Effects of prednisone withdrawal on the new metabolic triad in cyclosporine-treated kidney transplant patients

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality after renal transplantation. Prednisone (Pred) maintenance therapy is associated with risk factors for atherosclerosis. Therefore, we were interested in quantifying the effects of Pred withdrawal on body weight and waist circumference as well as on metabolic markers of coronary heart disease risk. METHODS: Twenty-six cyclosporine-treated renal transplant patients (13 men and 13 women) were evaluated before and after at least 11 months (16 +/- 2.9 months) of Pred withdrawal. A complete fasting lipoprotein-lipid profile as well as anthropometric measurements were obtained from each patient. RESULTS: Pred withdrawal was associated with a 6.0% reduction of body weight (-4.34 +/- 5.40 kg; P < 0.05) and with a 7.7% decrease in waist girth (-7.13 +/- 5.75 cm; P < 0.005) in women, whereas no change in these variables were observed in men. In both genders, plasma low-density lipoprotein (LDL) cholesterol and triglyceride concentrations were unaffected by Pred withdrawal, whereas plasma high-density lipoprotein (HDL) cholesterol levels decreased by 14.0% in women (-0.22 +/- 0.22 mmol/L; P < 0.005) and 22.0% in men (-0.36 +/- 0.28 mmol/L; P < 0.005). Pred withdrawal was associated with a significant reduction in plasma apolipoprotein B concentrations in both women (-0.28 +/- 0.15 g/L; -24.6%; P < 0.0001) and men (-0.22 +/- 0.19 g/L; -20.5%; P < 0.005). A significant reduction in fasting insulin was observed in both women (-27.8 +/- 27.9 pmol/L; -25.3%; P < 0.005) and men (-25.0 +/- 32.8 pmol/L; -21.4%; P < 0.05), whereas the LDL peak particle size was unaffected by Pred withdrawal. CONCLUSIONS: Pred withdrawal modifies several anthropometric and metabolic cardiovascular risk factors in renal transplant patients. Furthermore, female patients may derive further benefits of Pred withdrawal resulting from the concomitant loss of body weight and abdominal fat.     

Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome

The metabolic syndrome is characterized by insulin resistance and abnormal apolipoprotein AI (apoAI) and apolipoprotein B-100 (apoB) metabolism that may collectively accelerate atherosclerosis. The effects of atorvastatin (40 mg/day) and micronised fenofibrate (200 mg/day) on the kinetics of apoAI and apoB were investigated in a controlled cross-over trial of 11 dyslipidemic men with the metabolic syndrome. ApoAI and apoB kinetics were studied following intravenous d(3)-leucine administration using gas-chromatography mass spectrometry with data analyzed by compartmental modeling. Compared with placebo, atorvastatin significantly decreased (P < 0.001) plasma concentrations of cholesterol, triglyceride, LDL cholesterol, VLDL apoB, intermediate-density lipoprotein (IDL) apoB, and LDL apoB. Fenofibrate significantly decreased (P < 0.001) plasma triglyceride and VLDL apoB and elevated HDL(2) cholesterol (P < 0.001), HDL(3) cholesterol (P < 0.01), apoAI (P = 0.01), and apoAII (P < 0.001) concentrations, but it did not significantly alter LDL cholesterol. Atorvastatin significantly increased (P < 0.002) the fractional catabolic rate (FCR) of VLDL apoB, IDL apoB, and LDL apoB but did not affect the production of apoB in any lipoprotein fraction or in the turnover of apoAI. Fenofibrate significantly increased (P < 0.01) the FCR of VLDL, IDL, and LDL apoB but did not affect the production of VLDL apoB. Relative to placebo and atorvastatin, fenofibrate significantly increased the production (P < 0.001) and FCR (P = 0.016) of apoAI. Both agents significantly lowered plasma triglycerides and apoCIII concentrations, but only atorvastatin significantly lowered (P < 0.001) plasma cholesteryl ester transfer protein activity. Neither treatment altered insulin resistance. In conclusion, these differential effects of atorvastatin and fenofibrate on apoAI and apoB kinetics support the use of combination therapy for optimally regulating dyslipoproteinemia in the metabolic syndrome.     

Studies of LDL particle size and susceptibility to oxidation and association with glucose metabolism in children after heart transplantation.

