高血压病患者胰岛素抵抗及其关联因素

目的 :探讨高血压患者同时存在多种代谢异常时胰岛素的敏感性。方法 :高血压组 79例 ,健康对照组 78例 ,分别进行口服葡萄糖耐量试验 （OGTT）、同步血清胰岛素释放试验 ,血清总胆固醇 （TC）、甘油三酯 （TG）、低密度脂蛋白胆固醇 （L DL- C）、高密度脂蛋白胆固醇 （HDL- C）及体质量指数 （BMI）测定 ,以胰岛素敏感性指数 （ISI）和胰岛素曲线下面积 （IS- AU C）作为胰岛素敏感性的判定指标。结果 :高血压组空腹胰岛素 （FINS）及餐后 2 h胰岛素 （15± 7及 70± 10 m U/L）均显著高于正常对照组 （8± 3及 9± 4 m U/L） ,均为 P<0 .0 1;OGTT显示葡萄糖耐量降低 ,P<0 .0 1。 TC、TG、L DL- C显著升高 ,均 P<0 .0 1,HDL- C升高 ,P<0 .0 5 ;ISI（绝对值 ）和 IS- AUC均显著增高 ,分别为 P<0 .0 5与 P<0 .0 1。二组 BMI与 ISI呈显著负相关 ,r分别为 - 0 .4 9,- 0 .37,P<0 .0 5 ;与 FINS呈显著正相关 ,r分别为 0 .5 3,0 .38,P<0 .0 1。结论 :高血压患者存在着高胰岛素血症 ,同时存在着糖代谢及脂蛋白代谢异常。血糖、血脂、体质量指数均影响胰岛素敏感性。     

Increased insulin resistance in salt sensitive essential hypertension

OBJECTIVE: To determine the possible relationship between insulin resistance and salt sensitivity in essential hypertension. DESIGN AND METHODS: We studied 17 non-obese, essential hypertensive patients (24-h blood pressure: 149 +/- 15/94 +/- 5 mm Hg) with normal glucose tolerance. Salt sensitivity was diagnosed in the presence of a significant increase (P < 0.05, more than 4 mm Hg) in 24-h mean blood pressure (MBP) when patients switched from a low-salt intake (50 mmol/day of Na(+)) to a high-salt intake (240 mmol/day of Na(+)), each period lasting 7 days. The insulin sensitivity index was determined by the euglycaemic hyperinsulinaemic clamp. RESULTS: Six patients were classified as salt sensitive (24-h MBP increase: 6.2 +/- 1.1 mm Hg), and 11 as salt resistant (24-h MBP increase: -1.2 +/- 3.8 mm Hg). No significant differences were observed between salt sensitive and salt resistant patients regarding baseline characteristics, fasting serum insulin, fasting serum glucose, glycosylated haemoglobin, total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, uric acid and microalbuminuria. Salt sensitive patients exhibited a reduced insulin sensitivity index compared with salt resistant patients (1.7 +/- 1.1 vs 3.5 +/- 1.2 mg/kg/min; P = 0.009). An inverse relationship (r -0.57; P = 0.016) between the insulin sensitivity index and 24-h MBP increase with high salt intake was found. CONCLUSION: Salt sensitive essential hypertensive patients are more insulin resistant than salt resistant patients when both salt sensitivity and insulin resistance are accurately measured. Indirect measures of both insulin and salt sensitivity and/or the presence of modifying factors, such as obesity or glucose intolerance, may account for differences in previous studies.     

