Cardiac Metabolic and Hemodynamic Effects of Insulin in Patients With Coronary Artery Disease

Thomassen, Anne; Nielsen, Torsten Toftegaard; Bagger, Jens Peder; Henningsen, P

doi:10.2337/diab.38.9.1175

Cited by 25 publications

(13 citation statements)

References 32 publications

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“…This is in accordance with findings after a bolus injection of insulin intravenously (26) and during a hyperinsulinemic clamp technique comparable to ours (27). Impairment of insulin-mediated skeletal muscle vasodilation has been reported in insulin resistance (6,28).…”

Section: Discussionsupporting

confidence: 80%

Myocardial insulin resistance in patients with syndrome X.

Bøtker¹,

Møller²,

Schmitz³

et al. 1997

J. Clin. Invest.

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Insulin resistance is common in patients with angina pectoris, a positive exercise electrocardiogram, and normal coronary angiograms (syndrome X). It is still not known whether insulin resistance affects the cardiac muscle itself and, if so, whether insulin resistance involves myocardial hemodynamics and energy metabolism. We investigated hemodynamics as well as metabolite exchanges across the heart and the forearm in eight patients with syndrome X and eight control subjects during a baseline period after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Myocardial hemodynamics and metabolism were studied at rest, during pace stress, and in the recovery period after pacing. Neither coronary sinus blood flow nor forearm blood flow differed between the groups before and during the clamp. Whole body insulin-stimulated glucose uptake was decreased in the patients (15.6 Ϯ 2.1 vs. 23.1 Ϯ 2.0 mol ϫ kg Ϫ 1 ϫ min Ϫ 1 ). Insulin-stimulated glucose uptake in the forearm and the cardiac muscle was equally reduced in the patients (46 Ϯ 5 and 48 Ϯ 5%). Myocardial glucose uptake correlated with total arterial delivery in the control subjects ( r ϭ 0.63, P Ͻ 0.01), but not in patients ( r ϭ 0.22, P ϭ 0.13). Carbohydrate and lipid oxidation was similar in the two groups at rest, and changes during the clamp were not different in control subjects and patients either at rest, during pacing, or in the recovery period. Patients with syndrome X exhibit myocardial insulin resistance, but cardiac energy metabolism remains unaffected. In patients with syndrome X, insulin-stimulated glucose uptake is independent from myocardial blood flow.

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Section: Discussionsupporting

confidence: 80%

Myocardial insulin resistance in patients with syndrome X.

Bøtker¹,

Møller²,

Schmitz³

et al. 1997

J. Clin. Invest.

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“…The findings of insulin's effects on blood pressure are controversial. Mean arterial pressure has been found to be decreased (44,48), unchanged (13,30,31,46,(52)(53)(54), or increased (51). In the present study, hyperinsulinemia and simultaneous adenosine infusion significantly increased blood pressure values, heart rates, and plasma catecholamine concentrations.…”

Section: Discussionsupporting

confidence: 53%

“…Studies of insulin action on myocardial perfusion in humans are sparse. In an early study, an intravenous bolus of 2 units did not change coronary sinus flow or coronary resistance (30). Moreover, physiological hyperinsulinemia for 100 min had no effect on basal myocardial perfusion (31).…”

Section: Discussionmentioning

confidence: 99%

Dose-Dependent Vasodilating Effects of Insulin on Adenosine-Stimulated Myocardial Blood Flow

et al. 2002

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In the peripheral vasculature, insulin induces time-and dose-dependent vasodilation. We have recently demonstrated that insulin potentiates adenosine-stimulated myocardial blood flow. However, it is unknown whether insulin's effects on the coronary vasculature are dose dependent. In this study, we quantitated myocardial blood flow and adenosine-stimulated coronary flow (140 g ⅐ kg -1 ⅐ min -1 for 5 min) in 10 healthy men (age, 32 ؎ 6 years; BMI, 24.1 ؎ 1.8 kg/m 2 ) using positron emission tomography and 15 O-labeled water. Hyperemic myocardial blood flow was measured in the basal state, during euglycemic physiological hyperinsulinemia (serum insulin ϳ65 mU/l) and during supraphysiological hyperinsulinemia (serum insulin ϳ460 mU/l). Basal myocardial blood flow was 0.84 ؎ 0.17 ml ⅐ g ؊1 ⅐ min ؊1 . Physiological hyperinsulinemia increased the adenosine-stimulated flow by 20% (from 3.92 ؎ 1.17 to 4.72 ؎ 0.96 ml ⅐ g ؊1 ⅐ min ؊1 ; P < 0.05). Supraphysiological hyperinsulinemia further enhanced the adenosine-stimulated flow by 19% (to 5.61 ؎ 1.03 ml ⅐ g ؊1 ⅐ min ؊1 ; P < 0.05). These effects were not explained by changes in systemic hemodynamics, since coronary resistance decreased during each insulin infusion (P < 0.05). In addition, hyperemic myocardial blood flow responses during insulin stimulation were positively correlated with whole-body glucose uptake. The results demonstrate that insulin is able to enhance hyperemic myocardial blood flow in a dosedependent manner in healthy subjects. These effects might contribute to the known beneficial dose-dependent effects of insulin on myocardial ischemia. Diabetes 51:1125-1130, 2002 I nsulin is known to be vasoactive in the peripheral vasculature, but its effects on myocardial perfusion are poorly known. Glucose-insulin-potassium (GIK) therapy has been found to be beneficial in the treatment of acute myocardial ischemia (1,2). Several metabolic mechanisms, such as changes in glucose (3,4) and free fatty acid (5,6) metabolism, may explain the beneficial effects of insulin. In addition to these actions on myocardial substrate metabolism, we have recently shown that insulin directly affects myocardial perfusion (7). In addition, Marano et al. (8) demonstrated using SPECT (single-photon emission computed tomography) that GIK therapy improved regional myocardial perfusion and function mainly in segments adjacent to the recently infarcted area.Insulin induces a dose-dependent vasodilation in the peripheral arteries (9 -11) that is blunted in insulin-resistant states (10,12,13). Insulin causes endothelium-dependent vasodilation by the L-arginine-nitric oxide pathway (14,15), and another important mediator of insulin-induced vasodilation is the sympathetic nervous system (14). Unlike studies of insulin's action on skeletal muscle perfusion, studies addressing insulin's action on myocardial perfusion are sparse. Because differences in the regulation of vasodilation between coronary and peripherial arteries have been observed (7), previous studies targeting insulin's effects on t...

