肥胖的高血压病人与高胰岛素血症及胰岛素抵抗的关系
摘要
目的：高血压病为中老年常见疾病之一，近20多年来在我国呈增加趋势，由于其主要是对心、脑、肾、血管等靶器官的损害，严重影响着人们的生活质量。到目前为止对高血压病的发病机制尚不完全清楚，但研究表明高胰岛素血症及胰岛素抵抗与高血压病的发生密切相关。高胰岛素血症及胰岛素抵抗引起高血压病是个复杂的过程。体内在高胰岛素血症的状态下通过以下机制使血压升高：①胰岛素使肾钠重吸收增加；②胰岛素使交感神经活性增加；③血管活性物质比例失调；④阳离子流动机制紊乱；⑤促进血管平滑肌的增生；⑥血管重塑；⑦脂质代谢紊乱等因素使血压升高。
高胰岛素血症可分为急性高胰岛素血症及慢性高胰岛素血症。前者见于胰岛素瘤、胰岛细胞腺瘤及嗜铬细胞腺瘤患者，后者继发胰岛素抵抗。在胰岛素抵抗状态下，血浆葡萄糖不能有效地从循环中移除，进而刺激胰岛素从细胞中释放，导致高胰岛素血症。此外，也可由于体内自主神经系统中支配胰腺迷走神经的作用过强可导致高胰岛素血症。高胰岛素血症可使脂质代谢紊乱而造成肥胖病人内脏脂肪进一步浸润出现腹型肥
胖，肥胖出现后，由于脂肪组织中GLUT4和肝葡萄糖激酶（GK）减少，这两个酶中均有胰岛素及过氧化物酶增殖性激活物受体-γ（PPAR）的应答成分，因此GLUT4及GK减少引起葡萄糖的利用降低。另一方面，脂肪组织中的瘦素及肿瘤坏死因子-α和相应受体的变化也可影响GLUT4及GK的活性。这样导致胰岛素敏感性降低，发生胰岛素抵抗。在胰岛素抵抗状态下代偿性引起高胰岛素血症。高胰岛素血症可使脂质在脂肪组织聚集，加重肥胖，从而形成恶性循环。肥胖的高血压病人主要是因为高胰岛素血症及胰岛素抵抗作用使血压升高。体内在肥胖、高胰岛素血症、胰岛素抵抗三者的共同作用下引起高血压。其中以高胰岛素血症及胰岛素抵抗作用尤为重要。一些研究已经证明，肥胖单独或/和高血压的病人存在胰岛素抵抗，胰岛素抵抗检验的金标准是钳夹试验，该方法价格昂贵、检查费时，只能做为科学研究，不易被临床所推广使用。本文通过对54例腹型肥胖的高血压病患者及54例非肥胖的高血压病患者进行腰臀比、体重指数、血清胰岛素水平、胆固醇、甘油三酯水平、糖耐量试验及血浆胰岛素、CP水平的测定的观察，探讨肥胖的高血压病患者血压升高的机制与高胰岛素血症及胰岛素抵抗的关系。以期认为在肥胖的高血压病患者中高胰岛素血症及胰岛素
抵抗是引起高血压病的一个重要因素。血清胰岛素水平的测定可以间接判断胰岛素抵抗，同时可以认为肥胖，尤其腹型肥胖是存在高胰岛素血症及胰岛素抵抗的一项标志。本研究结果为高血压病个体化诊断、治疗提供佐证。
方法：选取吉林大学第三临床医院2002年3月至2004年5月心内科病房治疗前的原发性高血压患者108例，分为两组。一组为高血压病伴腹型肥胖患者54例，其中男45例，女9例；另一组为高血压病无肥胖患者54例，男47例，女7例。患者入院后即进行测量腰臀比，男性采用腰臀比>0.91，女性采用腰臀比>0.81定为为腹型肥胖，同时测体重、身高，以体重（kg）/身高(cm)2公式计算出体重指数。体重指数以亚太地区肥胖和超重的诊断标准专题研讨会规定标准，BMI≥25为肥胖。血压测定于清晨静卧30min后进行，共测3次，取平均值。高血压病采用WHO诊断标准：SBP≥140mmHg及/或DBP≥90mmHg。胰岛素、CP的测定有本院放免室采用中国原子能科学研究院试剂盒按说明进行。OGTT试验、甘油三酯、总胆固醇在本院检验科使用美国贝克曼公司生产的CS9全自动生化分析仪，采用自动化试剂盒检查。
结果判定：观察结果采用双盲法，根据美国糖尿病协会
（ADA）1997年新建议，OGTT2h血糖≥7.8mmol/L，但<11.1mmol/L为糖耐量减退（也称糖耐量异常）；高血压病采用WHO诊断标准：SBP140~159mmHg及/或DBP90~99mmHg为一级；SBP160~179mmHg及/或DBP100~109mmHg为二级；SBP≥180mmHg及/或DBP≥110mmHg为三级；甘油三酯≥1.7mmol，胆固醇≥5.2mmol为血脂升高；胰岛素正常范围4.2～15.8mu/L；CP正常范围0.4～0.8pmol/L。全部数据均以X±S表示，采用t检验或Х2检验。
结果：肥胖组较非肥胖组患者血浆胰岛素及CP水平均升高（P<0.01）；肥胖组较非肥胖组患者糖耐量试验减低（P<0.05）；收缩压及舒张压危险程度肥胖组较非肥胖组患者升高（P<0.01；P<0.05）；肥胖组较非肥胖组患者甘油三酯、胆固醇水平升高（P<0.01；P<0.05）。
结论：本文所选病例为中心型肥胖的患者，中心型肥胖的高血压病患者明显存在高胰岛素血症及胰岛素抵抗。肥胖的高血压病患者的发病机制可能主要与高胰岛素血症及胰岛素抵抗有关。高胰岛素血症提示体内存在胰岛素抵抗。中心型肥胖的高血压病患者血压高于非肥胖患者，前者血清胰岛素、C肽、血脂水平平均高于后者，说明代谢障碍参与了高血压病的发病
机制。
结果提示：高胰岛素血症及胰岛素抵抗在肥胖高血压病的发病机制中发挥着重要作用。高胰岛素血症使血压升高，同时加重肥胖。故在临床治疗高血压病时应强调个体化，对肥胖的高血压患者应常规检查胰岛素及C肽水平，以确定是否存在高胰岛素血症及胰岛素抵抗，对这部分患者在应
