Metabolic syndrome in young adults – prevalence, childhood predictors and association with subclinical atherosclerosis

Background: Metabolic syndrome (MetS) is a cluster of cardiovascular risk factors including central obesity, insulin resistance, impaired glucose tolerance, hypertension and dyslipidemia. The prevalence of MetS is increasing worldwide in all age groups. MetS is associated with increased risk of cardiovascular disease and type 2 diabetes mellitus. Aims: The aim of the present study was to investigate the prevalence, secular trends and childhood predictors of MetS in young adults. Furthermore, the relations between MetS and subclinical atherosclerosis were studied and whether apolipoproteins (apo) B and A-I, C-reactive protein (CRP) and type II secretory phospholipase A2 (sPLA2) were associated with MetS, and to what extent the atherogenicity of MetS was explained by these factors. Participants and Methods: The present thesis is part of the large scale population-based, prospective study, the Cardiovascular Risk in Young Finns Study. The first cross-sectional study was conducted in 1980 and included 3,596 participants aged 3-18 years. Carotid and brachial ultrasound studies were performed for 2,283 of these participants in 2001 and 2,200 of these participants in 2007. Results: The overall prevalence of MetS in young adults aged 24-39 years in 2001 was 10-15 % and 6 years later in 30-45 year-old adults it was 15-23 % depending on the MetS definition used. Between the years 1986 and 2001, MetS prevalence increased from 1.0 % to 7.5 % (p<0.0001) in 24-year-old participants that was mostly driven by the increased central obesity. Participants with MetS had increased carotid intima-media thickness (cIMT) and decreased carotid elasticity compared to those without the syndrome. Impaired brachial flow-mediated dilatation (FMD) was not related to MetS but it modified the relationship between MetS and cIMT (P for interaction 0.023). High levels of apoB, CRP, sPLA2 and low levels of apoA-I associated with MetS in young adults. In prospective analysis both MetS and high apoB predicted (P<0.0001) incident high cIMT, defined as cIMT>90th percentile and/or plaque. The association between MetS and incident high cIMT was attenuated by ~40 % after adjustment with apoB. Conclusions: MetS is common in young adults and increases with age. Screening for risk factors, especially obesity, at an early life stage could help identify children and adolescents at increased risk of developing MetS and cardiovascular disease later in life. MetS identifies a population of young adults with evidence of increased subclinical atherosclerosis. Impaired brachial endothelial response is not a hallmark of MetS in young adults, but the status of endothelial function modifies the association between metabolic risk factors and atherosclerosis. In addition, the atherogenicity of MetS in this population assessed by incident high cIMT appears to be substantially mediated by elevated apoB.

Jejum pré-operatório de 8 horas ou de 2 horas: o que revela a evidência?

Insulin resistance is a transitory phenomenon of the metabolic response to trauma. In uncomplicated operations it lasts for 2-4 weeks postoperatively, and is directly related to the magnitude of the injury. The fasting status caused by conventional fasting protocols aggravates this resistance and may induce hyperglycemia. Conventional preoperative fasting time may aggravate this resistance and increment the elevation of glycemia especially because it is frequently longer than the expected 6-8h and may reach 10-16 hs. Additionally, overnight fasting may cause variable degrees of dehydration depending on the extension of the fasting period. Recently, various societies of anesthesia and nutrition have changed their guidelines to propose a reduction of preoperative fasting to 2h with clear fluids containing carbohydrates. These new protocols (ACERTO, ERAS) are based on the safety of this routine as consistently demonstrated by various randomized trials and a meta-analysis.

Polycystic ovary syndrome: implications of metabolic dysfunction

OBJECTIVE: To determine the prevalence of metabolic syndrome (MS) and its clinical interrelations in polycystic ovary syndrome (PCOS).METHODS: This was a cross-sectional, prospective study with 100 patients with diagnosed PCOS based on the consensus of Rotterdam (2003). We investigated the interrelationships of MS, with intrinsic PCOS data. Dermatological profile was analyzed, in addition to acanthosis nigricans (AN) in the presence of hirsutism and acne. The use of HOMA-IR (homeostatic model assessment of insulin resistance) aimed at the correlation with MS in order to establish the metabolic dysfunction with the state of insulin resistance.RESULTS: The mean and standard deviations corresponding figures for age, body mass index and waist circumference were, respectively, 25.72 (± 4.87), 30.63 (± 9.31) and 92.09 (± 18.73). The prevalence of MS was 36% and significantly correlated with BMI, AN, and in 51% of patients the state of insulin resistance (HOMA-IR). Regarding skin profile, only AN significant correlation with MS.CONCLUSION: We propose the routine inspection of metabolic components related to severe PCOS. These parameters configure the cardiovascular risk and such conduct is of undoubted importance to public health.

