Psoriasis and sexuality: Patients express their feelings.

Background: In France, psoriasis is a chronic inflammatory skin disease. For several years now, particular attention has been given to the quality of life (Qol) of psoriasis patients. Sexual dysfunction (SD) defined as not wanting or enjoying sexual experience is an important component of Qol. Psoriasis through its physical symptoms and psychological consequences can thus be responsible for SD. Method: The survey participants were recruited through the national psoriasis dermatitis patient association. Result: 41% (577) patients reported having SD related to their psoriasis. Women reported significantly more SD than men (387 [44.7%] vs. 190 [35%], p < 0.001). For 396 (28.1%) patients SD due to their psoriasis manifested as a reduction in the frequency of sexual activity, for 207 (14.7%) as change in their sexual practice, and for 284 (27.4%) as an absence of sexual activity without significant difference between women and men. The main consequence of sexual difficulties for patients was loss of self-confidence in 627 (44.5%) cases, guilt in 209 (14.8%) cases, couple life impairment in 214 (15.2%) cases, isolation in 260 (18.5%) cases and frustration. Discussion: In this study investigating SD related to psoriasis, we found that the disease impact sexual relations of 41% of patients of both gender. The main causes of SD were both physical alone and psychological alone, in the same proportions. The physical symptoms of psoriasis are therefore not the only ones responsible for the sexual discomfort reported from patients in their sexual relations. This may be due to a discomfort of the patient or the physician when talking about sexuality because they can't find the terms to talk about this subject often considered taboo and the age or gender difference. This aspect of the disease should be considered by physicians who care for patients with psoriasis, especially dermatologists. Finally, other strategies should be implemented, such as patient talk groups, referral guides or personalised therapeutic education.

Evaluation of factors associated with sexual dysfunction in psoriasis in a cohort of 1409 patients.

We report on the sexual disorders common in patients with psoriasis, and examine the underlying reasons, including the use of psoriasis treatments that can result in sexual difficulties.

Individual Burden of Psoriasis (I-BOP): Building and Validation of a New Scoring Tool for Patients with Psoriasis.

BACKGROUND: Psoriasis impacts independently of its severity on patients' lifestyle and quality of life (QoL). AIM: To build a tool for assessing the patient-reported psoriasis burden. METHODS: An expert group created a questionnaire using a standardized methodology building questionnaires assessing quality of life issues. The questionnaire was translated from French into a cultural and linguistically validated US English version. RESULTS: A conceptual questionnaire of 54 questions was created. The confirmatory analyses resulted in a 10-feature questionnaire divided into 4 internally consistent domains with a Cronbach's alpha coefficient of 0.9. It was reproducible and highly reliable. It correlated well with the Dermatology Life Quality Index (DLQI), Perceived Stress Scale (PSS), and SF-12 mental and SF12 physical scores. CONCLUSION: This tool allows for the first time to assess the burden of psoriasis patients. Its use may allow improving medical and nonmedical patient care, thus improving their daily life.

Adiponectin gene variants, adiponectin isoforms and cardiometabolic risk in type 2 diabetic patients.

AIMS/INTRODUCTION: The aim of the present study was to examine the associations of rs2241766 (+45T>G), rs1501299 (+276G>T), rs17300539 (-11391G>A) and rs182052 (-10069G>A) in the adiponectin (Ad) gene with adiponectin concentrations, and concomitantly the association of these variants with cardiometabolic risk in type 2 diabetic patients of African ancestry. MATERIALS AND METHODS: A cross-sectional study of 200 patients was carried out. Concentrations of total, high (HMW), middle (MMW) and low (LMW) molecular weight adiponectin isoforms were measured. The four polymorphisms were genotyped. RESULTS: Decreased values were noted for total Ad in overweight, dyslipidemia and coronary artery disease (CAD), for HMW in overweight and dyslipidemia, for MMW in CAD, for LMW in dyslipidemia and CAD, for the percentage HMW/total in overweight, and for MMW:HMW ratio in patients without hypertriglyceridemic waist (HTGW). Significant associations were noted between total Ad, HMW, and HMW/total Ad and rs182052 under a dominant model (P = 0.04, P = 0.03 and P = 0.04, respectively), and between MMW and rs17300539 (P = 0.006). No significant difference in adiponectin concentrations was noted according to rs2241766 and rs1501299 genotypes. Patients carrying the rs2241766 G allele (TG+GG) had an increased risk of HTGW (odds ratio [OR] 3.1; P = 0.04) and of CAD (OR 3.3; P = 0.01). The odds of having low total adiponectin concentrations (<25th percentile: 3.49 ng/mL) for carrying the rs182052A allele (AA+GA) was: OR 0.40; P = 0.009. The single-nucleotide polymorphism associated with adiponectin levels was not concomitantly associated with cardiometabolic risk factors. CONCLUSIONS: Adiponectin concentrations and ADIPOQ variants are implicated in the pathophysiological process leading to cardiovascular diseases, but the genetic effects seem to be independent of adiponectin concentrations in our Afro-Caribbean diabetic patients.

