[Relation between grip strength of independent elders and functional decline following an emergency department visit : a pan-Canadian study]. / Capacité de prédiction de la force de préhension et de la peur de tomber des personnes âgées autonomes quant au déclin fonctionnel suite à une consultation aux urgences. Une étude pancanadienne.

OBJECTIVE: To determine whether grip strength and fear of falling are associated with functional decline at 3 or 6 months after a minor trauma assessed in the emergency department. METHOD: Prospective multicenter cohort study of patient's aged 65 years and older, independent for activities of daily living, consulting the emergency department for minor trauma. Functional status, fear of falling, and grip strength measurements were collected. Functional decline was measured at 3 and 6 months. STATISTICS: Two groups were compared : one with functional decline, the other without. A ROC curve explored the predictive power of grip strength and initial fear of falling on the occurrence of functional decline. RESULTS: Participants were 74.7 years old, 52 % men. Initial peak grip strengths were identical (p superior to 0.05). Grip strength and fear of falling were not predictive of functional decline (p = 0.55 and p = 0.53). However, fear of falling was associated with functional decline (OR: 1.141 95 % CI [1.032-1.261]; p = 0.009). CONCLUSION: In the autonomous elder with minor trauma in the emergency department, grip strength is not associated with subsequent functional decline. But fear of falling is associated with decline at 6 months.

Objectif : Déterminer si la force de préhension et la peur de tomber sont associées au déclin fonctionnel à 3 ou 6 mois d'un traumatisme mineur évalué aux urgences. Méthode : Étude prospective de cohorte multicentrique des patients de 65 ans et plus, autonomes pour les activités de la vie quotidienne, consultant aux urgences pour traumatismes mineurs. Le statut fonctionnel, la peur de tomber, et la mesure de la force de préhension ont été recueillis. Le déclin fonctionnel a été mesuré à 3 et 6 mois. Statistiques : Deux groupes sont comparés : un avec déclin fonctionnel, l'autre sans. Une courbe ROC a exploré la puissance prédictive de la force de préhension et de la peur de tomber initiale sur l'apparition du déclin fonctionnel. Résultats : Les participants avaient 74 ± 7 ans, 52 % d'hommes. Les forces de préhension maximales initiales étaient identiques (p sup�rieur a 0,05). La force de préhension et la peur de tomber ne sont pas prédictives du déclin fonctionnel (p = 0,55 et p = 0,53). Cependant, la peur de tomber est associée au déclin fonctionnel (OR: 1,141 IC95 % [1,032-1,261]; p = 0,009). Conclusion : Chez l'aîné autonome avec un traumatisme mineur aux urgences, la force de préhension n'est pas associée au déclin fonctionnel ultérieur. Mais la peur de tomber est associée à un déclin à 6 mois.

Stress in Parents of Children With Genetically Determined Leukoencephalopathies: A Pilot Study.

Genetically determined leukoencephalopathies comprise a group of rare inherited white matter disorders. The majority are progressive diseases resulting in early death. We performed a cross-sectional pilot study including 55 parents from 36 families to assess the level of stress experienced by parents of patients with genetically determined leukoencephalopathies, aged 1 month to 12 years. Thirty-four mothers and 21 fathers completed the Parenting Stress Index-4th Edition. One demographic questionnaire was completed per family. Detailed clinical data was gathered on all patients. Statistical analysis was performed with total stress percentile score as the primary outcome. Mothers and fathers had significantly higher stress levels compared with the normative sample; 20% of parents had high levels of stress whereas 11% had clinically significant levels of stress. Mothers and fathers had comparable total stress percentile scores. We identified pediatric behavioral difficulties and gross motor function to be factors influencing stress in mothers. Our study is the first to examine parental stress in this population and highlights the need for parental support early in the disease course. In this pilot study, we demonstrated that using the Parenting Stress Index-4th Edition to assess stress levels in parents of patients with genetically determined leukoencephalopathies is feasible, leads to valuable and actionable results, and should be used in larger, prospective studies.