Correlação entre os níveis de proteína C reativa ultra-sensível e as características clínicas e laboratoriais em mulheres com síndrome do ovário policístico

OBJETIVO: avaliar a concentração plasmática da proteína C reativa ultra-sensível (PCRus) e a sua correlação com variáveis clínicas, hormonais e metabólicas em pacientes portadoras da síndrome do ovário policístico (SOP). Métodos: estudo transversal, que incluiu 46 pacientes portadoras de síndrome do ovário policístico, diagnosticadas segundo os critérios de Rotterdam (2003), e 44 pacientes controle, que foram submetidas a dosagem da PCRus. O índice de massa corporal (IMC), a idade, a circunferência abdominal e os níveis de insulina de jejum, de testosterona, do HOMA-IR (homeostasis model assessment-insulin resistance) e do colesterol total, além de frações foram correlacionados aos níveis de PCR, utilizando-se análise de regressão multivariada. RESULTADOS: as portadoras da SOP apresentavam idade, IMC, circunferência abdominal, insulina de jejum, HOMA-IR, colesterol total e lipoproteína de baixa densidade (LDL) em concentrações plasmáticas superiores às do controle. Houve diferença significante nos níveis da PCRus entre o grupo da SOP (2,7±2,17 mg/dL) e o controle (1,6±1,49 mg/dL), p<0,05. Quando os níveis da PCRus foram categorizados em baixo (<1,0 mg/L), médio (1-3,0 mg/L) e elevado (3,0 mg/L) risco cardiovascular, 28,3% das portadoras da SOP apresentaram níveis da PCRus para baixo risco, 34,8% para médio e 37% para elevado risco cardiovascular. A prevalência da síndrome metabólica foi mais elevada entre as portadoras da SOP (30,4%), quando comparadas ao grupo controle (6,8%). Após o ajuste das variáveis de confusão, por um modelo de regressão linear multivariada stepwise, a presença da SOP mostrou efeito independente das outras variáveis sobre os níveis da PCRus. CONCLUSÕES: os níveis da PCRus foram mais elevados nas mulheres portadoras da SOP. A SOP tem efeito independente na determinação dos níveis plasmáticos da PCR.

Indicadores antropométricos e as doenças crônicas não transmissíveis em mulheres na pós-menopausa da região Sudeste do Brasil

OBJETIVO: avaliar a influência dos indicadores antropométricos sobre os marcadores de risco cardiovascular e metabólico para doenças crônicas não-transmissíveis em mulheres na pós-menopausa. MÉTODOS: realizou-se estudo clínico transversal, com 120 mulheres sedentárias na pós-menopausa (com idades entre 45 e 70 anos e última menstruação há, pelo menos, 12 meses). Foram excluídas as diabéticas insulino-dependentes e usuárias de estatinas ou terapia hormonal até seis meses prévios. Para avaliação antropométrica, foram obtidos peso, estatura, índice de massa corpórea (IMC=peso/altura²) e circunferência da cintura (CC). As variáveis metabólicas avaliadas foram colesterol total (CT), HDL, LDL, triglicérides (TG), glicemia e insulina, para os cálculos do índice aterogênico plasmático (IAP) e resistência insulínica (Homeostasis model assessment-insulin resistance, HOMA-IR). Na análise estatística, utilizara-se análise de variância one-way (ANOVA) e Odds Ratio (OR). RESULTADOS: os dados médios caracterizaram amostra com sobrepeso, com obesidade central e dislipidêmica. Sobrepeso e obesidade estiveram presentes em 77,1% e deposição central de gordura ocorreu em 87,3% das participantes. Os valores médios de CT, LDL e TG estavam acima do recomendável em 67,8, 55,9 e 45,8% das mulheres, respectivamente, com HDL abaixo dos valores adequados em 40,7%. Valores de CC >88 cm ocorreram em 14,8% das mulheres eutróficas, 62,5% no grupo com sobrepeso e 100% nas obesas (p>0,05). Os valores médios de IAP, TG e HOMA-IR aumentaram significativamente com o aumento do IMC e da CC, enquanto que o HDL diminuiu (p<0,05). Na presença da CC >88 cm, encontrou-se risco de 5,8 (IC95%=2,3-14,8), 2,61 (IC95%=1,2-5,78), 3,4 (IC95%=1,2-9,7) e 3,6 (IC95%=1,3-10,3) para HDL reduzido, hipertrigliceridemia, IAP elevado e resistência a insulina, respectivamente (p<0,05). O IMC >30 kg/m² associou-se apenas com HDL reduzido (OR=3,1; IC95%=1,44-6,85). CONCLUSÕES: a associação de duas medidas antropométricas (CC e IMC) foi eficiente para adequado diagnóstico de obesidade relacionada a alterações metabólicas em mulheres na pós-menopausa. Contudo, a simples avaliação da CC pode ser indicativo do risco cardiovascular e metabólico das doenças crônicas não transmissíveis.

