TY - JOUR
T1 - Acute hyperglycemia reduces myocardial blood flow reserve and the magnitude of reduction is associated with insulin resistance
T2 - A study in nondiabetic humans using contrast echocardiography
AU - Abdelmoneim, Sahar S.
AU - Hagen, Mary E.
AU - Mendrick, Edward
AU - Pattan, Vishwanath
AU - Wong, Benjamin
AU - Norby, Barbara
AU - Roberson, Tamara
AU - Szydel, Troy
AU - Basu, Rita
AU - Basu, Ananda
AU - Mulvagh, Sharon L.
N1 - Funding Information:
Dr Sharon Mulvagh received research grants from Lantheus Medical Imaging and Astellas Pharma Global Inc. She has been a member of the Advisory Board for GE Healthcare. All other authors have no conflicts of interest to disclose.
Funding Information:
This project (clinicalTrial.gov identifier# NCT01021865) was supported by NIH/NCRR CTSA Grant Number NCATS UL1 TR000135 and by the Mayo Foundation, to Dr Sharon L Mulvagh Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health. Dr. Ananda Basu was supported by the grant DK 85516. Contrast agent (Definity) was provided by Lantheus Medical Imaging (North Billerica, MA). Vasodilator stress drug (Lexiscan) was provided by Astellas Pharma Global Inc.
PY - 2013/11
Y1 - 2013/11
N2 - The effect of acute hyperglycemia per se on coronary perfusion in humans is undefined. We evaluated the effects of short-term hyperglycemia on myocardial blood flow reserve (MBFR) in healthy nondiabetic volunteers. Twenty-one nondiabetic volunteers (76 % females, mean ± SD, age 48 ± 5 years) had noninvasive MBFR assessment while exposed to pancreatic clamp with somatostatin and replacement glucagon and growth hormone infusions, with frequent interval plasma glucose (PG) monitoring. Insulin was infused at 0.75 mU/kg/min to mimic postprandial plasma insulin concentrations, and glucose was infused to maintain euglycemia (PG 93.9 ± 7.3 mg/dl) followed by hyperglycemia (PG 231.5 ± 18.1 mg/dl). Myocardial contrast echocardiography (MCE) was performed during each glycemic steady state using continuous infusion of Definity at rest and during regadenoson (Lexiscan 5 ml (400 μg) intravenous bolus) infusion to quantify myocardial blood flow (MBF) and determine MBFR. Insulin resistance (IR) was assessed by glucose infusion rate (GIR; mg/kg/min) at euglycemia. Median stress MBF, MBFR, and β reserve were significantly reduced during acute hyperglycemia versus euglycemia (stress MBF 3.9 vs 5.4, P = 0.02; MBFR 2.0 vs 2.7, P < 0.0001; β reserve 1.45 vs 2.4, P = 0.007). Using a median threshold GIR of 5 mg/kg/min, there was a correlation between GIR and hyperglycemic MBFR (r = 0.506, P = 0.019). MBFR, as determined noninvasively by MCE, is significantly decreased during acute hyperglycemia in nondiabetic volunteers, and the magnitude of this reduction is modulated by IR.
AB - The effect of acute hyperglycemia per se on coronary perfusion in humans is undefined. We evaluated the effects of short-term hyperglycemia on myocardial blood flow reserve (MBFR) in healthy nondiabetic volunteers. Twenty-one nondiabetic volunteers (76 % females, mean ± SD, age 48 ± 5 years) had noninvasive MBFR assessment while exposed to pancreatic clamp with somatostatin and replacement glucagon and growth hormone infusions, with frequent interval plasma glucose (PG) monitoring. Insulin was infused at 0.75 mU/kg/min to mimic postprandial plasma insulin concentrations, and glucose was infused to maintain euglycemia (PG 93.9 ± 7.3 mg/dl) followed by hyperglycemia (PG 231.5 ± 18.1 mg/dl). Myocardial contrast echocardiography (MCE) was performed during each glycemic steady state using continuous infusion of Definity at rest and during regadenoson (Lexiscan 5 ml (400 μg) intravenous bolus) infusion to quantify myocardial blood flow (MBF) and determine MBFR. Insulin resistance (IR) was assessed by glucose infusion rate (GIR; mg/kg/min) at euglycemia. Median stress MBF, MBFR, and β reserve were significantly reduced during acute hyperglycemia versus euglycemia (stress MBF 3.9 vs 5.4, P = 0.02; MBFR 2.0 vs 2.7, P < 0.0001; β reserve 1.45 vs 2.4, P = 0.007). Using a median threshold GIR of 5 mg/kg/min, there was a correlation between GIR and hyperglycemic MBFR (r = 0.506, P = 0.019). MBFR, as determined noninvasively by MCE, is significantly decreased during acute hyperglycemia in nondiabetic volunteers, and the magnitude of this reduction is modulated by IR.
KW - Insulin resistance
KW - Myocardial blood flow reserve
KW - Myocardial perfusion contrast echocardiography
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U2 - 10.1007/s00380-012-0305-y
DO - 10.1007/s00380-012-0305-y
M3 - Article
C2 - 23180239
AN - SCOPUS:84890117171
SN - 0910-8327
VL - 28
SP - 757
EP - 768
JO - Heart and vessels
JF - Heart and vessels
IS - 6
ER -