Altered insulin sensitivity and immune function in patients with colorectal cancer

• Background & aims: Insulin resistance and chronic inflammation have been reported in patients with cancer. However, many of the underlying mechanisms and associations are yet to be unveiled. We examined both the level of insulin sensitivity and markers of inflammation in patients with colorectal cancer for comparison to controls.Methods: Clinical exploratory study of patients with colorectal cancer (n = 20) and matched controls (n = 10). Insulin sensitivity was quantified using the hyperinsulinemic normoglycemic clamp and blood samples were taken for quantification of several key, both intra- and extracellular, inflammatory markers. We analysed the differences in these parameters between the two groups.Results: Patients exhibited both insulin resistance (M-value, patients median (Mdn) 4.57 interquartile range (IQR) 3.49-5.75; controls Mdn 5.79 (IQR 5.20-6.81), p = 0.049), as well as increased plasma levels of the pro-inflammatory cytokines IL-1b(patients Mdn 0.48 (IQR 0.33-0.58); controls Mdn 0.36 (IQR 0.29-0.42), p = 0.02) and IL-6 (patients Mdn 3.21 (IQR 2.31-4.93); controls Mdn 2.16 (IQR 1.50-2.65), p = 0.02). The latter is present despite an almost two to three fold decrease (p < 0.01) in caspase-1 activity, a facilitating enzyme of IL-1b production, within circulating immune cells.Conclusion: Patients with colorectal cancer displayed insulin resistance and higher levels of plasma IL-1b and IL-6, in comparison to matched healthy controls. The finding of a seemingly disconnect between inflammasome (caspase-1) activity and plasma levels of key pro-inflammatory cytokines in cancer patients may suggest that, in parallel to dysregulated immune cells, tumour-driven inflammatory pathways also are in effect.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Hälsovetenskap -- Näringslära (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Health Sciences -- Nutrition and Dietetics (hsv//eng)

Nyckelord

Insulin resistance

Inflammation

Inflammasome

Cytokines

Cancer

Gastrointestinal adenocarcinoma

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