Arterial hypertension and metabolic profile in patients with polycystic ovary syndrome

PURPOSE: To evaluate parameters related with arterial pressure and metabolic profile in women with polycystic ovary syndrome (POS). METHODS: This monocentric study at the University Hospital Endocrinology Section included 60 women aged 18-45 years, 42 being diagnosed with POS and acting as 18 controls. All women were subjected to transvaginal ultrasound and monitored for arterial pressure for 24 h in the ambulatory (MAP). Venous blood samples were taken between 07.00 and 09.00, after 12 h fasting. Basal (BG) and fasting glucose concentrations, total cholesterol and its fractions, triglycerides and insulin (to calculate the homeostatic assay insulin-resistance, HOMA-IR) were measured. Collected data were the mean arterial blood pressure (24-h awake/sleep cycle), arterial pressure nocturnal descensus, glycemia and fasting glucose for HOMA-IR, and lipid profile. The Student's t test was used to compare homogeneous variables; the Mann-Whitney test was used to compare non-homogeneous variables; the Pearson's correlation coefficient was used to search for correlation between the variables. The c² test was used for comparison of the absence of nocturnal descensus. Significance was taken as p<0.05. RESULTS: The mean age of the patients with POS was 27.4±5.5 (18-45 years, n=42) and the body mass index (BMI) was 30.2±6.5 kg/m² (18.3-54.9). In the Control Group, the mean age was 31.4±6.1 (18-45 years) and the BMI was 27.1±6.2 kg/m² (18.3-54.9, n=18). No difference in the metabolic parameters and insulin resistance was observed between the two groups. Comparison between these parameters and MAP showed that the only parameter with a correlation was the BMI, independent of the POS diagnosis. This was not seen in nocturnal descensus, which was uncorrelated with POS and any of the other studied parameters. CONCLUSION: POS women do not show higher arterial blood pressure, glycemia, HDL-col, TG, HOMA-IR and BMI compared to non-POS women. However, POS patients showed correlation between arterial pressure and BMI, suggesting that obesity is a primary factor involved in arterial pressure changes in these patients.

Acantose nigricante: inter-relações metabólicas inerentes à síndrome dos ovários policísticos

OBJETIVO: Estabelecer a prevalência da acantose nigricante (AN) no contexto da síndrome dos ovários policísticos (SOP) e as respectivas associações com a obesidade, a resistência insulínica (RI), a insulinemia e a síndrome metabólica (SM).MÉTODOS: Em um estudo transversal e prospectivo, foram selecionadas cem pacientes acometidas pela SOP, diagnosticadas segundo o Consenso de Rotterdam (2003). O exame cutâneo incluiu, além da verificação da presença da AN, a presença do hirsutismo (escore ≥8) e da acne. Foram investigados os dados clínicos e bioquímicos, os fatores de risco cardiovascular que se fazem presentes na SM, como circunferência abdominal (CA), obesidade, hipertensão e os índices de HDL e triglicérides. O modelo de aferição da resistência insulínica foi realizado por meio do teste homeostatic model assessment of insulin resistance(HOMA-IR).RESULTADOS: A prevalência da AN (53%) mostrou correspondência significativa com o hirsutismo (p=0,02), o índice de massa corpórea (IMC) (p<0,01), a insulinemia basal (p<0,01), o HOMA-IR (p<0,01) e a SM (p<0,05). A SM alcançou a prevalência de 36% e associou-se significativamente apenas com a AN (p<0,01). Conquanto ausente o diabetes mellitus, sobressaem as conotações do HOMA-IR alterado (p=0,01) com a SM (p<5%) e a AN (p<0,01).CONCLUSÕES: A AN integra o quadro fenotípico grave da SOP como mais um signo previsível dos riscos da doença cardiovascular.

