C-reactive protein is elevated in obese patients with the metabolic syndrome

C-reactive protein (CRP) is associated with increased risk for cardiovascular disease and diabetes. Few studies have evaluated the importance of CRP in those with the cluster of cardiovascular risk factors known as the metabolic syndrome (MS). We studied 190 overweight subjects (83 men and 107 women), aged 25-75 years, screened for glucose intolerance, in order to assess whether CRP levels vary according to the presence of MS, and to examine the relationship between CRP levels and metabolic variables. The prevalence of the Adult Treatment Panel III MS was 36.8%. Subjects with the MS had a higher degree of insulin resistance (IR), measured by the homeostasis model assessment (HOMA) method (5.4+/-0.4 versus 3.6+/-0.3, p<0.001) and higher frequency of glucose intolerance (78.3% versus 44.4%, p<0.001) than those without the MS. CRP values were increased among those with the MS (4.85+/-0.47 mg/l versus 3.34+/-0.36 mg/l, p<0.05). CRP correlated with waist circumference (r=0.28, p<0.001) and body mass index (r=0.38, p<0.001) in both men and women; however the relationship of CRP with HOMA(IR) was only evident in men (r=0.37, p<0.01) while the association with free fatty acids (FFA) was only significant in women (r=0.20, p<0.05), even after adjusting for age, hispanic ethnicity and glucose tolerance status. Abdominal obesity (elevated waist circumference) was the single most important MS component associated with increased CRP levels (>3mg/dl) (OR=3.1, 95% C.I.: 1.4-10.1), followed by female gender and smoking. These results confirm that CRP levels are elevated in MS subjects at risk for glucose intolerance. In addition waist circumference, HOMA(IR) and FFA levels are associated with CRP levels, suggesting potential roles of obesity, insulin resistance and lipolysis in the development of the subclinical inflammation associated with the MS.     

The impact of ethnicity on glucose regulation and the metabolic syndrome following gestational diabetes

Aims/hypothesis We assessed the impact of ethnic origin on metabolism in women following gestational diabetes mellitus (GDM). Materials and methods Glucose regulation and other features of the metabolic syndrome were studied at 20.0 (18.2–22.1) months (geometric mean [95% CI]) post-partum in women with previous GDM (185 European, 103 Asian-Indian, 80 African-Caribbean). They were compared with the same features in 482 normal control subjects who had normal glucose regulation during and following pregnancy. Results Impaired glucose regulation or diabetes by WHO criteria were present in 37% of women with previous GDM (diabetes in 17%), especially in those of African-Caribbean and Asian-Indian origin (50 and 44%, respectively vs 28% in European, p=0.009). BMI, waist circumference, diastolic blood pressure, fasting triglyceride and insulin levels, and insulin resistance by homeostatic model assessment (HOMA), were increased following GDM (p<0.001 for all, vs control subjects). Where glucose regulation was normal following GDM, basal insulin secretion (by HOMA) was high (p<0.001 vs control subjects). Irrespective of glucose regulation in pregnancy, Asian-Indian origin was associated with high triglyceride and low HDL cholesterol levels, and African-Caribbean with increased waist circumference, blood pressure, and insulin levels, together with insulin resistance and low triglyceride concentrations. Nonetheless, the GDM-associated features were consistent within each ethnic group. The metabolic syndrome by International Diabetes Federation criteria was present in 37% of women with previous GDM, especially in non-Europeans (Asian-Indian 49%, African-Caribbean 43%, European 28%, p=0.001), and in 10% of controls. Conclusions/interpretation Following GDM, abnormal glucose regulation and the metabolic syndrome are common, especially in non-European women, indicating a need for diabetes and cardiovascular disease prevention strategies.     