1193例住院高血压病患者胰岛素分泌和敏感性情况

目的用口服葡萄糖耐量试验中各点血糖和胰岛素的值来计算反映胰岛素敏感性及β细胞功能的参数,回顾性研究住院高血压病人糖代谢情况。方法根据WHO和美国糖尿病协会标准计算血糖分布情况,去除新诊断的糖尿病病人后,分成正常血糖(NGT)、单纯性空腹血糖升高(IFG)、单纯性餐后血糖升高(IGT)和空腹、餐后血糖均升高(IFG,／IGT)组进行比较。再分别以口服75g葡萄糖后30min或60min血糖正常值为标准对NGT组和IGT组进行分组。用HOMA-IR和Composite胰岛素敏感性指数(ISI)计算胰岛素敏感性,HOMA-B和△I／AG计算β细胞功能。结果1193例住院的原发性高血压病人中,新诊断的糖尿病病人为11．1％,其中57．9％仅有餐后血糖升高。IGT、和IFG／ICT组的HOMA-IR高于NGT组,Composite ISI和AI／AG低于NGT组。无论是否30min或60min血糖升高,IGT组的Composite ISI均低于30min和60min血糖正常的NGT组。30min和(或)60min血糖升高的NGT组△I／AG低于30min和60min血糖正常的NGT组。结论IGT或IFG／IGT的高血压患者同时存在空腹和总体胰岛素敏感性的下降和糖负荷后早期β细胞分泌功能的受损。30min和(或)60min血糖升高的NGT高血压病人存在糖负荷后早期β细胞分泌功能的受损。     

Correlative factors of insulin resistance in essential hypertension.

Essential Hypertension (EH) is correlated with a metabolic disturbance characterized by insulin resistance (IR). In this study, there were observed in 47 subjects with EH and 30 subjects with normal blood pressure. Serum levels of insulin-like growth factor-1 (IGF-1), serum levels of growth hormone (GH), the activity of erythrocyte insulin receptors (EIR), and ATP levels in erythrocytes, the insulin sensitivity index (ISI) was used to study the correlative factors of essential hypertension. 1. Among patients with EH, ISI, GH, and low-affinity insulin binding sites of EIRs (RT2) were found to be in significantly lower amounts, IGF-1 levels and the KD2 of the erythrocyte insulin receptors were noted to be significantly higher. Compared with the control group, there was a marked difference between EH group and the control group. However, no statistical difference was observed between the hypertensive group and the group with normal blood pressure as regards erythrocyte ATP levels, high-affinity insulin binding sites of EIRs (RT1), and the KD1 of EIRs. 2. In the hypertensive group, the ISI was negatively correlated with mean arterial blood pressure (MBP), a family history of hypertension, the body mass index (BMI), the waist-hip ratio (WHR) and IGF-1 levels (r=-0.614delta, -0.354**, -0.386**, -0.472**, -0.298*, delta p < 0.001, **p < 0.01, *p < 0.05), were positively correlated with RT2 and GH levels (r=0.301**, 0.275*, **p < 0.01, *p < 0.05). There were no statistically significant differences between ISI and age, sex, smoking history, drinking, RT1, KD1, and ATP levels in erythrocytes. 3. The ISI was used as the dependent variable in multiple linear stepwise regression analysis. MBP (X1), a family history of EH (X2), WHR (X3), GH (X4), IGF-1 (X5), RT2 (X6), and the body mass index (X7) was used as independent variables. X1, X2, X3, X5, X6, and X7 were used in the equations. The results indicate that patients with EH also tend to have IR. We suggest that MBP, a family history of hypertension, BMI, WHR, IGF-1, and RT2 might be independent factors affecting IR in cases of essential hypertension.     

原发性高血压并发胰岛素抵抗的临床治疗进展

近年来胰岛素抵抗(IR)与原发性高血压(EH)的相互关系日益受到人们的关注。1966年Wel-burn发现EH患者同时存在胰岛素敏感性降低和高胰岛素血症现象。几十年来,大量的动物实验和流行病学研究证实了并发IR的多发性,后者占EH人群中的50%左右。患EH同时伴有代谢异常,如血脂异常、肥胖时,IR的发生率更高,而且其严重程度与EH呈正相关〔1,2〕。1IR与EH的关系EH是IR综合征的一个重要组成部分,IR与EH的形成紧密相联。目前研究认为,高胰岛素血症导致EH的机制可能与以下途径有关〔2~4〕:①增加近、远曲肾小管对钠、水重吸收,使血容量增加,…     

老年高血压病患者胰岛素抵抗及药物干预的观察

观察了１６例老年高血压病（ＥＨ）患者及１０例健康老年人口服葡萄糖耐量试验（ＯＧＴＴ）的血糖、胰岛素和Ｃ－肽浓度变化。结果显示，ＥＨ组空腹及ＯＧＴＴ后胰岛素、Ｃ－肽及胰岛素／血糖比值明显高于对照组，Ｃ－肽／胰岛素比值明显降低，糖耐量明显下降。老年ＥＨ组经伊拉地平治疗６周后，空腹及ＯＧＴＴ后胰岛素，Ｃ－肽和胰岛素／血糖比值较治疗前上明显下降，Ｃ－肽／胰岛素比值升高，糖耐量改善，但仍未完全恢复正常。提示老年ＥＨ患者存在胰岛素抵抗（ＩＲ），伊拉地平能在一定程度上改善ＥＨ患者的ＩＲ。     