Association between Lipid Accumulation Product and Hirsutism in Patients with Polycystic Ovary Syndrome

Objective Polycystic ovary syndrome (PCOS) is the most common endocrine metabolic disorder in women between menarche and menopause. Clinical hyperandrogenism is the most important diagnostic criterion of the syndrome, which manifests as hirsutism in 70% of cases. Hirsute carriers of PCOS have high cardiovascular risk. Lipid accumulation product (LAP) is an index for the evaluation of lipid accumulation in adults and the prediction of cardiovascular risk. The aim of this study was to evaluate the association between LAP and hirsutism in women with PCOS. Methods This was a cross-sectional observational study of a secondary database, which included 263 patients who had visited the Hyperandrogenism Outpatient Clinic from November 2009 to July 2014. The exclusion criteria were patients without Ferriman-Gallwey index (FGI) and/or LAP data. We used the Rotterdam criteria for the diagnosis of PCOS. All patients underwent medical assessment followed by measurement and recording of anthropometric data and the laboratory tests for measurement of the following: thyroid-stimulating hormone, follicle-stimulating hormone, prolactin, total testosterone, sex hormone binding globulin, 17-α-hydroxyprogesterone (follicular phase), glycohemoglobin A1c, and basal insulin. In addition, the subjects underwent lipid profiling and oral glucose tolerance tests. Other laboratory measurements were determined according to clinical criteria. LAP and the homeostatic model assessment index (HOMA-IR) were calculated using the data obtained. We divided patients into two groups: the PCOS group with normal LAP (< 34.5) and the PCOS group with altered LAP (> 34.5) to compare the occurrence of hirsutism. For statistical analysis, we used SPSS Statistics for Windows(r) and Microsoft Excel programs, with descriptive (frequencies, percentages, means, and standard deviations) and comparative analyses (Student's t-test and Chi-square test). We considered relations significant when the p-value was≤0.05. Results LAP was high in most patients (n = 177; 67.3%) and the FGI indicated that 58.5% of the patients (n = 154) had hirsutism. The analysis by LAP quartiles showed a positive correlation (p = 0.04) among patients with a high FGI and an upper quartile LAP (> 79.5) when compared with those with LAP < 29.0 (lower quartile). Conclusion This study demonstrated an association between high LAP and hirsutism. The FGI could represent a simple and low-cost tool to infer an increased cardiovascular risk in women with PCOS.

Low levels of sex hormone-binding globulin and hyperproinsulinemia as markers of increased pancreatic ß-cell demand in men

Low levels of sex hormone-binding globulin (SHBG) are considered to be an indirect index of hyperinsulinemia, predicting the later onset of diabetes mellitus type 2. In the insulin resistance state and in the presence of an increased pancreatic ß-cell demand (e.g. obesity) both absolute and relative increases in proinsulin secretion occur. In the present study we investigated the correlation between SHBG and pancreatic ß-cell secretion in men with different body compositions. Eighteen young men (30.0 ± 2.4 years) with normal glucose tolerance and body mass indexes (BMI) ranging from 22.6 to 43.2 kg/m2 were submitted to an oral glucose tolerance test (75 g) and baseline and 120-min blood samples were used to determine insulin, proinsulin and C-peptide by specific immunoassays. Baseline SHBG values were significantly correlated with baseline insulin (r = -0.58, P<0.05), proinsulin (r = -0.47, P<0.05), C-peptide (r = -0.55, P<0.05) and also with proinsulin at 120 min after glucose load (r = -0.58, P<0.05). Stepwise regression analysis revealed that proinsulin values at 120 min were the strongest predictor of SHBG (r = -0.58, P<0.05). When subjects were divided into obese (BMI >28 kg/m2, N = 8) and nonobese (BMI £25 kg/m2, N = 10) groups, significantly lower levels of SHBG were found in the obese subjects. The obese group had significantly higher baseline proinsulin, C-peptide and 120-min proinsulin and insulin levels. For the first time using a specific assay for insulin determination, a strong inverse correlation between insulinemia and SHBG levels was confirmed. The finding of a strong negative correlation between SHBG levels and pancreatic ß-cell secretion, mainly for the 120-min post-glucose load proinsulin levels, reinforces the concept that low SHBG levels are a suitable marker of increased pancreatic ß-cell demand.

