Insulin Resistance Rather than Hyperinsulinemia More Closely Associated with Essential Hypertension

In order to clarify which of the two, insulin resistance or hyperinsulinemia, are more contributable to non obese and non diabetic hypertension, insulin sensitivity test was performed. By multiple regression analysis, mean, systolic, and diastolic blood pressure were inversely correlated with glucose clearance. During insulin sensitivity test, plasma catecholamines levels and FENa were not changed by insulin infusion.

In the present study, it is demonstrated that insulin has no hypertensive effect under the mild hyperinsulinemia (45–55μU/ml). We conclude that insulin resistance rather than hyperinsulinemia may be more closely associated with non obese and non diabetic hypertension.     

肥胖对高血压病人胰岛素抵抗的影响

目的观察肥胖是否加重高血压病人的胰岛素抵抗。方法口服７５ｇ葡萄糖做葡萄糖耐量试验（ＯＧＴＴ），用己糖激酶法测血糖，放免法测胰岛素和Ｃ肽。结果糖负荷后高血压两组的葡萄糖、胰岛素和Ｃ肽浓度及曲线下面积（ＡＵＣ）高于对照组，而肥胖高血压组（ＯＥＨ）又高于非肥胖高血压组（ＮＯＥＨ）。在２ｈ和３ｈ时ＮＯＥＨ的Ｃ肽／胰岛素摩尔比显著低于对照组，高血压两组间的Ｃ肽／胰岛素摩尔比无显著差异。结论肥胖加重了高血压病人的胰岛素抵抗（ＩＳＲ）。     

Hyperinsulinemia instead of insulin resistance induces baroreflex dysfunction in chronic insulin-infused rats

BACKGROUND: The present study was undertaken to compare the effects of chronic hyperinsulinemia with or without insulin resistance on the autonomic control of heart rate (HR) in rats. METHODS: Male Sprague-Dawley rats were implanted subcutaneously with insulin (3 mU/kg x min) or vehicle-filled osmotic minipumps for 8 weeks. Insulin-infused rats were further divided into insulin resistant (IR) and insulin sensitive (IS) groups according to the results of the homeostasis model assessment method and euglycemic hyperinsulinemic clamp study. Autonomic function in HR control was indicated by arterial baroreflex sensitivity (BRS) after a bolus injection of phenylephrine or sodium nitroprusside. RESULTS: Compared with those in control group, plasma insulin levels were elevated about threefold and 1.5-fold in the IR and IS groups at the end of week 8, respectively. Blood glucose level remained basal in the IR group, but was significantly lower in the IS group. The elevated mean arterial pressure (MAP) observed in IR was not exhibited in IS. The HR and BRS in reflex tachycardia were significantly increased in the IR and IS groups, but the BRS in reflex bradycardia was not different among all rats. Propranolol eliminated the tachycardia and enhanced BRS responses in both groups. Methylatropine further accelerated tachycardia and diminished the enhanced BRS in the IR group. However, in IS, the enhanced BRS remained after methylatropine was given. The intrinsic HR was similar among all groups. The baseline MAP, HR, and BRS in reflex tachycardia were significantly correlated to plasma insulin levels but not to the Si value, an index of insulin sensitivity. CONCLUSIONS: The present results demonstrate that hyperinsulinemia but not insulin resistance is a dominant contributing factor to the development of arterial baroreflex abnormalities in this chronic hyperinsulinemic model, which may simultaneously enhance sympathetic nerve activity and possibly vagal withdrawal if insulin resistance coexisted.     

Elevated Glutathione Peroxidase in Newly Diagnosed Hypertension: Its Relation to Insulin Resistance

Several studies have reported that insulin resistance and compensatory hyperinsulinemia often coexist with hypertension. Increased activity of glutathione peroxidase has been reported in patients with essential hypertension. Recently, overexpression of glutathione peroxidase has also been linked to the etiology of insulin resistance. The aim of this study was to determine the possible relation between the activity of glutathione peroxidase and insulin resistance status in essential hypertensive patients. A case–control study was performed on 35 hypertensive patients and 30 control subjects. The levels of insulin and insulin resistance as measured by the homeostasis model assessment insulin resistance index (HOMA-IR) and glutathione peroxidase were significantly increased in hypertensive patients compared with control subjects. In this study, a direct association was observed between glutathione peroxidase with HOMA-IR and insulin levels in essential hypertensive subjects. In conclusion, our results suggest that increased glutathione peroxidase can be one of the detrimental factors in contributing to insulin resistance in essential hypertensive subjects.     

