Microalbuminuria and other cardiovascular risk factors in nondiabetic subjects.

The association between urinary albumin:creatinine ratio and other cardiovascular risk factors such as age, blood pressure, obesity, glycemic indices, insulin and lipid profile was examined in a population in a Chinese community consisting of 795 men (mean age 35.8 +/- 8.8 yr) and 538 women (mean age 37.9 +/- 8.9 yr) with a normal glucose tolerance defined by WHO criteria. Men with a urinary albumin:creatinine ratio above the 90th percentile had higher systolic and diastolic blood pressures, fasting plasma glucose, 2-h glucose after a 75 g oral glucose load, and fasting serum insulin. Women with high urinary albumin:creatinine values had higher systolic and diastolic blood pressures, body mass index, waist-hip ratio, fasting insulin and triglycerides. Multivariate analysis showed that only systolic blood pressure and fasting glucose in men, and diastolic blood pressure and fasting insulin in women, independently contributed to urinary albumin:creatinine. When the effect of blood pressure was eliminated by excluding subjects with systolic blood pressure > 140 and diastolic > 90 mm Hg, only fasting insulin was associated with urinary albumin:creatinine in women. No associations were found for men. We conclude that microalbuminuria may be a marker for cardiovascular disease only because of its association with blood pressure in men, while in women, there is an additional independent association with fasting serum insulin.     

Effect of indapamide SR in the treatment of hypertensive patients with type 2 diabetes

BACKGROUND: To evaluate the effect of the sustained-release formulation of indapamide (indapamide SR) in type 2 diabetic patients with mild-to-moderate hypertension and its possible side effects, particularly on glucose metabolism and lipid profiles. METHODS: A total of 64 patients randomly received 1.5 mg of indapamide SR or placebo once daily for 3 months. The effects were evaluated by 24-h ambulatory blood pressure monitor, fasting blood sampling for biochemistry, lipid profiles, and frequently sampled intravenous glucose tolerance test. RESULTS: The changes in standing and supine blood pressure (BP) were significant (154.7 +/- 9.4/94 +/- 2.9 mm Hg v 134.4 +/- 5.1/82.4 +/- 5 mm Hg and 155 +/- 9.8/94.6 +/- 3.6 mm Hg v 135.1 +/- 4.9/82.1 +/- 4.7 mm Hg) in the indapamide group, but not in the placebo group. According to the 24-h ambulatory blood pressure monitor reading, a significant reduction was observed in not only in the whole-day mean BP (mean systolic BP/mean diastolic BP, 149 +/- 19.3/87.6 +/- 11.3 mm Hg v 135.7 +/- 12.6/79.6 +/- 9 mm Hg) but also the whole-day mean median arterial pressure (109 +/- 12.7 mm Hg v 98.7 +/- 8.2 mm Hg) for the indapamide group, but not the placebo group. There were no changes in biochemical data including serum sodium, potassium, chloride, uric acid, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, lipid profiles, fasting blood glucose, insulin, hemoglobin Alc, and glucose metabolism parameters (insulin sensitivity, glucose effectiveness, and acute insulin response) from frequently sampled intravenous glucose tolerance test after indapamide or placebo therapy. CONCLUSIONS: Indapamide SR can significantly lower the whole-day BP in hypertensive patients with type 2 diabetes. Also, it did not alter or aggravate patients' lipid profiles, glucose metabolism, and did not exert possible side effects of hypokalemia and hyperuricemia. Therefore, monotherapy with indapamide SR should be suggested in type 2 diabetic patients with mild-to-moderate hypertension.     

