Relationships Among Physical Activity, Sleep, and Cancer-related Fatigue: Results From the International ColoCare Study.

BACKGROUND: Risk factors for cancer-related fatigue are understudied in colorectal cancer. PURPOSE: This study aimed to address this critical gap in the literature by (a) describing changes in colorectal cancer-related fatigue and health behavior (physical activity, sleep problems) and (b) examining if physical activity and sleep problems predict fatigue trajectories from baseline (approximately at the time of diagnosis), to 6- and 12 months after enrollment. METHODS: Patients participating in the international ColoCare Study completed self-report measures at baseline (approximately time of diagnosis), 6-, and 12 months assessing physical activity using the International Physical Activity Questionnaire (IPAQ) and fatigue and sleep using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). Mixed-effect models examined changes in physical activity, sleep problems, and fatigue. Cross-lagged panel models examined bidirectional relationships between physical activity or sleep and fatigue across time. RESULTS: Colorectal cancer patients (n = 649) had a mean age of 61 ± 13 years. Most were male (59%), non-Hispanic White (91%), diagnosed with Stages III-IV (56%) colon cancer (58%), and treated with surgery (98%). Within-person cross-lagged models indicated higher physical activity at Month 6 was associated with higher fatigue at Month 12 (ß = 0.26, p = .016). When stratified by cancer stage (I-II vs. III-IV), the relationship between physical activity at Month 6 and fatigue at Month 12 existed only for patients with advanced cancer (Stages III and IV, ß = 0.43, p = .035). Cross-lagged associations for sleep and fatigue from baseline to Month 6 were only observed in patients with Stages III or IV cancer, however, there was a clear cross-sectional association between sleep problems and fatigue at baseline and Month 6. CONCLUSIONS: Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced colorectal cancer the first year after diagnosis. In addition, sleep problems were consistently associated with higher fatigue in the first year, regardless of cancer stage. TRIAL REGISTRATION: The international ColoCare Study was registered on clinicaltrials.gov, NCT02328677, in December 2014.

Within-person and cross-lagged association models suggest fatiguability may become increasingly problematic for patients with advanced (Stages III and IV) colorectal cancer the first year after diagnosis.

Associations of combined physical activity and body mass index groups with colorectal cancer survival outcomes.

BACKGROUND: Physical activity and BMI have been individually associated with cancer survivorship but have not yet been studied in combinations in colorectal cancer patients. Here, we investigate individual and combined associations of physical activity and BMI groups with colorectal cancer survival outcomes. METHODS: Self-reported physical activity levels (MET hrs/wk) were assessed using an adapted version of the International Physical Activity Questionnaire (IPAQ) at baseline in 931 patients with stage I-III colorectal cancer and classified into 'highly active' and'not-highly active'(≥ / < 18 MET hrs/wk). BMI (kg/m2) was categorized into 'normal weight', 'overweight', and 'obese'. Patients were further classified into combined physical activity and BMI groups. Cox-proportional hazard models with Firth correction were computed to assess associations [hazard ratio (HR), 95% profile HR likelihood confidence interval (95% CI) between individual and combined physical activity and BMI groups with overall and disease-free survival in colorectal cancer patients. RESULTS: 'Not-highly active' compared to 'highly active' and 'overweight'/ 'obese' compared to 'normal weight' patients had a 40-50% increased risk of death or recurrence (HR: 1.41 (95% CI: 0.99-2.06), p = 0.03; HR: 1.49 (95% CI: 1.02-2.21) and HR: 1.51 (95% CI: 1.02-2.26), p = 0.04, respectively). 'Not-highly active' patients had worse disease-free survival outcomes, regardless of their BMI, compared to 'highly active/normal weight' patients. 'Not-highly active/obese' patients had a 3.66 times increased risk of death or recurrence compared to 'highly active/normal weight' patients (HR: 4.66 (95% CI: 1.75-9.10), p = 0.002). Lower activity thresholds yielded smaller effect sizes. CONCLUSION: Physical activity and BMI were individually associated with disease-free survival among colorectal cancer patients. Physical activity seems to improve survival outcomes in patients regardless of their BMI.

Association of Telomere Length with Colorectal Cancer Risk and Prognosis: A Systematic Review and Meta-Analysis.

