With Justine Hum, MD, Janice Jou, MD and Mandana Khalili, MD
Having hepatitis C virus (HCV) can worsen glycemic control in patients with type 2 diabetes (T2D).1 In patients who developed a sustained virologic response (SVR), both hemoglobin (Hb) A1c levels and use of insulin decreased as compared with patients who did not achieve SVR, according to findings published in Diabetes Care.1
By treating HCV with direct-acting antiviral treatment, the result will be improved glycemic control in patients with T2D,1 according to the authors.
“There are studies showing that the HCV, itself, interacts with insulin receptors in order to make a cell more insulin resistant.2-4 Additionally, infection with HCV causes a multitude of pro-inflammatory cytokines that leads to more gluconeogenesis and enhanced lipid accumulation in the liver,” co-authors Justine Hum, MD, and Janice Jou, MD, both from the Division of Gastroenterology at the Portland Veterans Affairs (VA) Medical Center in Portland, Oregon, told EndocrineWeb. And, this cascade promotes insulin resistance, they said.
“Diabetes is considered an extrahepatic manifestation of hepatitis C; therefore, the presence of diabetes is actually an indication for initiation of hepatitis C therapy. In standard clinical care, we treat patients with diabetes and hepatitis C frequently and actually prioritize the hepatitis C treatment in these patients,” said Mandana Khalili, MD, professor of medicine at the University of California, San Francisco and chief of clinical hepatology at Zuckerberg San Francisco General Hospital.
Dr. Hum and colleagues uniquely examined a possible relationship between SVR and glycemic control. They relied on HbA1c levels for both diagnostic and monitoring measures of T2D, as these levels can assess for glycemic control over the lifespan of a red blood cell.1
Physicians in the Veterans Administration healthcare system receive reminders annually to check the HbA1c in their patients with T2D, with HbA1c monitoring occurring as frequently as once every three months.
In this study,1 the researchers identified 2,435 patients with T2D and HCV from the VA healthcare system who underwent direct-acting antiviral treatment between January 2014 and October 2015. Patients who underwent regimens containing interferon or ribavirin were excluded.
All diabetic medications taken by the patients immediately prior to initiation of DAA therapy were identified and assessed again 15 months after the end of treatment. These medications were categorized into nine classes: insulin, metformin, sulfonylureas, thiazolidinediones, sodium–glucose cotransporter 2 inhibitors, dipeptidyl peptidase 4 inhibitors, meglitinides, a-glucosidase inhibitors, and glucagon-like peptide 1 agonists.
Researchers created three measurements of antidiabetic medication use, comparing pre-treatment and post-treatment use.1 These three categories were:
Of the 2,435 patients, their average age was 62.2 years, BMI was 30.2kg/m2, and nearly all (97.5%) were male. The overwhelming majority (99.3%) had genotype 1 HCV. Non-Hispanic black was the most frequent racial/ethnic groups (43.6%), followed by non-Hispanic white (38.3%) and Hispanic (5.4%). Both cirrhosis (37.3%) and decompensated cirrhosis (10.4%) were common. Over three-quarters of patients (75.2%) received at least one diabetic medication; 42.2% of patients received insulin.
Of the patients who underwent antiviral therapy, 2,180 achieved SVR and 255 did not. Patients who achieved SVR were less likely to have cirrhosis (35.3% vs. 54.5%) or decompensated cirrhosis (9.3% vs. 20%) compared with patients in whom antiviral treatment failed. Patients who achieved SVR were also less likely to be receiving antidiabetic medications (74.8% vs. 78.0%) or insulin (41.3% vs. 49.8%).1 Notably, the group in whom treatment failed displayed more severe markers of liver disease.
“It is difficult to answer whether the improvement in diabetes control observed in this paper is long-term as the paper only evaluated [changes] in glucose control for one year after achieving SVR, said Dr. Khalili. The authors concurred.
“It is unknown how long SVR-induced endocrine improvements will persist, but our study looked at averages of HbA1c percentages and also medication prescriptions for one year after treatment. The next step would be to evaluate if the response is durable and if there are improved microvascular morbidities from the treatment of HCV in the long run,” said Dr. Hum.
In patients achieving SVR, the decrease from pretreatment baseline in average HbA1c was larger (from 7.2% [55 mmol/mol] to 6.82% [51 mmol/mol]) than in the group not achieving SVR (from 7.27% [56 mmol/mol] to 7.08% [54 mmol/mol]),1 according to the findings. After adjustments for baseline characteristics, the mean difference in the HbA1c decrease between the SVR and treatment failure groups was 0.13, though this did not reach statistical significance (P =.1). Notably, levels of HbA1c prior to antiviral therapy were similar between those achieving SVR and the group that did not.
Although the group that achieved SVR experienced a larger decrease in the need for a number of classes of antidiabetic treatments, and a lower proportion of patients received antidiabetic medications than the treatment failure group, these differences were not statistically significant.1
The proportion of patients receiving insulin declined more in patients who achieved SVR (41.3% to 38%) than in the treatment failure group whose need for insulin increased significantly from 49.8% to 51% (P =.04). The decrease in insulin use in patients achieving SVR was not correlated with an increased use of metformin, which offered confirmation that the reduction in medication was not the result of the substitution of one medication for another, said Drs. Hum and Jou.
“The findings from this study indicate that there could be important endocrine benefits to treatment of chronic HCV. As insurance companies are evaluating who to treat for hepatitis C, the cost analysis of improving diabetes should also be considered,” concluded the co-authors.
A hepatitis C infection may lead to difficulty in managing diabetes for people who are newly diagnosed as well as patients who have been under good glucose control,5 according to the Centers for Disease Control and Prevention. Even patients with diabetes who were stabilized for long periods of time have had their glucose control disrupted by an increase in insulin resistance due to the HCV.
“In general, as diabetes is considered an extrahepatic manifestation of HCV disease, eradication of HCV is beneficial to patients with diabetes. Importantly, with the high effectiveness of current hepatitis C drugs, all patients with diabetes are likely to benefit from HCV eradication,” said Dr. Khalili.