Curing hepatitis C infection with direct-acting antiviral treatment improves diabetes control in people with more severe type 2 diabetes, a review of patients treated in the US Veterans Affairs health care system has found. The study is published in the journal Diabetes Care.
Hepatitis C infection greatly increases the risk of developing type 2 diabetes in people who are already at higher risk. One study found that in older people and those with higher body mass, hepatitis C infection increased the risk of diabetes eleven-fold.
Type 2 diabetes develops as a consequence of a loss of control of glucose levels due to insulin resistance. The body produces insulin to encourage the uptake of glucose as fuel for cells. Resistance to the effect of insulin can develop as a result of lack of exercise, a diet high in sugar and carbohydrates and obesity, leading to higher glucose levels and eventually to type 2 diabetes.
In type 2 diabetes, prolonged high levels of glucose in the blood can lead to damage to small blood vessels, kidney damage, nerve damage and blindness. Type 2 diabetes also increases the risk of heart disease.
The hepatitis C virus promotes insulin resistance through several pathways.
Although previous research has shown that insulin resistance declines in people cured of hepatitis C by interferon-based treatment, no large study has yet examined what happens to diabetes control after people are cured of hepatitis C by direct-acting antiviral treatment.
To investigate this question, researchers from Veterans Affairs clinics in Portland and Seattle looked at the effects of direct-acting antiviral treatment on diabetes control in everyone with diabetes who received direct-acting antiviral treatment between January 2014 and October 2015 in the US Veterans Affairs healthcare system.
A total of 12,020 people were treated with direct-acting antivirals, without pegylated interferon or ribavirin, during this period. People treated with ribavirin were excluded because anaemia caused by ribavirin can result in a reduction in glucose concentrations. The analysis also excluded previously treated people in order to exclude any impact of prior treatment on glucose control.
Just under ten per cent of people who underwent direct-acting antiviral treatment had pre-existing type 2 diabetes (2435 people). Of these, 2180 achieved a sustained virologic response (SVR) to treatment (cure).
Researchers compared changes in HbA1c, the measure of glucose concentrations in plasma, 12 months before and 12 months after treatment, and also looked at changes in antidiabetic medication over the same period. HbA1c is expressed either as a percentage or, more commonly, in mmol/mol or mmol/l. In this study researchers reported most changes as a percentage measurement.
The study population was predominantly male (97.5%), with an average age of 62 years and an average body mass index (BMI) of 30.2. Almost all had genotype 1 infection (99.3%), 43.6% were black and 38.3% were white.
People who did not achieve sustained virologic response were more likely to have cirrhosis (54.5 vs 35.3%) and decompensated cirrhosis (20 vs 9%), and slightly more likely to be receiving insulin as antidiabetic medication (49.8 vs 41.3%).
There was no significant difference in HbA1c levels at baseline between those who achieved SVR and those who did not (7.2 vs 7.27%, 55 vs 56 mmol/mol) and after adjusting for baseline characteristics there was no significant difference in the post-treatment reduction in HbA1c (-0.18%, p = 0.1). But, when the researchers looked only at the group of patients with higher HbA1c levels at baseline (above 7.2%, which was the median HbA1c in the study population), they found that people who achieved SVR had significantly larger reductions in HbA1c than those who were not cured (0.98 vs 0.34), an adjusted mean difference of 0.34% (p = 0.02).
To put this finding in context, a reduction of 1% (1.6 mmol/mol) in HbA1c is associated with substantial reduction in the risk of heart attack, microvascular disease, kidney damage and retinopathy.
There was no significant difference between the two groups of patients in reduction in medication use after treatment, but in those with a baseline HbA1c below 7.2% (55 mmol/mol, 8.9 mmol/l), insulin use rose among those who were not cured but fell slightly in those who were cured (difference in use, -6.1%, p = 0.03).
The authors say that the substantial improvement in glycemic control observed in people who were cured of hepatitis C, especially in those with higher baseline HbA1c, justifies consideration of direct-activing antiviral treatment for everyone with hepatitis C who has type 2 diabetes. Longer-term follow-up to check whether these improvements are sustained is necessary, they say.