Insulin resistance and hypertension in postmenopausal women

The aim of the study was to elucidate the role of hyperinsulinaemia/insulin resistance in hypertension of lean postmenopausal women. Twenty-four women with essential hypertension (systolic/diastolic > or =140/90 mm Hg) and a body mass index (BMI) less than 26 kg/m(2) not receiving antihypertensive treatment or who had been without treatment for a 4-week washout period, and 10 normotensive postmenopausal weight- and aged-matched controls were compared. Both groups were not receiving hormone replacement therapy. Hip and waist circumferences were measured and waist/hip ratios were calculated. Casual blood pressure was measured in triplicate. Neither the fasting plasma glucose nor serum insulin levels in hypertensive women and normotensives differed significantly. During 2 h oral glucose (75 g)-tolerance test the mean plasma glucose levels after 30 min (172.5 +/- 40.24 mg/dl vs. 143.67 +/- 20.16 mg/dl), 60 min (134.88 +/- 38.78 mg/dl vs. 112.33 +/- 5.44 mg/dl) and 120 min (116.08 +/- 26.65 mg/dl vs. 95.56 +/- 20.17 mg/dl) were significantly higher in hypertensives than that for normotensives (P < 0.05 for all three comparisons). The mean serum insulin levels of hypertensive women were significantly higher than that in normotensives after 15 min (92.04 +/- 59.90 microU/ml vs. 54.89 +/- 33.67 microU/ml) and 120 min (49.63 +/- 44.45 microU/ml vs. 19.22 +/- 24.10 microU/ml; P< 0.05 for both comparisons). The mean serum insulin: plasma glucose ratio for hypertensive women was significantly higher than that for normotensives after 15 min (0.596 +/- 0.46 vs. 0.359 +/- 0.20 microU/mg), 60 min (0.406 +/- 0.30 vs. 0.329 +/- 0.25 microU/mg) and 120 min (0.436 +/- 0.35 vs. 0.205 +/- 0.26 microU/mg) (P < 0.05 for all three comparisons). Significant correlations were observed between the daytime period and 24-h average ambulatory systolic blood pressure and the area under the serum insulin curve (r = 0.41 and 0.36, respectively). For non-dippers we found higher fasting insulinaemias but the AUC(insulin) did not differ. Plasma glucose levels did not differ either during fasting or during OGTT (AUC(glucose)). Insulinogenic index was higher in dippers than in non-dippers. We conclude that in lean, postmenopausal hypertensive women insulin resistance is increased compared with age- and weight-matched normotensive women. Also, hyperinsulinaemia correlates with ambulatory systolic blood pressure. Thus, insulin resistance may possibly be involved as a pathogenetic factor in lean, postmenopausal hypertensive women.     

A modified ambulatory arterial stiffness index is independently associated with all-cause mortality

Dependence of the ambulatory arterial stiffness index (AASI) on data scattering interferes with its potential clinical relevance. We assessed the correlates and all-cause mortality associations of a modified AASI (s-AASI). AASI was derived from the 24-h diastolic vs. systolic blood pressure linear regression line, whereas s-AASI was derived by symmetric regression (bisecting the line of diastolic vs systolic and systolic vs. diastolic). Of 2918 patients 55% were women; age was 56 +/- 16 years and body mass index was 27.3 +/- 4.5 kg/m(2). Average 24-h ambulatory blood pressure was 138 +/- 16/78 +/- 10 mm Hg. Applying the modified method for calculating AASI yielded a different measure: the negative correlation between AASI and blood pressure dipping (r = -0.304, P < 0.0001) was abolished (r = +0.223, P < 0.0001), s-AASI was more dependent on age (r = 0.266 vs. r = 0.089 for AASI), and prediction of all-cause mortality was enhanced; hazard ratio (95% confidence intervals) 1.17 (1.00-1.36) per 1 s.d. increase in s-AASI in the fully adjusted model as compared with 1.15 (0.97-1.36) for AASI.     

Hyperinsulinemia in patients with hypercholesterolemia.

An independent association between hypercholesterolemia and high insulin levels has not consistently emerged from large-scale epidemiologic observations. We selected 39 patients with elevated low-density (LDL) cholesterol levels but normal body weight, blood pressure, and glucose tolerance, and compared them to 36 normocholesterolemic, healthy control subjects accurately matched to the patients for age, gender, body mass index, and mean arterial blood pressure. Fasting serum total cholesterol concentrations and levels of LDL cholesterol, triglycerides, and apoprotein B were all higher in the patients with hypercholesterolemia than in controls (P < 0.025 or less), whereas high-density lipoprotein cholesterol and apoprotein A levels were significantly lower (P < 0.05 or less). Plasma insulin concentrations were elevated in hypercholesterolemic patients vs. controls both in the fasting state (86 +/- 6 vs. 59 +/- 8 pmol/L) and 2 h after a 75-g oral glucose load (412 +/- 16 vs. 276 +/- 18 pmol/L, P < 0.02 for both). Two-hour plasma glucose concentrations were also significantly raised in the patients (7.8 +/- 0.2 mmol/L) compared to controls (6.4 +/- 0.1 mmol/L, P < 0.025). In a multiple regression model including serum triglyceride concentrations, LDL cholesterol was still significantly related to both fasting and 2-h plasma insulin concentrations, contributing approximately 20% to the overall variability of these measures. Thus, in this group of patients with type IIa familial combined hyperlipoproteinemia hypercholesterolemia was associated with hyperinsulinemia even when controlling for other confounders (age, gender, body mass, glucose tolerance, and blood pressure).     

