Adiponectin ‘paradox’ may explain cancer risk in type 2 diabetes
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A registry analysis of Chinese adults with type 2 diabetes suggests that a higher concentration of circulating adiponectin, a protein typically associated with reduced cardiovascular risk, is associated with incident cancer and cancer-related mortality, according to findings published in The Journal of Clinical Endocrinology & Metabolism.
“Although adiponectin, a hormone from the fat cells, has been reported to protect against cancers in animal studies, mostly in mice, higher levels of adiponectin paradoxically predicted the development of cancer and death due to cancers in this study of more than 5,000 people with diabetes,” Karen Lam, MD, chair and professor of medicine at the University of Hong Kong, told Healio. “This adiponectin paradox had previously been demonstrated in people with cardiovascular and kidney diseases. One possible explanation is the presence of adiponectin resistance, which has been described in obesity and type 2 diabetes, both conditions known to be associated with increased risk of cancer.”
In a prospective cohort study, Lam and colleagues analyzed data from 5,658 adults with type 2 diabetes recruited from the Hong Kong West Diabetes Registry (median follow-up, 6.5 years). Researchers measured baseline serum adiponectin concentrations and stratified participants according to adiponectin tertiles (< 7.23 µg/mL, 7.23-12 µg/mL, 12 µg/mL), and used Cox regression analysis to estimate associations between circulating adiponectin concentrations with incident cancer and cancer-related mortality.
During follow-up, 396 participants (7.53%) developed cancer, for a cumulative incidence of 11.6 per 1,000 person-years. Researchers observed 170 cancer-related deaths (3%), for a cumulative incidence of 4.57 per 1,000 person-years.
Researchers found that adiponectin concentrations were higher among those who had incident cancer compared with those who did not develop cancer (mean, 9.8 µg/mL vs. 9.1 µg/mL; P < .001). Similarly, adiponectin concentrations were higher among participants who died from cancer-related causes vs. those who did not develop cancer (mean, 11.5 µg/mL vs. 9.3 µg/mL; P < .001).
In Cox regression analyses, serum adiponectin concentration was independently associated with incident cancer (HR = 1.19; 95% CI, 1.05-1.35) after adjustment for sex, BMI, hypertension, CVD, albuminuria, metformin use, LDL cholesterol level and estimated glomerular filtration rate at baseline.
“Although a significant interaction was found between age and serum adiponectin with incident cancer, serum adiponectin concentration remained an independent predictor of incident cancer (P = .002) after adjustment for the interaction term of age and adiponectin,” the researchers wrote.
Serum adiponectin concentration was similarly associated with cancer-related deaths (HR = 1.23; 95% CI, 1.03-1.47), with results persisting after adjustment. However, the association was attenuated in analyses that excluded participants with a history of cancer at baseline, a finding researchers attributed to the low number of events among those without a history of cancer at baseline.
In sex-stratified analyses, the association between serum adiponectin and incident cancer was only observed among men (HR = 1.23; 95% CI, 1.05-1.44).
“Whatever the underlying mechanism, our study suggested that an elevated circulating adiponectin concentration could be a risk marker of incident cancer in type 2 diabetes,” Lam said. “Whether and how medications which raise circulating adiponectin levels would impact on cancer development remains to be investigated.” – by Regina Schaffer
For more information:
Karen Lam, MD, can be reached at the Department of Medicine, University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Pokfulam, Hong Kong, China; email: ksllam@hku.hk.
Disclosures: The authors report no relevant financial disclosures.
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