Assessment of sexual dysfunction in male patients with Ankylosing Spondylitis

We evaluated sexual dysfunction in male patients with ankylosing spondylitis (AS) using the Brief Male Sexual Function Inventory (BMSFI). We assessed sexual dysfunction using the BMSFI in male patients with AS followed at the outpatient clinic and compared results with those in healthy controls. Depression status was measured by the Beck Depression Inventory in AS patient and control group. The Bath AS functional index was used to measure functional status, the Bath AS metrology index was used to measure joint mobility, and the Bath AS disease activity index was used to evaluate disease activity in AS cases. Compared to healthy controls patients with AS had significantly lower sexual drive, erection, problem assessment and overall satisfaction scores according to the BMSFI. Ejaculation scores were also lower but not statistically significant. According to the Beck Depression Inventory, AS patients had higher scores than healthy controls (14.9 ± 9.4 and 10.3 ± 11.8, P = 0.026, respectively). As for the relation between the BMSFI domains and BDI scores, relation was found only in the domains of problem assessment and overall satisfaction (P < 0.05). The incidence rate of sexual dysfunction is higher in patients with AS, when compared to the healthy people. In patients with AS, sexual dysfunction was associated with depression and limited joint mobility.     

Does the etiology affect the outcome and satisfaction rates of penile prosthesis implantation surgery?

Our aim was to compare the outcomes and satisfaction rates of men undergoing penile prostheses implantation (PPI) secondary to radical prostatectomy (RP) and other causes of vasculogenic erectile dysfunction (ED). A total of 142 patients, of whom 60 underwent PPI due to ED following RP (Group 1) and 82 underwent PPI due to ED with other vasculogenic causes (Group 2) were included in this study. The preoperative erectile status was evaluated with the International Index of Erectile Function (IIEF). The satisfaction of patients and partners were evaluated by a telephone interview using Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire and Erectile Dysfunction Inventory of Treatment Satisfaction Partner Survey. Preoperative mean IIEF scores were significantly lower in Group 1 (17.5 ± 6.4 vs. 24.2 ± 5.1, p = 0.01). For Groups 1 and 2, the mean EDITS scores of the patients were 58 ± 10 and 71 ± 8, respectively, and that for the partners were 46 ± 8 and 65 ± 7, respectively. Group 1 had significantly lower scores both for the EDITS and the EDITS Partner Survey (p = 0.03, p = 0.01, respectively). Patients who had undergone RP and their partners were found to have lower satisfaction rates compared to patients with other causes of vasculogenic ED who had penile implant surgery. From this point of view, it is important to know the patient's expectations about the treatment outcomes and a preoperative psychological and sexual counseling should be managed for possible treatment alternatives after RP.     

Indirect Ion Selective Electrode Methods Potentially Overestimate Peritoneal Dialysate Sodium Losses

Measurements of dialysate sodium are used to estimate peritoneal dialysis sodium losses and sodium sieving, a measure of hydraulic permeability of the peritoneum. Peritoneal dialysates differ from serum samples in terms of pH, osmolality, protein and glucose concentration. We wished to determine whether these factors affected sodium measurement. Dialysate samples were taken from 52 consecutive peritoneal dialysis patients attending for a standard peritoneal dialysis equilibrium test (PET), 20 with standard lactate dialysate and 32 with neutral pH dialysate and sodium was measured by both flame photometry and indirect ion selective electrode (ISE). Sodium measured by ISE consistently overestimated that measured by flame photometer, mean bias 1.5 mmol/L (95% confidence limits 1.2 to 1.8), P < 0.001. Sodium was lower in fresh neutral pH dialysates by both methods – flame 125.3 ± 1.17 vs. 131.6 ± 0.39 mmol/L, than standard lactate dialysates ISE 127.4 ± 1.05 vs 132.7 ± 0.27 mmol/L, P < 0.001. Glucose was higher in fresh neutral pH dialysates 122.7 ± 1.1 vs. standard lactate dialysates 116.7 ± 0.4 mmol/L, P < 0.001. On multiple regression analysis, only glucose was found to be an independent factor for sodium measurement, F = 14.78, β = ?0.0851, SEM 0.022, 95% confidence limits ?1.28 to ?0.042. In this study there was a small but consistent difference between sodium measurements by ISE and flame photometry during the PET. Sodium measurements by either method appeared to be affected by hypertonic dialysates, but there were differences with pH. This may potentially lead to errors in both overestimating peritoneal sodium losses and the proportion of patients with ultrafiltration failure due to loss of sodium sieving.     

