IGF-1 Levels are Inversely Associated With Metabolic Syndrome in Obstructive Sleep Apnea.

STUDY OBJECTIVES: This study examined insulin-like growth factor-1 (IGF-1) production and its association with the metabolic syndrome (MS) in men with obstructive sleep apnea (OSA). METHODS: In total, 47 overweight and obese men who had been referred for suspected OSA underwent polysomnography and were classified based on the apnea-hypopnea index (AHI) into three groups: no OSA, < 5 events/h (n = 11); mild OSA, ≥ 5 to < 15 events/h (n = 8); and moderate-severe OSA, ≥ 15 events/h (n = 28). The assessment of the somatotropic axis function included IGF-1 measurement. MS was diagnosed according to the National Cholesterol Education Program guidelines. RESULTS: IGF-1 level in the moderate-severe OSA group was lower than in the no-OSA group (156.8 ± 54.3 µg/L versus 225.5 ± 80.5 µg/L; p = 0.013). IGF-1 level was negatively correlated with body mass index, waist circumference (WC), AHI, and sleep duration with oxygen (O2) saturation < 90% and positively correlated with the average and minimum O2 saturation (p = 0.027). In a multivariable linear regression, considering WC and minimum O2 saturation as independent variables, only the minimum O2 saturation was a predictor of low IGF-1 levels. The proportions of patients with MS were different between the three groups (18.2% in no OSA; 25% in mild OSA, and 57.1% in moderate-severe OSA; p = 0.047). Furthermore, in the lowest tertile of IGF-1 value, 66.7% of patients were affected by MS (p = 0.049). Hemoglobin (Hb)A1c correlated negatively with the minimum O2 saturation and IGF-1 levels. However, in multivariable linear regression only IGF-1 levels were a predictor of HbA1c levels. CONCLUSION: The occurrence of OSA is associated with a reduction in IGF-1 levels. IGF-1 alterations in OSA also seem to be associated with a higher prevalence of MS.

Novel biomarkers of cardiometabolic risk are associated with plasma glucose within non-diabetic range. The Brazilian Longitudinal Study of Adult Health - ELSA-Brasil.

Abnormal glucose metabolism preceding overt diabetes is associated with increased cardiovascular risk. Whether novel biomarkers are useful to identify this condition is unclear. The objective was to investigate associations of biomarkers of atherogenesis with plasma glucose within non-diabetic range. 998 participants (35-54 years) of the Brazilian Longitudinal Study of Adult Health without diabetes or cardiovascular disease were classified as normal glucose tolerance (NGT), impaired fasting glycemia (IFG) and impaired glucose tolerance (IGT). Traditional risk factors and markers of atherogenesis were evaluated among groups and across plasma glucose concentrations. IFG and IGT had worse profile considering traditional cardiovascular risk factors than the NGT group, although these values were within the reference range. NGT, IFG and IGT groups differed (medians and interquartile intervals) regarding transforming growth factor-ß1 [12.2 (6.4-22.3), 16.8 (8.4-26.5), and 15.5 (8.0-26.1)pg/mL, p<0.05], C-reactive protein [1.1 (0.6-2.9), 1.2 (0.6-2.7), and 1.4 (0.8-3.7)ng/mL, p<0.001] and monocyte chemoattractant protein-1 [35.9 (21.2-57.8), 32.2 (18.7-55.8), and 34.1 (18.6-52.4)pg/mL, p<0.05]. TGF-ß1 and E-selectin concentrations increased while MCP-1 decreased across quartiles of fasting plasma glucose. C-reactive protein increased with increments in 2-h plasma glucose. In linear regression, TGF-ß1 was independently associated with fasting plasma glucose, and C-reactive protein with 2-h plasma glucose after adjustments. In conclusion, association of TGF-ß1, E-selectin, C-reactive protein and MCP-1 with slight elevations in glycemia may be anticipating alterations in traditional cardiovascular risk factors. Independent association of TGF-ß1 with plasma glucose suggests that this may be useful to identifying atherogenic process, deserving further investigation on the prediction of cardiovascular outcomes.

Consequences of obstructive sleep apnea on metabolic profile: a Population-Based Survey.

