Serum galectin-3 and S100A9 levels are strongly associated with pancreatic cancer-associated diabetes (PCDM) and might be useful in distinguishing PCDM from type 2 diabetes (T2D) in patients with new-onset diabetes, according to study results published in Diabetes Care.

Researchers conducted this study to identify diabetogenic factors that mediate PCDM and assess whether these factors are useful in distinguishing PCDM from T2D. The study included 2 cohorts: a training set and a test set. The training set consisted of 50 patients with PCDM, as well as 5 subgroups (n=50 for each) of patients with pancreatic cancer without diabetes, T2D, pancreatitis, other pancreatic/peripancreatic tumors, and healthy control patients. The test set consisted of patients with T2D (n=41) or PCDM (n=41).

The researchers first used proteomics to identify secreted proteins of PaCa-2 cells. Glucose uptake assay was then used to pinpoint candidate factors with ≥10-fold overexpression in the pancreatic cancer transcriptome data set from the Gene Expression Omnibus database. Each participant was measured for serum levels of galectin-3, S100A9, and other potential factors.

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Galectin-3 and S100A9 levels were overexpressed in tumors with PCDM and dose-dependently suppressed insulin-stimulated glucose uptake in muscle cells. These factors were only elevated in patients with PCDM, and thus distinguished PCDM from T2D; the area under the curve for galectin-3 and S100A9 in differentiating PCDM and T2D was 0.73 (95% CI, 0.64-0.83) and 0.79 (95% CI, 0.70-0.87), respectively. Galectin-3 and S100A9 were significantly higher in PCDM compared with the subgroups with other tumors and pancreatitis. The optimal cutoffs for galectin-3 and S100A9 were 6.5 ng/mL and 59.0 ng/mL, respectively.

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The researchers used the test set to validate these cutoff values derived from the training set. The test set yielded similar results, with an area under the curve of 0.83 (95% CI, 0.74-0.92) for galectin-3 and 0.77 (95% CI, 0.67-0.87) for S100A9 in differentiating PCDM and T2D. The cutoff value for galectin-3 had a sensitivity of 72.1% and a specificity of 86.1%. For S100A9, the cutoff value had a sensitivity of 69.8% and a specificity of 58.1%.

In summarizing their findings, the researchers said, “These results support that galectin-3 and S100A9 are [pancreatic cancer]-produced diabetogenic factors that mediate peripheral insulin resistance/PCDM and may facilitate identification of patients at high risk of PCDM for further evaluations among subjects with new-onset diabetes.”

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Liao WC, Huang BS, Yu YH, et al. Galectin-3 and S100A9: novel diabetogenic factors mediating pancreatic cancer–associated diabetes [published online July 1, 2019]. Diabetes Care. doi:10.2337/dc19-0217