(1) Background: Colorectal cancer risk and survival have previously been associated with telomere length in peripheral blood leukocytes and tumor tissue. A systematic review and meta-analysis of the literature was conducted. The PubMed, Embase, and Web of Science databases were searched through March 2022. (2) Methods: Relevant studies were identified through database searching following PRISMA guidelines. Risk estimates were extracted from identified studies; meta-analyses were conducted using random effects models. (3) Results: Fourteen studies were identified (eight on risk; six on survival) through systematic review. While no association was observed between circulating leukocyte telomere length and the risk of colorectal cancer [overall OR (95% CI) = 1.01 (0.82-1.24)], a worse survival for those with shorter telomeres in leukocytes and longer telomeres in tumor tissues was observed [Quartile1/Quartile2-4 overall HR (95% CI) = 1.41 (0.26-7.59) and 0.82 (0.69-0.98), respectively]. (4) Conclusions: Although there was no association with colorectal cancer risk, a poorer survival was observed among those with shorter leukocyte telomere length. Future larger studies evaluating a potentially non-linear relationship between telomeres and colorectal cancer are needed.

Associations of Individual and Combined Physical Activity and Body Mass Index Groups with Proinflammatory Biomarkers among Colorectal Cancer Patients.

BACKGROUND: Physical activity and obesity are well-established factors of colorectal cancer risk and prognosis. Here, we investigate associations of individual and combined physical activity and body mass index (BMI) groups with proinflammatory biomarkers in colorectal cancer patients. METHODS: Self-reported physical activity levels were classified as "active" (≥8.75 MET-hours/week) versus "inactive" (<8.75 MET-hours/week) in n = 579 stage I-IV colorectal cancer patients enrolled in the ColoCare Study. BMI [normal weight (≥18.5-<25 kg/m2), overweight (≥25-<30 kg/m2), and obese (≥30 kg/m2)] was abstracted from medical records. Patients were classified into four combinations of physical activity levels and BMI. Biomarkers [C-reactive protein (CRP), SAA, IL6, IL8, and TNFα] in presurgery serum samples were measured using the Mesoscale Discovery Platform. Regression models were used to compute relative percent differences in biomarker levels by physical activity and BMI groups. RESULTS: "Inactive" patients had non-statistically significant higher IL6 levels compared with "active" patients (+36%, P = 0.10). "Obese" patients had 88% and 17% higher CRP and TNFα levels compared with "normal weight" patients (P = 0.03 and 0.02, respectively). Highest CRP levels were observed among "overweight or obese/inactive" compared with "normal weight/active" patients (P = 0.03). CONCLUSIONS: We provide evidence of associations between individual and combined physical activity and BMI groups with proinflammatory biomarkers. Although BMI was identified as the key driver of inflammation, biomarker levels were higher among "inactive" patients across BMI groups. IMPACT: This is the largest study in colorectal cancer patients investigating associations of energy balance components with inflammatory biomarkers. Our results suggest that physical activity may reduce obesity-induced inflammation in colorectal cancer patients and support the design of randomized controlled trials testing this hypothesis.

Factors associated with changes in exercise behaviors during the COVID-19 pandemic.

PURPOSE: There is limited information on how the COVID-19 pandemic has changed health behaviors among cancer patients. We examined changes in exercise behaviors since the pandemic and identified characteristics associated with these changes among cancer patients. METHODS: Cancer patients (n = 1,210) completed a survey from August to September 2020 to assess COVID-19 pandemic-related changes in health behaviors and psychosocial factors. Patients were categorized into three groups: exercising less, exercising did not change, and exercising more. Patient characteristics were compared by exercise groups. RESULTS: One-third of the patients reported a decreased amount of regular exercise, while 10% reported exercising more during the pandemic. Patients who exercised less were more likely to be unemployed/retired and have poor health status and psychosocial stressors such as disruptions in daily life while less likely to be former smokers (all p < 0.05). In contrast, patients who exercised more were younger, had stage IV diagnosis, and also reported disruptions in daily life (all p < 0.05). Patients who were living in rural areas were also more likely not to experience changes in exercise habits (all p < 0.05), although rural-urban status was not identified as a strong predictor. CONCLUSION: A significant proportion of cancer patients experienced changes in exercise habits, especially exercising less, during the first 6 months of the COVID-19 pandemic. Age, employment status, tumor stage, health status, smoking status, and psychosocial factors were associated with changes in exercise behaviors. Our results highlight the importance of promoting physical activity guidelines for cancer survivorship during the COVID-19 pandemic and may help improve the identification of cancer patients susceptible to exercising less.