BACKGROUND: Increased concentrations of serum triglyceride and low-density lipoprotein (LDL) cholesterol are common after heart transplantation (HTx). These abnormalities may promote transplant vascular disease and atherosclerosis, especially if LDL is small, dense, and oxidized. There have been no previous studies of LDL particle size and LDL susceptibility to oxidation in children after HTx. METHODS: Twenty-three HTx recipients (aged 3-19 years) who received triple-drug immunosuppression therapy after HTx and 181 controls within the same age range participated in the study. Total, high-density lipoprotein, and LDL-cholesterol concentrations; triglyceride concentration, and glucose and insulin concentrations during oral glucose tolerance tests were determined an average of 3 years after HTx (range, 1-7 years). Moreover, we determined serum lipoprotein (a) concentration, apolipoprotein E phenotype, LDL particle size, and indices of LDL susceptibility to copper-induced oxidation in 12 HTx recipients. RESULTS: We found hypertriglyceridemia in 56.5% and hyperinsulinemia in 30.4% of patients. Triglyceride concentration and body mass index were associated significantly with insulin concentration (p < 0.008 for both). Low-density lipoprotein particle size, LDL susceptibility to in vitro oxidation, and lipoprotein (a) concentrations did not differ significantly between HTx patients and controls. Low-density lipoprotein particle size was associated inversely with cyclosporine through level (Neoral, r = -0.59, p = 0.045), whereas weight-adjusted dosage of cyclosporine correlated positively with longer lag time of LDL oxidation (r = 0.69, p = 0.013). CONCLUSIONS: Hypertriglyceridemia and hyperinsulinemia were common in children receiving triple-drug immunosuppression therapy after HTx. Increased cyclosporine through concentration was associated with small LDL particle size but did not increase LDL susceptibility to oxidation.     

Influence of Waist Circumference on the Metabolic Risk Associated with Impaired Fasting Glucose: Effect of Weight Loss after Gastric Bypass

Background Impaired fasting glucose (IFG) is a prediabetic state defined as a fasting plasma glucose (FPG) between 100 and 125 mg/dl. However, individuals in this group do not exhibit the same atherogenic risk. Methods The atherogenic profile of subjects with IFG >110 mg/dl (IFG110, n = 96) or <110 mg/dl (IFG100, n = 131) were compared and the potential differential impact of the waist circumference analyzed. In addition, the same clinical variables were measured in 18 morbidly obese patients (8 males, 10 females; BMI 45.3 ± 1.9 kg/m²) before and after weight loss following Roux-en-Y gastric bypass (RYGBP), in order to analyze the influence of the reduction in waist circumference on the improvement of the metabolic risk factors. Results Individuals in the IFG110 group showed decreased HDL-cholesterol levels together with an increased total cholesterol to HDL ratio (TC/HDL), accompanied by elevated homocysteine concentrations and white blood cell (WBC) count, and higher waist circumference (P < 0.05 for all). Significant correlations between waist circumference and HDL-cholesterol (r = −0.200, P < 0.05), TC/HDL (r = 0.190, P < 0.05), WBC count (r = 0.299, P < 0.05), and QUICKI (r = −0.375, P < 0.0001) were observed. An almost 3-fold increase in the prevalence of T2DM in subjects in the IFG110 group as compared to IFG100 was observed. In the group of patients who underwent RYGBP, the reduction in waist circumference was significantly associated with the improvement in insulin sensitivity as evidenced by the QUICKI index (r = −0.582, P < 0.05) and the reduction in TC/HDL (r = 0.595, P < 0.05). Conclusion Waist circumference is related to metabolic risk factors associated with increased levels of IFG. Our data support that individuals with IFG >110 mg/dl and a high waist circumference should undergo an OGTT to exclude the presence of diabetes.     

Features of insulin-resistance syndrome in men from French Caribbean Islands. The Telecom Study.

