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Elevated insulin resistance, leptin levels linked to cancer risk in Barrett’s esophagus
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Patients with Barrett’s esophagus were more likely to develop esophageal adenocarcinoma with higher levels of leptin and insulin resistance, while elevated high-molecular-weight adiponectin levels reduced risk in a recent study.
Researchers evaluated fasting levels of adiponectin, glucose, insulin and leptin in 392 participants with Barrett’s esophagus (BE) in the Seattle Barrett’s Esophagus Study. Participants underwent interview, anthropometric assessment and endoscopy and also provided blood samples at baseline, with follow-up evaluations and endoscopy at 6-month to 2-year intervals (median 80.5 months). Insulin sensitivity was measured via homeostatic model assessment (HOMA) scores.
Esophageal adenocarcinoma (EA) was observed in 43 cases during follow-up. Risk for EA was associated with increasing HOMA score (HR=1.64; 95% CI, 1.08-2.48), particularly within participants’ first 3 years in the study (HR=2.45; 95% CI, 1.43-4.19) and among patients with a BMI below 25 kg/m2 (HR=6.31; 95% CI, 1.13-34.98 vs. HR=1.37; 95% CI, 0.88-2.12 among those with higher BMI). Restricting analysis to patients without diabetes eliminated the significance of the association between HOMA and EA risk.
EA risk also was associated with leptin levels within 3 years (HR=2.51; 95% CI, 1.09-5.81) and 6 years (HR=2.07; 95% CI, 1.01-4.26) of enrollment, but not overall (HR=1.58; 95% CI, 0.83-3). No association was observed between metabolic syndrome and EA risk. Investigators noted an inverse association between EA risk and high-molecular-weight adiponectin, particularly within the second tertile (HR=0.34; 95% CI, 0.14-0.82), and when analysis was restricted to men (HR=0.36; 95% CI, 0.15-0.88).
“We report an association between HOMA scores … and leptin concentration and risk of progression from BE to EA,” the researchers conclude. “Although further studies are required to confirm these findings, we believe that the biological effects of these hormones … may mediate the effects of obesity on risk of EA. Insulin levels can be decreased successfully via behavioral/lifestyle interventions … and may represent a method of reducing risk of progression to EA.”
Disclosure: Researcher Brian Reid is employed at and receives 20% of his salary from the National Cancer Institute, via the Intergovernmental Personnel Act.
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