Recent studies at our institution using positron emission tomography (PET) provide evidence that both myocardial blood flow (MBF) and glucose metabolism may be affected in patients with diabetes mellitus. A retrospective study revealed inadequate myocardial glucose uptake as assessed by 2-[18F]fluoro-2-deoxyglucose (18FDG) in 64% of type I (insulin-dependent diabetes mellitus, IDDM) and 36% of type II (non-insulin-dependent diabetes mellitus, NIDDM) patients. However, a study in 7 patients with IDDM and 9 controls showed that metabolic standardization using hyperinsulinemic-euglycemic clamp is associated with similar myocardial glucose uptake in both groups (0.43 +/- 0.16 vs 0.44 +/- 0.12 micromol/g per min; p = nonsignificant). Furthermore, we studied MBF as assessed by [13N]ammonia in 15 IDDM patients without coronary artery disease. We found an impairment in flow reserve in diabetic patients as compared with a control group of 13 healthy volunteers (2.6 +/- 1.3 vs 4.0 +/- 0.6; p <0.01), which was primarily due to a significantly higher resting MBF (95.3 +/- 27.7 vs 69.1 +/- 8.1 mL/100 g per min; p <0.01). Hyperemic flow during adenosine infusion tended to be lower in diabetics, but was not significantly different (236.3 +/- 105.7 vs 273.0 +/- 26.0 mL/100 g per min; p = nonsignificant). Morphologic and functional abnormalities of the coronary microcirculation have been reported in diabetic animals and humans. Furthermore, there is an ongoing controversy regarding the existence of a specific diabetic cardiomyopathy that is not related to epicardial coronary disease. However, few studies have explored the effect of diabetes, hyperinsulinemia, or hyperglycemia on MBF and glucose metabolism in humans. With PET it is possible to perform comprehensive noninvasive studies of various aspects of cardiac function in patients with diabetes mellitus.