Cannabis Use Is Associated With a Lower Risk of Diabetes in Chronic Hepatitis C-infected Patients

(ANRS CO22 Hepather cohort)

Tangui Barré; Marie Libérée Nishimwe; Camelia Protopopescu; Fabienne Marcellin; Fabrice Carrat; Céline Dorival; Elisabeth Delarocque-Astagneau; Dominique Larrey; Marc Bourlière; Ventzislava Petrov-Sanchez; Mélanie Simony; Stanislas Pol; Hélène Fontaine; Patrizia Carrieri

Disclosures

J Viral Hepat. 2020;27(12):1473-1483. 

In This Article

Abstract and Introduction

Abstract

Chronic hepatitis C virus (HCV) infection is a risk factor of insulin resistance, and HCV-infected patients are at a high risk of developing diabetes. In the general population, research has shown the potential benefit of cannabis use for the prevention of diabetes and related metabolic disorders. We aimed to test whether cannabis use is associated with a lower risk of diabetes in chronic HCV-infected patients. Chronic HCV-infected patients (n = 10 445) were selected from the French national, multicenter, observational ANRS CO22 Hepather cohort. Cross-sectional data collected at cohort enrollment were used to assess the association between patients' clinical and behavioural characteristics and the risk of diabetes. Logistic regression model was performed with cannabis use as the main independent variable and a significance level set at 5%. A similar model stratified by the presence of advanced liver fibrosis (FIB-4 > 3.25) was also run. After multivariable adjustment, current (AOR [95%CI]: 0.49 [0.38–0.63]) and former (0.81 [0.67–0.98], P < .001) cannabis use were both associated with a reduced odds of diabetes. Conversely, male gender, tobacco use, elevated BMI, poverty, being a migrant and advanced fibrosis were associated with increased odds of diabetes. The association between cannabis use and diabetes was maintained in the stratified analysis. In this large cross-sectional study of chronic HCV-infected patients, cannabis use was associated with a lower risk of diabetes independently of clinical and socio-behavioural factors. Further studies are needed to elucidate a potential causal link and shed light on cannabis compounds and mechanisms involved in this relationship.

Introduction

With a global prevalence of over 500 million cases in 2018, type 2 diabetes is a growing health and economic burden,[1,2] associated with increased all-cause mortality.[3] In 2015, the number of hepatitis C virus (HCV) viremic infections was estimated at more than 71 million worldwide. HCV is a leading cause of death and disability, especially through cirrhosis.[4,5] HCV and diabetes are reciprocally intertwined: HCV infection triggers diabetes (mostly type 2) and diabetes worsens HCV outcomes, for instance by increasing the risk for cirrhosis.[6] Furthermore, the treatment of diabetes in cirrhotic patients is complex.[7] Diabetes is the second most common extrahepatic manifestation of HCV infection.[8] HCV infection is assumed to lead to hepatic insulin resistance through direct impairment of the hepatocyte insulin signalling pathway and to peripheral insulin resistance through hepatic production of mediators.[9] Insulin resistance constitutes the pathological background for type 2 diabetes development, and may also trigger hepatic steatosis, the latter being also promoted directly by HCV infection.[10] A difference is sometimes made between type 2 diabetes and a state of impaired glucose regulation caused by loss of liver function as a consequence of cirrhosis (referred to as 'hepatogenous diabetes').[7]

In high-income countries, the HCV burden is mainly felt in marginalized populations[11] such as people who inject drugs and homeless people. In Europe, injecting drug use is the main route of HCV transmission.[12] Moreover, people who inject drugs face many barriers to access to care.[13,14] A higher HCV prevalence is associated with lower income, lower education level and less employment.[15] In parallel, a low socioeconomic status is associated with poorer health in general,[16] and with higher type 2 diabetes incidence in particular.[17] HCV-infected patients' susceptibility to diabetes may therefore be exacerbated by socioeconomic factors.

In the general population, studies examining the association between cannabis use and the risk of diabetes have yielded inconclusive results, while results showing the protective effect of cannabis in terms of other metabolic disorders seem more conclusive.[18] In a cross-sectional analysis of HIV-HCV co-infected patients, cannabis use, irrespective of frequency, was associated with lower odds of insulin resistance after adjustment for known confounders.[19] In chronic HCV-infected patients, cannabis use was also associated with better liver disease outcomes.[20] However, there is still a lack of data regarding the association between cannabis use and the risk of type 2 diabetes in HCV mono-infected patients. Using data from the French ANRS CO22 Hepather cohort, we aimed to test whether cannabis use is inversely associated with type 2 diabetes in HCV-infected patients.

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