Oxidized LDL lipids as a risk factor for atherosclerosis

University of Turku, Faculty of Medicine, Department of Clinical Medicine, Department of Physical Activity and Health, Paavo Nurmi Centre, Doctoral Programme of Clinical Investigation, University of Turku, Turku, Finland. Annales Universitatis Turkuensis. Medica – Odontologica, Turku, Finland, 2014. Background: Atherosclerosis progression spans an entire lifetime and has a wide pool of risk factors. Oxidized LDL (oxLDL) is a crucial element in the progression of atherosclerosis. As a rather new member in the atherosclerosis risk factor family, its interaction with the traditional pro-atherogenic contributors that occur at different ages is poorly known. Aims: The aim of this study was to investigate oxLDL and its relation to major contributing risk factors in estimating atherosclerosis risk in data consisting mostly of adult men. The study subjects of this study consisted of four different sets of data, one of which contained also women. The age range of participants was 18-100 years and totaled 2337 participants (of whom 69% were men). Data on anthropometric and hormonal parameters, laboratory measures and medical records were assessed during 1998-2009. Results: Obesity was paralleled with high concentrations of oxLDL, which consequentially was reduced by weight reduction. Importantly, successful weight maintenance preserveed this benefit. A shift from insulin sensitivity to insulin resistance increased oxLDL. Smokers had more oxLDL than non-smokers. A combination of obesity and smoking, or smoking and low serum total testosterone,resulted in even higher levels of oxLDL than any of the three conditions alone. Proportioning oxLDL to HDL-c or apoA1 stood out as a risk factor of all-cause mortality in the elderly. Conclusions: OxLDL was associated with aging, androgens, smoking, obesity, insulin metabolism, weight balance and other circulating lipid classes. Through this variety of metabolic environments containing both constant conditions (aging and gender) as well as lifestyle issues, these findings supported an essential and multidimensional role that oxLDL plays in atherosclerosis pathogenesis.

Abnormalities of glucose metabolism in spontaneously hypertensive rats

Abnormalities in glucose metabolism and insulin action are frequently detected in patients with essential hypertension. Spontaneously hypertensive rats (SHR) have been used as an experimental model to understand this pathological condition. The objective of the present study was to assess glucose metabolism and insulin action in SHR and Wistar rats under fed and fasting conditions. Peripheral glucose utilization was estimated by kinetic studies with [6-³H]-glucose and gluconeogenetic activity was measured during continuous [14C]-bicarbonate infusion. Plasma glucose levels were higher in the SHR group. Plasma insulin levels in the fed state were higher in the SHR group (99.8 ± 6.5 µM) than in the control group (70.4 ± 3.6 µM). Muscle glycogen content was reduced in SHR compared to control under the various experimental conditions. Peripheral glucose utilization was slightly lower in the SHR group in the fed state (8.72 ± 0.55 vs 9.52 ± 0.80 mg kg-1 min-1 in controls). Serum free fatty acid levels, hepatic glycogen levels, hepatic phosphoenolpyruvate carboxykinase activity and gluconeogenetic activity were similar in the two groups. The presence of hyperglycemia and hyperinsulinemia and the slightly reduced peripheral glucose utilization suggest the presence of resistance to the action of insulin in peripheral tissues of SHR. Hepatic gluconeogenesis does not seem to contribute to the metabolic alterations detected in these animals.