Changes in hemodynamics and left ventricular structure after menopause

To evaluate the cardiovascular changes associated with menopause, we studied hemodynamics at rest, ambulatory blood pressure, and left ventricular structure in a biracial cohort of pre- and postmenopausal women of similar age, race, weight, and blood pressure. Despite similar levels of blood pressure, postmenopausal women had a higher indexed peripheral resistance (2,722 +/- 757 vs 2,262 +/- 661 dynes.s.m(2)/cm(5), p <0.01) and a lower cardiac index (2.64 +/- 0.73 vs 3.10 +/- 0.71 L/min.m(2), p <0.01) than premenopausal women. Postmenopausal women also had less nocturnal decreases in both systolic (15 +/- 8 vs 19 +/- 8 mm Hg, p <0.01) and diastolic (12 +/- 6 vs 15 +/- 6 mm Hg, p = 0.05) pressures during ambulatory monitoring and higher levels of hematocrit (40 +/- 2% vs 38 +/- 3%, p <0.01). In association with this greater hemodynamic load, postmenopausal women had evidence of early concentric left ventricular remodeling, manifested by a greater relative wall thickness (0.38 +/- 0.06 vs 0.35 +/- 0.06, p <0.01) than that observed in premenopausal women. Differences between pre- and postmenopausal women in hemodynamics, diurnal blood pressure variation, and left ventricular structure were observed in white and African-American subjects. These results suggest that menopause is associated with hemodynamic changes and left ventricular remodeling, which may contribute to the enhanced cardiovascular risk observed in postmenopausal women.     

Pulse wave velocity as an index of arterial stiffness: a comparison between newly diagnosed (untreated) hypertensive and normotensive middle-aged Malay men and its relationship with fasting insulin

BACKGROUND: Arterial stiffness, an aging process which is accelerated by hypertension, is emerging as a useful index of vascular health. There are evidences to suggest that hyperinsulinaemia may be an independent risk factor for coronary artery disease, besides its possible pathogenic role in essential hypertension. The main objectives of this study were to compare arterial stiffness between untreated hypertensives and normotensives and to investigate the relationship between fasting serum insulin and arterial stiffness. METHODS: A cross-sectional observational study was designed. Forty normotensive (median age 47 +/- 6 yrs.) and twenty untreated hypertensive Malay men (median age 50 +/- 7 yrs.) without clinical evidence of cardiovascular complications were selected. Pulse wave velocity measured using the automated Complior machine was used as an index of arterial stiffness. Other measurements obtained were blood pressure, body mass index, fasting insulin, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, glucose and creatinine level. RESULTS: The blood pressure and pulse wave velocity (PWV) were significantly higher in the hypertensives compared to the normotensives (blood pressure 169/100 mm Hg +/- 14/7 vs. 120/80 mm Hg +/- 10/4, p < 0.001; PWV 11.69 m/s +/- 1.12 vs. 8.83 m/s +/- 1.35, p < 0.001). Other variables such as body mass index, fasting insulin, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides and haematocrit were comparable among the two groups. Within each group, there was a significant positive correlation between pulse wave velocity and systolic blood pressure (r = 0.76, p < 0.001 in normotensives; r = 0.73, p < 0.001 in hypertensives) and mean arterial pressure (r = 0.74, p < 0.001 in normotensives; r = 0.73, p < 0.001 in hypertensives). No correlation was noted between pulse wave velocity and diastolic blood pressure, age, body mass index, fasting insulin level, cholesterol, HDL-cholesterol, LDL-cholesterol or triglyceride levels. CONCLUSION: Arterial stiffness as determined by PWV is increased in newly diagnosed untreated hypertensive subjects even before clinically evident cardiovascular disease. However, arterial stiffness is not correlated with the fasting insulin level in normotensives and newly diagnosed hypertensives.     

Relationship between left ventricular mass index and 24-h urinary free cortisol and cortisone in essential arterial hypertension

OBJECTIVE: Besides arterial blood pressure, nonhemodynamic factors are known to induce cardiac hypertrophy. In Cushing's syndrome, severe ventricular hypertrophy has been linked not only to increased aortic pressure, but also to elevated plasma cortisol. The aim of this study was to examine the relationship between the cortisol/cortisone levels and left ventricular mass index (LVMI) in essential arterial hypertension with and without echocardiographic left ventricular hypertrophy (LVH). DESIGN: Eighteen untreated Caucasian patients (nine men, nine women, mean age 48+/-6 years) with essential hypertension (163+/-26/100+/-14 mm Hg) were enrolled. An age-matched control group of 13 subjects (seven men, six women) with normotension (121+/-9/79+/-7 mm Hg) were enrolled also. Left ventricular dimensions were echocardiographically assessed and cortisol production evaluated by 24-h urinary free cortisol and cortisone concentrations. RESULTS: LVMI averaged 115+/-31 g/m2 and 24-h urinary free cortisol and cortisone were 23+/-14 microg per 24 h and 31+/-18 microg per 24 h. Prevalence of echocardiographic LVH was 56%. LVMI correlated significantly with 24-h urinary free cortisol (r = 0.61, P = 0.007) and cortisone (r = 0.60, P = 0.009). Patients with echocardiographic LVH were characterized by higher daytime ambulatory blood pressure, LVMI (particularly the posterior wall), and 24-h urinary cortisol, while office blood pressure, septal: posterior wall ratio and 24-h urinary cortisone were comparable in all patients. In control individuals, LVMI averaged 91+/-18 g/m2 and 24-h urinary free cortisol and cortisone, respectively, were 34.7+/-6.6 microg per 24 h and 64.3+/-10.8 microg per 24 h (P<0.05 versus patients). Neither LVMI nor the contributing ventricular dimensions showed significant correlation with 24-h urinary free cortisol or cortisone in the control group. CONCLUSIONS: Our data provide evidence for a significant relationship between LVMI and cortisol production independently of arterial blood pressure in untreated mild to moderate hypertension.     