Hyperadiponectinemia is independent of kidney function, diabetes duration, and control in type 1 diabetic patients without microangiopathy.

INTRODUCTION: High total adiponectin (ADPN) levels were reported in type 1 diabetes (T1D) and related to long diabetes duration and nephropathy. We studied whether ADPN and its specific isoforms were elevated in T1D without microangiopathy and whether they were related to kidney function. MATERIALS AND METHODS: Total, high, medium, and low molecular weight ADPN and insulin levels were measured in 47 consecutive normoalbuminuric, normotensive T1D patients without retinopathy and in 47 age-, sex-, and body mass index-matched controls. Glomerular filtration rate was estimated by (51)Cr-EDTA plasma clearance. RESULTS: Total and high molecular weight ADPN ratio were higher in T1D patients than in controls. ADPN levels were not related to anthropometric measures, whereas they were in controls. In T1D, ADPN levels were not related to glycosylated hemoglobin, diabetes duration, or glomerular filtration rate. Peripheral insulin levels were higher in T1D patients than in controls, but they were not related to ADPN levels. In controls, insulin levels were positively related to total ADPN. CONCLUSION: In T1D without microangiopathy, high ADPN levels could not be related to anthropometric diabetes parameters, kidney function, or high insulin levels. The nature of this elevation remains unknown.

Association of common variants in NPPA and NPPB with blood pressure does not translate into kidney damage in a general population study.

BACKGROUND: The polymorphisms rs198358, rs5068 and rs632793 in the natriuretic peptide precursor A-B gene region [encoding atrial natriuretic peptides (ANP) and brain natriuretic peptides (BNP)] have been recently associated with ANP and BNP plasma concentrations and blood pressure (BP) in a large cohort study. METHODS: We observed that GCG, the haplotype based on these polymorphisms and combining the three rare alleles associated with higher natriuretic peptides and lower BP in a recent report, was associated with BNP plasma levels and BP in a French study of 5212 middle-aged participants, Epidemiological Data on Insulin Resistance Syndrome study. With the 9-year follow-up of Epidemiological Data on Insulin Resistance Syndrome study, we were able to analyze the association of incident microalbuminuria (576 patients) and low estimated glomerular filtration rate (<60 ml/min; 246 incident patients) with the tested haplotypes. RESULTS: No haplotype, including GCG, the one combining the three rare alleles, was associated with incident patients of either microalbuminuria [odds ratio 1.27 (0.91-1.78), P = 0.15] or low estimated glomerular filtration rate [odds ratio 0.88 (0.54-1.46), P = 0.63]. CONCLUSION: This was consistent with a lack of effect on clinical renal outcomes found in previous studies and showed that even replicated and biologically plausible genetic association studies based on surrogate markers do not easily translate into clinically meaningful prognosis.

Association of ADIPOQ genetic variants and plasma adiponectin isoforms with the risk of incident renal events in type 2 diabetes.

