Independent associations of fasting insulin, glucose, and glycated haemoglobin with stroke and coronary heart disease in older women.
Independent associations of fasting insulin, glucose, and glycated haemoglobin with stroke and coronary heart disease in older women.
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DOI：
10.1371/journal.pmed.0040263
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发表时间：
2007-08
期刊：
影响因子：
15.8
通讯作者：
Smith GD
中科院分区：
文献类型：
--
作者：
Lawlor DA;Fraser A;Ebrahim S;Smith GD
有证据表明，在没有明显 2 型糖尿病的人群中，空腹血糖和胰岛素的变化是心血管疾病的重要决定因素。然而，空腹胰岛素、血糖和糖化血红蛋白的变化作为非糖尿病女性心血管疾病危险因素的相对重要性尚不清楚。我们的目的是确定老年女性空腹胰岛素、血糖和糖化血红蛋白与冠心病和中风的独立关联。我们对 3,246 名 60-79 岁的英国女性进行了一项前瞻性队列研究，她们都没有基线冠心病、中风和糖尿病，并且空腹血糖水平都低于 7 mmol/l。空腹胰岛素和胰岛素敏感性稳态模型评估 (HOMA-S) 与冠心病或中风的综合结果线性相关（n = 219 事件），但空腹血糖或糖化血红蛋白与这些结果没有关联。冠心病和中风作为单独的结局，结果相似。年龄、生命全程社会经济地位、吸烟和体力活动调整后每空腹胰岛素一个标准差发生冠心病或中风的综合结果的风险比为 1.14 (95% CI 1.02-1.33)。对代谢综合征的其他成分、低密度脂蛋白胆固醇、空腹血糖和糖化血红蛋白的额外调整对此结果影响不大。我们的研究结果表明，在 60-79 岁年龄范围的女性中，胰岛素抵抗，而不是胰岛素分泌或慢性高血糖，是冠心病和中风的更重要的危险因素。低于目前用于定义糖尿病的空腹血糖阈值，空腹血糖和糖化血红蛋白都与心血管疾病无关。 Debbie Lawlor 及其同事通过对 60-79 岁女性的前瞻性研究得出结论，胰岛素抵抗是冠心病和中风的重要危险因素。将血液输送到心脏和大脑的血管变窄是心血管疾病的常见形式，即心脏和血管疾病。它是疾病和死亡的主要原因。由于心脏和大脑缺氧，这种情况会导致冠心病（CHD；心绞痛和心脏病等心脏问题）和中风。冠心病和中风的一个主要危险因素是糖尿病，这是一种常见的慢性疾病，其特征是血液中糖分（葡萄糖）含量高。对于没有糖尿病的人来说，胰岛素可以控制血糖水平。进食后胰腺释放的胰岛素“指示”胰岛素反应性肌肉和脂肪细胞从血液中吸收葡萄糖（从食物中释放）。在 2 型糖尿病（最常见的糖尿病类型，也称为“成人发病”或“非胰岛素依赖型糖尿病”）的早期阶段，肌肉和脂肪细胞对胰岛素没有反应，因此血糖水平升高。这称为“胰岛素抵抗”。胰腺通过产生更多胰岛素来做出反应。因此，患有胰岛素抵抗的人血液中胰岛素（高胰岛素血症）和葡萄糖（高血糖）水平都很高。最终，胰腺中产生胰岛素的细胞开始出现故障，胰岛素分泌减少，从而导致 2 型糖尿病。目前尚不清楚是胰岛素抵抗还是胰岛素分泌减少导致了糖尿病与心血管疾病之间的关联。医生希望了解这些信息，以帮助他们预防患者患冠心病和中风。有证据表明，空腹血糖水平（饭后 8 小时以上测量的血糖）和空腹胰岛素水平的变化（可以指示胰腺细胞产生胰岛素的情况）和空腹胰岛素水平（可以指示胰岛素抵抗）决定了非 2 型糖尿病患者的心血管疾病风险，但这些风险因素的相对重要性尚不清楚。在这项研究中，研究人员调查了胰岛素抵抗标志物（空腹高胰岛素血症）和胰岛素分泌改变（空腹高血糖和糖化血红蛋白增加，表明过去几个月血液中的糖分含量）是否与无糖尿病老年女性的冠心病和中风有关。他们的目标是获得关于糖尿病如何影响心血管疾病风险的新见解。研究人员测量了约 3000 名 60-79 岁女性参加英国女性心脏与健康研究时的空腹血样中的葡萄糖、胰岛素和糖化血红蛋白。所有女性在入组时均未患有冠心病，没有中风史，没有诊断出糖尿病，并且空腹血糖均低于 7 mmol/l（读数较高表明患有糖尿病）。在对这些女性进行近 5 年的冠心病和中风监测后，研究人员寻找心血管疾病的发生与胰岛素抵抗和胰岛素分泌减少标志物之间的统计关联。他们发现，即使考虑到吸烟和体力活动等影响心血管疾病风险的其他因素，空腹胰岛素水平（而非空腹血糖或糖化血红蛋白水平）与冠心病和中风相关。换句话说，空腹胰岛素水平升高会增加女性患心血管疾病的风险。这些结果表明，在没有糖尿病的老年女性中，空腹胰岛素（胰岛素抵抗的标志物）比空腹血糖或糖化血红蛋白（胰岛素分泌减少的标志物）更能预测未来心血管疾病的风险。这表明胰岛素抵抗可能是老年女性 2 型糖尿病与冠心病和中风之间的主要机制。 （众所周知，老年女性患这些疾病的风险很高，但在之前对心血管疾病危险因素的研究中，她们相对被忽视了。）然而，由于在研究期间患冠心病的女性相对较少，中风的女性更少，这一结论需要在更大规模的研究中得到证实，最好包括更严格的胰岛素抵抗和分泌测试，并且还包括比本研究更多种族背景的女性。如果空腹胰岛素水平与心血管疾病风险之间的关联得到证实，那么预防或逆转胰岛素抵抗的治疗干预措施或生活方式干预措施（例如，增加体力活动或减肥）可能比预防慢性高血糖的干预措施更好地降低心血管疾病风险。请通过此摘要的在线版本访问这些网站：http://dx.doi.org/10.1371/journal.pmed.0040263。有关冠心病、中风和糖尿病的 MedlinePlus 百科全书页面（英语和西班牙语） 美国国家糖尿病信息交换所为患者和护理人员提供的有关糖尿病的信息，包括胰岛素抵抗以及糖尿病、心脏病和中风的信息 英国妇女心脏与健康研究的信息
Evidence suggests that variations in fasting glucose and insulin amongst those without frank type 2 diabetes mellitus are important determinants of cardiovascular disease. However, the relative importance of variations in fasting insulin, glucose, and glycated haemoglobin as risk factors for cardiovascular disease in women without diabetes is unclear. Our aim was to determine the independent associations of fasting insulin, glucose, and glycated haemoglobin with coronary heart disease and stroke in older women. We undertook a prospective cohort study of 3,246 British women aged 60–79 y, all of whom were free of baseline coronary heart disease, stroke, and diabetes, and all of whom had fasting glucose levels below 7 mmol/l. Fasting insulin and homeostasis model assessment