国产比索洛尔对高血压2型糖尿病患者糖代谢的影响

目的观察国产比索洛尔对高血压合并2型糖尿病患者糖代谢及血压的影响情况。方法将符合纳入标准的高血压合并2型糖尿病患者随机分组。观察治疗前后患者糖化血红蛋白(HbA1c)、空腹血糖、糖耐量和血压等的变化。结果共有92例患者完成研究,其中比索洛尔组47例,卡托普利组45例。治疗前和经12周治疗后两组HbA1c、空腹血糖、餐后2h血糖、收缩压和舒张压差异均无统计学意义(P=0.05)。结论本研究表明比索洛尔作为高选择性β1受体阻滞剂,对于原发性高血压合并2型糖尿病患者糖代谢无明显不良影响,同时具有良好的降压效果。     

高血压病患者动态血压参数与左室肥厚及颈动脉内-中膜厚度的关系

目的探讨高血压病患者动态血压参数对左室肥厚及颈动脉内-中膜厚度检测的意义.方法将初诊的高血压病患者147例经超声心动图和颈动脉超声检查分为左室肥厚组(n=45例)和非左室肥厚组(n=102例),颈动脉内-中膜增厚组(n=52例)和非内-中膜增厚组(n=95例),经询问病史、体检、测定动态血压参数,血脂、血糖等生化指标进行比较.结果 (1)左室肥厚组与非左室肥厚组的临床指标比较差异无统计学意义(P>0.05).(2)左室肥厚组与非左室肥厚组的动态血压参数比较分别为24 h平均收缩压(140.7±14.1)比(128.3±12.3)mm Hg(1 mm Hg=0.133 kPa),24 h平均舒张压(86.4±8.9)比(81.6±9.3)mm Hg,白昼平均收缩压(142.8±13.9)比(130.9±11.1)mm Hg,白昼平均舒张压(86.9±8.8)比(83.4±9.0)mm Hg,夜间平均收缩压(129.0±13.2)比(114.6±11.4)mm Hg,夜间平均舒张压(77.2±9.4)比(67.5±8.1)mm Hg,24 h脉压(54.2±10.2)比(46.9±9.6) mm Hg,白昼脉压(55.9±10.5)比(47.5±9.1)mm Hg,夜间脉压(51.8±10.7)比(47.1±8.7)mm Hg,24 h收缩压变异系数(8.4±2.0)比(7.2±1.9),24 h舒张压变异系数(9.5±2.2)比(8.0±2.1),动态血压非勺型昼夜节律55.6%比25.5%,其差异有统计学意义(P<0.05).(3)颈动脉内-中膜增厚组与非内-中膜增厚组的上述临床指标比较,差异无统计学意义(P>0.05),与动态血压参数比较差异有统计学意义(P<0.05).结论高血压病动态血压参数异常者左室肥厚及颈动脉内-中膜增厚的发生率增多.     

Cardiac arrhythmias and left ventricular hypertrophy in dipper and nondipper patients with essential hypertension

To evaluate the behavior of cardiac arrhythmias in dipper and nondipper hypertensive patients, 48-h ambulatory blood pressure monitoring, 24-h Holter electrocardiogram recording and echocardiographic studies were performed in 56 untreated outpatients with essential hypertension. These patients were divided into 2 groups according to the presence (dipper, n=33) or absence (nondipper, n=23) of reduction of both systolic and diastolic blood pressure during nighttime by an average of more than 10% of daytime blood pressure. Mean 48-h systolic and diastolic blood pressures did not differ between the 2 groups. Nondipper patients had a significantly larger left atrial dimension (31.9+/-3.8 vs 35.6+/-3.7 mm; p<0.01), left ventricular mass index (114+/-26 vs 136+/-36 g/m2; p<0.05), as well as a larger number of total supraventricular (16+/-19 vs 89+/-197 beats; p<0.05) and ventricular ectopic beats (7+/-14 vs 47+/-96 beats; p<0.05) during daytime as compared with dippers. In conclusion, nondipper hypertensive patients are likely to experience supraventricular and ventricular arrhythmias more frequently than dippers. A blunted nocturnal blood pressure fall may be involved in the appearance of cardiac arrhythmias in patients with essential hypertension.     

