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
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
Anti-HCV antibodies were detected in eight diabetic
patients and six blood donors (3.09% vs. 0.04%, P
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
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
Possible Pathophysiologic Mechanisms
The current literature suggests
several possible mechanisms:
Insulin deficiency/decreased insulin
Nonalcoholic fatty liver disease
Increased iron stores
Direct infection of the pancreas by
Autoimmune B cell damage
The underlying pathophysiologic mechanisms for the
association between HCV and diabetes are far from
clear. The current literature suggests several
- Insulin resistance/hyperinsulinemia
- Insulin deficiency/decreased
- Nonalcoholic fatty liver
- 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.
Bahtiyar G, Shin JJ, Aytaman A, et al.
Association of diabetes and hepatitis C infection:
epidemiologic evidence and pathophysiologic
insights. Curr Diab Rep.
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.
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.
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.
Simo R, Hernandez C, Genesca J, et al.
High prevalence of hepatitis C infection in diabetic
patient. Diabetes Care.
Samy I. McFarlane, MD, FACP, of SUNY
Downstate Medical Center, Brooklyn, N.Y., is
Associate Medical Editor of our sister newspaper