The prevalence of diabetes is known to be high in the West Indies, whereas CVD seems relatively rare. This apparently contradicts the existence of the insulin-resistance syndrome, a cluster of metabolic abnormalities supposedly favoring both diabetes and cardiovascular complications. To address the question of whether this contradiction could be accounted for by specific features of this syndrome, we compared 1505 Caucasian and 181 Afro-Caribbean men, all participants in the French Telecom Study. The Afro-Caribbeans were of the same age and had the same BMI as the Caucasians; they also had significantly higher subscapular skin-fold thickness and fasting insulin level, but similar BP and blood glucose level, and significantly lower plasma triglyceride level. Thus, although some features of the insulin-resistance syndrome were present (central adiposity and high insulin levels), none of the associated metabolic abnormalities were present. However, within the Afro-Caribbean group, subjects with plasma insulin concentrations above the median (> 52 pM) had higher mean BP and glucose and triglyceride levels compared with subjects with insulin concentrations < or = 52 pM (P < 0.001). After adjustment for age and BMI, these differences, though smaller, still were statistically significant. These findings confirm that higher insulin concentrations are associated with higher levels of potentially atherogenic and diabetogenic metabolic parameters. However, depending on ethnic origin, the mean levels of these parameters seem to be different, with the consequence that, even if they are elevated with increasing insulin levels, they may not reach values high enough to determine a substantial risk of disease.     

Genome-wide scan for metabolic syndrome and related quantitative traits in Hong Kong Chinese and confirmation of a susceptibility locus on chromosome 1q21-q25

We conducted autosomal genome scans to map loci for metabolic syndrome (MES) and related traits in the Hong Kong Family Diabetes Study. We selected 55 families with 137 affected members (121 affected relative pairs) for nonparametric linkage analysis on MES. We also selected 179 families with 897 members (2,127 relative pairs) for variance component-based linkage analyses on seven MES-related traits: waist circumference, systolic and diastolic blood pressure (BP), triglyceride, HDL cholesterol, fasting plasma glucose, and insulin resistance index (insulin resistance index by homeostasis model assessment [HOMA%IR]). Analyses revealed three regions that showed suggestive linkage for MES and also showed overlapping signals for metabolic traits: chromosome 1 at 169.5-181.5 cM (logarithm of odds [LOD] = 4.50 for MES, 3.71 for waist circumference, and 1.24 for diastolic BP), chromosome 2 at 44.1-57.3 cM (LOD = 2.22 for MES, 2.07 for fasting plasma glucose, and 1.29 for diastolic BP), and chromosome 16 at 45.2-65.4 cM (LOD = 1.75 for MES, 1.61 for HOMA%IR, and 1.25 for HDL cholesterol). Other regions that showed suggestive linkages included chromosome 5q for diastolic BP; 2q, 3q, 6q, 9q, 10q, and 17q for triglyceride; 12p, 12q, and 22q for HDL-C; and 6q for HOMA%IR. Simulation studies demonstrated genome-wide significant linkage of the chromosome 1 region to both MES and waist circumference (P(genome-wide) = 0.002 and 0.019, respectively). In summary, we have found a susceptibility locus on chromosome 1q21-q25 involved in the pathogenesis of multiple metabolic abnormalities, in particular obesity. Our results confirm the findings of previous studies on diabetes and related phenotypes. We also suggest the locations of other loci that may contribute to the development of MES in Hong Kong Chinese.     

Fasting plasma ghrelin levels are negatively correlated with insulin resistance and PAI-1, but not with leptin,in obese children and adolescents

Ghrelin is a novel growth hormone-releasing peptide isolated from human and rat stomach that induces weight gain by increasing food intake and reducing fat utilization. Although recent data indicate that ghrelin is downregulated in human adult obesity, the characteristics of human obesity are heterogeneous, especially in children and adolescents, and depend on the distribution of subcutaneous and visceral fat tissue. We measured fasting plasma ghrelin concentrations by radioimmunoassay in 49 obese Japanese children and adolescents (38 boys and 11 girls; mean age 10.2 +/- 2.8 years; BMI 28.0 +/- 4.5 kg/m(2), percent overweight 56.0 +/- 20.7%), and analyzed associations of their ghrelin concentrations with their body composition, insulin resistance, and adipocytokine concentrations. Fasting plasma ghrelin levels were negatively correlated with BMI and waist circumference, but not with percent overweight or percent body fat, whereas fasting leptin levels were positively correlated with all of the following parameters: BMI, waist circumference, percent overweight, and percent body fat. Plasma ghrelin levels were negatively correlated with fasting immunoreactive insulin, homeostasis model assessment insulin resistance index, and quantitative insulin sensitivity check index values. There was no correlation between plasma ghrelin and leptin, but ghrelin was negatively correlated with the PAI-1 concentrations. The results suggest that the downregulation of ghrelin secretion may be a consequence of higher insulin resistance associated with visceral fat accumulation and elevated PAI-1 concentrations, and not a consequence of total body fat accumulation associated with elevated leptin concentrations.     