Influence of aerobic exercise training on the neural correlates of motor learning in Parkinson's disease individuals.

BACKGROUND: Aerobic exercise training (AET) has been shown to provide general health benefits, and to improve motor behaviours in particular, in individuals with Parkinson's disease (PD). However, the influence of AET on their motor learning capacities, as well as the change in neural substrates mediating this effect remains to be explored. OBJECTIVE: In the current study, we employed functional Magnetic Resonance Imaging (fMRI) to assess the effect of a 3-month AET program on the neural correlates of implicit motor sequence learning (MSL). METHODS: 20 healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike training program (3 times/week for 12 weeks). Exercise prescription started at 20 min (+ 5 min/week up to 40 min) based on participant's maximal aerobic power. Before and after the AET program, participants' brain was scanned while performing an implicit version of the serial reaction time task. RESULTS: Brain data revealed pre-post MSL-related increases in functional activity in the hippocampus, striatum and cerebellum in PD patients, as well as in the striatum in HC individuals. Importantly, the functional brain changes in PD individuals correlated with changes in aerobic fitness: a positive relationship was found with increased activity in the hippocampus and striatum, while a negative relationship was observed with the cerebellar activity. CONCLUSION: Our results reveal, for the first time, that exercise training produces functional changes in known motor learning related brain structures that are consistent with improved behavioural performance observed in PD patients. As such, AET can be a valuable non-pharmacological intervention to promote, not only physical fitness in early PD, but also better motor learning capacity useful in day-to-day activities through increased plasticity in motor related structures.

Immunopathogenesis of olmesartan-associated enteropathy.

BACKGROUND: Olmesartan-associated enteropathy (OAE) is characterised by diarrhoea, nausea, vomiting, abdominal pain, weight loss and severe sprue-like enteropathy, all of which are resolved after discontinuation of olmesartan medoximil. AIM: To determine the mechanistic similarities of OAE with coeliac sprue. METHODS: Duodenal biopsies were extracted from OAE patients before (n = 11) or after (n = 17) discontinuation of olmesartan medoxomil (on or off olmesartan medoxomil). There were seven 'on/off' paired samples. Formalin-fixed biopsies were stained for CD8, CD4, FoxP3, IL-15R and psmad 2/3. Caco2 cells (human colonic epithelial line) were treated with olmesartan medoxomil and stained for IL-15, IL-15R and ZO-1. RESULTS: In the 'on olmesartan medoxomil' duodenal biopsies, a significant increase in the numbers of CD8+ cells and the number of cells that are FoxP3+ (a regulatory T-cell marker) are present in the duodenum as compared to the duodenal biopsies from patients who discontinued olmesartan medoxomil. IL15R expression is also increased with olmesartan medoxomil use. Evaluation of the effect of olmesartan medoxomil upon Caco-2 cells demonstrated that IL15 expression is increased in response to olmesartan medoxomil treatment. Further, ZO-1, a tight junction protein, is disrupted in olmesartan medoxomil-treated Caco-2 cells. CONCLUSIONS: Olmesartan-associated enteropathy shares many features with coeliac disease, including symptoms and immunopathogenic pathways, such as increased numbers of CD8+ cells and corresponding overexpression of IL15 by epithelial cells. Taken together, the treatment of epithelial cells with olmesartan medoxomil induces a response by intestinal epithelial cells that is similar to the innate effects of gluten upon the epithelium of coeliac patients.

Enhancing both motor and cognitive functioning in Parkinson's disease: Aerobic exercise as a rehabilitative intervention.