A high-fructose diet induces changes in pp185 phosphorylation in muscle and liver of rats

Insulin stimulates the tyrosine kinase activity of its receptor resulting in the tyrosine phosphorylation of pp185, which contains insulin receptor substrates IRS-1 and IRS-2. These early steps in insulin action are essential for the metabolic effects of insulin. Feeding animals a high-fructose diet results in insulin resistance. However, the exact molecular mechanism underlying this effect is unknown. In the present study, we determined the levels and phosphorylation status of the insulin receptor and pp185 (IRS-1/2) in liver and muscle of rats submitted to a high-fructose diet evaluated by immunoblotting with specific antibodies. Feeding fructose (28 days) induced a discrete insulin resistance, as demonstrated by the insulin tolerance test. Plasma glucose and serum insulin and cholesterol levels of the two groups of rats, fructose-fed and control, were similar, whereas plasma triacylglycerol concentration was significantly increased in the rats submitted to the fructose diet (P<0.05). There were no changes in insulin receptor concentration in the liver or muscle of either group. However, insulin-stimulated receptor autophosphorylation was reduced to 72 ± 4% (P<0.05) in the liver of high-fructose rats. The IRS-1 protein levels were similar in both liver and muscle of the two groups of rats. In contrast, there was a significant decrease in insulin-induced pp185 (IRS-1/2) phosphorylation, to 83 ± 5% (P<0.05) in liver and to 77 ± 4% (P<0.05) in muscle of the high-fructose rats. These data suggest that changes in the early steps of insulin signal transduction may have an important role in the insulin resistance induced by high-fructose feeding.

GLUT4 protein expression in obese and lean 12-month-old rats: insights from different types of data analysis

GLUT4 protein expression in white adipose tissue (WAT) and skeletal muscle (SM) was investigated in 2-month-old, 12-month-old spontaneously obese or 12-month-old calorie-restricted lean Wistar rats, by considering different parameters of analysis, such as tissue and body weight, and total protein yield of the tissue. In WAT, a ~70% decrease was observed in plasma membrane and microsomal GLUT4 protein, expressed as µg protein or g tissue, in both 12-month-old obese and 12-month-old lean rats compared to 2-month-old rats. However, when plasma membrane and microsomal GLUT4 tissue contents were expressed as g body weight, they were the same. In SM, GLUT4 protein content, expressed as µg protein, was similar in 2-month-old and 12-month-old obese rats, whereas it was reduced in 12-month-old obese rats, when expressed as g tissue or g body weight, which may play an important role in insulin resistance. Weight loss did not change the SM GLUT4 content. These results show that altered insulin sensitivity is accompanied by modulation of GLUT4 protein expression. However, the true role of WAT and SM GLUT4 contents in whole-body or tissue insulin sensitivity should be determined considering not only GLUT4 protein expression, but also the strong morphostructural changes in these tissues, which require different types of data analysis.

Association of acanthosis nigricans with race and metabolic disturbances in obese women

Acanthosis nigricans (AN) has been recognized as a marker of insulin resistance and diabetes mellitus. We have compared frequency of race and metabolic disturbances in obese women with several degrees of AN (AN group, N = 190) to a group without AN (non-AN group, N = 61) from a mixed racial population. The groups were similar regarding age and body mass index. All patients (except the diabetic patients) underwent an oral glucose tolerance test (75 g). The racial distribution of this population was 35.1% white, 37.8% mulatto and 27.1% black and the frequency of AN was 62.5, 82.1 and 83.8%, respectively, higher in black versus white (P = 0.003) and mulatto versus white (P = 0.002) women. The frequencies of diabetes mellitus and impaired glucose tolerance were 5.8 and 12.6% in the AN group and 1.6 and 8.2% in the non-AN group, respectively (P>0.05). Fasting glucose, ß cell function determined by the homeostasis model of assessment (HOMA), fasting insulin and insulin area under the curve were similar for the AN and non-AN groups. A higher HOMA insulin resistance was observed in the AN group compared to the non-AN group (P = 0.02) and in the subgroup of highest degree of AN compared to those with other degrees. The mean lipid levels and the frequency of dyslipidemia were similar for the two groups. AN was strongly associated with the black or mulatto rather than the white race, even after taking into account the effect of age, body mass index and HOMA insulin resistance.

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.