Bioimpedance Analysis: Should it be Used in Morbid Obesity?

Objectives: Questions about reliability of bioimpedance analysis (BIA) in morbidly obese subjects have curtailed its use in this setting, but metabolic implications might reignite the debate. In a prospective study, it was aimed to analyze anthropometric and clinical associations. Methods: Bariatric candidates (n = 94) with or without metabolic syndrome were consecutively investigated. Age was 34.9 +/- 10.4 years (68.1% females), and BMI was 40.8 +/- 4.6 kg m(-2). Methods included single-frequency BIA, anthropometrics, inflammatory indices, and general biochemical profile. Results: Body composition results (water, fat) in females, but not in males, were entirely consistent with the literature. In both genders good association was observed with anthropometrics (BMI, waist circumference), inflammatory indices (ferritin, C-reactive protein) and general biochemical variables. Anthropometric measurements also displayed comparable associations. Multivariate tests including the two sets of measurements indicated no predominance of one method over the other, one complementing the other as metabolic marker. Conclusions: BIA limitations were mostly relevant for males, not females. Despite such discrepancies, good associations with anthropometry were demonstrated for both genders. Correlations with liver enzymes, and indices of protein, carbohydrate, and lipid metabolism could be demonstrated. BIA deserves more investigations concerning liver steatosis and ongoing inflammation, and it could contribute as well, synergistically with anthropometry, to monitor weight loss, body fat shifts, and metabolic risk. Am. J. Hum. Biol. 23: 420-422, 2011. (c) 2011 Wiley-Liss, Inc.

Inflammation and Biochemical Features of Bariatric Candidates: Does Gender Matter?

Background Accumulated fat is an accepted trigger of inflammation and metabolic syndrome but specific biochemical associations in males and females are still debated. In a prospective study, multiple variables were analyzed to search for gender-related correlations. Methods Bariatric candidates (n=94) were consecutively investigated. Age was 34.9 +/- 10.4 years (68.1% females) and body mass index (BMI) was 40.8 +/- 4.6 kg/m(2). Methods included anthropometrics, inflammatory indices (C-reactive protein (CRP), white blood cell count (WBC), ferritin) and general biochemical profile. Results Ferritin, but not CRP or WBC, was substantially more elevated in males. Serum albumin, uric acid, creatinine, and liver enzymes AST and ALT were also higher in men. Even after BMI was adjusted, all differences remained significant, and several, notably ferritin, withstood waist circumference control. Ferritin and CRP correlated with anthropometrics, glucose-related measurements, and liver enzymes, whereas WBC was only associated with triglycerides in females. Conclusions (1) Males displayed more severe inflammation according to ferritin profile, and also more signs of liver derangement; (2) all differences continued after BMI discrepancies were adjusted for, and ferritin was significant also after control of waist girth; (3) in both genders inflammatory markers often correlated with different anthropometrics, liver enzymes, and markers of glucose homeostasis; and (4) inflammatory and biochemical gender-related dissimilarities might have prognostic implications for cardiovascular risk and other comorbidities, and deserve additional studies.

Combination of N-acetylcysteine and metformin improves histological steatosis and fibrosis in patients with non-alcoholic steatohepatitis

Aim: There is no proven medical therapy for the treatment of non-alcoholic steatohepatitis (NASH). Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. The aim of our study was to evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) in improving the aminotransferases and histological parameters (steatosis, inflammation, hepatocellular ballooning, and fibrosis) after 12 months of treatment. Methods: Twenty consecutive patients (mean age 53 +/- 2 years [36-68] and body mass index [BMI] 29 [25-35]) with biopsy-proven NASH were enrolled in the study. NAC (1.2 g/day) and MTF (850-1000 mg/day) were given orally for 12 months. All patients underwent evaluation of serum aminotransferases, fasting lipid profile and serum glucose, anthropometric parameters, and nutritional status at 0 and 12 months. A low calorie diet was prescribed for all patients. Results: Serum alanine aminotransferase, high-density lipoprotein, insulin, and glucose concentrations and thehomeostasis model assessment-insulin resistance (HOMA-IR) index were reduced significantly at the end of study (P < 0.05). The BMI declined, but without statistical significance. Aspartate aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, cholesterol, and triglycerides levels were not altered with the treatment. Liver steatosis and fibrosis decreased (P < 0.05), but no improvement was noted in lobular inflammation or hepatocellular ballooning. The NASH activity score was significantly improved after treatment. Conclusion: Based on the biochemical and histological evidence in this pilot study, NAC in combination with MTF appears to ameliorate several aspects of NASH, including fibrosis. Further studies of this form of combination therapy are warranted to assess its potential efficacy.

