Weight-losing Patients Research Articles

Glucose‐induced thermogenesis in patients with small cell lung carcinoma. Before and after inhibition of tumour growth by chemotherapy

Seven weight-losing patients with histologically verified small cell lung carcinoma were given an oral glucose load of 75 g before and at least 3 weeks after the end of chemotherapy to examine the effect of glucose on whole body and skeletal muscle thermogenesis before and after reduction of tumour. Whole body energy expenditure was measured by the open circuit ventilated hood system. Forearm blood flow was measured by venous-occlusion strain-gauge plethysmography. The uptake of oxygen in skeletal muscle was calculated as the product of the forearm blood flow and the difference in a-v oxygen concentration. Whole body resting energy expenditure (REE) did not increase, it was 4.4 +/- 0.3 kJ min-1 (mean +/- SE) before chemotherapy and 4.4 +/- 0.2 kJ min-1 after chemotherapy. The glucose-induced thermogenesis in the 180 min following the glucose load was 93.6 +/- 9.9 kJ 180 min-1 before chemotherapy. This is significantly increased compared to that found in a healthy control group (74.7 +/- 4.8 kJ 180 min-1, P < 0.02). The glucose-induced thermogenesis was significantly reduced to 47.7 +/- 10.2 kJ 180 min-1 (P < 0.05) after chemotherapy. The oxygen uptake in resting skeletal muscles was 6.9 +/- 0.3 mumol 100 g-1 min-1 before chemotherapy and 7.0 +/- 0.7 mumol 100 g-1 min-1 after chemotherapy. This did not increase during the first 90 min following the glucose load in either investigations. In the period 90-180 min following the glucose load, the oxygen uptake was significantly increased before chemotherapy as compared to after chemotherapy, which suggests that the reduced whole body thermogenesis after chemotherapy in part was due to reduced skeletal muscle thermogenesis.

Resting energy expenditure, the acute phase response and cytokines in weight-losing patients with pancreatic cancer

Resting energy expenditure, the acute phase response and cytokines in weight-losing patients with pancreatic cancer

The interrelationship of weight loss, dietary intake, and quality of life in ambulatory patients with cancer of the lung, breast, and ovary.

One hundred four consecutive patients with newly diagnosed small cell lung cancer, metastatic breast cancer, and ovarian cancer in good physical functional condition (performance rating 0-1 on Eastern Cooperative Oncology Group scale) were divided into a weight-losing group (> or = 5% unintentional weight loss within 3 mo; n = 48) and a weight-stable group (n = 56). Dietary intakes in relation to fat-free mass were not different in the two groups. According to the Quality of Life index and the General Health Questionnaire, weight-losing patients had significantly lower quality of life than weight-stable patients. In patients with weight loss, daily intakes of energy and protein correlated significantly with scores on the General Health Questionnaire. This study has shown that many ambulatory cancer patients do not eat enough to maintain weight and that even a moderate weight loss is associated with psychological distress and lower quality of life.

Resting energy expenditure in patients with chronic obstructive pulmonary disease

Resting energy expenditure (REE) was measured in 68 patients with stable chronic obstructive pulmonary disease (COPD) and in 34 weight-stable, age-matched (65 +/- 8 y; means +/- SD) healthy control subjects. Fat-free mass (FFM) determined by bioelectrical resistance explained 84% of the variation in REE in the control group but only 34% in the COPD patients. REE could not reliably be predicted from regression equations either developed in healthy subjects or in COPD patients. REE adjusted for FFM was significantly higher (P less than 0.05) in weight-losing (n = 34) than in weight-stable (n = 34) patients (6851 +/- 781 and 6495 +/- 650 kJ/d, respectively). Pulmonary function was more compromised in weight-losing patients. Adjusted REE in weight-stable patients was significantly higher (P less than 0.01) than in the healthy control group (6131 +/- 405 kJ/d). In patients with COPD, factors in addition to FFM are important determinants of REE. A disease-related increase in REE develops, which may contribute to weight loss in COPD in combination with a lack of an adaptive response to undernutrition in weight-losing patients.

