Prostaglandin E2 (PGE2) Levels As a Predictor of Type 2 Diabetes Control in Human Subjects: A cross‐sectional view of initial cohort study data
Authors: Fenske Rachel , Weeks Alicia , Brill Allison , Nall Randall , Pabitch Samantha , Punt Margaret , Daniels Michael , Blaha Stephanie , Davis Dawn Belt , Kimple Michelle 
Published: November 2023

Introduction

Non‐response to pharmacotherapy in patients with Type 2 Diabetes (T2D) is poorly understood. The glucagon‐like peptide 1 (GLP‐1) signaling cascade can promote glucose‐stimulated insulin secretion from the beta cell and is one of the mostly highly targeted pharmacological pathways. GLP‐1 analogs (ie. exenatide or liraglutide) and inhibitors of dipeptidyl peptidase‐4 (DPP‐4), the enzyme that breaks down GLP‐1 (ie. sitagliptin), are some of the most commonly prescribed drugs, but are not effective in all T2D patients. Prostaglandin E2 (PGE2) mediates a counter‐regulatory pathway to the action of GLP‐1 in the beta cell and preliminary evidence suggests that tonic inhibition by PGE2 is pathologically up regulated in T2D. Use of biomarkers, such as PGE2, to identify potential non‐responders at the onset of disease is needed to guide clinical management and tailor individual pharmacotherapy.

Objectives

The primary aims of this study were to investigate if plasma prostaglandin E2 (PGE2) levels are higher in T2D versus non‐diabetic (ND) human subjects and if levels differ in T2D patients who were prescribed GLP‐1 analogs or DPP‐IV inhibitors. We also sought to determine if PGE2 levels in T2D patients correlate with disease severity or glycemic control.

Methods

This is a cross‐sectional analysis of the initial data collected for a prospective cohort study. Patients were recruited from ambulatory practices at the University of Wisconsin Hospitals & Clinics in Madison, WI. This study included a total of 171 patients: Type 2 diabetics (T2D; N = 136); and non‐diabetic controls (ND = 35). The T2D samples were separated for analyses into 2 groups; patients prescribed GLP‐1 analogs/DPP‐IV inhibitors (N = 32) and those who were not (N = 104). The dynamics of prostaglandin E2 in each of the 3 groups were assessed via demographic measures (gender, ethnicity, and BMI), as well as plasma PGE2, hemoglobin A1c (HgA1c), erythrocyte sedimentation rate (ESR), C‐reactive protein (CRP), and triglyceride levels.

Results

PGE2 levels were higher in T2D patients versus ND controls (P=0.0051). Plasma PGE2 levels positively correlate with plasma glucose level (P=0.0271), but were not significantly different between T2D samples grouped by HgA1c. ESR and triglyceride levels were increased in T2D samples (P=0.0002 and P=0.0063, respectively) and show a moderate positive correlation with HgA1c levels (P=0.0054 and P=0.0016, respectively). Interestingly, of the T2D samples, those that were positive for CRP also had increased PGE2 levels (P=0.0158).

Conclusions

Although we did not find that plasma PGE2 levels correlate with glycemic control as determined by HbA1c, we found that PGE2 levels do correlate with plasma glucose levels and other T2D plasma parameters used in clinic. Our results suggest that plasma PGE2 levels could be indicative of T2D patients that may be non‐responsive to pharmacotherapy.