Impairments in glucose and lipid metabolism in breast cancer patients

Abstract

BACKGROUND: Breast cancer patients typically present with unhealthy body composition (high fat mass and low muscularity) near diagnosis. These body composition characteristics often worsen during treatment and ultimately contribute to the development of secondary diseases like diabetes and cardiovascular disease in survivorship. Inflammation in overweight or obese individuals is associated with impaired glucose metabolism; the presence of the tumour may lead to greater impairments in glucose metabolism in breast cancer patients. OBJECTIVES AND HYPOTHESES: The objectives of this study were to: 1) evaluate breast cancer patients near the onset of treatment for metabolic measures including an oral glucose tolerance test (OGTT), cytokine profiles, as well as body composition, nutritional status and fitness and, 2) make comparisons between breast cancer patients, age- and BMI-matched females (HM females), and a group of young, non-malignant females with healthy BMIs (HY females) on these measures. We hypothesized that breast cancer patients would demonstrate impaired glucose metabolism relative to HM females, and that this would be attributed to systemic inflammation. We also hypothesized that both breast cancer patients and HM females would present with unhealthy body composition, impaired glucose and lipid metabolism, systemic inflammation, poor fitness and greater caloric intake compared to HY females. METHODS: We evaluated body composition using % body fat (skinfold callipers) and waist circumference. Following collection of fasting blood samples, an OGTT was conducted to assess glucose, insulin, c-peptide and glucagon dynamics. Fasting blood samples were analysed for lipids and pro- and anti-inflammatory cytokines. Incremental exercise tests were conducted to assess VO2peak, and estimated 1-RM tests assessed strength of the biceps, triceps and quadriceps muscles. Baecke and CHAMPS questionnaires provided an indication of habitual physical activity. A 3-day food record was used to analyze daily caloric intake and macronutrient distribution. Breast cancer patients and HM females were compared using paired t-tests. Patients and HM females were compared to HY females using t-tests. Statistical significance was accepted at p < 0.05. RESULTS: Overall, breast cancer patients were overweight (BMI: 28.8 ± 6.0 kg/m2) and presented with abdominal obesity (waist circumference: 94.6 ± 14.0 cm) and dyslipidemia (TAG: 1.84 ± 1.17 mM and HDL-c: 1.08 ± 0.23 mM), indicating risk for metabolic syndrome. Although fasting glucose concentrations did not differ between the 3 groups, breast cancer patients demonstrated higher glucose concentrations at 30 min during an OGTT. Similar to glucose, fasting insulin concentrations did not differ between the 3 groups, but patients demonstrated higher insulin at 150 min during an OGTT. Breast cancer patients had elevated fasting serum c-peptide (2.6 ± 1.2 ng/mL vs. 1.9 ± 0.8 ng/mL, p = 0.005). C-peptide remained elevated in patients compared to non-malignant females during the last hour of the OGTT, indicating that insulin secretion was sustained in breast cancer patients. We observed no difference in serum cytokines between patients and HM females or between patients and HY females. VO2peak, although lower compared to HY females, was similar in patients and HM females. There were no differences in habitual physical activity or nutrition measures between any groups. DISCUSSION AND CONCLUSIONS: Breast cancer patients presented with poorer glucose features during an OGTT compared to HM and HY females. However, systemic inflammation, body composition, energy expenditure and energy intake were similar in breast cancer patients and HM females. Thus, these impairments may be tumour-related. Future studies need to specifically elucidate the effects of the tumour in host glucose metabolism.