BACKGROUND: Adiponectin levels are high in cases of diabetic nephropathy, but it remains unclear whether these high levels are a cause or a consequence of the disease. We investigated the possible association of polymorphisms in the adiponectin gene and baseline adiponectin levels with the incidence of renal events in subjects with type 2 diabetes. METHODS: We studied three adiponectin polymorphisms (-11391G > A, +45T > G and +276G > T) in 3086 subjects with type 2 diabetes and high levels of albumin excretion from the diabetes, hypertension, microalbuminuria or proteinuria, cardiovascular events and ramipril (DIABHYCAR) trial. Baseline concentrations of total adiponectin and of adiponectin isoforms were determined in cases with incident renal events and in controls matched for sex, age, body mass index (BMI) and adiponectin genotype. We used another cohort of type 2 diabetes patients-the survie, diabète de type 2 et génétique(SURDIAGENE) study (n = 1004)-for the replication of genetic data. RESULTS: In DIABHYCAR, the -11391A and +45G alleles were associated with a higher incidence of renal events [hazard ratio (HR) = 1.73; 95% confidence interval (CI), 1.10-2.71; and HR = 1.68; 95% CI, 1.14-2.47, respectively]. The haplotype containing susceptibility alleles, -11391A/+45G/+276G, was more frequent in cases with renal events (5.1% vs. 1.9% in those without, P = 0.005). In SURDIAGENE, the -11391A/+45G/+276G haplotype was also associated with renal events (5.6% vs. 1.9% in those without, P = 0.03). In DIABHYCAR, all isoforms were more abundant in subjects carrying the -11391A or +45G alleles. Medium- (MMW) and low-molecular weight (LMW) isoforms were more abundant in cases with renal events. CONCLUSIONS: In subjects with type 2 diabetes and early renal dysfunction, adiponectin gene variants are determinants of the renal risk. The -11391A and +45G alleles may affect renal risk by leading to high circulating adiponectin concentrations, at least those of MMW and LMW isoforms.

Sex-dependent associations of leptin with metabolic syndrome-related variables: the Stanislas study.

Serum leptin has been reported to be associated in a sex-dependent manner with C-reactive protein (CRP), independently of adiposity. We tested the hypothesis that leptin is associated, independently of anthropometry indexes and in a sex-dependent way, with other inflammatory markers and variables related to metabolic syndrome (MS). In 384 healthy middle-aged adults (192 men and 192 women) total fat mass (FM), waist circumference (WC), serum leptin and 15 MS-related parameters (systolic and diastolic blood pressure, triglycerides, cholesterol, high density lipoprotein (HDL)-cholesterol, apo AI and B, fasting glucose, uric acid, CRP, orosomucoid and haptoglobin levels and aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and gamma-glutamyl transferase (GGT) activities) were measured. After adjustment for age, alcohol and cigarette consumption, WC, and total FM, leptin concentration was significantly associated with serum triglycerides, total cholesterol, apo B, uric acid and haptoglobin concentrations and liver enzyme activity only in men, and with apo AI, HDL-cholesterol (only borderline) and CRP only in women. Sex interaction terms were significant for total cholesterol, apo B, HDL cholesterol, uric acid, ALAT and GGT, and borderline significant for triglycerides, apo AI and ASAT. In this healthy population, leptin is significantly associated with various MS factors, independently of WC and total FM, depending on gender. Our study provides further evidence of sex-related differences mediated by leptin in inflammatory mechanisms and other MS-related metabolic pathways.

Adiponectin multimers and ADIPOQ T45G in coronary artery disease in Caribbean type 2 diabetic subjects of African descent.

Ethnic differences may affect the association of adiponectin (Ad) multimers with coronary artery disease (CAD). We analyzed the associations of total Ad, Ad multimers, and T45G polymorphism of ADIPOQ gene with pre-existing CAD. We carried out a cross-sectional study of 216 Afro-Caribbean type 2 diabetic (T2D) subjects. Levels of total Ad, high molecular weight (HMW), middle molecular weight (MMW), and low molecular weight (LMW) isoforms were measured. Subjects were genotyped. Of the subjects studied, 57 had pre-existing CAD, 77% of whom have had myocardial infarction. Subjects with CAD had lower Ad levels (total and multimers) and a higher frequency carried the minor allele 45G, GG/TG, (18% vs. 8%, P = 0.03) than subjects without CAD. In logistic regression analysis, the models used evaluate Ad in the context of adjustment for metabolic syndrome characteristics. The adjusted odds ratio (OR) of CAD was increased significantly (by factors of 1.05-3.27) for males, older subjects, low high-density lipoprotein cholesterol (HDL-C), high triglycerides (TGs), and carriers of the 45 G allele. For Ad, in model 1 (including only total Ad) the adjusted OR was 2.30; P = 0.03 and, in model 2 (including the three multimers, but not total Ad), the adjusted ORs were 0.73; P = 0.52 (HMW), 2.90; P = 0.01 (MMW), and 2.08; P = 0.09 (LMW). The T45G polymorphism in the ADIPOQ gene and hypoadiponectinemia were associated with CAD in our T2D subjects of predominantly African background. This effect of Ad level was mainly related to the MMW Ad form.