Adrenal incidentaloma: a new cause of the metabolic syndrome?

A number of patients with adrenal incidentaloma are exposed to a slight degree of cortisol excess resulting from functional autonomy of the adrenal mass (usually a cortical adenoma). At present, there are only scant data on the unwanted effects of this endocrine condition referred to as subclinical Cushing's syndrome. The aim of the present study was to look for some features of the metabolic syndrome in patients with incidental adrenal adenoma. Forty-one patients (9 men and 32 women) bearing adrenal incidentaloma with typical computed tomography features of cortical adenoma were studied. For both patients and controls, exclusion criteria were age equal to 70 yr or greater, previous history of fasting hyperglycemia, or impaired glucose tolerance (IGT), severe hypertension, current use of medication or concomitant relevant illnesses, and body mass index (BMI) equal to 30 kg/m(2) or greater. Forty-one patients with euthyroid multinodular goiter accurately matched for sex, age, and BMI served for a 1:1 case-control analysis. The study design included an oral glucose tolerance test (75 g) and an endocrine workup aimed at the study of the hypothalamic-pituitary-adrenal axis. Age and BMI were fully comparable between patients (54.0 +/- 10.7 yr, 23.8 +/- 2.4 kg/m(2)) and controls (52.2 +/- 11.6 yr, 23.5 +/- 2.8 kg/m(2)). Fasting glucose and fasting insulin levels were not different between the two groups (4.96 +/- 0.61 mmol/liter vs. 4.88 +/- 0.58 mmol/liter; 67 +/- 34 pmol/liter vs. 59 +/- 32 pmol/liter), but the 2-h postchallenge glucose was significantly higher in patients than in controls (7.43 +/- 2.49 mmol/liter vs. 6.10 plus minus 1.44 mmol/liter, P = 0.01). Fifteen patients (36%) reached the World Health Organization criteria for IGT and two other patients (5%) reached those for diabetes, and 14% of the controls qualified for IGT (P = 0.01). No difference in the lipid pattern was seen between the two groups, but either systolic or diastolic blood pressure were higher in patients (135.4 +/- 15.5 mm Hg vs. 125.0 +/- 15.6 mm Hg, P = 0.003; 82.9 +/- 9.1 mm Hg vs. 75.3 +/- 6.6 mm Hg, P < 0.0001). We calculated the whole-body insulin sensitivity index derived from the oral glucose tolerance test that was significantly reduced in the patients (4.3 +/- 1.7 vs. 5.7 +/- 2.5, P = 0.01). In a multiple regression analysis, 2-h glucose was associated with BMI and midnight cortisol values (r(2) = 0.36, P = 0.002). The comparison of the patients with nonfunctioning adenoma (n = 29) with those with subclinical Cushing's syndrome (n = 12) yielded significant differences as to 2-h glucose and triglyceride levels, which were significantly higher in the second group (7.02 +/- 1.76 mmol/liter vs. 8.72 +/- 3.17 mmol/liter, P = 0.03; 1.06 +/- 0.4 mmol/liter vs. 1.73 +/- 0.96 mmol/liter, P = 0.002), but the insulin sensitivity index was conversely reduced (5.2 +/- 1.4 vs. 2.9 +/- 1.2, P < 0.0001). In conclusion, many patients with incidental adrenal adenoma display altered glucose tolerance, that may be explained by reduced insulin sensitivity, and increased blood pressure levels in comparison with carefully age- and BMI-matched controls. The slight hypercortisolism observed in some such patients may significantly contribute to this state of insulin resistance. Midnight serum cortisol appears as a sensitive marker of the metabolic effects of subclinical Cushing's syndrome.     

Fasting insulin and leptin serum levels are associated with systolic blood pressure independent of percentage body fat and body mass index.

