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In recent years, increasing evidence has suggested a strong association between diabetes mellitus (DM) and hepatocellular carcinoma (HCC). To provide a quantitative assessment of this association, we performed a systematic review and metaanalysis of cohort studies. We collected studies through a literature search of Medline from January 1, 1966 and EMBASE from January 1, 1974, through July 31, 2010. Summary relative risks (SRRs) with their corresponding 95% confidence intervals (CIs) were calculated using a random-effects model. A total of 25 cohort studies that met our inclusion and exclusion criteria were included in our analysis. Among these, 18 studies showed that DM was associated with an increased incidence of HCC (SRRs 5 2.01, 95% CI: 1.61-2.51), compared with individuals without DM. There was a statistically significant heterogeneity among these studies (Q 5 136.68, p < 0.001, I 2 5 87.6%). Analyses subgrouped by controlling confounders revealed that the increased incidence of HCC was independent of geographic location, alcohol consumption, history of cirrhosis, or infections with hepatitis B (HBV) or hepatitis C virus (HCV). In addition, DM was also positively associated with HCC mortality (SRR 5 1.56; 95% CI: 1.30-1.87), with no significant evidence of heterogeneity among studies (Q 5 1.16, p 5 0.56, I 2 50%). There were no significant publication bias (p 5 0.79 for Egger's regression asymmetry test). These findings strongly support a positive association between DM and increased risk of HCC in both males and females.Hepatocellular carcinoma (HCC) is one of the most prevalent tumor types, with increased incidence and mortality in recent years. Annually, approximately 500,000 new cases are diagnosed worldwide and a nearly equivalent number die of this disease. Chronic infection with hepatitis B (HBV) or hepatitis C virus (HCV) has been considered the most important etiologic risk factors for human HCC. 1 In addition, excessive alcohol consumption, cigarette smoking, and environmental exposure to aflatoxin are also risk factors for HCC development. 2 However, many individuals who have been exposed to these risk factors never develop HCC, while 15-50% of cases occur among those without exposure. 3 Coinciding with increased HCC incidence, the prevalence of DM has also grown markedly over the past two decades in most countries. 4,5 In recent years, DM has become highly suspect as a risk factor for several malignancies, including cancers of the breast, 6 endometrium, 7 pancreas, 8 and liver. 9 A systematic review and meta-analysis of 26 studies (13 case-control and 13 cohort) conducted in 2005 showed that individuals with DM had a 2.5-fold greater risk of HCC [pooled odds ratio in caseÀcontrol studies ¼ 2.5; 95% confidence interval (CI): 1.8-3.5; pooled relative risk (RR) in cohort studies ¼ 2.5; 95% CI: 1.9-3.2] compared to controls. This significant association between diabetes and HCC was independent of alcohol consumption or hepatitis viral infections. 9 Since then, other relevant studies on the associat...

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