M.T. Zanella

Effect of blood glucose on left ventricular mass in patients with hypertension and type 2 diabetes mellitus

The aim of our prospective study was to evaluate the influence of blood glucose (BG) on left ventricular mass and diastolic function in patients with hypertension and type 2 diabetes mellitus (DM). Fifty-six hypertensive patients with type 2 DM and 26 healthy controls were investigated. They were submitted to echocardiography (ECHO) with Doppler and we calculated the mean of their fasting BG values, office blood pressure (OBP), cholesterol and fractions, and triglycerides during the previous 4 years. The diabetic patients were then followed-up for 1 year with OBP, fasting BG, and lipids measured every 2 months. After this period, the patients were again submitted to ECHO and in 22 patients (group I [GI]), reductions greater than 10% in left ventricular mass index (LVMI) were observed (122 +/- 35 v 89 +/- 23 g/m2, P < .01), whereas increases greater than 10% (group II [GII], n = 17) (94 +/- 18 v 115 +/- 27 g/m2, P < .01) or no changes (group III [GIII], n = 17) (98 +/- 16 v 99 +/- 18 g/m2, NS) in LVMI were detected in the remaining patients. The OBP values did not change during the follow-up. In GI the reduction of LVMI was associated with a BG fall from 178 +/- 36 to 147 +/- 30 mg/dL (P < .01) and a correlation was observed between BG and LVMI percent variations (delta) (r = 0.48, P < .01). No important changes in left ventricular diastolic function were observed during the follow-up. We concluded that the improvement in glycemic control may contribute to LVH regression in hypertensive patients with type 2 DM.

Metabolic and haemodynamic effects of metformin in patients with type 2 diabetes mellitus and hypertension

SUMMARY

Serum Insulin Levels, 24-Hour Blood Pressure Profile, and Left Ventricular Mass in Nonobese Hypertensive Patients

In essential hypertensive patients, considered to be insulin-resistant, a blunted decline in nocturnal blood pressure is associated with increased adrenergic tone and left ventricular mass. Since insulin stimulates the sympathetic system, we tested whether insulin resistance and insulinemia influence left ventricular mass and the 24-hour blood pressure profile. We studied 29 nonobese hypertensive patients with office diastolic pressure between 95 and 110 mm Hg and normal oral glucose tolerance test after a 4-month washout period. They were then assigned to M-mode echocardiographic evaluation and 24-hour ambulatory blood pressure monitoring. The glucose and insulin responses to a 75-g oral glucose load were compared with those obtained in 16 weight-matched normotensive control subjects. During the oral glucose tolerance test the hypertensive patients compared with control subjects presented higher levels of glucose at 60 minutes (138.7 +/- 30.3 versus 108.7 +/- 35.7 mg/dL; P < .05) and 90 minutes (114.0 +/- 23.8 versus 94.8 +/- 31.1 mg/dL; P < .05) and insulin at 60 minutes (287.1 +/- 259.4 versus 142.1 +/- 83.9 pmol/L; P < .05). However, peak insulin levels after glucose load did not correlate with ambulatory blood pressure values or left ventricular mass index. Left ventricular mass index showed significant correlation with mean sleeping systolic pressure (rs = 56, P < .05) and diurnal systolic pressure (rs = .37, P < .05) but not with mean diurnal or sleeping diastolic pressures. In conclusion, our results indicate that in nonobese hypertensive patients, insulin resistance does not have any influence on the 24-hour blood pressure profile or on left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS)

The Role of Angiotensin II Antagonism in Type 2 Diabetes Mellitus: A Review of Renoprotection Studies

BACKGROUND Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in Western and Asian countries. Effective antihypertensive therapy reduces the rate of decline in renal function and postpones ESRD in patients with diabetic nephropathy. OBJECTIVE This review presents evidence from studies on how blood pressure control, plasma glucose control, and the presence of proteinuria determine outcomes in diabetic patients. The role of angiotensin II (All) in the development of diabetic nephropathy and the reno- and cardiobeneficial effects of AII antagonism in patients with type 2 diabetes mellitus (DM-2) and diabetic nephropathy also are addressed. METHODS Articles included in this review were found using a MEDLINE search for studies published from 1991 to 2001 and including the search terms diabetic nephropathy, type 2 diabetes mellitus, microalbuminuria, proteinuria, angiotensin receptor blockade, angiotensin-converting enzyme inhibition, and cardiovascular disease. Articles reporting new data, new mechanisms, major clinical trials, and our own data were included. RESULTS Recently, the Reduction of Endpoints in NIDDM (non-insulin-dependent diabetes mellitus) with the Angiotensin II Antagonist Losartan (RENAAL) trial provided sufficient data to conclude that the blockade of the All AT1 receptor with losartan confers renoprotection in patients with DM-2 and nephropathy. Similar results were obtained with irbesartan in the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria study (IRMA 2). The results of RENAAL indicate that the renoprotective effects of losartan were attributable to effects beyond blood pressure control. In addition to the favorable impact of the All blockade on blood pressure and renal hemodynamics, the blockade of the growth-promoting, profibrotic, nonhemodynamic actions of AII also may be important for renoprotection. Intensive blood pressure control also confers cardiovascular protection in pa- tients with DM-2. Some studies suggest that the blockade of the renin-angiotensin system confers superior cardioprotective effects in patients with DM-2. The RENAAL study also showed cardioprotection with losartan, with an important reduction in the risk for first hospitalization for heart failure. CONCLUSION Evidence supports the importance of an effective blockade of AII action for both reno- and cardioprotection in patients with DM-2.

