Division of Endocrinology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea.
JAMA Netw Open. 2022 Feb 1;5(2):e220262. doi: 10.1001/jamanetworkopen.2022.0262.
Previous studies have indicated that liver cirrhosis is associated with hypoglycemia, but there have been no studies investigating the association between nonalcoholic fatty liver disease (NAFLD) and hypoglycemia in noncirrhotic populations with type 2 diabetes.
To explore the association of NAFLD with severe hypoglycemia among patients with type 2 diabetes.
DESIGN, SETTING, AND PARTICIPANTS: This nationwide population-based retrospective cohort study using the National Health Insurance System of South Korea included individuals aged 20 years or older who had undergone a medical health examination between January 1, 2009, and December 31, 2012, and were diagnosed with type 2 diabetes. Participants were followed up until December 31, 2015. Data analyses were performed between January 1, 2019, and February 2, 2021.
The baseline fatty liver index (FLI) was used as a surrogate marker for NAFLD.
The outcome of interest, severe hypoglycemia, was measured using hospital admission and emergency department visit records with a primary diagnosis of hypoglycemia.
Among 1 946 581 individuals with type 2 diabetes, 1 125 187 (57.8%) were male. During a median (IQR) follow-up of 5.2 (4.1-6.1) years, 45 135 (2.3%) experienced 1 or more severe hypoglycemia events. Participants with severe hypoglycemia, vs those without severe hypoglycemia, were older (mean [SD] age, 67.9 [9.9] years vs 57.2 [12.3] years; P < .001) and had lower mean (SD) body mass index (24.2 [3.43] vs 25.1 [3.4]; P < .001). Patients with NAFLD tended to have less severe hypoglycemia without consideration of obesity status. However, after adjustment of multiple clinical covariates, including body mass index, there was a J-shaped association between FLI and severe hypoglycemia (5th decile: adjusted hazard ratio [aHR], 0.86; 95% CI, 0.83-0.90; 9th decile: aHR, 1.02; 95% CI, 0.96-1.08; 10th decile: aHR, 1.29; 95% CI, 1.22-1.37), and the estimated risk of hypoglycemia was higher in participants with NAFLD (aHR, 1.26; 95% CI, 1.22-1.30). The association was more prominent in female participants (aHR, 1.29; 95% CI, 1.23-1.36) and those with underweight (aHR, 1.71; 95% CI, 1.02-2.88).
In this study, NAFLD was associated with a higher risk of severe hypoglycemia in patients with type 2 diabetes independent of obesity status. Presence of NAFLD should be considered when evaluating vulnerability to hypoglycemia in patients with type 2 diabetes.
先前的研究表明肝硬化与低血糖有关，但没有研究调查非肝硬化 2 型糖尿病患者中非酒精性脂肪性肝病（NAFLD）与低血糖之间的关系。
探讨 NAFLD 与 2 型糖尿病患者严重低血糖之间的关系。
设计、地点和参与者：本研究使用韩国国家健康保险系统进行了一项全国性基于人群的回顾性队列研究，纳入了 20 岁或以上在 2009 年 1 月 1 日至 2012 年 12 月 31 日期间接受过健康体检且被诊断为 2 型糖尿病的个体。参与者随访至 2015 年 12 月 31 日。数据分析于 2019 年 1 月 1 日至 2021 年 2 月 2 日进行。
基线脂肪性肝病指数（FLI）用作 NAFLD 的替代标志物。
感兴趣的结局为严重低血糖，通过低血糖的主要诊断记录的住院和急诊就诊来衡量。
在 1946581 例 2 型糖尿病患者中，1125187 例（57.8%）为男性。在中位数（IQR）随访 5.2（4.1-6.1）年期间，45135 例（2.3%）发生 1 次或多次严重低血糖事件。与无严重低血糖的患者相比，发生严重低血糖的患者年龄更大（平均[标准差]年龄，67.9[9.9]岁比 57.2[12.3]岁；P<0.001），平均（标准差）体重指数（24.2[3.43]比 25.1[3.4]；P<0.001）较低。考虑到肥胖状况，NAFLD 患者倾向于发生不太严重的低血糖。然而，在调整了包括体重指数在内的多个临床协变量后，FLI 与严重低血糖之间存在 J 形关联（第 5 个十分位数：调整后的危险比[aHR]，0.86；95%CI，0.83-0.90；第 9 个十分位数：aHR，1.02；95%CI，0.96-1.08；第 10 个十分位数：aHR，1.29；95%CI，1.22-1.37），并且 NAFLD 患者发生低血糖的风险更高（aHR，1.26；95%CI，1.22-1.30）。这种关联在女性参与者（aHR，1.29；95%CI，1.23-1.36）和体重不足的参与者（aHR，1.71；95%CI，1.02-2.88）中更为明显。
在这项研究中，NAFLD 与 2 型糖尿病患者严重低血糖的风险增加独立于肥胖状况有关。在评估 2 型糖尿病患者对低血糖的易感性时，应考虑到 NAFLD 的存在。
