胎球蛋白-A 介导了年轻成年巴基斯坦和挪威 2 型糖尿病患者脂肪组织胰岛素抵抗的差异。
Fetuin-A mediates the difference in adipose tissue insulin resistance between young adult pakistani and norwegian patients with type 2 diabetes.
机构信息
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.
出版信息
BMC Endocr Disord. 2022 Aug 17;22(1):208. doi: 10.1186/s12902-022-01127-y.
BACKGROUND
South-Asian immigrants to Western countries have a high prevalence of type 2 diabetes mellitus (T2DM) and increased adipose tissue insulin resistance (AT-IR), as compared to their Western counterparts. Fetuin-A is a hepatokine known to influence AT-IR.
AIM
Can plasma fetuin-A concentrations explain an ethnic difference in adipose tissue insulin resistance?
METHODS
We performed a two-step euglycemic-hyperinsulinaemic clamp and measured plasma concentrations of fetuin-A and non-esterified fatty acids (NEFA), in 18 Pakistani and 21 Norwegians with T2DM (age 29-45y) in Norway. AT-IR was calculated as NEFA-suppression during the clamp. The adipokines/cytokines leptin, adiponectin, visfatin, PTX3, IL-1β, INF-γ, and IL-4 were measured in fasting plasma. Liver fat was estimated by CT-scans.
RESULTS
Despite a lower BMI, Pakistani patients displayed higher AT-IR than Norwegians. NEFA-suppression during clamp was lower in Pakistani than Norwegians (mean=-20.6%, 95%CI=[-40.8, -0.01] and p = 0.046). Plasma fetuin-A concentration was higher in Pakistani than Norwegians (43.4 ng/mL[12.7,74.0], p = 0.007) and correlated negatively to %NEFA-suppression during clamp (rho=-0.39, p = 0.039). Plasma fetuin-A concentration explained 22% of the ethnic difference in NEFA-suppression during the clamp. Pakistani patients exhibited higher plasma leptin and lower PTX3 levels than Norwegian, and plasma visfatin correlated positively to plasma fetuin-A levels in the Pakistani patients. We observed no correlation between plasma fetuin-A and liver fat, but fetuin-A correlated negatively with plasma IL-1β, INF-γ, and IL-4 concentrations. Plasma IL-4 concentration was lower in Pakistani than in Norwegian patients.
CONCLUSION
Fetuin-A may contribute to explain the discrepancy in T2DM prevalence between Pakistani and Norwegians patients by influencing AT-IR.
背景
与西方同龄人相比，南亚移民到西方国家后，2 型糖尿病（T2DM）和脂肪组织胰岛素抵抗（AT-IR）的患病率较高。胎球蛋白-A 是一种已知能影响 AT-IR 的肝分泌物。
目的
血浆胎球蛋白-A 浓度能否解释脂肪组织胰岛素抵抗的种族差异？
方法
我们对 18 名巴基斯坦人和 21 名挪威 T2DM 患者（年龄 29-45 岁）进行了两步法正葡萄糖高胰岛素钳夹试验，并测量了血浆胎球蛋白-A 和非酯化脂肪酸（NEFA）浓度。钳夹试验期间，通过 NEFA 抑制来计算 AT-IR。空腹血浆中测量了瘦素、脂联素、内脏脂肪素、PTX3、IL-1β、INF-γ 和 IL-4 等脂肪细胞因子/细胞因子。通过 CT 扫描估计肝脂肪。
结果
尽管巴基斯坦患者的 BMI 较低，但他们的 AT-IR 却高于挪威患者。巴基斯坦患者在钳夹试验期间的 NEFA 抑制率低于挪威患者（平均为-20.6%，95%CI=[-40.8，-0.01]，p=0.046）。巴基斯坦患者的血浆胎球蛋白-A 浓度高于挪威患者（43.4ng/ml[12.7，74.0]，p=0.007），且与钳夹试验期间的%NEFA 抑制率呈负相关（rho=-0.39，p=0.039）。血浆胎球蛋白-A 浓度解释了钳夹试验期间 NEFA 抑制的种族差异的 22%。与挪威患者相比，巴基斯坦患者的血浆瘦素水平更高，PTX3 水平更低，且血浆内脏脂肪素水平与巴基斯坦患者的血浆胎球蛋白-A 水平呈正相关。我们未发现血浆胎球蛋白-A 与肝脂肪之间的相关性，但胎球蛋白-A 与血浆 IL-1β、INF-γ 和 IL-4 浓度呈负相关。与挪威患者相比，巴基斯坦患者的血浆 IL-4 浓度更低。
结论
胎球蛋白-A 可能通过影响 AT-IR 来解释巴基斯坦和挪威 T2DM 患者患病率差异的原因。
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