Serum glucose level at hospital admission correlates with left ventricular systolic dysfunction in nondiabetic, acute coronary patients: the Hellenic Heart Failure Study

The purpose of this work was to evaluate the relation between serum glucose levels at hospital admission and left ventricular systolic function in nondiabetic patients with an acute coronary syndrome (ACS). Of the 1000 ACS patients who were consecutively enrolled during 2007–2008, 583 (63 ± 13 years, 20% females) nondiabetic patients were studied in this work. Of these, 254 presented left ventricular systolic dysfunction (ejection fraction <40%). Biochemical measurements and detailed medical information were recorded in all participants. Patients having glucose levels at hospital admission in the highest tertile (>155 mg/dl) had lower left ventricular ejection fraction (40% vs 45%, P = 0.003), were older (66 ± 11 vs 61 ± 13, P = 0.004) and less physically active (49% vs 63%, P = 0.02), had higher troponin (14.7 ± 39.7 vs 5.6 ± 13.5, P = 0.03), higher brain natriuretic peptide (510.39 ± 932.33 vs 213.4 ± 301.14, P = 0.008), higher C-RP (42.26 ± 55.26 vs 26.46 ± 38.18, P = 0.04), lower creatinine clearance levels (68 ± 33 vs.81 ± 31, P = 0.009), higher white blood cell count (13 416 ± 16 420 vs 9310 ± 3020, P = 0.001), and lower body mass index (26.8 ± 4 vs 27.2 ± 4.4, P = 0.07), compared to those in the lowest tertile (<114 mg/dl). The multiadjusted logistic regression analysis revealed that a 10 mg/dl difference in glucose levels was independently associated with 8% (95% confidence interval 2%–14%) higher likelihood of left ventricular systolic dysfunction. Low glucose concentrations at hospital admission in nondiabetic post-ACS patients is a predictor for the appearance of left ventricular dysfunction, and could be a target marker for risk stratification.     

Impact of Renal Survival on the Course and Outcome of Systemic Lupus Erythematosus Patients Treated With Chronic Peritoneal Dialysis

This longitudinal study investigated whether renal survival can affect the course and outcome of systemic lupus erythematosus (SLE) patients treated with chronic peritoneal dialysis (PD). Thirty-five SLE patients, out of 1115 end-stage renal disease (ESRD) patients treated with chronic PD, were seen between 1990 and 2007 at the Chang Gung Memorial Hospital. Patients were followed up for a mean of 38.8 ± 22.9 months. There were no significant differences between patients with short renal survival (<3 years) and long renal survival (>3 years) for the various demographic variables such as age, sex, PD duration, immunosuppressive drug administration, or exchange system (P > 0.05). Interestingly, before PD, patients with short renal survival had lower serum complement levels than patients with long renal survival (C3, 40.2 ± 14.4 vs 76.3 ± 18.5 mg/dL, P < 0.001; and C4, 14.8 ± 4.7 vs 22.4 ± 8.1 mg/dL, P < 0.05). However, the differences in complement levels between the groups disappeared after PD (C3, 76.5 ± 27.3 vs 84.2 ± 27.8 mg/dL; and C4, 26.7 ± 11.3 vs 22.6 ± 10.8 mg/dL, both P > 0.05). Patients with short renal survival were more likely to have a high peritoneal solute transporter rate (PSTR) than their long renal survival counterparts (χ²-test, P = 0.02, and AUROC = 0.744 and P = 0.040); however, there were no significant differences for other variables such as cardiothoracic ratio (CTR), Kt/V, residual renal function, exit site infection, and peritonitis (P > 0.05). Finally, Kaplan–Meier analysis revealed that the two groups did not differ in patient and technical survival (P > 0.05). Therefore it was concluded that renal survival might be associated with PSTR, but not with patient and technical survival in SLE patients treated with PD.     

