Insulin secretion, glucose production, and insulin sensitivity in underweight and normal-weight volunteers, and in underweight and normal-weight cancer patients: a Clinical Research Center study.

Severe malnutrition (< 65% ideal body weight [IBW]) is associated with reduced insulin secretion, decreased receptor affinity, and glucose intolerance. To characterize the abnormality of mild malnutrition in terms of insulin action, both the insulin sensitivity index and insulin secretion were measured in 15 underweight and 15 normal-weight volunteers. Ten patients had localized squamous cell carcinomas of the head and neck, and 20 were normal controls. After a 10-hour overnight fast, all volunteers were studied using Bergman's modified intravenous (IV) glucose tolerance test (IVGTT). Body weight and diagnosis were compared using a 2 x 2 ANOVA. The acute insulin response to IV glucose was reduced in normal-weight and underweight cancer patients by approximately 40% to 50% (P < .05). Both groups of cancer patients had a significantly reduced rate of glucose disposal (1.25 +/- 0.29 and 1.27 +/- 0.23 %/min) compared with the healthy volunteers (1.82 +/- 0.21 and 1.81 +/- 0.24 %/min, respectively, P < .05). Glucose production (GP) was significantly increased in the underweight cancer patients versus the weight-matched volunteers (13.9 +/- 1.3 v 10.8 +/- 0.5 micromol/kg/min, P < .05). Normal-weight and underweight cancer patients had a 32% to 44% reduction in insulin sensitivity (P < .05). In contrast to the effects of cancer, underweight controls had twice the insulin sensitivity compared with normal-weight controls (P < .01). Since insulin secretion decreased in underweight controls, the increased insulin sensitivity may have been due to an increased insulin action and to factors associated with leanness.

Altered metabolism and mortality in patients with colon cancer receiving chemotherapy.

To identify the metabolic effects of 5-fluorouracil and hydrazine sulfate therapy, 22 patients with colon cancer were admitted prospectively to a Clinical Research Center for serial measurement of counter-regulatory hormones, fasting hepatic glucose production (HGP), intravenous glucose tolerance test, plasma leucine appearance (LA) and leucine oxidation. Combined therapy was associated with a significant reduction in fasting glucose level (98 +/- 2 mg/dL to 94 +/- 2, P < 0.025) without a significant fall in fasting HGP (2.09 +/- 0.11 mg/kg/min versus 2.03 +/- 0.13; P > 0.05). The decreased fasting glucose value was associated with a mild but not statistically improved glucose disposal rate in response to the intravenous glucose tolerance test (1.34 +/- 0.07 %/min vs 1.47 +/- 0.11, P = 0.15). Plasma leucine appearance was significantly reduced after 2 months of therapy (63.3 +/- 3.0 mumol/kg/hr vs 57.1 +/- 3.9 mumol/kg/hr; P < 0.025), but leucine oxidation (11.5 +/- 1.1 mumol/kg/hr vs 11.2 +/- 1.1 mumol/kg/hr) was not altered. Despite the fact that plasma triiodothyronine concentrations significantly increased with therapy, it was not associated with plasma LA. Half of the patients with cancer died 14 +/- 4 months after the study, and the other half were alive 58 +/- 2 months later. Survival time can be estimated with 59% accuracy using plasma LA, HGP, carcino-embryonic antigen, and insulin concentration. Multiple regression analysis identified that plasma LA was related directly to length of survival time, and baseline HGP, carcino-embryonic antigen, and insulin concentration were related inversely to length of survival.(ABSTRACT TRUNCATED AT 250 WORDS)