Synergistic effect of portal glucose and glucagon-like peptide-1 to lower systemic glucose and stimulate counter-regulatory hormones.

AIMS: Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone released from the gut in response to nutrients. Besides its well-established direct effect on pancreatic beta cells, GLP-1 may also act by activating sensors in the hepatoportal area. We therefore studied the impact of putative GLP-1 sensors in the splanchnic circulation. METHODS: We infused GLP-1 into the portal vein of conscious dogs, while also infusing glucose intraportally or systemically. In the first experiment, we infused glucose intraportally, simulating portal glucose values obtained during a previous mixed-meal test, with or without co-infusion of intraportal GLP-1. In the second experiment, by infusing glucose systemically, with or without intraportal GLP-1, we investigated whether the effects of systemic glucose with or without portal GLP-1 infusion are similar to those observed in the first experiment. RESULTS: Intraportal infusion of GLP-1 and glucose significantly raised peripheral GLP-1 levels, but did not produce an insulin response different from intraportal glucose alone. However, the resulting peripheral glycaemia was significantly lower compared to glucose infusion alone, and there were elevations in glucagon, cortisol and lactate. In contrast to the portal glucose infusions, there were no significant differences in glucose, insulin, glucagon, cortisol or lactate levels between systemic glucose infusion with or without GLP-1. CONCLUSIONS/INTERPRETATION: Portal GLP-1 and portal glucose, but not systemic glucose, can produce decreased peripheral glucose levels independently of hyperinsulinaemia. This suggests that portal GLP-1 and glucose receptors mediate insulin-independent changes in peripheral glycaemia and determine a strong counter-regulatory response, as reflected by changes in glucagon and cortisol.

A simple bedside test of 1-minute heart rate variability during deep breathing as a prognostic index after myocardial infarction.

BACKGROUND: We evaluate a simple, bedside test that measures 1-minute heart rate variability in deep breathing as a predictor of death after myocardial infarction. METHODS: Bedside heart rate variability was assessed in 185 consecutive patients 5.1 +/- 2.5 days after a first myocardial infarction. Patients were instructed to take 6 deep respirations in 1 minute while changes in heart rate were measured and calculated by an electrocardiographic recorder. An abnormal test result was defined as a difference of less than 10 beats/min between the shortest and longest heart rate interval. RESULTS: Heart rate variability <10 beats/min was found in 65 patients (35%) and was significantly lower (P <.05) in women, patients >60 years of age, patients with diabetes, patients with congestive heart failure, and patients taking angiotensin-converting enzyme inhibitors. Mean follow-up period was 16 months. Ten patients died during follow-up: 9 of cardiac causes and 1 of stroke. Nine of these 10 patients had heart rate variability <10 beats/min (P =.004). The sensitivity and specificity of this test for cardiovascular mortality is 90.0% and 68.0%, respectively. The negative predictive value is 99.2% and the relative risk is 16.6. Heart rate variability <10 beats/min remained a significant predictor of death after adjusting for clinical, demographic, and left ventricular function with an odds ratio of 1.38 (95% confidence interval, 1.13-1.63). CONCLUSIONS: This simple, brief bedside deep breathing test of heart rate variability in patients after myocardial infarction appears to be a good predictor for all-cause mortality and sudden death. It may be used as a clinical test for risk stratification after myocardial infarction.