Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals

Abstract

ObjectiveFollow-up studies have shown that non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of incident diabetes, but currently, it is uncertain whether this risk changes with increasing severity of NAFLD. We performed a meta-analysis of relevant studies to quantify the magnitude of the association between NAFLD and risk of incident diabetes.DesignWe systematically searched PubMed, Scopus and Web of Science databases from January 2000 to June 2020 using predefined keywords to identify observational studies with a follow-up duration of at least 1 year, in which NAFLD was diagnosed by imaging techniques or biopsy. Meta-analysis was performed using random-effects modelling.Results33 studies with 501 022 individuals (30.8% with NAFLD) and 27 953 cases of incident diabetes over a median of 5 years (IQR: 4.0–19 years) were included. Patients with NAFLD had a higher risk of incident diabetes than those without NAFLD (n=26 studies; random-effects HR 2.19, 95% CI 1.93 to 2.48; I2=91.2%). Patients with more ‘severe’ NAFLD were also more likely to develop incident diabetes (n=9 studies; random-effects HR 2.69, 95% CI 2.08 to 3.49; I2=69%). This risk markedly increased across the severity of liver fibrosis (n=5 studies; random-effects HR 3.42, 95% CI 2.29 to 5.11; I2=44.6%). All risks were independent of age, sex, adiposity measures and other common metabolic risk factors. Sensitivity analyses did not alter these findings. Funnel plots did not reveal any significant publication bias.ConclusionThis updated meta-analysis shows that NAFLD is associated with a ~2.2-fold increased risk of incident diabetes. This risk parallels the underlying severity of NAFLD.

Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials

“…Indeed, most of the eligible RCTs have a small sample size (most RCTs included nearly 25-30 individuals for each arm of treatment) and a relatively short period of treatment (i.e., a median period of 26 weeks with only two RCTs with a treatment duration of 48 weeks or more). Most importantly, to date, there are only two RCTs testing the effects of once-daily subcutaneous treatment with liraglutide or semaglutide on resolution of NASH and/or improvement in liver fibrosis stage, which are the two histological features of NAFLD most strongly associated with risk of adverse liver-related and extra-hepatic outcomes in people with NAFLD [10,[42][43][44]. Conversely, there is now a large body of evidence showing that treatment with liraglutide or other long-acting GLP-1 RAs exerts beneficial effects on cardiovascular, mortality, and kidney outcomes in people with T2DM [45][46][47][48][49].…”

Mechanisms of Non-Alcoholic Fatty Liver Disease in the Metabolic Syndrome. A Narrative Review

“…A recent meta-analysis by Mantovani et al examined over 122,000 patients with a NAFLD prevalence of 28% and almost 34,000 cases of incident CKD with stage 3 or higher monitored for a mean follow-up of 9 years. The authors found a risk of CKD in NAFLD 1.43 times higher, regardless of risk factors such as age, sex, obesity, hypertension, diabetes [ 228 ].…”

Perspectives on Precision Medicine Approaches to NAFLD Diagnosis and Management

“…As mentioned above, on the basis of the common association of both conditions, patients with NAFLD should be screened for T2D [100]. Additionally, given that NAFLD is a definite risk factor for incident T2D [159], a preventive approach is justified in these patients [160]. Importantly, significant liver fibrosis is an independent risk factor for T2D appearance with a hazard ratio of 2.95 (95% CI 1.19-7.31) [161].…”