Insulin resistance and weight gain in women treated for early stage breast cancer.

PURPOSE: Both weight gain and insulin resistance have been associated with poorer prognosis in women receiving adjuvant therapy for early stage breast cancer, however, interactions between weight gain and insulin resistance have not been explored longitudinally throughout the breast cancer treatment continuum. METHODS: One hundred non-diabetic women with early stage breast cancer receiving adjuvant chemotherapy and /or hormonal therapy were enrolled in this prospective, observational study. Metrics of weight, body composition (BMI, waist/hip circumference ratio (WHR)), and cardiometabolic health (fasting insulin, glucose and triglycerides) were obtained prior to adjuvant therapy (baseline) and repeated 6, 12, and 24 months post-diagnosis. Insulin resistance was calculated using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). RESULTS: Complete data were available for 95 participants. Compared to baseline, body weight was significantly higher at the 12-month time-point (75.3 ± 15.7 vs. 76.2 ± 16.7, p = 0.03), however there was no difference in waist circumference (p = 0.96) or WHR (p = 0.52). HOMA-IR tended to increase 6 months after diagnosis (2.36 ± 2.17 vs. 2.70 ± 2.83, p = 0.06), largely driven by adverse responses in patients treated with chemotherapy (mean change + 0.53 (chemotherapy) vs - 0.64 (no chemotherapy), p = 0.005). Despite 12-month weight gain, the 6-month increase in HOMA-IR was fully abrogated 12 months after diagnosis. CONCLUSION: Breast cancer patients experience small but significant weight gain in the year following diagnosis, and those who receive chemotherapy experience significant short-term metabolic impairments suggestive of insulin resistance. While the acute insulin resistance appears to attenuate over time, the long-term ramifications are unclear and may help explain weight gain in this population.

Impact of the COVID-19 pandemic on exercise habits among cancer patients.

Purpose There is limited information on how the COVID-19 pandemic has changed health behaviors among cancer patients. We examined the impact of the pandemic on changes in exercise behaviors and identified characteristics associated with these changes among cancer patients. Methods Cancer patients (n = 1,361) completed a survey from August-September 2020 to assess COVID-19 pandemic-related changes in health behaviors and psychosocial factors. Patients were categorized into 3 groups: exercising less, exercising did not change, and exercising more. Patient characteristics were compared by exercise groups. Results One-third of the patients reported a decreased amount of regular exercise, while 11% reported exercising more during the pandemic. Patients who exercised less were more likely to be unemployed/retired, undergoing active treatment, and had increased pandemic-related alcohol consumption and psychosocial stressors such as loneliness and financial stress (all p < 0.05). In contrast, patients who exercised more were younger, female, full-time employed, did not consume alcohol, and had good health status and more social interactions (all p < 0.05). Patients who were living in rural areas and did not experience changes in daily life, were also more likely not to experience changes in exercise habits (all p < 0.05). Conclusion Our results indicate that a significant proportion of cancer patients experienced changes in exercise habits during the first 6 months of the COVID-19 pandemic. Age, sex, employment status, health status, alcohol consumption, and psychosocial factors were associated with changes in exercise behaviors. Providers should monitor for changes in health behaviors, such as exercise, because of their importance in improving cancer survivorship.

Understanding the Prevalence of Prediabetes and Diabetes in Patients With Cancer in Clinical Practice: A Real-World Cohort Study.

