Insulin resistance in patients with cancer: relationships with tumor site, tumor stage, body-weight loss, acute-phase response, and energy expenditure

doi:10.1016/S0899-9007(01)00561-5

Nutrition

Volume 17, Issues 7–8, July–August 2001, Pages 590-593

https://doi.org/10.1016/S0899-9007(01)00561-5 Get rights and content

Abstract

We examined peripheral insulin sensitivity in 32 patients with cancer (17 with stomach cancer, 7 with colorectal cancer, and 8 with lung cancer) and 6 normal control subjects by the euglycemic hyperinsulinemic glucose clamp technique. The relationships between insulin resistance and tumor factors (type and stage), malnutrition, and inflammatory reaction were evaluated. Insulin sensitivity often was reduced in patients with cancer; however, the amount of glucose metabolized was not related to tumor site or stage. The decreased glucose uptake was negatively correlated with the acute-phase response but was not correlated with body-weight loss, serum albumin, or resting energy expenditure. Our results suggest that insulin resistance in cancer patients was not induced by malnutrition. Although the qualitative presence of tumor might be the major factor inducing insulin resistance, other factors such as inflammatory reactions might be involved in the development of insulin resistance.

Introduction

Cancer cachexia is characterized by a loss of appetite and a variety of metabolic alterations.1, 2 The recognition of glucose intolerance in cancer patients was reported as early as 1919.3 Abnormalities in oral and intravenous glucose tolerance tests were noted before the development of cachexia in patients with sarcoma4 and lung cancer5 and after the development of cachexia in patients with gastrointestinal cancer.6

Since the development of the euglycemic glucose clamp technique by DeFronzo et al.7 to evaluate insulin sensitivity in peripheral tissues, several studies have shown insulin resistance in a variety of cancer patients with or without body-weight loss.8, 9, 10, 11, 12 We previously reported that insulin resistance in cancer patients is partly reversed immediately after tumor removal, suggesting that it was caused, at least in part, by the tumor itself or the tumor-influenced host.12

The precise causes of insulin resistance in cancer patients have not been elucidated. We previously documented a negative correlation between serum interleukin-6 concentration and insulin sensitivity in peripheral tissues.13 In the present study, we investigated whether the insulin resistance in cancer patients is related to tumor site, tumor burden, the effects of malnutrition, or the inflammatory response.

Section snippets

Materials and methods

Thirty-two cancer patients (17 with gastric cancer, 7 with colorectal cancer, and 8 with lung cancer) and six healthy control subjects were included in the study. A diagnosis of malignancy was confirmed histologically, and all patients had normal liver and kidney functions and normal electrolyte concentrations. Before entering into the study, all patients and control subjects gave informed consent. All subjects were evaluated at 8 am after an overnight fast.

Peripheral insulin sensitivity was

Results

The clinical characteristics of normal controls and patients with gastric, colorectal, and lung cancers are shown in Table I. Serum albumin concentrations in patients with gastric and lung cancers were significantly reduced compared with those in control subjects. Serum CRP concentration in patients with lung cancer was significantly higher than that in controls. REE and REE/HB were comparable among all cancer patients and controls.

Blood glucose and plasma insulin concentrations, insulin

Discussion

The euglycemic glucose clamp is accepted as an appropriate technique for measuring peripheral insulin sensitivity if endogenous glucose-production is suppressed. Under a high physiologic insulin concentration (100 μU/mL), the endogenous glucose production was found to be completely suppressed in normal subjects and in cancer patients who had sustained weight loss.10 Therefore, it can be concluded that at this high insulin concentration, the glucose-disposal rate reflected the insulin-stimulated

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Applied nutritional investigationInsulin resistance in patients with cancer: relationships with tumor site, tumor stage, body-weight loss, acute-phase response, and energy expenditure

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Metabolism

Metabolism

Am J Surg

Amino acid metabolism in human cancer cachexia

Annu Rev Nutr

Cancer cacehxia

JPEN

Sugar tolerance in cancer

JAMA

Glucose intolerance in sarcoma patients

Cancer

Abnormalities in glucose and protein metabolism in non-cachectic lung cancer patients

Cancer Res

Mechanism of impaired glucose tolerance in patients with neoplasia

Br J Surg

Glucose clamp techniquea method for quantifying insulin secretion and resistance

Am J Physiol

Mechanism of insulin resistance in cancer patients

Clin Physiol

Insulin resistance in patients with colorectal cancer

Br J Surg

The effects of graded doses of insulin on peripheral glucose uptake and lactate release in cancer cachexia

Surgery

Applied nutritional investigation
Insulin resistance in patients with cancer: relationships with tumor site, tumor stage, body-weight loss, acute-phase response, and energy expenditure