Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
Nutr Metab Cardiovasc Dis. 2013 Jun;23(6):505-10. doi: 10.1016/j.numecd.2011.11.003. Epub 2012 Mar 7.
Several studies have reported that the ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) K121Q polymorphism (rs1044498) interacts with increased adiposity in affecting glucose homeostasis and insulin sensitivity. Conversely, one would expect that the amelioration of glucose homeostasis observed after weight loss is modulated by the ENPP1 K121Q polymorphism. The aim of our study was to test such hypothesis, in non-diabetic overweight-obese individuals.
Two hundred eleven non-diabetic overweight-obese individuals were studied. Body mass index (BMI), fasting glucose, homeostasis model assessment of insulin resistance (HOMA-IR index) and lipid levels were obtained before and after 6-week lifestyle intervention (LI; diet and exercise) and their changes calculated as baseline minus 6-week values. LI decreased BMI, glucose, HOMA-IR and triglyceride levels (p < 0.001 for all). No difference across genotype groups (160 KK and 51 KQ or QQ - named as XQ - individuals) was observed in these changes. In a multivariate model, BMI changes predicted fasting glucose changes (β = 0.139 mmol/L (2.50 mg/dl) for 1 unit BMI change, p = 0.005). This correlation was not significant among KK individuals (β = 0.082; p = 0.15), while much steeper and highly significant among XQ individuals (β = 0.336; p = 0.00008) (p-value for Q121-by-weight loss interaction = 0.047).
Individuals carrying the ENPP1 Q121 variant are highly responsive to the effect of weight loss on fasting glucose. This reinforces the previously suggested hypothesis that the Q121 variant interacts with adiposity in modulating glucose homeostasis.
多项研究表明，核苷酸焦磷酸酶/磷酸二酯酶 1（ENPP1）K121Q 多态性（rs1044498）与肥胖程度增加相互作用，影响葡萄糖稳态和胰岛素敏感性。相反，人们预计在减轻体重后观察到的葡萄糖稳态改善会受到 ENPP1 K121Q 多态性的调节。我们的研究旨在在非糖尿病超重肥胖个体中检验这一假设。
研究了 211 名非糖尿病超重肥胖个体。在生活方式干预（LI；饮食和运动）前后测量了体重指数（BMI）、空腹血糖、稳态模型评估的胰岛素抵抗指数（HOMA-IR 指数）和血脂水平，并计算了从基线到 6 周的变化。LI 降低了 BMI、血糖、HOMA-IR 和甘油三酯水平（所有 P<0.001）。在这些变化中，基因型组（160 名 KK 和 51 名 KQ 或 QQ 个体，命名为 XQ 个体）之间没有差异。在多变量模型中，BMI 变化预测空腹血糖变化（BMI 每单位变化 0.139mmol/L（2.50mg/dl），P=0.005）。在 KK 个体中，这种相关性不显著（β=0.082；P=0.15），而在 XQ 个体中则更为陡峭且具有高度显著性（β=0.336；P=0.00008）（Q121 与体重减轻交互作用的 P 值=0.047）。
携带 ENPP1 Q121 变体的个体对体重减轻对空腹血糖的影响高度敏感。这进一步证实了先前提出的假设，即 Q121 变体与肥胖程度相互作用，调节葡萄糖稳态。
