Interferon induces insulin resistance in patients with chronic active hepatitis 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 for 2 weeks): (1) oral glucose tolerance tests to measure insulin secretion; (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 hormones. Results: The oral glucose tolerance test showed that a 2-week treatment with interferon did not induce apparent change in plasma glucose and insulin profiles, Nevertheless, interferon therapy worsened insulin-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). Furthermore, interferon therapy significantly decreased splanchnic glucose uptake by 38% from 47 +/- 2% to 29 +/- 3% (p<0.01). No changes were noted for plasma glucoregulatory hormones, such as epinephrine, norepinephrine, cortisol and growth hormone, after interferon therapy. Conclusions: 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 observation may be needed during interferon therapy in subjects with impaired glucose tolerance.