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Original Article
- Pathophysiology
- Distinct Dose-Dependent Association of Free Fatty Acids with Diabetes Development in Nonalcoholic Fatty Liver Disease Patients
- Fuxi Li, Junzhao Ye, Yanhong Sun, Yansong Lin, Tingfeng Wu, Congxiang Shao, Qianqian Ma, Xianhua Liao, Shiting Feng, Bihui Zhong
- Diabetes Metab J. 2021;45(3):417-429. Published online March 15, 2021
- DOI: https://doi.org/10.4093/dmj.2020.0039
- 7,326 View
- 173 Download
- 10 Web of Science
- 9 Crossref
-
Graphical Abstract
Abstract
PDF
Supplementary Material
PubReader 
ePub - 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 μmol/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. -
Citations
Citations to this article as recorded by
- Mortality in metabolic dysfunction-associated steatotic liver disease: A nationwide population-based cohort study
Eugene Han, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Sang Hoon Ahn, Yong-ho Lee, Seung Up Kim
Metabolism.2024; 152: 155789. CrossRef - Global epidemiology of type 2 diabetes in patients with NAFLD or MAFLD: a systematic review and meta-analysis
Limin Cao, Yu An, Huiyuan Liu, Jinguo Jiang, Wenqi Liu, Yuhan Zhou, Mengyuan Shi, Wei Dai, Yanling Lv, Yuhong Zhao, Yanhui Lu, Liangkai Chen, Yang Xia
BMC Medicine.2024;[Epub] CrossRef - Nutrition, health benefits, and processing of sand rice (Agriophyllum squarrosum): Comparisons with quinoa and buckwheat
Xiaofan Yang, Wenting Fu, Liuyang Xiao, Zhaojun Wei, Lihong Han
Food Science & Nutrition.2024; 12(10): 7060. CrossRef - Research progress on the relationship between free fatty acid profile and type 2 diabetes complicated by coronary heart disease
Xiuyan Liu, Ming Gong, Na Wu
Frontiers in Endocrinology.2024;[Epub] CrossRef - Metabolic Dysfunction-Associated Fatty Liver Disease and Mortality: A Population-Based Cohort Study
Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
Diabetes & Metabolism Journal.2023; 47(2): 220. CrossRef - Experimental model and novel therapeutic targets for non-alcoholic fatty liver disease development
Yujin Jin, Kyung-Sun Heo
The Korean Journal of Physiology & Pharmacology.2023; 27(4): 299. CrossRef - Triglyceride and glucose index is a simple and easy‐to‐calculate marker associated with nonalcoholic fatty liver disease
Kyung‐Soo Kim, Sangmo Hong, Hong‐Yup Ahn, Cheol‐Young Park
Obesity.2022; 30(6): 1279. CrossRef - Mongolian medicine in treating type 2 diabetes mellitus combined with nonalcoholic fatty liver disease via FXR/LXR-mediated P2X7R/NLRP3/NF-κB pathway activation
Shuyin Bao, Xiuzhi Wang, Qianqian Ma, Chengxi Wei, Jixing Nan, Wuliji Ao
Chinese Herbal Medicines.2022; 14(3): 367. CrossRef - Triglyceride Glucose-Waist Circumference Is Superior to the Homeostasis Model Assessment of Insulin Resistance in Identifying Nonalcoholic Fatty Liver Disease in Healthy Subjects
Hwi Seung Kim, Yun Kyung Cho, Eun Hee Kim, Min Jung Lee, Chang Hee Jung, Joong-Yeol Park, Hong-Kyu Kim, Woo Je Lee
Journal of Clinical Medicine.2021; 11(1): 41. CrossRef
- Mortality in metabolic dysfunction-associated steatotic liver disease: A nationwide population-based cohort study
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