for insulin sensitivity (HOMA-S) were linearly associated with a combined outcome of coronary heart disease or stroke (n = 219 events), but there was no association of fasting glucose or glycated haemoglobin with these outcomes. Results were similar for coronary heart disease and stroke as separate outcomes. The age, life-course socioeconomic position, smoking, and physical activity adjusted hazard ratio for a combined outcome of incident coronary heart disease or stroke per one standard deviation of fasting insulin was 1.14 (95% CI 1.02–1.33). Additional adjustment for other components of metabolic syndrome, low-density lipoprotein cholesterol, fasting glucose, and glycated haemoglobin had little effect on this result. Our findings suggest that in women in the 60–79 y age range, insulin resistance, rather than insulin secretion or chronic hyperglycaemia, is a more important risk factor for coronary heart disease and stroke. Below currently used thresholds of fasting glucose for defining diabetes, neither fasting glucose nor glycated haemoglobin are associated with cardiovascular disease. From a prospective study of women aged 60-79 years, Debbie Lawlor and colleagues conclude that insulin resistance is an important risk factor for coronary heart disease and stroke. Narrowing of the vessels that take blood to the heart and brain is a common form of cardiovascular disease—i.e., a disorder of the heart and blood vessels. It is a major cause of illness and death. By starving the heart and brain of oxygen, this condition causes coronary heart disease (CHD; heart problems such as angina and heart attacks) and strokes. A major risk factor for CHD and strokes is diabetes, a common chronic disease characterized by high levels of sugar (glucose) in the blood. In people who don't have diabetes, the hormone insulin controls blood-sugar levels. Insulin, which is released by the pancreas after eating, “instructs” insulin-responsive muscle and fat cells to absorb the glucose (released from food) from the bloodstream. In the very early stages of type 2 diabetes (the commonest type of diabetes, also called “adult onset” or “noninsulin-dependent” diabetes”), muscle and fat cells become unresponsive to insulin, so blood-sugar levels increase. This is called “insulin resistance.” The pancreas responds by making more insulin. As a result, people with insulin resistance have high blood levels of both insulin (hyperinsulinemia) and glucose (hyperglycemia). Eventually, the insulin-producing cells in the pancreas start to malfunction, insulin secretion decreases, and type 2 diabetes is the result. It is not yet clear whether it is insulin resistance or reduced insulin secretion that is responsible for the association between diabetes and cardiovascular disease. Physicians would like to know this information to help them to prevent CHD and strokes in their patients. There is evidence that variations in fasting glucose levels (blood glucose measured more than 8 h after eating), which provide an indication of how well pancreatic cells are producing insulin, and in fasting insulin levels, which provide an indication of insulin resistance, determine cardiovascular disease risk among people without type 2 diabetes, but the relative importance of these risk factors is unclear. In this study, the researchers have investigated whether markers of insulin resistance (fasting