Association between nonalcoholic fatty liver disease and incident diabetes mellitus among Japanese: a retrospective cohort study using propensity score matching

Lipids Health Dis. 2021 Jun 15;20(1):59. doi: 10.1186/s12944-021-01485-x.

Abstract

Background: Previous studies have demonstrated that nonalcoholic fatty liver disease (NAFLD) is a significant risk factor for diabetes mellitus (DM). However, these studies did not completely determine the relationship between NAFLD and DM due to unbalanced confounding factors. The propensity score (PS) is the conditional probability of having a particular exposure, given a set of baseline measured covariates. Propensity score matching (PSM) analysis could minimise the effects of potential confounders. Thus, this study aimed to use PSM analysis to explore the association between NAFLD and DM in a large Japanese cohort.

Methods: This retrospective PSM cohort study was performed on 14,280 Japanese participants without DM at baseline in Murakami Memorial Hospital between 2004 and 2015. The independent variable was NAFLD at baseline, and the outcome was the incidence of DM during follow-up. One-to-one PSM revealed 1671 participants with and without NAFLD. A doubly robust estimation method was applied to verify the correlation between NAFLD and DM.

Results: The risk of developing DM in participants with NAFLD increased by 98% according to the PSM analysis (HR = 1.98, 95% confidence interval [CI]: 1.41-2.80, P < 0.0001). The risk of developing DM in the NAFLD participants was 2.33 times that of the non-NAFLD participants in the PSM cohort after adjusting for the demographic and laboratory biochemical variables (HR = 2.33, 95% CI: 1.63-3.32, P < 0.0001). The participants with NAFLD had a 95% increased risk of DM after adjusting for PS (HR = 1.95, 95% CI: 1.39-2.75, P = 0.0001). All potential confounding variables were not significantly associated with NAFLD and DM after PSM in the subgroup analysis. In the sensitivity analysis, the participants with NAFLD had a 2.17-fold higher risk of developing DM in the original cohort (HR = 2.17, 95% CI: 1.63-2.88, P < 0.0001) and were 2.27-fold more likely to develop DM in the weighted cohort (HR = 2.27, 95% CI: 1.91-2.69, P < 0.00001).

Conclusions: NAFLD was an independent risk factor for the development of DM. The risk of developing DM in the NAFLD participants was 2.33 times that of the non-NAFLD participants in the PSM cohort after adjusting for the demographic and laboratory biochemical variables. The participants with NAFLD had a 95% increased risk of DM after adjusting for PS.

Keywords: Cox proportional hazards regression; Diabetes mellitus; Inverse probability of treatment weights; Nonalcoholic fatty liver disease; Propensity-score matching; Sensitivity analysis.

MeSH terms

  • Adult
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / etiology*
  • Female
  • Glycated Hemoglobin / analysis
  • Humans
  • Incidence
  • Japan / epidemiology
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / complications*
  • Non-alcoholic Fatty Liver Disease / epidemiology
  • Propensity Score
  • Retrospective Studies
  • Risk Factors

Substances

  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human