Acute effects of pharmacological modifications of fatty acid metabolism on human satiety.

The role of NEFA in eating behaviour is still poorly known. Our objective was to examine whether etomoxir (ETO), an inhibitor of NEFA oxidation, or ( - )-hydroxycitrate (HCA), an inhibitor of lipogenesis which may indirectly stimulate NEFA oxidation, alters satiety. Post-lunch satiety was measured in eight normal-weight male subjects who were deprived of time cues and received on three occasions either ETO (320 mg), HCA (2 g) or placebo (PLA) in random order. Between lunch and dinner, blood was withdrawn continuously and collected every 10 min for measures of plasma concentrations of glucose, insulin, lactate, TAG, NEFA, beta-hydroxybutyrate (BHB), leptin and ghrelin. Results showed that HCA began to decrease hunger and desire to eat compared to PLA and ETO 210 min after lunch and increased satiety duration compared to PLA by 70 (se 23) min (P < 0.05), but did not modify energy intake at dinner. ETO did not affect any variable of satiety. HCA increased NEFA concentrations during the pre-dinner period, whereas ETO increased and decreased plasma concentrations of NEFA and BHB, respectively. Mean differences in plasma NEFA concentrations between HCA and PLA were predictive of the differences in satiety duration between treatments (r2 0.71, P < 0.01). Among treatments, plasma leptin concentration at dinner onset was the only blood variable correlated with energy intake at this meal (r - 0.75, P < 0.0005). In healthy, normal-weight men, acute HCA increased the intensity and duration of satiety possibly via increased NEFA disposal for oxidation.

Intestinal gluconeogenesis is a key factor for early metabolic changes after gastric bypass but not after gastric lap-band in mice.

Unlike the adjustable gastric banding procedure (AGB), Roux-en-Y gastric bypass surgery (RYGBP) in humans has an intriguing effect: a rapid and substantial control of type 2 diabetes mellitus (T2DM). We performed gastric lap-band (GLB) and entero-gastro anastomosis (EGA) procedures in C57Bl6 mice that were fed a high-fat diet. The EGA procedure specifically reduced food intake and increased insulin sensitivity as measured by endogenous glucose production. Intestinal gluconeogenesis increased after the EGA procedure, but not after gastric banding. All EGA effects were abolished in GLUT-2 knockout mice and in mice with portal vein denervation. We thus provide mechanistic evidence that the beneficial effects of the EGA procedure on food intake and glucose homeostasis involve intestinal gluconeogenesis and its detection via a GLUT-2 and hepatoportal sensor pathway.

The PPARG Pro12Ala polymorphism is associated with a decreased risk of developing hyperglycemia over 6 years and combines with the effect of the APM1 G-11391A single nucleotide polymorphism: the Data From an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study.

Although cross-sectional studies have associated the Pro12Ala polymorphism of PPARG with type 2 diabetes, prospective studies offer more opportunities to investigate genetic variants. Associations between PPARG polymorphisms with insulin resistance parameters and with the 6-year incidence of impaired fasting glucose or type 2 diabetes were tested in 3,914 French Caucasians from the DESIR (Data From an Epidemiological Study on the Insulin Resistance Syndrome) cohort. In subjects normoglycemic at baseline (n = 3,498), the 6-year risk of hyperglycemia was lower in PPARG Ala carriers (odds ratio [OR] vs. ProPro = 0.66 [95% CI 0.44-0.99], P = 0.046 adjusted for sex, age, and BMI). Similar results were found with the PPARG C1431T single nucleotide polymorphism (SNP; adjusted OR = 0.65 [0.44-0.96], P = 0.036). Both alleles are in strong linkage disequilibrium (D' = 0.669, P < 0.001). The baseline mean fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were lower in Ala carriers compared with ProPro homozygotes (P = 0.001 for both), with smaller increases in mean insulin and HOMA-IR during follow-up (P = 0.007 and 0.018, respectively). No association with insulin levels or HOMA-IR was found with C1431T. In this cohort, the APM1 G-11391A SNP is associated with the development of hyperglycemia. The combined effects of PPARG Pro12Ala and APM1 G-11391A SNPs showed no interaction on the risk of 6-year hyperglycemia. The PPARG Ala allele showed a relatively high protective effect in developing hyperglycemia and hyperinsulinemia during a 6-year period. Cumulative rather than synergistic effects of PPARG Pro12Ala and APM1 SNPs on diabetes risk are suggested.

