Insulin, physical activity, and caloric intake in postmenopausal women: Breast cancer implications

Los Angeles Biomedical Research Institute at Harbor-UCLA, Torrance, CA 90502, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 11/2004; 22(22):4507-13. DOI: 10.1200/JCO.2004.04.119
Source: PubMed

ABSTRACT Increased physical activity and programs to reduce body mass index (BMI) with both increased physical activity and decreased caloric intake have been proposed to reduce insulin as a potential mediator of breast cancer and other chronic diseases. However, there are few data on the relative contribution of physical activity, caloric intake, and BMI to fasting insulin levels.
An ethnically diverse subsample of 2,996 mostly healthy postmenopausal women with no prior cancer history was randomly identified from the 161,809 participants in the Women's Health Initiative clinical trials and observational study. Information was collected on diet, recreational physical activity, and anthropometrics including BMI. Fasting insulin levels were determined. Using a cross-sectional design, insulin levels were then compared across quintiles of caloric intake and physical activity in linear regression model analyses controlled for BMI and other factors.
Lower BMI (P < .0001), higher levels of physical activity (P < .0001), and lower caloric intake (P < .02) were all independently associated with significantly lower mean fasting insulin levels throughout the range of observed values. Insulin levels of 8.74 microU/mL +/- 4.16 SD were seen in the highest physical activity and lowest caloric intake quintile compared with insulin levels of 15.08 microU/mL +/- 16.32 SD in the lowest physical activity and highest caloric intake quintile (P < .0001).
These findings suggest that reduction in BMI achieved by increasing physical activity, reducing caloric intake, or both, should lower insulin levels, providing support for clinical trials evaluating insulin level change and breast cancer risk.

