INTERFERON INDUCES INSULIN-RESISTANCE IN PATIENTS WITH CHRONIC ACTIVEHEPATITIS-C

Aim / Methods: To elucidate the metabolic effect of interferon alpha, the following tests were performed on 14 patients with chronic active hepatitis C before and after interferon therapy (6 million units/day f or 2 weeks): (1) oral glucose tolerance tests to measure insulin secre tion; (2) euglycemic hyperinsulinemic clamp with oral glucose load to measure peripheral and hepatic insulin sensitivity (splanchnic glucose uptake); and (3) measurements of plasma levels of glucoregulatory hor mones. Results: The oral glucose tolerance test showed that a 2-week t reatment with interferon did not induce apparent change in plasma gluc ose and insulin profiles, Nevertheless, interferon therapy worsened in sulin-mediated glucose uptake in the peripheral tissues by 17% from 44 .4 +/- 3.2 to 37.3 +/- 3.0 mu mol . kg(-1) . min(-1) (p<0.05). Further more, interferon therapy significantly decreased splanchnic glucose up take by 38% from 47 +/- 2% to 29 +/- 3% (p<0.01). No changes were note d for plasma glucoregulatory hormones, such as epinephrine, norepineph rine, cortisol and growth hormone, after interferon therapy. Conclusio ns: These results indicate that interferon therapy for 2 weeks induces insulin resistance in the splanchnic, as well as peripheral tissues, in patients with chronic active hepatitis C, Therefore, more careful o bservation may be needed during interferon therapy in subjects with im paired glucose tolerance.