OBJECTIVE: Epidemiologic studies that control for potential confounders are needed to assess the independent associations of obstructive sleep apnea (OSA) with metabolic abnormalities. The aim of our study was to evaluate the associations of OSA with metabolic abnormalities among the adult population of Sao Paulo, Brazil. DESIGN AND METHODS: Questionnaires were applied face-to-face, full night polysomnography (PSG) was performed, and blood samples were collected in a population-based survey in Sao Paulo, Brazil, adopting a probabilistic three-stage cluster sample method. The metabolic profile included fasting glucose, insulin, and lipid levels. The hepatic insulin resistance index was assessed by the homeostasis model assessment-estimated insulin resistance (HOMAIR ). RESULTS: A total of 1,042 volunteers underwent PSG. Mild OSA and moderate to severe OSA comprised 21.2% and 16.7% of the population, respectively. Subjects with severe to moderate OSA were older, more obese, had higher fasting glucose, HOMAIR , and triglycerides (TG) levels than did the mild and non-OSA group (P < 0.001). Multivariate regression analyses showed that an apnea-hypopnea index (AHI) ≥ 15 and a time of oxy-hemoglobin saturation <90% were independently associated with impaired fasting glucose, elevated TG, and HOMAIR . CONCLUSIONS: The results of this large cross-sectional epidemiological study showed that the associations of OSA and metabolic abnormalities were independent of other risk factors.

Diuretic-induced potassium depletion and glucose intolerance are not related to hyperactivity of the renin-angiotensin-aldosterone system in hypertensive patients with the metabolic syndrome.

The metabolic syndrome (MS) has been associated with hyperactivity of the renin-angiotensin-aldosterone system (RAAS). To assess the hypothesis that diuretic therapy in MS patients through further stimulation of RAAS would elicit greater potassium (K) depletion, two groups of hypertensive patients with (MS group [MSG]; n=20) and without (control group [CG]; n=19) MS were studied. Plasma renin activity (PRA), aldosterone (PA), and K levels were determined and an oral glucose tolerance test with plasma insulin determinations for calculation of homeostasis model assessment of insulin resistance (HOMA-IR), sensitivity (ISI), and secretion (HOMA-beta) was performed, both before and 12 weeks after hydrochlorothiazide (HCT; 25 mg/d) therapy. At baseline, higher HOMA IR and HOMA-beta and lower ISI and plasma K were found in the MSG than in the CG, with no differences in PA and PRA between groups. With therapy, PRA increased similarly in both groups while PA increased only in the MSG. However, greater reduction in plasma K occurred in the CG, and the 2 groups reached similar final K values. Impairment in glucose tolerance occurred in both groups, with no change in HOMA-beta in the CG and reduction in the MSG, suggesting that diuretic therapy increases insulin resistance and impairs insulin secretion independent of abdominal obesity. These alterations could not be attributed to hyperactivity of RAAS.

[Visceral fat and metabolic syndrome: more than a simple association]. / Gordura visceral e síndrome metabólica: mais que uma simples associação.

Metabolic syndrome (MS) is seen nowadays as a worldwide epidemic event associated with high cardiovascular morbi-mortality and high socioeconomic cost. The ponderal gain is an independent predictor for the development of MS, although not all obese individuals present it. On the other hand, some populations with low obesity prevalence present high prevalence of MS and cardiovascular mortality. The distribution of corporal fat is relevant and visceral fat (VF), specifically, seems to be the link between adipose tissue and insulin resistance (IR), a mean feature of MS. Adipose tissue is now considered a complex organ with multiple functions. VF presents metabolic properties, which are different from the gluteo-femoral subcutaneous fat and related to IR. Several studies show the narrow relationship of abdominal adiposity with the glucose tolerance, hyperinsulinemia, hypertriglyceridemia and arterial hypertension. More than a simple association, recently it is thought that the VF plays a central part in the physiopathology of MS. Consequently, the quantification of VF plays an important role to identify individuals with larger risk for development of MS, who should be chosen for early interventions in the attempt of reducing the impact of metabolic abnormalities on cardiovascular mortality. This article discusses particularities of the central distribution of fat in MS context, possible physiopathogenic mechanisms related to the VF and available methods for the evaluation of abdominal adiposity.

