Postprandial whole-body glycolysis is similar in insulin-resistant and insulin-sensitive non-diabetic humans

Abstract

Aims/hypothesis: 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.

Fig. 1

Serum glucose (a), serum insulin (b), whole-body resting metabolic rate (c) and whole-body carbohydrate oxidation (d) before and after a 75 g oral glucose dose in insulin-resistant (continuous line) and insulin-sensitive (dashed line) individuals. Insert: 4 h AUC for the increase in resting metabolic rate relative to fasting values after a 75 g oral glucose dose in insulin-resistant (black bar) and insulin-sensitive (white bar) individuals. *p<0.05 and †p=0.06 for comparison between groups. **p<0.01 compared with its respective fasting value in each group

Fig. 2

a Plasma net ²H₂O production before and after a 75 g oral glucose dose containing 15 g [6,6-²H₂]glucose in insulin-resistant (black line/circles) and insulin-sensitive (dashed line/white circles) participants. b Relationship between insulin-stimulated glucose disposal rate measured by hyperinsulinaemic clamp and 4 h net ²H₂O production. c Ratio between 4 h net ²H₂O production and 4 h glucose AUC in insulin-resistant (black bar) and insulin-sensitive (white bar) participants. Pearson value: −0.07; p=0.72. **p=0.01 for comparison between groups