[show abstract][hide abstract] ABSTRACT: Bone mineral density (BMD) is a biomarker for cumulative exposure to multiple factors including estrogen, calcium, vitamin D and physical activity, which have all been independently associated with colorectal cancer. Furthermore, higher levels of BMD have been inversely associated with colorectal cancer risk, particularly in postmenopausal women. However, no prior studies have examined the potential association between BMD and colorectal adenomas, which are precursor lesions to most colorectal cancers. Therefore, we evaluated the association between BMD, which was measured using a whole body, dual-energy X-ray absorptiometry scan and colorectal adenomas in 167 patients who underwent colonoscopy screening. We found that patients in the highest tertile of total body BMD (>1.294 g/cm(2)) and in the middle tertile (≥1.167 to ≤1.294 g/cm(2)) compared to those with a total body BMD in the lowest tertile (<1.167 g/cm(2)) had a lower risk of colorectal adenomas (highest vs. lowest tertile: OR = 0.29 (0.10-0.84); middle vs. lowest tertile: OR=0.26 (0.08-0.80); p-trend=0.02). Stratification by gender revealed that this association was more pronounced in women (highest (>1.280 g/cm(2)) vs. lowest (<1.130 g/cm(2)) tertile: OR=0.08 (0.01-0.70); middle (≥1.130 to ≤1.280 g/cm(2)) vs. lowest tertile: OR=0.15 (0.04-0.94); p-trend=0.02) even after excluding hormone replacement therapy users (highest (>1.295 g/cm(2)) and middle (≥1.132 to ≤1.295 g/cm(2)) vs. lowest (<1.132 g/cm(2)) tertile: OR=0.17 (0.03-0.97); p-trend=0.04). Our results show, for the first time, that BMD is inversely associated with colorectal adenomas, particularly in women. Although additional larger, prospective studies are needed, our results suggest that BMD may be a biomarker for colorectal cancer precursor lesions.
International Journal of Cancer 08/2011; 129(4):956-64. · 6.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: High-molecular weight (HMW) adiponectin is the biologically active form of adiponectin and is related to enhanced insulin sensitivity and metabolic function. Previously, we found that 7 d of exercise improves insulin sensitivity in obese subjects; however, whether short-term exercise training affects HMW adiponectin in obese persons is unknown.
We examined the effect of seven consecutive days of supervised vigorous exercise (60 min · d(-1), 85% HRmax) on HMW adiponectin and leptin secretion in 17 obese individuals (age = 55 ± 3 yr; body mass index = 33.7 ± 0.9 kg · m(-2)). Insulin sensitivity was calculated from an oral glucose tolerance test (ISIOGTT) using the Matsuda Index. Fasting plasma HMW adiponectin and leptin were quantified from blood samples obtained before the ISIOGTT. Glucose and insulin measures were obtained before and every 30 min during the test. Dual-energy x-ray absorptiometry was used to determine body composition, and indirect calorimetry was used to assess fat oxidation.
After the intervention, there was a significant increase in HMW adiponectin (3202 ± 543 vs 3878 ± 682 ng · mL(-1), P = 0.02) and a decrease in leptin (36.8 ± 5.1 vs 31.1 ± 4.2 μg · mL(-1), P = 0.03). Further, we observed an increase in ISIOGTT (1.7 ± 0.3 vs 2.1 ± 0.3, P = 0.04) and a decrease in glucose area under the curve (30,871 ± 2105 vs 28,469 ± 1657 mg · dL(-1) for 3 h, P = 0.01). The increase in HMW adiponectin was positively associated with the increase in basal fat oxidation (r = 0.57, P = 0.03), consistent with an improvement in adipose tissue metabolic function.
The data suggest that 7 d of exercise is sufficient not only to improve insulin sensitivity and fat oxidation but also to favorably alter adipokine secretion, independent of changes in body weight or composition.
Medicine and science in sports and exercise 06/2011; 44(1):69-74. · 3.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: Low-glycemic index diets and exercise independently improve glucose tolerance and reduce diabetes risk. However, the combined effect of a low-glycemic index diet and exercise on inflammation and glucose metabolism is not known. Therefore, we randomized 28 insulin-resistant adults (age: 66 ± 1 y; BMI: 34.2 ± 0.7 kg · m(-2)) to a 12-wk, low (LGI = 40) or high- (HGI = 80) glycemic index diet plus aerobic exercise (5 d · wk(-1), 60 min · d(-1), 80-85% heart rate(max)) intervention. All food and fluids were provided during the study. Inflammation was assessed from cytokine (TNFα and IL-6) secretion using peripheral blood mononuclear cells (MNC) stimulated overnight with LPS. Glycemic response was determined following ingestion of a 75-g glucose solution. Fasting blood samples were collected for additional cytokine [TNFα, IL-6, and monocyte chemoattractant protein 1 (MCP-1)] analysis. Both interventions decreased BMI (P < 0.001), fasting plasma glucose (P = 0.01), and insulin (P = 0.02). The glycemic response was reduced only in the LGI group (P = 0.04). Plasma and MNC-derived TNFα secretion were reduced in the LGI group (P = 0.02) but increased in the HGI group (P = 0.02). Secretion of IL-6 from MNC and plasma IL-6 and MCP-1 concentrations were reduced in the LGI group. The change in MNC-derived TNFα (r = 0.43; P = 0.04) and plasma MCP-1 (r = 0.44; P = 0.04) correlated with decreases in the glycemic response. These data highlight the importance of diet composition in the treatment and prevention of inflammation and hyperglycemia. A low-glycemic index diet has antiinflammatory and antidiabetogenic effects when combined with exercise in older, obese prediabetics.
Journal of Nutrition 06/2011; 141(6):1089-94. · 4.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is a rapidly emerging chronic liver disease and is reported to affect up to 70-80% of overweight and obese individuals. NAFLD represents a spectrum of liver diseases that range from simple hepatic steatosis, to a more severe and treatment resistant stage that features steatosis plus inflammation, termed nonalcoholic steatohepatitis (NASH), which may in turn progress to hepatic fibrosis, cirrhosis, and sub-acute liver failure. Thus, NAFLD and its subsequent complications create a significant health burden, and currently there is no effective treatment strategy. The biochemical mechanisms that underlie NAFLD are unclear at this time, but there is evidence that insulin resistance is a major contributing factor. In addition, circulating concentrations of inflammatory cytokines (e.g., TNF-alpha, IL-6) as well as decreased antiinflammatory factors (e.g., adiponectin, IL-10) are not only implicated in the development of insulin resistance and type 2 diabetes, but are also related to NAFLD. Such inflammatory mechanisms are fundamental in the progression of NAFLD toward higher risk cirrhotic states. This review outlines the leading theories of pathogenesis of NAFLD and highlights the potential role of exercise in treating and preventing NAFLD. Regular exercise can reverse insulin resistance, suppress low-grade systemic inflammation, and attenuate inflammatory markers associated with NAFLD. Thus, exercise has the potential to become an effective treatment and prevention modality for NAFLD and NASH.