Circulating PANDER concentration is associated with increased HbA1c and fasting blood glucose in Type 2 diabetic subjects

Abstract

Aim: PANcreatic-DERived factor (PANDER, FAM3B) is a novel hormone that regulates glucose levels via interaction with both the endocrine pancreas and liver. Prior studies examining PANDER were primarily conducted in murine models or in vitro but little is known regarding the circulating concentration of PANDER in humans, especially with regard to the association of type 2 diabetes (T2D) or overall glycemic regulation. To address this limitation, we performed a cross-sectional analysis of circulating serum PANDER concentration in association with other hormones that serve as either markers of insulin resistance (insulin and adiponectin) or to metabolic parameters of glycemic control such as fasting HbA1c and blood glucose (FBG). Methods: Fasting serum was obtained from a commercial biorepository from 300 de-identified adult subjects with 150 T2D and non-T2D adult subjects collected from a population within the United States, respectively, matched on gender, age group and race/ethnicity. Concentration of PANDER, insulin and adiponectin were measured for all samples as determined by commercial ELISA. Metadata was provided for each subject including demography, anthropometry, and cigarette and alcohol use. In addition, fasting blood glucose (FBG) and HbA1c were available on T2D subjects. Results: Multiple linear regression analyses were performed to examine the relationships between circulating log PANDER concentration on HbA1c, fasting glucose, log insulin, log HOMA-β and log HOMA-IR among T2D subjects and for insulin and adiponectin in non-T2D subjects. A significant linear association was identified between PANDER with fasting HbA1c (β 0.832 ± SE 0.22, p = 0.0003) and FBG (β 20.66 ± SE 7.43, p = 0.006) within T2D subjects. However, insulin, HOMA-β, HOMA-IR and adiponectin (p > 0.05) were not found to be linearly associated with PANDER concentration. Conclusion: Within T2D subjects, PANDER is modestly linearly associated with increased HbA1c and FBG in a US population. In addition, highest circulating PANDER levels were measured in T2D subjects with HbA1c above 9.9. No association was identified with PANDER and insulin resistance or pancreatic β-cell function in T2D subjects. Keywords: Fam3B, PANDER, Type 2 diabetes, HbA1c, Glucose