Relationship between fasting plasma glucagon level and renal function - A cross-sectional study in individuals with type 2 diabetes

Abstract

Background and Aim: The kidney is the main site for glucagon clearance. However, a recent study showed that hyperglucagonemia in patients with end-stage renal disease might not be caused by fulllength intact glucagon. Additionally, the relationship between glucagon and renal function in earlystage chronic kidney disease (CKD) has not yet been characterized. We studied the association of fasting glucagon with renal function across a wide range of glomerular filtration rates (GFRs) in participants with type 2 diabetes. Participants and Methods: 326 participants with type 2 diabetes and renal function spanning CKD stage 1 to 5 were included in the present cross-sectional study. Fasting full-length plasma glucagon was quantified using a newly developed ELISA (Mercodia AB, Uppsala, Sweden). Results: The fasting plasma glucagon level was elevated linearly from CKD stage 1 to 5 [from a median of 2.5 pM (interquartile range, 1.4 to 4.7) in CKD 1 to a median of 8.3 pM (interquartile range, 5.9 to 12.8) in CKD 5; P for trend , 0.0001], from as early as CKD stage 2 compared with that in stage 1 (Bonferroni-corrected P , 0.0001). The estimated GFR and homeostatic model of assessment-insulin resistance were the main determinants of the fasting glucagon level. These explained 14.3% and 10.3% of the glucagon variance, respectively. Albuminuria was not associated with fasting glucagon after adjustment for estimated GFR. Conclusions: Fasting full-length glucagon was elevated linearly with the deterioration in renal function in individuals with type 2 diabetes, even in those with early CKD. In addition to renal function, insulin sensitivity was also a main determinant of glucagon variance. © 2019 Endocrine Society.