Effect of Hyperglycemia on Microvascular Perfusion in Healthy Adults

Summary

The investigators are studying the effects of Hyperglycemia on vascular function and insulin sensitivity on healthy adults

Timeline

Start

2019-02-04

Primary completion

2021-04-01

Completion

2021-04-01

Publications

• Background Deedwania P, Kosiborod M, Barrett E, Ceriello A, Isley W, Mazzone T, Raskin P. Hyperglycemia and acute coronary syndrome: a scientific statement from the American Heart Association Diabetes Committee of the Council on Nutrition, Physical Activity, and Metabolism. Anesthesiology. 2008 Jul;109(1):14-24. doi: 10.1097/ALN.0b013e31817dced3.
• Background Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001 Dec 13;414(6865):813-20. doi: 10.1038/414813a.
• Background Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res. 2010 Oct 29;107(9):1058-70. doi: 10.1161/CIRCRESAHA.110.223545.
• Background Brouwers O, Niessen PM, Haenen G, Miyata T, Brownlee M, Stehouwer CD, De Mey JG, Schalkwijk CG. Hyperglycaemia-induced impairment of endothelium-dependent vasorelaxation in rat mesenteric arteries is mediated by intracellular methylglyoxal levels in a pathway dependent on oxidative stress. Diabetologia. 2010 May;53(5):989-1000. doi: 10.1007/s00125-010-1677-0. Epub 2010 Feb 26.
• Background Ceriello A, Taboga C, Tonutti L, Quagliaro L, Piconi L, Bais B, Da Ros R, Motz E. Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment. Circulation. 2002 Sep 3;106(10):1211-8. doi: 10.1161/01.cir.0000027569.76671.a8.
• Background Suzuki K, Watanabe K, Futami-Suda S, Yano H, Motoyama M, Matsumura N, Igari Y, Suzuki T, Nakano H, Oba K. The effects of postprandial glucose and insulin levels on postprandial endothelial function in subjects with normal glucose tolerance. Cardiovasc Diabetol. 2012 Aug 14;11:98. doi: 10.1186/1475-2840-11-98.
• Background Ceriello A, Novials A, Ortega E, Canivell S, La Sala L, Pujadas G, Esposito K, Giugliano D, Genovese S. Glucagon-like peptide 1 reduces endothelial dysfunction, inflammation, and oxidative stress induced by both hyperglycemia and hypoglycemia in type 1 diabetes. Diabetes Care. 2013 Aug;36(8):2346-50. doi: 10.2337/dc12-2469. Epub 2013 Apr 5.
• Background Perkins JM, Joy NG, Tate DB, Davis SN. Acute effects of hyperinsulinemia and hyperglycemia on vascular inflammatory biomarkers and endothelial function in overweight and obese humans. Am J Physiol Endocrinol Metab. 2015 Jul 15;309(2):E168-76. doi: 10.1152/ajpendo.00064.2015. Epub 2015 May 26.
• Background Giugliano D, Marfella R, Coppola L, Verrazzo G, Acampora R, Giunta R, Nappo F, Lucarelli C, D'Onofrio F. Vascular effects of acute hyperglycemia in humans are reversed by L-arginine. Evidence for reduced availability of nitric oxide during hyperglycemia. Circulation. 1997 Apr 1;95(7):1783-90. doi: 10.1161/01.cir.95.7.1783.
• Background Cuypers MH, Kasanardjo JS, Polak BC. Retinal blood flow changes in diabetic retinopathy measured with the Heidelberg scanning laser Doppler flowmeter. Graefes Arch Clin Exp Ophthalmol. 2000 Dec;238(12):935-41. doi: 10.1007/s004170000207.
• Background Horova E, Mazoch J, Hiigertova J, Kvasnicka J, Skrha J, Soupal J, Prazny M. Acute hyperglycemia does not impair microvascular reactivity and endothelial function during hyperinsulinemic isoglycemic and hyperglycemic clamp in type 1 diabetic patients. Exp Diabetes Res. 2012;2012:851487. doi: 10.1155/2012/851487. Epub 2012 Jan 4.
• Background Burgansky-Eliash Z, Barak A, Barash H, Nelson DA, Pupko O, Lowenstein A, Grinvald A, Rubinstein A. Increased retinal blood flow velocity in patients with early diabetes mellitus. Retina. 2012 Jan;32(1):112-9. doi: 10.1097/IAE.0b013e31821ba2c4.
• Background Rattigan S, Clark MG, Barrett EJ. Hemodynamic actions of insulin in rat skeletal muscle: evidence for capillary recruitment. Diabetes. 1997 Sep;46(9):1381-8. doi: 10.2337/diab.46.9.1381.
• Background Chai W, Zhang X, Barrett EJ, Liu Z. Glucagon-like peptide 1 recruits muscle microvasculature and improves insulin's metabolic action in the presence of insulin resistance. Diabetes. 2014 Aug;63(8):2788-99. doi: 10.2337/db13-1597. Epub 2014 Mar 21.
• Background Vincent MA, Dawson D, Clark AD, Lindner JR, Rattigan S, Clark MG, Barrett EJ. Skeletal muscle microvascular recruitment by physiological hyperinsulinemia precedes increases in total blood flow. Diabetes. 2002 Jan;51(1):42-8. doi: 10.2337/diabetes.51.1.42.