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。     

胰岛素抵抗与糖脂代谢

近些年,对胰岛素抵抗的认识逐渐增加,其在心脑血管疾病发展中所起的重要作用倍受关注.胰岛素抵抗时常伴有糖和脂代谢紊乱发生,通过异常的代谢途径最终使疾病向不可逆方向发展.因此,在改善胰岛素抵抗的同时,还要注重对糖和脂代谢的调节,即从整体对异常代谢环境进行治疗.     

糖尿病并高血压、高胰岛素血症

对１１２例Ⅱ型糖尿病（并高血压及无高血压各５６例和２０例高血压患者测定空腹胰岛索水平，发现高血压、糖尿病并高血压的胰岛素与血清甘油三酯水平均明显高于正常值，也高于糖尿病无高血压组（Ｐ＜０．００１）。糖尿病并高血压的并发症以冠心病为多。     

HOMA-Estimated Insulin Resistance Is Associated with Hypertension in Iranian Diabetic and Non-Diabetic Subjects

The relationship between insulin resistance (IR) and essential hypertension (HTN) is controversial. The aim of this study was to determine the association of IR estimated by homeostasis model assessment of insulin resistance (HOMA-IR) and HTN in a large sample of Iranian diabetic and non-diabetic population. A total of 2047 diabetic and non-diabetic individuals with or without HTN, aged 30–75 yrs, who were referred to a university general hospital between November 2004 and April 2007 were included in this study. Demographic data and anthropometric characteristics of participants were recorded. Fasting blood samples were collected, and fasting plasma glucose (FPG), serum creatinine, lipids, insulin, C-peptide and HbA1c were measured. HOMA-IR and HOMA derived Beta-cell function (HOMA-B) were also calculated. Age, sex and waist girth adjusted HOMA-IR values were compared between hypertensive and normotensive subjects. Hypertensive patients had significantly higher HOMA-IR than age-, sex-, and waist girth-adjusted normotensive individuals in both non-diabetic (2.163 ± 0.08 and 1.75 ± 0.03, p < 0.001) and diabetic (3.40 ± 0.10 and 3.07 ± 0.09, p < 0.05) groups. Multivariate logistic regression analysis showed that after adjustment for age, sex, waist girth, BMI, triglyceride, total cholesterol, FPG, and C-peptide, HOMA-IR was a significant independent predictor of HTN in all subjects (odds ratio = 1.117, CI 95% = 1.026–1.216, p < 0.05) and in diabetic and non-diabetic subjects separately (odds ratio?=?1.102, CI 95% = 1.009–1.203, p < 0.05 and odds ratio = 1.328, CI 95% = 1.116–1.580, p < 0.01, respectively). In conclusion, this study showed that IR is associated with HTN in Iranian diabetic and non-diabetic subjects.     

Homozygous Mutation in the Insulin Receptor Gene Associated with Mild Type A Insulin Resistance Syndrome: A Case Report

Insulin receptor (INSR) mutations lead to heterogeneous disorders that may be as severe as Donohue syndrome or as mild as “type A insulin resistance syndrome”. Patients with severe disorders usually harbor homozygous or compound heterozygous mutations. In contrast, type A insulin resistance syndrome has been associated with heterozygous mutations; homozygous mutations are rarely responsible for this condition. We report a novel, homozygous mutation, p.Leu260Arg in exon 3, of the INSR gene in a female adolescent patient with type A insulin resistance syndrome together with clinical details of her medical follow-up. Different mutations in the INSR gene cause different phenotype and vary depending on the inheritance pattern. This report adds to the literature, increases understanding of the disease mechanism and aids in genetic counseling.     