High-sensitivity C-reactive protein in patients with metabolic syndrome

High-sensitivity C-reactive protein (CRP) has been shown to predict cardiovascular disease. Metabolic syndrome has been found to play a critical role in the development of cardiovascular disease. The purpose of this report is to assess the relationship between CRP and the metabolic syndrome. A total of 50 patients with metabolic syndrome and 40 healthy persons were included in the study. Plasma concentrations of CRP were measured by means of particle-enhanced immunonephelometry with the Behring nephelometer using N Latex CRP mono reagent. CRP levels were higher in patients with metabolic syndrome than control group (10.6 +/-5.4 mg/L vs 3.5 +/-0.8 mg/L, p<0.001). In partial correlation, plasma CRP positively correlated with body mass index (p<0.001), waist circumference (p<0.001), waist-to-hip ratio (p<0.01), total cholesterol (p<0.001), LDL-cholesterol (p=0.033), triglyceride (p=0.023), and fasting blood glucose (p=0.043) in patients with metabolic syndrome. HDL-cholesterol did not significantly correlate with CRP (p>0.05). In multiple regression analysis, body mass index (p<0.01), waist circumference (p<0.01), and fasting blood glucose (p<0.01) showed independent correlations with plasma CRP. CRP levels were found higher in patients with metabolic syndrome. These results suggest that abdominal obesity is the critical correlates of elevated plasma CRP levels found in patients with metabolic syndrome. These patients carrying high risk for cardiovascular events must be followed closely.     

Associations between γ-glutamyl transferase, metabolic abnormalities and inflammation in healthy subjects from a population-based cohort： A possible implication for oxidative stress

AIM: To examine the relationships between gamma-glutamyl-transferase (GGT), alanine-aminotransferase (ALT), aspartate-aminotransferase (AST) and various metabolic parameters, C-reactive protein (CRP) and an oxidative stress marker (nitrotyrosine, NT) in subjects without any metabolic abnormalities from a population-based sample. METHODS: Two hundred and five subjects with normal body mass index (BMI), glucose tolerance, and without any metabolic abnormality were studied out of 1 339 subjects, without known liver diseases, alcohol abuse or use of hepatotoxic drugs, who are representative of the 45-64 aged population of Asti (north-western Italy). RESULTS: In all patients metabolic parameters and hs-CRP levels linearly increase from the lowest to the highest ALT and GGT tertiles, while in subjects without metabolic abnormalities, there is a significant association between fasting glucose, uric acid, waist circumference, hs-CRP, triglyceride values, and GGT levels. In these subjects, male sex, higher hs-CRP and glucose levels are associated with GGT levels in a multiple regression model, after adjustments for multiple confounders. In the same model, median NT levels are significantly associated with the increasing GGT tertile (beta = 1.06; 95%CI 0.67-1.45), but not with the AST and ALT tertiles. In a multiple regression model, after adjusting for age, sex, BMI, waist, smoking, and alcohol consumption, both NT (beta = 0.05; 95%CI 0.02-0.08) and hs-CRP levels (beta = 0.09; 95%CI 0.03-0.15) are significantly associated with fasting glycemia. CONCLUSION: GGT, an easy, universally standardized and available measurement, could represent an early marker of sub-clinical inflammation and oxidative stress in otherwise healthy individuals. Prospective studies are needed to establish if GGT could predict future diabetes in these subjects.     

Associations between γ-glutamyl transferase, metabolic abnormalities and inflammation in healthy subjects from a population-based cohort: A possible implication for oxidative stress

AIM: To examine the relationships between γ -glutamyltransferase (GGT), alanine-aminotransferase (ALT),aspartate-aminotransferase (AST) and various metabolic parameters, C-reactive protein (CRP) and an oxidative stress marker (nitrotyrosine, NT) in subjects without any metabolic abnormalities from a population-based sample.METHODS: Two hundred and five subjects with normal body mass index (BMI), glucose tolerance, and without any metabolic abnormality were studied out of 1339subjects, without known liver diseases, alcohol abuse or use of hepatotoxic drugs, who are representative of the 45-64 aged population of Asti (north-western Italy).RESULTS: In all patients metabolic parameters and hs-CRP levels linearly increase from the lowest to the highest ALT and GGT tertiles, while in subjects without metabolic abnormalities, there is a significant association between fasting glucose, uric acid, waist circumference,hs-CRP, triglyceride values, and GGT levels. In these subjects, male sex, higher hs-CRP and glucose levels are associated with GGT levels in a multiple regression model, after adjustments for multiple confounders.In the same model, median NT levels are significantly associated with the increasing GGT tertile (β = 1.06;95%CI 0.67-1.45), but not with the AST and ALT tertiles.In a multiple regression model, after adjusting for age,sex, BMI, waist, smoking, and alcohol consumption, both NT (β = 0.05; 95%CI 0.02-0.08) and hs-CRP levels (β =0.09; 95%CI 0.03-0.15) are significantly associated with fasting glycemia.CONCLUSION: GGT, an easy, universally standardized and available measurement, could represent an early marker of sub-clinical inflammation and oxidative stress in otherwise healthy individuals. Prospective studies are needed to establish if GGT could predict future diabetes in these subjects.     

