Non-invasive assessment of vascular function; paradoxical vascular response to intravenous glucose in coronary heart disease.

BACKGROUND In healthy individuals, insulin administration causes an increase in forearm blood flow which is dependent on the effects of insulin on the vascular endothelium. Glucose, administered as an intravenous bolus, produces a transient hyperinsulinaemic response. We hypothesized that the insulin response to an intravenous glucose challenge during the intravenous glucose tolerance test might lead to increases in forearm blood flow in healthy individuals, and that such a response might be altered in patients with coronary heart disease. METHODS AND RESULTS Healthy individuals (n=10, aged 41.6+/-3. 0 years, mean+/-SEM) and patients with angiographically proven coronary heart disease (n=13, aged 65.5+/-2.4 years) underwent an intravenous glucose tolerance test with simultaneous measurement of right forearm blood flow at 28 time points, using mercury-in-silastic venous occlusion plethysmography. In controls, forearm blood flow increased to a mean of 31.7% above baseline values at 7 min and remained above baseline up to 180 min after intravenous glucose. In contrast, patients with coronary heart disease exhibited an opposite response, with forearm blood flow decreasing to a mean of -16.2% below baseline values at 7 min and -25.8% at 180 min. Marked group differences emerged in net changes from baseline in forearm blood flow throughout the intravenous glucose tolerance test, expressed as incremental areas under the forearm blood flow profiles (controls: +351.3+/-121.7; coronary heart disease patients: -244.3+/-72.4 min ml(-1). 100 ml(-1), P=0. 001). CONCLUSIONS We have demonstrated for the first time that in healthy individuals forearm blood flow increases after an intravenous bolus of glucose, and that paradoxically, this response is reduced below baseline forearm blood flow in patients with coronary heart disease. Further studies are needed to determine whether plethysmographic measurement of forearm blood flow after an intravenous bolus of glucose could provide a clinically useful non-invasive test for the diagnosis of occult coronary heart disease.

[1]  Carla J Greenbaum,et al.  Insulin resistance in type 1 diabetes , 2002, Diabetes/metabolism research and reviews.

[2]  Farris K. Timimi,et al.  Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. , 1998, Circulation.

[3]  H. Lindholm,et al.  Physical fitness and endothelial function (nitric oxide synthesis) are independent determinants of insulin-stimulated blood flow in normal subjects. , 1996, The Journal of clinical endocrinology and metabolism.

[4]  S. Mäkimattila,et al.  Insulin resistance in type I diabetes mellitus: a major role for reduced glucose extraction. , 1996, The Journal of clinical endocrinology and metabolism.

[5]  P. Vollenweider,et al.  Nitric oxide release accounts for insulin's vascular effects in humans. , 1994, The Journal of clinical investigation.

[6]  N. Fineberg,et al.  Insulin-mediated skeletal muscle vasodilation is nitric oxide dependent. A novel action of insulin to increase nitric oxide release. , 1994, The Journal of clinical investigation.

[7]  W. Hsueh,et al.  Endothelial-Dependent Vascular Effects of Insulin and Insulin-Like Growth Factor I in the Perfused Rat Mesenteric Artery and Aortic Ring , 1994, Diabetes.

[8]  A. Baron,et al.  Hemodynamic actions of insulin. , 1994, The American journal of physiology.

[9]  J. Hodgson,et al.  Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis. , 1994, Journal of the American College of Cardiology.

[10]  I. Godsland,et al.  Assessment of insulin sensitivity in man: a comparison of minimal model- and euglycaemic clamp-derived measures in health and heart failure. , 1994, Clinical science.

[11]  J. Hill,et al.  Constrictor and dilator responses to intracoronary acetylcholine in adjacent segments of the same coronary artery in patients with coronary artery disease. Endothelial function revisited. , 1994, Circulation.

[12]  R. Busse,et al.  Insulin-like growth factor I inhibits induction of nitric oxide synthase in vascular smooth muscle cells. , 1994, Circulation research.

[13]  H. Bohlen,et al.  Topical hyperglycemia rapidly suppresses EDRF-mediated vasodilation of normal rat arterioles. , 1993, The American journal of physiology.

[14]  M. Zemel,et al.  Insulin increases vascular smooth muscle recovery from intracellular calcium loads. , 1993, Hypertension.

[15]  P. Vollenweider,et al.  Differential effects of hyperinsulinemia and carbohydrate metabolism on sympathetic nerve activity and muscle blood flow in humans. , 1993, The Journal of clinical investigation.

[16]  P. Vallance,et al.  Inhibition and stimulation of nitric oxide synthesis in the human forearm arterial bed of patients with insulin-dependent diabetes. , 1992, The Journal of clinical investigation.

[17]  T Gustavsson,et al.  Ultrasound measurement of wall thickness in the carotid artery: fundamental principles and description of a computerized analysing system. , 1991, Clinical physiology.

[18]  C. Scrimgeour,et al.  Euglycemic hyperinsulinemia augments amino acid uptake by human leg tissues during hyperaminoacidemia. , 1990, The American journal of physiology.

[19]  B. Healy.  Endothelial cell dysfunction: an emerging endocrinopathy linked to coronary disease. , 1990, Journal of the American College of Cardiology.

[20]  E. Nabel,et al.  Large coronary arteries in humans are responsive to changing blood flow: an endothelium-dependent mechanism that fails in patients with atherosclerosis. , 1990, Journal of the American College of Cardiology.

[21]  A. Quyyumi,et al.  Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. , 1990, The New England journal of medicine.

[22]  M. Laakso,et al.  Reduced postprandial skeletal muscle blood flow contributes to glucose intolerance in human obesity. , 1990, The Journal of clinical endocrinology and metabolism.

[23]  M. Laakso,et al.  Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. , 1990, The Journal of clinical investigation.

[24]  R. Cohen,et al.  Elevated glucose promotes generation of endothelium-derived vasoconstrictor prostanoids in rabbit aorta. , 1990, The Journal of clinical investigation.

[25]  A. Yeung,et al.  Coronary vasomotor response to acetylcholine relates to risk factors for coronary artery disease. , 1990, Circulation.

[26]  P. Ganz,et al.  Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. , 1986, The New England journal of medicine.

[27]  R Busse,et al.  Crucial role of endothelium in the vasodilator response to increased flow in vivo. , 1986, Hypertension.

[28]  G. Sanz,et al.  Determinants of prognosis in survivors of myocardial infarction: a prospective clinical angiographic study. , 1982, The New England journal of medicine.

[29]  G. Grimby,et al.  Adaptive structural changes of the vascular walls in hypertension and their relation to the control of the peripheral resistance. , 1958, Acta physiologica Scandinavica.