Department of Endocrinology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Transplant Medical Center, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530007, China.
Int J Med Sci. 2023 Sep 4;20(11):1417-1424. doi: 10.7150/ijms.83371. eCollection 2023.
Serum triglyceride (TG) was an important biomarker for nonalcoholic fatty liver disease (NAFLD), and the association between TG and incident type 2 diabetes mellitus is still under debate with some studies suggesting that elevated TG increase the risk of incident T2DM while others indicative of a negative relationship. These controversial findings may be partially due to the inclusion of the participants with NAFLD. The association between TG and incident type 2 diabetes mellitus in people with NAFLD remained unclear. Therefore, this study aimed to characterize the relationship between the baseline TG levels and incident type 2 diabetes mellitus in a male Japanese cohort with NAFLD. A total of 1221 males with NAFLD were enrolled from the Nagala (NAFLD in the Gifu Area Longitudinal analysis) study conducted from 2004 to 2015. Cox proportional hazards models were performed to examine the relationship between baseline TG concentration and incident type 2 diabetes mellitus. A two-piecewise linear regression model was explored to evaluate the threshold effect of the baseline TG levels on type 2 diabetes mellitus incidence by using a smoothing function. During a median follow-up of 6.05 years, 39 males with NAFLD at baseline developed type 2 diabetes mellitus. The risk of incident type 2 diabetes mellitus was significantly associated with baseline TG concentration in males with NAFLD after fully adjustment for confounders, with per 10 mg/dl elevation in TG levels increasing the risk of incident diabetes by 8.5% (HR=1.085, CI=1.039-1.132; P<0.001). However, no typical dose-dependent positive association between type 2 diabetes mellitus incidence and the TG levels was observed across the TG tertiles. Interestingly, a U-shaped association between TG concentration and risk of incident type 2 diabetes mellitus was revealed by the two-piecewise linear regression analysis. Baseline TG concentration lower than the threshold values (TG <53mg/dl) were negatively associated with risk of incident type 2 diabetes mellitus. With each 10mg/dl increase in baseline TG levels, the risk of incident type 2 diabetes mellitus decreased by nearly 59% (HR=0.413, 95% CI=0.220-0.778). In contrast, when TG levels were higher than the threshold values (TG>53mg/dl), the risk of incident diabetes increased 9.1% with every 10mg TG elevation (HR=1.091, 95% CI=1.046-1.137). A U-shaped relationship was observed between baseline TG levels and incident type 2 diabetes mellitus in a male normoglycemic Japanese population with NAFLD, although extrapolation of the finding to other populations should be made with caution.
血清三酰甘油（TG）是非酒精性脂肪性肝病（NAFLD）的重要生物标志物，而 TG 与 2 型糖尿病（T2DM）发病风险之间的关联仍存在争议，一些研究表明升高的 TG 会增加 T2DM 的发病风险，而另一些研究则表明两者呈负相关。这些有争议的发现可能部分归因于纳入了伴有 NAFLD 的参与者。在伴有 NAFLD 的人群中，TG 与 2 型糖尿病发病之间的关系仍不清楚。因此，本研究旨在描述日本男性伴有 NAFLD 的队列中基线 TG 水平与 2 型糖尿病发病之间的关系。
从 2004 年至 2015 年进行的长野（岐阜地区的非酒精性脂肪肝纵向分析）研究中纳入了 1221 名男性伴有 NAFLD 的患者。使用 Cox 比例风险模型检查基线 TG 浓度与 2 型糖尿病发病之间的关系。使用平滑函数通过两段线性回归模型探讨基线 TG 水平对 2 型糖尿病发病的阈值效应。
在中位随访 6.05 年期间，基线时患有 NAFLD 的 39 名男性患有 2 型糖尿病。在充分调整混杂因素后，男性伴有 NAFLD 的基线 TG 浓度与 2 型糖尿病发病风险显著相关，TG 水平每升高 10mg/dl，发病风险增加 8.5%（HR=1.085，95%CI=1.039-1.132；P<0.001）。然而，在 TG 三分位组中未观察到 2 型糖尿病发病与 TG 水平之间典型的剂量依赖性正相关关系。有趣的是，两段线性回归分析显示，TG 浓度与 2 型糖尿病发病风险之间呈 U 型关联。低于阈值（TG<53mg/dl）的基线 TG 浓度与 2 型糖尿病发病风险呈负相关。基线 TG 水平每增加 10mg/dl，2 型糖尿病发病风险降低近 59%（HR=0.413，95%CI=0.220-0.778）。相比之下，当 TG 水平高于阈值（TG>53mg/dl）时，TG 每升高 10mg，糖尿病发病风险增加 9.1%（HR=1.091，95%CI=1.046-1.137）。
在日本男性非糖尿病伴 NAFLD 人群中，基线 TG 水平与 2 型糖尿病发病之间呈 U 型关系，尽管应谨慎将这一发现外推至其他人群。
