Vinay Sundaram, MD, a hepatologist from Cedars-Sinai Medical Center in Los Angeles, cautions that an association between HCV infection and T2D does not imply causality. “While there is a link between HCV infection and insulin resistance, I do not think HCV causes diabetes. However, HCV may predispose to diabetes,” he said.

Dr Tomer agrees that causality between these conditions cannot be established with the current evidence. “It’s unclear if HCV actually causes diabetes, or if HCV triggers diabetes in somebody who is susceptible for other reasons,” he said.


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How HCV Infection Might Increase T2D Risk

Several hypotheses have been proposed to explain how HCV infection might increase the risk for T2D. According to Dr Tomer, one way HCV might influence the development of T2D is through promoting inflammation. “We know that inflammation is associated with T2D, and one hypothesis is that the virus causes inflammation by inducing cytokines, which are inflammatory mediators.”

Another hypothesis is that viral replication within infected cells may disturb normal insulin signaling, particularly in the liver, Dr Tomer said. He added that HCV may also induce reactive oxygen species and create oxidative stress in the liver, disrupting glucose metabolism and glucose homeostasis.

Lastly, HCV may not only infect liver cells, but also the pancreatic islet beta cells that secrete insulin, according to Dr Tomer. “Some studies have shown virus-like particles inside the islets,” he said. “But just seeing virus particles does not prove that HCV infects islet cells. HCV could be attaching to the cells and not actually infecting them. But this is a very intriguing hypothesis if indeed the virus can somehow cause direct infection of the pancreatic islets.”

Screening for T2D in HCV: A Public Health Matter

Diabetes, like HCV, has a high prevalence worldwide, affecting 415 million people around the globe. T2D causes significant morbidity and mortality from cardiovascular and other complications and is a major public health issue.3

According to Dr Tomer, screening for T2D in the HCV population is important because approximately 29 million people in the United States have diabetes and 86 million have prediabetes, and many of them are unaware that they have these conditions. “The longer a patient has untreated diabetes, the more likely they are to develop complications such as nephropathy and retinopathy,” he said. “The other reason to screen for diabetes in HCV patients is that having high sugars in itself accelerates the progression of diabetes, a phenomenon known as glucose toxicity.”

Dr Tomer believes that every patient with HCV should be screened for T2D. He and his colleagues, including Sara S Hammerstad, MD, from the Oslo University Hospital Ullevål in Norway, proposed an algorithm for T2D screening in this population in a review article published in Frontiers in Endocrinology.2

However, Dr Sundaram does not agree that T2D screening should be performed in all patients with HCV. “At this point, I do not believe there’s enough evidence to routinely screen for T2D in these patients unless they have additional risk factors,” he said.

“While diabetes screening in HCV patients could potentially reduce healthcare costs, HCV does not appear to be a strong enough risk factor to warrant early diabetes screening in this population,” he added.

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References

  1. Desbois AC, Cacoub P. Diabetes mellitus, insulin resistance and hepatitis C virus infection: A contemporary review. World J Gastroenterol. 2017;23:1697-1711. doi:10.3748/wjg.v23.i9.1697
  2. Hammerstad SS, Grock SF, Lee HJ, Hasham A, Sundaram N, Tomer Y. Diabetes and hepatitis C: a two-way association. Front Endocrinol (Lausanne). 2015;6:134. doi:10.3389/fendo.2015.00134
  3. Gastaldi G, Goossens N, Clément S, Negro F. Current level of evidence on causal association between hepatitis C virus and type 2 diabetes: A review. J Adv Res. 2017;8:149-159. doi:10.1016/j.jare.2016.11.003
  4. Mangia A, Schiavone G, Lezzi G, et al. HCV and diabetes mellitus: evidence for a negative association. Am J Gastroenterol. 1998;93:2363-2367. doi:10.1111/j.1572-0241.1998.00688.x
  5. Ruhl CE, Menke A, Cowie CC, Everhart JE. Relationship of hepatitis C virus infection with diabetes in the U.S. population. Hepatology. 2014;60:1139-1149. doi:10.1002/hep.27047

This article originally appeared on Infectious Disease Advisor