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Mechanisms of insulin resistance in cancer disease
0.45 FAILURE OF TOTAL PARENTERAL NUTRITLON (TPN) TO RESTORE A NORMAL NUTRITIONAL STATE IN SEVERELY CACHECTIC CANCER PATIENTS S. Migliavacca, F. Bozzetti, M. Ammatuna, A. Pupa, M.G. Bonalumi, G. Facchetti, G. Terno (Istituto Nazionale Tumori, Milan, Italy) The purpose of this study was to evaluate, in a prospective group of patients, the efficacy of TPN in reversing malnutrition. Twelve severely malnourished patients with advanced disease (mean performance status, 30; mean weight loss, 18%; mean body mass index, 19) received continuous TPN for 20 days. The nutritional regimen included 50 non-protein Real/kg/day + 2 g amino acids/kg/day. The following nutritional parameters were measured before, during and after TPN: weight (BW), arm circumference (AC), arm muscle circumference (AMC), triceps skinfold (TS), serum protein (S-Pro), serum albumin (S-Alb), serum cholinesterase (S-CHE), serum transferrin (TIBC), prealbumin (preA), retlnol binding protein (RBP), peripheral lymphocytes (PL), nitrogen balance (NB), and 3-methyl-histidine (3-MeH). Statistical analysis was performed by Student's I test. Results are reported in the table. BW Pre TPN Post TPN P
kg
AC cm
AMC cm
TS mm
g%
S-Alb g%
S-CHE mu/ml
TIBC mg%
preA mg%
RBP ug%
PL /mm3
52.4 57.1
23.4 23.4
20.9 20.5
1.8 9.2
6.1 5.9
3.2 2.9
1370 1615
265 274
20.6 22.6
2.5 5.1
1972 1745
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
S-Pro
The mean NB was 0.09 g/kg/day and the mean daily urinary 3-MeH was 4.05 mg/kg. These data show that TPN, in severely cachectic cancer patients can prevent further deterioration but fails to restore the nutritional state to normal.
0.46 MECHANISMS OF INSULIN RESISTANCE IN CANCER DISEASE K. Bennegard, F. Lundqren & K. Lundholm. Surgical Metabolic Research Laboratory, University of Gothenburg, Sahlgrenska Hospital, Gothenburg, Sweden. We have previously reported that malnourished cancer patients have an "insulin resistance." This study was undertaken to re-evaluate insulin resistance in cancer patients with regard to sensitivity and responsiveness. Patients: Weight-losing cancer patients were compared with weight-stable Intensive Care Unit patients and weight-stable normals. Methods: The glucose/insulin clamp technique was used at five insulin levels in each patient. Whole body uptake of glucose was compared to peripheral uptake of glucose. In addition to this we measured the balance of glycerol, tyrosine and FFA across the leg in three cancer patients. Isolated muscle fibers from the rectus abdominis muscle were incubated in vitro with and without insulin in the incubation medium. Results: Weight-losing cancer patients and weight-stable Intensive Care Unit patients had a 50% reduced responsiveness to insulin at supraphysiologic concentrations of plasma insulin (glucose uptake: 5 - 6 mg/kg/min versus 14 mg/kg/min in controls). The sensitivity to insulin was not significantly changed in cancer patients but tended to be so in the Intensive care Unit patients. Around 80% of the whole body uptake of glucose was cleared across peripheral tissues. Glucose uptake across the whole body was more sensitive to insulin than glucose uptake across the peripheral bed. Cancer patients showed a decreased responsiveness to insulin with regard to glucose metabolism in incubated muscle tissue but not with regard to protein synthesis. Conclusions: Insulin resistance in cancer patients is essentially a post-receptor alteration. 53
kg
AC cm
AMC cm
TS mm
g%
S-Alb g%
S-CHE mu/ml
TIBC mg%
preA mg%
RBP ug%
PL /mm3
52.4 57.1
23.4 23.4
20.9 20.5
1.8 9.2
6.1 5.9
3.2 2.9
1370 1615
265 274
20.6 22.6
2.5 5.1
1972 1745
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
S-Pro
The mean NB was 0.09 g/kg/day and the mean daily urinary 3-MeH was 4.05 mg/kg. These data show that TPN, in severely cachectic cancer patients can prevent further deterioration but fails to restore the nutritional state to normal.
0.46 MECHANISMS OF INSULIN RESISTANCE IN CANCER DISEASE K. Bennegard, F. Lundqren & K. Lundholm. Surgical Metabolic Research Laboratory, University of Gothenburg, Sahlgrenska Hospital, Gothenburg, Sweden. We have previously reported that malnourished cancer patients have an "insulin resistance." This study was undertaken to re-evaluate insulin resistance in cancer patients with regard to sensitivity and responsiveness. Patients: Weight-losing cancer patients were compared with weight-stable Intensive Care Unit patients and weight-stable normals. Methods: The glucose/insulin clamp technique was used at five insulin levels in each patient. Whole body uptake of glucose was compared to peripheral uptake of glucose. In addition to this we measured the balance of glycerol, tyrosine and FFA across the leg in three cancer patients. Isolated muscle fibers from the rectus abdominis muscle were incubated in vitro with and without insulin in the incubation medium. Results: Weight-losing cancer patients and weight-stable Intensive Care Unit patients had a 50% reduced responsiveness to insulin at supraphysiologic concentrations of plasma insulin (glucose uptake: 5 - 6 mg/kg/min versus 14 mg/kg/min in controls). The sensitivity to insulin was not significantly changed in cancer patients but tended to be so in the Intensive care Unit patients. Around 80% of the whole body uptake of glucose was cleared across peripheral tissues. Glucose uptake across the whole body was more sensitive to insulin than glucose uptake across the peripheral bed. Cancer patients showed a decreased responsiveness to insulin with regard to glucose metabolism in incubated muscle tissue but not with regard to protein synthesis. Conclusions: Insulin resistance in cancer patients is essentially a post-receptor alteration. 53