Effects of a lifestyle modification program in HIV-infected patients with the metabolic syndrome

OBJECTIVES: A large percentage of HIV-infected patients receiving HAART develop the metabolic syndrome. In this study, we sought to determine whether lifestyle modification improves metabolic syndrome criteria, including waist circumference, blood pressure, fasting blood sugar, triglycerides, and HDL-cholesterol among HIV-infected patients with the metabolic syndrome. DESIGN: We conducted a randomized, 6-month study in HIV-infected patients with metabolic syndrome as defined by the National Cholesterol Education Program. Subjects were randomly assigned to an intensive lifestyle modification program, which included weekly one-on-one counseling sessions with a registered dietician, or observation (control group). METHODS: Metabolic syndrome criteria and cardiovascular parameters, including blood pressure, body composition, submaximal stress testing, lipids and other biochemical parameters were determined. RESULTS: Thirty-four patients were randomly assigned and 28 subjects completed the study. Compared with the control group, subjects randomly assigned to the lifestyle modification program demonstrated significant decreases in waist circumference (-2.6 +/- 1.1 versus 1.2 +/- 1.0 cm, P = 0.022), systolic blood pressure (-13 +/- 4 versus 4 +/- 4 mmHg, P = 0.008), hemoglobin A1C (-0.1 +/- 0.1 versus 0.2 +/- 0.1%, P = 0.017), lipodystrophy score (-1.2 +/- 0.3 versus 0.9 +/- 0.6, P = 0.006) and increased activity (17.7 +/- 14.3 versus -33.1 +/- 12.7 metabolic equivalents, P = 0.014) as measured by the Modifiable Activity Questionnaire, but lipid levels did not improve. CONCLUSION: These data demonstrate that intensive lifestyle modification significantly improved important cardiovascular risk indices in HIV-infected patients with the metabolic syndrome. Lifestyle modification may be a useful strategy to decrease cardiovascular risk in this population.     

Waist circumference estimation from BMI in Japanese children

Waist circumference, not BMI, is one of the factors in the definition of metabolic syndrome in adults. In children, waist circumference is also a well known predictor of metabolic syndrome. However, waist circumference measurement is not as commonly recorded as weight and height measurements in physical examinations in schools. This means BMI data is available for every child, but waist circumference is not. Therefore, we investigated whether there is an alternative way to estimate waist circumference even in those children whose waist circumference measurement has not been taken. We evaluated the relationship between BMI and the waist circumference of schoolchildren using a relatively large-scale population-based cohort in Japan. There was a significant linear relationship between BMI and waist circumference noted in each age- and sex-divided group [9-10-year-old boys: waist=13.99+2.63BMI (r=0.940, p<0.001), 9-10-year-old girls: waist=15.09+2.61BMI (r=0.933, p<0.001), 12-13-year-old boys: waist=23.67+2.22BMI (r=0.880, p<0.001), 12-13-year-old girls: waist=23.83+2.15BMI (r=0.859, p<0.001)]. This means it is possible to estimate waist circumference from height and weight, at least among those age groups of children in Japan. This estimation could be an alternative way and useful in detecting childhood metabolic syndrome or obesity disease in which a waist circumference figure is necessary.     

Insulin resistance, body mass index, waist circumference are independent risk factor for high blood pressure

OBJECTIVES: The purpose of the present study was to investigate the relationships between blood pressure (BP), insulin resistance as determined by a homeostasis model (HOMA-IR), and body fat distribution. METHODS: Anthropometric indices of adiposity, metabolic variables (fasting serum insulin and a homeostasis model assessment [HOMA] index of insulin sensitivity), BP and several cardiovascular risk factors were measured during a cross sectional survey of 53477 apparently healthy Korean subjects who requested a health status check. Hypertension was defined as a systolic BP > or = 140 mmHg or a diastolic BP > or = 90 mmHg and we excluded the subjects taking BP-lowering medication. RESULTS: Systolic and diastolic blood pressure (SBP, DBP) were positively and significantly associated with age, body mass index, waist circumference, and waist/hip ratio. In addition, SBP and DBP were positively associated with fasting serum insulin levels and the HOMA index. By multiple regression analysis age, waist circumference, body mass index, HOMA index and female sex were independently associated with either increased SBP or DBP. When the population is divided into quintiles according to insulin resistance (measured by HOMA analysis) prevalence of hypertension in the second, third, fourth and fifth quintiles compared to subjects in the first quintile are 1.004(95% CI 0.875-1.152, p = 0.957), 1.200(95% CI 1.052-1.369, p = 0.007), 1.312(95% CI 1.151-1.494 p < 0.001 ), and 1.603(95% CI 1.408-1.825 p < 0.001). In addition age, sex, body mass index and waist circumference were found to be significantly associated with hypertension. CONCLUSION: Our results showed that insulin resistance, body mass index and waist circumference are independent risk factors of a high BP in Koreans.     