Consequence of omitting or adding a meal in man on body composition, food intake, and metabolism.

OBJECTIVE: To investigate in man the consequence on body composition and related biological and metabolic parameters of omitting or adding a meal. RESEARCH METHODS AND PROCEDURES: Twenty-four young normal-weight male subjects were recruited, 12 usual four-meal and 12 usual three-meal eaters, differing only in the consumption of an afternoon meal. They omitted or added a fourth meal during a 28-day habituation period and were asked to report their intake on three 3-day occasions. Before and after this habituation period, subjects participated in a session with a time-blinded procedure, and blood was collected continuously from lunch to the spontaneously requested dinner. Body composition, respiratory quotient, and biochemical parameters were measured in the late evening preceding each session. RESULTS: Omitting a meal was followed by increases in fat mass (360 +/- 115 grams, p < 0.05), late evening leptin concentration (20.7 +/- 11.0%, p < 0.05), and respiratory quotient (3.7 +/- 1.4%, p < 0.05). Increase in the percentage of dietary fat during the habituation period (+4.1 +/- 2.0%, p < 0.05) was correlated with fat mass (r = 0.66, p < 0.05). Adding a meal had no effect, but, in both groups, the change in energy content at this fourth eating occasion was correlated with the change in adiposity. DISCUSSION: Our results suggest that adiposity may increase when young lean male subjects switch from a four- to a three-meal pattern by removing their usual afternoon meal. This effect could be partly mediated by a change in the macronutrient composition of the diet.

Simulated high altitude selectively decreases protein intake and lean mass gain in rats.

The aim of this study was to find out whether high altitude (HA)-induced hypophagia was macronutrient-specific using a self-selection procedure. Body composition was assessed by dual X-ray absorptiometry before and after exposure and by dissection at the end of the experiment. Energy intake, macronutrient selection, body composition, plasma insulin and leptin concentrations were measured in rats (FHx) exposed 16 h daily for 10 days to hypobaric hypoxia (HH) simulating an altitude of 5500 m. Rats were fasted during the exposure to HH and had access to food only during the 8 h of normoxia in their active period. This group was compared to control group (C) with ad libitum access to food and a group of rats submitted only to the 16-h fast (FNx). Results showed that sustained hypophagia was specific to protein (55 +/- 5% of C, P < .05), whereas after a decline, carbohydrate intake reached its basal level on the 5th day. HH dramatically reduced fat-free mass gain (P < .05 and P < .0001 compared to C and FNx, respectively). Plasma leptin concentrations at the onset of the period of access to food were not significantly different from those of controls. Across groups, leptin was positively correlated with fat mass (r = .71, P < .001) and negatively with energy intake (r = -.52, P < .05), more specifically with protein intake (r = -.57, P < .05). These results suggest that HA leads to a reduced preference for protein impairing fat-free mass gain and that leptin may contribute to this hypophagia.

Polymorphism of the 5-HT2A receptor gene and food intakes in children and adolescents: the Stanislas Family Study.

