Epistemological and ethical assessment of obesity bias in industrialized countries

Bernard Lonergan's cognitive theory challenges us to raise questions about both the cognitive process through which obesity is perceived as a behaviour change issue and the objectivity of such a moral judgment. Lonergan's theory provides the theoretical tools to affirm that anti-fat discrimination, in the United States of America and in many industrialized countries, is the result of both a group bias that resists insights into the good of other groups and a general bias of anti-intellectualism that tends to set common sense against insights that require any thorough scientific analyses. While general bias diverts the public's attention away from the true aetiology of obesity, group bias sustains an anti-fat culture that subtly legitimates discriminatory practices and policies against obese people. Although anti-discrimination laws may seem to be a reasonable way of protecting obese and overweight individuals from discrimination, obesity bias can be best addressed by reframing the obesity debate from an environmental perspective from which tools and strategies to address both the social and individual determinants of obesity can be developed. Attention should not be concentrated on individuals' behaviour as it is related to lifestyle choices, without giving due consideration to the all-encompassing constraining factors which challenge the social and rational blindness of obesity bias

Evaluation of adipose tissue volume quantification with IDEAL fat-water separation

Purpose: To validate iterative decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL) for adipose tissue volume quantification. IDEAL allows MRI images to be produced only from adipose-containing tissues; hence, quantifying adipose tissue should be simpler and more accurate than with current methods. Materials and Methods: Ten healthy controls were imaged with 1.5 Tesla (T) Spin Echo (SE), 3.0T T1-weighted spoiled gradient echo (SPGR), and 3.0T IDEAL-SPGR. Images were acquired from the abdomen, pelvis, mid-thigh, and mid-calf. Mean subcutaneous and visceral adipose tissue volumes were compared between the three acquisitions for each subject. Results: There were no significant differences (P \u3e 0.05) between the three acquisitions for subcutaneous adipose tissue volumes. However, there was a significant difference (P = 0.0002) for visceral adipose tissue volumes in the abdomen. Post hoc analysis showed significantly lower visceral adipose tissue volumes measured by IDEAL versus 1.5T (P \u3c 0.0001) and 3.0T SPGR (P \u3c 0.002). The lower volumes given by IDEAL are due to its ability to differentiate true visceral adipose tissue from other bright structures like blood vessels and bowel content that are mistaken for adipose tissue in non-fat suppressed images. Conclusion: IDEAL measurements of adipose tissue are equivalent to established 1.5T measurement techniques for subcutaneous depots and have improved accuracy for visceral depots, which are more metabolically relevant. © 2011 Wiley-Liss, Inc

Alstrom syndrome (OMIM 203800): a case report and literature review

<p>Abstract</p> <p>Background</p> <p>Alstrom syndrome (AS) is a rare autosomal recessive disease characterized by multiorgan dysfunction. The key features are childhood obesity, blindness due to congenital retinal dystrophy, and sensorineural hearing loss. Associated endocrinologic features include hyperinsulinemia, early-onset type 2 diabetes, and hypertriglyceridemia. Thus, AS shares several features with the common metabolic syndrome, namely obesity, hyperinsulinemia, and hypertriglyceridemia. Mutations in the <it>ALMS1 </it>gene have been found to be causative for AS with a total of 79 disease-causing mutations having been described.</p> <p>Case presentation</p> <p>We describe the case of a 27-year old female from an English (Caucasian) kindred. She had been initially referred for hypertriglyceridemia, but demonstrated other features suggestive of AS, including blindness, obesity, type 2 diabetes, renal dysfunction, and hypertension. DNA analysis revealed that she is a compound heterozygote with two novel mutations in the <it>ALMS1 </it>gene – H3882Y and V424I. Examination of her family revealed that her phenotypically unaffected mother and younger sister also had heterozygous mutations in the <it>ALMS1 </it>gene. In addition to presenting these novel molecular findings for AS, we review the clinical and genetic features of AS in the context of our case.</p> <p>Conclusion</p> <p>Two novel mutations in the <it>ALMS1 </it>gene causative for AS have been reported here, thereby increasing the number of reported mutations to 81 and providing a wider basis for mutational screening among affected individuals.</p

Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial

AIM To evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of nonalcoholic steatohepatitis (NASH). METHODS Twelve patients with biopsy-proven NASH were randomized to sitagliptin (100 mg daily) (n = 6) or placebo (n = 6) for 24 wk. The primary outcome was improvement in liver fibrosis after 24 wk. Secondary outcomes included evaluation of changes in NAFLD activity score (NAS), individual components of NAS (hepatocyte ballooning, lobular inflammation, and steatosis), glycemic control and insulin resistance [including measurements of glycated hemoglobin (HbA1C) and adipocytokines], lipid profile including free fatty acids, adipose distribution measured using magnetic resonance imaging (MRI), and thrombosis markers (platelet aggregation and plasminogen activator inhibitor 1 levels). We also sought to determine the correlation between changes in hepatic fat fraction (%) [as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) MRI technique] and changes in hepatic steatosis on liver biopsy. RESULTS Sitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy (mean difference between sitagliptin and placebo arms, 0.40, P = 0.82). There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS. Compared to baseline, those patients who received sitagliptin demonstrated improved HbA1C (6.7% ± 0.4% vs 7.9% ± 1.0%, P = 0.02), and trended towards improved adiponectin levels (4.7 ± 3.5 μg/mL vs 3.9 ± 2.7 μg/mL, P = 0.06) and triglyceride levels (1.26 ± 0.43 mmol/L vs 2.80 ± 1.64 mmol/L, P = 0.08). However, when compared with placebo, sitagliptin did not cause a statistically significant improvement in HbA1C (mean difference, -0.7%, P = 0.19) nor triglyceride levels (mean difference -1.10 mmol/L, P = 0.19) but did trend towards improved adiponectin levels only (mean difference, 0.60 μg/mL, P = 0.095). No significant changes in anthropometrics, liver enzymes, other adipocytokines, lipid profile, thrombosis parameters, or adipose distribution were demonstrated. The MRI IDEAL procedure correlated well with steatosis scores obtained on liver biopsy in both groups at baseline and post-treatment, and the Spearman correlation coefficients ranged from r = 0.819 (baseline) to r = 0.878 (post-treatment), P = 0.002. CONCLUSION Sitagliptin does not improve fibrosis score or NAS after 24 wk of therapy. The MRI IDEAL technique may be useful for non-invasive measurement of hepatic steatosis

Intra-thoracic fat volume is associated with myocardial infarction in patients with metabolic syndrome

Background: Visceral adiposity is increased in those with Metabolic Syndrome (MetS) and atherosclerotic disease burden. In this study we evaluate for associations between intra-thoracic fat volume (ITFV) and myocardial infarction (MI) in patients with MetS. Methods. Ninety-four patients with MetS, MI or both were identified from a cardiovascular CMR clinical registry. MetS was defined in accordance to published guidelines; where-as MI was defined as the presence of subendocardial-based injury on late gadolinium enhancement imaging in a coronary vascular distribution. A healthy control group was also obtained from the same registry. Patients were selected into the following groups: MetS+/MI- (N = 32), MetS-/MI + (N = 30), MetS+/MI + (N = 32), MetS-/MI- (N = 16). ITFV quantification was performed using signal threshold analysis of sequential sagittal CMR datasets (HASTE) and indexed to body mass index. Results: The mean age of the population was 59.8 ± 12.5 years. MetS+ patients (N=64) demonstrated a significantly higher indexed ITFV compared to MetS- patients (p = 0.05). Patients in respective MetS-/MI-, MetS+/MI-, MetS-/MI+, and MetS+/MI + study groups demonstrated a progressive elevation in the indexed ITFV (22.3 ± 10.6, 28.6 ± 12.6, 30.6 ± 12.3, and 35.2 ± 11.4 ml/kg/m2, (p = 0.002)). Among MetS+ patients those with MI showed a significantly higher indexed ITFV compared to those without MI (p = 0.02). Conclusions: ITFV is elevated in patients with MetS and incrementally elevated among those with evidence of prior ischemic myocardial injury. Accordingly, the quantification of ITFV may be a valuable marker of myocardial infarction risk among patients with MetS and warrants further investigation. © 2013 Jolly et al.; licensee BioMed Central Ltd

The End of the Road for CETP Inhibitors after Torcetrapib?

PURPOSE OF REVIEW: Because high-density lipoprotein cholesterol (HDL-C) levels are inversely related to cardiovascular disease (CVD), raising HDL-C levels would seem intuitively valuable. However, the recent failure of the cholesteryl ester transfer protein (CETP) inhibitor torcetrapib to decrease CVD has raised doubts regarding HDL-C raising in general and CETP inhibition in particular for CVD prevention. We briefly discuss the complexity of HDL metabolism, caveats of CETP inhibition, possible mechanisms for torcetrapib\u27s failure, and the potential utility of other CETP inhibitors. RECENT FINDINGS: Torcetrapib likely failed because of off-target effects, since other CETP inhibitors, such as dalcetrapib (JTT-705/R1658) or anacetrapib (MK-0859), do not increase blood pressure, a specific pressor effect of tocetrapib that appears to be CETP-independent. In small human trials of short duration, anacetrapib and dalcetrapib appear to improve the lipoprotein profile without obvious adverse effects, so far. SUMMARY: The relationship between HDL metabolism, pharmacologic CETP inhibition, and atherosclerosis requires further elucidation. There seems to be sufficient evidence that evaluation of CETP inhibitors such as dalcetrapib and anacetrapib should proceed, if cautiously, since it remains uncertain whether the increased CVD risk with torcetrapib was related to agent-specific off-target effects or more generally to CETP inhibition as a mechanism to raise HDL