Relation between leptin and the metabolic syndrome in elderly women

BACKGROUND: Leptin has been shown to be linked to adiposity and insulin resistance in middle-aged participants. However, the association between leptin and metabolic syndrome independently of body fat and body fat distribution has not been evaluated in healthy elderly people. METHODS: We studied the independent relation between leptin and the components of the metabolic syndrome in 107 women aged 67-78 years with body mass index (BMI) ranging from 18.19 to 36.16 kg/m2. In all participants, we evaluated BMI, waist and hip circumferences, body composition by dual energy X-ray absorptiometry, fasting, and 2-hour glucose, lipids, insulin, homeostasis model assessment of insulin resistance (HOMA), systolic (SBP), diastolic blood pressure (DBP), and leptin. RESULTS: Significant correlation was found between leptin, BMI, waist circumference, fat mass, DBP, SBP, cholesterol, triglycerides, insulin, and HOMA. After adjusting for age and waist circumference, as well for age and fat mass, leptin was significantly related to insulin levels, HOMA, and cholesterol. In a stepwise multiple regression analysis using insulin levels or HOMA as dependent variables and age, waist circumference, fat mass, leptin, SBP, DBP, cholesterol, and triglycerides as independent variables, leptin entered the regression first, waist circumference second, and age third. CONCLUSION: Our study shows that leptin is significantly related to indices of adiposity in elderly women, and leptin is significantly associated with insulin levels, HOMA, and cholesterol independent of age, body fat, and fat distribution. Leptin, waist circumference, and age together explained 31% and 33% of insulin levels and HOMA variance, respectively, in healthy elderly women.     

In normoglycemic Koreans, insulin resistance and adipocity are independently correlated with high blood pressure.

BACKGROUND: There is some controversy about the role of insulin resistance (IR) in the regulation of blood pressure (BP). Moreover, a large study of the association between BP and IR has not been conducted in normal glucose tolerance Asians. The present study investigated the relationships between IR, body mass index (BMI) and waist circumference and BP in normoglycemic Koreans. METHODS AND RESULTS: Anthropometric indices of adiposity, metabolic variables (fasting serum insulin and a homeostasis model assessment (HOMA) index of insulin sensitivity), BP and several cardiovascular risk factors were measured during a cross-sectional survey of 49,076 normoglycemic Korean subjects. A high BP was defined as a systolic BP >/=140 mmHg or a diastolic BP >/=90 mmHg. The prevalence of high BP by HOMA grading was 0.985 (95% confidence interval (CI) 0.857-1.132, p=0.835), 1.180 (95% CI 1.032-1.350, p=0.016), 1.289 (95% CI 1.129-1.472, p<0.001), and 1.540 (95% CI 1.341-1.768, p<0.001) times higher in subjects in the second, third, fourth, and fifth quintiles, respectively, compared with those in the first quintile. In addition, age, sex, waist circumference and BMI were found to be significantly associated with a high BP. CONCLUSION: IR, BMI and waist circumference are independently correlated with high BP in normoglycemic Koreans.     

