TY - JOUR AU - Mook, W.N. van AU - Koek, G.H. AU - Ven, A.J.A.M. van der AU - Ceelen, T.L. AU - Bos, R.P. PY - 2004 UR - https://hdl.handle.net/2066/58281 AB - Spirochaetes are well known causative agents of diarrhoea in veterinary medicine. In human medicine the relationship between presence of spirochaetes in the colon on the one hand, and its clinical significance on the other, is far less clear. In the majority of cases the colonization of the colon with these micro-organisms seems to represent a commensal relationship with the host, and is almost always a coincidental finding with no association with the clinical symptoms of the patient whatsoever. Very infrequently the organism may become invasive. In this article the literature on human intestinal spirochaetosis is reviewed, and key points for daily clinical practice are emphasized. TI - Human intestinal spirochaetosis: any clinical significance? EP - 87 SN - 0954-691X IS - iss. 1 SP - 83 JF - European Journal of Gastroenterology & Hepatology VL - vol. 16 DO - https://doi.org/10.1097/00042737-200401000-00013 ER - TY - JOUR AU - Ginneken, E.E.M. van AU - Meijer, P. AU - Verkaik, N.S. AU - Smits, P. AU - Rongen, G.A.P.J.M. PY - 2004 UR - https://hdl.handle.net/2066/57594 AB - 1. The purine nucleotide adenosine-5'-triphosphate (ATP) exerts pronounced effects on the cardiovascular system. The mechanism of action of the vasodilator response to ATP in humans has not been elucidated yet. The proposed endothelium-derived relaxing factors (EDRFs) were studied in a series of experiments, using the perfused forearm technique. 2. Adenosine 5'-triphosphate (0.2, 0.6, 6 and 20 nmol dl(-1) forearm volume min(-1)) evoked a dose-dependent forearm vasodilator response, which could not be inhibited by separate infusion of the nonselective COX inhibitor indomethacin (5 microg dl(-1) min(-1), n=10), the blocker of Na(+)/K(+)-ATPase ouabain (0.2 microg dl(-1) min(-1), n=8), the blocker of K(Ca) channels tetraethylammonium chloride (TEA, 0.1 microg dl(-1) min(-1), n=10), nor by the K(ATP)-channel blocker glibenclamide (2 microg dl(-1) min(-1), n=10). All blockers, except glibenclamide, caused a significant increase in baseline vascular tone. The obtained results might be due to compensatory actions of unblocked EDRFs. Combined infusion of TEA, indomethacin and l-NMMA (n=6) significantly increased the baseline forearm vascular resistance. The ATP-induced relative decreases in forearm vascular resistance were 48+/-5, 67+/-3, 88+/-2, and 92+/-2% in the absence and 23+/-7, 62+/-4, 89+/-2, and 93+/-1% in the presence of the combination of TEA, indomethacin and l-NMMA (P<0.05, repeated-measures ANOVA, n=6). A similar inhibition was obtained for sodium nitroprusside (SNP, P<0.05 repeated-measures ANOVA, n=6), indicating a nonspecific interaction due to the blocker-induced vasoconstriction. 3. ATP-induced vasodilation in the human forearm cannot be inhibited by separate infusion of indomethacin, ouabain, glibenclamide or TEA, or by a combined infusion of TEA, indomethacin, and l-NMMA. Endothelium-independent mechanisms and involvement of unblocked EDRFs, such as CO, might play a role, and call for further studies. TI - ATP-induced vasodilation in human skeletal muscle. EP - 850 SN - 0007-1188 IS - iss. 5 SP - 842 JF - British Journal of Pharmacology VL - vol. 141 DO - https://doi.org/10.1038/sj.bjp.0705589 ER - TY - JOUR AU - Pickkers, P. AU - Rosendaal, A.J. van AU - Hoeven, J.G. van der AU - Smits, P. PY - 2004 UR - https://hdl.handle.net/2066/57698 AB - Sepsis-induced vasodilation is characterized by an attenuated sensitivity to vasoconstrictor substances such as norepinephrine, possibly mediated by activation of vascular potassium channels. We determined whether vasodilation associated with potassium channel activation resulted in an attenuated vasoconstrictive response to norepinephrine in humans and whether the vasodilation associated with potassium channel activation could be inhibited by pharmacological potassium channel blockers. In 30 volunteers, the brachial artery was cannulated for infusion of drugs. Forearm blood flow (FBF) was