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CLINICAL RESEARCH: CORONARY ARTERY DISEASE

The Effects of Plasma Insulin and Glucose on Myocardial Blood Flow in Patients With Type 1 Diabetes Mellitus

Muthayyah Srinivasan, MBBS, MS^_*, Pilar Herrero, MS, Janet B. McGill, MD, Jasper Bennik, MD, Bastiaan Heere, MD, Donna Lesniak, RN, Victor G. Davila-Roman, MD^_* and Robert J. Gropler, MD^_*,,_*

^_* Cardiovascular Division, Department of Medicine, Edward Mallinckrodt Institute of Radiology, St. Louis, Missouri.
Division of Radiological Sciences, Edward Mallinckrodt Institute of Radiology, St. Louis, Missouri.
Division of Endocrinology and Metabolism, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.

Manuscript received September 29, 2004; revised manuscript received February 4, 2005, accepted March 10, 2005.

^_* Reprint requests and correspondence: Dr. Robert J. Gropler, Cardiovascular Imaging Laboratory, Mallinckrodt Institute of Radiology, 510 South Kingshighway Boulevard, St. Louis, Missouri 63110. (Email: groplerr{at}mir.wustl.edu).

OBJECTIVES: The objective of this study was to determine the impact of insulin and glucose on myocardial vasodilator function in patients with type 1 diabetes mellitus (T1DM).

BACKGROUND: The relative importance of plasma insulin and glucose levels on the abnormal vasodilator function observed in T1DM is unknown.

METHODS: Twenty T1DM patients underwent positron emission tomography studies to measure myocardial blood flow (MBF) (in ml/g/min) at rest (MBFr) and during adenosine (MBFa), both under baseline metabolic conditions and then during either hyperinsulinemic-euglycemic clamp (HE) (n = 10; 40 ± 9 years, 8 female subjects, hemoglobin A1c [HbA1c] 7.8 ± 1.1%) or hyperinsulinemic-hyperglycemic clamp (HH) (n = 10; 44 ± 12 years, 8 female subjects, hemoglobin A1c 7.7 ± 0.6%).

RESULTS: Both groups showed similar MBFr and MBFa under baseline metabolic conditions (p = NS). Compared with baseline conditions, MBFr increased in the HH group (p < 0.005), whereas it did not change in the HE group. Compared with baseline conditions, MBFa decreased in the HH group (p < 0.05) but did not change in the HE group. Myocardial perfusion reserve (MPR) (MBFa /MBFr) was similar between the HE and HH groups at baseline (p = NS). During clamp, MPR tended to decrease in the HH group (p < 0.1) but did not change in the HE group (p = NS) when compared with baseline conditions. However, during the clamp MPR was significantly lower in the HH group when compared with the HE group (p < 0.0001).

CONCLUSIONS: In the short term, hyperglycemia has a deleterious effect on myocardial vasodilator function, which outweighs the beneficial effect of hyperinsulinemia.

Abbreviations and Acronyms   HbA1c = hemoglobin A   HE = hyperinsulinemic-euglycemic clamp   HH = hyperinsulinemic-hyperglycemic clamp   MBF = myocardial blood flow   MBFa = myocardial blood flow during adenosine   MBFr = myocardial blood flow at rest   MPR = myocardial perfusion reserve   RPP = rate-pressure product   T1DM = type 1 diabetes mellitus   T2DM = type 2 diabetes mellitus

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