Nitric oxide, cholesterol oxides and endothelium-dependent vasodilation in plasma of patients with essential hypertension

The objective of the present study was to identify disturbances of nitric oxide radical (.NO) metabolism and the formation of cholesterol oxidation products in human essential hypertension. The concentrations of.NO derivatives (nitrite, nitrate, S-nitrosothiols and nitrotyrosine), water and lipid-soluble antioxidants and cholesterol oxides were measured in plasma of 11 patients with mild essential hypertension (H: 57.8 +/- 9.7 years; blood pressure, 148.3 +/- 24.8/90.8 +/- 10.2 mmHg) and in 11 healthy subjects (N: 48.4 +/- 7.0 years; blood pressure, 119.4 +/- 9.4/75.0 +/- 8.0 mmHg). Nitrite, nitrate and S-nitrosothiols were measured by chemiluminescence and nitrotyrosine was determined by ELISA. Antioxidants were determined by reverse-phase HPLC and cholesterol oxides by gas chromatography. Hypertensive patients had reduced endothelium-dependent vasodilation in response to reactive hyperemia (H: 9.3 and N: 15.1% increase of diameter 90 s after hyperemia), and lower levels of ascorbate (H: 29.2 +/- 26.0, N: 54.2 +/- 24.9 micro M), urate (H: 108.5 +/- 18.9, N: 156.4 +/- 26.3 micro M), beta-carotene (H: 1.1 +/- 0.8, N: 2.5 +/- 1.2 nmol/mg cholesterol), and lycopene (H: 0.4 +/- 0.2, N: 0.7 +/- 0.2 nmol/mg cholesterol), in plasma, compared to normotensive subjects. The content of 7-ketocholesterol, 5alpha-cholestane-3beta,5,6beta-triol and 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol in LDL, and the concentration of endothelin-1 (H: 0.9 +/- 0.2, N: 0.7 +/- 0.1 ng/ml) in plasma were increased in hypertensive patients. No differences were found for.NO derivatives between groups. These data suggest that an increase in cholesterol oxidation is associated with endothelium dysfunction in essential hypertension and oxidative stress, although.NO metabolite levels in plasma are not modified in the presence of elevated cholesterol oxides.

Effects of sibutramine on abdominal fat mass, insulin resistance and blood pressure in obese hypertensive patients

Objective:  The objective of this study is to assess the effects of sibutramine on body weight, body fat distribution, insulin resistance, plasma leptin, lipid profile and blood pressure profiles in hypertensive obese patients.

Improved glycemic control by acarbose therapy in hypertensive diabetic patients: effects on blood pressure and hormonal parameters.

A double-blind, randomized, placebo-controlled study was carried out on 44 hypertensive type 2 diabetic subjects previously treated by diet associated or not with sulfonylurea to assess the effects of acarbose-induced glycemic control on blood pressure (BP) and hormonal parameters. Before randomization and after a 22-week treatment period (100 to 300 mg/day), the subjects were submitted to a standard meal test and to 24-h ambulatory BP monitoring (ABPM) and had plasma glucose, glycosylated hemoglobin, lipid profile, insulin, proinsulin and leptin levels determined. Weight loss was found only in the acarbose-treated group (75.1 +/- 11.6 to 73.1 +/- 11.6 kg, P<0.01). Glycosylated hemoglobin decreased only in the acarbose group (6.4 +/- 1.7 to 5.6 +/- 1.9%, P<0.05). Fasting proinsulin decreased only in the acarbose group (23.4 +/- 19.3 to 14.3 +/- 13.6 pmol/l, P<0.05), while leptin decreased in both (placebo group: 26.3 +/- 6.1 to 23.3 +/- 9.4 and acarbose group: 25.0 +/- 5.5 to 22.7 +/- 7.9 ng/ml, P<0.05). When the subset of acarbose-treated patients who improved glycemic control was considered, significant reductions in diurnal systolic, diastolic and mean BP (102.3 +/- 6.0 to 99.0 +/- 6.6 mmHg, P<0.05) were found. Acarbose monotherapy or combined with sulfonylurea was effective in improving glycemic control in hypertensive diabetic patients. Acarbose-induced improvement in metabolic control may reduce BP in these patients. Our data did not suggest a direct action of acarbose on insulin resistance or leptin levels.

