Department of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Clinical Laboratory, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Diabetes Metab J. 2021 May;45(3):417-429. doi: 10.4093/dmj.2020.0039. Epub 2021 Mar 15.
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.
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.
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.
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.
过多的游离脂肪酸（FFAs）输送到肝脏会导致脂肪变性和胰岛素抵抗（IR），IR 的定义为正常胰岛素水平下葡萄糖摄取、糖原合成和抗脂肪分解减少。FFAs 与糖尿病发展之间的关联在患有和不患有非酒精性脂肪性肝病（NAFLD）的患者之间是否不同尚不清楚。
中山大学第一附属医院于 2009 年至 2019 年连续纳入了 2220 名符合超声成像标准的 NAFLD 患者和 1790 名非 NAFLD 患者。计算了胰岛素抵抗的稳态模型评估（HOMA-IR）。
在 NAFLD 组中，FFA 水平与 HOMA-IR 之间存在近似的 J 形关系。较高的 FFA 浓度四分位数与 IR（比值比 [OR]，9.24；95%置信区间 [CI]，6.43 至 13.36）、糖尿病前期（OR，10.48；95%CI，5.66 至 19.39）和 2 型糖尿病（T2DM；OR，19.43；95%CI，12.75 至 29.81）的风险增加相关，但在非 NAFLD 组中并非如此。在 NAFLD 组中，FFA 水平的截断值在区分 IR、糖尿病前期和 T2DM（573、697 和 715 μmol/L）时呈逐步增加趋势，但在非 NAFLD 个体中并非如此。
在 NAFLD 患者中，FFA 水平与 IR、糖尿病前期和 T2DM 之间存在明显的剂量依赖性关系。在 NAFLD 患者中筛查血清 FFA 水平对于预防糖尿病的发生可能具有重要价值。
