Glucose-Dependent Insulinotropic Polypeptide Is Associated With Lower Low-Density Lipoprotein But Unhealthy Fat Distribution, Independent of Insulin: The ADDITION-PRO Study
Glucose-Dependent Insulinotropic Polypeptide Is Associated With Lower Low-Density Lipoprotein But Unhealthy Fat Distribution, Independent of Insulin: The ADDITION-PRO Study
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DOI：
10.1210/jc.2015-3133
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发表时间：
2016-02-01
影响因子：
5.8
通讯作者：
Holst, Jens Juul
中科院分区：
文献类型：
--
作者：
Moller, Cathrine Laustrup;Vistisen, Dorte;Holst, Jens Juul
背景：葡萄糖依赖性胰岛素多肽（GIP）可能通过刺激脂质摄取来增加脂质清除。然而，鉴于GIP促进胰腺释放胰岛素，而胰岛素具有抗脂溶作用，其作用可能是间接的。目的：在本研究中，我们研究了低至高风险2型糖尿病个体中GIP与脂质代谢之间的关系，并评估了这种关系是否被胰岛素改变或通过胰岛素介导。设计、环境和参与者：分析基于丹麦横断面add - pro研究（n = 1405）。脂质代谢测量空腹血脂和肥胖，包括腹部脂肪分布评估超声。在口服葡萄糖耐量试验（0、30和120 min）期间测量GIP和胰岛素。线性回归分析用于研究GIP、血脂和肥胖测量之间的关系。结果：空腹GIP水平加倍与男性（平均[95% CI] -0.10 mmol/l[-0.18—0.03]）和女性（-0.14 mmol/l[-0.23—0.04]）的低密度脂蛋白降低有关，与女性高密度脂蛋白升高有关（0.06 mmol/l[-0.02—0.10]）。在男性中，刺激的GIP增加一倍与脂肪减少0.13 cm （0.01-0.25 sc）相关，但与腹部内脏脂肪增加（0.45 cm[0.12-0.78]）和腰臀比增加（0.011[0.004-0.019]）相关。结论：与之前认为的相反，GIP可能与改善低密度脂蛋白清除率有关，但与不依赖于胰岛素的不健康脂肪分布有关。GIP对肥胖测量的影响在男性和女性之间有很大的不同。GIP对内脏和脂肪组织生理的潜在影响值得进一步研究。
Context: Glucose-dependent insulinotropic polypeptide (GIP) may increase lipid clearance by stimulating lipid uptake. However, given that GIP promotes release of insulin by the pancreas and insulin is anti-lipolytic, the effect may be indirect.Objective: In this study we examined the association between GIP and lipid metabolism in individuals with low to high risk of type 2 diabetes and assessed whether the associations were modified by or mediated through insulin.Design, Setting, and Participants: Analyses were based on the Danish cross-sectional ADDITION-PRO study (n = 1405). Lipid metabolism was measured by fasting plasma lipids and obesity including abdominal fat distribution assessed by ultrasonography. GIP and insulin were measured during an oral glucose tolerance test (0, 30 and 120 min). Linear regression analysis was used to study the associations between GIP, plasma lipids, and obesity measures.Results: A doubling in fasting GIP levels was associated with lower low-density lipoprotein in both men (mean [95% CI] -0.10 mmol/l [-0.18--0.03]) and women (-0.14 mmol/l [-0.23--0.04]) and with higher high-density lipoprotein in women (0.06 mmol/l [-0.02-0.10]). In men, a doubling in stimulated GIP was associated with 0.13 cm less 0.01-0.25 sc fat but with more visceral abdominal fat (0.45 cm [0.12-0.78]) and higher waist-hip ratio (0.011 [0.004-0.019]).Conclusions: Contrary to what was previously thought, GIP may be associated with improved low-density lipoprotein clearance but with an unhealthy fat distribution independent of insulin. The effect of GIP on obesity measures was substantially different between men and women. The potential effect of GIP on visceral and sc adipose tissue physiology warrants further examination.