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Journal of Renin-Angiotensin-Aldosterone System
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Angiotensin-converting enzyme activity and cognitive impairment during hypoglycaemia in healthy humans

Ulrik Pedersen-Bjergaard

Endocrinology Section, Division of Internal Medicine I, Hillerød Hospital, Hillerød, ulpebj@ noh.regionh.dk

Carsten E Thomsen

Department of Oral Pathology, Copenhagen School of Dentistry, Copenhagen

Hans Høgenhaven

Department of Neurophysiology, Rigshospitalet, Copenhagen

Annelise Smed

Department of Neurology, Rigshospitalet, Copenhagen

Troels W Kjær

Department of Neurophysiology, Rigshospitalet, Copenhagen

Jens J Holst

Department of Medical Physiology, , Rigshospitalet, Copenhagen

Flemming Dela

Copenhagen Muscle Research Centre, Department of Medical Physiology, University of Copenhagen

Linda Hilsted

Department of Clinical Biochemistry, Rigshospitalet, Copenhagen

Erik Frandsen

Department of Clinical Physiology, Glostrup University Hospital, Glostrup

Stig Pramming

Novo Nordisk A/S, Bagsværd, Denmark

Birger Thorsteinsson

Endocrinology Section, Division of Internal Medicine I, Hillerød Hospital, Hillerød

Introduction: In type 1 diabetes increased risk of severe hypoglycaemia is associated with high angiotensin-converting enzyme (ACE) activity. We tested in healthy humans the hypothesis that this association is explained by the reduced ability of subjects with high ACE activity to maintain normal cognitive function during hypoglycaemia.

Methods: Sixteen healthy volunteers selected by either particularly high or low serum ACE activity were subjected to hypoglycaemia (plasma glucose 2.7 mmol/L). Cognitive function was assessed by choice reaction tests.

Results: Despite a similar hypoglycaemic stimulus in the two groups, only the group with high ACE activity showed significant deterioration in cognitive performance during hypoglycaemia. In the high ACE group mean reaction time (MRT) in the most complex choice reaction task was prolonged and error rate (ER) was increased in contrast to the low ACE group. The total hypoglycaemic symptom response was greater in the high ACE group than in the low ACE group (p=0.031).There were no differences in responses of counterregulatory hormones or in concentrations of substrates between the groups.

Conclusion: Healthy humans with high ACE activity are more susceptible to cognitive dysfunction and report higher symptom scores during mild hypoglycaemia than subjects with low ACE activity.

Key Words: angiotensin-converting enzyme • hypoglycaemia • cognition • counterregulation

