The hyperinsulinaemic-euglycaemic glucose clamp: reproducibility and metabolic effects of prolonged insulin infusion in healthy subjects

To examine the reproducibility of the hyperinsulinaemic-euglycaemic clamp t echnique at mid-physiological hyperinsulinaemia, seven healthy subjects {ag e 50 (25, 59) years [median (range)]. body mass index 23.1 (20.8, 25.5) kg. m(-2)} were investigated with three 2 h hyperinsulinaemic (60 mu mol.l(-1)) -euglycaemic (4.5 mmol.l(-1)) clamps performed 48 h and 14 days apart respe ctively. The third clamp was prolonged to 8 h in order to examine effects o n glucose disposal during prolonged clamps. The glucose infusion rates (GIR s) during the three 2 h clamps were 7.41 (4.28, 10.96), 7.26 (5.38, 11.02) and 6.63 (4.42, 10.3) mg.kg(-1).min(-1), with a median intra-individual coe fficient of variation of 5.8 (2.6, 22) %. During the 8 h clamp a highly var iable gradual increase in GIR was observed, reaching a plateau between 4 an d 5 h at 32 (5, 101) % above the GIR between 1 and 2 h (P < 0.05). This inc rease was correlated inversely with the GIR between 1 and 2 h (r = -0.82; P < 0.05), and directly with age (r = 0.86; P < 0.05). Carbohydrate oxidatio n measured by indirect calorimetry was stable during the repeated 2 h clamp s and the 8 h clamp. Endogenous glucose production measured by infusion of [6,6-H-2(2)]glucose was suppressed during the 8 h clamp. The 2 h hyperinsul inaemic-euglycaemic clamp is reproducible at a mid-physiological range of h yperinsulinaemia. If prolonged, it results in a delayed increase in non-oxi dative glucose disposal, which is most pronounced in subjects with low insu lin sensitivity. The findings underline the importance of selecting age-mat ched controls in studies of insulin resistance.