Insulin Resistance,Body Mass Index,Waist Circumference are Independent Risk Factor for High Blood Pressure

Objectives: The purpose of the present study was to investigate the relationships between blood pressure (BP), insulin resistance as determined by a homeostasis model (HOMA‐IR), and body fat distribution. Methods: Anthropometric indices of adiposity, metabolic variables (fasting serum insulin and a homeostasis model assessment [HOMA] index of insulin sensitivity), BP and several cardiovascular risk factors were measured during a cross sectional survey of 53477 apparently healthy Korean subjects who requested a health status check. Hypertension was defined as a systolic BP ≥ 140 mmHg or a diastolic BP ≥ 90 mmHg and we excluded the subjects taking BP‐lowering medication. Results: Systolic and diastolic blood pressure (SBP, DBP) were positively and significantly associated with age, body mass index, waist circumference, and waist/hip ratio. In addition, SBP and DBP were positively associated with fasting serum insulin levels and the HOMA index. By multiple regression analysis age, waist circumference, body mass index, HOMA index and female sex were independently associated with either increased SBP or DBP. When the population is divided into quintiles according to insulin resistance (measured by HOMA analysis) prevalence of hypertension in the second, third, fourth and fifth quintiles compared to subjects in the first quintile are 1.004(95% CI 0.875–1.152, p=0.957), 1.200(95% CI 1.052–1.369, p=0.007), 1.312(95% CI 1.151–1.494 p < 0.001), and 1.603(95% CI 1.408–1.825 p < 0.001). In addition age, sex, body mass index and waist circumference were found to be significantly associated with hypertension. Conclusion: Our results showed that insulin resistance, body mass index and waist circumference are independent risk factors of a high BP in Koreans.     

藏族人群代谢综合征对早期动脉粥样硬化的影响

目的:探讨藏族人群代谢综合征对早期动脉粥样硬化的影响。方法:在查体的藏族人群中筛选代谢综合征(MS)患者。记录身高、体重、腰围、血压,测定空腹血糖(FPG)、空腹胰岛素(FINS)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDL-C)。超声检查颈动脉内中膜(IMT)厚度。结果:总共1187人参加筛选,其中MS患者206人。分为MS组和对照组。MS组的体重指数、收缩压、舒张压、TC、TG、FPG、FINS、胰岛素抵抗指数(HOMA指数)均显著高于对照组(P<0.01)。MS组的IMT较对照组增厚(P<0.001)。多元回归分析结果显示FPG、收缩压、舒张压、TG、HDL-C、腰围和HOMA指数均为颈动脉IMT的危险因子(P<0.05)。结论:藏族人群代谢综合征对早期动脉粥样硬化的形成有不利影响。     

Effect of age on interdependence and hierarchy of cardiovascular risk factors in hypertensive patients

The prognostic significance, interdependence, and hierarchy of cardiovascular risk factors could evolve with advancing age. Our study reports on the interdependence among blood pressure (BP), other metabolic syndrome components, and high-sensitivity C-reactive protein according to age in hypertensive subjects. A total of 5,712 nondiabetic patients (50.1% men, age range 40 to 95 years) evaluated in outpatient hypertension clinics were included and divided into 5 age groups (age 40 to 49, 50 to 59, 60 to 69, 70 to 79, and >80 years). BP, evaluated by both office and 24-hour ambulatory BP monitoring, and the metabolic and inflammation parameters were determined after a ≥2-week drug washout period. The prevalence of the metabolic syndrome (Adult Treatment Panel III definition) remained stable across the age groups. We observed a stable or increased association between waist circumference and insulin resistance (Homeostasis Model of Assessment-Insulin Resistance index) and fasting plasma glucose. However, the association between waist circumference and ambulatory BP monitoring systolic BP (r(2) decrease from 9.9% to 1.0%, p <0.001), high-density lipoprotein cholesterol (r(2) decreased from 21% to 4.9%, p = 0.002), and triglyceride levels (r(2) decreased from 17.5% to 1.9%, p <0.001) decreased with age. High-sensitivity C-reactive protein correlated with all metabolic syndrome components in all age groups (p <0.001 for all). It became the strongest determinant of ambulatory BP monitoring systolic BP (p <0.001) and high-density lipoprotein cholesterol (p <0.05) in patients >80 years old. In contrast, its association with waist circumference markedly decreased. In conclusion, hypertension and dyslipidemia, but not fasting plasma glucose, dissociate from central obesity with advancing age. They are increasingly determined by low-grade inflammation, independently of central obesity. These changing associations might underlie the weakening of obesity as a cardiovascular risk factor in older persons.     