Palmitate turnover and its response to glucose infusion in weight-losing cancer patients

Palmitate turnover in weight-stable control subjects (n = 4) and weight-losing patients with progressive malignant disease (n = 4) has been determined. Measurements were made after an overnight fast and during glucose infusion (3.5 mg/kg/min). Turnover rates were calculated from plateau isotopic enrichment of palmitate in plasma during a continuous infusion of 1–13C palmitate. Palmitate turnover was higher in the cancer group before (180%) and during glucose loading (170%) compared with the control group. Palmitate turnover was reduced during glucose administration by approximately 34% in both groups. Plasma concentration of insulin was decreased and of cortisol was increased in the cancer group compared with the control group before and during glucose infusion. We conclude that cancer patients with weight loss have increased rates of fatty acid turnover indicative of enhanced mobilisation of body fat stores. Altered plasma concentrations of insulin and cortisol may mediate this effect. Nonetheless, even at more advanced stages of cachexia cancer patients have normal control mechanisms for inhibiting fatty acid turnover following administration of carbohydrate.

Cardiovascular and metabolic response to adrenaline infusion in weight-losing patients with and without cancer.

Fasting is generally accompanied by a decrease in energy metabolism and hormones. On the other hand, indirect evidence has suggested that the response to adrenergic agonists may be maintained or even increased in malnutrition. The present study evaluated whether weight-losing patients with and without cancer have increased plasma concentrations of catecholamines and different responses to intravenously infused adrenaline compared to weight-stable individuals. Eight malnourished cancer and 10 non-cancer patients (11% weight loss) were compared to seven well-nourished and weight-stable patients. Adrenaline was infused i.v. at a rate of 0.005 microgram min-1 kg-1 body weight during 40 min followed by a 40 min rest period (without infusion) and then a final 40 min period with i.v. adrenaline infusion (0.02 microgram min-1 kg-1 body weight). Plasma glycerol concentration at fast was higher in weight-losing patients compared to weight-stable individuals. Whole body oxygen uptake, carbon dioxide production, heart rate and plasma concentrations of free fatty acids (FFA) increased while the mean arterial pressure decreased significantly in response to adrenaline infusion at 0.02 microgram kg-1 min-1 in both weight-losing and weight-stable patients. Adrenaline at 0.005 microgram kg-1 min-1 increased plasma FFA levels by 19% (P less than 0.05) in weight-losing patients while no significant alteration was observed in well-nourished patients. Adrenaline infusion at 0.02 microgram kg-1 min-1 decreased the mean arterial blood pressure and stimulated respiratory gas exchange and heart rate significantly more in weight-losing than in weight-stable patients. The slopes for oxygen uptake, carbon dioxide production, heart rate, plasma FFA and plasma glycerol vs. plasma adrenaline and noradrenaline were all significantly steeper (P less than 0.05-0.01) in malnourished patients than in well-nourished controls. The present study suggests an increased sensitivity to adrenaline in weight-losing patients compared to matched controls with normal nutritional state and stable weight.

Nutrient intake and nitrogen metabolism in cancer patients during oncological chemotherapy

Aggressive oncological chemotherapy often impairs the nutritional status of tumor patients. To evaluate the pathogenetic mechanisms, food intake in 13 cancer patients was investigated in correlation with nitrogen losses, N balances, muscle wasting, and weight course, during cytostatic therapy. Median daily N and energy intakes were reduced only in patients with weight loss [0.55 g protein, 16.5 kcal/kg ideal body wt (IBW)]. Patients with constant weight had the same intake as control subjects (1.27 g protein, 37.2 kcal IBW). N balances and creatinine height index (CHI) correlated with daily nutrient intake. Fecal N excretions did not correlate with urinary losses; there was no excess of fecal N loss because of cytostatic treatment. The impairment of cancer patients' nutritional status seems to depend primarily on the decrease of spontaneous oral intake as a consequence of the side effects of tumor therapy. Changes in CHI, compared before and after chemotherapy, indicated muscle wasting of weight-losing patients.