BACKGROUND: Aerobic exercise training (AET) has been shown to provide health benefits in individuals with Parkinson's disease (PD). However, it is yet unknown to what extent AET also improves cognitive and procedural learning capacities, which ensure an optimal daily functioning. OBJECTIVE: In the current study, we assessed the effects of a 3-month AET program on executive functions (EF), implicit motor sequence learning (MSL) capacity, as well as on different health-related outcome indicators. METHODS: Twenty healthy controls (HC) and 19 early PD individuals participated in a supervised, high-intensity, stationary recumbent bike-training program (3 times/week for 12 weeks). Exercise prescription started at 20 min (+5 min/week up to 40 min) based on participant's maximal aerobic power. Before and after AET, EF tests assessed participants' inhibition and flexibility functions, whereas implicit MSL capacity was evaluated using a version of the Serial Reaction Time Task. RESULTS: The AET program was effective as indicated by significant improvement in aerobic capacity in all participants. Most importantly, AET improved inhibition but not flexibility, and motor learning skill, in both groups. CONCLUSION: Our results suggest that AET can be a valuable non-pharmacological intervention to promote physical fitness in early PD, but also better cognitive and procedural functioning.

Prevalence of colonic motor or evacuation disorders in patients presenting with chronic nausea and vomiting evaluated by a single gastroenterologist in a tertiary referral practice.

BACKGROUND: Nausea and vomiting are thought to result from upper gastrointestinal dysfunctions. Our clinical observations led to the hypothesis that colonic motor dysfunction is associated with nausea and vomiting. METHODS: We reviewed electronic medical records (EMR) of 149 patients presenting with complaints of nausea and/or vomiting in a tertiary gastroenterology practice to investigate the association with disorders of colonic motor or evacuation disorders. We extracted demographics, gastric emptying (GE in 149) and colonic transit (CT in 138) of solids, ascending colon emptying half-time (AC t1/2 ), rectal evacuation by anorectal manometry (ARM) in 91 and balloon expulsion test (BE) in 55 patients. We estimated the proportions with delayed GE or CT, based on the 5th percentile of GE (in 319) and CT in 220 healthy volunteers using same method. KEY RESULTS: Among 11 patients with nausea and/or vomiting with only GE measured, five had delayed and six normal GE. Among the 149 patients, 77 (52%) patients had evacuation disorders, confirmed by objective tests in 68 patients, and clinical examination in nine patients. In the 138 patients with both GE and CT measured, 106 (76%) had both normal GE and CT, 11 (8%) only delayed GE, 16 (11%) normal GE with delayed CT, and five (3%) delayed GE and CT. Among 21 patients (15%) with delayed CT, nine had slow AC t1/2 and 12 evacuation disorder. CONCLUSIONS & INFERENCES: In patients with chronic nausea and/or vomiting in gastroenterology practice, evaluation of colonic motility and rectal evacuation should be considered, since about half the patients have abnormal functions that conceivably contribute to the presenting nausea and/or vomiting.

Interpretation of overall colonic transit in defecation disorders in males and females.

BACKGROUND: There is little information regarding gender-specific measurements of colonic transit and anorectal function in patients with defecation disorders (DD). To compare overall colonic transit by gender in DD. METHODS: In 407 patients with constipation due to DD diagnosed by a single gastroenterologist (1994-2012), DD was characterized by anorectal manometry, balloon expulsion test, and colonic transit by scintigraphy. The primary endpoint was overall colonic transit (geometric center, GC) at 24 h (GC24). Effects of gender in DD on colonic transit, and comparison with transit in 208 healthy controls were assessed by Mann-Whitney rank sum test. Secondary endpoints were maximum anal resting (ARP) and squeeze (ASP) pressures. We also tested association of the physiological endpoints among DD females by pregnancy history and among DD patients by colectomy history. KEY RESULTS: The DD patients were 67 males (M) and 340 females (F). Significant differences by gender in DD patients were observed in GC24 (median: M: 2.2; F: 1.8; P = 0.01), ARP (median: M: 87.8 mmHg; F: 82.4 mmHg; P = 0.04), and ASP (median: M: 182.4 mmHg; F: 128.7 mmHg; P < 0.001). GC24 was slower in DD compared with same-gender healthy controls. GC24 did not differ among DD females by pregnancy history. Anorectal functions and upper GI transit did not differ among DD patients by colectomy history. CONCLUSIONS & INFERENCES: Patients with DD have slower colonic transit compared with gender-matched controls. Among DD patients, males have higher ARP and ASP, and females have slower colonic transit. Although the clinical significance of these differences may be unclear, findings suggest that interpretation of these tests in suspected DD should be based on same-gender control data.

