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Glucose Flux in Relation to Energy Expenditure in Malnourished Patients with and Without Cancer During Periods of Fasting and Feeding1

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Glucose Flux in Relation to Energy Expenditure in Malnourished Patients with and Without Cancer During Periods of Fasting and Feeding1 [CANCER RESEARCH 44, 1718-1724, April 1984] Glucose Flux in Relation to Energy Expenditure in Malnourished Patients with and without Cancer during Periods of Fasting and Feeding1 Elisabeth Edén,Staffar) Edström,Klas Bennegárd, Tore Scherstén,and Kent Lundholm2 Surgical Metabolic Research Laboratory, Department of Surgery I [T. S., K. L], Anaesthasiology l-ll [E. E., K. B.] and Otolaryngology [S. £.],Sahlgrenska Hospital, University of Gothenburg, Gothenburg, Sweden ABSTRACT fuel economy in progressive neoplasia (12). Our recent evidence suggests that elevated lactate turnover in cancer patients may Glucose dynamics, energy metabolism, and nitrogen balance be counteracted by depressed recycling of carbon in the glucose- were studied in eight malnourished cancer patients and seven alanine cycle (2), supported by the findings that a decreased malnourished patients without cancer. Glucose flux was mea alanine release occurred in combination with a diminished glu sured by single injection of [6-3H]glucose and [U-14C]glucose. cose uptake across the leg in cancer patients after an overnight Energy expenditure was measured by indirect calorimetry. Each fast (2), and that intrahepatic cycling of glucose carbon was patient was studied after an overnight fast and during constant decreased in sarcoma-bearing mice (21). Thus, the evidence gastric infusion of a formula diet. points to the possibility that net recycling of glucose in cancer Cancer patients had elevated glucose flux when fasting, cor cachexia may not influence the overall fuel economy, even if the responding to 42% of their spontaneous daily intake of glucose. Cori cycle activity is highly elevated (16). Instead, it is rather the At least one-half of the elevated flux in cancer patients compared sum of whole-body gluconeogenesis and glycogenolysis, mea with controls was due to increased recycling of glucose carbon sured as glucose turnover, that may be of quantitative impor after an overnight fast. Feeding doubled the total glucose flux in tance in weight loss. Net recycling probably represents a minor both cancer and control patients. The recycling was unchanged part of the total flux of glucose through the plasma pool in cancer in the cancer group and disappeared in the controls during patients, provided that hepatic glycogen is available (32). feeding. The increased glucose flux in cancer patients was We have calculated that elevated glucose turnover may im concomitant with normal resting energy expenditure during pe pose an energy cost of up to 40% of increased energy expend riods of both fasting and feeding. Glucose flux in relation to iture in metastatic cancer (22). Although the elevation in energy energy expenditure was doubled in cancer patients compared to expenditure is low in cancer patients3 (250 to 300 kcal/day; Refs. controls, and the glucose flux in fed cancer patients was similar 7,24, and 34), the cumulative effect may be one important factor to the rate of glucose infusion, which shows that the endogenous behind the negative energy balance. This is most obvious in production of glucose was not inhibited. Cancer and control those patients with a very low caloric intake. It was reported patients reached a comparable positive energy and nitrogen recently that some human soft tissue sarcoma have a very high balance, allowing for their overall caloric intake. glucose uptake (130 mg/min/tumor) (26). This amount of glucose Our results show that cancer patients seem to have a char contains more than 700 kcal/day, assuming normal and complete acteristically increased glucose demand, which contributes to oxidation of glucose. However, if this glucose is metabolized their weight loss when fasting. The energy drain by this elevated only to lactate, then a significant energy wastage is imposted on glucose flux can explain, as a maximum estimate, a loss of about the host, considering that lactate production in the tumor tissue 0.9 kg of body fat per 30-day period. would extract only 5 to 10% of the energy content of the glucose molecule. INTRODUCTION This study evaluates the role of elevated overall flux of glucose as a metabolic pathway of energy drain on cancer patients. As the glucose use and the metabolic rate are normally low ered in the phase of caloric deprivation, findings of elevated MATERIALS AND METHODS glucose flux have been taken to suggest an increased demand for glucose in weight-losing cancer patients (17, 22, 35, 37). Patients. Malnourished cancer patients were compared with malnour Consistent evidence suggests that an increased lactate turnover ished patients without cancer. The clinical details and the nutritional state contributes significantly to the increase in