BACKGROUND: This study aimed to understand the prevalence of prediabetes (preDM) and diabetes mellitus (DM) in patients with cancer overall and by tumor site, cancer treatment, and time point in the cancer continuum. METHODS: This cohort study was conducted at Huntsman Cancer Institute at the University of Utah. Patients with a first primary invasive cancer enrolled in the Total Cancer Care protocol between July 2016 and July 2018 were eligible. Prevalence of preDM and DM was based on ICD code, laboratory tests for hemoglobin A1c, fasting plasma glucose, nonfasting blood glucose, or insulin prescription. RESULTS: The final cohort comprised 3,512 patients with cancer, with a mean age of 57.8 years at cancer diagnosis. Of all patients, 49.1% (n=1,724) were female. At cancer diagnosis, the prevalence of preDM and DM was 6.0% (95% CI, 5.3%-6.8%) and 12.2% (95% CI, 11.2%-13.3%), respectively. One year after diagnosis the prevalence was 16.6% (95% CI, 15.4%-17.9%) and 25.0% (95% CI, 23.6%-26.4%), respectively. At the end of the observation period, the prevalence of preDM and DM was 21.2% (95% CI, 19.9%-22.6%) and 32.6% (95% CI, 31.1%-34.2%), respectively. Patients with myeloma (39.2%; 95% CI, 32.6%-46.2%) had the highest prevalence of preDM, and those with pancreatic cancer had the highest prevalence of DM (65.1%; 95% CI, 57.0%-72.3%). Patients who underwent chemotherapy, radiotherapy, or immunotherapy had a higher prevalence of preDM and DM compared with those who did not undergo these therapies. CONCLUSIONS: Every second patient with cancer experiences preDM or DM. It is essential to foster interprofessional collaboration and to develop evidence-based practice guidelines. A better understanding of the impact of cancer treatment on the development of preDM and DM remains critical.

Fusobacterium nucleatum and Clinicopathologic Features of Colorectal Cancer: Results From the ColoCare Study.

BACKGROUND: Fusobacterium nucleatum (Fn), a bacterium associated with a wide spectrum of infections, has emerged as a key microbe in colorectal carcinogenesis. However, the underlying mechanisms and clinical relevance of Fn in colorectal cancer (CRC) remain incompletely understood. PATIENTS AND METHODS: We examined associations between Fn abundance and clinicopathologic characteristics among 105 treatment-naïve CRC patients enrolled in the international, prospective ColoCare Study. Electronic medical charts, including pathological reports, were reviewed to document clinicopathologic features. Quantitative real-time polymerase chain reaction (PCR) was used to amplify/detect Fn DNA in preoperative fecal samples. Multinomial logistic regression was used to analyze associations between Fn abundance and patient sex, age, tumor stage, grade, site, microsatellite instability, body mass index (BMI), alcohol consumption, and smoking history. Cox proportional hazards models were used to investigate associations of Fn abundance with overall survival in adjusted models. RESULTS: Compared to patients with undetectable or low Fn abundance, patients with high Fn abundance (n = 22) were 3-fold more likely to be diagnosed with rectal versus colon cancer (odds ratio [OR] = 3.01; 95% confidence interval [CI], 1.06-8.57; P = .04) after adjustment for patient sex, age, BMI, and study site. Patients with high Fn abundance also had a 5-fold increased risk of being diagnosed with rectal cancer versus right-sided colon cancer (OR = 5.32; 95% CI, 1.23-22.98; P = .03). There was no statistically significant association between Fn abundance and overall survival. CONCLUSION: Our findings suggest that Fn abundance in fecal samples collected prior to surgery varies by tumor site among treatment-naïve CRC patients. Overall, fecal Fn abundance may have diagnostic and prognostic significance in the clinical management of CRC.

Diabetes, Body Fatness, and Insulin Prescription Among Adolescents and Young Adults with Cancer.

Purpose: Rates of obesity and obesity-related health consequences, including type 2 diabetes (T2D) and cancer, continue to rise. While cancer patients are at an increased risk of developing T2D, the prevalence of T2D and insulin prescription among young patients with cancer remains unknown. Methods: Using the Total Cancer Care Study cohort at Huntsman Cancer Institute (Salt Lake City, UT), we identified individuals age 18-39 years at cancer diagnosis between 2009 and 2019. Multivariable logistic regression was used to investigate associations between body mass index (BMI) with insulin prescription within 1 year of cancer diagnosis. Results: In total, 344 adolescents and young adults (AYAs) were diagnosed with primary invasive cancer. Within this cohort, 19 patients (5.5%) were ever diagnosed with T2D, 48 AYAs ever received an insulin prescription (14.0%), and 197 were overweight or obese (BMI: 25+ kg/m2) at cancer diagnosis. Each kg/m2 unit increase in BMI was associated with 6% increased odds of first insulin prescription within 1 year of cancer diagnosis among AYAs, even after adjustment for age, sex, smoking history, marital status, glucocorticoid prescription, and cancer treatments (odds ratio = 1.06, 95% confidence interval 1.02-1.11; p = 0.005). Conclusion: One in every 18 AYAs with cancer ever had T2D, 1 in 7 AYA patients with cancer ever received an insulin prescription, and higher BMI was associated with increased risk of insulin prescription within a year of cancer diagnosis among AYAs. Understanding the incidence of T2D and insulin prescription/use is critical for short-term and long-term clinical management of AYAs with cancer.