Obesidade, hipertensão arterial e suas influências sobre a massa e função do ventrículo esquerdo

In order to evaluate the influences of obesity and hypertension on left ventricular mass (LVM), we studied 121 women stratified into 4 groups: normotensive non-obeses (n = 25), hypertensive non-obeses (n = 30), normotensive obeses (n = 24) and hypertensive obeses (n = 42) according to their anthropometric and echocardiographic parameters and ambulatory blood pressure monitoring (ABPM). Hypertensive obeses showed higher LVM than the other groups - normotensive non-obeses, hypertensive non-obeses and normotensive obeses (167 ± 38.8 vs. 113 ± 26.4; vs. 133 ± 26.5; vs. 132 ± 29.2g; respectively, p < 0.05) ond higher diameter of left atrium (LA) as compared to the non-obese groups with or without hypertension (36 ± 4.3 vs. 33 ±5.1; vs. 35 ± 3.9mm; p < 0.05, respectively). Normotensive obese patients showed similar LVM to the hypertensive non-obeses (133 ± 26.5 vs. 132 ± 29.5g; NS) and increased LA as compared to the normotensive non-obeses (35 ± 3.9 vs. 31 ± 4.6mm; p < 0.05). A correlation between the waist circumference and waist-to-hip ratio with the blood pressure levels obtained by the ABPM, as well as between these measurements with the echocardiographic parameters, which reflect cardiac mass; body mass index only showed to be correlated to the LA diameter. The adjustment of LVM by the height instead of body surface resulted in an increase on the prevalence of LV hypertrophy among obese patients (10.6 vs. 36.7%, p < 0.01), but not among non-obeses. Lack of nocturnal blood pressure fall assessed by ABPM (non-dipper) was more prevalent among obese patients with or without hypertension; however, non-dipper hypertensive obese patients did not differ from the dippers according to the LVM. Our data demonstrate that obesity associated to hypertension provoke a more pronounced increase in LVM as compared to the condition separately. We also conclude that obese patients showed increased frequency of abnormal 24-hr blood pressure profile, characterized by decreased tensional drop during sleep.

The imbalance of sex-hormones related to depressive symptoms in obese men

Abstract Obese men may present hypogonadothrofic hypogonadism, mainly related to higher insulinemia and aromatase activity. Our objectives were to evaluate the relationship of sex-hormones profiles and frequency of depressive symptoms in 43 obese men, in a cross-sectional study. They had 19–60 years, and body mass index 30–50 kg/m2. LH, total and free testosterone (TT and FT), estradiol (E2), sex hormone binding globulin, estradiol/total testosterone ratio (E2/T) were analyzed. Depressive symptoms were evaluated by “beck depression inventory” (BDI), and significant depression was considered if BDI ≥ 16.Thirty-four (80%) presented low TT levels, but only 4 (14%) had low free testosterone and hypogonadism symptoms; 12 of 43 (28%) presented increased E2. Forty five (56%) presented depressive symptoms, but 16 (28% of the 45) had significant depression. BDI correlated positively with E2 (r = 0.407; p = 0.001) and E2/T (r = 0.473; p = 0.001), but not TT or FT. Patients with significant depressive showed higher levels of estradiol (136 ± 48 versus 103 ± 48 pg/ml, p = 0.02) and E2/T (16.0 ± 9.9 versus 9.8 ± 4.6; p = 0.002) (mean ± SD).In conclusion, obese men may present relatively excess of estradiol and deficiency in testosterone, leading to an imbalance between these two hormones. The greater this imbalance, the more depressive symptoms had our patients.

Intima-media thickness evaluation by B-mode ultrasound: Correlation with blood pressure levels and cardiac structures

The aim of this study was to analyze the thickness of the intima-media complex (IMC) using a noninvasive method. The carotid and femoral common arteries were evaluated by noninvasive B-mode ultrasound in 63 normotensive and in 52 hypertensive subjects and the thickness of the IMC was tested for correlation with blood pressure, cardiac structures and several clinical and biological parameters. The IMC was thicker in hypertensive than in normotensive subjects (0.67 +/- 0.13 and 0.62 +/- 0.16 vs 0.54 +/- 0.09 and 0.52 +/- 0.11 mm, respectively, P<0.0001). In normotensive patients, the simple linear regression showed significant correlations between IMC and age, body mass index and 24-h systolic blood pressure for both the carotid and femoral arteries. In hypertensives the carotid IMC was correlated with age and 24-h systolic blood pressure while femoral IMC was correlated only with 24-h diastolic blood pressure. Forward stepwise regression showed that age, body mass index and 24-h systolic blood pressure influenced the carotid IMC relationship (r2 = 0.39) in normotensives. On the other hand, the femoral IMC relationship was influenced by 24-h systolic blood pressure and age (r2 = 0.40). In hypertensives, age and 24-h systolic blood pressure were the most important determinants of carotid IMC (r2 = 0.37), while femoral IMC was influenced only by 24-h diastolic blood pressure (r2 = 0.10). There was an association between carotid IMC and echocardiographic findings in normotensives, while in hypertensives only the left posterior wall and interventricular septum were associated with femoral IMC. We conclude that age and blood pressure influence the intima-media thickness, while echocardiographic changes are associated with the IMC.