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Diabetologia:器官内脂肪水平和肝脂代谢的性别差异:饮食减肥后对心血管健康和2型糖尿病缓解的影响

2021-11-14 从医路漫漫 MedSci原创

2型糖尿病的发展导致女性心血管疾病风险的不成比例增加,接近男性。女性较高的皮下脂肪(SAT)会导致多余的体脂储存,这可能是由肝脏脂肪代谢的不同所导致的。

2型糖尿病的发展导致女性心血管疾病风险的不成比例增加,接近男性。女性较高的皮下脂肪(SAT)会导致多余体脂储存,这可能是由肝脏脂肪代谢的不同所导致肝脏内过多的脂肪积累增加了肝脏VLDL1-三酰甘油(VLDL1-TG)的输出和血浆VLDL1-TG的浓度。在糖尿病缓解和再发展期间,我们已经证实了双循环假说的这一方面。这一假说假定2型糖尿病是由相互关联的恶性循环导致三酰甘油在肝脏和胰腺过度堆积所致。过量的VLDL1-TG输出不仅会将三酰甘油输送到胰腺,导致β细胞功能障碍,而且还会输送到可以在异位脂肪聚集的所有部位,导致冠状动脉和脑动脉中脂蛋白残留物的沉积,增加心血管疾病的风险。很少有关于女性糖尿病患者的脂质相关研究,许多研究忽略了性别的影响,女性心血管疾病增加的潜在差异尚未得到令人满意的解释。本研究的主要目的是量化患有2型糖尿病的女性和男性器官内脂肪沉积、肝脂蛋白代谢和心血管疾病风险的差异,以及这些变量在饮食减肥后的变化。

目的:与男性相比,2型糖尿病使女性患心血管疾病的风险相对增加更多。我们检测了主要饮食减肥前后内脏脂肪和肝脏VLDL1-三酰甘油(VLDL1-TG)输出量的性别差异。

方法:研究对象为2型糖尿病组(n=64,男30/34女)和健康人组(n=25,男13/12女)。内脏脂肪和脏器内脂肪用磁共振定量,VLDL1-TG输出用脂肪灌注技术。具体流程如下:

参与者和研究设计:这项研究是DiRECT的一部分(n= 64,30名男性/34名女性;年龄52.3±1.0岁;身体质量指数,35.1±0.6千克/平方米[2,4]。非糖尿病组(13男/12女;年龄55.8±1.2岁;身体质量指数,29.7±0.8公斤/平方米)体重减轻后被选入糖尿病组。代谢研究在基线和饮食减肥后进行(电子补充材料[ESM]图1)。

VLDL1-TG的定量:这是使用非同位素方法进行的[5]。密度梯度超速离心技术用于分离VLDL1级分。

磁共振研究:使用3.0特斯拉扫描仪(飞利浦,荷兰)采集磁共振(MR)数据。该方案包括3点Dixon采集,以及用于胰腺内脂肪/腹部脂肪测量的MR-opsy/分水岭方法。

糖尿病缓解期:这被定义为HbA1c<6。5%(48.0 mmol/mol),空腹血糖<7.0 mmol/l。复发者被定义为根据同样的标准失去缓解的个人。

生化和心血管疾病风险分析:用标准方法测定三酰甘油、胰岛素、葡萄糖和其他血液代谢物。采用QRISK3(https://qrisk.org/three))量表评估心血管病的危险性。

结果:糖尿病患者肝脏和胰腺中三酰甘油含量升高,无性别差异(女性肝脏16.4%[9.3~25.0%],男性11.9%[7.0~23.1%],p=0.57;胰腺8.3±0.5%vs 8.5±0.4%,p=0。分别为8.3)。在无糖尿病的情况下,女性两个器官的脂肪水平均低于男性(分别为1.0%[0.9-1.7%]vs4.5%[1.9-8.0%],p=0.005和4.7±0.4%vs7.6±0.5%,p<0.0001)。糖尿病女性肝脏VLDL1-TG生成率和血浆VLDL1-TG水平均高于健康女性(559.3±32.9vs 403.2±45.7mgkg−1day−1,p=0.01和0.45vs0.25[0.13~0.33]−/l,p=0.02),而男性差异无统计学意义(548.8±39.8vs506.7±29.2mgkg−1day−1,p=0.34)。0.72[0.53~1.15]和0.50[0.32~0.68]mmol/l,p=0。2、6)。男女糖尿病缓解率(65.4%vs71.0%)和心血管风险降低(59.8%vs41.5%)无性别差异。

表 男性和女性在减肥前和减肥后的临床和代谢特征

图 女性和男性减肥后血脂变量的变化。显示了5个月、12个月和24个月时基线(Δ值)的变化。每组内的统计反映的是实际值之间的差异,组间的统计是根据男性和女性在每个时间点的绝对变化的差异来计算的。(A)体重、(B)空腹血浆胰岛素、(C)肝脏脂肪、(D)胰腺脂肪、(E)VLDL1-TG产生率、(F)血浆VLDL1-TG、(G)血浆总TG和(H)NEFA的变化男性(虚线)和(H)NEFA(实线)。数据采用均值±扫描电镜(Mean±SEM)表示。**p<0.001.0 1,*p<0.0 1与基线比较(男性);†p<0.0。0.001 5,††p<0.0 1,†††p<0.0 1,‡p<0.0。0.001.5,‡‡‡P<0.0 5,男性与女性比较。TG、三酰甘油、VLDL-TG-PR、VLDL-TG产生率

结论:在2型糖尿病患者中,女性的肝脏和胰腺脂肪水平与男性一样高,与肝脏VLDL1-TG生成率升高有关。2型糖尿病和减肥后三酰甘油周转的动态在性别间存在差异。这些变化可能会导致糖尿病女性心血管风险的不成比例增加。

原文出处:

Jesuthasan A,  Zhyzhneuskaya S,  Peters C,et al.Sex differences in intraorgan fat levels and hepatic lipid metabolism: implications for cardiovascular health and remission of type 2 diabetes after dietary weight loss.Diabetologia 2021 Oct 16

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    2021-11-16 huangdf
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    2021-11-14 419040982

    好好

    0

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    2021-11-14 CHANGE

    什么时候有懒人用的减肥神药?

    0

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