Endocrine disruptors and obesity

The purpose of this review is to summarise current evidence that some environmental chemicals may be able to interfere in endocrine regulation of energy metabolism and adipose tissue structure. Recent findings demonstrate that such endocrine disrupting chemicals, termed “obesogens”, can promote adipogenesis and cause weight gain. This includes compounds to which the human population is exposed in daily life through their use in pesticides/herbicides, industrial and household products, plastics, detergents, flame retardants and ingredients in personal care products. Animal models and epidemiological studies have shown that an especially sensitive time for exposure is in utero or the neonatal period. In summarising the actions of obesogens, it is noteworthy that as their structures are mainly lipophilic, their ability to increase fat deposition has the added consequence of increasing the capacity for their own retention. This has the potential for a vicious spiral not only of increasing obesity but also increasing retention of other lipophilic pollutant chemicals with an even broader range of adverse actions. This might offer an explanation as to why obesity is an underlying risk factor for so many diseases including cancer

Genetic Testing for Early Detection of Individuals at Risk of Coronary Heart Disease and Monitoring Response to Therapy: Challenges and Promises

Coronary heart disease (CHD) often presents suddenly with little warning. Traditional risk factors are inadequate to identify the asymptomatic high-risk individuals. Early identification of patients with subclinical coronary artery disease using noninvasive imaging modalities would allow the early adoption of aggressive preventative interventions. Currently, it is impractical to screen the entire population with noninvasive coronary imaging tools. The use of relatively simple and inexpensive genetic markers of increased CHD risk can identify a population subgroup in which benefit of atherosclerotic imaging modalities would be increased despite nominal cost and radiation exposure. Additionally, genetic markers are fixed and need only be measured once in a patient’s lifetime, can help guide therapy selection, and may be of utility in family counseling

Diagnosis and complications of Cushing's disease: gender-related differences.

Abstract OBJECTIVE: Cushing's disease (CD) presents a remarkable preponderance in female gender, with a female-to-male ratio of 3-8:1. The aim of this study was to evaluate gender-related differences in the presentation of CD, as regards: biochemical indices of hypercortisolism; sensitivity of diagnostic tests; clinical features and complications of disease. METHODS: We retrospectively studied 84 adult patients with CD, 67 women and 17 men, evaluated at diagnosis. We compared the features of the disease between the sexes and analysed the effect of gender on CD complications, adjusted for potential confounders (age, gonadal status, BMI, urinary free cortisol values). RESULTS: We observed no differences between males and females as regards age at diagnosis, disease duration and BMI. Men, compared with women, presented higher urinary free cortisol values (P < 0\ub7001) and ACTH values (P < 0\ub705). As regards diagnostic tests, men presented a lower ACTH response to DDAVP stimulation (P < 0\ub705). The pituitary tumour itself was less easily visualized by pituitary MRI in males compared with females (P < 0\ub705). Furthermore, some complications of disease were more frequent or more severe in men, in particular hypokalaemia (P < 0\ub705), hypercoagulable state and osteoporosis at lumbar spine (P < 0\ub701), with consequent higher risk of vertebral fractures. Male gender was found to be an independent risk factor for dyslipidaemia, severity of hypertension, lumbar osteoporosis and fractures. CONCLUSIONS: Although CD is less frequent in male patients, in this gender, it presents with more florid clinical manifestations and may imply more diagnostic difficulties

Long-term effect of CB1 blockade with rimonabant on cardiometabolic risk factors: two year results from the RIO-Europe Study.

AIMS: Rimonabant, the first selective cannabinoid type 1 receptor blocker, has been shown to produce weight loss and improvements in several cardiometabolic risk factors over 1 year. We report the 2 year efficacy and tolerability data of rimonabant. METHODS AND RESULTS: Patients with a body mass index > or =30 or >27 kg/m(2) with treated/untreated hypertension, dyslipidaemia, or both, were randomized to double-blind treatment with placebo, rimonabant 5 or 20 mg once daily plus a calorie-restricted diet for 2 years. Weight loss from baseline to 2 years in the intention-to-treat population was significantly greater with rimonabant 20 mg (mean +/- SD: -5.5 +/- 7.7 kg; P 11) were similar in all treatment groups. CONCLUSION: Rimonabant 20 mg over 2 years promoted clinically relevant and durable weight loss and improvements in cardiometabolic risk factors

Skeletal muscle microvascular exchange capacity is associated with hyperglycaemia in subjects with central obesity

Aims: poor glycaemic control is associated with increased risk of microvascular disease in various organs including the eye and kidney, but the relationship between glycated haemoglobin (HbA1c) and microvascular function in skeletal muscle has not been described. We tested the association between HbA1c and a measure of microvascular exchange capacity (Kf) in skeletal muscle in people with central obesity at risk of developing Type 2 diabetes.Methods: microvascular function was measured in 28 women and 19 men [mean (± sd) age 51 ± 9 years] with central obesity who did not have diabetes. We estimated insulin sensitivity by hyperinsulinaemic–euglycaemic clamp, visceral and total fatness by magnetic resonance imaging, fitness (VO2 max by treadmill testing), physical activity energy expenditure [metabolic equivalents of tasks (METS) by use of the SenseWear Pro armband] and skeletal muscle microvascular exchange capacity (Kf) by venous occlusion plethysmography.Results: in regression modelling, age, sex and fasting plasma glucose accounted for 30.5% of the variance in HbA1c (r2 = 0.31, P = 0.001). Adding Kf to this model explained an additional 26.5% of the variance in HbA1c (r2 = 0.57, P = 0.0001 and Kf was strongly and independently associated with HbA1c (standardized B coefficient ?0.45 (95% confidence interval ?0.19, ?0.06), P = 0.001).Conclusions: we found a strong negative independent association between a measure of skeletal muscle microvascular exchange capacity (Kf) and HbA1c. Kf was associated with almost as much of the variance in HbA1c as fasting plasma glucos