Gordura visceral e síndrome metabólica: mais que uma simples associação / Visceral fat and metabolic syndrome: more than a simple association

A síndrome metabólica (SM) é vista atualmente como uma epidemia mundial, com números alarmantes, associada a alta morbi-mortalidade cardiovascular e elevado custo sócio-econômico. O ganho ponderal é preditor independente para o desenvolvimento da SM, embora nem todos os indivíduos obesos a apresentem. Por outro lado, certas populações com baixa prevalência de obesidade apresentam elevada prevalência da SM e mortalidade cardiovascular. A distribuição da gordura corporal é relevante, e especificamente a gordura visceral (GV) parece ser o elo entre o tecido adiposo e a resistência à insulina (RI), característica da SM. Na última década, o tecido adiposo deixou de ser um simples reservatório de energia para se transformar num complexo órgão com múltiplas funções. A GV apresenta características metabólicas diferentes da gordura subcutânea glúteo-femoral, as quais favorecem a instalação do quadro de RI. Diversos estudos revelam a estreita relação da adiposidade abdominal com a tolerância à glicose, hiperinsulinemia, hipertrigliceridemia e hipertensão arterial. Mais que uma simples associação, recentemente, acredita-se que a GV desempenha um papel central na fisiopatologia da SM. Assim, a quantificação da GV se torna importante para identificar indivíduos com maior risco para o desenvolvimento da SM, eleitos para sofrer intervenções precoces na tentativa de reduzir o impacto das anormalidades metabólicas sobre a mortalidade cardiovascular. Este artigo discute particularidades da distribuição central de gordura, no contexto da SM, possíveis mecanismos fisiopatogênicos relacionados à GV e os métodos disponíveis para a avaliação da adiposidade abdominal.

Metabolic syndrome (MS) is seen nowadays as a worldwide epidemic event associated with high cardiovascular morbi-mortality and high socioeconomic cost. The ponderal gain is an independent predictor for the development of MS, although not all obese individuals present it. On the other hand, some populations with low obesity prevalence present high prevalence of MS and cardiovascular mortality. The distribution of corporal fat is relevant and visceral fat (VF), specifically, seems to be the link between adipose tissue and insulin resistance (IR), a mean feature of MS. Adipose tissue is now considered a complex organ with multiple functions. VF presents metabolic properties, which are different from the gluteo-femoral subcutaneous fat and related to IR. Several studies show the narrow relationship of abdominal adiposity with the glucose tolerance, hyperinsulinemia, hypertriglyceridemia and arterial hypertension. More than a simple association, recently it is thought that the VF plays a central part in the physiopathology of MS. Consequently, the quantification of VF plays an important role to identify individuals with larger risk for development of MS, who should be chosen for early interventions in the attempt of reducing the impact of metabolic abnormalities on cardiovascular mortality. This article discusses particularities of the central distribution of fat in MS context, possible physiopathogenic mechanisms related to the VF and available methods for the evaluation of abdominal adiposity.

Leptin is associated with insulin resistance in Japanese migrants.

BACKGROUND: Leptin and insulin are both influenced by body adiposity. Insulin plays an important role in the context of the metabolic syndrome (MS). We evaluated whether leptin was associated with insulin resistance and MS after adjusting for confounders in Japanese-Brazilian women. METHODS: A total of 717 Japanese-Brazilian women aged >/=30 years were investigated for the presence of MS. They were submitted to clinical examination and laboratory measurements, including oral GTT, lipid profile, uric acid, C-reactive protein (CRP), insulin, and leptin levels. Insulin sensitivity was assessed by HOMA. Diagnosis of MS was based on the National Cholesterol Education Program criteria modified for Asians. Pearson correlation coefficient and logistic regression analysis were used. RESULTS: MS was diagnosed in 56% (95% CI 52-59); these subjects were older and had higher body mass index (BMI) and fat mass, and worse metabolic profile. Leptin and CRP levels were statistically greater in women with MS when compared to those without the syndrome (8.6 +/- 8.0 vs. 7.2 +/- 5.9 ng/mL and 0.219 +/- 0.848 vs. 0.360 +/- 0.852 mg/dL, p < 0.05). Leptin was significantly correlated to BMI, fat mass, waist circumference, HOMA-IR, and insulin but not to other components of MS, such as fasting plasma glucose, blood pressure, HDL-cholesterol, triglyceride, and CRP levels. Correlation between leptin and HOMA-IR or fasting insulinemia was maintained after adjustments for body adiposity. However, in logistic regression model, age, BMI, 2-h glucose, and uric acid were independently associated with MS, but not leptin. CONCLUSIONS: Adiposity-adjusted correlation of leptin with HOMA-IR and fasting insulinemia suggested that the former is associated with insulin resistance, despite the lack of independent association with the definition of the MS according to NCEP-ATP III. These findings in such Japanese-Brazilian population of high prevalence of MS need to be confirmed in other populations.