Dyslipidemia in women with polycystic ovary syndrome: incidence, pattern and predictors

One hundred forty-two women with polycystic ovary syndrome (PCOS) with an average body mass index (BMI) of 29.1 kg/m(2) and average age of 25.12 years were studied. By BMI, 30.2% were normal, 38.0% were overweight and 31.6% were obese. Thirty-one eumenorrheic women matched for BMI and age, with no evidence of hyperandrogenism, were recruited as controls. The incidence of dyslipidemia in the PCOS group was twice that of the Control group (76.1% versus 32.25%). The most frequent abnormalities were low high-density lipoprotein cholesterol (HDL-C; 57.6%) and high triglyceride (TG) (28.3%). HDL-C was significantly lower in all subgroups of women with PCOS when compared to the subgroups of normal women. No significant differences were seen in the total cholesterol (p = 0.307), low-density lipoprotein cholesterol (LDL-C; p = 0.283) and TGs (p = 0.113) levels among the subgroups. An independent effect on HDL-C was detected for glucose (p = 0.004) and fasting insulin (p = 0.01); on TG for age (p = 0.003) and homeostatic model assessment insulin resistance (p = 0.03) and on total cholesterol and LDL-C for age (p = 0.02 and p = 0.033, respectively). In conclusion, dyslipidemia is common in women with PCOS, mainly due to low HDL-C levels. BMI has a significant impact on this abnormality.

Metabolism of triglyceride-rich lipoproteins and lipid transfer to high-density lipoprotein in young obese and normal-weight patients with polycystic ovary syndrome

Objective: To clarify whether the metabolism of triglyceride-rich lipoproteins and lipid transfer to high-density lipoprotein (HDL) are altered in patients with polycystic ovary syndrome (PCOS). Design: Case control study. Setting: Endocrinology clinics. Patient(s): Eight normal-weight (NW) and 15 obese (013) patients with PCOS were compared with 10 NW and 10 Ob women without PCOS paired for age and body mass index. Intervention(s): Determination of triglyceride-rich lipoprotein metabolism and lipid transfer to HDL. Main Outcome Measure(s): Participants were injected triglyceride-rich emulsions labeled with (14)C-cholesteryl esters and (3)H-triglycerides and the fractional clearance rate (FCR, in min(-1)) of labels was determined. Lipid transfer from artificial nanoemulsions to HDL was performed by incubating radioactively labeled lipid nanoemulsions with plasma during 1 hour, followed by radioactive counting of HDL-containing supernatant after chemical precipitation. Result(s): Lipolysis estimated by triglyceride FCR was equal in PCOS groups (NW = 0.043 +/- 0.032, Ob = 0.033 +/- 0.009) and respective controls (NW = 0.039 +/- 0.015, Ob = 0.044 +/- 0.019). However, the remnant removal as estimated by cholesteryl ester FCR was reduced in both PCOS groups (NW = 0.005 +/- 0.006, Ob = 0.005 +/- 0.005) compared with controls (NW = 0.016 +/- 0.006, Ob = 0.011 +/- 0.072). Lipid transfer rates were not different among groups, but triglyceride transfer rates were positively correlated with homeostasis model assessment estimate of insulin resistance in PCOS. Conclusion(s): PCOS patients showed decreased removal of atherogenic remnants even when fasting glucose was <100 mg/dL. This reinforces the usefulness of the measures taken to prevent cardiovascular events in PCOS patients. (Fertil Steril (R) 2010;93:1948-56. (C)2010 by American Society for Reproductive Medicine.)

Influence of LH and high-density lipoprotein cholesterol (HDL-C) on metformin response in women with polycystic ovary syndrome

Objective: To search for predictors of metformin response in women with polycystic ovary syndrome (PCOS) through a detailed analysis of clinical and laboratory parameters. Study design: We designed a prospective study to investigate clinical and laboratory parameters to search for predictors of metformin response in women with PCOS. A total of 53 PCOS patients were given metformin 850 mg twice a day for 6 months, after which patients were classified as responders or non-responders. Parameters analyzed for comparison between the two groups were: plasma fasting insulin glucose/insulin ratio; oral glucose tolerance test (OGTT) with insulin (120 min); HOMA and QUICKI tests; total cholesterol and fractions, triglycerides; LH, FSH, estradiol, progesterone, testosterone, androstenedione, 17-OH progesterone, and DHEAS. Results: From all patients, 30(56.6%) were responders and 23(43.3%) were non-responders. Multinomial analysis showed that the positive response to metformin was associated with higher levels of basal LH (p = 0.038) and lower levels of high-density lipoprotein cholesterol (HDL-C) (p = 0.015). Conclusion: In weight-matched PCOS subjects, laboratory markers might predict the metformin response. Higher levels of basal LH and lower levels of HDL-C are correlated with a positive response to metformin treatment in PCOS subjects. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Metabolic differences between male and female adolescents with non-alcoholic fatty liver disease, as detected by ultrasound