measured in both arms using strain-gauge venous occlusion plethysmography. Forearm vascular resistance (FVR, mean arterial pressure/FBF) was calculated. The effects of vasodilation induced by sodium nitroprusside (SNP, nitric oxide donor) or diazoxide (activator of the ATP-dependent potassium channel) on norepinephrine-mediated vasoconstriction were examined. Also, the effects of potassium channel blockers on vasodilation associated with potassium channel activation were determined. Intraarterial SNP infusion (2 microg/min/dL) increased forearm blood flow by 235%, from (mean +/- SEM) 2.8 +/- 0.7 to 9.4 +/- 1.5 mL/min/dL (P < 0.0001). Subsequent norepinephrine infusion (10, 30, 100, 300, 1000 ng/min/dL) increased FVR dose-dependently from 13 +/- 4 AU to 249 +/- 45 AU at the highest norepinephrine infusion. Intraarterial diazoxide infusion (1 mg/min/dL) increased FBF by 209% from 2.2 +/- 0.3 to 6.8 +/- 1.0 mL/min/dL (P < 0.001). Subsequent norepinephrine infusion increased FVR from 18 +/- 5 to 51 +/- 6 AU at the highest norepinephrine infusion rate (n = 10), significantly different from the norepinephrine-induced effects during SNP coinfusion (P < 0.001). Diazoxide-induced fall in FVR in the infused forearm was inhibited by potassium channel blockers tetraethyl ammonium (1 mg/min/dL, n = 10, P = 0.004) and quinine (50 microg/min/dL, n = 10, P = 0.016). Vasodilation induced by vascular potassium channel activation is associated with an impressive reduction in the vasoconstrictor response to norepinephrine in humans. In accordance with animal experiments, this indicates that potassium channel activation could account for the diminished norepinephrine sensitivity in septic patients. Vasodilation associated with potassium channel activation can be inhibited by pharmacological potassium channel blockade. The possible role of potassium channel blockers during sepsis-induced potassium channel activation and vasodilation in humans needs further elucidation. TI - Activation of the ATP-dependent potassium channel attenuates norepinephrine-induced vasoconstriction in the human forearm. EP - 325 SN - 1073-2322 IS - iss. 4 SP - 320 JF - Shock VL - vol. 22 DO - https://doi.org/10.1097/01.shk.0000142250.85264.10 ER - TY - JOUR AU - Abbink-Zandbergen, E.J. AU - Wal, P.S. van der AU - Sweep, C.G.J. AU - Smits, P. AU - Tack, C.J.J. PY - 2004 UR - https://hdl.handle.net/2066/57764 AB - BACKGROUND: The more rapid onset of action and the shorter half-life of repaglinide may reduce the post-load glucose excursion and limit sustained insulin secretion compared to sulphonylurea (SU) derivatives. METHODS: We studied 12 patients with type 2 diabetes (age 62 +/- 2 years, BMI 28.3 +/- 1.3 kg m(-2), HbA1c 6.7 +/- 0.2%) on SU monotherapy at submaximal dose. Patients were treated for 3 weeks with repaglinide or glibenclamide in a randomized, crossover trial. At the end of each treatment period, patients underwent a 60-min hyperglycaemic clamp (glucose 12 mmol L(-1)) followed by 4-h observation (60-300 min) with frequent blood sampling for determination of glucose, insulin, proinsulin and C-peptide levels. Before the clamp (5 min for repaglinide, 30 min for glibenclamide), patients ingested their usual morning drug dose. RESULTS: After the end of the hyperglycaemic clamp, mean plasma glucose fell to a level of 5 mmol L(-1) after approximately 150 min with repaglinide, and after approximately 190 min with glibenclamide. While initially quite similar, in the period from 240 to 300 min, insulin, proinsulin and C-peptide levels were lower during repaglinide treatment (insulin 133 +/- 20 vs 153 +/- 25 pmol L(-1) (P < 0.05), proinsulin 14 +/- 3 vs 19 +/- 4 pmol L(-1) (P = 0.06) and C-peptide 0.81 +/- 0.19 vs 1.14 +/- 0.18 nmol L(-1) (P = 0.05) for repaglinide vs glibenclamide, respectively). CONCLUSIONS: Following glucose stimulation, plasma glucose levels, and insulin concentration decrease more rapidly after repaglinide treatment than after glibenclamide. Proinsulin and C-peptide secretion tended to fall more rapidly as well. These findings are consistent with a more rapid onset and shorter duration