非糖尿病人群中补体C3、超敏C反应蛋白与胰岛素抵抗指数(HOMA2-IR)相关性分析

目的 观察非糖尿病人群血清补体C3、超敏C反应蛋白(hs-CRP)水平及其与胰岛素抵抗的关系.方法 纳入587例非糖尿病个体,测定体重、身高、血压、腰围、空腹血浆葡萄糖、血清胰岛素、血脂、补体C3及hs-CRP等,计算胰岛素抵抗指数(HOMA2-IR).以HOMA2-IR上四分位为切点划分胰岛素抵抗与非胰岛素抵抗.结果 胰岛素抵抗人群补体C3和hs-CRP显著高于非胰岛素抵抗人群.校正性别、年龄、BMI及腰围后,部分相关分析发现补体C3与HOMA2-IR显著正相关(r=0.19,P＜0.01).去除性别、年龄、收缩压、舒张压、总胆固醇、甘油三酯、高密度脂蛋白胆固醇和腰围的影响后,随着补体C3的升高发生胰岛素抵抗的危险增加3.78倍(OR=3.78,P＜0.05);而hs-CRP与胰岛素抵抗的发生无统计学意义.结论 在非糖尿病人群中,补体C3与胰岛素抵抗的相关性强于hs-CRP.

Abstract：

Objective To observe and compare the association of serum levels of of complement component 3(C3)and high-sensitive C-reactive protein(hs-CRP)with insulin resistance in non-diabetic subjects. Methods 587non-diabetic Chinese were recruited. Weight, height, blood pressure, waist circumference, fasting plasma glucose,fasting serum insulin, blood lipids, C3 and hs-CRP were measured. HOMA index(HOMA2-IR)was calculated.Insulin resistance was defined as the upper quartile of HOMA2-IR. Results C3 and hs-CRP were significantly higher in subjects with insulin resistance compared with subjects without insulin resistance. After controlling for age, gender,body mass index, and waist circumference, C3 was positively and significantly correlated with HOMA2-IR(r = 0.19,P＜0.01). As C3 increased, subjects were 3.78(OR= 3.78, P＜0.05)times more likely to suffer from insulin resistance, after adjustment for age, gender, systolic blood pressure, diastolic blood pressure, total cholesterol,triglycerides,high-density lipoprotein cholesterol, and waist circumference. However, hs-CRP was not significantly correlated with insulin resistance. Conclusions Serum complement component 3 has a more marked association with insulin resistance than hs-CRP in non-diabetic Chinese.     

Neuroadrenergic and reflex abnormalities in patients with metabolic syndrome

Aims/hypothesis Previous studies have shown that alterations in vascular, metabolic, inflammatory and haemocoagulative functions characterise the metabolic syndrome. Whether this is also the case for sympathetic function is not clear. We therefore aimed to clarify this issue and to determine whether metabolic or reflex mechanisms might be responsible for the possible adrenergic dysfunction.Methods In 43 healthy control subjects (age 48.2±1.0 years, mean±SEM) and in 48 untreated age-matched subjects with metabolic syndrome (National Cholesterol Education Programs Adult Treatment Panel III Report criteria) we measured, along with anthropometric and metabolic variables, blood pressure (Finapres), heart rate (ECG) and efferent postganglionic muscle sympathetic nerve activity (microneurography) at rest and during baroreceptor manipulation (vasoactive drug infusion technique).Results Compared with control subjects, subjects with metabolic syndrome had higher BMI, waist circumference, blood pressure, cholesterol, triglycerides, insulin and homeostasis model assessment (HOMA) index values but lower HDL cholesterol values. Sympathetic nerve traffic was significantly greater in subjects with metabolic syndrome than in control subjects (61.1±2.6 vs 43.8±2.8 bursts/100 heartbeats, p<0.01), the presence of sympathetic activation also being detectable when the metabolic syndrome did not include hypertension as a component. Muscle sympathetic nerve traffic correlated directly and significantly with waist circumference (r=0.46, p<0.001) and HOMA index (r=0.49, p<0.001) and was inversely related to baroreflex sensitivity (r=–0.44, p<0.001), which was impaired in the metabolic syndrome.Conclusions/interpretation These data provide evidence that the metabolic syndrome is characterised by sympathetic activation and that this abnormality (1) is also detectable when blood pressure is normal and (2) depends on insulin resistance as well as on reflex alterations.     