Risk factors for impaired glucose tolerance in obese children and adolescents

AIM: To investigate which obese children have an increased risk for impaired glucose tolerance (IGT), a risk factor for later diabetes.METHODS: We studied 169 European untreated obese children and adolescents with normal glucose tolerance at baseline. Waist circumference, fasting glucose, lipids, blood pressure, pubertal stage, 2 h glucose in oral glucose tolerance test (oGTT), and HbA1c were determined at baseline and 1 year later.RESULTS: One year after baseline, 19 (11.2%) children demonstrated IGT, 4 (2.4%) children had impaired fasting glucose, no (0%) child suffered from diabetes, and 146 (86%) children still showed normal glucose tolerance. At baseline, the children with IGT and with normal glucose tolerance in a one-year follow-up did not differ significantly in respect of any analyzed parameter, apart from pubertal stage. The children developing IGT entered puberty significantly more frequently (37% vs 3%, P < 0.001). One year after baseline, the children with IGT demonstrated significantly increased waist circumference, blood pressure values, insulin and triglyceride concentrations, and insulin resistance index HOMA. The children remaining in the normal glucose tolerance status 1 year after baseline did not demonstrate any significant changes.CONCLUSION: During the study period of 1 year, more than 10% of the obese children with normal glucose tolerance converted to IGT. Repeated screening with oGTT seems meaningful in obese children entering puberty or demonstrating increased insulin resistance, waist circumference, blood pressure, or triglyceride concentrations.     

Telmisartan and metabolic syndrome after heart transplantation

Luknar M, Goncalvesova E, Lesny P, Fabian J. Telmisartan and metabolic syndrome after heart transplantation.
Clin Transplant 2010: 24: 36–39. © 2009 John Wiley & Sons A/S. Abstract: Introduction: Metabolic syndrome (MS) is a cardiovascular risk predictor. Prevalence of MS after heart transplantation (HTx) is high. Recent data suggest a positive metabolic effect of telmisartan. Aim: To describe the influence of telmisartan on lipid and glycide metabolism in MS after HTx. Methods: Fifteen patients aged 55+/?12 yr, 88+/?25 months after HTx with MS receiving statins were followed. The reason for telmisartan administration was arterial hypertension with either drug intolerance or poor control. Body mass index (BMI), waist circumference, total cholesterol, low density lipoprotein LDL‐cholesterol, high density lipoprotein‐cholesterol, triglycerides, C‐reactive protein (CRP), fasting glucose, immunoreactive insulin (IRI), C‐peptide and the homeostasis model assessment (HOMA) index were determined. Ambulatory blood pressure monitoring was performed. After initial evaluation, telmisartan 80 mg was started. After 20 ± 5 wk follow‐up, identical parameters were measured. Statistical significance was evaluated using Student’s t‐test. Results: BMI, waist circumference, systolic and diastolic blood pressures, serum lipids and CRP remained unchanged after telmisartan. Significant reduction in fasting glucose (6.7 vs. 5.6 mmol/L, p < 0.02), IRI (8.8 vs. 8.5 U/mL p = 0.05), HOMA (7.3 vs. 5.8 mmol/L × μU/mL, p < 0.05) and C‐peptide (4.0 vs. 3.3 ng/mL, p < 0.02) was found. Conclusions: Telmisartan had a positive impact on insulin sensitivity parameters (fasting glucose, IRI, C‐peptide and HOMA) in this population. No effect on obesity, serum lipids and systemic inflammation was observed.     