References

  • Cryer PE Hypoglycaemia: The limiting factor in the glycaemic management of Type I and Type II diabetes. Diabetologia 2002;45:637-48.
  • Høi-Hansen T., Pedersen-Bjergaard U., Pramming S., Thorsteinsson B. Risk factors of severe hypoglycemia and occurrence of silent hypoglycemia in patients with type 1 diabetes assessed by continuous glucose monitoring. Diabetes 2005;54(suppl 1): A153.
  • The Diabetes Control and Complications Trial Research Group. Hypoglycemia in the Diabetes Control and Complications Trial. Diabetes 1997;46:271-86.[Abstract]
  • Pedersen-Bjergaard U., Pramming S., Heller SR et al. Severe hypoglycaemia in 1076 patients with type 1 diabetes: influence of risk markers and selection. Diabet Metab Res Rev 2004;20:479-86.[CrossRef]
  • Pedersen-Bjergaard U., Agerholm-Larsen B., Pramming S., Hougaard P., Thorsteinsson B. Activity of angiotensin-converting enzyme and risk of severe hypoglycaemia in type 1 diabetes mellitus. Lancet 2001;357:1248-53.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Pedersen-Bjergaard U., Agerholm-Larsen B., Pramming S., Hougaard P., Thorsteinsson B. Prediction of severe hypoglycaemia by angiotensin-converting enzyme activity and genotype in type 1 diabetes. Diabetologia 2003;46:89-96. 7. Nordfeldt S., Samuelsson U. Serum ACE predicts severe[Web of Science][Medline] [Order article via Infotrieve]
  • hypoglycemia in children and adolescents with type 1 diabetes. Diabetes Care 2003;26:274-8.[Abstract/Free Full Text]
  • Zammitt NN, Geddes J., Warren RE, Marioni R., Ashby JP, Frier BM Serum angiotensin-converting enzyme activity and frequency of severe hyoiglycaemia in type 1 diabetes: does a relationship exist? Diabet Med 2007;24:1449-54.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Agerholm-Larsen P.B., Nordestgaard BG, Steffensen R., Sørensen TI, Jensen G., Tybjærg-Hansen A. ACE gene polymorphism: ischaemic heart disease and longevity in 10,150 individuals. A case-referent and retrospective cohort study based on the Copenhagen City Heart Study. Circulation 1997;95:2358-67.[Abstract/Free Full Text]
  • Chang L., Ernst T., Speck O., Patel H., DeSilva M., Leonido-Yee M., Miller EN Perfusion MRI and computerized cognitive test abnormalities in abstinent methamphetamine users. Psychiatry Res 2002;114:65-79.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Hepburn DA, Deary IJ, MacLeod KM, Frier BM Structural equation modeling of symptoms, awareness and fear of hypoglycemia, and personality in patients with insulin-treated diabetes. Diabetes Care 1994;17:1273-80.[Abstract]
  • Holst JJ Molecular heterogeneity of glucagon in normal subjects and in patients with glucagon producing tumours. Diabetologia 1983;24:359-65.[Web of Science][Medline] [Order article via Infotrieve]
  • Appel E., Bayer P., Hajdu P., Palm D., Shofer J., Uihlein M. Determination of plasma catecholamines by means of radioenzymatic labeling and high pressure liquid chromatographic separation. Naunyn Schmiedebergs Arch Pharmacol 1981;315:233-9.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Klaniecki TS, Corder CN, McDonald RH Jr, Feldman JA High-performance liquid chromatographic radioenzymatic assay for plasma catecholamines. J Lab Clin Med 1977;90:604-12.[Web of Science][Medline] [Order article via Infotrieve]
  • Schwartz TW, Holst JJ, Fahrenkrug J. et al. cholinergic regulation of pancreatic polypeptide secretion. J Clin Invest 1978;61:781-9.[Web of Science][Medline] [Order article via Infotrieve]
  • Poulsen K., Jørgensen J. An easy radioimmunological microassay of renin activity, concentration and substrate in human and animal plasma and tissues based on angiotensin I trapping by antibody. J Clin Endocrinol Metab 1974;39:816-25.[Abstract/Free Full Text]
  • Millar JA, Leckie BJ, Morton JJ, Jordan J., Tree M. A micro assay for active and total renin concentration in human plasma based on antibody trapping. Clinica Chimica Acta 1980;101:5-15.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Kappelgaard AM, Nielsen MD, Giese J. Measurement of angiotensin II in human plasma: Technical modifications and practical experience. Clinica Chimica Acta 1976;67:299-306.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Bulsara MK, Holman CDJ, van Bockxmeer FM, et al. The relationship between ACE genotype and risk of severe hypoglycaemia in a large population-based cohort of children and adolescents with type 1 diabetes. Diabetologia. 2007;50:965-71.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Pedersen-Bjergaard U., Dhamrait SS, Sethi AA et al. Genetic variation and activity of the renin-angiotensin system and severe hypoglycemia in type 1 Diabetes. Am J Med 2008;121:246E1-E8.
  • DeRosa MA, Cryer PE Hypoglycemia and the sympathoadrenal system: neurogenic symptoms are largely the result of sympathetic neural, rather than adrenomedullary, activation. Am J Physiol 2004;287:E32-E41.[Web of Science]
  • Porcellati F., Pampanelli S., Rossetti P., Cordoni C., Marzotti S., Scionti L., Bolli GB, Fanelli CG Counterregulatory hormone and symptom responses to insulin-induced hypoglycemia in the postprandial state in humans. Diabetes 2003;52:2774-83.[Abstract/Free Full Text]
