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Hematologic malignancies magnify the effect of body mass index on insulin
resistance in cancer survivors.
Authors Sahinoz M, Luther JM, Mashayekhi M, Jung DK, Ikizler TA, Engelhardt BG
Submitted By Submitted Externally on 6/21/2022
Status Published
Journal Blood advances
Year 2022
Date Published 4/1/2022
Volume : Pages 6 : 1981 - 1990
PubMed Reference 35130338
Abstract Cancer survivors are at increased risk of type 2 diabetes, which usually
develops from obesity and insulin resistance. Whether diabetes susceptibility is
due to shared risk factors for cancer and insulin resistance or directly related
to cancer and its treatment is unknown. We investigated effect modification
between malignancy and body mass index (BMI) as determinants of insulin
sensitivity in patients with hematologic malignancies and controls without
cancer. In a cross-sectional study of 43 individuals without diabetes (20
patients with treated hematologic malignancies; 23 controls without
malignancies), we measured insulin-stimulated whole-body glucose use (M) by
hyperinsulinemic euglycemic clamp. Insulin sensitivity index (ISI) was
calculated by dividing M over steady-state plasma insulin. Inflammatory
cytokines were measured in plasma. Controls were more obese and included more
non-White individuals and women vs patients with hematologic malignancies.
Patients with cancer exhibited greater insulin sensitivity (median ISI, 42.4
mg/kg/min/[µU/mL]; interquartile range [IQR], 33.9-67.2 vs 23.4
mg/kg/min/[µU/mL]; IQR, 12.9-29.2; P < .001) and higher interleukin-6 (IL-6) and
monocyte chemoattractant protein-1 (MCP-1) concentrations vs controls. Patients
with cancer demonstrated greater reduction in ISI with increasing BMI vs
controls, which remained significant after adjustment for sex and race (ß = -2.6
units; 95% confidence interval, -4.8 to -0.4; P interaction = .024). This
interaction also remained significant after adjusting for log IL-6 (P
interaction = .048) and log MCP-1 (P interaction = .021). Cancer survivors had
disproportionately greater insulin resistance with increasing BMI vs controls
without malignancies. Effect modification between cancer and BMI in determining
insulin sensitivity implicated cancer-specific etiologies in glucose
dysregulation and could partially explain excess diabetes diagnoses among
oncology patients.


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