Circulating cytokines as biomarkers for early stages of type 2 diabetes in the db/db mouse

Inflammatory factors are thought to play an important role in the development of type 2 diabetes (T2D). In this study, we examined 32 cytokines by serum assay from db/db and aged-matched heterozygous (het) mice as controls to create a cytokine profile in early T2D at 5, 6–7, and 11 weeks of age. Serum cytokine levels were correlated with body weight, blood glucose, and body fat content. Db/db mice had increased serum levels of CXCR5 and decreased IL-1a and IL-13 levels. At 5 weeks of age, db/db and het mice showed no signs of obesity or hyperglycemia but db/db mice had increased % body fat and reduced IL-1a levels compared to het mice. At age 6–7 weeks, db/db mice showed variable cytokine profiles while transitioning to obesity and T2D. By 11 weeks, db/db mice were diabetic and obese and had increased CXCR5 levels compared to het mice. Among db/db mice only, increased body weight was associated with increased serum levels of KC and CXCR5. Also among db/db mice, elevated blood glucose was linked with lower eotaxin and higher MCP-1 levels. These data reveal relationships among serum cytokine levels, blood glucose, and body weight that may play a key role in T2D progression. Supported by NIH K01 DK081621.