This review focuses on the associations between testosterone, insulin resistance and metabolic syndrome in men. Testosterone deficiency may contribute to the development of the metabolic syndrome, especially to the accumulation of intra-abdominal (visceral) adipose tissue and insulin resistance. On the other hand, inflammatory and metabolic disorders associated with visceral intra-abdominal tissue contribute to the generation of hypogonadism. This review discusses some possible pathophysiological mechanisms underlying this vicious cycle. Some studies have suggested the use of testosterone substitution in order to prevent or attenuate metabolic syndrome. However, data on testosterone substitution are still controversial and larger controlled trials are needed to establish the population with the optimal benefit/risk ratio.

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Considering the well-accepted notion that abdominal obesity is more closely associated with cardiovascular disease risk than body weight, this epidemiological study examined the association of both general and abdominal obesity with the risk of death in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. During a mean follow-up of 9.7 years, 14,723 of the initial 359,387 participants died from various causes. After adjustment for body mass index (BMI), waist circumference and waist-to-hip ratio were highly associated with the risk of death and this association tended to be stronger among participants with a lower BMI, as compared with those who had a higher BMI. The current results highlight the importance of assessing the distribution of body fat even among persons of normal weight. The addition of waist circumference or waist-to-hip ratio to BMI more accurately stratified participants into higher-risk or lower-risk categories. These data suggest that both general and abdominal adiposity are associated with the risk of death and support the use of waist circumference or waist-to-hip ratio in addition to BMI to better assess the risk of obesity/abdominal obesity.

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The purpose of this study was to investigate the impact of 9 days of bed rest on in vivo insulin metabolism in 13 first-degree relatives (FDR subjects) of patients with type 2 diabetes and 20 control subjects. The results showed that bed rest caused a significant decrease in whole-body insulin sensitivity in both groups. FDR subjects exhibited hepatic insulin resistance prior to bed rest and a significant deterioration in response to physical inactivity which was not observed in control subjects. Moreover, FDR subjects showed reduced insulin secretion in relation to their degree of hepatic insulin resistance but not peripheral insulin resistance. These data confirm the serious adverse effects of physical inactivity on whole-body insulin action in healthy subjects with and without a positive family history of diabetes.

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This study compared two types of diet (low-carbohydrate vs. low-fat) on weight loss, insulin resistance and cardiovascular risk in 24 overweight/obese subjects in an 8-week randomized controlled trial. The two groups showed significant weight loss (>7%; p<0.01), with no difference between groups. The two diets had comparable effects on insulin sensitivity. However, there was a significant difference in systemic arterial stiffness between the diets suggesting a potentially negative effect of a low-carbohydrate diet on long-term vascular health.

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The major factors responsible for the obesity epidemic are an increased energy intake combined with reduced physical activity. The authors of the study wanted to determine the relative contributions of increased energy intake and reduced physical activity to the U.S. obesity epidemic. Using data from the National Health and Nutrition Examination Surveys (NHANES) for mean weights and the U.S. food supply for the per capita energy supply estimate, they predicted the changes in weight from the changes in estimated energy intakes in U.S. children and adults between the 1970s and 2000s. Body weight increases predicted from the equations were compared with weight increases measured in representative U.S. surveys over the same period. The predicted changes in weights derived from the equations suggest that increase in estimated energy intake is sufficient, by itself, to explain the increase in weight in the U.S. population. These data reinforce the fact that population approaches to reduce obesity should focus on energy intake.

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The purpose of this study was to investigate the association between the Mediterranean-style dietary pattern and metabolic syndrome. The Mediterranean-style dietary pattern score (MSDPS) was developed to characterize a Mediterranean-style dietary pattern in the prospective Framingham Heart Study Offspring Cohort. In this nondiabetic sample, an elevated MSDPS was associated with lower waist circumference (p<0.001), homeostasis model assessment-insulin resistance (p=0.02), fasting glucose (p=0.03), and triglycerides (p<0.001) as well as higher HDL cholesterol (p=0.02). Moreover, participants in the highest quintile category of the MSDPS had a lower incidence of metabolic syndrome compared to those in the lowest quintile category (38.5% compared with 30.1%; p=0.01). These data suggest that the adherence to a Mediterranean-style diet may protect against the development of the metabolic syndrome in Americans.

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This study sought to determine the impact of exercise on 24-hour fat oxidation and fat balance in lean sedentary, obese sedentary, and lean endurance-trained men and women. Twenty-four-hour energy expenditure and substrate oxidation rates were measured under sedentary (control) and exercise conditions while maintaining energy balance. The data showed that even in endurance-trained individuals, exercise did not increase 24-hour fat oxidation when subjects were studied in energy balance. Therefore, the authors suggest that the state of energy balance is an underappreciated factor when studying the effect of exercise on fat oxidation and probably body fat mass.