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    • "They include lowering of the endogenous sex hormones levels (McTiernan et al., 2006; Coyle, 2008), leptin concentrations (Tworoger et al., 2007), enhancing immunity and reducing chronic inflammation (Wetmore and Ulrich, 2006; McTiernan, 2008). A reduced breast cancer risk among postmenopausal women with higher physical activity occupations as measured by either sitting time or job titles is biologically plausible because there is some evidence that a high intensity or long-lasting practice moderate physical activity is associated with a reduction of estradiol (Jasienska et al., 2006), androgen levels (Coyle, 2008) and enhanced sensitivity to insulin (Chlebowski et al., 2004). Exercise may also increase serum levels of sex hormone-binding globulin, which may reduce concentrations of estradiol, and by reducing estrogen bioavilability (Neilson et al., 2009). "
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    ABSTRACT: Epidemiological studies have shown that physical activity is a protective factor for breast cancer, although research findings are inconsistent regarding menopausal status. To determine the impact of occupational physical activity for breast cancer, a hospital-based case-control study was conducted in Poland in 2003-2007. In total, data on physical activity of 858 invasive breast cancer cases and 1,085 controls were analyzed. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Separate calculations were performed for premenopausal and postmenopausal women. Occupational physical activity was measured by sitting time and job titles. The risk estimates were controlled for potential risk factors and lifetime household and recreational activities. A significantly decreased breast cancer risk was found among postmenopausal women declaring physically active jobs (requiring more than 80% of time spent standing, walking) compared with those with low activity jobs (more than 80% of the working time spent in a sitting position, during workhours) (OR= 0.66; 95%CI 0.44-0.98, P trend= 0.03). A similar inverse association between occupational physical activity and breast cancer risk was also found when activity was evaluated according to job titles provided by subjects. Postmenopausal women with physically demanding jobs, in particular, had a lower risk compared to those in sedentary occupations (OR= 0.57; 95%CI 0.36-0.91, P trend= 0.02). These findings support observations from previous studies that sufficiently high occupational physical activity may reduce breast cancer risk, particularly among postmenopausal women.
    Asian Pacific journal of cancer prevention: APJCP 04/2009; 10(3):443-8. · 2.51 Impact Factor
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    • "Higher estrogen and lower levels of sex hormone-binding globulin are associated with heightened breast cancer risk in postmenopausal women [50]. Other potential mechanisms include the prevention of weight gain, regulation of insulin sensitivity, and alterations in immune function [51–54]. "
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    ABSTRACT: Several lifestyle factors play a significant role in determining an individual's risk of breast cancer. Many of them could be modified to protect against the malignancy. A nested case-control study was conducted to examine the association between selected lifestyle factors and non-BRCA-related breast cancer risk among French-Canadian women. Some 280 women with breast cancer and who were nongene carriers of mutated BRCA gene were recruited as cases. Another 280 women, without any cancer and nongene carriers of mutated BRCA gene served as controls. A tested lifestyle questionnaire was interviewer administered to incident cases to obtain information on weight history, smoking, physical activity, and other lifestyle risk factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in logistic regression models. Comparing cases to controls, breast cancer risk was higher among subjects who reached their maximum body mass index (BMI) at an older age (>50 years) (OR = 2.83; 95% CI: 2.34–2.91). A positive association was noted between breast cancer risk and weight gain of >34 lbs compared to weight gain of ≤15 lbs, since the age of 20 (OR = 1.68; 95% CI: 1.10–2.58). Weight gain of >24 lbs compared to weight gain of ≤9 lbs, since the age of 30 also resulted in the same relationship (OR = 1.96; 95% CI: 1.46–3.06). Similarly, since the age of 40, weight gain of >12 lbs compared to weight gain of ≤1 lb was associated with increased breast cancer risk (OR = 1.91; 95% CI: 1.53–2.66). Women who smoked >9 pack-years of cigarettes had a 59% higher breast cancer risk (P = .05). Subjects who engaged in >24.8 metabolic-equivalent- (MET-) hours per week compared to ≤10.7 MET-hours per week of moderate physical activity had a 52% (P = .01) decreased risk and total physical activity between 16.2 and 33.2 MET-hours per week compared to ≤16.2 MET-hours per week, resulted in a 43% (P = .05) lower risk of breast cancer. In conclusion, weight history did affect breast cancer risk. Moreover, smoking appeared to raise the risk, whereas moderate physical activity had a protective effect.
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    • "Another possible mediator in the relation between physical activity and breast cancer risk may be insulin (resistance). Several studies have shown inverse associations between physical activity and markers for insulin sensitivity independent of body size [41-45]. "
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    ABSTRACT: Physical activity has been associated with a decreased risk for breast cancer. The biological mechanism(s) underlying the association between physical activity and breast cancer is not clear. Most prominent hypothesis is that physical activity may protect against breast cancer through reduced lifetime exposure to endogenous hormones either direct, or indirect by preventing overweight and abdominal adiposity. In order to get more insight in the causal pathway between physical activity and breast cancer risk, we designed the Sex Hormones and Physical Exercise (SHAPE) study. Purpose of SHAPE study is to examine the effects of a 1-year moderate-to-vigorous intensity exercise programme on endogenous hormone levels associated with breast cancer among sedentary postmenopausal women and whether the amount of total body fat or abdominal fat mediates the effects. In the SHAPE study, 189 sedentary postmenopausal women, aged 50-69 years, are randomly allocated to an intervention or a control group. The intervention consists of an 1-year moderate-to-vigorous intensity aerobic and strength training exercise programme. Participants allocated to the control group are requested to retain their habitual exercise pattern. Primary study parameters measured at baseline, at four months and at 12 months are: serum concentrations of endogenous estrogens, endogenous androgens, sex hormone binding globuline and insuline. Other study parameters include: amount of total and abdominal fat, weight, BMI, body fat distribution, physical fitness, blood pressure and lifestyle factors. This study will contribute to the body of evidence relating physical activity and breast cancer risk and will provide insight into possible mechanisms through which physical activity might be associated with reduced risk of breast cancer in postmenopausal women.
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