Dyslipidemia and renal disease: pathogenesis and clinical consequences

Patients with chronic renal disease suffer from a secondary form of complex dyslipidemia. The most important abnormalities are an increase in serum triglyceride levels (elevated VLDL-remnants/IDL), small LDL particles and a low HDL cholesterol level. The highly atherogenic LDL subclass, namely LDL-6 or small dense LDL, accumulates preferentially in hypertriglyceridemic diabetic patients with nephropathy or on hemodialysis treatment. All these lipoprotein particles contain apolipoprotein B, thus the complex disorder can be summarized as an elevation of triglyceride-rich apolipoprotein B-containing complex lipoprotein particles. Growing evidence suggests that all of the components of this type of dyslipidemia are independently atherogenic. These particles, specifically the apolipoprotein B moiety, are predominantly prone to modification such as oxidation and glycosilation, which contributes to impaired clearance by the LDL receptor. These complex alterations in lipoprotein composition not only passively accompany chronic renal disease but on the contrary also promote its progression and the development of atherosclerosis. Therefore, renal patients with dyslipidemia should be subjected to lipid-lowering therapy. The effectiveness of lipid lowering on the reduction of cardiovascular endpoints or the progression of renal disease is under investigation or remains to be studied.     

Insulin resistance, LDL particle size, and LDL susceptibility to oxidation in pediatric kidney and liver recipients

BACKGROUND: Dyslipidemia is common after solid organ transplantation. We have described hypertriglyceridemia in about 50% of our pediatric kidney, and in about 30% of our liver recipients. The aim of the present study was to find out whether this post-transplantation hypertriglyceridemia after pediatric solid organ transplantation is associated with insulin resistance and the occurrence of small, dense low-density lipoprotein (LDL). METHODS: Fifty kidney and 25 liver recipients (aged 4 to 18 years) on triple immunosuppression, and 181 control children participated in the study for an average of 5.3 and 6.4 years after kidney and liver transplantation (range 1 to 11 years), respectively. Homeostasis model assessments for insulin resistance (HOMA) were calculated and fasting lipoprotein lipid profile, apolipoprotein A-I and B concentrations, LDL particle diameter, and indices of LDL susceptibility to copper-induced oxidation determined. RESULTS: Kidney patients had significantly higher serum total, high-density, and low-density lipoprotein cholesterol, triglyceride, apolipoprotein A-I and B concentrations than liver patients or control subjects (P < 0.003 for all). HOMA indices higher than the 95th percentile of Canadian normal children were seen in 50.0% of kidney (of liver 41.2%) recipients younger than 11 years, and in 27.3% of older recipients (of liver 37.5%). Smaller sized LDL or LDL of increased oxidizability was not more frequent in patients than in control children. CONCLUSION: Pediatric kidney recipients had significantly higher lipid and insulin concentrations than healthy control children. Combined hyperlipidemia and features of the dysmetabolic syndrome were common in children after kidney and liver transplantation. However, no small, dense LDL, or LDL prone to oxidation was seen in either group.     

Influence of obesity, impaired glucose tolerance, and NIDDM on LDL structure and composition. Possible link between hyperinsulinemia and atherosclerosis

The possible causes of the enhanced risk for coronary heart disease (CHD) were examined in morbidly obese women with normoglycemia, impaired glucose tolerance (IGT), and non-insulin-dependent diabetes mellitus (NIDDM) before and after gastric bypass surgery. Compared with age-matched lean women, plasma lipid and apolipoprotein concentrations of the obese women before surgery favored atherogenesis. The risk for CHD may further be exacerbated in the IGT and NIDDM groups by the prevalence of smaller and denser low-density-lipoprotein (LDL) particles. LDL size correlated negatively with plasma insulin levels independent of triglyceride levels, age, or body mass index (BMI). After surgery, BMI, plasma insulin, and triglyceride levels decreased, but LDL size increased, and LDL density decreased. Neither cholesterol nor LDL cholesterol levels were affected after surgery, but high-density-lipoprotein cholesterol was increased in all patients after surgery. Although the mechanisms underlying the changes in the properties of LDL could not be determined from this study, these changes appear to be of benefit in reducing CHD risk in these patients.     