BACKGROUND: Serotonin (5-hydroxytryptamine; 5-HT) is a key mediator in the control of food intake and is probably involved in the etiology of anorexia nervosa. An association between a polymorphism of the 5-HT receptor (5-HT2A) gene promoter (-1438G/A) and anorexia nervosa has been reported. OBJECTIVE: We investigated the relation between the -1438G/A polymorphism of the 5-HT(2A) gene and the energy and macronutrient intakes of children and adolescents. DESIGN: This cross-sectional study included 370 children and adolescents aged 10-20 y (176 boys and 194 girls from 251 families) drawn from the Stanislas Family Study. Energy and macronutrient intakes were assessed by using 3-d food records. The -1438G/A polymorphism was analyzed by polymerase chain reaction and then by Hpa II digestion. RESULTS: In the overall group, after adjustment for age, sex, weight, height, and family correlation, the A allele was significantly associated with lower energy (P for trend = 0.045) and with total, monounsaturated, and saturated fat intakes expressed in g/d (P for trend = 0.007, 0.005, and 0.006, respectively). Subjects with the GA genotype had intermediate values. In addition, genotype x sex and genotype x age interactions were not significant. CONCLUSIONS: The 5-HT2A gene polymorphism in the promoter region is associated with energy and fat intakes in young people. This could be explained by the role of the serotonergic system as a determinant of food intakes and eating behavior.

Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues.

Ghrelin is an orexigenic hormone that is implicated in meal initiation, in part because circulating levels rise before meals. Because previous human studies have examined subjects fed on known schedules, the observed preprandial ghrelin increases could have been a secondary consequence of meal anticipation. A causal role for ghrelin in meal initiation would be better supported if preprandial increases occurred before spontaneously initiated meals not prompted by external cues. We measured plasma ghrelin levels among human subjects initiating meals voluntarily without cues related to time or food. Samples were drawn every 5 min between a scheduled lunch and a freely requested dinner, and hunger scores were obtained using visual analog scales. Insulin, glucose, fatty acids, leptin, and triglycerides were also measured. Ghrelin levels decreased shortly after the first meal in all subjects. A subsequent preprandial increase occurred over a wide range of intermeal intervals (IMI; 320-425 min) in all but one subject. Hunger scores and ghrelin levels showed similar temporal profiles and similar relative differences in magnitude between lunch and dinner. One subject displayed no preprandial ghrelin increase and was also the only individual whose insulin levels did not return to baseline between meals. This finding, along with a correlation between area-under-the-curve values of ghrelin and insulin, suggests a role for insulin in ghrelin regulation. The preprandial increase of ghrelin levels that we observed among humans initiating meals voluntarily, without time- or food-related cues, and the overlap between these levels and hunger scores are consistent with a role for ghrelin in meal initiation.

Adiponectin gene polymorphisms and adiponectin levels are independently associated with the development of hyperglycemia during a 3-year period: the epidemiologic data on the insulin resistance syndrome prospective study.

The plasma concentration of the adipocyte-derived peptide adiponectin is decreased in patients with obesity and type 2 diabetes. The adiponectin gene is located on chromosome 3q27, where a diabetes susceptibility locus has been mapped. Adiponectin gene polymorphisms (single nucleotide polymorphisms [SNPs]) have been associated with BMI, insulin sensitivity, and type 2 diabetes in some cross-sectional studies. Our aim was to assess the contribution of these SNPs in the development of features of the insulin resistance syndrome in a 3-year prospective study in approximately 4,500 French Caucasian subjects from the Epidemiologic Data on the Insulin Resistance Syndrome (DESIR) cohort. For subjects who were normoglycemic at baseline, the 3-year risk of becoming hyperglycemic (diabetes or impaired fasting glucose) was affected by two SNPs: G-11391A and T45G. For G-11391A, the risk was increased in GA carriers (odds ratio [OR] adjusted for sex [versus GG] = 1.60 [95% CI 1.16-2.20]; P = 0.004). For T45G, it was increased in GG carriers (OR [versus TT] = 2.71 [1.31-5.60]; P = 0.007). After 3 years, GG subjects had a greater increase in BMI (P = 0.009) and waist-to-hip ratio (P = 0.007). Adiponectin levels at baseline were associated with the development of hyperglycemia (P = 0.005), but the predictive effects on the risk for hyperglycemia were independent of adiponectin genotypes. In conclusion, in the DESIR study, variations at the adiponectin locus affect body weight gain, body fat distribution, and onset of hyperglycemia, as well as adiponectin levels. Adiponectin gene SNPs may have several phenotypic effects that co-occur with the development of the metabolic syndrome.