Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Medicine, Nephrology and Clinical Chemistry, University of Tübingen, Tübingen, Germany.
Diabetes. 2010 Dec;59(12):3167-73. doi: 10.2337/db10-0179. Epub 2010 Sep 14.
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 (1)H-MR spectroscopy in 225 subjects. Insulin sensitivity was estimated from a 75-g oral glucose tolerance test (IS(OGTT)) and measured by a euglycemic hyperinsulinemic clamp (IS(clamp), n = 172). Insulin secretion was measured during the OGTT and an ivGTT (n = 172).
SHBG levels correlated positively with insulin sensitivity (IS(OGTT), P = 0.037; IS(clamp), 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 (IS(OGTT), P = 0.0096; IS(clamp), 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.
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）水平会降低，而循环中的 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 9 个月的生活方式干预之前和期间，通过磁共振（MR）断层扫描精确测量全身和内脏脂肪，通过（1）H-MR 光谱测量肝脏脂肪，共 225 例受试者。通过口服葡萄糖耐量试验（OGTT）估算胰岛素敏感性（IS(OGTT)），通过正葡萄糖高胰岛素钳夹试验（IS(clamp)，n = 172）进行测量。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（IS(OGTT)，P = 0.037；IS(clamp)，P = 0.057）呈正相关，与年龄、性别和全身脂肪无关。在多变量模型中，在进一步调整脂联素和 fetuin-A 等脂肪因子和肝因子水平后，这些关系仍然显著（IS(OGTT)，P = 0.0096；IS(clamp)，P = 0.029）。将循环 SHBG 调整为肝脂肪后，SHBG 与胰岛素敏感性的关系消失。相反，循环 SHBG 与空腹血糖呈负相关，在调整肝脂肪之前（r = -0.17，P = 0.009）和之后（r = -0.14，P = 0.04）。循环 SHBG 与调整后的胰岛素分泌无相关性（OGTT，P = 0.16；ivGTT，P = 0.35）。SHBG 中的 SNP rs1799941 与循环 SHBG 相关（P ≤ 0.025），但与代谢特征无关（所有 P > 0.18）。
高循环 SHBG 预防 2 型糖尿病发展的可能机制涉及调节空腹血糖，而不是改变胰岛素分泌功能。
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