{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T15:57:03Z","timestamp":1761580623158},"reference-count":25,"publisher":"American Diabetes Association","issue":"11","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,11,1]]},"abstract":"<jats:p>OBJECTIVE\u2014Insulin has opposing influences on blood pressure by simultaneously increasing adrenergic activity and vasodilatating peripheral blood vessels. In this study, we sought to determine whether hyperinsulinemia affects tilt table responses in older adults with type 2 diabetes not complicated by orthostatic hypotension.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014Twenty-two older adults (mean age 71.7 \u00b1 1.1) with diet-controlled or oral hypoglycemic drug\u2013controlled type 2 diabetes were recruited. All subjects with orthostatic hypotension, diabetic nephropathy, and sensory neuropathy were excluded. Subjects underwent euglycemic-hyperinsulinemic clamp and placebo \u201csham clamp\u201d sessions. Sequential euglycemic-hyperinsulinemic clamps were performed for 2 h at 40 mU \u00b7 m\u22122 \u00b7 min\u22121 (low dose) and 2 h at 80 mU \u00b7 m\u22122 \u00b7 min\u22121 (high dose), and each was followed by a head-up tilt table test at 70\u00b0C for 10 min.<\/jats:p>\n               <jats:p>RESULTS\u2014There were no incidents of presyncope during the sham clamp, whereas there were four presyncopal events during both the low-dose and high-dose tilts. Although the low-dose clamp showed no difference in the response between sessions (two-way ANOVA), subjects demonstrated a significantly larger decrease in mean arterial pressure (P = 0.005) and diastolic blood pressure (P = 0.08) during the high-dose tilt. Doppler measures of middle cerebral artery velocity were no different between the two sessions at either dose.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014The vasodilatory response to insulin can unmask orthostatic intolerance in older adults with type 2 diabetes, resulting in presyncopal symptoms. This could contribute to orthostatic hypotension in combination with other factors such as hyperthermia, hypovolemia, and adverse effects from medications.<\/jats:p>","DOI":"10.2337\/dc08-1058","type":"journal-article","created":{"date-parts":[[2008,8,21]],"date-time":"2008-08-21T00:45:55Z","timestamp":1219279555000},"page":"2203-2208","update-policy":"http:\/\/dx.doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":7,"title":["Euglycemic Hyperinsulinemia Alters the Response to Orthostatic Stress in Older Adults With Type 2 Diabetes"],"prefix":"10.2337","volume":"31","author":[{"given":"Kenneth M.","family":"Madden","sequence":"first","affiliation":[{"name":"From the Division of Geriatric Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gale","family":"Tedder","sequence":"additional","affiliation":[{"name":"From the Division of Geriatric Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Lockhart","sequence":"additional","affiliation":[{"name":"From the Division of Geriatric Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graydon S.","family":"Meneilly","sequence":"additional","affiliation":[{"name":"From the Division of Geriatric Medicine, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1167","reference":[{"key":"2022031217264098000_R1","doi-asserted-by":"crossref","unstructured":"de Kanter M, Lilja B, Elmstahl S, Eriksson KF, Sundkvist G: A prospective study of orthostatic blood pressure in diabetic patients. Clin Auton Res\u20088: 189\u2013193, 1998","DOI":"10.1007\/BF02267780"},{"key":"2022031217264098000_R2","doi-asserted-by":"crossref","unstructured":"Gupta V, Lipsitz LA: Orthostatic hypotension in the elderly: diagnosis and treatment. Am J Med\u2008120:841\u2013847, 