Objective hypertension, Which is very common in the old, accociated with seversal agents. But until now , studys indicted that Major hypertension present hyperinsulinism and insulin resistance. Meanwhile， presence of obesity and hyperinsulinism were commonly found in some studys. Obesity can be considered as an insulin-resistance which comprises a constellation of clinical, biochemical and hemodynamic abnormalities . hyperinsulinism can accumulate lipid in fatty tissue, result in obesitybesity will induce insulin-resistance state, in which precent hyperinsulinism, thereby foaming vicious cycle.furthermore hypersulinism can lead to dyslipidemia. Hyperinsulinism and insulin-resistance are major risk facters with high incidence in the obese population. These risk factors have the capacity to induce hypertension. Howere, golden standard of insulin-resistance is euglycemic insulin clamp the method are expensive and time-consuming. So it doesn‘t suit to clinical usage. The purpose of this study was to discuss the relation of
hypertension with hyperinsulinism. In order to find envidence of a individualizing therapy and diagnosis of hypertension，this study was performed.
Method Fasting insulin and C peptid （CP）were measured and 2-h oral glucose tolerace tests （OGTT）were performed in 54 obese patients and 54 controls (irobese patients). All patients come from the Third Hospital of Jilin University (2002～2004) and weren‘t given antihypertensive therapy after hospitalize. Meanwhile， the level of triglyceridemia , total cholesterol, blood pressure ,ratio of waist and buttock were detected.
Result‘ standard According to suggestion of American Diabetes Association(ADA) in 1997, plasma glucose concentrations≥7.8mmol/L and <11.1mmol/L was considered as abnormality in 2-h oral glucose tolerance test; normal range of insulin is 4.2～15.8mu/L; normal range of CP is 0.4～0.8pmol/L; Triglyceridemia≥1.7mmol and total cholesterol≥5.2mmol were considered as hyperlipidemia.
Results The level of insulin and CP in obese group is higer than that in irobese group(P<0.01) , oral glucose tolerance test in
obese group is lower than that in irobese group(P<0.05), degree of systolic pressure and diastolic pressure in obese group is higher that of irobese group(P<0.01, P<0.05), the level of triglyceridemia and total cholesterol in obese group are higher than that in irobese group(P<0.01, P<0.05).
Conclusion The center-obesity patients were selected in our study. Obese hypertension exist hyperinsulinism and insulin-resistance. Pathogenesis of obese hypertension have possible relation with hyperinsulinism and insulin-resistance. Among of these facters, hyperinsulinism is very important. Risk degress of hypertension , insulin, CP, lipid in obesity were higher than that in irobesity, indicating allo-metabolism is involved in Pathogenesis of hypertension.
