[Sickle cell syndrome. Association between hemoglobin S and ß thalassemia]. / Síndrome drepanocítico. Asociación de hemoglobina S y ß talasemia.

Sickle cell syndrome HbS/ß thalassemia is an inheritable mendelian type disease where two affected alleles are simultaneously present, one from HbS (ßS) and the other from ß thalassemia. That situation is mainly linked to individuals who share African and Mediterranean ancestors. The mutation responsible for HbS is a point mutation, whereas for ß thalassemia, there are more than 200 mutations that cause different degrees of deficiency synthesis of ß globin chain, which justifies the clinical and genetic heterogeneity of this syndrome. It is presented a clinical case of a young adult man with limited resources that consulted by longstanding bone pain. The patient presented anemia with a marked microcytosis. Hemoglobin electrophoresis was performed, an abnormal peak in position of HbS and high HbA2 fraction were detected. These last results indicated two possible molecular alterations simultaneously, for this reason the molecular study was performed looking for the most common ß thalassemia mutations in our population and, the point mutation responsible for S hemoglobinopathy. Clinical data and biochemical laboratory allowed the diagnosis of sickle cell syndrome. The molecular study confirmed the syndrome carrying mutations IVS-I nt 110 G > A, responsible for ß thalassemia and, codon 6 A > T (GAG → GTG: Glu → Val) responsible for S hemoglobinophaty. Since it is a disease of high health impact, it is important to provide genetic counseling to the whole family.

Síndrome drepanocítico: Asociación de hemoglobina S Y &ß talasemia / Sickle cell syndrome. Association between hemoglobin S and ß thalassemia

El síndrome drepanocítico HbS/β talasemia responde a la herencia de tipo mendeliana en simultáneo de un alelo βs de la hemoglobina S (HbS) y un alelo de β talasemia. Vinculado fundamentalmente a individuos que comparten ascendencia africana y de países del Mediterráneo. La mutación responsable de la HbS es puntual, mientras que para la β talasemia existen más de 200 mutaciones que causan diferentes grados de deficiencia de síntesis de la cadena de β globina, lo cual justifica la heterogeneidad clínica y genética de este síndrome. Se presenta el caso clínico de un adulto joven de escasos recursos que consulta por dolores óseos de larga data. Registra hemogramas con anemia y marcada microcitosis. Se le realizó electroforesis de Hb detectándose un pico anómalo en posición de HbS y elevada fracción de HbA2. El resultado de la electroforesis de hemoglobina indica dos posibles alteraciones moleculares en simultáneo, por tal motivo se realizó el estudio molecular de las mutaciones más frecuentes en nuestra población de β talasemia y de la mutación puntual responsable de la hemoglobinopatía S. A partir de la clínica y datos del laboratorio bioquímico se diagnosticó el síndrome drepanocítico y se confirmó por biología molecular la portación de las mutaciones IVS-Int 110 G > A (β talasemia) y del codón 6 A > T (GAG→GTG: Glu→Val) responsable de la hemoglobinopatía S. Dado que es una enfermedad de alto impacto sanitario, es importante un adecuado asesoramiento genético a toda la familia.

Sickle cell syndrome HbS/β thalassemia is an inheritable mendelian type disease where two affected alleles are simultaneously present, one from HbS (βS) and the other from β thalassemia. That situation is mainly linked to individuals who share African and Mediterranean ancestors. The mutation responsible for HbS is a point mutation, whereas for β thalassemia, there are more than 200 mutations that cause different degrees of deficiency synthesis of β globin chain, which justifies the clinical and genetic heterogeneity of this syndrome. It is presented a clinical case of a young adult man with limited resources that consulted by longstanding bone pain. The patient presented anemia with a marked microcytosis. Hemoglobin electrophoresis was performed, an abnormal peak in position of HbS and high HbA2 fraction were detected. These last results indicated two possible molecular alterations simultaneously, for this reason the molecular study was performed looking for the most common β thalassemia mutations in our population and, the point mutation responsible for S hemoglobinopathy. Clinical data and biochemical laboratory allowed the diagnosis of sickle cell syndrome. The molecular study confirmed the syndrome carrying mutations IVS-I nt 110 G > A, responsible for β thalassemia and, codon 6 A > T (GAG → GTG: Glu → Val) responsible for S hemoglobinophaty. Since it is a disease of high health impact, it is important to provide genetic counseling to the whole family.

