Author information
1
Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Rd, Leicester, LE5 4PW, United Kingdom.
2
Leicester Real World Evidence Unit, Leicester General Hospital, Gwendolen Rd, Leicester, LE5 4PW, United Kingdom.
Abstract
BACKGROUND & AIMS:
A causal association of non-alcoholic fatty liver disease (NAFLD) with cardiovascular disease (CVD) and type 2 diabetes (T2DM) remains unproved. We aimed to quantify the likelihood of causality examining the sensitivity of observational associations to possible confounding.
METHODS:
Studies investigating longitudinal associations of NAFLD with CVD or T2DM were searched on June 5th , 2018. Study-specific relative risks (RRs) were combined in random-effects meta-analyses and pooled estimates used in bias analyses.
RESULTS:
Associations of NAFLD with CVD and T2DM were reported in 13 (258743/18383 participants/events) and 20 (240251/12891) studies, respectively. Comparing patients with NAFLD to those without, the pooled RR was 1.48 (95% CI: 0.96, 2.29) for CVD and 2.17 (1.77, 2.65) for T2DM. In bias analyses, for an unmeasured confounder associated to both NAFLD and CVD with a RR of 1.25, the proportion of studies with a true (causal) effect of NAFLD on CVD surpassing a RR of 1.10 (i.e., 10% increased risk of CVD in participants with NAFLD) was 0.67 (95% CI: 0.42, 0.92) while for 75% increase it was 0.36 (0.11, 0.62). Corresponding figures for T2DM were 0.97 (0.91, 1.00) for a 10% increased risk of T2DM in participants with NAFLD to 0.70 (0.49, 0.92) for a 75% increase.
CONCLUSIONS:
The results of this study are strongly suggestive for a causal relationship between NAFLD and T2DM, while the evidence for a causal link between NAFLD and CVD is less robust. Therapeutic strategies targeting NAFLD are likely to reduce the risk of developing T2DM.