Multi-omics Analysis Reveals Adipose-tumor Crosstalk in Patients with Colorectal Cancer.

Obesity and obesity-driven cancer rates are continuing to rise worldwide. We hypothesize that adipocyte-colonocyte interactions are a key driver of obesity-associated cancers. To understand the clinical relevance of visceral adipose tissue in advancing tumor growth, we analyzed paired tumor-adjacent visceral adipose, normal mucosa, and colorectal tumor tissues as well as presurgery blood samples from patients with sporadic colorectal cancer. We report that high peroxisome proliferator-activated receptor gamma (PPARG) visceral adipose tissue expression is associated with glycoprotein VI (GPVI) signaling-the major signaling receptor for collagen-as well as fibrosis and adipogenesis pathway signaling in colorectal tumors. These associations were supported by correlations between PPARG visceral adipose tissue expression and circulating levels of plasma 4-hydroxyproline and serum intercellular adhesion molecule 1 (ICAM1), as well as gene set enrichment analysis and joint gene-metabolite pathway results integration that yielded significant enrichment of genes defining epithelial-to-mesenchymal transition-as in fibrosis and metastasis-and genes involved in glycolytic metabolism, confirmed this association. We also reveal that elevated prostaglandin-endoperoxide synthase 2 (PTGS2) colorectal tumor expression is associated with a fibrotic signature in adipose-tumor crosstalk via GPVI signaling and dendritic cell maturation in visceral adipose tissue. Systemic metabolite and biomarker profiling confirmed that high PTGS2 expression in colorectal tumors is significantly associated with higher concentrations of serum amyloid A and glycine, and lower concentrations of sphingomyelin, in patients with colorectal cancer. This multi-omics study suggests that adipose-tumor crosstalk in patients with colorectal cancer is a critical microenvironment interaction that could be therapeutically targeted.See related spotlight by Colacino et al., p. 803.

Associations between physical activity, sedentary behavior, and urinary oxidized guanine in colorectal cancer patients: results from the ColoCare Study.

To determine associations between physical activity (PA), sedentary behavior (SB), and oxidative stress in colorectal cancer patients, ColoCare Study participants in Germany wore an accelerometer 6 and/or 12 months after surgery. Spearman partial correlations were used to assess associations between PA and urinary concentrations of oxidized guanine, a validated marker of oxidative stress. There were no significant associations between PA or SB and oxidized guanine in n = 76 measurements (ng/mg creatinine; r = 0.03, p = 0.76 for PA, r = -0.05, p = 0.69 for SB). Novelty Objectively measured PA was not associated with a marker of oxidative stress in colorectal cancer patients.

Metrics of Diabetes Risk Are Only Minimally Improved by Exercise Training in Postmenopausal Breast Cancer Survivors.

CONTEXT: Insulin resistance is a risk factor for breast cancer recurrence. How exercise training changes fasting and postglucose insulin resistance in breast cancer survivors is unknown. OBJECTIVE: To evaluate exercise-induced changes in postglucose ingestion insulin concentrations, insulin resistance, and their associations with cancer-relevant biomarkers in breast cancer survivors. SETTING: The University of Massachusetts Kinesiology Department. PARTICIPANTS: 15 postmenopausal breast cancer survivors not meeting the physical activity guidelines (150 min/week of exercise). INTERVENTION: A supervised 12-week aerobic exercise program (60 min/day, 3-4 days/week). MAIN OUTCOME MEASURES: Postglucose ingestion insulin was determined by peak insulin and area under the insulin curve (iAUC) during a 5-sample oral glucose tolerance test. Insulin sensitivity was estimated from the Matsuda composite insulin sensitivity index (C-ISI). Changes in fitness and body composition were determined from submaximal VO2peak and dual energy X-ray absorptiometry. RESULTS: Participants averaged 156.8 ± 16.6 min/week of supervised exercise. Estimated VO2peak significantly increased (+2.8 ± 1.4 mL/kg/min, P < .05) and body weight significantly decreased (-1.1 ± 0.8 kg, P < .05) following the intervention. There were no differences in fasting insulin, iAUC, C-ISI, or peak insulin following the intervention. Insulin was only significantly lower 120 min following glucose consumption (68.8 ± 34.5 vs 56.2 ± 31.9 uU/mL, P < .05), and there was a significant interaction with past/present aromatase inhibitor (AI) use for peak insulin (-11.99 non-AI vs +13.91 AI uU/mL) and iAUC (-24.03 non-AI vs +32.73 AI uU/mL). CONCLUSIONS: Exercise training had limited overall benefits on insulin concentrations following glucose ingestion in breast cancer survivors but was strongly influenced by AI use.