ß-1 and ß-2 adrenergic receptor polymorphism and association with cardiovascular response to orthostatic screening.

Variation in the beta-1 and beta-2 adrenergic receptor genes (ADRB1 and ADRB2, respectively) may influence cardiovascular reactivity including orthostatic stress. We tested this hypothesis in a head-up tilt (HUT) screening protocol in healthy young adults without history of syncope. Following brachial arterial catheter insertion, 120 subjects (age 18-40, 72 females, Caucasian) underwent 5min 60° HUT. Polymorphisms tested were: Ser49/Gly and Arg389/Gly in ADRB1; and Arg16/Gly, Gln27/Glu, and Thr164/Ile in ADRB2. Three statistical models (recessive, dominant, additive) were evaluated using general linear models with analysis for each physiologic variable. A recessive model demonstrated a significant association between Arg16/Gly and: absolute supine and upright HR; HUT-induced change in cardiac index (CI), stroke index (SI) and systemic vascular resistance (SVR); and supine and upright norepinephrine values. Blood pressure was not influenced by genotype. Fewer associations were present for other polymorphisms: Ser49/Gly and the change in SI (dominant model), and Arg389/Gly and supine and HUT norepinephrine (additive model). We conclude that in this population, there is a robust association between Arg16/Gly and HUT responses, such that 2 copies of Arg16 increase supine and upright HR, and greater HUT-induced decreases in CI and SI, with greater increases in SVR and norepinephrine. ADRB1 gene variation appears to impact SI and plasma NE levels but not HR. Whether ADRB2 gene variation is ultimately disease-causing or disease-modifying, this study suggests an association between Arg16/Gly and postural hemodynamics, with sympathetic noradrenergic activity affected in a similar direction. This may have implications in the development of orthostatic disorders.

Muscle histology vs MRI in Duchenne muscular dystrophy.

OBJECTIVE: There are currently no effective treatments to halt the muscle breakdown in Duchenne muscular dystrophy (DMD), although genetic-based clinical trials are being piloted. Most of these trials have as an endpoint the restoration of dystrophin in muscle fibers, hence requiring sufficiently well-preserved muscle of recruited patients. The choice of the muscles to be studied and the role of noninvasive methods to assess muscle preservation therefore require further evaluation. METHODS: We studied the degree of muscle involvement in the lower leg muscles of 34 patients with DMD >8 years, using muscle MRI. In a subgroup of 15 patients we correlated the muscle MRI findings with the histology of open extensor digitorum brevis (EDB) muscle biopsies. Muscle MRI involvement was assigned using a scale 0-4 (normal-severe). RESULTS: In all patients we documented a gradient of involvement of the lower leg muscles: the posterior compartment (gastrocnemius > soleus) was most severely affected; the anterior compartment (tibialis anterior/posterior, popliteus, extensor digitorum longus) least affected. Muscle MRI showed EDB involvement that correlated with the patient's age (p = 0.055). We show a correlation between the MRI and EDB histopathologic changes, with MRI 3-4 grades associated with a more severe fibro-adipose tissue replacement. The EDB was sufficiently preserved for bulk and signal intensity in 18/22 wheelchair users aged 10-16.6 years. CONCLUSION: This study provides a detailed correlation between muscle histology and MRI changes in DMD and demonstrates the value of this imaging technique as a reliable tool for the selection of muscles in patients recruited into clinical trials.

