STUDIES ON THE MASS-ACTION EFFECT OF GLUCOSE IN NIDDM AND IDDM - EVIDENCE FOR GLUCOSE RESISTANCE

The ability of hyperglycaemia to enhance glucose uptake was evaluated in 9 non-insulin-dependent (NIDDM), 7 insulin-dependent (IDDM) diabeti c subjects, and in 6 young and 9 older normal volunteers. Following ov ernight insulin-induced euglycaemia, a sequential three-step hyperglyc aemic clamp (+ 2.8 + 5.6, and + 11.2 mmol/l above baseline) was perfor med with somatostatin plus replacing doses of basal insulin and glucag on, 3-H-3-glucose infusion and indirect calorimetry. In the control su bjects as a whole, glucose disposal increased at each hyperglycaemic s tep (13.1+/-0.6, 15.7+/-0.7, and 26.3+/-1.1 mu mol/kg.min). In NIDDM ( 10.5+/-0.2, 12.1+/-1.0, and 17.5+/-1.1 mu mol/kg.min), and IDDM (11.2/-0.8, 12.9+/-1.0, and 15.6+/-1.1 mu mol/kg.min) glucose disposal was lower during all three steps (p<0.05-0.005). Hepatic glucose productio n declined proportionally to plasma glucose concentration to a similar extent in all. four groups of patients. In control subjects, hypergly caemia stimulated glucose oxidation (+ 4.4+/-0.7 mu mol/kg.min) only a t + 11.2 mmol/l (p < 0.05), while non-oxidative glucose metabolism inc reased at each hyperglycaemic step (+ 3.1+/-0.7; + 3.5+/-0.9, and + 10 .8+/-1.7 mu mol/kg.min; all p < 0.05). In diabetic patients, no increm ent in glucose oxidation was elicited even at the highest hyperglycaem ic plateau (IDDM = + 0.5+/-1.5; NIDDM = + 0.2+/-0.6 mu mol/kg.min) and non-oxidative glucose metabolism was hampered (IDDM = + 1.8+/-1.5, 3.1+/-1.7, and + 4.3+/-1.8; NIDDM = + 0.7+/-0.6, 2.1+/-0.9, and + 7.0/-0.8 mu mol/kg.min; p<0.05-0.005). Blood lactate concentration increa sed and plasma non-esterified fatty acid (NEFA) fell in control (p < 0 .05) but not in diabetic subjects. The increments in blood lactate wer e correlated with the increase in non-oxidative glucose disposal and w ith the decrease in plasma NEFA. In conclusion: 1) the ability of hype rglycaemia to promote glucose disposal is impaired in NIDDM and IDDM; 2) stimulation of glucose oxidation and non-oxidative glucose metaboli sm accounts for glucose disposal; 3) both pathways of glucose metaboli sm are impaired in diabetic patients; 4) impaired ability of hyperglyc aemia to suppress plasma NEFA is present in these patients. These resu lts suggest that glucose resistance, that is the ability of glucose it self to promote glucose utilization, is impaired in both IDDM and NIDD M patients.