Insulin resistance in secondary hypertension.

The insulin sensitivity of five essential hypertensive patients was compared to five patients with renovascular hypertension, five patients with primary hyperaldosteronism, and five normotensive subjects, using the euglycemic hyperinsulinemic clamp technique. Essential hypertensive patients had significantly lower insulin sensitivity than patients with hyperaldosteronism and renovascular hypertensive patients (P = .0066, P = .004, respectively). Hyperaldosteronism patients also had less insulin sensitivity than renovascular hypertensive patients (P = .016). A significant negative correlation was found between body mass index and insulin sensitivity index for essential hypertension patients only (r = -0.87, P less than .003). No such correlation was found in the secondary hypertension patients. The findings suggest a causal relationship between insulin resistance and the development of essential hypertension. Secondary hypertension, on the other hand, is not such an insulin resistant state.     

Decreased insulin clearance as a feature of essential hypertension.

Several studies report that essential hypertension is associated with hyperinsulinemia. This condition may depend on enhanced pancreatic insulin secretion and/or a decreased MCR of the circulating hormone. Twenty-five nonobese glucose-normotolerant patients with primary hypertension were divided into 5 groups, each consisting of 5 subjects. Each group was submitted to continuous 120-min double infusion of different doses of insulin (group I, 0.025; II, 0.05; III, 0.1; IV, 0.2; V, 0.4 U/kg.h) and glucose (I, 2; II, 3.5; III, 6; IV, 8; V, 10 mg/kg.min). The same procedures were applied to 25 healthy normotensive volunteers. Basal and steady state plasma levels of glucose, insulin, and C-peptide were significantly (P less than 0.05 or less) higher in hypertensive patients than in control subjects of all groups. The MCR of insulin (milliliters per kg/min) at all insulin-glucose infusion rates was significantly (P less than 0.05 or less) lower in hypertensive than normotensive subjects. Despite the significantly higher steady state plasma insulin levels in hypertensives, the MCR of glucose (milliliters per kg/min) was significantly (P less than 0.05 or less) lower in hypertensive than normotensive subjects. These results suggest that an altered insulin removal may contribute to the hyperinsulinemia found in the essential hypertensive subjects. In addition, a defect in insulin-stimulated glucose uptake which persists at supraphysiological insulin concentrations is confirmed in this population.     

Insulin action and hepatic glucose cycling in essential hypertension.

Peripheral insulin resistance is a feature of essential hypertension, but there is little information about hepatic insulin sensitivity. To investigate peripheral and hepatic insulin sensitivity and activity of the hepatic glucose/glucose 6-phosphate (G/G6P) substrate cycle in essential hypertension, euglycemic glucose clamps were performed in eight untreated patients and eight matched controls at insulin infusion rates of 0.2 and 1.0 mU.kg-1.min-1. A simultaneous infusion of (2(3)H)- and (6(3)H)glucose, combined with a selective detritiation procedure, was used to determine glucose turnover, the difference being G/G6P cycle activity. Endogenous hepatic glucose production (EGP) determined with (6(3)H)glucose was similar in hypertensive and control groups in the postabsorptive state (11.0 +/- 0.3 v 10.9 +/- 0.3 mumol.kg-1.min-1) and with the 0.2 mU insulin infusion (4.9 +/- 0.5 v 4.0 +/- 0.8 mumol.kg-1.min-1). With the 1.0 mU insulin infusion, glucose disappearance determined with (6(3)H)glucose was lower in the hypertensive group (21.8 +/- 2.4 v 29.9 +/- 2.4 mumol.kg-1.min-1, P less than .001). G/G6P cycle activity was similar both in the postabsorptive state (2.2 +/- 0.4 v 2.7 +/- 0.4 mumol.kg-1.min-1) and during insulin infusion (0.2 mU, 2.5 +/- 0.3 v 2.9 +/- 0.4; 1.0 mU, 4.7 +/- 0.3 v 5.3 +/- 1.1 mumol.kg-1.min-1 for hypertensive and control groups, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Insulin resistance and insulin pulsatility in essential hypertension