Peritoneal Protein Losses Depend on More Than Just Peritoneal Dialysis Modality and Peritoneal Membrane Transporter Status

Peritoneal protein clearance (PPCl) depends upon vascular supply and size selective permeability. Some previous reports suggested PPCl can distinguish fast peritoneal membrane transport due to local or systemic inflammation. However, as studies have been discordant, we wished to determine factors associated with an increased PPCl. Consecutive patients starting peritoneal dialysis (PD) who were peritonitis-free were studied. Data included a baseline peritoneal equilibration test (PET), measurement of dialysis adequacy, 24-h dialysate PPCl and body composition measured by multifrequency bioimpedance. 411 patients, mean age 57.2 ± 16.6 years, 60.8% male, 39.4% diabetic, 20.2% treated by continuous ambulatory peritoneal dialysis (CAPD) were studied. Mean PET 4-h Dialysate/Serum creatinine was 0.73 ± 0.13, with daily peritoneal protein loss 4.6 (3.3–6.4) g, and median PPCl 69.6 (49.1–99.6) mL/day. On multivariate analysis, PPCl was most strongly associated with CAPD (β 0.25, P < 0.001), extracellular water (ECW)/total body water (TBW) ratio (β 0.21, P < 0.001), skeletal muscle mass index (β 0.21, P < 0.001), log N-terminal brain natriuretic peptide (NT-proBNP) (β 0.17, P = 0.001), faster PET transport (β 0.15, P = 0.005), and normalized nitrogen appearance rate (β 0.13, P = 0.008). In addition to the longer dwell times of CAPD, greater peritoneal creatinine clearance and faster PET transporter status, we observed an association between increased PPCl and ECW expansion, increased NT-proBNP, estimated dietary protein intake and muscle mass, suggesting a link to sodium intake and sodium balance, increasing both ECW and conduit artery hydrostatic pressure resulting in greater vascular protein permeability. This latter association may explain reports linking PPCl to patient mortality.     

Metabolic syndrome is not associated with erectile dysfunction in apparently healthy men

AimsTo investigate whether metabolic syndrome (MetS) is associated with erectile dysfunction (ED) among apparently healthy men when depressive symptoms and serum testosterone levels are taken into account.MethodsA study population of 549 men at risk for cardiovascular disease or type 2 diabetes was drawn from the participants of a population survey, the Harmonica Project. MetS was diagnosed with the United States National Cholesterol Education Program Third Adult Treatment Panel (ATPIII) 2005 definition, the International Diabetes Federation (IDF) 2005 definition and the Harmonization 2009 definition. ED was evaluated by the International Index of Erectile Function (IIEF-5) questionnaire. Depressive symptoms were assessed with Beck’s Depression Inventory (BDI).ResultsOf the 549 men (mean age 58.4 ± 6.7 years), 56.5 % reported ED. The prevalence of MetS was 48.6%, 35.5%, and 50.6% according to the IDF, the ATPIII, and the Harmonization criteria, respectively. We found no difference in the prevalence of ED between men with or without MetS. In a multivariate analysis, age, presence of depressive symptoms and lower education were significant predictors of ED.ConclusionsThe prevalence of ED is quite high even in apparently healthy men. Depressive symptoms are a critical component to consider in men suffering from ED.     

Risk Factors for Encapsulating Peritoneal Sclerosis in Long‐Term Peritoneal Dialysis: A Retrospective Observational Study

Encapsulating peritoneal sclerosis (EPS) is a serious complication that occurs in patients with long‐term peritoneal dialysis (PD). Investigation of risk factors that contribute to EPS in patients on long‐term PD therapy is needed. In a retrospective, observational study, data were collected for 107 patients treated with PD therapy for more than 5 years. Fifty cases of EPS were compared with 57 cases of non‐EPS. To evaluate the impact of PD‐associated peritonitis in EPS, univariate and multivariate logistic regression models were applied. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis were included as explanatory variables in addition to previously reported risk factors. D/P Cr and serum β2MG levels in the EPS and non‐EPS groups were: 0.82 ± 0.10 and 0.67 ± 0.12 (P < 0.01), and 33.8 ± 8.54 and 29.2 ± 8.18 mg/L (P < 0.01), respectively. Episodes of peritonitis, number of peritonitis episodes and the duration of peritonitis was 68% and 42% (P < 0.01), 1.80 ± 2.19 and 0.75 ± 1.07 times (P < 0.01), and 18.1 ± 15.3 and 10.2 ± 4.90 days (P < 0.01), in the EPS and non‐EPS groups, respectively. Furthermore, multivariate logistic regression models demonstrated that both D/P Cr and the duration of peritonitis were independently associated with EPS (P < 0.01 and P < 0.05, respectively). In patients on long‐term PD therapy, D/P Cr and the duration of peritonitis are independently associated with EPS. Earlier treatment to promote an early recovery from PD‐associated peritonitis could be critical in preventing EPS.     

