title: The hyperinsulinaemic-euglycaemic glucose clamp: reproducibility and metabolic effects of prolonged insulin infusion in healthy subjects.
abstract: To examine the reproducibility of the hyperinsulinaemic-euglycaemic clamp technique at mid-physiological hyperinsulinaemia, seven healthy subjects ¿age 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 micromol.l(-1))-euglycaemic (4.5 mmol.l(-1)) clamps performed 48 h and 14 days apart respectively. The third clamp was prolonged to 8 h in order to examine effects on glucose disposal during prolonged clamps. The glucose infusion rates (GIRs) 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 coefficient of variation of 5.8 (2.6, 22) %. During the 8 h clamp a highly variable gradual increase in GIR was observed, reaching a plateau between 4 and 5 h at 32 (5, 101) % above the GIR between 1 and 2 h (P<0.05). This increase 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 oxidation measured by indirect calorimetry was stable during the repeated 2 h clamps and the 8 h clamp. Endogenous glucose production measured by infusion of [6, 6-(2)H(2)]glucose was suppressed during the 8 h clamp. The 2 h hyperinsulinaemic-euglycaemic clamp is reproducible at a mid-physiological range of hyperinsulinaemia. If prolonged, it results in a delayed increase in non-oxidative glucose disposal, which is most pronounced in subjects with low insulin sensitivity. The findings underline the importance of selecting age-matched controls in studies of insulin resistance.
authors.affiliation: Department of Surgery, Karolinska Hospital, S-171 76 Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Soop
authors.forename: J
authors.initials: J
authors.lastname: Nygren
authors.forename: K
authors.initials: K
authors.lastname: Brismar
authors.forename: A
authors.initials: A
authors.lastname: Thorell
authors.forename: O
authors.initials: O
authors.lastname: Ljungqvist
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002153:Calorimetry, Indirect; D004334:Drug Administration Schedule; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D015309:Glucose Clamp Technique; D006728:Hormones / Q000097:blood; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood*; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006728:Hormones; D007004:Hypoglycemic Agents; D007328:Insulin