脂联素与胰岛素抵抗

脂联素是最近发现的一种脂肪特异性蛋白质、胰岛素、噻唑烷二酮类、β肾上腺能拮抗剂等 ,也参与调节脂联素的分泌与表达 ,动物实验及临床研究均表明 ,脂联素与空腹胰岛素浓度负相关 ,与胰岛素敏感指数正相关 ,罗格列酮治疗可使血浆脂联素明显增加 ,胰岛素敏感性增加。脂联素通过抑制单核细胞黏附 ,减低其细胞周期活性 ,降低血管壁脂蛋白的沉积 ,而抑制动脉硬化过程。     

Relationships Between Plasma Leptin and Insulin Concentrations,But Not Insulin Resistance,in Non-insulin-Dependent (Type 2) Diabetes Mellitus

In non-diabetic subjects, insulin concentrations and insulin resistance are clearly connected, and both correlate with leptin levels, making interpretations about mechanisms difficult. In non-insulin-dependent (Type 2) diabetes mellitus (NIDDM), however, insulin concentrations and insulin resistance are less closely associated. Therefore, we examined the relationship of plasma leptin concentrations within insulin resistance and insulin levels in 32 subjects with NIDDM, who underwent measurement of insulin resistance with an insulin sensitivity test. Plasma leptin was measured with an in-house monoclonal immunoradiometric assay. Fasting leptin level correlated with BMI (r = 0.78; p < 0.001), metabolic clearance rate of glucose (= −0.44; p = 0.015), and fasting specific insulin (r = 0.58; p = 0.001), but not with age, cholesterol, triglycerides or blood pressure (r = −0.26 to 0.21; p = NS). In linear regression analysis, after adjustment for BMI and gender, leptin concentrations correlated with those of insulin (partial r = 0.42; p = 0.025), but not insulin resistance (partial r = −0.10; p = NS). We conclude that in NIDDM, concentrations of plasma leptin are closely related to those of insulin per se and to obesity, but not to insulin resistance. Insulin may be an important regulator of leptin concentration in NIDDM. © 1997 by John Wiley & Sons, Ltd.     

胰岛素抵抗与脑梗死关系的研究

目的探讨胰岛素抵抗与脑梗死之间的关系.方法分别对30例无并发症脑梗死、40例合并有高血压脑梗死、20例合并有冠心病脑梗死及20例合并有高血压和冠心病脑梗死的病人及30例同期住院病人(对照组),进行空腹血糖(BG)、空腹血胰岛素(FINS)、胆固醇(TC)、三酰甘油(TG)、血尿酸(UA)、体重指数(BMI)等测定.结果 4组脑梗死病人分别与对照组相比,FINS水平明显升高,胰岛素敏感指数(ISI)显著降低(P<0.05).结论胰岛素抵抗与脑梗死有密切关系,可能是脑梗死的一个独立的重要危险因素.     

原发性高血压胰岛素抵抗与红细胞胰岛素受体的关系

目的探讨胰岛素受体和胰岛素敏感性指数之间的关系。方法用改良Ｇａｍｂｈａｉｒ法检测定３７例原发性高血压患者和１３例正常人的红细胞胰岛素受体，并以胰岛素敏感性指标作对照。结果高血压患者的红细胞胰岛素受体明显降低，和胰岛素敏感指数之间呈明显的负相关，而健康人的两者之间呈明显的正相关。结论高血压患者的胰岛素受体的减少在胰岛素抵抗发病上起重要作用。     

高血压病的胰岛素抵抗

对 17例治疗的 ,2 0例未治疗的高血压病人和 2 5例正常对照者 ,测定空腹及 75 g葡萄糖刺激后血浆葡萄糖和胰岛素浓度、红细胞胰岛素受体、血脂及脂蛋白。结果表明 :治疗和未治疗的高血压病人 ,血糖和胰岛素对葡萄糖刺激后的反应及胰岛素释放指数均显著高于对照组 ,血甘油三酯 (TG)、低密度脂蛋白(L DL )显著增高 ,高密度脂蛋白 (HDL )显著降低 ,红细胞胰岛素受体分析各组间差异无显著性。葡萄糖刺激后血浆胰岛素反应曲线下面积 (AIA )与收缩期和舒张期血压呈显著正相关 ,与TG,TC,L DL 也呈显著正相关 ,调整年龄、体重指数和血糖后 ,其相关性依然存在 ,说明高血压病存在着胰岛素抵抗 ,后者在高血压病因和临床中起重要作用     