Quality of life,depression, and sexual dysfunction in spouses of female patients with fibromyalgia

The aim of this study was to investigate the effects of the quality of life and psychological condition of female patients with fibromyalgia and their spouses on sexual function. A total of 32 female patients diagnosed with fibromyalgia and their spouses were analyzed. Thirty married couples were included in the study as the control group. The demographic data of the fibromyalgia patients were recorded, a visual analog scale was used to evaluate the level of pain, and the Fibromyalgia Impact Questionnaire was used to evaluate the impact of the symptoms on the quality of life of the patients. The quality of life of both the patients and the control group were evaluated using the Short Form 36 (SF-36), and psychological variables were evaluated using the Beck Depression Inventory (BDI) and Beck Anxiety Inventory. Sexual function was assessed using the Female Sexual Function Index for female participants and the International Index of Erectile Function (IIEF) for male participants. The IIEF erectile dysfunction scores were significantly lower in the spouses of female patients with fibromyalgia than in the control group (p < 0.05), and the BDI scores were significantly higher in the spouses of the female patients with fibromyalgia (p < 0.05). Among the SF-36 scores, the emotional and physical roles were significantly lower in the spouses of the female patients with fibromyalgia (p = 0.003 and p = 0.004, respectively). In all spouses of FMS patients and controls, there was a significantly negative correlation between erectile function, the BDI score, and to be married with FMS patient and positive correlations between erectile function and emotional role, social function, mental health, SF-36 pain score, and general health (p < 0.05 for all). In a linear regression model, BDI, to be married with FMS patient and general health were found to affect erectile function (beta regression coefficient = ?0.572, SE = 0.082, p = 0.001; beta regression coefficient = ?0.332, SE = 1.619, p = 0.007; beta regression coefficient = 0.445, SE = 0.065, p = 0.005, respectively). Being a spouse of a patient with fibromyalgia might significantly interfere with quality of life and lead to a high rate of sexual dysfunction. Spouses of patients with fibromyalgia might also be investigated for sexual dysfunction and quality of life. Treatment programs for this group should be considered.     

Glycaemia‐independent ethnic differences in HbA1c in subjects with impaired glucose tolerance

Aim To study the ethnic differences in HbA_1c between Whites and South Asians with impaired glucose tolerance. Methods We audited 75g oral glucose tolerance tests (OGTT) performed in Clinical Chemistry, New Cross Hospital, Wolverhampton over 1 year. HbA_1c and glycaemia were compared between Whites and South Asians with impaired glucose intolerance (IGT). Results There were 46 South Asians (22 female) and 88 Whites (41 female). South Asian subjects were younger (59.2 ± 14.31 vs. 67.6 ± 12.63 yrs; P < 0.001) and weighed less (78.1 ± 17.2 vs. 87.47 ± 19.1 kgs; P < 0.001) than White subjects. HbA_1c levels were higher (6.5 ± 0.7 vs. 6.1 ± 0.6%; P < 0.001) in South Asians compared to Whites. Fasting glucose (5.71 ± 0.5 vs. 5.93 ± 0.7; P = 0.039) was lower in South Asians but 2hour glucose (10.5 ± 1.0 vs. 10.40 ± 0.9; P = 0.404) was similar in both ethnic groups. Conclusion South Asians have higher HbA_1c levels than Whites despite lower fasting glucose value on OGTT, indicating ethnic differences in HbA_1c are due to glycaemia‐independent factors     

Serum Antioxidant Capacity is Preserved in Peritoneal Dialysis Contrary to Its Robust Depletion After Hemodialysis and Hemodiafiltration Sessions

