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KMID : 1200020210450030417
Diabetes & Metabolism Journal
2021 Volume.45 No. 3 p.417 ~ p.429
Distinct Dose-Dependent Association of Free Fatty Acids with Diabetes Development in Nonalcoholic Fatty Liver Disease Patients
Li Fuxi

Ye Junzhao
Sun Yanhong
Lin Yansong
Wu Tingfeng
Shao Congxiang
Ma Qianqian
Liao Xianhua
Feng Shiting
Zhong Bihui
Abstract
Background: Excessive delivery of free fatty acids (FFAs) to the liver promotes steatosis and insulin resistance (IR), with IR defined as reduced glucose uptake, glycogen synthesis and anti-lipolysis stimulated by normal insulin levels. Whether the associations between FFAs and diabetes development differ between patients with and without nonalcoholic fatty liver disease (NAFLD) remains unclear.

Methods: Consecutive subjects (2,220 NAFLD subjects and 1,790 non-NAFLD subjects according to ultrasound imaging) were enrolled from the First Affiliated Hospital of Sun Yat-sen University between 2009 and 2019. The homeostasis model assessment of insulin resistance (HOMA-IR) was calculated.

Results: There was an approximate J-shaped relationship between FFA levels and HOMA-IR in the NAFLD group. Higher FFA concentration quartiles were associated with higher risks of IR (odds ratio [OR], 9.24; 95% confidence interval [CI], 6.43 to 13.36), prediabetes (OR, 10.48; 95% CI, 5.66 to 19.39), and type 2 diabetes mellitus (T2DM; OR, 19.43; 95% CI, 12.75 to 29.81) in the NAFLD group but not in the non-NAFLD group. The cut-off points for the FFA levels increased in a stepwise manner in discriminating IR, prediabetes and T2DM (573, 697, and 715 ¥ìmol/L) in the NAFLD group but not in non-NAFLD individuals.

Conclusion: A distinct dose-dependent relationship of FFA levels was found with IR, prediabetes and T2DM in NAFLD patients. Screening serum FFA levels in NAFLD patients would be valuable in preventing diabetes development.
KEYWORD
Diabetes mellitus, type 2, Fatty acids, nonesterifie, Non-alcoholic fatty liver disease
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