Highlights
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Lean non-alcoholic fatty liver disease and risk of incident type 2 diabetes mellitus: literature review and meta-analysis
Summary
Aim
There are limited data regarding the risk of incidence of type 2 diabetes mellitus (T2DM) among people with nonalcoholic fatty liver disease (NAFLD). A meta-analysis of relevant studies was performed.
Research design and methods
We collected data using PubMed, Scopus, Cochrane, and Web of Science from database inception to December 2022. We included cohort studies in which lean NAFLD was diagnosed by imaging or biopsy methods. Eligible studies were selected based on predefined keywords and clinical outcomes.
Results
A total of 16 observational studies with 304,975 adult individuals (7.7% with lean NAFLD) and almost 1300 cases of incident diabetes followed for a mean period of 5.05 years were included in the final analysis .
Patients with lean NAFLD had a higher risk of incident diabetes than those without NAFLD (random effects hazard ratio [HR] 2.72, 95% CI 1.56–4.74; I 2 = 93.8%) .
Compared with the lean group without NAFLD, the adjusted HRs (95% CI) 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 higher among NAFLD patients with a high advanced NAFLD fibrosis score (random effects HR 3.48, 95% CI 1.92–6.31).
Sensitivity analyzes and publication bias did not alter these findings.
Conclusions
Lean fatty liver disease (NAFLD) is significantly associated with at least two times the 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.
Comments
Although nonalcoholic fatty liver disease (NAFLD) occurs most commonly in people who are overweight/obese , it also occurs in people who are of normal weight . ’NAFLD-lean’ is estimated to account for around 15% of people with NAFLD in Western countries and around 30% of people with NAFLD in Asian countries. Results from a series of studies suggest that the prevalence of adverse cardiometabolic outcomes, including diabetes, is lower in lean NAFLD people than in obese NAFLD people.
A recent meta-analysis reported by Gao et al., which included 16 observational studies and a total of ~ 300,000 adults followed for a median of 5 years , assessed the importance of NAFLD-lean on the risk of developing new diabetes. Data show that people with lean NAFLD had a higher risk of incident diabetes than lean people without NAFLD (HR 2.72, 95% CI: 1.56-4.74). Furthermore, the risk of developing diabetes in the lean-NAFLD group was not significantly different from the risk observed in overweight/obese-NAFLD individuals (HR 2.98, 95% CI: 1.66-5.32).
A limitation of the meta-analysis is that 13 of the 16 included studies were conducted in East Asian populations, so generalizability to other populations is unclear. However, the results of this meta-analysis demonstrate that NAFLD is an important risk factor for developing diabetes even in lean people.
