Serum pigment epithelium-derived factor (PEDF) levels are correlated with adiposity, dyslipidemia, and renal dysfunction in type 2 diabetes (T2D) men. Major sources of circulating PEDF include the liver and adipose tissue. Cross-sectional studies have reported higher serum PEDF levels in T2D vs. controls. Although studies have suggested PEDF’s role in mediating insulin resistance, its potential role with regard to glycemic control remains unclear. We examined the association of serum PEDF and glycemic control in individuals with T2D (n=50; 21 men/29 women; age=63±10 years; CKD<stage 3b). PEDF was higher for those in poor (HbA1c≥7%; n=26) glycemic control (12.8±3.3 vs. 11.2±2.2 µg/mL; p=0.047) and for those that were insulin resistant (HOMA-IR>1.8; n=23; p<0.05). Spearman rank correlations of PEDF included: HbA1c≥7% (r=0.27, p=0.059), HOMA-IR>1.8 (r=0.30, p=0.037), triglycerides (r=0.53, p<0.001), creatinine (r=0.51, p<0.001), and AST (r=0.33, p=0.02). Linear regression, with PEDF as the dependent variable, revealed that AST (p=0.003), creatinine (p=0.001), triglycerides (p<0.001), and poor glycemic control (HbA1c≥7%) (p=0.009) were significant correlates (model R2=0.63, p<0.001); whereas insulin resistance (HOMA-IR>1.8) was not (p=0.70). There was also a significant interaction of AST x creatinine (p=0.02). While some suggest that elevated PEDF levels are associated with insulin resistance, the lack of an association in our data is intriguing. It is possible that gluconeogenesis by the liver and kidney is associated with elevation in circulating PEDF and PEDF may be part of an incomplete self-defensive regulatory mechanism to limit hyperglycemia. The significant interaction suggests that the relationship between creatinine and PEDF depends on AST. Taken together, the association between PEDF and poor glycemic control in persons with T2D may suggest a preferentially protective compensatory response of PEDF against hyperglycemia but not insulin resistance.
R.E. Maser: None. J. Lenhard: Speaker's Bureau; Self; Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Sanofi. R. Pohlig: None. P. Balagopal: None.