Endocrine Abstracts

Background: Glucagon-like peptide-1 (GLP-1) is secreted from L cell at a small intestine and decreases blood glucose by stimulating insulin secretion. Therefore, GLP-1 receptor antagonists (GLP1-RA) is used to treat type 2 diabetes mellitus. In addition to the hypoglycemic effect, GLP-1 has been reported to reduce heart disease and renal dysfunctions. GLP-1 action on the kidneys is a natriuretic effect. Therefore, it may have a renoprotection effect. However, it is unknown whether there is any correlation between kidney function and GLP-1 secretion. Long oral glucose tolerance test (OGTT) can detects glucose metabolism (i.e.: reactive hypoglycemia) more precisely than 2-h OGTT. In this study, we investigated the relationship between GLP-1 levels and estimated glomerular filtration rate (eGFR) in patients with heart disease, using long OGTT.

Methods: In this prospective observational study, we enrolled 30 non-diabetic patients (age 69±10 years, 70% males, HbA1c 43 mmol/mol). A 4-h OGTT was performed, and glucose, insulin, glucagon (radioimmunoassay [RIA] and sandwich ELISA [S-W] methods) and active GLP-1 were evaluated during 4-h. We compared these factors and eGFR.

Results: HbA1c and area under the curve (AUC) of the glucose, insulin and glucagon during long OGTT are not correlated with eGFR. Although fasting activated GLP-1 is not correlated with eGFR, AUC of the activate GLP-1 after long OGTT is significantly negatively correlated with eGFR (R=−0.385 P=0.043). Divided into 3 tertials, although HbA1c (Lowest eGFR group: 42±4 vs. the other eGFR group: 43±3 mmol·min/l, P=0.43), fasting active GLP-1 (Lowest eGFR group: 2.00 [2.00–2.00] vs. the other eGFR group: 2.00 [2.00–2.40] pmol·min/l, P=0.59) and AUC of the glucose (Lowest eGFR group: 1789.2±261.0 vs. the other eGFR group: 1864.4±353.5 mmol·min/l, P=0.57), insulin and glucagon after long OGTT were not different, AUC of the active GLP-1 after long OGTT was significantly greater in the lowest eGFR group (38±10 ml/min/1.73 m²), than that in the other group (70±12 ml/min/1.73 m²) (Lowest eGFR group: 1773.0 [1000.5–2958.0] vs. the other group: 982.5 [825.8–1551.0] pmol·min/l, P≤0.05).

Conclusion: In non-diabetes patients with heart disease, fasting GLP-1 secretion and other glucometabolic factors were not correlated with eGRF. However, GLP-1 secretion after oral glucose load was negatively correlated with eGFR. Greater GLP-1 secretion was observed as eGFR was lower. These data suggest that GLP-1is assumed have renoprotective effect besides glycemic control.