OBJECTIVE: To examine the relationship between leptin and insulin serum levels and systolic and diastolic blood pressure in young men. SETTING: Kobe University of Mercantile Marine, Kobe, Japan. Participants: One hundred and ninety-eight male students aged 18-20 years (comprising 100% of those eligible). DESIGN AND MEASUREMENTS: A cross-sectional survey of a sample of male college students was performed, with measurements to include anthropometry, blood pressure and blood tests after overnight fasting. RESULTS: Compared with 90 men with an optimal blood pressure, 56 men with high-normal and high blood pressure had an increase in body mass index (23.7 +/- 5.2 versus 20.4 +/- 2.2 kg/m2), percentage body fat (21.7 +/- 8.0 versus 16.3 +/- 4.2%) and serum leptin (3.7 +/- 4.7 versus 1.5 +/- 0.8 ng/ml). In addition, they had greater serum insulin (59 +/- 31 versus 43 +/- 12 pmol/l) despite there being no differences in plasma glucose, resulting in a reduction of the ratio of glucose to insulin (x 10(6)) (107 +/- 43 versus 126 +/-, which is an estimate of insulin sensitivity in a nondiabetic population. Furthermore, the 56 men had higher serum triglyceride levels, although there was no difference in low density lipoprotein-cholesterol and high density lipoprotein-cholesterol between men with optimal and high-normal plus high blood pressure. Similar differences were found between men in a top versus low tertile of systolic and diastolic blood pressure. In multiple regression analysis, both log leptin and log insulin emerged as determinants for systolic blood pressure independent of body mass index and percentage body fat, but an association with diastolic blood pressure was only shown for log leptin. CONCLUSION: Hyperleptinemia and hyperinsulinemia may be regulators of arterial pressure, independent of body mass index or percentage body fat.     

Ambulatory blood pressure reduction after rosiglitazone treatment in patients with type 2 diabetes and hypertension correlates with insulin sensitivity increase

BACKGROUND: Within the metabolic syndrome, insulin resistance and compensatory hyperinsulinemia are associated with blood pressure (BP) elevation through various potential mechanisms. Thiazolidinediones are antihyperglycemic agents that decrease insulin resistance. OBJECTIVE: To determine the effect of the thiazolidinedione rosiglitazone on BP and insulin resistance in patients with type 2 diabetes and hypertension. METHODS: In 20 subjects (nine men and 11 women) with type 2 diabetes but with a poor glycemic control, and with poorly controlled or newly diagnosed hypertension, rosiglitazone 4 mg daily was added-on therapy for 26 weeks. At baseline and at the end of the treatment period patients underwent ambulatory blood pressure monitoring, a hyperinsulinemic euglycemic clamp, and blood tests for glucose, insulin, HbA1c, lipids, and routine laboratory parameters. RESULTS: Insulin sensitivity estimated with the clamp significantly increased (Mbw/I index changed from 33.9 +/- 2.6 to 41.9 +/- 3.2 micromol/min per kg per nmol/l, P < 0.001) and the HOMA-IR index significantly decreased (6.34 +/- 0.39 versus 4.40 +/- 0.33, P < 0.001) during rosiglitazone treatment. Ambulatory BP presented small but significant reductions for the total 24-h period (135.3 +/- 1.8 versus 129.9 +/- 1.7 mmHg, P < 0.001 for systolic BP and 76.0 +/- 1.6 versus 71.9 +/- 1.6 mmHg, P < 0.001 for diastolic BP), daytime and night-time. The changes in systolic and diastolic BP correlated with the change in insulin sensitivity (r = -0.78, P < 0.01 and r = -0.68, P < 0.01, respectively). There were also significant reductions in fasting plasma glucose (9.39 +/- 0.41 versus 7.55 +/- 0.31 mmol/l, P < 0.001), insulin (94.0 +/- 0.41 versus 79.5 +/- 5.6 pmol/l, P < 0.01) and HbA1c (8.15 +/- 0.24 versus 7.24 +/- 0.19%, P < 0.001). CONCLUSIONS: Treatment of type 2 diabetic hypertensive patients with rosiglitazone significantly increased insulin sensitivity and lowered ambulatory BP. These changes were strongly correlated. Thiazolidinediones may thus possess a BP-lowering effect beyond their antihyperglycemic properties.     

Insulin resistance, beta-cell function, and glucose tolerance in Brazilian adolescents with obesity or risk factors for type 2 diabetes mellitus

