Summary
The aim of this study was to characterize the acute effect of euglycemic (glucose
5.2 ± 0.6 mrnol/1) hyperinsulinemia (mean 118 ± 32 mU/1) on fibrinolytic variables,
free fatty acids (FFA) and counter-regulatory hormones. In addition, the effect of
chronic treatment with metformin, an oral antidiabetic agent which enhances insulin
action, and metoprolol CR, a relatively betaj-selective adrenergic antagonist, was
also evaluated. A randomized, double-blind, placebo-controlled, cross-over study including
18 non-obese men, aged 53 ± 6 years, was performed. The investigations were performed
after each treatment period of 6 weeks in both the postabsorptive state and during
a euglycemic, hyperinsulinemic clamp.
Compared to the postabsorptive state, plasminogen activator inhibitor (PAI-1) activity
and antigen, tissue plasminogen activator (t-PA) antigen and FFA decreased (p <0.001)
after 120 min of euglycemic hyperinsulinemia. In addition, t-PA activity increased
(p <0.01) while blood levels of lipoprotein (a), catecholamines and cortisol remained
unchanged. Growth hormone increased during the clamps and this was most pronounced
after treatment with metoprolol CR.
When the effect of treatment was compared, postabsorptive levels of C-peptide, FFA
and t-PA antigen were lower after metformin than after the placebo period (p <0.05).
t-PA antigen also remained lower during the clamp after metformin treatment. No significant
effects of metformin or metoprolol CR were seen on insulin-stimulated glucose uptake
during the clamps or on postabsorptive levels of counterregulatory hormones, PAI-1
or Lp(a).
Thus, the rapidly increased fibrinolytic activity after 2 h hyperinsulinemia with
maintained euglycemia can not be explained by the concomitant changes in counterregulatory
hormones. It is more likely that the decreased FFA and/or triglyceride levels play
a role.