Metabolic syndrome and insulin resistance in the TROPHY sub-study: contrasting views in patients with high-normal blood pressure

BACKGROUND: Although insulin resistance and metabolic syndrome are often used synonymously, concordance is not established. METHODS: Metabolic, hemodynamic, and hormonal data were analyzed on 141 patients in the Trial of Preventing Hypertension (TROPHY) Sub-Study with high-normal blood pressure (BP) (130 to 139/85 to 89 mm Hg [mean +/- SD, 133 +/- 8/85 +/- 6 mm Hg]; age, 48 +/- 9 years; body mass index 30 +/- 5 kg/m(2)). RESULTS: Fifty-three of 141 subjects (37.6%; approximately 3/8) had the metabolic syndrome based on three or more of the five risk factors (BP, waist circumference, fasting triglycerides, HDL-cholesterol, glucose). To maintain consistency in proportions, insulin resistance was defined as the upper 3/8 of the distribution on the homeostatic model assessment (HOMA), which uses fasting glucose and insulin and a modified Matsuda-DeFronzo index, based on fasting, 1- and 2-h glucose and insulin values. Among metabolic syndrome patients, 57% and 55% were in the upper 3/8 of the distribution for insulin resistance by HOMA and Matsuda-DeFronzo, respectively. Among subjects without the metabolic syndrome, 26% and 27% were insulin resistant by HOMA and Matsuda-DeFronzo criteria. The proportion of patients with metabolic syndrome and insulin resistance increased strongly and similarly with increasing body mass index. However, metabolic syndrome and insulin resistance were different compared with their respective controls in the lower 5/8 of the distribution, in waist/hip ratios, fasting and 1-h insulin, HDL-cholesterol, heart rate, and systolic BP responses to exercise and plasma renin, angiotensin, and aldosterone. CONCLUSIONS: The findings suggest that metabolic syndrome and insulin resistance are not synonymous anthropometrically, metabolically, hemodynamically, or hormonally in patients with high-normal BP.     

Association of adrenal steroids with hypertension and the metabolic syndrome in blacks

Blacks have a high prevalence of hypertension and adrenal cortical adenomas/hyperplasia. We evaluated the hypothesis that adrenal steroids are associated with hypertension and the metabolic syndrome in blacks. Ambulatory blood pressures, anthropometric measurements, and measurements of plasma renin activity (PRA), aldosterone, fasting lipids, glucose, and insulin were obtained in 397 subjects (46% hypertensive and 50% female) after discontinuing antihypertensive and lipid-lowering medications. Hypertension was defined as average ambulatory blood pressure >130/85 mm Hg. Late-night and early morning salivary cortisol, 24-hour urine-free cortisol, and cortisone excretion were measured in a consecutive subsample of 97 subjects (40% hypertensive and 52% female). Compared with normotensive subjects, hypertensive subjects had greater waist circumference and unfavorable lipid profiles, were more insulin resistant, and had lower PRA and higher plasma aldosterone and both late-night and early morning salivary cortisol concentrations. Twenty-four-hour urine-free cortisol and cortisone did not differ. Overall, ambulatory blood pressure was positively correlated with plasma aldosterone (r=0.22; P<0.0001) and late-night salivary cortisol (r=0.23; P=0.03) and inversely correlated with PRA (r=-0.21; P<0.001). Plasma aldosterone correlated significantly with waist circumference, total cholesterol, triglycerides, insulin, and the insulin-resistance index. Based on Adult Treatment Panel III criteria, 17% of all of the subjects were classified as having the metabolic syndrome. Plasma aldosterone levels, but not PRA, were elevated in subjects with the metabolic syndrome (P=0.0002). The association of aldosterone with blood pressure, waist circumference, and insulin resistance suggests that aldosterone may contribute to obesity-related hypertension in blacks. In addition, we speculate that relatively high aldosterone and low PRA in these hypertensive individuals may reflect a mild variant of primary aldosteronism.     

Is the white coat effect an alert reaction?