Background: Age, developmental stage and gender are risk factors for paediatric non-alcoholic fatty liver disease (NAFLD). Aims: The aim of this study was to identify differences in clinical or laboratory variables between sexes in adolescents with NAFLD. Methodology: Ninety obese adolescents including 36 males and 54 females were evaluated. Inclusion criteria for this study were a Body Mass Index above the 95th percentile, as set forth by the National Center for Health Statistics, and an age of 10-19 years. A clinical and laboratory evaluation was conducted for all adolescents. Results: The variables that were found to be predictive of NAFLD in adolescence were visceral fat, Aminotransferase, Gamma-Glutamyl Transferase, triglyderides, cholesterol and LDL-cholesterol. We also observed that cholesterol and LDL-cholesterol variables were influenced by gender, i.e. there was a significant statistical difference in the values of these variables between male and female adolescents. With regard to cholesterol serum concentrations, the risk was 6.99 times greater for females, compared with 1.2 times for males; and for LDL-cholesterol serum concentrations the risk was 8.15 times greater for females, compared with and 1.26 times for males. Conclusion: Female adolescents with NAFLD showed a significantly different metabolic behaviour than males.

High-fat diet: A trigger of non-alcoholic steatohepatitis? Preliminary findings in obese subjects

Objective: We correlated dietary profile and markers of visceral and somatic obesities in nonalcoholic fatty liver disease. Methods: Patients with histologically proven fatty infiltration of the liver (n = 25, 52 +/- 11 y of age, 64% women) underwent abdominal computed tomography, bioelectrical impedance, and anthropometric measurements. Insulin resistance was evaluated (homeostasis model assessment) and dietary intake of macronutrients was estimated by 24-h recall. Main outcome measurements were correlation of carbohydrate and fat ingestion with liver histology. Results: Metabolic syndrome was present in 72% of the population, and increased waist circumference and low high-density lipoprotein cholesterol occurred in 66%. Total body fat (bioimpedance) and dietary intake of lipids were higher in patients with non-alcoholic steatohepatitis (P < 0.05), but not in diabetic subjects who exhibited more steatosis than non-alcoholic steatohepatitis. Waist circumference exhibited a good correlation with homeostasis model assessment, total energy intake, and ingestion of specific fatty acids. Body mass index correlated well with somatic and visceral adiposities. Conclusion: Energy intake and visceral adiposity were predisposing factors for fatty liver disease. Lipid input correlated with non-alcoholic steatohepatitis in the entire group and after stratification for diabetes. These findings suggest that lipid intake may play a greater role in non-alcoholic steatohepatitis than hitherto suspected. (C) 2008 Elsevier Inc. All rights reserved.

Diabetes, hyperglycemia and the management of cerebrovascular disease

Purpose of review Hyperglycemia is frequent in patients with cerebrovascular disease. This review article aims to summarize the recent evidence from observational studies that examined the adverse cerebrovascular effects of dysglycemic states as well as interventional studies assessing intensive management strategies for hyperglycemia. Recent findings In recent years, diabetes, prediabetic states and insulin resistance and their association with cerebrovascular disease were an important focus of research. The cerebrovascular consequences of these metabolic abnormalities were found to extend beyond ischemic stroke to covert brain infarcts, other structural brain changes and to cognitive impairment with and without dementia. Interventional studies did not reveal that more intensive management of chronic hyperglycemia and of hyperglycemia in the setting of acute stroke improves outcome. There is clear evidence, however, that the overall management of multiple risk factors and behavior modification in patients with dysglycemia may reduce the burden of cerebrovascular disease. Summary Observational studies reveal the growing burden and adverse cerebrovascular effects of dysglycemic states. Currently available interventional studies assessing more intensive strategies for the management of hyperglycemia did not prove, however, to be effective. We discuss the current evidence, pathophysiological considerations and management implications.