老年高血压病及冠心病的胰岛素抵抗及其与血脂的关系

目的：探讨老年高血压和冠心病患的胰岛素抵抗及其与血脂的关系。方法：以胰岛素曲线下面积／葡萄糖曲线下面积（Ｉ／Ｇ）和胰岛素抵抗指数作为胰岛素抵抗指标,与空腹因脂指标进行直线相关分析。结果：与正常对照组（ｎ＝２０）比较,高血压组（ｎ＝２５）与冠心病组（ｎ＝２０）的血清甘油三酯（ＴＧ）、低密度脂蛋白（ＬＤＬ－Ｃ）、空腹胰岛素、空腹胰岛素／空腹葡萄糖比值、胰岛素曲线下面积、葡萄糖曲线下面积和Ｉ／Ｇ均显     

原发性高血压患者胰岛素抵抗与血浆肾上腺髓质素的关系

目的:观察原发性高血压(EH)患者胰岛素抵抗与血浆肾上腺髓质素(ADM)的关系,以探讨ADM在EH 患者的意义。方法:40例EH患者按血压水平(<140/90 mmHg,<160/100 mmHg,≥160/100 mmHg)被分为三组,分别测定其血浆ADM、空腹胰岛素、空腹血糖及胰岛素敏感指数(ISI)。结果:血压不同三组间的ISI及ADM 比较均有显著性差异(P<0.05),相关分析结果显示ISI与ADM呈明显负相关(r=-0.61,P<0.05)。结论:ADM 与原发性高血压患者合并的胰岛素抵抗密切相关。     

Insulin resistance versus insulin secretion in the hypertension of obesity.

We measured the degree of association between obesity, blood pressure, insulin resistance, and insulin secretion in 72 male and female obese hypertensive, obese nonhypertensive, and normal weight control subjects. Baseline weight, body mass index, percent body fat, waist/hip ratio, and systolic and diastolic blood pressures were obtained. Insulin sensitivity was assessed according to Bergman's minimal model. Twelve-hour urinary c-peptide was measured after a standard liquid meal. Insulin action was inversely associated with blood pressure status, obesity status, and age. Meal-stimulated c-peptide excretion significantly correlated with systolic blood pressure and percent fat but not with body mass index or age. Multivariate regression analysis indicated that, of the measures of body composition, percent fat and waist/hip ratio had the strongest correlation with insulin action either alone or in combination with c-peptide excretion. Obese hypertensive patients had an index of insulin action (10(-4).min-1/[microunits/ml]) of 1.34 +/- 0.19, which was significantly (p less than 0.003) lower than in the obese nonhypertensive patients (index, 2.26 +/- 0.10) or the nonobese subjects (index, 5.41 +/- 0.26, p less than 0.001). Meal-stimulated c-peptide excretion (nmol/kg lean body mass) was increased only in the obese hypertensive group (0.32 +/- 0.01) and was significantly higher (p less than 0.001) than in the obese nonhypertensive (0.16 +/- 0.01) or the nonobese subjects (0.14 +/- 0.01). These results support the hypothesis that abnormalities in blood pressure regulation, insulin-stimulated glucose uptake, and insulin secretion coexist.     

Insulin resistance and hypertension

A common mechanism which may be involved in the development of hypertension in both type I and type II diabetes mellitus is a deficiency of insulin at the cellular level. Observations from a number of laboratories suggest that impaired cellular response to insulin rather than hyperinsulinemia predisposes to increased vascular smooth muscle tone (the hallmark of hypertension in the diabetic state). This review presents some of the data which suggest that there is a relationship between impaired cellular action of insulin, altered cellular calcium metabolism and the development of hypertension.     