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“…Furthermore, increased myocardial glucose supply increases myocyte resistance to toxic effects of intracellular release of calcium during hypoxia (15,16). Insulin not only lowers glucose levels, it also decreases arterial levels of free fatty acids and, thereby, myocardial uptake of free fatty acids (17). In contrast, hyperglycemia is found in insulin deficiency and insulin-resistant states and is associated with increased lipolytic activity and high circulating levels of free fatty acids (15,18).…”

Section: Metabolic Interactionsmentioning

confidence: 99%

Admission Plasma Glucose

2001

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OBJECTIVE -To investigate the relationship between admission plasma glucose and 30-day mortality after primary isolated coronary artery bypass grafting (CABG) in nondiabetic patients.RESEARCH DESIGN AND METHODS -All nondiabetic patients with admission plasma glucose measurement undergoing primary isolated CABG from 1993 to 1997 were included in this study.RESULTS -In 878 consecutive patients (155 women), overall mortality was 3.4% (95% CI 2.3-4.8). The mortality rate in women (n ϭ 11; 7.1%, 3.6 -12.3) was higher than in men (n ϭ 19; 2.6%, 1.6 -4.1) (P ϭ 0.01). There was a positive correlation between plasma glucose and 30-day mortality among women only (P ϭ 0.0001). There was a higher mortality rate in the upper two glucose quartiles (11.7%, 5.5-21.0) compared with the lower two quartiles (2.6%, 3.0 -8.9) in the female patients (P ϭ 0.03); a plasma glucose of 6.0 mmol/l separated high-and low-mortality groups. Furthermore, women in the upper two glucose quartiles had a fourfold higher mortality rate than men in the similar quartiles (P ϭ 0.002). Among men, there was no difference in mortality rate across glucose quartiles. In a multivariate analysis, admission plasma glucose, history of thyroid disease, left ventricular ejection fraction Ͻ0.35, operation bypass time, and perioperative myocardial infarction were independently associated with mortality.CONCLUSIONS -Women with admission plasma glucose Յ6.0 mmol/l and men across the whole range of glucose values had similar mortality rates after CABG. The surplus female mortality was found only in subjects with plasma glucose Ͼ6 mmol/l. Further studies are needed to appraise the possible influence of glucose status on outcome from CABG in nondiabetic subjects. Diabetes Care 24:1634 -1639, 2001T he relationship between diabetes and high mortality and morbidity after coronary artery bypass grafting (CABG) is well established (1,2). A relationship also exists between high admission plasma glucose levels and in-hospital mortality from acute myocardial infarction in diabetic patients (3,4). Recent studies have, furthermore, shown higher myocardial infarction mortality in nondiabetic subjects with high admission plasma glucose (5,6). To our knowledge, no study has been conducted to examine a relationship between glycemic state and CABG mortality in nondiabetic subjects. Therefore, we examined the possible relationship between admission plasma glucose and outcome in nondiabetic patients undergoing first-time isolated CABG. RESEARCH DESIGN ANDMETHODS -All nondiabetic patients admitted to the Cardiothoracic Surgery Unit, Hammersmith Hospital between January 1993 and December 1997 and undergoing primary isolated CABG were eligible for this study. Patient data were entered into a database at admission, and operative data were entered at the time of operation. Admission plasma glucose was measured by the colorimetric glucose oxidase method. All data were validated after computer entry by one of the investigators (D.Z.). The clinical information included age, gender, angina stat...

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Cardiac Metabolic and Hemodynamic Effects of Insulin in Patients With Coronary Artery Disease

Cited by 25 publications

References 32 publications

Myocardial insulin resistance in patients with syndrome X.

Myocardial insulin resistance in patients with syndrome X.

Dose-Dependent Vasodilating Effects of Insulin on Adenosine-Stimulated Myocardial Blood Flow

Admission Plasma Glucose

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