• Background Clerk LH, Vincent MA, Jahn LA, Liu Z, Lindner JR, Barrett EJ. Obesity blunts insulin-mediated microvascular recruitment in human forearm muscle. Diabetes. 2006 May;55(5):1436-42. doi: 10.2337/db05-1373.
• Background Clerk LH, Vincent MA, Barrett EJ, Lankford MF, Lindner JR. Skeletal muscle capillary responses to insulin are abnormal in late-stage diabetes and are restored by angiotensin-converting enzyme inhibition. Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1804-9. doi: 10.1152/ajpendo.00498.2007. Epub 2007 Oct 2.
• Background Jahn LA, Hartline L, Rao N, Logan B, Kim JJ, Aylor K, Gan LM, Westergren HU, Barrett EJ. Insulin Enhances Endothelial Function Throughout the Arterial Tree in Healthy But Not Metabolic Syndrome Subjects. J Clin Endocrinol Metab. 2016 Mar;101(3):1198-206. doi: 10.1210/jc.2015-3293. Epub 2016 Jan 12.
• Background Inyard AC, Chong DG, Klibanov AL, Barrett EJ. Muscle contraction, but not insulin, increases microvascular blood volume in the presence of free fatty acid-induced insulin resistance. Diabetes. 2009 Nov;58(11):2457-63. doi: 10.2337/db08-1077. Epub 2009 Aug 12.
• Background Liu J, Jahn LA, Fowler DE, Barrett EJ, Cao W, Liu Z. Free fatty acids induce insulin resistance in both cardiac and skeletal muscle microvasculature in humans. J Clin Endocrinol Metab. 2011 Feb;96(2):438-46. doi: 10.1210/jc.2010-1174. Epub 2010 Nov 3.
• Background Marfella R, Nappo F, De Angelis L, Siniscalchi M, Rossi F, Giugliano D. The effect of acute hyperglycaemia on QTc duration in healthy man. Diabetologia. 2000 May;43(5):571-5. doi: 10.1007/s001250051345.
• Background Glaser N, Ngo C, Anderson S, Yuen N, Trifu A, O'Donnell M. Effects of hyperglycemia and effects of ketosis on cerebral perfusion, cerebral water distribution, and cerebral metabolism. Diabetes. 2012 Jul;61(7):1831-7. doi: 10.2337/db11-1286. Epub 2012 Apr 12.
• Background Wei K, Jayaweera AR, Firoozan S, Linka A, Skyba DM, Kaul S. Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. Circulation. 1998 Feb 10;97(5):473-83. doi: 10.1161/01.cir.97.5.473.
• Background Chai W, Liu J, Jahn LA, Fowler DE, Barrett EJ, Liu Z. Salsalate attenuates free fatty acid-induced microvascular and metabolic insulin resistance in humans. Diabetes Care. 2011 Jul;34(7):1634-8. doi: 10.2337/dc10-2345. Epub 2011 May 26.
• Background Scognamiglio R, Negut C, De Kreutzenberg SV, Tiengo A, Avogaro A. Postprandial myocardial perfusion in healthy subjects and in type 2 diabetic patients. Circulation. 2005 Jul 12;112(2):179-84. doi: 10.1161/CIRCULATIONAHA.104.495127. Epub 2005 Jul 5.
• Background Abdelmoneim SS, Hagen ME, Mendrick E, Pattan V, Wong B, Norby B, Roberson T, Szydel T, Basu R, Basu A, Mulvagh SL. Acute hyperglycemia reduces myocardial blood flow reserve and the magnitude of reduction is associated with insulin resistance: a study in nondiabetic humans using contrast echocardiography. Heart Vessels. 2013 Nov;28(6):757-68. doi: 10.1007/s00380-012-0305-y. Epub 2012 Nov 23.
• Background Eggleston EM, Jahn LA, Barrett EJ. Hyperinsulinemia rapidly increases human muscle microvascular perfusion but fails to increase muscle insulin clearance: evidence that a saturable process mediates muscle insulin uptake. Diabetes. 2007 Dec;56(12):2958-63. doi: 10.2337/db07-0670. Epub 2007 Aug 24.
• Background DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979 Sep;237(3):E214-23. doi: 10.1152/ajpendo.1979.237.3.E214.
• Background Cardillo C, Nambi SS, Kilcoyne CM, Choucair WK, Katz A, Quon MJ, Panza JA. Insulin stimulates both endothelin and nitric oxide activity in the human forearm. Circulation. 1999 Aug 24;100(8):820-5. doi: 10.1161/01.cir.100.8.820.
• Horton WB, Jahn LA, Hartline LM, Aylor KW, Patrie JT, Barrett EJ. Insulin increases central aortic stiffness in response to hyperglycemia in healthy humans: A randomized four-arm study. Diab Vasc Dis Res. 2021 Mar-Apr;18(2):14791641211011009. doi: 10.1177/14791641211011009.
• Horton WB, Jahn LA, Hartline LM, Aylor KW, Patrie JT, Barrett EJ. Acute hyperglycaemia enhances both vascular endothelial function and cardiac and skeletal muscle microvascular function in healthy humans. J Physiol. 2022 Feb;600(4):949-962. doi: 10.1113/JP281286. Epub 2021 Feb 2.

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