Insulin resistance and hypertension

The author has reviewed the development of the concept that insulin resistance is related not only to the hypertensive state but potentially to the initiation and maintenance of high blood pressure. Potential sequelae of insulin resistance and hyperinsulinemia, as they apply to atherogenesis, are also discussed. The impact of present antihypertensive pharmacologic therapy on insulin resistance is addressed, as are future directions in pharmacologic and nonpharmacologic management of hypertension. In addition, the author speculates on possible mechanisms leading to insulin resistance in hypertension.     

Cytosolic calcium and insulin resistance in elderly patients with essential hypertension.

We evaluated insulin sensitivity in normotensive (blood pressure, BP, less than 135/85 mm Hg) and hypertensive (BP greater than 160/90 mm Hg) elderly subjects over 65 years old who were stratified as normal weight (body mass index, BMI, less than 27) and obese (BMI greater than 27). Obese hypertensive individuals demonstrated marked hyperinsulinemia (P less than .01) and significantly reduced (P less than .05) submaximally stimulated adipocyte 2-deoxyglucose (2-DOG) uptake (abdominal wall fat biopsy). Normal weight hypertensive subjects also demonstrated higher levels of insulinemia and lower insulin-stimulated 2-DOG uptake than nonobese controls. Adipocyte [Ca2+]i levels were elevated in all elderly subjects compared to young individuals (P less than .01). Basal and maximally stimulated 2-DOG uptake were similar in all groups. One month of therapy with a calcium channel blocker, 10 mg nitrendipine twice daily, reduced blood pressure in the hypertensive subjects, reduced plasma insulin to control values during an oral glucose tolerance test in obese hypertensive individuals (P less than .01), and restored adipocyte 2-DOG uptake at submaximally effective insulin concentration to control values in normal weight and obese hypertensive subjects. In summary, older hypertensive, and particularly older obese hypertensive, patients manifest significant insulin resistance accompanied by elevated levels of [Ca2+]i in their adipocytes.     

原发性高血压患者血清脂联素水平及与血压、胰岛素抵抗的关系

目的探讨原发性高血压患者血清脂联素水平及其与血压、胰岛素抵抗之间的关系。方法选取原发性高血压患者65例及健康对照者40名,用酶联免疫吸附法检测各组空腹血清脂联素浓度,同时测定各组的血压、体重指数、腰围、血糖、胰岛素等指标,采用稳态模型法计算胰岛素抵抗指数(IRI)和胰岛素敏感指数(ISI),并分析血清脂联素与各指标间的相关性。结果原发性高血压组血清脂联素水平显著低于健康对照组[(10.30±0.93)μg/ml比(12.83±1.66)μg/ml),P=0.000]。Pearson相关性分析显示,原发性高血压组血清脂联素与收缩压(r=-0.304,P=0.032)、体重指数(r=-0.496,P=0.000)、腰围(r=-0.539,P=0.000)、空腹胰岛素(r=-0.291,P=0.040)、IRI(r=-0.334,P=0.018)之间呈负相关,与ISI呈正相关(r=0.297,P=0.037)。多元逐步回归分析显示,收缩压、腰围是影响脂联素水平的独立危险因素。结论原发性高血压患者血清脂联素水平下降,且与收缩压、胰岛素抵抗具有一定的相关性。     

原发性高血压患者胰岛β细胞功能和胰岛素抵抗研究

目的:探讨不同糖代谢状态下原发性高血压(EH)患者空腹胰岛β细胞功能(FBCI)和胰岛素抵抗(IR)状况。方法:选取符合入选标准的150例EH患者,分为伴糖尿病组与不伴糖尿病组,以健康者50例作为对照组,分别进行OGTT试验和同步胰岛素释放试验,计算胰岛素抵抗指数(HOMA-IR)和FBCI。结果:不伴糖尿病的EH患者FBCI和HOMA-IR高于对照组;伴糖尿病的EH患者FBCI和HOMA-IR显著升高,与不伴糖尿病的EH者比较,差异有统计学意义(P<0.01)。结论:不同糖代谢状态下EH患者均存在糖代谢紊乱和IR,简单的FBCI计算公式不能够反映真实EH患者的胰岛β细胞功能。     

