Lean nonalcoholic fatty liver disease and risk of incident type 2 diabetes mellitus: A literature review and meta-analysis

Objective There is limited data regarding the risk of incident type 2 diabetes mellitus (T2DM) among lean nonalcoholic fatty liver disease (NAFLD) individuals. We performed a meta-analysis of relevant studies. Research design and methods We collected data using PubMed, Scopus, Cochrane and Web of Science from the databases' inception until December 2022. We included cohort studies in which lean NAFLD was diagnosed through imaging methods or biopsy. Eligible studies were selected according to predefined keywords and clinical outcomes. Results A total of 16 observational studies with 304,975 adult individuals (7.7% with lean NAFLD) and nearly 1300 cases of incident diabetes followed up over a median period of 5.05 years were included in the final analysis. Patients with lean NAFLD had a greater risk of incident diabetes than those without NAFLD (random-effects hazard ratio [HR] 2.72, 95% CI 1.56–4.74; I2 = 93.8%). Compared with the lean without NAFLD group, the adjusted HRs (95% CIs) of incident diabetes for participants in the overweight/obese without NAFLD and overweight/obese with NAFLD groups were 1.32 (0.99– 1.77) and 2.98(1.66–5.32). It appeared to be even greater among NAFLD patients with advanced high NAFLD fibrosis score (random-effects HR 3.48, 95% CI 1.92–6.31). Sensitivity analyses and publication bias did not alter these findings. Conclusions Lean NAFLD is significantly associated with at least twofold increased risk of incident diabetes in non-overweight subjects. This risk parallels the underlying severity of NAFLD. The presence of NAFLD in non-overweight individuals had a more significant impact on the development of diabetes than being overweight itself.