Lean and fat mass loss in obese patients before and after Roux-en-Y gastric bypass: a new application for ultrasound technique.

OBJECTIVE: This study aims to evaluate the thickness of the femoral quadriceps and biceps brachii and brachialis muscles bilaterally and the adjacent subcutaneous fat in patients undergoing gastric bypass Roux-en-Y before and after surgery, using ultrasound as the diagnostic method of choice. METHODS: We studied 12 patients undergoing this surgical method preoperatively and during the first, third, and sixth postoperative months. During these periods, patients were evaluated by ultrasound to determine the thickness of subcutaneous adipose tissue and muscle of the upper and lower limbs. RESULTS: Postoperatively, these patients showed a reduction in the thickness of the upper and lower extremities muscle and adipose tissue as compared to their preoperative values. There was a significant difference in the loss of muscle thickness in all postoperative months and in the thickness of fatty tissue in the sixth month after surgery, compared to the preoperative muscle and fatty tissue thickness. CONCLUSIONS: Ultrasound can be considered as the diagnostic method of choice when assessment of the fat and lean body mass is required in morbidly obese patients before and after bariatric surgery.

Effects of fluvastatin on insulin resistance and cardiac morphology in hypertensive patients.

Among hypertensive patients, cardiovascular disease morbidity is common, even in those who are adequately treated. New pharmacological strategies to mitigate the burden of arterial hypertension are needed. This 12-month, randomized, double-blind placebo-controlled study investigated the effect of statin (fluvastatin) treatment on ambulatory blood pressure (ABP), exercise blood pressure (EBP), myocardial structure, endothelial function and insulin resistance in 50 hypertensive patients. At baseline, the groups were comparable in terms of demographic characteristics, ABP, EBP, endothelial function and homeostasis model assessment of insulin resistance (HOMA-IR). At the end of the study, there was no difference between groups in terms of resting systolic blood pressure. However, maximum systolic EBP was lower in the treatment group than in the placebo group (175 ± 18 vs 192 ± 23 mm Hg, P<0.05), as was left ventricular mass index (LVMI; 82 ± 15 vs 100 ± 23, P<0.05), and HOMA-IR index was lower after fluvastatin treatment (2.77 ± 1.46 vs 3.33 ± 1.73, P<0.05). Changes in lipid profile were not correlated with blood pressure, endothelial function, LVMI or HOMA-IR data. In hypertensive patients, fluvastatin can improve maximum systolic EBP, myocardial remodelling and insulin resistance, independently of lipid profile variations and endothelial function.

Association of carotid intima-media thickness and cardiovascular risk factors in women pre- and post-bariatric surgery.

BACKGROUND: Obesity is associated with cardiovascular risk factors (CVRFs), such as hypertension, hypertriglyceridemia, and low levels of high-density cholesterol (HDL-C). In obese patients with a body mass index (BMI) of >or=40 kg/m2 or 35-40 kg/m2 associated with CVRFs, weight loss may be achieved more effectively by bariatric surgery on reducing several CVRFs. Carotid intima-media thickness (C-IMT) is an indicator of early atherosclerosis, and may be correlated with CVRFs. Our objective was to correlate C-IMT with CVRFs before (baseline data) and after surgery, and to observe whether weight loss is followed by a regression of C-IMT. METHODS: Eighteen women who had undergone bariatric surgery participated in this study. Assessments were carried out on the baseline date, and 3, 6, and 12 months after surgery. Some of the CVRFs analyzed were: total cholesterol (TC) levels, HDL-C, triglycerides to HDL-C ratio (TG/HDL-C) and fasting plasma glucose. C-IMT was measured by B-mode ultrasound. RESULTS: A positive correlation was found between C-IMT and age and triglyceride level (p=0.002 and p=0.02, respectively). Six months after surgery, we found a significant reduction in C-IMT (p<0.05), which was significantly correlated with TG level and systolic pressure (p<0.05). CONCLUSION: The weight loss achieved with bariatric surgery resulted in regression of C-IMT. This regression could be observed 6 months following surgery, with an additional benefit at 12 months. Also, this finding was correlated with a reduction in triglyceride levels and systolic blood pressure.

