Contribution of Impaired Muscle Glucose Clearance to Reduced Postabsorptive Systemic Glucose Clearance in NIDDM

The reduced postabsorptive rates of systemic glucose clearance in non-insulin-dependent diabetes mellitus (NIDDM) are thought to be the consequence of insulin resistance in peripheral tissues. Although the peripheral tissues involved have not been identified, it is generally assumed to be primarily muscle, the major site of insulin-mediated glucose disposal. To test this hypothesis, we measured postabsorptive systemic and forearm glucose utilization and clearance in 15 volunteers with NIDDM and 15 age- and weightmatched nondiabetic volunteers. Although systemic glucose utilization was increased in NIDDM subjects (14.5 ± 0.5 vs. 11.2 ± 0.2 μmol · kg⁻¹ · min⁻¹, P < 0.001), systemic glucose clearance was reduced 1.40 ± 0.06 vs. 2.13 ± 0.05 ml · kg⁻¹ · min⁻¹, P < 0.01). Although forearm glucose utilization was increased in NIDDM subjects (0.663 ± 0.058 vs. 0.411 ± 0.019 μmol · dl⁻¹ · min⁻¹, P < 0.001), forearm glucose dl⁻¹ clearance was reduced (0.628 ± 0.044 vs. 0.774 ± 0.037 ml · L⁻¹ · min⁻¹, P < 0.01). However, extrapolation of forearm data to total-body muscle indicated that impaired clearance reduced muscle glucose disposal by only 61 ± 21 μmol<min, whereas impaired systemic clearance reduced systemic glucose disposal by 662 ± 82 μmol<min. Thus, impaired muscle glucose clearance accounted for <10% of the reduced systemic glucose clearance in NIDDM subjects. Therefore, we conclude that muscle insulin resistance plays only a minor role in the reduced systemic glucose clearance found in NIDDM in the postabsorptive state and propose that reduced brain glucose clearance is largely responsible.