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This short communication addresses the emerging topic of the association between ceramides, inflammation and insulin resistance. This study reported a strong correlation between total plasma ceramide and serum interleukin-6 (IL-6) concentrations (r=0.59, p<0.0001) in a cross-sectional study of 33 patients with cardiovascular disease. Multivariate analysis revealed that circulating levels of ceramides and tumor-necrosis factor-α (TNF-α independently explained 41% of  the variation of IL-6 concentrations. The present results suggest that the link between ceramides, insulin resistance and inflammation could be related to the inflammatory marker IL-6 and that the proposed negative effect of IL-6 on insulin resistance could be mediated by ceramides.

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This article was accompanied by an editorial (Diabetologia 2009;52:2475-77) underlining the fact that these findings are concordant with a study reported earlier by Haus JM et al., who described a link between plasma ceramides concentrations, plasma TNF-α and insulin sensitivity. Moreover, the author suggests that several studies are needed to determine the biological relevance of plasma ceramides and their importance in terms of clinical endpoints.

This study derived from the Third National Health and Nutrition Examination Survey (NHANES III) examined the particular subgroup of obese individuals who are referred to as “metabolically normal” and compared their all-cause mortality risk with “metabolically abnormal obese” individuals. The data revealed that a metabolically normal obese individual was a very rare phenotype, representing 1.3% of the U.S. population. Moreover, obese individuals had an increased risk for all-cause mortality, irrespective of whether or not they had insulin resistance or a clustering of metabolic risk factors. Therefore, weight management is an important target for reducing morbidity and mortality in all obese individuals.

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The purpose of this study was to determine the impact of the metabolic syndrome on hs-C-reactive protein (CRP) levels in patients with and without a first acute coronary syndrome (ACS) event. The study group included 273 patients with a first ACS event and 261 controls. The present study showed that metabolic syndrome had a significant impact on hs-CRP elevation among patients with first ACS event. This finding was confirmed even when using different clinical criteria to identify the presence of the metabolic syndrome. These findings suggest that metabolic syndrome may predispose ACS patients to an exaggerated hs-CRP response during an ACS.

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The objective of this study was to determine the effect of exercise training on lipoprotein-lipids and an inflammatory profile in post-menopausal overweight/obese women. A total of 267 women from the Dose-Response to Exercise in post-menopausal Women (DREW) study were analyzed before and after a 6-month exercise training program and compared to a control group (n=82). The results from this prospective randomized exercise trial revealed that exercise training significantly increased cardiorespiratory fitness of healthy overweight/obese, post-menopausal women, but had no major impact on the cardiometabolic risk profile, probably because they were characterized by a low risk cardiometabolic profile at baseline.

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Obesity is a well-known cardiovascular risk factor in the general population, however studies have reported an inverse correlation between body mass index (BMI) and mortality in patients with cardiovascular disease. This association has been termed the “obesity paradox”. This retrospective study investigates the “obesity paradox” in a cohort of 529 patients with coronary artery disease registered in a cardiac rehabilitation and exercise training (CRET) program. In order to assess the impact of obesity on mortality in patients with coronary artery disease, a traditional index of obesity was used, BMI, as well as a more direct measure of adiposity such as percent body fat. Analyses with both measures revealed that total mortality was considerably lower in the baseline overweight/obese than in patients with baseline BMI <25 kg/m² (4.1% vs. 13.2%; p<0.001), as well as in those with high baseline fat compared with those with low fat (3.8% vs. 10.6%; p<0.01). Additionnal results also revealed marked improvements in overall coronary risk factors for the overweight and obese coronary patients with greater weight loss. These data suggest that purposeful weight loss in overweight and obese coronary patients is not harmful and can lead to marked improvements in coronary risk factors.

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In his comment, Fonarow GC (Am J Med 2009;122:1069) recognized the importance of determining whether weight loss should be recommended as a therapeutic goal in overweight and obese patients with coronary artery disease. However, he pointed out the substantial bias concerning the design of the study because all patients who were overweight or obese were advised to lose weight. Consequently the comparison was between the responders and the non responders. He therefore proposed prospective randomized clinical trials to address this important question.

This prospective cohort study of 20,757 men investigated the independent and joint associations between vigorous activity and body mass index (BMI) on diabetes risk in men. When BMI and physical activity were analyzed jointly, results showed that diabetes risk was most strongly related to increasing BMI and comparatively less influenced by activity. Even among active participants, increasing BMI was strongly associated with increased diabetes risk. The risk from elevated BMI was modestly but significantly reduced by weekly physical activity in normal weight and overweight men. The risk attenuation among obese men was observed only when the frequency of vigorous activity reached ≥5 times weekly. These data underscore the important association between obesity and diabetes.

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This prospective study tested interventions directed at 32 physicians and 574 patients over an 18-month time period aiming at lowering blood pressure. The physician interventions included Internet-base learning, self-monitoring, and quarterly feedback reports. For the patients, the intervention included 20 weekly group sessions over 6 months, followed by 12 monthly telephone counseling contacts. The Hypertension improvement project (HIP) trial showed that the main effect of the patient intervention was -2.6 mm Hg (95% CI: -4.4 to -0.7; p=0.01) which was explained by the adoption of a healthy dietary pattern and weight loss. The intervention for the physician alone did not lead to better blood pressure management. The key finding of the trial was that the largest impact on blood pressure was observed with the combination of both interventions. However, difference between treatment groups did not persist at 18 months. 

