Alessandro Mantovani1, Christopher D Byrne2,3, Enzo Bonora1, Giovanni Targher4. 1. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy. 2. Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, U.K. 3. Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton, U.K. 4. Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy giovanni.targher@univr.it.
Abstract
OBJECTIVE: Several studies have explored the impact of nonalcoholic fatty liver disease (NAFLD) on risk of incident type 2 diabetes. However, the extent to which NAFLD may confer risk of incident diabetes remains uncertain. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident diabetes. RESEARCH DESIGN AND METHODS: We collected data using PubMed, Scopus, and Web of Science from January 2000 to July 2017. We included only large (n ≥500) observational studies with a follow-up duration of at least 1 year in which NAFLD was diagnosed on imaging methods. Eligible studies were selected according to predefined keywords and clinical outcomes. Data from selected studies were extracted, and meta-analysis was performed using random-effects modeling. RESULTS: A total of 19 observational studies with 296,439 individuals (30.1% with NAFLD) and nearly 16,000 cases of incident diabetes over a median of 5 years were included in the final analysis. Patients with NAFLD had a greater risk of incident diabetes than those without NAFLD (random-effects hazard ratio [HR] 2.22, 95% CI 1.84-2.60; I2 = 79.2%). Patients with more "severe" NAFLD were also more likely to develop incident diabetes; this risk increased across the ultrasonographic scores of steatosis (n = 3 studies), but it appeared to be even greater among NAFLD patients with advanced high NAFLD fibrosis score (n = 1 study; random-effects HR 4.74, 95% CI 3.54-5.94). Sensitivity analyses did not alter these findings. Funnel plot and Egger test did not reveal significant publication bias. Study limitations included high heterogeneity, varying degrees of confounder adjustment across individual studies, and lack of studies using liver biopsy. CONCLUSIONS: NAFLD is significantly associated with a twofold increased risk of incident diabetes. However, the observational design of the eligible studies does not allow for proving causality.
OBJECTIVE: Several studies have explored the impact of nonalcoholic fatty liver disease (NAFLD) on risk of incident type 2 diabetes. However, the extent to which NAFLD may confer risk of incident diabetes remains uncertain. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident diabetes. RESEARCH DESIGN AND METHODS: We collected data using PubMed, Scopus, and Web of Science from January 2000 to July 2017. We included only large (n ≥500) observational studies with a follow-up duration of at least 1 year in which NAFLD was diagnosed on imaging methods. Eligible studies were selected according to predefined keywords and clinical outcomes. Data from selected studies were extracted, and meta-analysis was performed using random-effects modeling. RESULTS: A total of 19 observational studies with 296,439 individuals (30.1% with NAFLD) and nearly 16,000 cases of incident diabetes over a median of 5 years were included in the final analysis. Patients with NAFLD had a greater risk of incident diabetes than those without NAFLD (random-effects hazard ratio [HR] 2.22, 95% CI 1.84-2.60; I2 = 79.2%). Patients with more "severe" NAFLD were also more likely to develop incident diabetes; this risk increased across the ultrasonographic scores of steatosis (n = 3 studies), but it appeared to be even greater among NAFLD patients with advanced high NAFLD fibrosis score (n = 1 study; random-effects HR 4.74, 95% CI 3.54-5.94). Sensitivity analyses did not alter these findings. Funnel plot and Egger test did not reveal significant publication bias. Study limitations included high heterogeneity, varying degrees of confounder adjustment across individual studies, and lack of studies using liver biopsy. CONCLUSIONS: NAFLD is significantly associated with a twofold increased risk of incident diabetes. However, the observational design of the eligible studies does not allow for proving causality.
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