Metabolic consequences of intermittent hypoxia: Relevance to obstructive sleep apnea

Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway leading to sleep fragmentation and intermittent hypoxia (IH) during sleep. There is growing evidence from animal models of OSA that IH is independently associated with metabolic dysfunction, including dyslipidemia and insulin resistance. The precise mechanisms by which IH induces metabolic disturbances are not fully understood. Over the last decade, several groups of investigators developed a rodent model of IH, which emulates the oxyhemoglobin profile in human USA. In the mouse model, IH induces dyslipidemia, insulin resistance and pancreatic endocrine dysfunction, similar to those observed in human USA. Recent reports provided new insights in possible mechanisms by which IH affects lipid and glucose metabolism. IH may induce dyslipidemia by up-regulating lipid biosynthesis in the liver, increasing adipose tissue lipolysis with subsequent free fatty acid flux to the liver, and inhibiting lipoprotein clearance. IH may affect glucose metabolism by inducing sympathetic activation, increasing systemic inflammation, increasing counter-regulatory hormones and fatty acids, and causing direct pancreatic beta-cell injury. IH models of USA have improved our understanding of the metabolic impact of USA, but further studies are needed before we can translate recent basic research findings to clinical practice. (C) 2010 Elsevier Ltd. All rights reserved.

Effects of anti-TNF therapy on glucose metabolism in patients with ankylosing spondylitis, psoriatic arthritis or juvenile idiopathic arthritis

The objective of this study was to evaluate the influence of anti-tumor necrosis factor (anti-TNF) in juvenile idiopathic arthritis (DA), ankylosing spondylitis (AS) or psoriatic arthritis (PsA). Sixty-two patients were investigated: 7 DA; 37 AS; and 18 PsA. Caucasian race accounted for 79% and 29% were female. Mean age was 40.4 +/- 12.6years. None of the patients had a history of diabetes, and none had used oral hypoglycemic agents or insulin. Treatment was with adalimumab, infliximab and etanercept. Glucose, inflammatory markers and prednisone dose were assessed at baseline, as well as after three and six months of treatment. The mean erythrocyte sedimentation rate was significantly lower at three months and six months than at baseline (13.7 +/- 18.0 and 18 +/- 22.5 vs. 27.9 +/- 23.4 mm; p = 0.001). At baseline, three months and six months, we found the following: mean C-reactive protein levels were comparable (22.1 +/- 22.7, 14.5 +/- 30.7 and 16.0 +/- 23.8 mg/L, respectively; p = 0.26); mean glucose levels remained unchanged (90.8 +/- 22.2 mg/dl, 89.5 +/- 14.6 mg/dl and 89.8 +/- 13.6 mg/dl, respectively; p = 0.91); and mean prednisone doses were low and stable (3.9 +/- 4.9 mg/day, 3.7 +/- 4.8 mg/day and 2.6 +/- 4.0 mg/day, respectively; p = 0.23). During the first six months of treatment, anti-TNF therapy does not seem to influence glucose metabolism in JIA, AS or PsA. (C) 2010 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved.

Obstructive Sleep Apnea An Emerging Risk Factor for Atherosclerosis

Obstructive sleep apnea (OSA) is independently associated with death from cardiovascular diseases, including myocardial infarction and stroke. Myocardial infarction and stroke are complications of atherosclerosis; therefore, over the last decade investigators have tried to unravel relationships between OSA and atherosclerosis. OSA may accelerate atherosclerosis by exacerbating key atherogenic risk factors. For instance, OSA is a recognized secondary cause of hypertension and may contribute to insulin resistance, diabetes, and dyslipidemia. In addition, clinical data and experimental evidence in animal models suggest that OSA can have direct proatherogenic effects inducing systemic inflammation, oxidative stress, vascular smooth cell activation, increased adhesion molecule expression, monocyte/lymphocyte activation, increased lipid loading in macrophages, lipid peroxidation, and endothelial dysfunction. Several cross-sectional studies have shown consistently that OSA is independently associated with surrogate markers of premature atherosclerosis, most of them in the carotid bed. Moreover, OSA treatment with continuous positive airway pressure may attenuate carotid atherosclerosis, as has been shown in a randomized clinical trial. This review provides an update on the role of OSA in atherogenesis and highlights future perspectives in this important research area. CHEST 2011; 140(2):534-542

Relation between visceral fat and coronary artery disease evaluated by multidetector computed tomography