OBJECTIVE: Studies in normal humans and in patients with type 2 diabetes mellitus have demonstrated a close inverse relationship between peripheral insulin sensitivity and the frequency of short-term insulin secretory pulses in the systemic circulation. Our objective was to study this relationship in essential hypertension. DESIGN: Study of insulin sensitivity and insulin pulse characteristics in hypertensive subjects and normotensive controls using well-established techniques. METHODS: Twelve subjects with essential hypertension and 12 age- and sex-matched normotensive controls were recruited. Insulin action was measured using the glucose clamp technique combined with isotope dilution methodology. Insulin pulsatility in the peripheral circulation was assessed by sampling every 2 min for 90 min after an overnight fast Pulses were identified using the computer program Pulsar. RESULTS: Insulin sensitivity index (glucose infusion rate/ serum insulin) was lower in the hypertensive patients (P= 0.01) and fasting insulin was increased (P= 0.008) compared to controls. The frequency and amplitude of insulin pulses were similar in the two groups. Insulin pulse frequency and insulin sensitivity were inversely related in the normotensive group (r= -0.68, P= 0.015), but not in the hypertensive group (r= -0.23, P= 0.48). Insulin clearance was reduced in the hypertensive group (P= 0.03), and was inversely related to insulin pulse frequency in the two groups combined (r = -0.51, P= 0.01). CONCLUSIONS: Insulin action was not related to insulin pulse frequency in essential hypertension, in contrast to the situation in normal man.     

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。     

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。     

Relationship between oxidative stress and essential hypertension.

This study investigated the association of blood pressure with blood oxidative stress-related parameters in normotensive and hypertensive subjects. A cross-sectional design was applied to 31 hypertensive patients and 35 healthy normotensive subjects. All subjects were men between the ages of 35 and 60 years. Exclusion criteria were obesity, dyslipidemia, diabetes mellitus, smoking and current use of any medication. All patients underwent 24-h ambulatory blood pressure monitoring and sampling of blood and urine. Antioxidant enzymes activity, reduced/oxidized glutathione ratio (GSH/GSSG), and lipid peroxidation (malondialdehyde) were determined in erythrocytes. Parameters measured in the plasma of test subjects were plasma antioxidant status, lipid peroxidation (8-isoprostane), plasma vitamin C and E, and the blood pressure modulators renin, aldosterone, endothelin-1 and homocysteine. Daytime systolic and diastolic blood pressures of hypertensives were negatively correlated with plasma antioxidant capacity (r=-0.46, p<0.009 and r=-0.48, p<0.007), plasma vitamin C levels (r=-0.53, p<0.003 and r=-0.44, p<0.02), erythrocyte activity of antioxidant enzymes, and erythrocyte GSH/GSSG ratio, with hypertensives showing higher levels of oxidative stress. Blood pressures showed a positive correlation with both plasma and urine 8-isoprostane. Neither plasma vitamin E nor the assessed blood pressure modulator levels showed significant differences between the groups or correlation with blood pressures. These findings demonstrate a strong association between blood pressure and some oxidative stress-related parameters and suggest a possible role of oxidative stress in the pathophysiology of essential hypertension.     

胰岛素样生长因子1与原发性高血压

目的:探讨原发性高血压病的发病机制。方法:对28例原发性高血压患者和16名正常人测定了血清胰岛素样生长因子1(IGF1),并与高血压分级进行了相关分析。结果:原发性高血压患者IGF1水平显著低于正常人(分别为26.22μg/L±20.23μg/L和48.02μg/L±33.43μ/L,P<0.05),且IGF1水平与临床分级呈负相关(=-0.437,P<0.05)。 结论:IGF1可能参与了原发性高血压的病理生理过程。     

Insulin resistance is a characteristic feature of primary hypertension independent of obesity

The relationship between abnormalities in carbohydrate metabolism and hypertension was studied in 143 newly detected hypertensive patients (59% obese) of both sexes (90 males, 53 females) and compared with 51 normotensive controls. Insulin-mediated glucose disposal assessed with the euglycemic insulin clamp technique was significantly decreased in both non-obese (7.2 +/- 2.1 mg/kg/min; P less than .05) and obese hypertensives (5.1 +/- 2.1 mg/kg/min; P less than .01) compared with the controls (8.4 +/- 1.8 mg/kg/min). The decrease in insulin sensitivity and increase in basal insulin as well as a decreased rate of glucose disposal after an intravenous glucose tolerance test (IVGTT) were verified also after statistical adjustment for sex, age, body mass index, and waist-hip ratio. The insulin index (ratio between peak and basal insulin) during IVGTT was significantly decreased in the hypertensive patients (P less than .001). After the statistical adjustment for the factors mentioned the following lipid abnormalities were still significant: total cholesterol (6.25 +/- 1.12 mmol/L non-obese; 6.06 +/- 1.20 mmol/L obese; 5.41 +/- 1.02 mmol/L controls), triglycerides (1.70 +/- 0.74 mmol/L nonobese; 2.26 +/- 1.13 mmol/L obese; 1.24 +/- 0.53 mmol/L controls) and free fatty acids (0.57 +/- 0.20 mmol/L nonobese; 0.59 +/- 0.20 mmol/L obese; 0.48 +/- 0.15 mmol/L controls). This study shows that after correction for a series of probable confounding variables, hypertension emerges as part of a syndrome characterized by major abnormalities of carbohydrate, insulin, and lipid metabolism, which independently or in concert may act as important risk factors for cardiovascular disease.     

