Bone Microarchitecture and Obese Men
December 15, 2012
Obesity has long been considered to be “protective” against osteoporosis, largely due to mechanical loading and adipocyte-derived hormones. More recent evidence implicates the accumulation of abdominal and visceral fat with bone loss in middle-aged men. Obesity dysregulates the GH/IGF-1 and HPG axes, both of which are important regulators of bone homeostasis. Testosterone, which promotes bone mineral density (BMD) and muscle mass, is often reduced in obese men, whereas estrogen levels increase proportionally to body weight.
A recent study sought to determine hormonal and body composition predictors of bone microarchitecture in young and healthy men with abdominal obesity. The authors hypothesized that obese men with significant abdominal adiposity would have impaired bone microarchitecture and strength and increased bone marrow fat associated with dysregulation of the GH/IGF-1 and gonadal steroid axes. This cross-sectional study evaluated 35 men mean age 33.8 years and mean body mass index 36.5 kg/m2.
A high degree of visceral adipose tissue was found to be inversely associated with mechanical properties of bone, whereas bone marrow fat was inversely associated with cortical parameters. Free estradiol was positively correlated with total bone density and free testosterone was positively associated with trabecular thickness yet inversely associated with trabecular number.
The authors concluded that visceral adipose tissue and bone marrow fat are negative predictors and muscle mass is a positive predictor of bone microarchitecture and mechanical properties in obese men. Testosterone, estradiol, and GH are positive determinants of trabecular microarchitecture, and IGF-I is a positive determinant of cortical microarchitecture. This supports the notion that VAT is detrimental to bone and that decreased GH and testosterone, characteristic of male obesity, may exert deleterious effects on microarchitecture, whereas higher estradiol may be protective. Limitations of this study include a small number of test subjects, cross-sectional study design (limits ability to prove causality), and since the study was limited to obese men, the resultant data cannot be extrapolated to normal-weight men or women. Larger studies across male and female populations are necessary to draw more substantial conclusions regarding these relationships.
Reference: Bredella MA, Lin E, Gerweck, AV, et al. Determinants of bone microarchitecture and mechanical properties in obese men. J Clin Endo Metab 2012;97(11):4115-4122.
Prediction of Insulin Resistance via Anthropometric Measures
August 24, 2012
Obesity has reached epidemic proportions around the developed world, and the prevalence still seems to be steadily increasing. Great attention in recent years has focused on the prevalence of obesity in adolescents, relative to the potential risks of developing chronic diseases in adulthood. Recent focus on anthropometric measurements of obesity (e.g. waist circumference, body composition estimated via bioelectrical impedance analysis, estimations of body fat and skeletal muscle mass) has shifted attention to a homeostatic model assessment of insulin resistance (HOMA-IR).
A recent study conducted in New York aimed to determine the most accurate measurements to predict insulin resistance in both obese and non-obese subjects. Nearly 1300 predominantly Hispanic and African American subjects between 14 and 20 years of age (714 females and 584 males) were recruited and measured for body mass index; serum triglycerides, glucose and insulin, and HOMA-IR.
This study found that waist circumference combined with body fat percentage was the best predictor of HOMA-IR. While body mass index was found to be poor in predicting insulin resistance, the prospect of measuring body fat composition versus lean muscle mass in adolescents holds promise in detecting insulin resistance during this age range.
Most relevant to men's health, this model of prediction for males predicted a higher percentage of variance compared to females. The secondary conclusion of this study suggests that body fat composition has a higher likelihood of predicting HOMA-IR in leaner subjects. The authors admit that the lack of significant ethnic diversity may present a limitation in interpretation of results. In conclusion, body mass index is not sufficient for assessing insulin resistance, as waist circumference and body fat composition lend more accurate prediction of insulin resistance.
Reference: Wedin W, Diaz-Gimenez L, Convit AJ. Prediction of insulin resistance with anthropometric measure: lessons from a large adolescent population. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2012;5:219-225.
Vitamin D and Development of Metabolic Syndrome
July 23, 2012
To date, the relationship between serum 25-hydroxyvitamin D [25(OH)D] and metabolic syndrome has not been clearly validated, with respect to a prospective and predictive model. Several small retrospective trials have demonstrated a link between the 2 conditions, with an estimate that low baseline 25(OH)D was inversely associated with 10-year risk of future development of metabolic syndrome when adjusted for age, gender, smoking status, seasonal variation, and body habitus.
