Metabolic syndrome, insulin resistance, and sedentary behavior among overweight and obese breast cancer survivors

Introduction: Over half of breast cancer survivors living in the United States are overweight or obese at the time of their diagnosis. Metabolic syndrome (MetS) is a clustering of risk factors linked to insulin resistance that has important long-term health implications for breast cancer survivors. Fasting insulin is associated with breast cancer recurrence and death; however, postprandial measures may be better indicators of insulin resistance among breast cancer survivors. Weight management through diet and physical activity play an important role in improving insulin sensitivity and MetS in the general population, but less is known about these effects among breast cancer survivors. Furthermore, sedentary behavior is a growing problem among the general population and breast cancer survivors alike. Little research has been done to determine effective ways to reduce sedentary behavior and barriers to sitting less are not well understood. The goals of this project were to 1) assess the impact of weight loss and weight loss maintenance on components of MetS among obese and overweight breast cancer survivors, 2) determine relationships between changes in dietary and physical activity variables and changes in the components of MetS, 3) examine changes in fasting and postprandial glucose and insulin, and measures of insulin resistance following the same weight management intervention among breast cancer survivors, 4) determine if change in weight, dietary intake or physical activity are predictors of improvements in insulin sensitivity after a weight management intervention, 5) assess barriers to reduce sedentary behavior within a weight maintenance intervention among breast cancer survivors. Methods: Twenty-four obese and overweight women were recruited and enrolled in a 10 month weight management intervention and 22 participants completed the study. Phase one (baseline - 4 months) focused on weight loss through reduced caloric intake and increased physical activity. Phase two (4 months - 10 months) focused on weight loss maintenance. During phase two, participants were randomized to receive our standard weight loss maintenance program (MAINT) or to the same weight maintenance program with an added intervention aimed to reduce sedentary behavior (MAINT + SED). The MAINT + SED received technology-based tools for tracking weight, diet and physical activity. Assessment visits took place at baseline, 4 months and 10 months. At each time point, anthropometric measurements were completed and fasting blood samples were collected. Participants were fed a standardized meal at each time point and five subsequent blood samples were collected at 30 minutes, 45 minutes, 60 minutes, 90 minutes, and 120 minutes post meal. MetS components (waist circumference, blood pressure, high density lipoprotein cholesterol (HDL-C), triglycerides, fasting glucose), fasting insulin, postprandial insulin as measured by total area under the curve and positive incremental area under the curve (AUC and iAUC), glucose (AUC and iAUC), and two surrogate measures of insulin resistance (HOMA-IR and Matsuda Index) were analyzed and/or calculated at baseline, 4 months and 10 months. Self reported measures of diet (24 hour dietary recalls), moderate to vigorous physical activity (MVPA) (Modifiable Activity Questionnaire) and sedentary time (Multi-context Sitting Time Questionnaire) were assessed at each time point. Qualitative surveys based on the Theory of Planned Behavior were administered to participants in MAINT + SED to assess perceived barriers to reducing sitting time and satisfaction of technology. Results: After phase one, participants lost a mean of 10.7% +/- 3.9% of their baseline weight and significantly reduced their waist circumference (-7.03 cm), fasting glucose (-7.14 mg/dl), triglycerides (-22.23 mg/dl) and HDL-C (-5.59 mg/dl). From baseline to 4 months, fasting insulin decreased (-5.66 mU/l), postprandial insulin (AUC and iAUC) decreased by 32% and 28% respectively, and insulin sensitivity significantly improved, as evidenced by a 47% decrease in HOMA-IR and a 44% increase in Matsuda Index. The participants who lost the greatest percent of baseline weight at 4 months had the greatest decreases in waist circumference (r=0.67), decreases in percent calories from fat (r=0.52) and increases in fruit and vegetable intake( r=-0.54). During phase two, participants successfully maintained their weight loss and waist circumference further decreased (-2.76 cm) and HDL-C increased (+11.82 mg/dl). Postprandial insulin (AUC and iAUC), HOMA-IR, and Matsuda Index scores did not significantly change from 4 to 10 months. Dietary changes, MVPA changes and sedentary time changes were not predictive of changes in fasting insulin or changes in insulin sensitivity. Percent weight loss from baseline to 10 months was not significantly related to changes in fasting insulin (r=0.32) or HOMA-IR (r=0.27) from baseline to 10 months. However, changes in Matsuda Index scores were correlated with percent weight loss from baseline to 10 months (r=-0.545). Furthermore, participants in the MAINT + SED arm were not able to successfully reduce their sedentary time during the maintenance phase. Perceived barriers to reducing sitting time included perceived lack of control over changing their sitting behaviors at the workplace. Conclusion: The 10 month weight management intervention successfully improved components of metabolic syndrome and insulin sensitivity among overweight and obese breast cancer survivors. Reducing sedentary time within a weight maintenance intervention was unsuccessful and the most important perceived barriers were workplace activities. Future interventions should focus on identifying effective lifestyle strategies to alleviate metabolic syndrome and insulin resistance among breast cancer survivors on a larger scale. Feasible strategies to reduce sedentary time should also be identified in this high-risk group.