whole-body flux of of the patients are given in Table 1. The patients were selected on the glucose in metastatic cancer (16, 18). Neosynthesis of glucose clinical grounds that all patients were in the need of nutritional support from lactate is an energy-requiring metabolic process. The pos and that they were chosen to be comparable with the patients in our recent studies with respect to tumor stage and degree of malnutrition sible role of a wasteful metabolic pathway through recycling of (2,3,22). Anthropométrie and biochemical assessments and the patients' glucose carbon may therefore contribute significantly to overall history of weight loss were used to judge the degree of malnutrition (5). All patients had normal body temperature, and none of them was 1This work was supported by grants from the Swedish Cancer Society (Project suffering from acute illness. None was severely anemic. Both cancer and 93), the Swedish Medical Research Council (Project 536), the Assar Gabrielsson Foundation, the Serena Ehrenström Foundation, and the Gothenburg Medical control patients had an increased erythrocyte sedimentation rate, and 7 Society. 2 To whom requests for reprints should be addressed, at Department of Surgery 3 L. Ljndmark, K. Bennegárd, E. Edén,L. Ekman, T. Scherstén,G. Svaninger, I. Sahlgrenska Hospital, S-413 45 Gothenberg, Sweden. and K. Lundholm. Resting energy expenditure in malnourished patients with and Received March 23, 1983; accepted January 4, 1984. without cancer, submitted for publication. 1718 CANCER RESEARCH VOL. 44 Downloaded from cancerres.aacrjournals.org on October 1, 2021. © 1984 American Association for Cancer Research. Glucose Turnover in Patients with Cancer Table 1 Nutritional status of weight-losing cancer and noncancerous patients Wt-losing cancer patients Controls BAge A* (n = 8) (n = 7)A63 (yr)Height ±173 (cm)Wt ±10 toss(kg)Wt(kg)1IIWt ±62.2 ±65.6 ±0.78 wt)1IITotalindex (actual/ideal ±0.82 ±2740 (mmol)1IITricepsbody potassium ±2948 ±7.3 (mm)1IIArmskinfold ±8.2 ±23.4 (cm)1IIHemoglobincircumference ±25.3 ±132 c88210.030.0622220.10.1321111 (g/liter)1IISerumconcentration "71 ±119 ±37 (g/liter)1IISerumalbumin "2 ±36 "0.03 ±0.25 (g/liter)1IIErythrocyteprealbumin "0.0312110.20.111427/87/8Wt-tosing ±0.31 ±49 (mm/hr)1IIRectalsedimentation rate ±50 5437.237.21817102106++±±±±±±±±±±+±±±±+±+±±±±±±±5"112.63.30.050.051152151.51.21.31.07 ±37.0 (°C)1IIRespiratorytemperature ±37.0 ±24 (breaths/min)1IIMeanfrequency ±20 ±105 (beats/mm)1IIAbnormaldaily heart rate ±104 ±2/72/75418.99.40.070.083583621.61.52.72.6 tests1II551741050.454.70.680.7320502481727.321.723.311611329290.140.1349cliver function A, comparison before/after nutrition; B, comparison between the groups; I, before nutrition; II, after nutrition. 6 Mean ±S.E. °p< 0.05. "p< 0.025. "p<0.01. of 8 cancer patients had abnormal liver function test results. However, the study. The diagnoses were: (a) one testicular carcinoma; (o) one none of them had elevated levels of plasma bilirubin, and transaminases gastric carcinoma; (c) 2 hepatic carcinomas; (d) 2 head and neck were lower than 2 /ikat/liter (normal value, <0.7 /¿kat/liter)and alkaline carcinomomas; (e) one esophageal carcinoma; and (f) one colon carci phosphatases <10 jtkat/liter (normal value, <5 /tkat/liter). The hepatic noma. influence was qualitatative rather than quantitative. All patients were Group 2: Malnourished Patients without Cancer. The group con subjected to isotopie scintigrams and computerized tomography of the sisted of 7 malnourished patients without cancer (one with chronic liver. The heart rate was high in both cancer and control patients. All malnutrition due to gastric resection 4 years earlier, one with chronic patients had normal blood pressure. None of the patients had received pancreatitis, one with senile depression due to generalized arterioscle any diuretics which could influence total body potassium. The metabolic rosis, one with previous bile fistula without extrarenai losses, and 2 with response of whole-body and peripheral tissues to the enterai nutrition in senile depression). All of these patients were manifestly malnourished 7 of the 8 cancer patients and ¡n5 of the malnourished noncancer but without any other signs of disease when studied. They had lost patients has been reported in detail eslewhere (3). about 14% of their normal body weight. This study was approved by the Ethical Committee of the Faculty of Investigative Protocol. For all patients who entered this study, total Medicine of the University of Gothenburg. body potassium, nutritional assessment, food intake, energy expendi Group 1: Cachetic Cancer Patients. This group consisted of 8 weight- ture, and glucose turnover were measured during 3 days (Days 1 to 3) losing cancer patients with generalized disease (Stages III and IV) and a before nasograstric tube feeding was started. Spontaneous food intake history of weight loss corresponding to about 15% of their normal body and whole-body energy expenditure were recorded 24 hr a day, and weight.
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