Understanding measurements of intestinal permeability in healthy humans with urine lactulose and mannitol excretion.

Our aim was to understand the information from differential two-sugar excretion (2-SE) in measuring intestinal permeability. In a crossover study in 12 healthy volunteers, we compared urinary excretion ratios of lactulose (L) to mannitol [(M) LMR] after ingestion in liquid formulation (LF) or in delayed-release, methacrylate-coated capsules (CAP). Both formulations were radiolabelled. Urine was collected every 2 h from 0 to 8 h, and from 8 to 24 h. Two hours after LF, gastric residual was 15.9 +/- 6.2% (SEM), and the percentage in colon was 49.6 +/- 7.8%; in 11/12 participants, liquid had entered colon within 2 h. Average CAP arrival time in colon was 5.16 +/- 0.46 h (mode 6 h). After LF, mannitol was extensively absorbed in the first 8 h; lactulose absorption was low throughout the 24 h. After the LF, the LMR (geometric mean, 95% CI per h) in the 0-2 h urine was [0.08 (0.05, 0.11)], which was lower than in 8-24 h urine [0.32 (0.16, 0.46); P < 0.05]. Urine LMRs at 8-24 h were similar after LF or CAP. We concluded that, after LF, sugar excretion in 0-2 h urine may reflect both SI and colon permeability. Colonic permeability is reflected by urine sugar excretion between 6 and 24 h. CAP delivery reduces mannitol excreted at 0-6 h, compared with LF. The 0-5 or 6 h 2-SE urine likely reflects both SI and colon permeability; the higher LMR in the 8-24 h urine relative to 0-2 h urine should be interpreted with caution and does not mean that colon is more permeable than SI.

Natural history of Ullrich congenital muscular dystrophy.

OBJECTIVE: To describe the course, complications, and prognosis of Ullrich congenital muscular dystrophy (UCMD), with special reference to life-changing events, including loss of ambulation, respiratory insufficiency, and death. METHODS: Review of the case notes of 13 patients with UCMD, aged 15 years or older at last visit, followed up at a tertiary neuromuscular centre, London, UK, from 1977 to 2007. Data collected were age at onset of symptoms, presenting symptoms, mobility, contractures, scoliosis, skin abnormalities, respiratory function, and feeding difficulties. RESULTS: The mean age at onset of symptoms was 12 months (SD 14 months). Eight patients (61.5%) acquired independent ambulation at a mean age of 1.7 years (SD 0.8 years). Nine patients (69.2%) became constant wheelchair users at a mean age of 11.1 years (SD 4.8 years). Three patients continued to ambulate indoors with assistance. Forced vital capacity (FVC) values were abnormal in all patients from age 6 years. The mean FVC (% predicted) declined at a mean rate of 2.6% (SD 4.1%) yearly. Nine patients (69.2%) started noninvasive ventilation at a mean age of 14.3 years (SD 5.0 years). Two patients died of respiratory insufficiency. CONCLUSION: In Ullrich congenital muscular dystrophy (UCMD), the decline in motor and respiratory functions is more rapid in the first decade of life. The deterioration is invariable, but not always correlated with age or severity at presentation. This information should be of help to better anticipate the difficulties encountered by patients with UCMD and in planning future therapeutic trials in this condition.

Measurement of serum 7alpha-hydroxy-4-cholesten-3-one (or 7alphaC4), a surrogate test for bile acid malabsorption in health, ileal disease and irritable bowel syndrome using liquid chromatography-tandem mass spectrometry.