OBJECTIVE: To evaluate insulin resistance (IR), beta-cell function, and glucose tolerance in 119 Brazilian adolescents with obesity or risk factors (RF) for type 2 diabetes mellitus (T2DM). STUDY DESIGN: We analyzed weight (kg), height (m), body mass index (BMI; kg/m(2)), waist (W; cm), acanthosis nigricans (AN), systolic and diastolic blood pressure (SBP and DBP; mm Hg), fasting plasma glucose (FPG), and 2-h plasma glucose (2hPG) on oral glucose tolerance test (OGTT; 1.75 g of glucose/weight), lipid profile [total cholesterol (TC), fractions, and triglycerides (TGs)], fasting insulin (FI) and 2-h insulin on OGTT (2hI-RIA), HOMA-B (%; beta-cell function--HOMA program), HOMA-S (%; insulin sensitivity--HOMA program) and HOMA-IR [fasting plasma insulin (mU/ml)xfasting plasma glucose (mmol/L)/22.5]. Division according to number of RF-family history of T2DM (FHT2DM), obesity, hypertension, dyslipidemia, polycystic ovary syndrome (PCOS), and AN. G1: subjects with no or one RF; G2: subjects with two or more RFs. Statistical data were nonparametrical. RESULTS: Fasting plasma glucose (G2: 81.6+/-10.2 vs. G1: 79.8+/-9.9 mg/dl) and 2hPG (88.1+/-18.0 vs. 87.0+/-19.9 mg/dl) were not different between G2 (n=67) and G1 (n=52), and all adolescents had normal glucose tolerance (NGT). Fasting insulin (13.0+/-7.9 vs. 7.6+/-3.9 microIU/ml; P<.001) and 2hI (60.2+/-39.1 vs. 38.3+/-40.0 microIU/ml; P<.001), HOMA-B (169.1+/-131.6% vs. 106.1+/-39.9%; P<.001), and HOMA-IR (2.62+/-1.7 vs. 1.52+/-0.8; P<.001) were higher in G2. HOMA-S (92.5+/-59.5% vs. 152.2+/-100.5%; P<.001) was also lower in this latter group. CONCLUSION: Brazilian adolescents with two or more RFs for the development of T2DM have higher IR and beta-cell function and lower insulin sensitivity. However, adolescents with impaired glucose tolerance (IGT) or DM have not been found, differently from similar studies. Differences in ethnic background, environment, and lifestyle factors may account for this disparity.     

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.     

Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men

We determined whether interindividual variation in hepatic insulin sensitivity could be attributed to variation in liver fat content (LFAT) independent of obesity. We recruited 30 healthy nondiabetic men whose LFAT (determined by proton spectroscopy); intraabdominal, sc, and total (determined by magnetic resonance imaging) fat; and insulin sensitivity of endogenous glucose rate of production (R(a)) and suppression of serum FFA [euglycemic insulin clamp combined with [3-(3)H]glucose (0-300 min); insulin infusion rate, 0.3 mU/kg.min, 120-300 min] were measured. The men were divided into groups of low (mean +/- SD, 1.7 +/- 0.2%) and high (10.5 +/- 2.0%) LFAT based on their median fat content. The low and high LFAT groups were comparable with respect to age (44 +/- 2 vs. 42 +/- 2 yr), body mass index (25 +/- 1 vs. 26 +/- 1 kg/m(2) ), waist to hip ratio (0.953 +/- 0.013 vs. 0.953 +/- 0.013), maximal oxygen uptake (35.6 +/- 1.5 vs. 33.5 +/- 1.5 ml/kg.min), and intraabdominal, sc, and total fat. The high compared with the low LFAT group had several features of insulin resistance, including fasting hyperinsulinemia (7.3 +/- 0.6 vs. 5.3 +/- 0.6 mU/liter; P < 0.02, high vs. low LFAT) hypertriglyceridemia (1.4 +/- 0.2 vs. 0.9 +/- 0.1 mmol/liter; P < 0.02), a low high density lipoprotein (HDL) cholesterol concentration (1.4 +/- 0.1 vs. 1.6 +/- 0.1 mmol/liter; P < 0.05), and a higher ambulatory 24-h systolic blood pressure (130 +/- 3 vs. 122 +/- 3 mm Hg; P < 0.05). Basal glucose R(a) and serum FFA were comparable between the groups, whereas insulin suppression of glucose R(a) [51 +/- 8 vs. 20 +/- 12 mg/m(2).min during 240-300 min (P < 0.05) or -55 +/- 7 vs. -85 +/- 12% below basal (P < 0.05, high vs. low LFAT)] and of serum FFA (299 +/- 33 vs. 212 +/- 13 micromol/liter; 240-300 min; P < 0.02) were impaired in the high compared with the low LFAT group. Insulin stimulation of glucose Rd were comparable in the men with high LFAT (141 +/- 12 mg/m(2).min) and those with low LFAT (156 +/- 14 mg/m(2).min; P = NS). Fat accumulation in the liver is, independent of body mass index and intraabdominal and overall obesity, characterized by several features of insulin resistance in normal weight and moderately overweight subjects.     

Effect of estrogen replacement therapy on insulin sensitivity of glucose metabolism and preresistance and resistance vessel function in healthy postmenopausal women

