Background The gut incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose- dependent insulinotropic peptide) are secreted by enteroendocrine cells following food intake leading to insulin secretion and glucose lowering. Beyond its regulatory effects in glucose metabolism GIP has been found to reduce atherosclerotic lesion size and to increase plaque stability in mice. Furthermore GIP improved left ventricular function in experimental models of ischemic cardiomyopathy. The aim of this study was to characterize endogenous GIP secretion in patients with acute myocardial infarction.

Methods and Results Serum concentrations of GIP were assessed in 971 patients who presented with clinical indication of coronary angiography. Circulating GIP levels were significantly lower in patients with STEMI (ST- elevation myocardial infarction; n=102) compared to clinically stable patients with angiographic exclusion of coronary artery disease and no myocardial infarction (n=259) (292.2 ± 274.3 vs. 369.2 ± 314.2 pg/mL, p = 0.019). GIP levels in patients with NSTEMI (n=134) compared to patients without myocardial infarction showed no significant difference (335.88 ± 334.56 vs. 369.2 ± 314.2 pg/mL, p = 0.128). GIP levels were not associated with hypertension, diabetes, CRP, WBC, serum creatinine, troponin or LDL-cholesterol. To further elucidate the underlying mechanisms we prospectively enrolled 18 non-diabetic patients (10 male, 8 female) scheduled for cardiac surgery with cardiopulmonary bypass and requirement of extracorporeal circulation as a reproducible inflammatory stimulus and cardiac injury. Blood samples were drawn directly before surgery (baseline), upon arrival at the intensive care unit (ICU) (4 to 6 h time point), 6 h post arrival to the ICU (10 to 12 h time point) and at the morning of the first and second postoperative day. Mean circulating GIP concentrations decreased in response to surgery from 53.3 ± 16.8 pg/mL at baseline to a minimum of 42.9 ± 14.3 pg/mL at the first postoperative day (p = 0.009) and rose again at the second postoperative day (58.6 ± 21.7 pg/mL). This was preceded by an early drop of leptin, which was significantly associated with GIP post surgery but not at baseline. GIP levels did not correlate with markers of inflammation (IL-6, CRP). These results might suggest nutrition-independent regulation of GIP secretion following cardiac injury.

Conclusion GIP secretion is downregulated in patients with myocardial infarction and in patients post cardiac surgery. Future studies are needed to foster our understanding of the gut - heart axis to potentially develop novel therapeutical avenues for the treatment of cardiovascular disease.