Visceral abdominal fat has been associated to cardiovascular risk factors and coronary artery disease (CAD). Computed tomography (CT) coronary angiography is an emerging technology allowing detection of both obstructive and nonobstructive CAD adding information to clinical risk strati. cation. The aim of this study was to evaluate the association between CAD and adiposity measurements assessed clinically and by CT. We prospectively evaluated 125 consecutive subjects (57% men, age 56.0 +/- 12 years) referred to perform CT angiography. Clinical and laboratory variables were determined and CT angiography and abdominal CT were performed in a 64-slice scanner. CAD was defined as any plaque calcified or not detected by CT angiography. Visceral and subcutaneous adiposity areas were determined at different intervertebral levels. CT angiography detected CAD in 70 (56%) subjects, and no association was found with usual anthropometric adiposity measurements (waist and hip circumferences and body mass index). Otherwise, CT visceral fat areas (VFA) were significantly related to CAD. VFA T12-L1 values >= 145 cm(2) had an odds ratio of 2.85 (95% CI 1.30-6.26) and VFA L4-L5 >= 150 cm(2) had a 2.87-fold (95% CI 1.31-6.30) CAD risk. The multivariate analysis determined age and VFA T12-L1 as the only independent variables associated to CAD. Visceral fat assessed by CT is an independent marker of CAD determined by CT angiography. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

HDL atheroprotection by aerobic exercise training in type 2 diabetes mellitus

Purpose: In this study we analyzed the role played by aerobic exercise training in the plasma lipoprotein profile, prebeta 1-HDL concentration, and in the in vitro HDL3 ability to remove cholesterol from macrophages and inhibit LDL oxidation in type 2 diabetes mellitus (DM) patients and control subjects, in the fasting and postprandial states. Methods: Healthy controls (HTC, N = 11; 1 M/10 F) and subjects with type 2 diabetes mellitus (DMT, N = 11; 3M/ 8F) were engaged in a 4-month aerobic training program, and compared with a group of sedentary subjects with type 2 diabetes mellitus (DMS, N = 10; 4 M/6 F). All groups were submitted to an oral fat load test to analyze all parameters, both at the beginning of the investigation protocol (basal) and at the end of the study period (final). Results: Exercising did not modify body weight, BMI, plasma concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides (TG), glucose, insulin, or HOMA-IR, but it reduced the waist circumference. The HDL3 Composition did not change, and its ability to remove cell cholesterol was unaltered by aerobic training. In DMT but not in HTC, aerobic training improved 15% the HDL3 protective effect against LDL maximal oxidation rate in the fasting state, and reduced 24% the plasma prebeta 1-HDL concentration in the postprandial state, suggesting an enhanced prebeta 1-HDL conversion into larger, more mature HDL particles. In this regard, regular aerobic exercise enriched HDL2 with TG in the fasting and postprandial states in HTC and in the fasting phase in DMT. Conclusion: Our results show that aerobic exercise training in diabetes mellitus improves the HDL efficiency against LDL oxidation and favors HDL maturation. These findings were independent of changes in insulin resistance and of the rise of plasma HDL cholesterol concentration.

Association of a homozygous nonsense caveolin-1 mutation with Berardinelli-Seip congenital lipodystrophy

Context: Berardinelli-Seip congenital lipodystrophy (BSCL) is a rare recessive disease characterized by near absence of adipose tissue, resulting in severe dyslipidemia and insulin resistance. In most reported cases, BSCL is due to alterations in either seipin, of unknown function, or 1-acylglycerol-3- phosphate acyltransferase-beta (AGPAT2), which catalyzes the formation of phosphatidic acid. Objective: We sought to determine the genetic origin of the unexplained cases of BSCL. We thus sequenced CAV1, encoding caveolin-1, as a candidate gene involved in insulin signaling and lipid homeostasis. CAV1 is a key structural component of plasma membrane caveolae, and Cav1-deficient mice display progressive loss of adipose tissue and insulin resistance. Design: We undertook phenotyping studies and molecular screening of CAV1 in four patients with BSCL with no mutation in the genes encoding either seipin or AGPAT2. Results: A homozygous nonsense mutation (p.Glu38X) was identified in CAV1 in a patient with BSCL born from a consanguineous union. This mutation affects both the alpha-and beta-CAV1 isoforms and ablates CAV1 expression in skin fibroblasts. Detailed magnetic resonance imaging of the proband confirmed near total absence of both sc and visceral adipose tissue, with only vestigial amounts in the dorsal sc regions. In keeping with the lack of adipose tissue, the proband was also severely insulin resistant and dyslipidemic. In addition, the proband had mild hypocalcemia likely due to vitamin D resistance. Conclusions: These findings identify CAV1 as a new BSCL-related gene and support a critical role for caveolins in human adipocyte function.