Bile acid malabsorption (BAM) is reported in up to 50% of patients with functional diarrhoea and irritable bowel syndrome with diarrhoea (IBS-D). Serum 7alpha-hydroxy-4-cholesten-3-one (7alphaHCO or 7alphaC4), an indirect measurement of hepatic bile acid synthesis, has been validated as a measurement of BAM relative to the (75)SeHCAT retention test. Our aim was to develop a serum 7alphaC4 assay, normal values, and compare results from healthy controls, patients with ileal Crohn's disease or resection, and patients with IBS-D or IBS with constipation (IBS-C). Stored serum samples were used from adult men and women in the following groups: 111 normal healthy controls, 15 IBS-D, 15 IBS-C, 24 with distal ileal Crohn's disease and 20 with distal ileal resection for Crohn's disease. We adapted a published high pressure liquid chromatography, tandem mass spectrometry (HPLC-MS/MS) assay. The HPLC-MS/MS assay showed good linearity in concentration range 0-200 ng mL(-1), sensitivity (lowest limit of detection 0.04 ng mL(-1)), and high analytical recovery (average 99%, range 93-107%). The 5th to 95th percentile for 111 normal healthy controls was 6-60.7 ng mL(-1). There were significant overall group differences (anovaon ranks, P < 0.001), with significantly higher values for terminal ileal disease or resection. There were significant differences between health and IBS (anova, P = 0.043) with higher mean values in IBS-D relative to controls (rank sum test, P = 0.027). We have established a sensitive non-isotopic assay based on HPLC-MS/MS, determined normal 7alphaC4 values, and identified increased 7alphaC4 in IBS-D and in distal ileal resection and disease. This assay has potential as a non-invasive test for BAM in IBS.

Impact of fasting and postprandial state on plasma carnitine concentrations during aerobic exercise in type 2 diabetes.

The effects of metabolic states of fasting and post-absorption on plasma concentrations of free carnitine (FC), acylcarnitine (AC) and total carnitine (TC) were compared during submaximal exercise in subjects with type 2 diabetes mellitus. Ten sedentary men (54+/-5 years) treated with oral hypoglycaemic agents were tested on two separate occasions: following an overnight fast and 2 h after a 395-kcal standardised breakfast. Exercise was performed at 60% of [Formula: see text]O(2peak) on a cycle ergometer for 60 min. Blood samples were drawn at rest for baseline values and following 60 min of exercise and 30 min of recovery. Our results show that: (1) baseline levels of TC, FC and AC were similar in fasted and postprandial groups, (2) TC and AC levels were increased during exercise in the fasted group only, (3) FC levels were decreased during exercise in both fasted and postprandial state and (4) the AC/FC ratio increased during exercise in the fasted group. Our results indicate that the metabolic state of the diabetic patient is associated with a different plasma carnitine status. These patterns may reflect differences in energy metabolism associated with fasting and postprandial hyperglycaemia.

Disinhibition, as assessed by the Three-Factor Eating Questionnaire, is inversely related to psychological well-being in postmenopausal women.

UNLABELLED: Psychological correlates of obesity remain under controversy. As eating behaviors and dieting history have been previously related to obesity status, these dietary variables may contribute to identify overweight and obese individuals who are at higher risk of having an impaired psychological well-being. OBJECTIVE: The main purpose of this cross-sectional study was to verify the hypothesis of a relationship between weight status and psychological well-being, and to examine whether cognitive dietary restraint, disinhibition, susceptibility to hunger and dieting history could be related to psychological well-being. DESIGN AND SUBJECTS: In a sample of 101 postmenopausal women, we performed anthropometric measurements (weight, height and body mass index (BMI)), and measured psychological well-being (PER Questionnaire). The Three-Factor Eating Questionnaire (TFEQ) and a questionnaire about dieting history (dieters: had already been on a diet; non-dieters: had never been on a diet) were also administrated. RESULTS: A trend for a significant relationship was observed between BMI and psychological well-being (r=-0.17; P=0.08). Significant negative relationships were observed for disinhibition, susceptibility to hunger and all their subscales with psychological well-being (-0.28

Clinical significance of isolated hippocampal volume asymmetry in childhood epilepsy.