hyperinsulinemia) and of altered insulin secretion (fasting hyperglycemia, and increased glycated hemoglobin, which indicates how much sugar has been in the blood over the past few months) are associated with CHD and strokes in elderly women without diabetes. Their aim is to gain new insights into how diabetes affects cardiovascular disease risk. The researchers measured glucose, insulin, and glycated hemoglobulin in fasting blood samples taken from about 3,000 women aged 60–79 y when they enrolled in the British Women's Heart and Health Study. None of the women had CHD at enrollment, none had had a stroke, none had diagnosed diabetes, and all had a fasting blood glucose below 7 mmol/l (a higher reading indicates diabetes). After monitoring the women for nearly 5 y for CHD and strokes, the researchers looked for statistical associations between the occurrence of cardiovascular disease and markers of insulin resistance and reduced insulin secretion. They found that fasting insulin levels, but not fasting glucose or glycated hemoglobin levels, were associated with CHD and stroke, even after allowing for other factors that affect cardiovascular disease risk such as smoking and physical activity. In other words, raised fasting insulin levels increased the women's risk of developing cardiovascular disease. These results indicate that in elderly women without diabetes, fasting insulin (a marker of insulin resistance) is a better predictor of future cardiovascular disease risk than fasting glucose or glycated hemoglobin (markers of reduced insulin secretion). This suggests that insulin resistance might be the main mechanism linking type 2 diabetes to CHD and stroke in elderly women. (Elderly women are known to run a high risk of developing these conditions, but they have been relatively neglected in previous studies of the risk factors for cardiovascular disease.) However, because relatively few women developed CHD during the study and even fewer had a stroke, this conclusion needs confirming in larger studies, preferably ones that include more rigorous tests of insulin resistance and secretion and also include women from more ethnic backgrounds than this study did. If the association between fasting insulin levels and cardiovascular disease risk is confirmed, therapeutic interventions or lifestyle interventions (for example, increased physical activity or weight loss) that prevent or reverse insulin resistance might reduce cardiovascular disease risk better than interventions that prevent chronic hyperglycemia. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040263. MedlinePlus encyclopedia page on coronary heart disease, stroke, and diabetes (in English and Spanish) Information for patients and caregivers from the US National Diabetes Information Clearinghouse on diabetes, including information on insulin resistance and on diabetes, heart disease, and stroke Information on the British Women's Heart and Health Study
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影响因子：
105.7
作者：
Huxley, R;Barzi, F;Woodward, M
通讯作者：
Woodward, M
DOI：
10.1111/j.1365-2362.2006.01623.x
发表时间：
2006-04-01
影响因子：
5.5
作者：
Monnier, L;Colette, C;Lapinski, H
通讯作者：
Lapinski, H
影响因子：
37.8
作者：
Jorgensen, L;Jenssen, T;Jacobsen, BK
通讯作者：
Jacobsen, BK
影响因子：
8.3
作者：
Kothari, V;Stevens, RJ;Holman, RR
通讯作者：
Holman, RR
影响因子：
168.9
作者：
Lawlor, DA;Smith, GD;Ebrahim, S
通讯作者：
Ebrahim, S