原发性高血压患者心率与胰岛素抵抗水平的相关性研究

目的 :研究原发性高血压 (EH)患者心率 (HR)与胰岛素抵抗 (IR)、血脂代谢、血压水平的关系。方法 :测定 2 0 5例EH患者 (男 85例 ,女 12 0例 )的HR、收缩压、舒张压 (DBP)、体重指数 (BMI)、血糖、胰岛素、总胆固醇、三酰甘油 (TG)、高密度脂蛋白胆固醇 (HDL C)、低密度脂蛋白胆固醇 ,稳态模式评估法计算IR指数(HOMA IR)。分析HR与其他各项参数的相关性。结果 :以HOMA IR 5 0 %位点作为判断IR的切割点 ,将EH患者分为IR组与胰岛素敏感 (IS)组 ,IR组HR[(84 .5± 11.9)次 /min]显著高于IS组 [(76 .8± 10 .8)次 /min]。HR与HOMA IR、DBP、TG呈显著正相关 ,与HDL C呈显著负相关 ;逐步回归分析显示 ,HOMA IR与TG为HR的独立预测因素 ;Logistic回归分析显示 ,HR与IR关系显著。 结论 :与IS的EH患者相比 ,伴IR的EH患者有较快的HR ;EH患者HR与IR、血脂代谢直接相关 ,独立于年龄、血压、BMI。     

Relationship between plasma nitric oxide concentration and insulin resistance in essential hypertension

BACKGROUND: Plasma nitric oxide (NOx) concentrations in patients with essential hypertension (EH) have been reported to be higher, lower, or no different than in normotensives. This study was initiated to determine whether these inconsistent findings were related to differences in insulin resistance. METHODS: Fasting plasma NOx and insulin concentrations were measured in 78 patients with EH and the relationship between these variables evaluated by regression analysis. Patients with hypertension were also divided into tertiles based on their fasting plasma insulin concentration: the highest tertile classified as insulin resistant (EH-IR) and the lowest as insulin sensitive (EH-IS). Plasma NOx concentrations were compared among these two groups and a third group of 21 normotensive, insulin resistant (N-IR) individuals by one-way ANOVA. RESULTS: Plasma insulin and NOx concentrations were correlated (r = 0.31, P <.01) in patients with hypertension, independently of differences in age, body mass index, waist circumference, and blood pressure. Plasma NOx concentrations were different in the three experimental groups (P <.001), being significantly higher (P <.05) in the EH-IR than in either of the other two groups. Despite being hyperinsulinemic, NOx levels in N-IR individuals were lower than in EH-IR subjects and no different from EH-IS individuals. CONCLUSIONS: Plasma NOx concentrations are highest in those patients with EH who are also insulin resistant/hyperinsulinemic (EH-IR). Furthermore, because plasma NOx concentrations were as high in the EH-IS as in the N-IR populations, it could be speculated that plasma NOx concentrations are also modulated by EH, per se.     

氯沙坦对原发性高血压病人胰岛素抵抗性的影响

目的　探索氯沙坦对高血压病的疗效及对胰岛素抵抗的影响。　 方法　采用随机单盲对照法治疗原发性高血压 32例 ,用氯沙坦 5 0mg·d-1,疗程 6周。对照组为 31例 ,用福辛普利 10mg·d-1,疗程 6周。　 结果　氯沙坦组治疗后收缩压下降 (18± 6 )mmHg(P <0 0 1) ,舒张压下降 (12± 7)mmHg(P <0 0 1) ,福辛普利组治疗后收缩压下降 (15± 8)mmHg(P <0 0 1) ,舒张压下降 (14± 6 8)mmHg(P <0 0 1) ,氯沙坦组治疗后糖负荷后 12 0min胰岛素下降 (13± 11)mU·L-1(P <0 0 5 ) ,胰岛素敏感指数下降 (3 1± 2 ) (P <0 0 5 ) ,福辛普利组治疗后 12 0min时胰岛素下降(17± 15 )mU·L-1(P <0 0 1) ,胰岛素敏感指数下降 (3 8± 3) (P <0 0 1) ,氯沙坦组治疗后血清尿酸水平降低 (0 0 4±0 0 1)mmol·L-1(P <0 0 5 ) ,福辛普利组治疗后血清尿酸水平无明显变化。　 结论　氯沙坦治疗高血压病人有改善胰岛素抵抗和降低血尿酸水平的作用。