Colberg, Sheri R., James M. Hagberg, Steve D. McCole, Joseph M. Zmuda, Paul D. Thompson, and David E. Kelley. Utilization of glycogen but not plasma glucose is reduced in individuals with NIDDM during mild-intensity exercise. J. Appl. Physiol. 81(4): 2027–2033, 1996.—To test the hypothesis that substrate utilization during mild-intensity exercise differs in non-insulin-dependent diabetes mellitus (NIDDM) compared with nondiabetic subjects, seven lean healthy subjects (L), seven obese healthy subjects (O), and seven individuals with NIDDM were studied during 40 min of mild-intensity cycling (40% of peak O2 uptake). Systemic utilization of plasma glucose (Glc Rd) was determined by using isotope dilution methods. Gas exchange was measured to determine rates of carbohydrate (CHO) and lipid oxidation. During exercise, when CHO oxidation was greater than Glc Rd, the net oxidation of glycogen was calculated as the difference: CHO oxidation − Glc Rd. During mild-intensity cycling, the respiratory exchange ratio was similar across groups (0.87 ± 0.02, 0.85 ± 0.02, and 0.86 ± 0.01 in L, O, and NIDDM subjects, respectively), and CHO oxidation accounted for one-half of total energy expenditure during exercise. Glc Rd increased during exercise and was greatest in subjects with NIDDM (3.0 ± 0.2, 2.9 ± 0.2, and 4.5 ± 0.4 ml ⋅ kg−1 ⋅ min−1in L, O, and NIDDM subjects, respectively, P < 0.05), yet Glc Rd was less than CHO oxidation during exercise, indicating net oxidation of glycogen. Glycogen oxidation was greater in L and O than in NIDDM subjects (3.4 ± 1.0, 2.5 ± 0.9, and 1.7 ± 0.8 ml ⋅ kg−1 ⋅ min−1; P < 0.05). In summary, during mild-intensity exercise, NIDDM subjects have an increased Glc Rd and a decreased oxidation of muscle glycogen.