Renal replacement therapy (RRT) may differentially affect systemic generation of reactive oxygen species and depletion of antioxidant pools of low molecular weight molecules and proteins. This study was designed to assess the magnitude of the impairment of serum total antioxidant capacity (TAC) in relation to different RRT modalities. The study included patients on continuous ambulatory peritoneal dialysis (CAPD, N = 21), hemodialysis (HD, N = 21), hemodiafiltration (HDF, N = 20), and healthy controls (N = 33). TAC was assessed by the ferric reducing ability of plasma (FRAP) and with the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. In CAPD patients, predialysis FRAP and DPPH were increased: 1.46 mM and 10.5% vs. control 1.19 mM and 7.2%, respectively (P < 0.001 in each). In HD and HDF patients, the FRAP and DPPH were significantly increased before and lowered after the RRT session (P < 0.05) if compared with healthy controls. During an HD session, FRAP was decreased from pre-HD 1.71 ± 0.29 mM to post-HD 0.85 ± 0.20 mM (P = 0.0001). The decrease of FRAP was lower during HDF (P < 0.05 vs. HD), it decreased from pre-HDF 1.41 ± 0.43 mM to post-HDF 0.87 ± 0.23 mM (P = 0.0001 vs. pre-HDF). The HD session decreased DPPH from the pre-HD median 10.3%, interquartile range (IR) 9.3–12.0% to post-HD 2.6% IR 2.3–3.1% (P < 0.0001). The adjustment of either urate or bilirubin up to pre-HD levels did not restore lowered post-HD levels of TAC. TAC remains preserved in CAPD, whereas the robust depletion of TAC, lower after HDF than HD sessions, cannot be attributed solely to the washout of dialyzable compounds.     

Insulin Deficiency Rather Than Hyperinsulinaemia in Newly Diagnosed Type 2 Diabetes Mellitus

This paper reports beta cell function as assessed during OGTT using specific IRMAs for insulin, intact and 32/33 split proinsulin in subjects with newly diagnosed Type 2 diabetes matched to normal controls. The relationships between insulin and the proinsulins to risk factors for cardiovascular disease were also examined. Similar fasting insulin concentrations but lower 30-min post-glucose-load insulin concentrations were found in diabetic subjects (mean ± SEM 143 ± 12 pmol^?1 vs 304 ± 19 (p < 0.001). Subjects with diabetes had increased fasting intact (10.6 ± 1.1 pmol^?1 vs 3.3 ± 0.2, p < 0.001) and 32/33 split proinsulin concentrations (8.1 ± 0.9 pmol^?1 vs 2.2 ± 0.3, p < 0.0001). Beta cell dysfunction, as expressed by a reduction in the 30-min insulin to glucose ratio (9.4 ± 1 vs 34.8 ± 2.3, p < 0.0001) and an increase in the fasting percentage of total proinsulin-like to total insulin-like molecules (24.5 ± 9% vs 11.6 ± 5, p < 0.001), was present in subjects with diabetes. In diabetic subjects beta cell dysfunction and insulin deficiency increased relative to the degree of fasting hyperglycaemia. It seems clear that beta cell dysfunction and insulin deficiency are major features of Type 2 diabetes. Only the fasting concentration of 32/33 split proinsulin positively correlated with both the waist/hip ratio (r = 0.36, p < 0.001), diastolic blood pressure (r = 0.23, p < 0.01) in addition to plasma triglyceride concentration (r = 0.46, p < 0.001). It is questionable whether hyperinsulinaemia plays a pathogenic role in cardiovascular disease in subjects with glucose intolerance.     

Evidence for Impaired Pancreatic Beta Cell Function in South African Indians with Impaired Glucose Tolerance

In a prospective study of South African Indians with impaired glucose tolerance (IGT), the serum insulin response during a 75 g oral glucose tolerance test (OGTT) was examined in 128 subjects who were classified as IGT 1 year previously (year 0) and in 60 matched control subjects. Based on the results at year 1, study subjects were divided into three groups, using World Health Organization criteria for glucose tolerance: IGT (n = 47), diabetes (n = 41), and transient IGT (normal glucose tolerance) (n = 40). When compared with the control group, despite higher plasma glucose concentrations, the IGT group showed similar fasting insulin, but lower 30-min insulin response (57.4 ± 1.9 mUI^?1 vs 86.5 ± 1.8, p<0.001) and lower 30-min insulin/glucose ratio (7.4 ± 5.2 vs 13.3 ± 8.7, p < 0.001). The insulinogenic index was lower in the IGT group than in the control group at 30, 60, 90, and 120 min (p < 0.01, p < 0.001, p < 0.001, p < 0.001, respectively). The 2-h insulin response was higher in the IGT group (106.7 ± 1.9 mUI^?1 vs 59.2 ± 1.9, p < 0.01). The IGT group displayed a delayed pattern of insulin response with maximum levels only at 2-h. Insulin area was similar in the two groups. In the transient IGT group, despite similar plasma glucose levels, the insulin responses at 0, 15, 30, and 60 min (p < 0.01, p < 0.001, p < 0.001, p < 0.001, respectively) were lower than in the control group; the 30-min insulin/glucose ratio (7.1 ± 5.1 vs 13.3 ± 8.7, p < 0.001) and 60-min insulinogenic index (46.9 ± 86.3 vs 123.4 ± 206.3, p < 0.001) were also lower in the transient IGT group. This study has shown that IGT in South African Indians is characterized by a diminished early phase insulin response and delayed (2-h) hyperinsulinaemia during OGTT. Such findings would suggest that in this population group impaired early beta cell function is an important pathophysiological abnormality underlying IGT.     