2007","DOI":"10.1016\/j.amjmed.2007.02.023"},{"key":"2022031217264098000_R3","doi-asserted-by":"crossref","unstructured":"Vinik AI, Erbas T: Cardiovascular autonomic neuropathy: diagnosis and management. Curr Diab Rep\u20086:424\u2013430, 2006","DOI":"10.1007\/s11892-006-0074-z"},{"key":"2022031217264098000_R4","doi-asserted-by":"crossref","unstructured":"Tack CJ, Lenders JW, Willemsen JJ, van Druten JA, Thien T, Lutterman JA, Smits P: Insulin stimulates epinephrine release under euglycemic conditions in humans. Metabolism\u200847:243\u2013249, 1998","DOI":"10.1016\/S0026-0495(98)90251-7"},{"key":"2022031217264098000_R5","doi-asserted-by":"crossref","unstructured":"Tack CJ, Smits P, Willemsen JJ, Lenders JW, Thien T, Lutterman JA: Effects of insulin on vascular tone and sympathetic nervous system in NIDDM. Diabetes\u200845:15\u201322, 1996","DOI":"10.2337\/diabetes.45.1.15"},{"key":"2022031217264098000_R6","doi-asserted-by":"crossref","unstructured":"Meneilly GS, Elliott T, Battistini B, Floras JS: NG-Monomethyl-l-arginine alters insulin-mediated calf blood flow but not glucose disposal in the elderly. Metabolism\u200850:306\u2013310, 2001","DOI":"10.1053\/meta.2001.19493"},{"key":"2022031217264098000_R7","doi-asserted-by":"crossref","unstructured":"Lipsitz LA, Pluchino FC, Wei JY, Rowe JW: Syncope in institutionalized elderly: the impact of multiple pathological conditions and situational stress. J Chronic Dis\u200839:619\u2013630, 1986","DOI":"10.1016\/0021-9681(86)90187-6"},{"key":"2022031217264098000_R8","doi-asserted-by":"crossref","unstructured":"Ruiz GA, Calvar C, Hermes R, Rivadeneira D, Bengolea V, Chirife R, Tentori MC, Gelpi RJ: Insulin sensitivity in young women with vasovagal syncope. Am Heart J\u2008145:834\u2013840, 2003","DOI":"10.1016\/S0002-8703(02)94707-1"},{"key":"2022031217264098000_R9","doi-asserted-by":"crossref","unstructured":"Porcellati F, Fanelli C, Bottini P, Epifano L, Rambotti AM, Lalli C, Pampanelli S, Scionti L, Santeusanio F, Brunetti P, et al.: Mechanisms of arterial hypotension after therapeutic dose of subcutaneous insulin in diabetic autonomic neuropathy. Diabetes\u200842:1055\u20131064, 1993","DOI":"10.2337\/diabetes.42.7.1055"},{"key":"2022031217264098000_R10","doi-asserted-by":"crossref","unstructured":"Stratton JR, Cerqueira MD, Schwartz RS, Levy WC, Veith RC, Kahn SE, Abrass IB: Differences in cardiovascular responses to isoproterenol in relation to age and exercise training in healthy men. Circulation\u200886:504\u2013512, 1992","DOI":"10.1161\/01.CIR.86.2.504"},{"key":"2022031217264098000_R11","unstructured":"Petrofsky JS, Besonis C, Rivera D, Schwab E, Lee S: Impairment in orthostatic tolerance during heat exposure in individuals with type I and type II diabetes. Med Sci Monit\u200811:CR153\u2013CR159, 2005"},{"key":"2022031217264098000_R12","doi-asserted-by":"crossref","unstructured":"Patel NP, Pugh ME, Goldberg S, Eiger G: Hyperinsulinemic euglycemia therapy for verapamil poisoning: a review. Am J Crit Care\u200816:498\u2013503, 2007","DOI":"10.4037\/ajcc2007.16.5.498"},{"key":"2022031217264098000_R13","doi-asserted-by":"crossref","unstructured":"Ziegler D, Laux G, Dannehl K, Spuler M, Muhlen H, Mayer P, Gries FA: Assessment of cardiovascular autonomic function: age-related normal ranges and reproducibility of spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses. Diabet Med\u20089:166\u2013175, 1992","DOI":"10.1111\/j.1464-5491.1992.tb01754.x"},{"key":"2022031217264098000_R14","doi-asserted-by":"crossref","unstructured":"Meneilly GS: A comparison of insulin aspart and regular insulin in elderly patients with type 2 diabetes. Diabetes Obes Metab\u20089:754\u2013755, 2007","DOI":"10.1111\/j.1463-1326.2006.00639.x"},{"key":"2022031217264098000_R15","doi-asserted-by":"crossref","unstructured":"McGuire