THE ROLE OF GUT-DERIVED GLP-1 IN HYPOGLYCEMIA UNAWARENESS

Abstract

Hypoglycemia unawareness is a dangerous complication of diabetes, marked by a diminished perception of low blood glucose levels and an impaired counter-regulatory response. Emerging evidence suggests that gut-derived glucagon-like peptide-1 (GLP-1), a key incretin hormone, may play a role in modulating hypoglycemia awareness through its influence on hormonal and autonomic pathways.To study how levels of GLP-1 are linked to hypoglycemia unawareness among people with diabetes and whether higher GLP-1 causes people to lose the ability to fight low blood sugar. People with diabetes separated into two groups, one aware of hypoglycemia and one not and were examined in a cross-sectional study.  Among the other important counter-regulating hormones (glucagon, cortisol, epinephrine) and insulin, glucose readings and the frequency of low blood sugar detected by CGM, I also examined GLP-1 levels both while fasting and after meals.  A statistical approach was used to check for similarities between groups of awareness and groups of unawareness. Those with hypoglycemia unawareness had much higher fasting GLP-1 (29.93 ± 5.50 pmol/L) and more GLP-1 AUC (2402 ± 342) compared to conscious participants and their glucagon (50.12 ± 12.03 pg/mL), cortisol (9.03 ± 3.12 µg/dL) and epinephrine (59.84 ± 20.04 pg/m  Moreover, people without awareness had about four times as many hypoglycemia episodes (6.49 ± 1.96 vs. 2.53 ± 1.12, p < 0.01).  The frequency of hypoglycemia increased as GLP-1 levels in the blood went up, as seen during the study. The study suggests that when GLP-1 acts too much, people may become unaware of hypoglycemia because their hormones cannot balance it properly.  These findings suggest it is necessary to design custom diabetes treatment plans, mainly for GLP-1-based medications.