Peritoneal instillation of taurolidine or polihexanide modulates intestinal microcirculation in experimental endotoxemia

Background and aims Treatment of peritonitis may include peritoneal lavage/instillation with anti-infective agents like taurolidine or chlorhexidine. Materials and methods We examined the effects of peritoneal instillation (INST, 5-ml solution) with taurolidine (TAURO) or polihexanide (POLI-LS) on intestinal microcirculation using intravital microscopy (IVM) in experimental endotoxemia (15 mg/kg lipopolysaccharide i.v.; LPS) in the rat (n = 8 each group), their direct effects on local small blood vessels, aortal rings, and myocardial strips in vitro, as well as plasma interleukin levels. Results It was found that LPS produced hypotension (98.8 ± 9.5 vs 130.4 ± 10.5 mmHg; mean arterial pressure [MAP], mean ± standard deviation [SD]), which was further pronounced after INST of TAURO (78.8 ± 10.8; P < 0.005) or POLI-LS (78.1 ± 6.0; P < 0.001). IVM revealed a reduction in temporary adhering leucocytes and an increase in firmly adhering leucocytes after INST with TAURO and POLI-LS. Both agents reduced functional capillary density either in the mucosa (POLI-LS vs sham: 259.7 ± 54 cm/cm² vs 337.1 ± 35.5) or longitudinal muscular layer in LPS rats (TAURO vs sham: 119.8 ± 14.8 vs 153.7 ± 11.0). POLI-LS induced local vasodilatation, whereas TAURO induced small vasoconstriction; in vitro, both agents showed vasodilating properties and did not have any effect on myocardial strip contraction. Conclusion Some of the observed microcirculatory changes could be a result of the direct vascular effects of these agents.     

Hyperinsulinaemia,obesity, and syndrome X

Abstract. Objective . The major aim of this study was to compare various aspects of carbohydrate, insulin, and lipoprotein metabolism, serum uric acid concentration, and blood pressure in normal subjects stratified on the basis of both plasma insulin concentration and degree of obesity. The hypothesis to be tested was that hyperinsulinaemia, per se, was associated with relative glucose intolerance, higher triglyceride and uric acid concentrations, lower high-density lipoprotein cholesterol concentration and higher blood pressure, irrespective of degree of obesity. Design . This represents a case-control study, in which normal volunteers were subdivided into four equal groups based upon degree of obesity and plasma insulin response to a 74 g oral glucose challenge. Setting . The study was performed in the out-patient clinic of a university hospital. Subjects . Sixty-four individuals were recruited for this study, subdivided into four groups based upon their plasma insulin concentration and body mass index. Subjects were classified as hyperinsulinaemic if their plasma insulin concentrations in response to an oral glucose challenge were more than two standard deviations above the mean of 732 volunteers previously studied [1]. Obesity was defined as a body mass index of > 30 kg m^-2, and individuals were classified as non-obese if their body mass index was < 27.0 kg m^-2. Based upon these criteria, four experimental groups were created: (i) non-obese hyperinsulinaemic (NOB hyper); (ii) obese hyperinsulinaemic (OB hyper); (iii) non-obese normo-insulinaemic (NOB normo); and (iv) obese normo-insulinaemic (OB normo). Main outcome measures . Subject groups were compared on the basis of the integrated plasma glucose response to a 75 g oral glucose challenge, fasting plasma triglyceride, cholesterol, high-density lipoprotein cholesterol, and uric acid concentrations, and blood pressure. Results . Mean (± standard error of the mean) integrated plasma glucose response area for 2 h following a 75 g oral glucose load was significantly higher (13.4 ± 0.4 vs. 11.0 ± 0.4 mmol 1^-1, P < 0.001) in the hyperinsulinaemic group, as were the fasting triglyceride levels (2.4 ± 0.2 vs. 1.4 ± 0.1 mmol 1^-1, P < 0.001) and uric acid (5.3 ± 0.2 vs. 4.4 ± 0.2 mmol 1^-1, P < 0.05) concentrations. In contrast, high-density lipoprotein concentrations were lower in the hyperinsulinaemic group (1.06.0.05 vs. 1.32 ± 0.05 mmol 1^-1, P < 0.001). In addition, blood pressure was higher in the hyperinsulinaemic group (136 ± 5/87 ± 2 vs. 123 ± 2/82 ± 1 mmHg, P < 0.05). Furthermore, when each of the two groups were divided into obese (n = 16) and non-obese (n = 16) groups, all of the differences outlined above persisted. These changes were independent of age, gender distribution, generalized and abdominal obesity, cigarette smoking, and estimated physical activity. Conclusions . The cluster of changes subsumed under the heading of syndrome X are closely associated with hyperinsulinaemia (and presumably insulin resistance), and can be discerned irrespective of degree of obesity.     