Community Health Behaviors and Geographic Variation in Early-Onset Colorectal Cancer Survival Among Women.

INTRODUCTION: Despite overall reductions in colorectal cancer (CRC) morbidity and mortality, survival disparities by sex persist among young patients (age <50 years). Our study sought to quantify variance in early-onset CRC survival accounted for by individual/community-level characteristics among a population-based cohort of US women. METHODS: Geographic hot spots-counties with high early-onset CRC mortality rates among women-were derived using 3 geospatial autocorrelation approaches with Centers for Disease Control and Prevention national mortality data. We identified women (age: 15-49 years) diagnosed with CRC from 1999 to 2016 in the National Institutes of Health/National Cancer Institute's Surveillance, Epidemiology, and End Results program. Patterns of community health behaviors by hot spot classification were assessed by Spearman correlation (ρ). Generalized R values were used to evaluate variance in survival attributed to individual/community-level features. RESULTS: Approximately 1 in every 16 contiguous US counties identified as hot spots (191 of 3,108), and 52.9% of hot spot counties (n = 101) were located in the South. Among 28,790 women with early-onset CRC, 13.7% of cases (n = 3,954) resided in hot spot counties. Physical inactivity and fertility were community health behaviors that modestly correlated with hot spot residence among women with early-onset CRC (ρ = 0.21 and ρ = -0.23, respectively; P < 0.01). Together, individual/community-level features accounted for distinct variance patterns in early-onset CRC survival among women (hot spot counties: 33.8%; non-hot spot counties: 34.1%). DISCUSSION: Individual/community-level features accounted for approximately one-third of variation in early-onset CRC survival among women and differed between hot spot vs non-hot spot counties. Understanding the impact of community health behaviors-particularly in regions with high early-onset CRC mortality rates-is critical for tailoring strategies to reduce early-onset CRC disparities.

Elevated insulin levels following 7 days of increased sedentary time are due to lower hepatic extraction and not higher insulin secretion.

Higher insulin following sedentary behavior may be due to increased insulin secretion (IS), decreased hepatic insulin extraction (HIE), or a combination of both. Ten healthy adults completed glucose tolerance tests following 7 days of normal activity and 7 days of increased sitting. There were no differences in IS; however, HIE at 120 min after ingestion (85.4% ± 7.2% vs. 74.6% ± 6.6%, p < 0.05) and the area under the curve (73.6% ± 9.4% vs. 67.5% ± 11.3%, p < 0.05) were reduced following 7 days of increased sedentary time.

The ColoCare Study: A Paradigm of Transdisciplinary Science in Colorectal Cancer Outcomes.

BACKGROUND: Colorectal cancer is a leading cause of cancer death. Biomarkers to predict treatment outcomes are needed, as is evidence whether postdiagnosis diet and lifestyle can affect well-being and clinical outcomes. The international ColoCare Consortium aims to identify new biologic markers (e.g., metabolomic, transcriptomic, metagenomic, genetic, epigenetic, proteomic markers) that predict clinical outcomes, and to characterize associations between modifiable risk factors (e.g., diet, supplement use, physical activity) with short-term and long-term patient-reported and clinical outcomes among patients with colorectal cancer.Methods/Results: ColoCare is recruiting newly diagnosed patients with colorectal cancer across six sites in the United States and one site in Germany. As of April 2018, we have recruited >2,000 patients across all sites. Our projected enrollment is >4,000 multiethnic patients with colorectal cancer. The study includes uniformly collected, comprehensive sets of data and biospecimens at multiple time points up to 5 years after diagnosis. Treatment and clinical data are abstracted from medical records and centrally harmonized. Biospecimens are archived according to standardized procedures. Our initial studies demonstrated metabolic differences in adipose tissue types. We further reported on associations of biological factors (e.g., inflammation, DNA methylation, metabolomics) with lifestyle factors (e.g., adiposity, smoking, physical activity, dietary supplement use) or joint associations with clinical outcomes. CONCLUSIONS: ColoCare is a consortium for the investigation of multilevel factors relevant to colorectal cancer survivorship. IMPACT: The combination of a comprehensive set of biospecimens collected at multiple time points, jointly with detailed assessments of health behaviors and other prognostic factors, results in a unique resource that facilitates wide-ranging, innovative, and impactful research on colorectal cancer.