Is the white coat effect an alert reaction? In this cross-sectional study we compared the white coat effect on systolic blood pressure with the systolic blood pressure reactivity obtained during a stress test. The influence of the sympathetic system (LF band of systolic BP) and the parasympathetic system (HF band of pulse rate) on white coat systolic blood pressure and stress test systolic blood pressure were analysed. We stratified 174 subjects into two groups, according to their blood pressure: hypertensives (HT, n=44, BP>140/90 mmHg) and normotensives (NT, n=130). The BP was recorded during an occupational health consultation, over 24 hours, and beat to beat during a stress test (Finapress). White coat systolic BP was calculated as the difference between the consultation BP and the average systolic BP over 24 hours. The white coat systolic BP was not related with an increase in pulse rate. In contrast, during the stress test the increases in systolic BP and pulse rate were correlated (r=0.44; p<0.001). The white coat systolic BP was lower than the stress test systolic BP in the NT (6.6 +/- 7.2 vs 23 +/- 12 mmHg; p<0.001) and in the HT (16 +/- 11 vs 29 +/- 17 mmHg; p<0.001). The HT had a lower parasympathetic index than the NT (0.45 +/- 0.43 vs 0.92 +/- 0.83 bpm2; p<0.001). In the HT the white coat systolic BP was positively correlated with the stress test systolic BP (r=0.47: p<0.01) and negatively with the parasympathetic activity index. In conclusion, for recently diagnosed and untreated HT an early alteration of the parasympathetic system reveals that the white coat effect is a low amplitude alert reaction.     

Insulin resistance is associated with arterial stiffness in nondiabetic hypertensives independent of metabolic status.

We sought to determine whether insulin resistance (IR) is related to arterial stiffness in nondiabetic hypertensive patients, independent of metabolic status and gender. IR has been associated with increased arterial stiffness in patients with diabetes. In nondiabetic hypertensive patients, the correlation between IR and arterial stiffness has yet to be investigated. We enrolled 284 nondiabetic patients who were being treated for hypertension. At the time of enrollment, the patients underwent a baseline laboratory assessment including homeostatic model assessment (HOMA) IR index and pulse wave velocity (PWV). The HOMA IR index is used as a marker of IR, and brachial to ankle PWV (baPWV) was used as a marker of arterial stiffness. Of the 284 study subjects, 121 were classified as having metabolic syndrome. The patients with metabolic syndrome were older than the non-metabolic syndrome patients (55.4+/-10.7 vs. 52.1+/-11.6 years, p=0.013), but there was no gender difference between the two groups. The average baPWV was significantly higher in the patients with metabolic syndrome (1,506+/-235 vs. 1,435+/-211 cm/s, p=0.009). The HOMA index was independently associated with an increase in arterial stiffness (r=0.548, p<0.001) after controlling for age, systolic blood pressure (SBP), heart rate, medication and gender. The independent association of HOMA with arterial stiffness was demonstrated in subgroup analysis, regardless of the metabolic status and gender. In conclusion, increased IR was associated with arterial stiffness, independent of age, baseline SBP, gender and heart rate. This independent association of IR was demonstrated regardless of gender and metabolic status.     

Insulin sensitivity and hepatic steatosis in obese subjects with normal glucose tolerance

BACKGROUND AND AIM: Hepatic steatosis has recently been associated with insulin resistance and other metabolic abnormalities as a possible feature of the metabolic syndrome, but it is still uncertain how hepatic steatosis and insulin sensitivity are connected. Furthermore, obesity is a well characterized insulin resistant condition that is often associated with hepatic steatosis. The aim of this study was to verify whether hepatic steatosis further worsens insulin sensitivity in obese subjects by comparing the degree of insulin sensitivity in obese subjects with normal glucose tolerance on the basis of the presence or absence of hepatic steatosis. METHODS AND RESULTS: We analyzed 86 obese patients whose alcohol intake was less than 20 g/day and who showed no signs of viral hepatopathy. All of the subjects had normal glucose tolerance as shown by an oral glucose tolerance test. Insulin resistance was estimated using the homeostasis model assessment (HOMA) method and the diagnosis of steatosis was determined by an ultrasound scan of the liver. The subjects were comparable in terms of body mass index (BMI), lipid profile and serum uric acid levels; those with hepatic steatosis were slightly older and tended to have higher systolic blood pressure and fasting glycemia levels. The HOMA values were significantly higher in the group with hepatic steatosis (4.48 +/- 2.22 vs 3.11 +/- 1.47, p=0.002). There was no linear correlation between HOMA and alanine aminotransferase (ALT) levels, but a close linear correlation between HOMA and BMI (r=0.40; p<0.001). The effect of hepatic steatosis on HOMA remained significant after adjusting for age and gender (covariance analysis, p=0.006). When BMI was added to the covariance analysis, hepatic steatosis retained its statistical significance. CONCLUSION: Our data suggest that hepatic steatosis can increase insulin resistance independently of obesity.