Insulin resistance and hypertension.

Insulin resistance, a common accompaniment of essential hypertension, increases cardiovascular risk both directly, and via its adverse effect on other cardiovascular risk factors. Decreasing insulin resistance by lifestyle modification including diet, weight loss, and physical exercise is an important component of therapy in all patients. With the exception of thiazide diuretics as monotherapy, the currently utilized classes of agent appear equally effective in lowering blood pressure in insulin resistant patients. Currently utilized agents do, however, differ substantially in their effect on insulin resistance and associated risk factors. Agents that diminish insulin resistance may have a rationale in treating insulin resistant patients with hypertension although a decisive recommendation about class of agent in this group of patients must await several prospective large scale trials currently underway. Lower intervention thresholds and lower therapeutic goals would appear to apply to hypertensive patients with insulin resistance especially in the presence of impaired glucose tolerance or overt diabetes mellitus.     

Renal vascular tone in essential and secondary hypertension: hemodynamic and angiographic responses to vasodilators.

The renal vascular response to graded doses of acetylcholine, dopamine and phentolamine, assessed by xenon washout and selective arteriography was used to define the relative contribution of fixed and reversible vascular abnormalities to increased renal vascular resistance in patients with essential or secondary hypertension. The increase in blood flow induced by acetylcholine and dopamine was blunted strikingly in patients with advanced nephrosclerosis, chronic pyelonephritis and polycystic kidney disease and was normal in the kidney contralateral to a significant renal artery stenosis. Conversely, the response to both was potentiated in 9 of 13 (69%) patients with mild essential hypertension. Equivalent potentiation of the response to acetylcholine was induced in normal subjects by increasing renal vascular tone pharmacologically with angiotensin. Phentolamine infused into the renal artery also increased renal blood flow significantly in 6 of 9 (67%) patients with mild essential hypertension, but in none of 15 normal subjects, over a dose reange that paralleled that for alpha-adrenergic blockade. Changes in the selective renal arteriogram were in excellent accord: potentiated response to acetylcholine, phentolamine or dopamine was associated with reversal of the small vessel abnormalities visualized in the arteriogram. The reduced blood flow response in advanced nephrosclerosis or parenchymal disease was associated with a reduced angiographic change during dilator infusion. The results suggest a quantitatively important, functional renal vascular abnormality--perhaps mediated by the sympathetic nervous system--in many patients with mild essential hypertension. Conversely the renal vascular abnormality associated with advanced nephrosclerosis or renal parenchymal disease is largely fixed and is probably due to organic changes.     

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。     

Insulin resistance in essential hypertension: a psychophysiological approach to the "chicken and egg" question

AIMS: High levels of plasma insulin have frequently been found in patients with high blood pressure. The causal role of insulin resistance in essential hypertension, however, is still debated. Epidemiological and clinical studies have not provided complete responses to the original pathophysiological speculations, while the suggestion that enhanced sympathetic tone may induce both insulin resistance and hypertension is gaining ground. DATA SYNTHESIS: Many studies indicate that the high sympathetic drive in hypertensive patients originates within the brain, while other studies show that insulin resistance is associated with reduced vasodilatory capacity and increased vasoconstrictive functional responses ascribed to endothelial impairment. The sympathetic overdrive and enhanced cardiovascular reactivity, detectable since the earliest stages of hypertension lead to endothelial damage and, hence, impair the vasodilatory response, peripheral blood flow and flow-dependent metabolism. Thus, the link between hyperinsulinemia and high blood pressure might lie in the vascular abnormalities secondary to elevated sympathetic tone and exaggerated hemodynamic stress response. CONCLUSIONS: Examination of the literature and the results of recent pilot studies of the stress systemic and regional hemodynamic reactivity in the present paper suggests that behavioral characteristics and cardiovascular stress responses play a pivotal role in determining the hyperinsulinemic state in hypertensive patients. High sympathetic tone, with consequent vascular impairment and altered functional responses, may be the primary event causing hyperinsulinemia and start very early in patients with high blood pressure. In turn, hyperinsulinemia further contributes to vascular damage and aggravates the metabolic and hypertensive disease.     

