Showing papers by "Bastiaan E. de Galan published in 2002"
TL;DR: Caffeine can decrease insulin sensitivity in healthy humans, possibly as a result of elevated plasma epinephrine levels, and peripheral adenosine receptor antagonism does not appear to contribute to this effect.
Abstract: OBJECTIVE —Caffeine is a central stimulant that increases the release of catecholamines. As a component of popular beverages, caffeine is widely used around the world. Its pharmacological effects are predominantly due to adenosine receptor antagonism and include release of catecholamines. We hypothesized that caffeine reduces insulin sensitivity, either due to catecholamines and/or as a result of blocking adenosine-mediated stimulation of peripheral glucose uptake. RESEARCH DESIGN AND METHODS —Hyperinsulinemic-euglycemic glucose clamps were used to assess insulin sensitivity. Caffeine or placebo was administered intravenously to 12 healthy volunteers in a randomized, double-blind, crossover design. Measurements included plasma levels of insulin, catecholamines, free fatty acids (FFAs), and hemodynamic parameters. Insulin sensitivity was calculated as whole-body glucose uptake corrected for the insulin concentration. In a second study, the adenosine reuptake inhibitor dipyridamole was tested using an identical protocol in 10 healthy subjects. RESULTS —Caffeine decreased insulin sensitivity by 15% ( P P P P P P CONCLUSIONS —Caffeine can decrease insulin sensitivity in healthy humans, possibly as a result of elevated plasma epinephrine levels. Because dipyridamole did not affect glucose uptake, peripheral adenosine receptor antagonism does not appear to contribute to this effect.
343 citations
TL;DR: It is concluded that theophylline improves counterregulatory responses to and perception of hypoglycemia in diabetic patients with impaired awareness of hypglycemia.
Abstract: Iatrogenic hypoglycemias and the subsequent occurrence of hypoglycemia unawareness are well-known complications of intensive insulin therapy in type 1 diabetic patients that limit glycemic management. From a pharmacological point of view, the adenosine-receptor antagonist theophylline might be beneficial in the management of hypoglycemia unawareness. Theophylline stimulates the release of catecholamines and reduces cerebral blood flow, thereby facilitating stronger metabolic responses to and a prompter perception of decreasing glucose levels. To test the effect of theophylline on responses to hypoglycemia, we performed paired hyperinsulinemic-hypoglycemic clamp studies in 15 diabetic patients with hypoglycemia unawareness and 15 matched healthy control subjects. In random order, we concurrently infused either theophylline or placebo. Measurements included counterregulatory hormones, symptoms, hemodynamic parameters, and sweat detection using a dew-point electrode. Additionally, middle cerebral artery velocities (V(MCA)) using transcranial Doppler were monitored as an estimate of cerebral blood flow. When compared with placebo, theophylline significantly enhanced responses of plasma epinephrine, norepinephrine, and cortisol levels in both diabetic patients and control subjects. Because of the theophylline, sweat production started at approximately 0.3 mmol/l higher glucose levels in both groups (P < 0.01), and symptom scores in diabetic patients approached those in control subjects. Theophylline decreased V(MCA) in both groups (P < 0.001), but significantly greater in diabetic patients (P < 0.01), and prevented the hypoglycemia-induced increase of V(MCA) that occurred during the placebo studies. We conclude that theophylline improves counterregulatory responses to and perception of hypoglycemia in diabetic patients with impaired awareness of hypoglycemia.
54 citations
TL;DR: It is concluded that low-dose heparin in the solution to flush an arterial catheter has no short-term vasodilator effect in the human forearm vascular bed and the results of studies using the perfused-forearm technique are not confounded by flushes with a low- dose heparIn solution.
Abstract: Objective. Recent reports show that heparin induces vasodilation. This heparin-induced vasodilation might interfere with the results of vascular studies using the perfused-forearm technique because the arterial catheter is often flushed with a heparin solution in those experiments. Therefore, we investigated the vascular effects of flushing an arterial catheter with a heparin solution compared with a placebo solution (NaCl 0.9%) in six healthy volunteers. Methods. During the first half of each experiment, the arterial catheter was flushed several times with the placebo solution. In the second half, identical flushes were performed with a solution of heparin diluted in NaCl 0.9% (4U·ml–1). Results. Forearm blood flow (venous occlusion plethysmography) response was similar with heparin and placebo after all flushes. Conclusion. We conclude that low-dose heparin in the solution to flush an arterial catheter has no short-term vasodilator effect in the human forearm vascular bed. Therefore, the results of studies using the perfused-forearm technique are not confounded by flushes with a low-dose heparin solution.