Insulin resistance is characterised by impaired glucose utilisation when measured by a euglycaemic-hyperinsulinaemic clamp. We hypothesised that, in response to postprandial conditions, non-diabetic individuals would have similar intracellular glycolytic and oxidative glucose metabolism independent of the degree of insulin resistance.Methods
Fourteen (seven male) sedentary, insulin-sensitive participants (mean±SD: BMI 25 ± 4 kg/m2; age 39 ± 10 years; glucose disposal rate 9.4 ± 2.1 mg [kg estimated metabolic body size]-1 min-1) and 14 (six male) sedentary, non-diabetic, insulin-resistant volunteers (29 ± 4 kg/m2; 34 ± 13 years; 5.3 ± 1.2 mg [kg estimated metabolic body size]-1 min-1) received after a 10 h fast 60 g glucose plus 15 g [6,6-2H2]glucose. Serum glucose and insulin concentrations, plasma 2H enrichment and whole-body gas exchange were determined before glucose ingestion and hourly thereafter for 4 h. Plasma 2H2O production is an index of glycolytic disposal. On day 2, participants received a weight-maintenance diet. On day 3, a euglycaemic-hyperinsulinaemic clamp was performed.Results
Insulin-resistant individuals had about a twofold higher postprandial insulin response than insulin-sensitive individuals (p = 0.003). Resting metabolic rate was similar in the two groups before (p = 0.29) and after (p = 0.33–0.99 over time) glucose ingestion, whereas a trend for blunted glucose-induced thermogenesis was observed in insulin-resistant vs insulin-sensitive individuals (p = 0.06). However, over the 4 h after the 75 g glucose ingestion, glycolytic glucose disposal was the same in insulin-sensitive and insulin-resistant individuals (36.5 ± 3.7 and 36.2 ± 6.4 mmol, respectively; p = 0.99). Similarly, whole-body carbohydrate oxidation did not differ between the groups either before or after glucose ingestion (p = 0.41).Conclusions/interpretation
Postprandial hyperinsulinaemia and modest hyperglycaemia overcome insulin resistance by enhancing tissue glucose uptake and intracellular glucose utilisation.