Serum sex hormone-binding globulin is a mediator of the association between intrahepatic lipid content and type 2 diabetes: the Maastricht Study,Diabetologia

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Serum sex hormone-binding globulin is a mediator of the association between intrahepatic lipid content and type 2 diabetes: the Maastricht Study
Diabetologia ( IF 8.2 ) Pub Date : 2022-09-17 , DOI: 10.1007/s00125-022-05790-7
Pomme I H G Simons _{1,

2,

3} , Olivier Valkenburg ₄ , Marjo P H van de Waarenburg _{2,

3} , Marleen M J van Greevenbroek _{2,

3} , M Eline Kooi _{3,

5} , Jacobus F A Jansen _{5,

6,

7} , Casper G Schalkwijk _{2,

3} , Coen D A Stehouwer _{2,

3,

8} , Martijn C G J Brouwers _{1,

3}

Affiliation

Aims/hypothesis

Serum sex hormone-binding globulin (SHBG) has been proposed to act as a hepatokine that contributes to the extrahepatic complications observed in non-alcoholic fatty liver disease (NAFLD). However, it remains uncertain whether serum SHBG mediates the association between intrahepatic lipids (IHL) and type 2 diabetes. Therefore, we studied whether, and to what extent, serum SHBG mediates the association between IHL content and type 2 diabetes.

Methods

We used cross-sectional data from the Maastricht Study (n=1554), a population-based cohort study with oversampling of individuals with type 2 diabetes. Type 2 diabetes status was assessed by oral glucose tolerance test, and IHL content was measured using 3T Dixon MRI. Mediation analyses were performed to assess the role of serum SHBG in mediating the association between IHL content and type 2 diabetes.

Results

IHL content was significantly associated with type 2 diabetes in women and men (OR 1.08 [95% CI 1.04, 1.14] and OR 1.12 [95% CI 1.08, 1.17], respectively). Serum SHBG significantly mediated the association between IHL content and type 2 diabetes. The contribution of serum SHBG was higher in women (OR 1.04 [95% CI 1.02, 1.07]; proportion mediated 50.9% [95% CI 26.7, 81.3]) than in men (OR 1.02 [95% CI 1.01, 1.03]; proportion mediated 17.2% [95% CI 9.6, 27.6]). Repeat analyses with proxies of type 2 diabetes and adjustment for covariates did not substantially affect the results.

Conclusions/interpretation

In this large-scale population-based cohort study, serum SHBG was found to be a mediator of the association between IHL content and type 2 diabetes. These findings extend our understanding of the potential mechanisms by which NAFLD is a risk factor for type 2 diabetes, and further elaborate on the role of SHBG as a hepatokine.

Graphical abstract

中文翻译：

血清性激素结合球蛋白是肝内脂质含量与 2 型糖尿病之间关联的介质：马斯特里赫特研究

目标/假设

血清性激素结合球蛋白 (SHBG) 已被提议充当肝因子，导致在非酒精性脂肪性肝病 (NAFLD) 中观察到的肝外并发症。然而，血清 SHBG 是否介导肝内脂质 (IHL) 与 2 型糖尿病之间的关联仍不确定。因此，我们研究了血清 SHBG 是否以及在何种程度上介导了 IHL 含量与 2 型糖尿病之间的关联。

方法

我们使用了来自马斯特里赫特研究（ n = 1554）的横断面数据，这是一项基于人群的队列研究，对 2 型糖尿病患者进行了过度抽样。通过口服葡萄糖耐量试验评估 2 型糖尿病状态，并使用 3T Dixon MRI 测量 IHL 含量。进行中介分析以评估血清 SHBG 在中介 IHL 含量与 2 型糖尿病之间的关联中的作用。

结果

IHL 内容与女性和男性的 2 型糖尿病显着相关（分别为 OR 1.08 [95% CI 1.04, 1.14] 和 OR 1.12 [95% CI 1.08, 1.17]）。血清 SHBG 显着介导 IHL 含量与 2 型糖尿病之间的关联。血清 SHBG 对女性的贡献 (OR 1.04 [95% CI 1.02, 1.07]；比例介导 50.9% [95% CI 26.7, 81.3]) 高于男性 (OR 1.02 [95% CI 1.01, 1.03]；比例介导的 17.2% [95% CI 9.6, 27.6]）。对 2 型糖尿病的替代物进行重复分析并调整协变量对结果没有显着影响。