Low-density lipoprotein subfraction profiles in dialysis patients

Summary: Uraemic dyslipidaemia is a major risk factor for cardiovascular disease in end-stage renal failure patients. In patients without renal failure, high levels and qualitative abnormalities of low-density lipoprotein (LDL) are known to be atherogenic. Recently, LDL subfraction analysis has associated premature coronary artery disease with a high prevalence of small, dense LDL particles characterizing the LDL subclass phenotype B. We therefore examined the lipid profiles, LDL subfraction distribution and phenotypes in our population of haemodialysis (HD; n = 30) and peritoneal dialysis patients (PD; n = 17), and compared them to 40 asymptomatic, non-uraemic volunteers. Dialysis patients had significantly higher triglyceride and VLDL cholesterol concentrations and lower HDL cholesterol and smaller LDL peak particle diameters. PD patients had significantly higher total cholesterol, glycated haemoglobin and fasting blood glucose levels with smaller LDL peak particle diameters (24.4 [0.1] vs 24.8 [0.1 nm] than HD. Both groups showed significant negative correlations between plasma triglyceride and LDL peak particle diameter, and positive correlations between HDL cholesterol and LDL peak particle diameter. All the PD patients expressed the B phenotype (LDL peak diameter ± 25.5 nm) compared to 73% of HD patients. This study demonstrates that HD and especially PD patients have atherogenic lipid profiles which are associated with a predominance of small dense LDL particles and the highly atherogenic LDL subclass phenotype B.     

Intra-abdominal fat is a major determinant of the National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome

The underlying pathophysiology of the metabolic syndrome is the subject of debate, with both insulin resistance and obesity considered as important factors. We evaluated the differential effects of insulin resistance and central body fat distribution in determining the metabolic syndrome as defined by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III. In addition, we determined which NCEP criteria were associated with insulin resistance and central adiposity. The subjects, 218 healthy men (n = 89) and women (n = 129) with a broad range of age (26-75 years) and BMI (18.4-46.8 kg/m2), underwent quantification of the insulin sensitivity index (Si) and intra-abdominal fat (IAF) and subcutaneous fat (SCF) areas. The metabolic syndrome was present in 34 (15.6%) of subjects who had a lower Si [median: 3.13 vs. 6.09 x 10(-5) min(-1)/(pmol/l)] and higher IAF (166.3 vs. 79.1 cm2) and SCF (285.1 vs. 179.8 cm2) areas compared with subjects without the syndrome (P < 0.001). Multivariate models including Si, IAF, and SCF demonstrated that each parameter was associated with the syndrome. However, IAF was independently associated with all five of the metabolic syndrome criteria. In multivariable models containing the criteria as covariates, waist circumference and triglyceride levels were independently associated with Si and IAF and SCF areas (P < 0.001). Although insulin resistance and central body fat are both associated with the metabolic syndrome, IAF is independently associated with all of the criteria, suggesting that it may have a pathophysiological role. Of the NCEP criteria, waist circumference and triglycerides may best identify insulin resistance and visceral adiposity in individuals with a fasting plasma glucose <6.4 mmol/l.     

Evaluation of microalbuminuria in obese children and its relation to metabolic syndrome

Several epidemiologic studies have clearly demonstrated that obesity increases the risk of kidney diseases. We have attempted to evaluate the association of obesity with albuminuria, an early marker of kidney disease, among obese children and its relation to metabolic syndrome. This study included 150 obese children. Blood pressure, fasting blood glucose, plasma insulin and the lipid profile were assessed. The homeostasis model assessment of insulin resistance (HOMA-IR) was used to calculate in vivo insulin resistance. Urinary albumin and creatinine were estimated. Microalbuminuria was detected in 22 (14.7%) of the obese children. Waist circumference, blood pressure, triglyceride, low-density lipoprotein (LDL), insulin resistance and fasting blood glucose were significantly higher in obese children with microalbuminuria than in those with normoalbuminuria and showed significant positive correlations with microalbuminuria. High-density lipoprotein (HDL) was significantly lower in obese children with microalbuminuria than in those with normoalbuminuria, with a significant negative correlation with microalbuminuria. We found that body mass index, abdominal obesity, hypertension, impaired fasting glucose level and insulin resistance significantly increased the odds of microalbuminuria in the obese children enrolled in this study. Moreover, high triglyceride, high LDL and low HDL were significantly associated with microalbuminuria. In our patient group, childhood obesity was a risk factor for the development of microalbuminuria, which in turn was significantly associated with metabolic syndrome and its different constituents.     