Pilot Study of Impact of a Pedal Desk on Postprandial Responses in Sedentary Workers.

Physical inactivity has been linked to rates of obesity, diabetes, and heart disease through insulin resistance and other mechanisms. Although sedentary workplace environments have unintentionally contributed to the risk for chronic diseases, innovations in the workplace environment could potentially rectify this public and occupational health problem. PURPOSE: To evaluate the effects of light-intensity physical activity using a pedal desk (PD) compared with a standard desk (STD) in a pilot study on postprandial metabolic responses and work skills. METHODS: Twelve overweight/obese full-time sedentary office workers (six men and six women; body mass index, 28.7 ± 3.6 kg·m) were tested in two conditions: 1) PD, pedaling at self-selected light-intensity pace for 2 h and 2) STD, remaining seated for 2 h in a conventional workstation setup while performing scripted computer-based work tasks. Blood samples were analyzed for plasma glucose, insulin, and free-fatty acids in response to a standardized meal and work skills were evaluated. Paired samples t-tests were used to examine the differences in metabolic responses and work performance tasks between the conditions. RESULTS: Pedal desk use required significantly less insulin to maintain glucose concentrations compared with STD condition (peak insulin concentration, 42.1 µU·mL vs 66.9 µU·mL; P = 0.03; and area under the curve, 302.6 vs 441.8 µU·min·mL; P < 0.001). No significant changes in plasma glucose and free-fatty acid concentrations were observed at any timepoints (all P > 0.05). In addition, pedaling at a self-paced rate caused no adverse effects on work skills (P > 0.05). CONCLUSIONS: The PD resulted in lower postmeal insulin concentrations without an overall negative impact on work skills. Thus, the PD could have the potential to achieve public and occupational health goals in sedentary work environments.

Exercise training and metformin, but not exercise training alone, decreases insulin production and increases insulin clearance in adults with prediabetes.

Adding metformin to exercise does not augment the effect of training alone to boost whole body insulin sensitivity and lower circulating insulin concentrations. Although lower insulin concentrations (lower supply) following lifestyle and/or pharmacological interventions are primarily attributed to reductions in insulin secretion that match increases in peripheral insulin sensitivity (lower demand), it is unclear whether exercise and/or metformin exert direct effects on insulin production, extraction, or clearance. Thirty-six middle-aged, obese, sedentary adults with prediabetes were randomized to placebo (P), metformin (M), exercise and placebo (E+P), or exercise and metformin (E+M) for 12 wk. Fasting plasma proinsulin (an indicator of insulin production), C-peptide, insulin, and glucose were collected before and after the intervention. Peripheral insulin sensitivity (euglycemic clamp), hepatic insulin extraction, insulin clearance, body weight, and cardiorespiratory fitness were also measured. Fasting proinsulin was unchanged following P (19.4 ± 10.1 vs. 22.6 ± 15.0 pmol/l), E+P (15.1 ± 7.4 vs. 15.5 ± 7.4 pmol/l), or M (24.8 ± 18.9 vs. 16.7 ± 20.3 pmol/l) but was significantly reduced after E+M (18.6 ± 11.9 vs. 13.9 ± 6.7 pmol/l; P = 0.04). Insulin clearance was significantly greater following M (384.6 ± 19.4 vs. 477.4 ± 49.9; P = 0.03) and E+M (400.1 ± 32.0 vs. 482.9 ± 33.9; P = 0.02) but was unchanged in P or E+P. In this study, metformin combined with exercise training reduced circulating proinsulin, and both groups taking metformin increased insulin clearance. This suggests that adding metformin to exercise may augment or attenuate training effects depending on the outcome or organ system being assessed.NEW & NOTEWORTHY Exercise is increasingly viewed as medication, creating a need to understand its interactions with other common medications. Research suggests metformin, a widely prescribed diabetes medication, may diminish the benefits of exercise when used in combination. In this study, however, metformin combined with exercise training, but not exercise alone, lowered proinsulin concentrations and increased insulin clearance in adults with prediabetes. This may directly influence personalized prescriptions of lifestyle and/or pharmacology to reduce diabetes risk.

