Insulin resistance induced by GH is transient and reversible: glucose clamp studies during different ambient GH levels in GH-deficient adults
Thomas Krusenstjerna-Hafstrøm, Niels Møller, Jens Sandahl Christiansen, Niels Jessen & Jens Otto Lunde Jørgensen
Background: The impact of GH on insulin sensitivity is ambiguous since both long standing GH-deficiency as well as acute GH exposure and prolonged GH-excess are associated with insulin resistance.
Aim: To test the hypotheses that the insulin antagonistic effect of GH i) is dynamic and depend on ambient GH levels and ii) subsides gradually with time after GH exposure.
Methods: Eight GHDA participated in a randomised crossover study. Each subject was studied thrice on three different occasions. On 2 study occasions a 7 h intravenous GH infusion (510 ng/kg per min) was given from 2000 to 0300 h (A) and 02000900 h (B), respectively. On the third occasion no GH was infused (C). The following morning a 6 h hyperinsulinemiceuglycemic clamp (0.5 mU/kg per min) was performed in combination with tritiated glucose, indirect calorimetry and muscle biopsies. Eight healthy control subjects were studied once without GH exposure.
Results: The total glucose infusion rate (M value), which reflects peripheral insulin sensitivity, differed significantly between GH 02000900 h (B) and no GH (C) (P=0.023), and between GH 20000300 h (A) and GH 02000900 h (B) (P=0.025), but not between (A) and (C) (P=0.176). The time course changes in the glucose infusion rate were different in study (B) versus study (C) (P=0.007), and between study (A) versus study (B) (P=0.004), but not between study (A) and (C) (P=0.172).
Conclusion: i) Acute GH exposure induces insulin resistance, which subsides within few hours after GH discontinuation, ii) the data suggest that insulin sensitivity during regular daily GH therapy may change as a function of time after each injection, iii) this should be considered when evaluating the clinical impact of GH therapy on glucose homeostasis.