Managing metabolic complications of peritoneal dialysis

AIMS: The purposes of this paper are: to report our experience employing a comprehensive, multifaceted treatment program to improve the metabolic disturbances of dyslipidemia, hyperglycemia and weight gain observed in our peritoneal dialysis patients, and by post-hoc analysis to demonstrate how the routine clinical lipid profile can be manipulated arithmetically to estimate levels of atherogenic low-density lipids and thereby achieve a more sophisticated clinical analysis of dyslipidemia and its response to therapy. METHODS: Data are reported for 56 patients who were stable on peritoneal dialysis for at least 6 months and who had metabolic data available prior to beginning peritoneal dialysis. Metabolic complications of peritoneal dialysis were treated by a comprehensive strategy involving diet, glycemic control and lipid-lowering medications with an emphasis on weight control and exercise. From the measured lipid profile (total cholesterol (TC), high-density lipoprotein (HDL) and triglyceride (TG)), levels of atherogenic low-density lipids (low-density lipoprotein (LDL), non-HDL, very-low-density lipoprotein (VLDL) and intermediate-low-density lipoprotein (IDL) were calculated. RESULTS: Before initiation of peritoneal dialysis therapy, the most common lipid abnormalities were low levels of HDL (59%) and elevated levels of triglyceride (41%) with infrequent elevations of total cholesterol (9%) and low-density lipoprotein (23%). After initiation of peritoneal dialysis therapy, all lipid levels, except HDL, increased significantly, and hyperlipidemia, hyperglycemia and obesity, singly or in combination, occurred in 84% of patients. With treatment, elevated lipid levels decreased significantly with reversal of the adverse cardiovascular risk profile of lipids that developed during peritoneal dialysis therapy, and HDL levels increased significantly. On peritoneal dialysis therapy, all diabetic patients required insulin, and glycemic control was achieved in most patients (79%). Excessive weight gain (10-24% body weight) occurred in 20% of peritoneal dialysis patients. Diabetic patients had a higher incidence of being overweight and obese. Post-hoc analysis revealed that levels of VLDL and IDL frequently were elevated both before (57-61%) and during (68-84%) peritoneal dialysis and that target levels of these atherogenic low-density lipoproteins infrequently (22-26%) were achieved. CONCLUSIONS: The metabolic complications of peritoneal dialysis are responsive to a comprehensive treatment strategy. Controlling weight gain on peritoneal dialysis therapy maybe a difficult challenge for some patients, particularly those who are diabetic. Patients with renal failure and on dialysis, especially peritoneal dialysis, frequently have elevated levels of the atherogenic lipoproteins fragments VLDL and IDL. Future clinical trials should focus on the efficacy and safety of aggressive therapy to achieve target levels of these atherogenic lipids.     

Small dense low-density lipoprotein in renal transplant recipients: a potential target for prevention of cardiovascular complications?

BACKGROUND: Immunosuppressive therapy is frequently associated with dyslipidemia, which is involved in cardiovascular morbidity and mortality in transplant patients. Beyond classical factors, such as low-density lipoprotein (LDL) cholesterol (LDL-C), qualitative abnormalities of lipoproteins, such as presence of the atherogenic factor, small dense LDL, may be of interest for a cardiovascular risk assessment. This study was designed to explore LDL size in renal transplant recipients in relation to quantitative lipid parameters and apolipoprotein (apo) CIII polymorphism. METHODS: Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), LDL-C, apoA1, apoB, apoCIII, and LDL size were measured in 62 patients of mean age 45 +/- 13 years including 71% men at 2 +/- 0.5 years after renal transplantation. Thirty-two patients received cyclosporine (CsA), while 30 received tacrolimus (FK). ApoCIII Sstl genotype was determined by restriction fragment length polymorphism. RESULTS: The CsA group exhibited higher TC (P = .001), LDL-C (P = .004), non-HDL-C (P = .009), HDL-C (P = .03), apoB (P = .008), and apoCIII (P = .002) levels than the FK group. However, LDL-C (CsA: 3.7 +/- 1.2, FK: 3.0 +/- 0.6 mmol/L) and triglyceride levels (CsA: 1.55 mmol/L, FK: 1.37 mmol/L) were near the normal range in both groups. Allelic frequency of the sparse A2 allele associated with hypertriglyceridemia was 6%, similar to the general population. LDL size, which was comparable in the CsA and FK groups (25.87 +/- 0.89 vs 25.75 +/- 0.62 nm, respectively), inversely correlated with TG/HDL ratio (P = 10(-4)). Prevalence of small dense LDL (defined as <25.5 nm) was 26% in the CsA group and 33% in the FK group. CONCLUSION: After LDL-C goal has been achieved, LDL size modulation may be taken into account in order to prevent cardiovascular complications.     