of beta-cell stimulation associated with repaglinide. TI - Compared to glibenclamide, repaglinide treatment results in a more rapid fall in glucose level and beta-cell secretion after glucose stimulation. EP - 471 SN - 1520-7552 IS - iss. 6 SP - 466 JF - Diabetes-Metabolism Research and Reviews VL - vol. 20 DO - https://doi.org/10.1002/dmrr.474 ER - TY - JOUR AU - Veldman, B.A.J. AU - Waanders, M. AU - Smits, P. PY - 2004 UR - https://hdl.handle.net/2066/57122 AB - RATIONALE: L-NMMA is widely used in venous occlusion plethysmography studies to determine baseline NO production. Studies using L-NMMA indicate that endothelial dysfunction is present early in the course of diabetic microvascular complications. However, the optimal dose to maximally inhibit NO-production is unknown. OBJECTIVE: To determine the L-NMMA-dose that maximally reduces basal forearm blood flow (FBF). To investigate whether there are any differences in the response to L-NMMA between non-complicated type 1 diabetes patients and control subjects. METHODS: In eight non-complicated type 1 diabetes patients and nine healthy subjects FBF-responses to intra-arterial infusion of increasing doses of L-NMMA (0.01-1.6 mg/min/dL forearm volume [FAV]) were measured using the perfused forearm technique. RESULTS: Infusion of 0.8 mg/min/dL maximally reduced FBF. The dose of 1.6 mg/min/dL did not additionally reduce FBF. No differences existed between non-complicated type 1 diabetes patients and controls with regard to EC50 (0.017 +/- 0.02 resp. 0.22 +/- 0.02 mg L-NMMA/min/dL) or maximal vasoconstrictive response (Delta FBF: 1.13 +/- 0.4 resp. 0.97 +/- 0.4 mL/min/dL). Throughout the study blood pressure increased significantly in both groups, possibly reflecting a systemic vasoconstrictive effect of L-NMMA. CONCLUSIONS: The maximal vasoconstrictive dose was 0.8 mg/min/dL in type 1 diabetes patients as well as the control subjects. There were no significant differences between non-complicated type 1 diabetes subjects and controls with regard to the pharmacodynamics of L-NMMA. At high dosages of L-NMMA a systemic effect can not be ruled out. TI - Pharmacodynamics of L-NMMA in type 1 diabetes patients and control subjects. EP - 234 SN - 0160-2446 IS - iss. 2 SP - 231 JF - Journal of Cardiovascular Pharmacology VL - vol. 44 DO - https://doi.org/10.1097/00005344-200408000-00013 ER - TY - JOUR AU - Bleeker-Rovers, C.P. AU - Ven, A.J.A.M. van der AU - Zomer, B. AU - Geus-Oei, L.F. de AU - Smits, P. AU - Corstens, F.H.M. AU - Koopmans †, P.P. AU - Oyen, W.J.G. PY - 2004 UR - https://hdl.handle.net/2066/58509 TI - F-18-fluorodeoxyglucose positron emission tomography for visualization of lipodystrophy in HIV-infected patients. EP - 2432 SN - 0269-9370 IS - iss. 18 SP - 2430 JF - Aids VL - vol. 18 ER - TY - JOUR AU - Bijlstra, P.J. AU - Ginneken, E.E.M. van AU - Huls, M. AU - Dijk, R. van AU - Smits, P. AU - Rongen, G.A.P.J.M. PY - 2004 UR - https://hdl.handle.net/2066/58379 AB - BACKGROUND: The mechanism of the vasodilator response to adenosine has not been elucidated in humans. Stimulation of adenosine receptors on endothelial and vascular smooth muscle cells with subsequent endothelial release of nitric oxide and opening of adenosine triphosphate (ATP)-sensitive potassium (K(ATP)) channels has been suggested. AIM: The aim of this study was to investigate the involvement of K(ATP) channels in the vasodilator response to adenosine and the nucleoside transport inhibitor dipyridamole.Methods and results In healthy male volunteers, adenosine (0.6, 1.9, 5.6, 19, 57, and 190 nmol. min(-1). dL(-1)) was infused into the brachial artery, and forearm blood flow (FBF) was measured by use of strain-gauge plethysmography. Adenosine increased the FBF ratio (FBF in experimental arm/FBF in control arm) from 1.3 +/- 0.2 to 1.2 +/- 0.2, 1.5 +/- 0.2, 2.8 +/- 0.4, 7.3 +/- 2.3, 11.1 +/- 4.1, and 12.9 +/- 3.7 for the six increasing adenosine doses, respectively. Simultaneous infusion of glyburide (INN, glibenclamide), a blocker of K(ATP) channels, did not affect this response (from 1.7 +/- 0.4 to 1.5 +/- 0.2, 2.2 +/- 0.3, 4.0 +/- 1.0, 9.3 +/- 4.0, 13.5 +/- 6.4, and 15.9 +/- 5.3 for the 6 increasing doses of adenosine, respectively; P =.439, n = 6). The increase in FBF ratio during infusion of the nucleoside transport inhibitor dipyridamole (20, 60, and 200 nmol. min(-1). dL(-1)) was significantly reduced by glyburide, as follows: from 1.2 +/- 0.1 to 1.7 +/- 0.2, 2.4 +/- 0.5, and 2.9 +/- 0.4, respectively, during saline solution and from 1.6 +/- 0.2 to 1.8 +/- 0.2, 2.1 +/- 0.3, and 2.2 +/- 0.4, respectively, during glyburide (P =.010 for effect of glyburide on response from baseline, ANOVA for repeated measures; n = 8). The vasodilator response to dipyridamole was significantly inhibited by the adenosine receptor antagonist theophylline. CONCLUSION: Opening of vascular K(ATP) channels is involved in the forearm vasodilator response to dipyridamole but not to adenosine. Differences in stimulated cell type (endothelium for adenosine versus smooth muscle cells for dipyridamole) may underlie this divergent pharmacologic profile. TI - Glyburide inhibits dipyridamole-induced forearm vasodilation but not adenosine-induced forearm vasodilation. EP - 156 SN - 0009-9236 IS - iss. 3 SP - 147 JF - Clinical Pharmacology and Therapeutics VL - vol. 75 DO - https://doi.org/10.1016/j.clpt.2003.09.016 ER - TY - JOUR AU - Riksen, N.P. AU - Smits, P. AU - Rongen, G.A.P.J.M. PY - 2004 UR - https://hdl.handle.net/2066/57665 AB - Ischaemic preconditioning was originally described in animal hearts as histological infarct-size limitation by a previous brief episode of ischaemia. In humans, ischaemic preconditioning has been demonstrated in several in vitro and in vivo models, including coronary artery bypass grafting and percutaneous transluminal coronary angiograplasty, using surrogate markers of ischaemia and reperfusion injury. Increasing knowledge of the molecular signalling pathways mediating protection by ischaemic preconditioning has provided rational targets for pharmacological intervention. Several widely used drugs are able to mimic ischaemic preconditioning (e.g. adenosine, adenosine-uptake inhibitors, ACE inhibitors, angiotensin II antagonists, statins, opioids, volatile anaesthetics and ethanol), whereas others inhibit ischaemic preconditioning-induced protection (e.g. sulphonylureas and adenosine antagonists). The present review focuses on these different classes of drugs. Prudent use or avoidance of these drugs in patients who are at risk for myocardial infarction could theoretically limit ischaemia and reperfusion injury. TI - Ischaemic preconditioning: from molecular characterisation to clinical application--part II. EP - 423 SN - 0300-2977 IS - iss. 11 SP - 409 JF - Netherlands Journal of Medicine VL - vol. 62 ER - TY - JOUR AU - Riksen, N.P. AU - Smits, P. AU - Rongen, G.A.P.J.M. PY - 2004 UR - https://hdl.handle.net/2066/57664 AB - Ischaemic preconditioning is defined as an increased tolerance to ischaemia and reperfusion induced by a previous sublethal period of ischaemia. Since this is the most powerful mechanism for limiting infarct size, other than timely reperfusion, an overwhelming number of studies have addressed the way in which this form of protection occurs. During the short preconditioning period of ischaemia, several trigger substances are released (adenosine, bradykinin, norepinephrine, opioids). By activation of membrane-bound receptors, these substances activate a complex intracellular signalling cascade, which converges on mitochondrial end-effectors, including the ATP-sensitive potassium channel and the mitochondrial permeability transition pore. Activation of this pathway protects cardiomyocytes against both necrosis and apoptosis during a subsequent more prolonged ischaemic episode. The protection afforded by preconditioning lasts only two to three hours, but reappears 24 hours after the preconditioning stimulus. This 'delayed preconditioning' requires synthesis of new proteins, including inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and heat shock proteins. Additionally, preconditioning is not confined to one organ, but can also limit infarct size in remote, non-preconditioned