This study defines the clinical characteristics and evolution of 16 epileptic children with hippocampal asymmetry (HA) without sclerosis on MRI. The association of a positive family history of epilepsy (11/16), low incidence of febrile seizures (2/16), and benign prognosis (seizure control in monotherapy in 11/16, mean follow-up = 4.3 years, range 1 to 10) suggest a different clinical presentation than patients with mesial temporal sclerosis. Genetic studies of these mostly French Canadian families should help confirm the existence of a distinct syndrome.

Impaired fasting glucose vs. glucose intolerance in pre-menopausal women: distinct metabolic entities and cardiovascular disease risk?

BACKGROUND: Impaired glucose tolerance (IGT) is associated with an increased cardiovascular disease risk. Less is known about cardiovascular disease risk among subjects with impaired fasting glucose (IFG) or with combined IFG and IGT. AIMS: To compare body composition, body fat distribution, plasma glucose-insulin homeostasis and plasma lipid-lipoprotein profile between pre-menopausal women having either a normal glucose tolerance (NGT), isolated IFG, isolated IGT or combined IFG and IGT. METHODS: Three hundred and thirty-four women with NGT, 11 women with IFG, 35 women with IGT and 10 women with both IFG and IGT were studied. RESULTS: Women with IFG were characterized by a higher visceral adipose tissue (AT) accumulation than women with NGT (P < 0.05). Also, they were characterized by a higher subcutaneous AT area and by higher body fat mass than NGT and IGT women (P < 0.05). However, their lipid-lipoprotein profile was comparable with that of NGT women, except for reduced HDL-cholesterol concentrations (P < 0.05). After adjustment for visceral AT, women with IFG had lower total cholesterol, LDL-cholesterol and apolipoprotein B (apoB) levels than the three other groups. They also had lower HDL(2)-cholesterol than NGT women and lower total cholesterol/HDL-cholesterol ratio than IGT women. Women with IGT showed higher triglyceride and apoB concentrations and a higher total cholesterol/HDL-cholesterol ratio than women with NGT (P < 0.05). Overall, women with combined IFG and IGT showed body fatness characteristics and alterations in their metabolic risk profile which were essentially similar to women with isolated IGT. CONCLUSIONS: These results indicate that there are significant differences in anthropometric and metabolic variables between pre-menopausal women with IFG vs. IGT and that the association between body fatness-body fat distribution indices and the metabolic profile may differ between IFG and IGT women.

Is the gender difference in LDL size explained by the metabolic complications of visceral obesity?

BACKGROUND: Several studies have reported a significant gender difference in low-density lipoprotein (LDL) size, with men being characterized by smaller, denser LDL particles than women, and it has been suggested that the contribution of the greater accumulation of visceral adipose tissue in men compared with women may be a factor potentially contributing to the gender difference in LDL heterogeneity. MATERIALS AND METHODS: We measured LDL particle size by 2-16% nondenaturing polyacrylamide gradient gel electrophoresis in 299 men and 231 women in whom visceral adipose tissue accumulation was measured by computed tomography. A fasting plasma lipoprotein-lipid profile was also obtained in all subjects. RESULTS: Overall, the men were characterized by a more deteriorated metabolic risk factor profile, which included higher plasma insulin and triglyceride levels, a greater visceral adipose tissue accumulation (P < 0.001) and smaller LDL particles (251.7 +/- 5.2 vs. 254.4 +/- 4.2 A, P < 0.0001). This gender difference in LDL peak particle diameter remained significant (252.4 +/- 4.3 vs. 253.5 +/- 4.3 A, P < 0.01) after adjustment for sex-specific differences in plasma triglyceride levels by covariance analysis. Significant negative correlations were noted between the LDL particle diameter and the triglyceride concentrations in both genders (r = -0.52 and r = -0.36, P < 0.0001 for the men and women, respectively), with no gender difference in this relationship being found. However, viscerally obese women (visceral adipose tissue levels > 100 cm2) with increased plasma triglyceride concentrations (> 2.0 mmol L-1) still had larger LDL particles than viscerally obese men with a similar elevation in their triglyceride levels (251.6 +/- 4.9 vs. 248.7 +/- 4.5 A, P < 0.01). CONCLUSIONS: Results of the present study suggest that the reduced LDL particle size observed in men compared with women cannot be entirely explained by their higher visceral adipose tissue accumulation and increased plasma triglyceride levels. Moreover, the gender difference in LDL size could be influenced, at least in part, by the severity of the hypertriglyceridaemic state.