In the present study, we hypothesized that estradiol, via its ability to vasodilate in an endothelium-dependent manner, might enhance vascular effects of insulin. Basal and insulin-stimulated peripheral blood flow and resistance, arterial stiffness, and glucose metabolism were determined in 27 healthy postmenopausal women before and after 12 weeks of treatment with either transdermal or oral estradiol or corresponding placebo preparations. Whole body insulin sensitivity was determined using the euglycemic insulin clamp technique (rate of continuous insulin infusion 1 mU/kg.min), forearm blood flow with a strain-gauge plethysmography, and arterial stiffness using pulse wave analysis. Estradiol therapy increased basal peripheral blood flow (1.5 +/- 0.1 vs. 1.9 +/- 0.1 mL/dL.min, 0 vs. 12 weeks; P: < 0.01), decreased peripheral vascular resistance (65 +/- 3 vs. 52 +/- 3 mm Hg/mL/dL.min, respectively; P: < 0.01), and diastolic blood pressure (78 +/- 2 vs. 75 +/- 2 mm Hg, respectively; P: < 0.05) but had no effect on large artery stiffness. Infusion of insulin did not acutely alter peripheral blood flow but diminished large artery stiffness significantly both before and after the 12-week period of estradiol therapy. No measure of acute insulin action (glucose metabolism, blood flow, or large artery stiffness) was altered by estradiol or placebo treatment. These data demonstrate that insulin and estradiol have distinct hemodynamic effects. Physiological doses of estradiol increase peripheral blood flow but have no effects on large artery stiffness, whereas physiological concentrations of insulin acutely decrease stiffness without changing peripheral blood flow. Putative vasculoprotection by estradiol is, thus, not mediated via alterations in arterial stiffness or insulin sensitivity.     

Effect of body weight changes on 24-hour blood pressure and left ventricular mass in hypertension: a 4-year follow-up

BACKGROUND: Few data are available on the long-term effects of weight loss on 24-h blood pressure (BP) and left ventricular mass in overweight hypertensive patients. METHODS: A total of 181 never-treated overweight hypertensive subjects (body mass index, 25 to 39 kg/m(2), office BP 145/94 +/- 12/7 mm Hg) had 24-h BP monitoring and echocardiography twice, at baseline and after 3.8 +/- 2 years (minimum 1 year). None of the subjects received antihypertensive drugs during the follow-up. Main outcome measures were changes in 24-h BP and in left ventricular mass. RESULTS: Percent change in body weight had a direct relationship with 24-h BP changes (r = 0.35 and 0.31 for systolic and diastolic BP, respectively; both P <.001). The associations with office BP changes (r = 0.13, P =.10 for systolic BP; r = 0.15, P =.06 for diastolic BP) were significantly weaker (both P <.01, z test). The patients who lost weight during follow-up (n = 106) had a significantly lower increase in 24-h BP (+0.6 +/- 9/ +0.2 +/- 6 v +4.9 +/- 9/ +2.7 +/- 7 mm Hg for systolic/diastolic BP, both P <.01) and in left ventricular mass (-3 +/- 30 g v +9 +/- 32 g, P <.02) than the remaining subjects. In a multiple linear regression, a 10% weight loss independently predicted a 4.3/3.8 mm Hg decrease in 24-h systolic/diastolic BP. CONCLUSIONS: Long-term weight loss determines a sustained BP reduction during the 24 h and a decrease in left ventricular mass in overweight hypertensive subjects. The relation of weight loss with ambulatory BP changes is closer than that with office BP.     

Echocardiographic left ventricular mass and electrolyte intake predict arterial hypertension

OBJECTIVE: To identify predictors of arterial hypertension. PATIENTS: One hundred thirty-two normotensive adults from a large employed population. METHODS: Echocardiography, standard blood tests, and 24-hour urine collection, at baseline and after an interval of 3 to 6 years (mean, 4.7 +/- 0.8 years). RESULTS: At follow-up, 15 subjects (11%; 7 men, 8 women) had a systolic blood pressure greater than 140 mm Hg or a diastolic blood pressure greater than 90 mm Hg or both (mean, 143 +/- 7 and 87 +/- 6 mm Hg, respectively). At baseline, subjects who developed hypertension had a greater left ventricular mass index than those who did not (92 +/- 25 compared with 77 +/- 19 g/m2 body surface area; P less than 0.005) and higher 24-hour urinary sodium/potassium excretion ratio (3.6 +/- 1.7 compared with 2.6 +/- 1.4; P less than 0.04); there were no differences in race, initial age, systolic or diastolic blood pressure, coronary risk factors, or plasma renin activity. The likelihood of developing hypertension rose from 3% in the lowest quartile of sex-adjusted left ventricular mass index to 24% in the highest quartile (P less than 0.005); a parallel trend was less regular for quartiles of the sodium/potassium excretion ratio (P less than 0.04). In multivariate analyses, follow-up systolic pressures in all subjects and in the 117 who remained normotensive were predicted by initial age, systolic blood pressure, black race, and sex-adjusted left ventricular mass index; final diastolic blood pressure was predicted by its initial value, plasma triglyceride levels, urinary sodium/potassium ratio, low renin activity, black race, and plasma glucose level. CONCLUSIONS: Echocardiographic left ventricular mass in normotensive adults is directly related to the risk for developing subsequent hypertension. Left ventricular mass improves prediction of future systolic pressure, whereas diastolic pressure is more related to initial metabolic status. Black race is also an independent determinant of higher subsequent blood pressure.