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. METHODS: Eighty-six central obese hypertensive patients (BMI = 39 +/- 5 kg/m(2), 84% of women, 48 +/- 8.5 years old) were placed on a hypocaloric diet and placebo therapy for 4 weeks. They were then randomized to receive sibutramine (10 mg) or placebo for 24 weeks. Both, before therapy and at the end of the study, the waist and hip circumferences were measured and the waist/hip ratio (WHR) was calculated; abdominal ultrasonography was performed in order to estimate the amount of subcutaneous fat (SF) and visceral fat (VF), and the visceral/subcutaneous ratio. Beyond HOMA-r, another insulin resistance index (IRIp) was calculated by means of the formula: peak of blood glucose after oral glucose load x plasma insulin level/10(4). Fasting plasma leptin and lipid levels were also determined. RESULTS: Sibutramine induced greater weight reduction than placebo (6.7 vs. 2.5%, p < 0.001). Reductions in WHR (0.97 +/- 0.08 vs. 0.94 +/- 0.07, p < 0.01), IRIp (0.11 +/- 0.07 vs. 0.09 +/- 0.06 mmol mu/l(2)) and VF (6.4 +/- 2.4-6.0 +/- 2.4 cm, p < 0.01) were observed only with sibutramine. Plasma leptin decreased with placebo (24 +/- 15 vs. 18 +/- 10 UI/l, p < 0.01), but not with sibutramine (18.8 +/- 8.4 vs. 18.2 +/- 13.2 UI/l). No clinically significant change in lipid profile was observed in both groups. Moreover, office and 24-h blood pressure values did not change during placebo or sibutramine therapy, whereas a significant increase in office heart rate, from 78.3 +/- 7.3-82 +/- 7.9 b.p.m., p = 0.02, was observed with sibutramine. CONCLUSIONS: Sibutramine therapy induced greater body weight loss than placebo in hypertensive obese patients. This was associated with WHR reduction, decreases in VF and insulin resistance. The maintenance of leptin levels during sibutramine therapy may be important to avoid weight recovery, although this finding must be confirmed by other prospective studies.

Latin-American trial of orlistat for weight loss and improvement in glycaemic profile in obese diabetic patients.

