Evidence of Increased Systemic Glucose Production and Gluconeogenesis in an Early Stage of NIDDM

To assess the mechanisms of fasting hyperglycemia in NIDDM patients with mild elevation of fasting plasma glucose (FPG) compared with NIDDM patients with overt hyperglycemia, we studied 29 patients with NIDDM, who were divided in two groups according to their fasting plasma glucose (<7.8 and ≥7.8 mmol/l for groups A and B, respectively), and 16 control subjects who were matched with NIDDM patients for age, sex, and body mass index. All subjects were infused with ]3-³H]glucose between 10:00 P.M. and 10:00 A.M. during overnight fasting to determine glucose fluxes. In 27 subjects (17 diabetic and 10 control), ]U-¹⁴C]alanine was simultaneously infused between 4:00 A.M. and 10:00 A.M. to measure gluconeogenesis (GNG) from alanine. Arterialized- venous plasma samples were collected every 30 min for measurement of glucose fluxes, GNG, and glucoregulatory hormones. In group A, plasma glucose, rate of systemic glucose production (SGP), and GNG were greater than in control subjects (7.2 ± 0.2 vs. 4.9 ± 0.1 mmol/l, 10.9 ± 0.2 vs. 9.5 ± 0.3 μmol · kg⁻¹ · min⁻¹, and 0.58 ± 0.04 vs. 0.37 ± 0.02 μmol · kg⁻¹ · min⁻¹, respectively, for group A and control subjects; mean value 8:00 A.M.-10:00 A.M., all P < 0.05). Both increased SGP and GNG correlated with plasma glucose in all subjects (r = 0.77 and r = 0.75, respectively, P < 0.005). Plasma counterregulatory hormones did not differ in NIDDM patients compared to control subjects. The present studies demonstrate that SGP and GNG are increased in NIDDM patients without overt fasting hyperglycemia.Thus these metabolic abnormalities primarily contribute to early development of overnight and fasting hyperglycemia in NIDDM.