organs ('remote preconditioning'). Knowledge of these mechanisms mediating ischaemic preconditioning is essential to understand which drugs are able to mimic preconditioning or interfere with pre-conditioning in patients at risk for myocardial ischaemia. This review aims to summarise current knowledge regarding the different forms and mechanisms of ischaemic preconditioning. TI - Ischaemic preconditioning: from molecular characterisation to clinical application--part I. EP - 363 SN - 0300-2977 IS - iss. 10 SP - 353 JF - Netherlands Journal of Medicine VL - vol. 62 ER - TY - JOUR AU - Bleeker, M.W.P. AU - Hopman, M.T.E. AU - Rongen, G.A.P.J.M. AU - Smits, P. PY - 2004 UR - https://hdl.handle.net/2066/59162 TI - Unilateral lower limb suspension can cause deep venous thrombosis. EP - 7 SN - 0363-6119 IS - iss. 6 SP - R1176 JF - American Journal of Physiology : Regulatory Integrative and Comparative Physiology VL - vol. 286 DO - https://doi.org/10.1152/ajpregu.00718.2003 ER - TY - JOUR AU - Ginneken, E.E.M. van AU - Droogleever Fortuyn, H.A. AU - Smits, P. AU - Rongen, G.A.P.J.M. PY - 2004 UR - https://hdl.handle.net/2066/59356 AB - Adenosine is an endogenous purine with vasodilating and cardioprotective properties. Animal experiments have shown that some benzodiazepine-induced effects can be explained by potentiation of adenosine effects, via inhibition of the nucleoside transport system. The objective of this study was to determine whether the frequently used benzodiazepines diazepam and midazolam increase adenosine-induced vasodilation in the human forearm vascular bed, measured by venous occlusion plethysmography. Adenosine (0.6, 6, 20, and 60 nmol/min/dl ForeArm Volume) was infused into the brachial artery with and without concomitant separate infusion of diazepam (21 nmol/min/dl, n = 9) and midazolam (23 nmol/min/dl, n = 8). Plasma concentrations of diazepam resp. midazolam at the end of the infusion protocol averaged 0.5 +/- 0.2 microg/ml plasma (1.6 microM) for diazepam versus 1.2 +/- 0.4 microg/ml plasma (3 microM) for midazolam. Intra-arterial infusion of the benzodiazepines did not alter baseline vascular tone, and had no significant influence on the forearm vasodilator response to adenosine. The adenosine-induced relative change in Forearm Vascular Resistance (FVR) was -3 +/- 7, -48 +/- 8, -75 +/- 6, and -85 +/- 3% in the absence and 3.5 +/- 11, -54 +/- 5, -74 +/- 5, and -82 +/- 3% resp. in the presence of diazepam (P > 0.1, repeated measures ANOVA, n = 9). Likewise, in the absence resp. presence of midazolam, FVR fell by 1 +/- 6, 55 +/- 5, 74 +/- 3, and 84 +/- 2% resp. 11 +/- 11, 59 +/- 2, 80 +/- 3, and 87 +/- 2% (P > 0.1, n = 7). Intra-brachial infusion of diazepam and midazolam resulting in forearm concentrations in the high therapeutic range does not augment adenosine-induced forearm vasodilation. A possible interaction at supra-therapeutic levels of the benzodiazepines can not be excluded from the present study, but lacks clinical significance. TI - The influence of diazepam and midazolam on adenosine-induced forearm vasodilation in humans. EP - 280 SN - 0160-2446 IS - iss. 2 SP - 276 JF - Journal of Cardiovascular Pharmacology VL - vol. 43 DO - https://doi.org/10.1097/00005344-200402000-00017 ER - TY - JOUR AU - Eijk, L.T.G.J. van AU - Pickkers, P. AU - Smits, P. AU - Bouw, M.P.W.J.M. AU - Hoeven, J.G. van der PY - 2004 UR - https://hdl.handle.net/2066/57759 AB - OBJECTIVE: Endotoxin administration to humans is a common means to study systemic inflammation. Worldwide, thousands of volunteers have received endotoxin, and adverse events are rarely reported. The aim of this report was to increase awareness of specific risks of the intravenous administration of endotoxin to human volunteers. DESIGN: Report of four cases who developed severe bradycardia or protracted asystole after administration of endotoxin. Interviews with investigators at three large centers that conduct normal volunteer endotoxin studies. SETTING: Clinical research unit. CASES: Four subjects developed severe bradycardia or protracted asystole, approximately 1 h after administration