This trial evaluated 6,537 adults aged 25 years or older (42% men). The authors of this study concluded that after a 5-year follow-up, low serum 25(OH)D concentrations were associated with an increased risk of development of metabolic syndrome, increased abdominal waist circumference, serum triglycerides, fasting glucose, and insulin resistance. The incidence of metabolic syndrome was highest in subjects with the lowest quintiles of 25(OH)D (<18-23 ng/ml); odds ratio [OR] 1.41-1.74). For each 10-ng/ml decrease in 25(OH)D, the risk of developing metabolic syndrome at 5 years increased by 23% (OR – 1.22).
Interestingly, this study found an association between baseline serum 25(OH)D and the risk of developing metabolic syndrome persisted after adjusting for body mass index in overweight or obese people but disappeared after taking into account baseline insulin resistance. One limitation of this trial was that it did not evaluate serum parathyroid hormone levels, a potentially important cofactor in vitamin D metabolism.
Reference: Gagnon C, Lu ZX, Magliano DJ, et al. Low serum 25-hydroxyvitamin D is associated with increased risk of the development of the metabolic syndrome at five years: results from a national, population-based prospective study (The Australian Diabetes, Obesity and Lifestyle Study: AusDiab). J Clin Endocrinol Metab 2012;97:1953-1961.
Testosterone and Metabolic Syndrome
April 20, 2012
The relationship between serum testosterone (T) and the metabolic syndrome was examined in a systematic review of 20 manuscripts (13 cross sectional, 3 longitudinal and 4 randomized controlled studies). Consistent outcomes of these papers were presented and compared.
Metabolic Syndrome (MetS) is a cluster of risk factors including abdominal obesity, increased blood glucose and/or insulin resistance, dyslipidemia and hypertension. MetS is associated with a two-fold increase of 5-10 year risk of cardiovascular (CV) diseases and five-fold increase in risk for type 2 diabetes (T2DM). The presence of hypogonadism in men with MetS and erectile dysfunction (ED) is associated with a greater severity of symptoms of sexual dysfunction, other than ED. ED and male hypogonadism have been recently recognized as possible predictors of forthcoming metabolic diseases and CV events. ED subjects have been considered paradoxically “lucky” because this symptom might offer them the opportunity to screen for the presence of ED-associated morbidities, including hypogonadism.
The specific mechanism through which hypogonadism might affect CV health have not been completely clarified, but both clinical and animal evidence shows that T exerts a favorable effect upon vascular reactivity, inflammation, cytokine production and adhesion molecule expressions, as well as on serum lipid concentration and hemostatic factors. It has been speculated that the presence of hypogonadism and ED in subjects with MetS should alert clinicians that such people deserve a more intensive lifestyle changes at an early stage to delay progression to a higher risk category. Unfortunately, no study has specifically evaluated this point in subjects with ED, whereas only a few RCTs on the metabolic effect of T replacement therapy in subjects with MetS have been published.
MetS is significantly associated with an overall lower total testosterone (TT). This difference is more evident in studies conducted in subjects with ED than in those without. The association among MetS, hypogonadism and ED is well recognized; in fact the syndrome is highly prevalent in subjects with ED and low T. The specific mechanisms linking MetS and male hypogonadism have not been completely clarified. Low T could be considered one of the many adverse consequences of overweight and obesity. On the other hand, hypogonadism could contribute to the accumulation of excess fat and to the reduction of insulin sensitive muscular mass, thus establishing a vicious cycle. Insulin resistance has been recently considered the common pathogenic link between ED, MetS and male hypogonadism.
Reference: Corona G, Monami M, et al. Testosterone and metabolic syndrome. J Sex Med 2011;8:272-283.
Erectile Dysfunction and Metabolic Syndrome
December 12, 2010
A recent study conducted in Turkey aimed to determine potential factors affecting penile vascular flow and predictability of vascular flow in men with erectile dysfunction (ED). It has been well established that ED and coronary artery disease (CAD) share common pathophysiologic pathways, yet the relationship between metabolic syndrome and penile vascular flow in men with ED has not yet been evaluated.
One hundred sixty-three men with ED of mean age 51 years were evaluated, and completed the IIEF-5 (International Index of Erectile Function) questionnaire (mean score – 12). Metabolic syndrome was present in 46% of subjects. The aim of the study was to determine the relationship among penile Doppler ultrasonography, hypertension, obesity, fasting blood glucose, and cholesterol. The study found no significant correlation between arterial insufficiency andmetabolic syndrome, but did determine a significant correlation between penileveno-occlusive dysfunction and metabolic syndrome.
The authors concluded that penile Doppler ultrasonography may be useful in the evaluation of penile blood flow in men with metabolic syndrome and complaints of erectile dysfunction.
Reference: Koca O, Caliskan S, Ozturk MI, et al. Vasculogenic erectile dysfunction and metabolic syndrome. J Sexual Medicine 2010; 7:3997-4002.