Suggestion This study suggested hyperinsulinism and insulin-resistance are important in pathogenesis of hypertension. Hyperinsulin makes blood pressure higher and add fat in fatty tissue. Thereby， the level of insulin and CP should be detected in hypertensive patients routinely. We should emphasize individualization in therapy of hypertension. When application of
anti-hypertension decrease blood pressure, ameliorat insulin sensibility, reduce the level of insulin, Progress of risk degress of blood pressure will be prevented. Coronary heart disease and diabetes mellitus will be prevented.
高胰岛素血症可分为急性高胰岛素血症及慢性高胰岛素血症。前者见于胰岛素瘤、胰岛细胞腺瘤及嗜铬细胞腺瘤患者，后者继发胰岛素抵抗。在胰岛素抵抗状态下，血浆葡萄糖不能有效地从循环中移除，进而刺激胰岛素从细胞中释放，导致高胰岛素血症。此外，也可由于体内自主神经系统中支配胰腺迷走神经的作用过强可导致高胰岛素血症。高胰岛素血症可使脂质代谢紊乱而造成肥胖病人内脏脂肪进一步浸润出现腹型肥
胖，肥胖出现后，由于脂肪组织中GLUT4和肝葡萄糖激酶（GK）减少，这两个酶中均有胰岛素及过氧化物酶增殖性激活物受体-γ（PPAR）的应答成分，因此GLUT4及GK减少引起葡萄糖的利用降低。另一方面，脂肪组织中的瘦素及肿瘤坏死因子-α和相应受体的变化也可影响GLUT4及GK的活性。这样导致胰岛素敏感性降低，发生胰岛素抵抗。在胰岛素抵抗状态下代偿性引起高胰岛素血症。高胰岛素血症可使脂质在脂肪组织聚集，加重肥胖，从而形成恶性循环。肥胖的高血压病人主要是因为高胰岛素血症及胰岛素抵抗作用使血压升高。体内在肥胖、高胰岛素血症、胰岛素抵抗三者的共同作用下引起高血压。其中以高胰岛素血症及胰岛素抵抗作用尤为重要。一些研究已经证明，肥胖单独或/和高血压的病人存在胰岛素抵抗，胰岛素抵抗检验的金标准是钳夹试验，该方法价格昂贵、检查费时，只能做为科学研究，不易被临床所推广使用。本文通过对54例腹型肥胖的高血压病患者及54例非肥胖的高血压病患者进行腰臀比、体重指数、血清胰岛素水平、胆固醇、甘油三酯水平、糖耐量试验及血浆胰岛素、CP水平的测定的观察，探讨肥胖的高血压病患者血压升高的机制与高胰岛素血症及胰岛素抵抗的关系。以期认为在肥胖的高血压病患者中高胰岛素血症及胰岛素
抵抗是引起高血压病的一个重要因素。血清胰岛素水平的测定可以间接判断胰岛素抵抗，同时可以认为肥胖，尤其腹型肥胖是存在高胰岛素血症及胰岛素抵抗的一项标志。本研究结果为高血压病个体化诊断、治疗提供佐证。
方法：选取吉林大学第三临床医院2002年3月至2004年5月心内科病房治疗前的原发性高血压患者108例，分为两组。一组为高血压病伴腹型肥胖患者54例，其中男45例，女9例；另一组为高血压病无肥胖患者54例，男47例，女7例。患者入院后即进行测量腰臀比，男性采用腰臀比>0.91，女性采用腰臀比>0.81定为为腹型肥胖，同时测体重、身高，以体重（kg）/身高(cm)2公式计算出体重指数。体重指数以亚太地区肥胖和超重的诊断标准专题研讨会规定标准，BMI≥25为肥胖。血压测定于清晨静卧30min后进行，共测3次，取平均值。高血压病采用WHO诊断标准：SBP≥140mmHg及/或DBP≥90mmHg。胰岛素、CP的测定有本院放免室采用中国原子能科学研究院试剂盒按说明进行。OGTT试验、甘油三酯、总胆固醇在本院检验科使用美国贝克曼公司生产的CS9全自动生化分析仪，采用自动化试剂盒检查。
结果判定：观察结果采用双盲法，根据美国糖尿病协会
（ADA）1997年新建议，OGTT2h血糖≥7.8mmol/L，但<11.1mmol/L为糖耐量减退（也称糖耐量异常）；高血压病采用WHO诊断标准：SBP140~159mmHg及/或DBP90~99mmHg为一级；SBP160~179mmHg及/或DBP100~109mmHg为二级；SBP≥180mmHg及/或DBP≥110mmHg为三级；甘油三酯≥1.7mmol，胆固醇≥5.2mmol为血脂升高；胰岛素正常范围4.2～15.8mu/L；CP正常范围0.4～0.8pmol/L。全部数据均以X±S表示，采用t检验或Х2检验。
结果：肥胖组较非肥胖组患者血浆胰岛素及CP水平均升高（P<0.01）；肥胖组较非肥胖组患者糖耐量试验减低（P<0.05）；收缩压及舒张压危险程度肥胖组较非肥胖组患者升高（P<0.01；P<0.05）；肥胖组较非肥胖组患者甘油三酯、胆固醇水平升高（P<0.01；P<0.05）。
结论：本文所选病例为中心型肥胖的患者，中心型肥胖的高血压病患者明显存在高胰岛素血症及胰岛素抵抗。肥胖的高血压病患者的发病机制可能主要与高胰岛素血症及胰岛素抵抗有关。高胰岛素血症提示体内存在胰岛素抵抗。中心型肥胖的高血压病患者血压高于非肥胖患者，前者血清胰岛素、C肽、血脂水平平均高于后者，说明代谢障碍参与了高血压病的发病
机制。
结果提示：高胰岛素血症及胰岛素抵抗在肥胖高血压病的发病机制中发挥着重要作用。高胰岛素血症使血压升高，同时加重肥胖。故在临床治疗高血压病时应强调个体化，对肥胖的高血压患者应常规检查胰岛素及C肽水平，以确定是否存在高胰岛素血症及胰岛素抵抗，对这部分患者在应
Objective hypertension, Which is very common in the old, accociated with seversal agents. But until now , studys indicted that Major hypertension present hyperinsulinism and insulin resistance. Meanwhile， presence of obesity and hyperinsulinism were commonly found in some studys. Obesity can be considered as an insulin-resistance which comprises a constellation of clinical, biochemical and hemodynamic abnormalities . hyperinsulinism can accumulate lipid in fatty tissue, result in obesitybesity