Corneal confocal microscopy detects severe small fiber neuropathy in diabetic patients with Charcot neuroarthropathy

Aims/Introduction

The aim of the present study was to identify the extent of small fiber neuropathy in diabetic patients with Charcot neuroarthropathy (CN).

Materials and Methods

A total of 20 patients with CN were compared with 20 age‐ and diabetes duration‐matched patients with type 2 diabetes and 20 age‐matched control participants. All patients underwent corneal confocal microscopy with quantification of corneal nerve morphology and assessment for vibration perception threshold, and a subset of patients with CN underwent assessment of sudomotor function and neuropathic pain.

Results

In patients with CN compared with type 2 diabetes patients and control participants, there was a significant reduction in corneal nerve fiber density (14.94 ± 8.23 vs 23.86 ± 7.71, P = 0.004 vs 34.84 ± 9.13, P < 0.001), corneal nerve branch density (18.61 ± 16.7 vs 41.62 ± 22.67, P = 0.032 vs 76.47 ± 38.44, P < 0.001) and corneal nerve fiber length (8.40 ± 4.83 vs 14.87 ± 4.76, P = 0.001 vs 21.24 ± 6.48, P < 0.001), electrochemical skin conductance on the feet (20.57 ± 13.99 vs 61.50 ± 22.26, P < 0.001 vs 76.23 ± 12.01, P < 0.001) and hands (30.86 ± 18.10 vs 61.13 ± 19.14, P = 0.001 vs 68.31 ± 11.96, P < 0.001), and a significant increase in the vibration perception threshold in the feet (38.46 ± 15.10 vs 14.15 ± 10.25, P < 0.001 vs 7.75 ± 4.01, P < 0.001).

Conclusions

Patients with diabetes and CN have severe large and particularly small fiber neuropathy.     

Short‐Term Effect of Atorvastatin on Endothelial Function in Healthy Offspring of Parents with Type 2 Diabetes Mellitus

Endothelial function is impaired in healthy subjects at risk of type 2 diabetes mellitus (DM). We investigated whether endothelial dysfunction can be normalized by statin therapy in this potentially predisposed population. Flow‐mediated dilation (FMD) was measured in 56 first‐degree relatives (FDRs) (normotensive, normal glucose tolerance) and 20 age‐, sex‐, and BMI‐matched controls with no family history of DM. Other measurements included insulin resistance index using the homeostasis model of insulin resistance (HOMA_IR), plasma lipids, and markers of inflammation. The FDRs were then randomized and treated with atorvastatin (80 mg) or placebo daily in a 4‐week double‐blind, placebo‐controlled trial. The FDRs had significantly impaired FMD (4.4 ± 8.1% vs. 13.0 ± 4.2%; P < 0.001), higher HOMA_IR (1.72 ± 1.45 vs. 1.25 ± 0.43; P= 0.002), and elevated levels of plasma markers of inflammation—highly sensitive C‐reactive protein (hsCRP) (2.6 ± 3.8 mg/L vs. 0.7 ± 1.0 mg/L; P= 0.06), interleukin (IL)‐6 (0.07 ± 0.13 ng/mL vs. 0.03 ± 0.01 ng/mL; P < 0.001), and soluble intercellular adhesion molecule (sICAM) (267.7 ± 30.7 ng/mL vs. 238.2 ± 20.4 ng/mL; P < 0.001). FMD improved in the atorvastatin‐treated subjects when compared with the placebo‐treated subjects (atorvastatin, from 3.7 ± 8.5% to 9.8 ± 7.3%; placebo, from 3.9 ± 5.6% to 4.7 ± 4.2%; P= 0.001). There were also reductions in the levels of IL‐6 (0.08 ± 0.02 ng/mL vs. 0.04 ± 0.01 ng/mL; P < 0.001) and hsCRP (3.0 ± 3.9 mg/L vs. 1.0 ± 1.3 mg/L; P= 0.006). Our study suggests that treatment with atorvastatin may improve endothelial function and decrease levels of inflammatory markers in FDRs of type 2 DM patients.     