  • Heller SR, Amiel SA, Evans ML, Kong MF, Macdonald IA, Peacey SR Does insulin lispro preserve the physiological defences to hypoglycaemia during intensive insulin therapy with a conventional basal bolus regimen? Diabetes Obes Metab 2002;4:106-12.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Sandoval DA, Guy DL, Richardson MA, Ertl AC, Davis SN Effects of low and moderate antecedent exercise on counterregulatory responses to subsequent hypoglycaemia in type 1 diabetes. Diabetes 2004;53:1798-106.[Abstract/Free Full Text]
  • Frier BM, Al-Dujaili EA, Corrall RJ, Pritchard JL, Edwards CR Autonomic neural control mechanisms and the release of adrenal steroids after hypoglycaemia in man. Horm Metab Res 1984;16(suppl 1):138-41.[Medline] [Order article via Infotrieve]
  • Amiel SA Cognitive function testing in studies of acute hypoglycaemia: rights and wrongs? Diabetologia 1998;41:713-19.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Strachan MW, Ewing FM, Frier BM, McCrimmon RJ, Deary IJ Effects of acute hypoglycaemia on auditory information processing in adults with Type I diabetes. Diabetologia 2003;46:97-105.[Web of Science][Medline] [Order article via Infotrieve]
  • Madsen BK, Hølmer P., Ibsen H., Christensen NJ The influence of captopril on the epinephrine response to insulin-induced hypoglycemia in humans. The interaction between the renin-angiotensin system and the sympathetic nervous system. Am J Hypertens 1992;5:361-5.[Web of Science][Medline] [Order article via Infotrieve]
  • Glorioso N., Dessi-Fulgheri P., Alagna S. et al. Angiotensin-converting enzyme inhibition reduces ACTH release due to hypoglycaemia. Clin Exp Hypertens A 1987;9:665-70.[Web of Science][Medline] [Order article via Infotrieve]
  • Oltmanns KM, Deininger E., Wellhoener P. et al. Influence of captopril on symptomatic and hormonal responses to hypoglycaemia in humans. B J Clin Pharmacol 2003:55:347-53. 31. Deininger E., Oltmanns KM, Wellhoener P. et al. Losartan attenuates symptomatic and hor-monal responses to hypoglycemia in humans. Clin Pharmacol Ther 2001;70:362-9.[Web of Science][Medline] [Order article via Infotrieve]
  • Hirsch IB, Heller SR, Cryer PE Increased symptoms of hypoglycaemia in the standing position in insulin-dependent diabetes mellitus. Clin Sci 1991;80:583-6.[Web of Science][Medline] [Order article via Infotrieve]
  • Walther T., Olah L., Harms C. et al. Ischemic injury in experimental stroke depends on angiotensin II. FASEB J 2002;16:169-76.[Abstract/Free Full Text]
  • Georgiev V., Opitz M. Participation of angiotensin receptors in acute hypoxia in mice. II. Effects of angiotensin II nonpeptide receptor ligands losartan (DuP-753) and PD-123319. Methods Find Exp Clin Pharmacol 1999;21:463-6.[Web of Science][Medline] [Order article via Infotrieve]
  • Tallroth G., Ryding E., Agardh CD Regional cerebral blood flow in normal man during insulin-induced hypoglycemia and in the recovery period following glucose infusion. Metabolism 1992;41:717-21.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Thomas M., Sherwin RS, Murphy J., Kerr D. Importance of cerebral blood flow to the recognition of and physiological responses to hypoglycemia. Diabetes 1997;46:829-33.[Abstract]
  • Maran A., Cranston I., Lomas J., Macdonald I., Amiel SA Protection by lactate of cerebral function during hypoglycaemia. Lancet 1994;343:16-20.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Dzau VJ Tissue renin-angiotensin system: physiologic and pharmacologic implications. Circulation 1988;77:11-13.
  • Montgomery HE, Marshall R., Hemingway H. et al. Human gene for physical performance. Nature 1998;393:221-2.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Nybo L., Møller K., Pedersen BK, Nielsen B., Secher NH Association between fatigue and failure to preserve cerebral energy turnover during prolonged exercise. Acta Physiol Scand 2003;179:67-74.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Morris AD, Boyle DIR, McMahon AD et al. ACE inhibitor use is associated with hospitalisation for severe hypoglycaemia in patients with diabetes. Diabetes Care 1997;20:1363-7.[Abstract]
  • The EUCLID study group. Randomised placebo-controlled trial of lisinopril in normotensive patients with insulin-dependent diabetes and normoalbuminuria or microalbuminuria. Lancet 1997;349:1787-92.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]

Journal of Renin-Angiotensin-Aldosterone System, Vol. 9, No. 1, 37-48 (2008)
DOI: 10.3317/jraas.2008.001


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This Article
Right arrow Abstract Freely available
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Citing Articles
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Right arrow Articles by Pedersen-Bjergaard, U.
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PubMed
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Right arrow Articles by Pedersen-Bjergaard, U.
Right arrow Articles by Thorsteinsson, B.
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*Substance via MeSH
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*Hypoglycemia
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