Hepatitis C and diabetes: two rising epidemics

June 2004

Hepatitis C virus (HCV) infection has become a growing worldwide epidemic.

Currently, it is the most common chronic bloodborne infection in the United States. It is estimated that 1.2% to 1.5% of the U.S. and Western European populations is infected with the virus, causing 8,000 to 10,000 deaths each year. Diabetes mellitus (DM) is also a major public health problem that is approaching epidemic proportions in our society and worldwide. It is estimated that by 2025 there will be more than 300 million people diagnosed with DM around the world.

Diabetes more common in HCV

An association between HCV infection and DM has been observed since a 1994 study by Allison and colleagues. In this study of 100 patients with cirrhosis, 50% of those with hepatitis C-related cirrhosis had diabetes, compared with only 9% of patients with cirrhosis unrelated to hepatitis C. The odds ratio for HCV by diabetes status was 10.0 (95% confidence interval, 3.4 to 29.3). This study was followed by several reports describing the association between DM and HCV infection and examining the risk factors for diabetes in HCV patients.

A study examined the prevalence of type 2 diabetes among a subset of 9,841 Third National Health and Nutrition Examination Survey (NHANES III) participants with HCV infection. It showed that type 2 diabetes occurred more often in people who were older, nonwhite, with a high body mass index and of low socioeconomic status. After adjusting for these factors, people 40 years of age or older with HCV infection were more than three times more likely to have type 2 diabetes than those without HCV infection. Interestingly, no increase in the prevalence of type 2 diabetes was found among people with hepatitis B virus infection.

Endocrinologists examined the association from the opposite perspective: ie, is HCV more common in diabetic people. In a study by Rudoni and colleagues, the prevalence of HCV antibodies in 259 patients with DM and 14,000 volunteer blood donors was compared.

Anti-HCV antibodies were detected in eight diabetic patients and six blood donors (3.09% vs. 0.04%, P <.001).

No differences were observed between anti-HCV positive and anti-HCV negative diabetic patients in terms of mode of treatment, previous hospital admissions in a diabetic unit and the use of finger stick device for capillary blood sampling, indicating that these medical practices play no role in nosocomial transmission of HCV in diabetic patients.

A similar study from Spain by Simo and colleagues showed a higher prevalence of HCV infection in diabetic patients compared with a control group of blood donors (odds ratio of 4.39). This study also examined the influence of several epidemiological and clinical factors on HCV infection. The authors concluded that there was no particular epidemiological risk factor for HCV infection that characterized those patients with HCV and DM.

Possible pathophysiologic mechanisms

The underlying pathophysiologic mechanisms for the association between HCV and diabetes are far from clear. The current literature suggests several possible mechanisms:

• Insulin resistance/hyperinsulinemia
• Insulin deficiency/decreased insulin secretion
• Nonalcoholic fatty liver disease
• Increased iron stores
• Direct infection of the pancreas by HCV
• Autoimmune B cell damage

Finally, with the current evidence at hand, which is far from conclusive, without establishing a temporal relationship for diabetes development in hepatitis C patients, HCV infection should not be regarded as a cause of DM.

Therefore, prospective studies are clearly indicated in this area. Also, demonstrating specific metabolic derangements associated with HCV infection and improvement in glucose intolerance with antiviral therapy for HCV would strengthen the association between the two disorders. Therefore, properly planned prospective studies are warranted and will certainly require collaboration between endocrinologists and hepatologists.

The prospect of the rising world epidemic of HCV contributing to an already growing diabetes epidemic certainly deserves the attention of both the endocrinologist and hepatologist communities.

For more information:

• Bahtiyar G, Shin JJ, Aytaman A, et al. Association of diabetes and hepatitis C infection: epidemiologic evidence and pathophysiologic insights. Curr Diab Rep. 2004;4(3):194-198.
• Allison ME, Wreghitt T, Palmer CR, et al. Evidence for a link between hepatitis C infection and diabetes mellitus in a cirrhotic population. J Hepatol. 1994;21:1135-1139.
• Mehta S, Brancati F, Sulkowski M, et al. Prevalence of type 2 diabetes mellitus among persons with hepatitis C virus infection in the United States. Ann Intern Med. 2000;133:592-599.
• Rudoni S, Petit JM, Bour JB, et al. HCV infection and diabetes mellitus: influence of the use of finger stick devices on nosocomial transmission. Diabet Metab. 1999;25:502-505.
• Simo R, Hernandez C, Genesca J, et al. High prevalence of hepatitis C infection in diabetic patient. Diabetes Care. 1996;19:998-1000.

• Samy I. McFarlane, MD, FACP, of SUNY Downstate Medical Center, Brooklyn, N.Y., is Associate Medical Editor of our sister newspaper Endocrine Today.