AIM: To determine if obese non-insulin-dependent diabetic patients lose more weight when treated for 24 weeks (6 months) with orlistat (120 mg t.i.d.), in conjunction with a hypocaloric diet plus behavioural counselling, than when treated by placebo (t.i.d.) plus similar instructions. The secondary objectives were to evaluate the effects on glucose profile and to determine the tolerability and safety of orlistat. DESIGN: Double-blind, parallel, randomized, placebo-controlled, multicentre study. SUBJECTS: Obese, non-insulin-dependent diabetic patients, aged 18-70 years old, with BMI > 27 kg/m2, evaluated at 10 Latin-American centres, in five countries. EFFICACY AND TOLERABILITY MEASUREMENTS: After screened, eligible patients passed by a 2-week placebo run-in period receiving a hypocaloric diet. On day 0, patients were randomized to orlistat or placebo for 24 weeks. At each visit, body weight, blood pressure and waist circumference were measured. At the screening visit, baseline visit (week 0), and at weeks 8, 16 and 24, a central laboratory was in charge of measuring fasting glucose and insulin, HbA1c, postprandial glucose and insulin, fasting total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, and postprandial triglycerides. Other safety laboratory assessments were measured locally at the screening visit, baseline visit and at the end of the study. Adverse events were assessed at each visit from baseline. RESULTS: After 24 weeks of treatment, the orlistat group lost an average of 4.7% of initial body weight vs. 3.0% in the placebo group (p = 0.0003). A greater weight loss was achieved in the orlistat compared with the placebo group (4.24 +/- 0.23 vs. 2.58 +/- 1.46 kg, p = 0.0003). Almost twice as many patients receiving orlistat (30% vs. 17%) lost > or = 5% of initial body weight (p = 0.003). Orlistat treatment plus diet compared to placebo plus diet was associated with significant improvement in glycaemic control, as reflected in decreases in HbA1c (p = 0.04), fasting plasma glucose (p = 0.036) and postprandial glucose (p = 0.05). Orlistat-treated patients had a mean decrease in glucose levels of 1.00 +/- 0.34 mmol/l [3.7%] vs. 0.01 +/- 0.30 mmol/l for placebo group, at week 24 and an absolute decrease of HbA1c of 0.61 +/- 0.15 vs. a decrease of 0.22 +/- 0.14% in the placebo group. Orlistat therapy also resulted in significantly greater improvements than placebo in lipid profile, with reductions in total cholesterol (p = 0.0001) and LDL-cholesterol (p = 0.002). Mild to moderate transient gastrointestinal events were reported, mainly with orlistat treatment, but their association with withdrawal from the study was low. CONCLUSION: Orlistat is a useful and an effective therapy in obese diabetic patients, promoting clinically significant weight loss and improved glycaemic control and lipid profile.

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.

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 (ANO) metabolism and the formation of cholesterol oxidation products in human essential hypertension. The concentrations ofANO 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 percent increase of diameter 90 s after hyperemia), and lower levels of ascorbate (H: 29.2 ± 26.0, N: 54.2 ± 24.9 æM), urate (H: 108.5 ± 18.9, N: 156.4 ± 26.3 æM), ß-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-3ß,5,6ß-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 ANO derivatives between groups. These data suggest that an increase in cholesterol oxidation is associated with endothelium dysfunction in essential hypertension and oxidative stress, although ANO metabolite levels in plasma are not modified in the presence of elevated cholesterol oxides

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.

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 percent, 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

Relationship between microalbuminuria and cardiac structural changes in mild hypertensive patients.

The aim of this study was to determine the relationship between urinary albumin excretion (UAE), cardiac structural changes upon echocardiography and 24-h ambulatory blood pressure (ABPM) levels. Twenty mild hypertensive patients (mean age 56.8 +/- 9.6 years) were evaluated. After 2 weeks of a washout period of all antihypertensive drugs, all patients underwent an echocardiographic evaluation, a 24-h ABPM and an overnight urine collection. Systolic and diastolic blood pressure during 24-h ABPM was 145 +/- 14/91 +/- 10 mmHg (daytime) and 130 +/- 14/76 +/- 8 mmHg (nighttime), respectively. Seven (35%) patients presented UAE > or = 15 microg/min, and for the whole group, the geometric mean value for UAE was 10.2 x// 3.86 microg/min. Cardiac measurements showed mean values of interventricular septum thickness (IVS) of 11 +/- 2.3 mm, left ventricular posterior wall thickness (PWT) of 10 +/- 2.0 mm, left ventricular mass (LVM) of 165 +/- 52 g, and left ventricular mass index (LVMI) of 99 +/- 31 g/m2. A forward stepwise regression model indicated that blood pressure levels did not influence UAE. Significant correlations were observed between UAE and cardiac structural parameters such as IVS (r = 0.71, P<0.001), PWT (r = 0.64, P<0.005), LVM (r = 0.65, P<0.005) and LVMI (r = 0.57, P<0.01). Compared with normoalbuminuric patients, those who had microalbuminuria presented higher values of all cardiac parameters measured. The predictive positive and negative values of UAE > or = 15 microg/min for the presence of geometric cardiac abnormalities were 75 and 91.6%. These data indicate that microalbuminuria in essential hypertension represents an early marker of cardiac structural damage.