Insulin binding to erythrocyte receptors in patients with essential hypertension

Recently many researchers have described the presence of insulin resistance and hyperinsulinemia in a substantial number of patients with essential hypertension. Reduced insulin binding to the receptors may play important role in development of insulin resistance in these patients. The study was aimed to assess the value of insulin binding to erythrocyte receptors in the patients with essential hypertension and compare to values in healthy persons. Additional purpose was the evaluation of insulin degradation by erythrocytes in patients with essential hypertension. 23 patients with essential hypertension (BMI 22.7 +/- 3.2) and 21 healthy persons (with BMI value 23.3 +/- 2.9) were studied. In all examined individuals the blood glucose and blood insulin concentrations were determined, insulin binding to erythrocyte receptors and insulin degradation by erythrocytes were measured by the method of Gambhir and al. Insulin concentration was significantly higher in patients with essential hypertension than in healthy subjects. We demonstrated a statistically significant positive correlation between body weight and insulin concentration in blood serum only in healthy people. Insulin binding to the receptors of red blood cells was significantly stronger (p < 0.001) in healthy persons than in patients with essential hypertension (0.972 +/- 0.395 pg 10(11) RBC and 0.446 +/- 0.14 pg 10(11) RBC respectively). In patients with hypertension insulin binding to receptors of red blood cells does not depend on body weight and insulin concentration in blood serum. Values of insulin degradation by erythrocyte in patients with essential hypertension and healthy persons were not significantly different. It seems that decreased insulin binding to insulin receptors is an important mechanism of insulin resistance patients with essential hypertension.     

Portopulmonary hypertension: distinctive hemodynamic and clinical manifestations

Portopulmonary hypertension is now recognized as one of the pulmonary complications of chronic liver disease. However, previous studies reported that the incidence ranged from 0.25% to 2%, excluding fortuitous coincidence. In this study, we aimed to determine the variant hemodynamic and clinical features of portopulmonary hypertension in an area with a high prevalence of viral cirrhosis. After reviewing the hemodynamic data of 322 patients with portal hypertension admitted to the Taipei Veterans General Hospital between 1987 and 1999, we found 10 with portopulmonary hypertension. The overall incidence was, therefore, 3.1% in all patients with portal hypertension. Most of the patients with portopulmonary hypertension experienced exertional dyspnea. The survival times ranged from 2 to 86 months. In our series, most of the patients who died, died of complications related to cirrhosis and portal hypertension, but not of complications related to pulmonary hypertension. This study suggested that portopulmonary hypertension was not a frequent complication in cirrhotic patients and was not associated with an adverse outcome. Received: June 15, 2000 / Accepted: September 8, 2000     

Association between essential hypertension and immunology]

Using the immunofluorescence method, autoantibodies of serum IgG was investigated in 100 consecutive patients of essential hypertension with or without family history of hypertension. 30 healthy normotensive subjects with family history of hypertension and 40 healthy normotensive subjects of the same age range were also studied. The results showed that in the treated patients, the frequency of smooth muscle antibodies (SMA), antimitochondrial antibodies (AMA), antinuclear antibodies (ANA) and heart reactive antibodies (HRA) was higher than that in healthy normotensive subjects. The frequency of these antibodies was not associated with difference in mean arterial blood pressure, sex, and clinical stage and a possible genetic predisposition is suggested. The autoantibodies may even appear before the elevation of blood pressure in patients with essential hypertension. The above-mentioned results show that lack of autoimmunity may be one of the pathogenetic factors of essential hypertension.     

老年原发性高血压病与高胰岛素血症关系的研究

目的：探讨老年原发性高血压病患者血清胰岛素水平及对胰岛素的敏感性。方法：测定无糖尿病老年原发性高血压组80例、健康对照组43例的空腹血糖（FBG）、餐后2h血糖（PBG）、空腹胰岛素（FINS）和餐后2h胰岛素（PINS）水平,计算胰岛素敏感指数（ISI）,并进行对比。结果：老年原发性高血压组患者FINS及PINS水平均较健康对照组显著升高[（13．5±5．0）mU／L：（9．2±4．6）mU／L,（40．9±10．4）mU／L：（16．1±6．9）mU／L,P〈0．01],老年原发性高血压组患者ISI较对照组明显降低[（-4．2±0．3）：（-3．4±0．3）,P〈0．05]。结论：老年原发性高血压患者多伴有高胰岛素血症和胰岛素抵抗。其发生与组织对胰岛素的敏感性下降,胰岛素的分泌异常增多有关。