Coronary circulatory dysfunction in insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus

John O. Prior, Manuel J. Quiñones, Miguel Hernandez-Pampaloni, Alvaro D. Facta, Thomas H. Schindler, James W. Sayre, Willa A. Hsueh, Heinrich R. Schelbert

Research output: Contribution to journalArticle

Abstract

Background - Abnormal coronary endothelial reactivity has been demonstrated in diabetes and is associated with an increased rate of cardiovascular events. Our objectives were to investigate the presence of functional coronary circulatory abnormalities over the full spectrum of insulin resistance and to determine whether these would differ in severity with more advanced states of insulin resistance. Methods and Results - Myocardial blood flow (MBF) was measured with positron emission tomography and 13N-ammonia to characterize coronary circulatory function in states of insulin resistance without carbohydrate intolerance (IR), impaired glucose tolerance (IGT), and normotensive and hypertensive type 2 diabetes mellitus (DM) compared with insulin-sensitive (IS) individuals. Indices of coronary function were total vasodilator capacity (mostly vascular smooth muscle-mediated) during pharmacological vasodilation and the nitric oxide-mediated, endothelium- dependent vasomotion in response to cold pressor testing. Total vasodilator capacity was similar in normoglycemic individuals (IS, IR, and IGT), whereas it was significantly decreased in normotensive (-17%) and hypertensive (-34%) DM patients. Compared with IS, endothelium-dependent coronary vasomotion was significantly diminished in IR (-56%), as well as in IGT and normotensive and hypertensive diabetic patients (-85%, -91%, and -120%, respectively). Conclusions - Progressively worsening functional coronary circulatory abnormalities of nitric oxide-mediated, endothelium-dependent vasomotion occur with increasing severity of insulin-resistance and carbohydrate intolerance. Attenuated total vasodilator capacity accompanies the more clinically evident metabolic abnormalities in diabetes.

Original languageEnglish (US)
Pages (from-to)2291-2298
Number of pages8
JournalCirculation
Volume111
Issue number18
DOIs
StatePublished - May 10 2005
Externally publishedYes

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Glucose Intolerance
Type 2 Diabetes Mellitus
Insulin Resistance
Vasodilator Agents
Endothelium
Insulin
Nitric Oxide
Vascular Smooth Muscle
Ammonia
Vasodilation
Positron-Emission Tomography
Diabetes Mellitus
Pharmacology
Glucose-Galactose Malabsorption

Keywords

  • Blood flow
  • Diabetes mellitus
  • Endothelium
  • Hypertension

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Prior, J. O., Quiñones, M. J., Hernandez-Pampaloni, M., Facta, A. D., Schindler, T. H., Sayre, J. W., ... Schelbert, H. R. (2005). Coronary circulatory dysfunction in insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus. Circulation, 111(18), 2291-2298. https://doi.org/10.1161/01.CIR.0000164232.62768.51

Coronary circulatory dysfunction in insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus. / Prior, John O.; Quiñones, Manuel J.; Hernandez-Pampaloni, Miguel; Facta, Alvaro D.; Schindler, Thomas H.; Sayre, James W.; Hsueh, Willa A.; Schelbert, Heinrich R.

In: Circulation, Vol. 111, No. 18, 10.05.2005, p. 2291-2298.

Research output: Contribution to journalArticle

Prior, JO, Quiñones, MJ, Hernandez-Pampaloni, M, Facta, AD, Schindler, TH, Sayre, JW, Hsueh, WA & Schelbert, HR 2005, 'Coronary circulatory dysfunction in insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus', Circulation, vol. 111, no. 18, pp. 2291-2298. https://doi.org/10.1161/01.CIR.0000164232.62768.51
Prior JO, Quiñones MJ, Hernandez-Pampaloni M, Facta AD, Schindler TH, Sayre JW et al. Coronary circulatory dysfunction in insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus. Circulation. 2005 May 10;111(18):2291-2298. https://doi.org/10.1161/01.CIR.0000164232.62768.51
Prior, John O. ; Quiñones, Manuel J. ; Hernandez-Pampaloni, Miguel ; Facta, Alvaro D. ; Schindler, Thomas H. ; Sayre, James W. ; Hsueh, Willa A. ; Schelbert, Heinrich R. / Coronary circulatory dysfunction in insulin resistance, impaired glucose tolerance, and type 2 diabetes mellitus. In: Circulation. 2005 ; Vol. 111, No. 18. pp. 2291-2298.
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AU - Schindler, Thomas H.

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N2 - Background - Abnormal coronary endothelial reactivity has been demonstrated in diabetes and is associated with an increased rate of cardiovascular events. Our objectives were to investigate the presence of functional coronary circulatory abnormalities over the full spectrum of insulin resistance and to determine whether these would differ in severity with more advanced states of insulin resistance. Methods and Results - Myocardial blood flow (MBF) was measured with positron emission tomography and 13N-ammonia to characterize coronary circulatory function in states of insulin resistance without carbohydrate intolerance (IR), impaired glucose tolerance (IGT), and normotensive and hypertensive type 2 diabetes mellitus (DM) compared with insulin-sensitive (IS) individuals. Indices of coronary function were total vasodilator capacity (mostly vascular smooth muscle-mediated) during pharmacological vasodilation and the nitric oxide-mediated, endothelium- dependent vasomotion in response to cold pressor testing. Total vasodilator capacity was similar in normoglycemic individuals (IS, IR, and IGT), whereas it was significantly decreased in normotensive (-17%) and hypertensive (-34%) DM patients. Compared with IS, endothelium-dependent coronary vasomotion was significantly diminished in IR (-56%), as well as in IGT and normotensive and hypertensive diabetic patients (-85%, -91%, and -120%, respectively). Conclusions - Progressively worsening functional coronary circulatory abnormalities of nitric oxide-mediated, endothelium-dependent vasomotion occur with increasing severity of insulin-resistance and carbohydrate intolerance. Attenuated total vasodilator capacity accompanies the more clinically evident metabolic abnormalities in diabetes.

AB - Background - Abnormal coronary endothelial reactivity has been demonstrated in diabetes and is associated with an increased rate of cardiovascular events. Our objectives were to investigate the presence of functional coronary circulatory abnormalities over the full spectrum of insulin resistance and to determine whether these would differ in severity with more advanced states of insulin resistance. Methods and Results - Myocardial blood flow (MBF) was measured with positron emission tomography and 13N-ammonia to characterize coronary circulatory function in states of insulin resistance without carbohydrate intolerance (IR), impaired glucose tolerance (IGT), and normotensive and hypertensive type 2 diabetes mellitus (DM) compared with insulin-sensitive (IS) individuals. Indices of coronary function were total vasodilator capacity (mostly vascular smooth muscle-mediated) during pharmacological vasodilation and the nitric oxide-mediated, endothelium- dependent vasomotion in response to cold pressor testing. Total vasodilator capacity was similar in normoglycemic individuals (IS, IR, and IGT), whereas it was significantly decreased in normotensive (-17%) and hypertensive (-34%) DM patients. Compared with IS, endothelium-dependent coronary vasomotion was significantly diminished in IR (-56%), as well as in IGT and normotensive and hypertensive diabetic patients (-85%, -91%, and -120%, respectively). Conclusions - Progressively worsening functional coronary circulatory abnormalities of nitric oxide-mediated, endothelium-dependent vasomotion occur with increasing severity of insulin-resistance and carbohydrate intolerance. Attenuated total vasodilator capacity accompanies the more clinically evident metabolic abnormalities in diabetes.

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