Relationship between microalbuminuria and cardiac structural changes in mild hypertensive patients

The aim of this study was to determine the relationship between urinary albumin excretion (UAE), cardiac structural changes upon echocardiography and 24-h ambulatory blood pressure (ABPM) levels. Twenty mild hypertensive patients (mean age 56.8 ± 9.6 years) were evaluated. After 2 weeks of a washout period of all antihypertensive drugs, all patients underwent an echocardiographic evaluation, a 24-h ABPM and an overnight urine collection. Systolic and diastolic blood pressure during 24-h ABPM was 145 ± 14/91 ± 10 mmHg (daytime) and 130 ± 14/76 ± 8 mmHg (nighttime), respectively. Seven (35 percent) patients presented UAE > or = 15 æg/min, and for the whole group, the geometric mean value for UAE was 10.2 x/÷ 3.86 æg/min. Cardiac measurements showed mean values of interventricular septum thickness (IVS) of 11 ± 2.3 mm, left ventricular posterior wall thickness (PWT) of 10 ± 2.0 mm, left ventricular mass (LVM) of 165 ± 52 g, and left ventricular mass index (LVMI) of 99 ± 31 g/m². A forward stepwise regression model indicated that blood pressure levels did not influence UAE. Significant correlations were observed between UAE and cardiac structural parameters such as IVS (r = 0.71, P<0.001), PWT (r = 0.64, P<0.005), LVM (r = 0.65, P<0.005) and LVMI (r = 0.57, P<0.01). Compared with normoalbuminuric patients, those who had microalbuminuria presented higher values of all cardiac parameters measured. The predictive positive and negative values of UAE > or = 15 æg/min for the presence of geometric cardiac abnormalities were 75 and 91.6 percent. These data indicate that microalbuminuria in essential hypertension represents an early marker of cardiac structural damage

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

BACKGROUND: Since metformin improves insulin sensitivity, it has been indicated for patients with diabetes and hypertension, which are insulin-resistant conditions. In contrast to its well-known effects on carbohydrate metabolism, its potential for reducing blood pressure (BP) and its effect on leptin levels have been investigated less frequently. PATIENTS AND METHODS: A double-blind, randomized, placebo-controlled trial was carried out with 26 overweight diabetic subjects with mild-to-moderate hypertension to assess the effects of metformin-induced glycaemic control on BP and metabolic parameters. After a 4-week placebo period, when BP was stabilized by calcium channel blockers, they received either metformin (MG) or placebo (PG) for 12 weeks. RESULTS: Neither group showed any change in weight throughout the study. Only metformin-treated patients reduced fasting plasma glucose (8.54 + 1.72 to 7.54 + 1.33 mmol/l, p < 0.05), although HbA(1c) had decreased in both groups (PG: 6.7+/-3.0 to 5.9+/-2.6%; MG: 5.3+/-1.5 to 4.6+/-0.9%; p < 0.05). The initial office mean BPs were similar and decreased at the end of the treatment period in both groups, reaching statistical significance only in MG (105.7+/-8.0 to 99.2+/-9.3 mmHg, p < 0.05). No difference was observed when comparing baseline and final values obtained by 24-h ambulatory BP monitoring. Metformin induced a reduction in both insulinaemia (71.0+/-62.4 to 38.0+/-23.0 pmol/l, p < 0.05) and the insulin resistance index (3.5+/-2.7 to 1.8+/-1.0, p < 0.05). The two groups had similar baseline leptin levels which remained unchanged after treatment (PG: 16.8+/-7.9 to 21.4+/-14.6 microg/l; MG: 18.5+/-10.3 to 18.4+/-8.9 microg/l). Dopamine levels increased significantly only in metformin-treated subjects. CONCLUSIONS: Reductions in both the insulin levels and the resistance index reinforced metformin capacity to improve peripheral sensitivity. Moreover, such benefits were not accompanied by any hypotensive effects. Since leptin levels were affected neither by metformin per se nor by the induced insulinaemia reduction, our data support the role of body weight as the major determinant of circulating leptin levels.

