From Reuters Health Information
By Will Boggs MD
NEW YORK (Reuters Health) Apr 09 - In nondiabetics with hepatitis C virus (HCV), insulin resistance (IR) may improve once the virus is treated - regardless of whether the treatment is successful, researchers say.
They pointed out in a recent paper that HCV infection is an independent risk factor for incident diabetes, particularly when other risk factors for diabetes are present. It may be, they suggest, "that individuals with higher degrees of IR may benefit from receipt of HCV therapy in an attempt to decrease their risk of clinical sequelae of IR."
"Host factors, especially obesity, play a great role in insulin resistance in the HCV population, similar to other populations, but HCV therapy appears to also decrease insulin resistance irrespective of sustained virologic response," Dr. Mandana Khalili from University of California San Francisco told Reuters Health in an email.
Dr. Khalili and colleagues used direct measurements of insulin sensitivity to evaluate the impact of insulin resistance on achieving a sustained virologic response (SVR) to HCV therapy -- and the impact of HCV eradication on insulin resistance. As a control group, they used patients with HCV who did not receive antivirals.
Fifty nondiabetic HCV patients ages 18 to 60 - including 23 on pegylated interferon and ribavirin -- participated in the study, as reported online March 7 in Diabetes Care. At baseline, rates of insulin resistance were statistically similar in patients who did and did not receive antivirals.
There were 14 SVRs, with significantly higher rates in patients with genotypes 2 and 3 (83%) than in those with genotype 1 (36%; p=0.03).
Host and viral factors were similar among patients who did and did not achieve SVR, and the odds of achieving SVR did not differ with the degree of insulin resistance before treatment, regardless of genotype.
Six months after HCV therapy ended, insulin resistance (as measured by steady state plasma glucose) improved among patients who received anti-HCV therapy - although wide confidence intervals, possibly related to the small sample size, meant the difference was not statistically significant.
Specifically, SSPG decreased by 36 mg/dL in those with SVR and by 28 mg/dL in those without SVR, compared with the untreated group.
On multivariate analysis, the improvement in insulin resistance did not differ significantly between patients who did and did not achieve SVR.
As expected, increasing BMI was associated with higher levels of insulin resistance and with higher fasting glucose levels. Interferon use was positively associated only with insulin resistance.
"The main purpose of this study was to evaluate the influence of insulin resistance on SVR as well as SVR on improvement of insulin resistance," the researchers note. "When using precise measurements of insulin resistance, insulin resistance did not appear to be substantially associated with achievement of SVR. Successful viral eradication did not appear to substantially influence insulin resistance when compared with HCV therapy that does not result in SVR."
They added, "Similar to other studies using the direct measurements of insulin resistance, our study is limited by small sample size, which may not have allowed for detection of other known host and viral factors that influence SVR."
"Any patient who is a candidate for HCV therapy should be considered for therapy, especially considering the more recent effective anti-HCV therapy regimens," Dr. Khalili said. "However, those who have known risk factors associated with insulin resistance, especially obesity, should address these factors (including weight loss) first, since they have a much higher impact on decrease in insulin resistance, but they should also be considered for HCV therapy."
"We are currently evaluating a large cohort of HCV patients to describe the distribution and variability of insulin resistance in an ethnically diverse HCV population," Dr. Khalili added.
"Further studies are necessary to determine if additional changes in insulin resistance occur after successful viral eradication beyond six months after discontinuation of HCV therapy," the investigators say.
Diabetes Care 2012.