Adipokines in Peritoneal Dialysis: Relevant Clinical Impact According to Body Composition

Adipokines impact on clinical outcomes is not adequately addressed in peritoneal dialysis (PD). We investigated the impact of leptin/adiponectin ratio (L/A) as a predictor of cardiovascular events (CVE) in PD, taking into consideration patient's body composition and the potential role of glucose load. We prospectively followed 66 prevalent PD patients for 47.0 ± 28.2 months. New CVE were evaluated. Lean tissue index (LTI), relative fat mass (relFM) and relative overhydration (relOH) using multifrequency bioimpedance (BCM) were assessed; serum lipids, interleukin‐6 (IL‐6), leptin and adiponectin were measured. We established the determinants of L/A using multiple linear regression and the impact of L/A on CVE. Obesity was present in 47 (73.4%) patients according to relFM, and in seven (10.6%) according to body mass index (BMI). Leptin and L/A exhibited a stronger correlation with relFM (both r = 0.62, P < 0.0001) than with BMI (r = 0.46 and r = 0.51, respectively, both P < 0.0001). L/A showed a significant correlation with triglycerides (r = 0.41, P = 0.001) and HDL‐cholesterol (r = ?0.358, P = 0.003), better than isolated leptin or adiponectin. RelFM (RR = 0.130, 95%confidence interval [CI]:0.086–0.174, P < 0.0001) and LTI (RR = 0.194, 95%CI:0.037–0.351, P = 0.016) were independent predictors of L/A (R² = 0.67). Patients who suffered new CVE were older (59.12 ± 12.41 vs. 47.52 ± 13.84years, P = 0.003) and had a higher relOH (11.28 ± 7.29 vs. 6.60 ± 8.16%, P = 0.028). L/A was significantly higher in patients with CVE[2.29 (1.79) vs. 0.65 (1.73), P = 0.028] but this association was only put on evidence after excluding patients with wasting. BMI is an inaccurate method to classify obesity in PD since it underestimates its prevalence compared with body composition assessment using BCM. High adiponectin and low leptin are associated with a more favorable metabolic risk profile in peritoneal dialysis. The L/A is determined by relFM and by LTI. A higher L/A is associated with CVE in PD patients without wasting.     

Resting myocardial dysfunction in cirrhosis quantified by tissue Doppler imaging

Background: Cirrhotic cardiomyopathy is described as latent cardiac failure. However, it remains to be investigated whether the myocardial dysfunction is present even at rest. Aims: The aim of the present study was to quantify left ventricular function at rest by means of tissue Doppler imaging in patients with cirrhosis and relate the findings to liver status and cirrhosis aetiology. Methods: Forty‐four consecutive patients and 23 age‐matched healthy controls were included. Conventional echocardiographic‐ and tissue Doppler‐derived indices of systolic and diastolic function were obtained. Liver function was quantified by the galactose elimination capacity and clinical stage by the Child–Pugh and MELD scores. Results: Both systolic and diastolic myocardial functions were compromised in the patients at rest. Left ventricular ejection fraction (56.4 ± 6.1 vs. 59.9 ± 3.9%, P<0.02), mean peak systolic tissue velocity (4.6 ± 0.9 vs. 5.6 ± 0.7 cm/s, P<0.001) and mean systolic strain rate (?1.23 ± 0.19 vs. ?1.5 ± 0.14/s, P<0.001) were all reduced in cirrhosis patients. Thirty‐four patients (54%) had diastolic dysfunction, 11 had impaired diastolic relaxation pattern (25%), 12 had the more severe pseudonormal filling pattern (27%) and one had restrictive filling or severe diastolic dysfunction (2%). None of the echocardiographic findings were related to the cirrhosis aetiology. Conclusion: Tissue Doppler imaging during rest detected substantial systolic and diastolic myocardial dysfunction in cirrhotic patients. This supports the existence of a distinct cirrhotic cardiomyopathy.