of endotoxin. Further analyses revealed that the subjects had a history of vasovagal syncope or a positive head-tilt test, indicating increased vagal sensitivity. Relative volume depletion associated with fasting overnight may have predisposed these subjects to this condition. CONCLUSIONS: These responses are very rare and are likely due to the cardioinhibitory Bezold-Jarisch reflex. A thorough screening regarding a history of vagal sensitivity and liberal oral or intravenous fluid administration prior to and during the endotoxin challenge may decrease the risk of these events. TI - Severe vagal response after endotoxin administration in humans. EP - 2281 SN - 0342-4642 IS - iss. 12 SP - 2279 JF - Intensive Care Medicine VL - vol. 30 DO - https://doi.org/10.1007/s00134-004-2477-0 ER - TY - JOUR AU - Pickkers, P. AU - Hoedemaekers, C.W.E. AU - Netea, M.G. AU - Galan, B.E. de AU - Smits, P. AU - Hoeven, J.G. van der AU - Deuren, M. van PY - 2004 UR - https://hdl.handle.net/2066/58239 AB - Recent trials investigating the effects of strict glucose regulation in critically ill patients have shown impressive reductions in morbidity and mortality. Although the literature focuses on the possible toxic effects of high blood glucose levels, the underlying mechanism for this improvement is unclear. We hypothesise that strict glucose regulation results in modulation of cytokine production, leading to a shift towards a more anti-inflammatory pattern. This shift in the cytokine balance accounts for the reduction in morbidity and mortality. To support our hypothesis, effects of glucose and insulin on cytokine release and effects of glucose, insulin, and cytokines on host defence, cardiac function and coagulation will be reviewed. TI - Hypothesis: Normalisation of cytokine dysbalance explains the favourable effects of strict glucose regulation in the critically ill. EP - 150 SN - 0300-2977 IS - iss. 5 SP - 143 JF - Netherlands Journal of Medicine VL - vol. 62 ER - TY - JOUR AU - Galan, B.E. de AU - Tack, C.J.J. AU - Willemsen, J.J. AU - Sweep, C.G.J. AU - Smits, P. AU - Lenders, J.W.M. PY - 2004 UR - https://hdl.handle.net/2066/57986 AB - A defective epinephrine response to hypoglycemia is a common disorder in type 1 diabetes. We assessed the role of the adrenomedullary capacity to secrete epinephrine in this disorder by measuring plasma metanephrine levels in affected type 1 diabetic patients compared with those in matched nondiabetic controls. Metanephrine is formed from epinephrine that leaks from adrenomedullary storage vesicles by catechol-O-methyl transferase (COMT) and is continuously released into the circulation. Thus, plasma metanephrine levels reflect adrenomedullary epinephrine content and, provided there is normal COMT activity, the adrenomedullary capacity to secrete epinephrine. Diabetic patients had approximately 25% lower plasma metanephrine levels than controls (0.18 +/- 0.09 vs. 0.24 +/- 0.02 nmol/liter; P = 0.012), whereas plasma epinephrine, norepinephrine, and normetanephrine levels were comparable between patients and controls. In response to hypoglycemia, the increments in plasma epinephrine and plasma metanephrine levels were both significantly lower in diabetic patients than in controls (P < 0.001), but the increase in plasma metanephrine as a percentage of the increase in plasma epinephrine was identical, indicating similar COMT activity. We conclude that type 1 diabetic patients with an impaired epinephrine response to hypoglycemia have lower plasma metanephrine levels than matched controls, reflecting decreased adrenomedullary stores of epinephrine and indicating reduced adrenomedullary capacity to secrete epinephrine. TI - Plasma metanephrine levels are decreased in type 1 diabetic patients with a severely impaired epinephrine response to hypoglycemia, indicating reduced adrenomedullary stores of epinephrine. EP - 2061 SN - 0021-972X IS - iss. 5 SP - 2057 JF - Journal of Clinical Endocrinology and Metabolism VL - vol. 89 DO - https://doi.org/10.1210/jc.2003-031289 L1 - https://repository.ubn.ru.nl/bitstream/handle/2066/57986/57986.pdf?sequence=1 ER -