Relationships of circulating sex hormone-binding globulin with metabolic traits in humans.
Relationships of circulating sex hormone-binding globulin with metabolic traits in humans.
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作者：
Peter A;Kantartzis K;Machann J;Schick F;Staiger H;Machicao F;Schleicher E;Fritsche A;Häring HU;Stefan N
最近的数据表明，当脂肪在肝脏中积累时，性激素结合球蛋白（SHBG）水平降低，循环SHBG可能与人类2型糖尿病的发病机制有关。在本研究中，我们研究了高SHBG可能预防糖尿病发展的机制。在进行为期9个月的生活方式干预之前和期间，225名受试者通过磁共振（MR）断层扫描精确测量了全身和内脏脂肪，并通过1H-MR光谱测量了肝脏脂肪。胰岛素敏感性通过75克口服葡萄糖耐量试验（ISOGTT）估计，并通过正糖高胰岛素钳（ISclamp, n = 172）测量。在OGTT和ivGTT期间测量胰岛素分泌（n = 172）。SHBG水平与胰岛素敏感性呈正相关（ISOGTT, P = 0.037; ISclamp, P = 0.057），独立于年龄、性别和体脂总量。在多变量模型中，在额外调整脂肪因子脂联素和肝因子胎儿素- a的水平后，这些关系也很显著（ISOGTT, P = 0.0096; ISclamp, P = 0.029）。调节循环SHBG对肝脏脂肪的影响消除了SHBG与胰岛素敏感性的关系。相比之下，在肝脏脂肪调整前（r = - 0.17, P = 0.009）和调整后（r = - 0.14, P = 0.04），循环SHBG与空腹血糖呈负相关。循环SHBG与胰岛素分泌调节无相关性（OGTT, P = 0.16; ivGTT, P = 0.35）。SHBG中SNP rs1799941与循环SHBG相关（P≤0.025），但与代谢特征无关（P均为0.18）。高循环SHBG预防2型糖尿病发展的可能机制包括调节空腹血糖，而不是改变胰岛素分泌功能。
Recent data suggested that sex hormone–binding globulin (SHBG) levels decrease when fat accumulates in the liver and that circulating SHBG may be causally involved in the pathogenesis of type 2 diabetes in humans. In the present study, we investigated mechanisms by which high SHBG may prevent development to diabetes. Before and during a 9-month lifestyle intervention, total body and visceral fat were precisely measured by magnetic resonance (MR) tomography and liver fat was measured by 1H-MR spectroscopy in 225 subjects. Insulin sensitivity was estimated from a 75-g oral glucose tolerance test (ISOGTT) and measured by a euglycemic hyperinsulinemic clamp (ISclamp, n = 172). Insulin secretion was measured during the OGTT and an ivGTT (n = 172). SHBG levels correlated positively with insulin sensitivity (ISOGTT, P = 0.037; ISclamp, P = 0.057), independently of age, sex, and total body fat. In a multivariate model, these relationships were also significant after additional adjustment for levels of the adipokine adiponectin and the hepatokine fetuin-A (ISOGTT, P = 0.0096; ISclamp, P = 0.029). Adjustment of circulating SHBG for liver fat abolished the relationships of SHBG with insulin sensitivity. In contrast, circulating SHBG correlated negatively with fasting glycemia, before (r = −0.17, P = 0.009) and after (r = −0.14, P = 0.04) adjustment for liver fat. No correlation of circulating SHBG with adjusted insulin secretion was observed (OGTT, P = 0.16; ivGTT, P = 0.35). The SNP rs1799941 in SHBG was associated with circulating SHBG (P ≤ 0.025) but not with metabolic characteristics (all P > 0.18). Possible mechanisms by which high circulating SHBG prevents the development of type 2 diabetes involve regulation of fasting glycemia but not alteration of insulin secretory function.