Abstract 3952: The Transition From Obesity with Insulin Resistance to Type-2 Diabetes Mellitus Is Associated With Progressively Worsening In Myocardial Substrate Metabolism
Background: We have shown previously, that in obese (OB) woman with insulin resistance, a syndrome that typically precedes type-2 diabetes mellitus (T2DM), is associated with an increase in myocardial fatty acid metabolism without a change in myocardial glucose use. Whether these metabolic abnormalities worsen in patients with T2DM is unknown.
Methods: Thirty-two normal volunteers (18F, 44 ± 21 yrs, body mass index [BMI] 25±3 Kg/ m2), 33 OB (30F, 35 ± 3 yrs, body mass index [BMI] 37±3 Kg/ m2) and 22 patients with T2DM (17F, 53±6 yrs, BMI 34±5 Kg/m2) were studied. All T2DM subjects were well-controlled (HbA1c < 7%) and had a normal rest/stress echocardiogram. Positron emission tomography (PET) was performed for the determination of myocardial blood flow (MBF), oxygen consumption (MVO2), glucose utilization (MGU), and fatty acid utilization (MFAU) and oxidation (MFAO).
Results: Plasma glucose, free fatty acid (FFA), insulin and lactate levels were significantly higher in T2DM group compare with OB and NV. Both MFAU and MFAO were increased in OB and T2DM compared with NV. Despite higher glucose levels, MGU was significantly lower in T2DM compared to OB and NV which exhibited similar levels. (Table⇓)
Conclusions: The transition from obesity with insulin resistance to T2DM is associated with more severe metabolic perturbations exemplified by a decline in myocardial glucose metabolism superimposed on the already present increase in myocardial fatty acid use. These metabolic abnormalities may be contributory to increased cardiovascular morbidity and mortality in T2DM.