EA, Helderman JH, Tobin JD, Andres R, Berman M: Effects of arterial versus venous sampling on analysis of glucose kinetics in man. J Appl Physiol\u200841:565\u2013573, 1976","DOI":"10.1152\/jappl.1976.41.4.565"},{"key":"2022031217264098000_R16","unstructured":"Andres R, Swerdloff R, Pozefsky T, Coleman D: Manual feedback technique for control of glucose concentration. In Automation in Analytic Chemistry. Skeggs LT Jr, Ed. New York, Medaid, 1966, p. 486\u2013501"},{"key":"2022031217264098000_R17","doi-asserted-by":"crossref","unstructured":"Egan JM, Meneilly GS, Habener JF, Elahi D: Glucagon-like peptide-1 augments insulin-mediated glucose uptake in the obese state. J Clin Endocrinol Metab\u200887:3768\u20133773, 2002","DOI":"10.1210\/jcem.87.8.8743"},{"key":"2022031217264098000_R18","doi-asserted-by":"crossref","unstructured":"Imholz BP, Wieling W, van Montfrans GA, Wesseling KH: Fifteen years experience with finger arterial pressure monitoring: assessment of the technology. Cardiovasc Res\u200838:605\u2013616, 1998","DOI":"10.1016\/S0008-6363(98)00067-4"},{"key":"2022031217264098000_R19","doi-asserted-by":"crossref","unstructured":"Rongen GA, Bos WJ, Lenders JW, van Montfrans GA, van Lier HJ, van Goudoever J, Wesseling KH, Thien T: Comparison of intrabrachial and finger blood pressure in healthy elderly volunteers. Am J Hypertens\u20088:237\u2013248, 1995","DOI":"10.1016\/0895-7061(94)00000-2"},{"key":"2022031217264098000_R20","doi-asserted-by":"crossref","unstructured":"Guelen I, Westerhof BE, Van Der Sar GL, Van Montfrans GA, Kiemeneij F, Wesseling KH, Bos WJ: Finometer, finger pressure measurements with the possibility to reconstruct brachial pressure. Blood Press Monit\u20088:27\u201330, 2003","DOI":"10.1097\/00126097-200302000-00006"},{"key":"2022031217264098000_R21","doi-asserted-by":"crossref","unstructured":"Lipsitz LA, Mukai S, Hamner J, Gagnon M, Babikian V: Dynamic regulation of middle cerebral artery blood flow velocity in aging and hypertension. Stroke\u200831:1897\u20131903, 2000","DOI":"10.1161\/01.STR.31.8.1897"},{"key":"2022031217264098000_R22","doi-asserted-by":"crossref","unstructured":"Wesseling KH, Jansen JR, Settels JJ, Schreuder JJ: Computation of aortic flow from pressure in humans using a nonlinear, three-element model. J Appl Physiol\u200874:2566\u20132573, 1993","DOI":"10.1152\/jappl.1993.74.5.2566"},{"key":"2022031217264098000_R23","unstructured":"Sollers JJ 3rd, Merritt MM, Silver RA, Sadle TN, Ferrucci L, Thayer JF: Comparison of arterial compliance indices derived via beat-to-beat blood pressure waveforms: aging and ethnicity. Biomed Sci Instrum\u200842:518\u2013523, 2006"},{"key":"2022031217264098000_R24","unstructured":"Dawson-Saunders B, Trapp RG: Basic and clinical biostatistics. Toronto, Prentice Hall of Canada, 1994"},{"key":"2022031217264098000_R25","doi-asserted-by":"crossref","unstructured":"Lau DC, Douketis JD, Morrison KM, Hramiak IM, Sharma AM, Ur E: 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary]. CMAJ\u2008176:S1\u2013S13, 2007","DOI":"10.1503\/cmaj.061409"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/31\/11\/2203\/596800\/zdc01108002203.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/31\/11\/2203\/596800\/zdc01108002203.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,12]],"date-time":"2022-03-12T18:18:29Z","timestamp":1647109109000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/31\/11\/2203\/26785\/Euglycemic-Hyperinsulinemia-Alters-the-Response-to"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,11,1]]},"references-count":25,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2008,11,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc08-1058","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,11,1]]}}}