系统评价睾酮治疗对男性性功能障碍患者代谢综合征相关因素的作用

目的:系统评价睾酮治疗对男性性功能障碍患者代谢综合征相关因素的作用。方法:检索PubMed(1980～2009.8)、EMBASE(1980～2009.8)、Cochrane图书馆临床对照试验资料库、中文期刊全文数据库(CNKI,1995～2009.8),按纳入与排除标准选择试验、评价质量、提取资料,用RevMan5.0对数据进行Meta分析。结果:共纳入6项随机对照试验(RCT),方法学质量评价中5项为B级,1项为C级。分析显示:睾酮治疗可显著改善男性性功能障碍患者的空腹血糖、总胆固醇(TC)水平及胰岛素抵抗(HOMA-IR)程度;可降低低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、甘油三酯(TG)和收缩压(SBP)水平,但并不优于对照治疗组;对腹围(WC)、腰臀比(WHR)和舒张压(DBP)的影响目前证据不足。结论:现有临床证据显示,睾酮治疗可以控制血糖(改善胰岛素抵抗,降低空腹血糖),调节血脂(降低TC、TG、LDL、HDL)。但由于纳入研究存在异质性和发生偏倚的高度可能性,势必影响结果的论证强度,期待针对睾酮治疗后代谢状况的全面的大规模的随机双盲对照试验进一步提供证据。     

Positive associations of bone mineral density with body mass index,physical activity,and blood triglyceride level in men over 70 years old: a TCVGHAGE study

It is known that osteoporosis decreases physical function in older males. However, the role of metabolic parameters and physical activity influencing older men's bone status remains unclear. Thus, this study was designed to evaluate calcaneus bone mass by ultrasonic screening and the associated physical and metabolic functions in older men. This was a cross-sectional study. Three hundred sixty-eight older men (average age, 78.8 years) living in a veterans' home were enrolled. We measured body height and weight, waist and hip circumference, body fat, lean body mass, blood pressure, 6-min walking distance, complete blood count, and blood biochemical profile. Broadband ultrasound attenuation (BUA) and T-score were recorded using Soundscan quantitative ultrasound over the right calcaneus. The range of calcaneus BUA was 27.3–134.0; T-score was from −4.78 to 3.43. Of the total participants, 36.4% were osteopenic (−2.5 < T-score < −1.0) and 16.3% were osteoporotic (T-score ≦ −2.5). BUA correlated with weight, body mass index (BMI), waist circumference, hip circumference, body fat, lean body mass, serum triglycerides, high-density lipoprotein-cholesterol, albumin, prealbumin, fasting and PC-2h blood insulin, red blood cell count, hemoglobin concentration, and 6-min walking distance. Multiple regression stepwise analysis revealed that only BMI, distance of 6-min walking, and blood triglyceride level were independently and positively associated with the values of BUA. Calcaneus bone mass is significantly and positively associated with BMI, blood triglycerides, and 6-min walking distance in older men.     

Hypoadiponectinemia correlates with metabolic syndrome in kidney transplantation patients

Serum adiponectin values correlate inversely with the presence of metabolic syndrome (MS). This study was undertaken to evaluate the relationship between MS and fasting serum adiponectin concentrations in 55 kidney transplantation patients. MS and its components were defined using the diagnostic criteria of the International Diabetes Federation. Thirteen subjects (23.6%) with MS showed negative correlations with adiponectin levels (P = .035), which also negatively correlated with a number of MS criteria (P = .015). Univariate linear regression analysis showed, serum adiponectin values to negatively correlate with waist circumference (r = −0.367; P = .006), body mass index (r = −0.306; P = .023), and body fat mass (r = −0.373; P = .005). Multivariate forward stepwise linear regression analysis of the significant variables revealed that body fat mass (R² change = 0.139; P = .035) and waist circumference (R² change = 0.067; P = .041) were independent predictors of fasting serum adiponectin concentrations. Thus, serum adiponectin concentrations correlated inversely with MS. Body fat mass and waist circumference were independent predictors of serum adiponectin values in kidney transplant patients.