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In her comment, Taler SJ (Hypertension 2009;54:1202-03) qualified this study as important since lifestyle modification interventions are associated with a reduction in blood pressure. She also pointed out the importance of interventions on both the physician and patients. She concluded by stating that the success of a lifestyle modification intervention in patients with elevated blood pressure requires the right techniques but also motivation.

This study examined the role of leptin in obesity-related higher blood pressure (BP) in Japanese Americans living in Hawaii (88 men and 94 women) and Japanese in Japan (123 men and 111 women). Using 2 population samples of common genetic background, diverse lifestyles and with a wide range of body mass index (BMI), the results showed that BMI, systolic BP, diastolic BP increased significantly across quartiles of leptin for both sexes and sites (p<0.01 to 0.02). Additionnal analyses revealed that BMI and log-leptin were significantly and independently related to systolic BP and diastolic BP. Therefore the authors suggest that leptin may be an independent mediator for obesity-related elevations in BP.

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This study investigated whether the anti-inflammatory effects of statins may be of benefit in heart failure, a condition characterized by inflammation in which the relationship between cholesterol and cardiovascular outcomes is reversed. This retrospective analysis from the CORONA clinical trial revealed that the effect of rosuvastatin in patients with heart failure was different according to baseline hs-C-reactive protein (CRP) concentration. For instance, patients with hs-CRP ≥2.0 mg/l presented better outcomes when treated with rosuvastatin. A prospective randomized trial is therefore needed to confirm this apparent therapeutic effect of statins in patients with heart failure and elevated CRP.

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This article describes the development of an assessment tool to predict global vascular risk in multiethnic individuals by including behavioral and anthropometric factors. They developed this prediction tool with the NOMAS (Northern Manhattan Study) cohort which is a prospective, population-based cohort of 2,737 community participants free of stroke and coronary artery disease with a follow-up period of approximately 9 years. The results showed a better prediction of global vascular risk (stroke, myocardial infarction, vascular death) by adding behavioral risk factors (alcohol consumption and physical activity) as well as waist circumference to the traditional cardiovascular profile. The authors highlighted the fact that waist circumference was a better predictor of risk than the body mass index and that the use of continuous variables rather than categorical classifications (fasting blood sugar instead of diabetes, blood pressure instead of hypertension) allowed a more precise risk assessment. The NOMAs score was developed from a multiethnic cohort including African-American and Hispanic individuals. The authors suggest that this global vascular risk score could improve primary prevention strategies for cardiovascular disease and stroke.

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In order to clarify important notions concerning the assessment of major lipids and apolipoproteins for the prediction of vascular risk, a large collaboration between several investigators studying this question was established which allowed the pooling of one hundred and twelve prospective studies of cardiovascular risk factors, involving a total of 1.2 million participants. The present paper including more than 300,000 individuals revealed that there was no difference in hazard ratios between non-HDL cholesterol or HDL cholesterol versus apolipoprotein B and A1 and that the feeding status did not influence the relationship between lipids and vascular diseases. Moreover, concentrations of HDL cholesterol and non-HDL cholesterol were both strongly associated, in opposite directions, with CHD risk. These results suggest that the measurement of either total and HDL cholesterol levels or apolipoproteins is the simplest way to assess vascular disease without the need to fast and without consideration for triglycerides.

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This study determined the effects of a physically inactive vs active lifestyle on high-risk (intra-abdominal (visceral), liver and intramuscular) fat in 16 (7 monozygotic and 9 dizygotic) middle-aged same-sex twin pairs with long-term discordance for physical activity habits. At baseline (1975), the active co-twins practiced more leisure-time activity than the inactive co-twins (p<0.0001), but they were no different in anthropometrics or work-related physical activity. Over the follow-up of 30 years, a significant difference in leisure-time activity persisted between the active and inactive co-twins and the inactive co-twins were less fit compared to their active co-twins. However, the most noticeable difference was in body fat distribution measured by magnetic resonance imaging. The physically inactive co-twins had 50% greater intra-abdominal fat area compared with the active co-twins. The liver fat score was 170% higher and the intramuscular fat area 54% higher among the inactive co-twins. This prospective study demonstrated that habitual physical activity could possibly prevent accumulation of high-risk fat such as intra-abdominal and ectopic adipose tissue, even after controlling for genetic liability. These results support the concept of preventing and targeting obesity by long-term maintenance of leisure-time physical activity.

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In this article, the authors examined whether physical activity predicted cardiovascular disease (CVD) independently of well-known cardiometabolic risk factors in men and women. The study included 5,882 adults from the 1999 to 2004 United States National Health and Nutrition Examination Survey. The participants were divided according to the volume of their moderate-to-vigorous intensity physical activity: active (≥150 min./week), somewhat active (30 to 149 min./week), and inactive (<30 min./week). Inactive participants were 52% more likely compared to active participants to have CVD (p<0.05) after adjustment for the basic confounding variables. Both physical activity and cardiometabolic risk factors were independent predictors of CVD (P_trend<0.0001). These results suggest that physical activity is associated with CVD, independent of the common cardiometabolic risk factors, in both men and women.

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