured; insulin sensitivity was calculated using HOMA. Black (HOMA = 2.62 +/- 0.99) and Asian-Indian subjects (HOMA = 3.41 +/- 2.85) were more insulin-resistant than BMI-matched white (HOMA = 1.76 +/- 0.63) subjects (p = 0.0001). Furthermore, the white subjects had higher adiponectin levels (8.11 +/- 4.39 microg/ml) compared to black (5.71 +/- 2.50 microg/ml) and Asian Indian (5.86 +/- 2.50 microg/ml) subjects (p = 0.003). When all ethnic groups were combined, multiple regression analysis demonstrated that serum adiponectin levels corrected for BMI and ethnicity did not correlate with HOMA, but did explain 10.0 % of the variance in HDL-cholesterol levels. Within each ethnic group, adiponectin only correlated inversely with HOMA in white subjects. Adiponectin may play a role in determining serum HDL-cholesterol levels, but ethnic variation in insulin sensitivity is not dependent on serum levels of this adipokine. The relationship between adiponectin and insulin resistance varies across ethnic groups.     

Differential effects of haloperidol and olanzapine on the expression of erythropoietin and its receptor in rat hippocampus and striatum

Compared with first-generation antipsychotics (FGAs), second-generation antipsychotics (SGAs) seem to be neuroprotective and trigger neuroplasticity. Because neuroplasticity is regulated by a variety of neurotrophic factors we studied differential effects of haloperidol (HAL, a FGA) and olanzapine (OLZ, a SGA) on temporal expression of erythropoietin (EPO), a potent neuroprotective factor and its receptor (EPOr) in rat brain. Rats (8-10/group) were treated with HAL or OLZ for 14 days (HAL-14 or OLZ-14) or 45 days (HAL-45 or OLZ-45). Animals were killed by decapitation or by perfusion to collect brains for immunoblotting and immunohistochemical analysis respectively. In hippocampus, the levels of both EPO and EPOr were significantly increased in HAL-14 (p < 0.001) and OLZ-14 (p < 0.001) groups. Their levels decreased in HAL-45 compared with levels in HAL-14 (EPO, p < 0.001; EPOr, p < 0.05), whereas the levels were further increased (EPO, p < 0.05) in OLZ-45 compared with OLZ-14. In striatum, the levels of both EPO and EPOr were unchanged in HAL-14 and EPO levels significantly decreased in HAL-45 (p < 0.05), whereas their levels were significantly increased in OLZ-14 and OLZ-45 compared with the vehicle-treated control (p < 0.001). Both EPO and EPOr were primarily expressed by neurons and endothelial cells. These data suggest that SGAs such as OLZ may have neuroprotective effects through expression of EPO that may be clinically relevant for long-term safe and beneficial management of psychotic patients.     

Serum adipocyte fatty acid binding protein levels in patients with type 2 diabetes mellitus and obesity: the influence of fenofibrate treatment

Recent studies have demonstrated that adipocyte fatty acid binding proteins (FABP) may play a role in the etiopathogenesis of insulin resistance. The aim of our study was to assess serum FABP levels in obese patients with type 2 diabetes mellitus (T2DM) before and after 3 months of treatment with PPAR-alpha agonist fenofibrate (F) and to explore the relationship of FABP to biochemical parameters and measures of insulin sensitivity assessed by hyperinsulinemic-isoglycemic clamp. We measured biochemical parameters by standard laboratory methods, insulin sensitivity by hyperinsulinemic-isoglycemic clamp and serum concentrations of FABP by commercial ELISA kit in 11 obese females with T2DM before and after three months of treatment with PPAR-alpha agonist fenofibrate and in 10 lean healthy control women (C). Serum FABP levels were 2.5-fold higher in T2DM group relative to C and were not affected by fenofibrate treatment (C: 20.6+/-2.1 microg/l, T2DM before F: 55.6+/-5.7 microg/l, T2DM after F: 54.2+/-5.4 microg/l, p 0.0001 for C vs. T2DM before F). Hyperinsulinemia during the clamp significantly suppressed FABP levels in both C and T2DM group. FABP levels positively correlated with BMI, triglyceride levels, blood glucose, glycated hemoglobin, atherogenic index and insulin levels. An inverse relationship was found between FABP and HDL levels, metabolic clearance rate of glucose, M/I and MCR(glc)/I sensitivity indexes. We conclude that FABP levels are closely related to BMI, parameters of insulin sensitivity, HDL levels and measures of diabetes compensation. This combination makes FABP a valuable marker of metabolic disturbances in patients with type 2 diabetes mellitus.     

Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients

Because chronic L-arginine supplementation improves insulin sensitivity and endothelial function in nonobese type 2 diabetic patients, the aim of this study was to evaluate the effects of a long-term oral L-arginine therapy on adipose fat mass (FM) and muscle free-fat mass (FFM) distribution, daily glucose levels, insulin sensitivity, endothelial function, oxidative stress, and adipokine release in obese type 2 diabetic patients with insulin resistance who were treated with a combined period of hypocaloric diet and exercise training. Thirty-three type 2 diabetic patients participated in a hypocaloric diet plus an exercise training program for 21 days. Furthermore, they were divided into two groups in randomized order: the first group was also treated with L-arginine (8.3 g/day), and the second group was treated with placebo. Although in the placebo group body weight, waist circumference, daily glucose profiles, fructosamine, insulin, and homeostasis model assessment index significantly decreased, L-arginine supplementation further decreased FM (P < 0.05) and waist circumference (P < 0.0001), preserving FFM (P < 0.03), and improved mean daily glucose profiles (P < 0.0001) and fructosamine (P < 0.03). Moreover, change in area under the curve of cGMP (second messenger of nitric oxide; P < 0.001), superoxide dismutase (index of antioxidant capacity; P < 0.01), and adiponectin levels (P < 0.02) increased, whereas basal endothelin-1 levels (P < 0.01) and leptin-to-adiponectin ratio (P < 0.05) decreased in the L-arginine group. Long-term oral L-arginine treatment resulted in an additive effect compared with a diet and exercise training program alone on glucose metabolism and insulin sensitivity. Furthermore, it improved endothelial function, oxidative stress, and adipokine release in obese type 2 diabetic patients with insulin resistance.     

The serum concentration of tumor necrosis factor alpha is not an index of growth-hormone- or obesity-induced insulin resistance

BACKGROUND: The tumor necrosis factor alpha (TNF-alpha) might play a central role in insulin resistance, a frequent correlate of obesity likely contributing to some obesity-associated complications. Adult growth hormone (GH) deficiency syndrome (GHDA) shares with obesity excessive fat mass, hyperlipidemia, increased cardiovascular risk, and insulin resistance. On the other hand, GH has been shown to induce transient deterioration of glucose metabolism and insulin resistance when administered in normal humans and in GHDA patients. No information is presently available on the relationship between serum TNF-alpha levels and insulin sensitivity in GHDA. METHODS: We compared the serum TNF-alpha levels found in 10 GHDA patients before and after a 6-month recombinant human GH therapy (Genotropin), in an insulin resistance prone population of 16 obese (OB) patients and in 38 normal-weight healthy blood donors (controls). The insulin sensitivity was assessed by a euglycemic-hyperinsulinemic glucose clamp in all the GHDA patients and in 10 OB and in 6 control subjects. RESULTS: The serum TNF-alpha levels were not significantly different in OB patients (42.2 +/- 12.81 pg/ml), in GHDA patients at baseline (71.3 +/- 23.97 pg/ml), and in controls (55.3 +/- 14.28 pg/ml). A slight decrease of TNF-alpha values was noted in GHDA patients after 6 months of recombinant human GH treatment (44.5 +/- 20.19 pg/ml; NS vs. baseline). The insulin sensitivity (M) was significantly reduced in OB patients (2.4 +/- 0.30 mg/kg/min) as compared with control subjects (7.5 +/- 0.39 mg/kg/min) and in GHDA patients both at baseline (6.6 +/- 0.6 mg/kg/min) and after recombinant human GH therapy (5.6 +/- 0.7 mg/kg/min). The insulin sensitivity in the GHDA patients, similar to that of controls at baseline, worsened after recombinant human GH treatment (p < 0.05 vs. baseline; p = 0.05 vs. controls). Linear regression analysis showed no correlation between TNF-alpha and M values (see text) in all patient groups. CONCLUSIONS: These data indicate that circulating concentrations of TNF-alpha do not reflect the degree of insulin resistance in obesity and GHDA. They, however, do not exclude that TNF-alpha may induce insulin resistance at tissue level.     

Trace Element Levels in Hashimoto Thyroiditis Patients with Subclinical Hypothyroidism

The present study was conducted to evaluate the serum copper, zinc, magnesium, and selenium levels in patients with subclinical hypothyroidism in the iodine-rich region of Ankara, Turkey. The effects of hormone replacement therapy on these elements were also studied in these patients. Basal levels of selenium and iron in patients were significantly lower than control group (67.7 +/- 10.4 vs. 83.7 +/- 17.3 microg/dl, p = 0.02; 55.7 +/- 38 vs 275.7 +/- 24, P = 0.03 microg/dl). Serum magnesium levels were significantly higher in patient group (2.16 +/- 0.31 vs 1.95 +/- 0.13 mg/dl, P < 0.0001). There was a correlation between selenium levels with hsCRP (r = -0.408, p = 0.007). HsCRP levels in patients with selenium levels <80 microg/l (n = 31) was significantly higher than hsCRP levels in patients with selenium levels >80 microg/l (n = 12; 1.99 +/- 1.0; 1.02 +/- 0.9, p = 0.014). None of these biochemical risk factors and trace elements have changed after euthyroidism in patients with SH when compared to pretreatment levels. Selenium deficiency may contribute to cardiovascular disease risk in these patients.