Hyaluronan is Increased Systemically in Type 2 but not Type 1 Diabetes Independently of Glycemic Control

Hyaluronan (HA), an extracellular matrix polysaccharide, is implicated in the pathogenesis of both type 1 diabetes mellitus (T1DM) as well as type 2 diabetes mellitus (T2DM) and has been suggested to be increased in these diseases due to hyperglycemia. Here, we examined the serum and tissue distribution of HA in human subjects with T1DM and T2DM and in mouse models of these diseases and evaluated the relationship between HA levels and glycemic control. We found that serum HA is increased in T2DM but not T1DM. Serum HA concentrations are independent of donor hemoglobin-A1c, C-peptide, body mass index, or time since diabetes diagnosis. HA is likewise increased in skeletal muscle in T2DM subjects relative to non-diabetic controls. Similar increases in serum and muscle HA were seen in diabetic db/db mice (T2D), but not in diabetic DORmO mice (T1D). Streptozotozin (STZ) induced diabetes leads to an increase in blood glucose but HA serum levels remain unchanged. These data indicate that HA content is increased in multiple tissue compartments in T2DM but not T1DM, independently of insulin levels or glycemic control. Given that T2DM but not T1DM is associated with systemic inflammation, these patterns are consistent with HA being increased due to inflammatory factors and not hyperglycemia. Serum HA may have value as a biomarker of systemic inflammation in T2DM.