Diet-induced thermogenesis in patients with gastrointestinal cancer cachexia.

1. Indirect calorimetry has been used to measure resting energy expenditure (REE) and the thermogenic response to a test meal (diet-induced thermogenesis) in groups of weight-stable and weight-losing patients with gastrointestinal adenocarcinoma. Average daily intakes of energy and protein were computed from dietary assessment for the week before hospitalization. Results were compared with a control group of patients with benign gastrointestinal disease. 2. Weight-losing cancer patients had a significantly reduced mean total energy and protein intake. 3. There was no significant difference in REE between the groups when results were normalized in terms of metabolic body size (kJ/kg 0.75) and lean body mass (kJ/kg). 4. Diet-induced thermogenesis was reduced in weight-losing cancer patients. 5. It is suggested that the reduction of diet-induced thermogenesis in weight-losing cancer patients is another element of starvation adaptation, subsequent to their weight loss, and that altered thermogenesis does not contribute to the weight loss seen in cancer cachexia.

Monocytic production and plasma bioactivities of interleukin-1 and tumour necrosis factor in human cancer.

Plasma concentrations and in-vitro production of interleukin-1 and tumour necrosis factor were evaluated in 23 weight-losing patients with cancer, six bacterially infected patients without cancer and six healthy controls. Bioactivity of interleukin-1 was found in the plasma from five of six bacterially infected patients but only from one of 23 cancer patients. Tumour necrosis factor activity was not detected in the plasma of any patient. In four of 23 patients with cancer, in-vitro stimulation of peripheral blood monocytes by either endotoxin or heat-killed Staphylococcus albus resulted in no significant production of interleukin-1. Such a defect was not seen in any of the bacterially infected or control patients. Tumour necrosis factor production by endotoxin-stimulated blood monocytes was unaffected by the presence of cancer or bacterial infections and was normal in the four individuals with defective interleukin-1 production. We can therefore conclude that interleukin-1 bioactivity is not generally found in the plasma of weight-losing cancer patients. Furthermore, in a fraction of such cancer patients, monocytic production of interleukin-1 is markedly down-regulated. However, this defect appears to be specific for interleukin-1 since in-vitro tumour necrosis factor production is normal.

Weight change in depression

This report describs the weight changes of 109 outpatients during the course of a depressive illness and relates these changes to several potential predictors: age, gender, diagnosis, and scores on the Hamilton Rating Scale for Depression (HRSD), the Beck Depression Inventory, and the three factors on the Eating Questionnaire. Weight changes ranged from -33 to +50 pounds, with 40% of the patients reporting weight gain, 30% weight loss, and 30% no change in weight. Weight loss occurred more rapidly than did weight gain. The disinhibition factor of the Eating Questionnaire was significantly correlated with weight change during depression and, on a stepwise discriminant function analysis,differentiated weight-gaining from weight-losing patients at a high level of statistical significance. Severity of depression also differentiated weight-gaining from weight-losing patients in the discriminant funntion analysis, but only on the HRSD and at a level of more modest statistical significance.

Serum amino acids in weight-losing patients with cancer and tuberculosis

A study of arterial and arterio-venous amino acid concentration differences across the forearm was performed in 19 weight-losing cancer (CWL) patients (9 with lung cancer and 10 with other types of cancer), 8 weight-losing patients with active pulmonary tuberculosis (TWL) and 10 normal controls. Arterial concentrations of many of the amino acids measured were found to be lower in CWL than in TWL patients. In addition, the data suggested a venous excess of amino acids in the CWL patients compared with TWL patients and controls. The increased release of alanine from forearm muscles in the CWL group, together with the low arterial glycogenic amino acid levels, supports the concept of enhanced gluconeogenesis in CWL patients. Low arterial amino acid levels and possible increased release of amino acids from forearm muscle in CWL patients implies enhanced proteolysis with increased central clearance or tumour sequestration of these amino acids, though decreased proteogenesis cannot be excluded in accounting for the venous excesses in this group. Hypocitrullinemia in lung cancer patients was marked, and possible mechanisms to account for this are discussed.