Treatment of obesity hypertension and diabetes syndrome.

Obesity has been shown to be an independent risk factor for coronary heart disease. The insulin resistance associated with obesity contributes to the development of other cardiovascular risk factors, including dyslipidemia, hypertension, and type 2 diabetes. The coexistence of hypertension and diabetes increases the risk for macrovascular and microvascular complications, thus predisposing patients to cardiac death, congestive heart failure, coronary heart disease, cerebral and peripheral vascular diseases, nephropathy, and retinopathy. Body weight reduction increases insulin sensitivity and improves both blood glucose and blood pressure control. Metformin therapy also improves insulin sensitivity and has been associated with decreases in cardiovascular events in obese diabetic patients. Antihypertensive treatment in diabetics decreases cardiovascular mortality and slows the decline in glomerular function. However, pharmacological treatment should take into account the effects of the antihypertensive agents on insulin sensitivity and lipid profile. Diuretics and beta-blockers are reported to reduce insulin sensitivity and increase triglyceride levels, whereas calcium channel blockers are metabolically neutral and ACE inhibitors increase insulin sensitivity. For the high-risk hypertensive diabetic patients, ACE inhibition has proven to confer additional renal and vascular protection. Because hypertension and glycemic control are very important determinants of cardiovascular outcome in obese diabetic hypertensive patients, weight reduction, physical exercise, and a combination of antihypertensive and insulin sensitizers agents are strongly recommended to achieve target blood pressure and glucose levels.

Ultrasonography for the evaluation of visceral fat and cardiovascular risk.

Visceral fat accumulation is associated with increased cardiovascular risk. Clinical evaluation of visceral fat is limited because of the lack of reliable and low-cost methods. To assess the correlation between ultrasonography and computed tomography (CT) for the evaluation of visceral fat, 101 obese women, age 50.5+/-7.7 years with a body mass index of 39.2+/-5.4 kg/m(2), were submitted to ultrasonograph and CT scans. Visceral fat measured by ultrasonography, 1 cm above the umbilical knot, showed a high correlation with CT-determined visceral fat (r=0.67, P<0.0001). The ultrasonograph method showed good reproducibility with an intra-observer variation coefficient of <2%. Both ultrasonograph and CT visceral fat values were correlated with fasting insulin (r=0.29 and r=0.27, P<0.01) and plasma glucose 2 hours after oral glucose load (r=0.22 and r=0.34, P<0.05), indicating that ultrasonography is a useful method to evaluate cardiovascular risk. A significant correlation was also found between visceral fat by CT and serum sodium (r=0.18, P<0.05). A ultrasonograph-determined visceral-to-subcutaneous fat ratio of 2.50 was established as a cutoff value to define patients with abdominal visceral obesity. This value also identified patients with higher levels of plasma glucose, serum insulin and triglycerides and lower levels of HDL-cholesterol, which are metabolic abnormalities characteristic of the metabolic syndrome. Our data demonstrate that ultrasonography is a precise and reliable method for evaluation of visceral fat and identification of patients with adverse metabolic profile.

Distribution of cardiac geometric patterns on echocardiography in essential hypertension. Impact of two criteria of stratification.