Reduced HDL particle size as an additional feature of the atherogenic dyslipidemia of abdominal obesity.

Reduced plasma HDL cholesterol concentration has been associated with an increased risk of coronary heart disease. However, a low HDL cholesterol concentration is usually not observed as an isolated disorder because this condition is often accompanied by additional metabolic alterations. The objective of this study was to document the relevance of assessing HDL particle size as another feature of the atherogenic dyslipidemia found among subjects with visceral obesity and insulin resistance. For that purpose, an average HDL particle size was computed by calculating an integrated HDL particle size using nondenaturing 4-30% gradient gel electrophoresis. Potential associations between this average HDL particle size versus morphometric and metabolic features of visceral obesity were examined in a sample of 238 men. Results of this study indicated that HDL particle size was a significant correlate of several features of an atherogenic dyslipidemic profile such as increased plasma TG, decreased HDL cholesterol, high apolipoprotein B, elevated cholesterol/HDL cholesterol ratio, and small LDL particles as well as increased levels of visceral adipose tissue (AT) (0.33 < or = absolute value of r < or = 0.61, P < 0.0001). Thus, men with large HDL particles had a more favorable plasma lipoprotein-lipid profile compared with those with smaller HDL particles. Furthermore, men with large HDL particles were also characterized by reduced overall adiposity and lower levels of visceral AT as well as reduced insulinemic-glycemic responses to an oral glucose load. In conclusion, small HDL particle size appears to represent another feature of the high TG- low HDL cholesterol dyslipidemia found in viscerally obese subjects characterized by hyperinsulinemia.

Effects of the FABP2 A54T mutation on triglyceride metabolism of viscerally obese men.

OBJECTIVE: Viscerally obese individuals are frequently characterized by a proatherogenic condition. A missense mutation (A54T) in the fatty acid binding protein type 2 (FABP2) gene has been associated with insulin resistance and obesity. This study examined the effect of this mutation on lipoprotein levels in viscerally obese hyperinsulinemic condition. RESEARCH METHODS AND PROCEDURES: A total of 217 men were assigned to one of two groups based on their FABP2 A54T polymorphism. RESULTS: The two genotypic groups showed no difference in either physiological characteristics or lipoprotein/lipid profile, before or after statistical adjustment for age. From this initial sample, 50 men accepted to have their postprandial lipid response assessed and 10 T54/A54 heterozygotes were then individually matched for visceral adipose tissue accumulation and fasting plasma triglyceride (TG) levels with 10 A54/A54 homozygotes. High-density lipoprotein (HDL)-TG levels were significantly increased in the fasting state as well as 4 hours after the test meal (p = 0.04 and p = 0.0008, respectively) in men bearing the A54T mutation. In addition, the area under the curve of postprandial HDL-TG levels was also significantly higher among T54/A54 heterozygotes than among A54/A54 homozygotes (p = 0.04). Interestingly, fasting TG concentrations in large TG-rich lipoproteins (large-TRL; S(f) > 400) were correlated with HDL-TG levels at 4 (r = 0.74, p = 0.01) and 8 hours (r = 0.73, p = 0.01) after the test meal in T54/A54 heterozygotes only. DISCUSSION: The FABP2 A54T missense mutation may contribute to the TG enrichment of HDL in the postprandial state that, in turn, may alter the risk of atherosclerotic vascular disease.