Department of Internal Medicine, Karolinska Institutet, Södersjukhuset AB, SE-118 83 Stockholm, Sweden.
Diabetologia. 2010 Feb;53(2):277-80. doi: 10.1007/s00125-009-1596-0. Epub 2009 Nov 21.
AIMS/HYPOTHESIS: Besides the insulinotropic effects of glucagon-like peptide-1 (GLP-1) mimetics, their effects on endothelial dysfunction and myocardial ischaemia are of interest. No previous study has investigated associations between plasma levels of GLP-1 and CHD.
We investigated longitudinal relationships of fasting GLP-1 with the dynamic GLP-1 response after OGTT (difference between 60 min OGTT-stimulated and fasting GLP-1 levels [DeltaGLP-1]) and CHD in a population-based cohort of 71-year-old men. In the same cohort, we also cross-sectionally investigated the association between stimulated GLP-1 levels and: (1) cardiovascular risk factors (blood pressure, lipids, urinary albumin, waist circumference and insulin sensitivity index [M/I] assessed by euglycaemic-hyperinsulinaemic clamp); and (2) impaired glucose tolerance (IGT) and type 2 diabetes mellitus.
During the follow-up period (maximum 13.8 years), of 294 participants with normal glucose tolerance (NGT), 69 experienced a CHD event (13.8 years), as did 42 of 141 with IGT and 32 of 74 with type 2 diabetes mellitus. DeltaGLP-1 did not predict CHD (HR 1.0, 95% CI 0.52-2.28). The prevalence of IGT was associated with DeltaGLP-1, lowest vs highest quartile (OR 0.3, 95% CI 0.12-0.58), with no such association for type 2 diabetes mellitus (OR 1.0, 95% CI 0.38-2.86). M/I was significantly associated with DeltaGLP-1 in the type 2 diabetes mellitus group (r = 0.38, p < 0.01), but not in the IGT (r = 0.11, p = 0.28) or NGT (r = 0.10, p = 0.16) groups.
CONCLUSIONS/INTERPRETATION: Impaired GLP-1 secretion is associated with IGT, but not with type 2 diabetes mellitus. This finding in the latter group might be confounded by oral glucose-lowering treatment. GLP-1 does not predict CHD. Although DeltaGLP-1 was associated with insulin sensitivity in the type 2 diabetes mellitus group, GLP-1 does not seem to be a predictor of CHD in insulin-resistant patients.
目的/假设：除了胰高血糖素样肽-1（GLP-1）类似物的胰岛素促分泌作用外，它们对内皮功能障碍和心肌缺血的作用也很重要。以前没有研究调查过血浆 GLP-1 水平与 CHD 之间的关系。
我们在一个 71 岁男性的人群队列中，研究了空腹 GLP-1 与 OGTT 后 GLP-1 动态反应（OGTT 刺激后 60 分钟 GLP-1 水平与空腹 GLP-1 水平的差值[DeltaGLP-1]）之间的纵向关系，以及 CHD。在同一队列中，我们还通过横断面研究了刺激后的 GLP-1 水平与以下因素之间的关系：（1）心血管危险因素（血压、血脂、尿白蛋白、腰围和通过正葡萄糖-高胰岛素钳夹评估的胰岛素敏感性指数[M/I]）；以及（2）糖耐量受损（IGT）和 2 型糖尿病。
在随访期间（最长 13.8 年），294 名糖耐量正常（NGT）参与者中有 69 人发生了 CHD 事件（13.8 年），141 名 IGT 患者中有 42 人，74 名 2 型糖尿病患者中有 32 人。DeltaGLP-1 不能预测 CHD（HR 1.0，95%CI 0.52-2.28）。IGT 的患病率与 DeltaGLP-1 相关，最低与最高四分位数（OR 0.3，95%CI 0.12-0.58），而 2 型糖尿病则没有这种关联（OR 1.0，95%CI 0.38-2.86）。M/I 与 2 型糖尿病组的 DeltaGLP-1 显著相关（r = 0.38，p < 0.01），但与 IGT 组（r = 0.11，p = 0.28）或 NGT 组（r = 0.10，p = 0.16）无关。
结论/解释：GLP-1 分泌受损与 IGT 相关，但与 2 型糖尿病无关。在后者中，这种发现可能因口服降血糖治疗而混淆。GLP-1 不能预测 CHD。虽然 DeltaGLP-1 与 2 型糖尿病组的胰岛素敏感性相关，但 GLP-1 似乎不是胰岛素抵抗患者 CHD 的预测因子。