Skeletal Muscle Vascular Function: A Counterbalance of Insulin Action

Insulin is a vasoactive hormone that regulates vascular homeostasis by maintaining balance of endothelial‐derived NO and ET‐1. Although there is general agreement that insulin resistance and the associated hyperinsulinemia disturb this balance, the vascular consequences for hyperinsulinemia in isolation from insulin resistance are still unclear. Presently, there is no simple answer for this question, especially in a background of mixed reports examining the effects of experimental hyperinsulinemia on endothelial‐mediated vasodilation. Understanding the mechanisms by which hyperinsulinemia induces vascular dysfunction is essential in advancing treatment and prevention of insulin resistance‐related vascular complications. Thus, we review literature addressing the effects of hyperinsulinemia on vascular function. Furthermore, we give special attention to the vasoregulatory effects of hyperinsulinemia on skeletal muscle, the largest insulin‐dependent organ in the body. This review also characterizes the differential vascular effects of hyperinsulinemia on large conduit vessels versus small resistance microvessels and the effects of metabolic variables in an effort to unravel potential sources of discrepancies in the literature. At the cellular level, we provide an overview of insulin signaling events governing vascular tone. Finally, we hypothesize a role for hyperinsulinemia and insulin resistance in the development of CVD.     

超重和肥胖成人心外膜脂肪组织和胰岛素抵抗的关系研究

目的研究超重和肥胖成人胰岛素敏感性、胰岛素抵抗及心外膜脂肪组织和胰岛素抵抗的关系。方法收集2005年3月至2005年12月在我院体检中心符合入选标准的资料210份,均具人体指标测量、空腹血生化检查和经超声测量心外膜脂肪组织厚度、腹壁脂肪厚度(SFT)等数据,根据中国肥胖工作组推荐的判定标准,分为超重肥胖组和体重正常组。采用稳态模式胰岛素抵抗指数(HOMA-IR)评价胰岛素抵抗。用SPSS 13.0软件进行统计分析。结果超重肥胖组SI显著低于体重正常组(P<0.01),FINS、HOMA-IR显著高于体重正常组(P<0.01),心外膜脂肪组织厚度明显厚于体重正常组(P<0.01);控制年龄、性别、腰围影响因素进行偏相关分析,显示心外膜脂肪组织厚度和FINS、HOMA-IR成正相关,相关系数分别为0.239、0.249,P<0.05;和SI成负相关,相关系数为0.249,P<0.05,SFT则与各个因素无相关性;逐步法多元线性回归分析显示,心外膜脂肪组织厚度和HOMA-IR呈正相关,标准化偏回归系数0.309,P<0.01,而SFT仅和BMI呈正相关。结论超重肥胖成人存在胰岛素敏感性降低、胰岛素抵抗,心外膜脂肪组织厚度和胰岛素抵抗成正相关,可能是新的心血管和代谢疾病的危险因素。     

The Influence of Insulin on the Raised Plasma Fibronectin Concentration in Human Obesity

ABSTRACT Plasma concentrations of fibronectin, free insulin, C-peptide and plasma glucose were determined in 40 morbidly obese subjects and in 51 normal weight controls, matched for sex and age. All plasma concentrations were significantly elevated (p<0.01) among the obese subjects. A significant correlation (r=0.34, p<0.05) between plasma fibronectin and plasma free insulin was found among the obese patients, but not among the controls (r=-0.02, p>0.05). No significant correlation was found between plasma fibronectin and plasma C-peptide, neither in the obese patients nor in the controls (obese r=0.06, controls r=0.02; p>0.05). Plasma fibronectin was insignificantly correlated with body weight (obese r=0.21, controls r=0.15; p>0.05) and percentage overweight (obese r=0.27, controls r=0.04; p>0.05). The raised level of circulating insulin may in part explain the excess of plasma fibronectin of obese subjects.