PURPOSE: To evaluate 2 left ventricular mass index (LVMI) normality criteria for the prevalence of left ventricular geometric patterns in a hypertensive population ( HT ). METHODS: 544 essential hypertensive patients, were evaluated by echocardiography, and different left ventricular hypertrophy criteria were applied: 1 - classic : men - 134 g/m2 and women - 110 g/m2; 2- obtained from the 95th percentil of LVMI from a normotensive population (NT). RESULTS: The prevalence of 4 left ventricular geometric patterns, respectively for criteria 1 and 2, were: normal geometry - 47.7% and 39.3%; concentric remodelying - 25.4% and 14.3%; concentric hypertrophy - 18.4% and 27.7% and excentric hypertrophy - 8.8% and 16.7%, which confered abnormal geometry to 52.6% and 60.7% of hypertensive. The comparative analysis between NT and normal geometry hypertensive group according to criteria 1, detected significative stuctural differences,"( *p < 0.05):LVMI- 78.4 +/- 1.50 vs 85.9 +/-0.95 g/m2 *; posterior wall thickness -8.5 +/- 0.1 vs 8.9 +/- 0.05 mm*; left atrium - 33.3 +/- 0.41 vs 34.7 +/- 0.30 mm *. With criteria 2, significative structural differences between the 2 groups were not observed. CONCLUSION: The use of a reference population based criteria, increased the abnormal left ventricular geometry prevalence in hypertensive patients and seemed more appropriate for left ventricular hypertrophy detection and risk stratification.

Angiotensin converting enzymes from human urine of mild hypertensive untreated patients resemble the N-terminal fragment of human angiotensin I-converting enzyme.

Angiotensin I-converting enzyme (ACE) activity was analyzed in human urine collected from mild hypertensive untreated patients. DEAE-cellulose chromatography using linear gradient elution revealed two forms of angiotensin I-converting enzyme, eluted in the conductivity of 0.75 and 1.25 mS. The fractions of each conductivity were pooled and submitted to direct gel filtration in an AcA-34 column, and the apparent molecular weights of urinary ACEs were estimated as 90 kDa (for ACE eluted in 0.75 mS) and 65 kDa (for ACE eluted in 1.25 mS). Both enzymes have a K(i) of the order of 10(-7) M for the specific inhibitors studied, and are able to hydrolyze luteinizing hormone-releasing hormone and N-acetyl-Ser-Asp-Lys-Pro as described for N-domain ACE. By Western blot analysis, both peaks were recognized by ACE-specific antibody Y4, confirming the molecular weight already described. A plate precipitation assay using monoclonal antibodies to the N-domain of ACE showed that both forms of ACE binds with all monoclonal antibodies to the active N-domain ACE, suggesting that these forms of human urine ACEs resemble the N-fragment of ACE. The HP2 ACE (65 kDa) is similar to low molecular weight (LMW) ACE from normal subjects, and the HP2 ACE (90 kDa) is different from high molecular weight (190 kDa) and LMW (65 kDa) normal ACEs. The 90 kDa ACE could have an important role in development of hypertension. It will be fundamental to elucidate the molecular mechanism responsible for the genesis of this isoform.

Validation study of an automated wrist monitor, omron model HEM-608, compared with the standard methods for blood pressure measurement.

OBJECTIVE - The aim of our study was to assess the profile of a wrist monitor, the Omron Model HEM-608, compared with the indirect method for blood pressure measurement. METHODS - Our study population consisted of 100 subjects, 29 being normotensive and 71 being hypertensive. Participants had their blood pressure checked 8 times with alternate techniques, 4 by the indirect method and 4 with the Omron wrist monitor. The validation criteria used to test this device were based on the internationally recognized protocols. RESULTS - Our data showed that the Omron HEM-608 reached a classification B for systolic and A for diastolic blood pressure, according to the one protocol. The mean differences between blood pressure values obtained with each of the methods were -2.3 +7.9mmHg for systolic and 0.97+5.5mmHg for diastolic blood pressure. Therefore, we considered this type of device approved according to the criteria selected. CONCLUSION - Our study leads us to conclude that this wrist monitor is not only easy to use, but also produces results very similar to those obtained by the standard indirect method.

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.