The independent and combined effects of exercise training and reducing sedentary behavior on cardiometabolic risk factors.

This pilot study examined if the combination of exercise training and reducing sedentary time (ST) results in greater changes to health markers than either intervention alone. Fifty-seven overweight/obese participants (19 males/39 females) (mean ± SD; age, 43.6 ± 9.9 years; body mass index (BMI), 35.1 ± 4.6 kg·m(-2)) completed the 12-week study and were randomly assigned to (i) EX: exercise 5 days·week(-1) for 40 min·session(-1) at moderate intensity; (ii) rST: reduce ST and increase nonexercise physical activity; (iii) EX-rST: combination of EX and rST; and (iv) CON: maintain behavior. Fasting lipids, blood pressure (BP), peak oxygen uptake, BMI, and 2-h oral glucose tolerance tests were completed pre- and post-intervention. EX and EX-rST increased peak oxygen uptake by ∼10% and decreased systolic BP (both p < 0.001). BMI decreased by -3.3% (95% confidence interval: -4.6% to -1.9%) for EX-rST and -2.2% (-3.5% to 0.0%) for EX. EX-rST significantly increased composite insulin-sensitivity index by 17.8% (2.8% to 32.8%) and decreased insulin area under the curve by 19.4% (-31.4% to -7.3%). No other groups improved in insulin action variables. rST group decreased ST by 7% (∼50 min·day(-1)); however, BP was the only health-related outcome that improved. EX and EX-rST improved peak oxygen uptake and BMI, providing further evidence that moderate-intensity exercise is beneficial. The within-group analysis provides preliminary evidence that exercising and reducing ST may result in improvements in metabolic biomarkers that are not seen with exercise alone, though between-group differences did not reach statistical significance. Future studies, with larger samples, should examine health-related outcomes resulting from greater reductions in ST over longer intervention periods.

Mild fasting hyperglycemia shifts fuel reliance toward fat during exercise in adults with impaired glucose tolerance.

Impaired glucose tolerance (IGT) is characterized by decreased oxidative capacity and reduced carbohydrate utilization during exercise. However, it is unclear if the presence of impaired fasting glucose (IFG) affects fuel utilization during exercise in adults with IGT. We tested the hypothesis that the presence of IFG in adults with IGT decreases reliance on carbohydrate during exercise. Middle-aged, obese, sedentary individuals (n = 6, IGT and n = 6, IFG+IGT) were compared during exercise at 60% peak O2 consumption for 45 min on a cycle ergometer. Glucose rates of appearance and disposal and muscle glycogen were assessed by stable isotope dilution methods, and fat utilization was estimated via indirect calorimetry. A 75-g oral glucose tolerance test was used to determine fasting and 2-h glucose concentrations. A glucose intolerance severity z-score was calculated from the oral glucose tolerance test. Glucose flux (i.e., rates of appearance and disposal) was not different between groups. However, individuals with IFG+IGT had lower muscle glycogen use (P < 0.05) and elevated fat oxidation (P < 0.01) during exercise compared with those with isolated IGT. Plasma nonesterified fatty acids and glucose were significantly higher during exercise in subjects with IFG+IGT vs. IGT alone (P < 0.05). Fat utilization during exercise correlated with fasting glucose (r = 0.57, P = 0.05), glucose intolerance severity z-score (r = 0.66, P = 0.01), and nonesterified fatty acids (trend; r = 0.55, P = 0.08). The presence of IFG shifts fuel selection toward increased fat oxidation and decreased muscle glycogen utilization during exercise in adults with IGT. Whether these differences in substrate use contribute to, or are the result of, movement along the continuum from prediabetes to type 2 diabetes awaits further work.