will induce insulin-resistance state, in which precent hyperinsulinism, thereby foaming vicious cycle.furthermore hypersulinism can lead to dyslipidemia. Hyperinsulinism and insulin-resistance are major risk facters with high incidence in the obese population. These risk factors have the capacity to induce hypertension. Howere, golden standard of insulin-resistance is euglycemic insulin clamp the method are expensive and time-consuming. So it doesn‘t suit to clinical usage. The purpose of this study was to discuss the relation of
hypertension with hyperinsulinism. In order to find envidence of a individualizing therapy and diagnosis of hypertension，this study was performed.
Method Fasting insulin and C peptid （CP）were measured and 2-h oral glucose tolerace tests （OGTT）were performed in 54 obese patients and 54 controls (irobese patients). All patients come from the Third Hospital of Jilin University (2002～2004) and weren‘t given antihypertensive therapy after hospitalize. Meanwhile， the level of triglyceridemia , total cholesterol, blood pressure ,ratio of waist and buttock were detected.
Result‘ standard According to suggestion of American Diabetes Association(ADA) in 1997, plasma glucose concentrations≥7.8mmol/L and <11.1mmol/L was considered as abnormality in 2-h oral glucose tolerance test; normal range of insulin is 4.2～15.8mu/L; normal range of CP is 0.4～0.8pmol/L; Triglyceridemia≥1.7mmol and total cholesterol≥5.2mmol were considered as hyperlipidemia.
Results The level of insulin and CP in obese group is higer than that in irobese group(P<0.01) , oral glucose tolerance test in
obese group is lower than that in irobese group(P<0.05), degree of systolic pressure and diastolic pressure in obese group is higher that of irobese group(P<0.01, P<0.05), the level of triglyceridemia and total cholesterol in obese group are higher than that in irobese group(P<0.01, P<0.05).
Conclusion The center-obesity patients were selected in our study. Obese hypertension exist hyperinsulinism and insulin-resistance. Pathogenesis of obese hypertension have possible relation with hyperinsulinism and insulin-resistance. Among of these facters, hyperinsulinism is very important. Risk degress of hypertension , insulin, CP, lipid in obesity were higher than that in irobesity, indicating allo-metabolism is involved in Pathogenesis of hypertension.
Suggestion This study suggested hyperinsulinism and insulin-resistance are important in pathogenesis of hypertension. Hyperinsulin makes blood pressure higher and add fat in fatty tissue. Thereby， the level of insulin and CP should be detected in hypertensive patients routinely. We should emphasize individualization in therapy of hypertension. When application of
anti-hypertension decrease blood pressure, ameliorat insulin sensibility, reduce the level of insulin, Progress of risk degress of blood pressure will be prevented. Coronary heart disease and diabetes mellitus will be prevented.
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