Methods of estimation of visceral fat: advantages of ultrasonography.

OBJECTIVE: To compare methods for the assessment of visceral fat with computed tomography (CT) and establish cutoffs to define visceral obesity based on such alternative methods. RESEARCH METHODS AND PROCEDURES: One hundred women (50.4 +/- 7.7 years; BMI 39.2 +/- 5.4 kg/m2 underwent anthropometric evaluation, bioelectrical impedance, DXA, abdominal ultrasonography (US), and CT scan. RESULTS: Waist circumference, waist-to-hip ratio (WHR), and US-determined visceral fat values showed the best correlation coefficients with visceral fat determined by CT (r = 0.55, 0.54, and 0.71, respectively; p < 0.01). Fat mass determined by DXA was inversely correlated with visceral-to-subcutaneous-fat ratio (r = -0.47, p < 0.01). Bioimpedance-determined fat mass and skinfolds were correlated with only subcutaneous abdominal fat quantified by CT. Linear regression indicated US visceral-fat distance and WHR as the main predictors of CT-determined visceral fat (adjusted r2 = 0.51, p < 0.01). A waist measurement of 107 cm (82.7% specificity, 60.6% sensitivity) and WHR of 0.97 (78.8% specificity, 63.8% sensitivity) were chosen as discriminator values corresponding with visceral obesity diagnosed by CT. A value of 6.90 cm for visceral fat US-determined diagnosed visceral obesity with a specificity of 82.8%, a sensitivity of 69.2%, and a diagnostic concordance of 74% with CT. DISCUSSION: US seemed to be the best alternative method for the assessment of intra-abdominal fat in obese women. Its diagnostic value could be optimized by an anthropometric measurement. Prospective studies are needed to establish CT and US cutoffs for defining visceral-fat levels related to elevated cardiovascular risk.

[Influence of body fat distribution on the prevalence of arterial hypertension and other cardiovascular risk factors in obese patients]. / Influência da distribuição da gordura corporal sobre a prevalência de hipertensão arterial e outros fatores de risco cardiovascular em indivíduos obesos.

INTRODUCTION: Obese people are at higher cardiovascular risk than people with normal body weight. The objective of this study was to establish the relationship between obesity, body fat distribution and cardiovascular risk factors. METHODS: Body mass index (BMI), waist-hip ratio (WHR) systolic (SBP) and diastolic blood pressure (DBP), plasma cholesterol, triglycerides and glucose levels were determined in a population of 499 overweight and obese patients (432F/67M; age 39 12.9y). RESULTS: High prevalence of abnormal glucose tolerance or diabetes (21.8%), hypercholesterolenemia (49.1%), hypertri glyceridemia (21.3%) and hypertension (43.8%) were found in this population. The prevalence of hypertension increased from 23% in patients with BMI 25-29.9 kg/m to 67.1% (p<0.05) in those with BMI > 40kg/m and also from 35.7% in patients with WHR between 0.73 and 0.88 to 66.6% in those with WHR >0.97 (p<0.05). In addition, a correlation was found between the waist circumference and SBP (r=0.35; p<0.0001). In the hypertensive group, but not in the normotensive, SBP increased with BMI, from 150 12 mmHg in the overweight group to 161 18mmHg in that with BMI > 40kg/m , (p<0.05). CONCLUSION: Our data reinforce the association between obesity and high cardiovascular risk. In addition, our findings suggested a role for body fat distribution in the development of hypertension in obese patients.

Influência da distribuiçäo da gordura corporal sobre a prevalência de hipertensäo arterial e outros fatores de risco cardiovascular em indivíduos obesos / Influence of body fat distribution on the prevalence of arterial hypertension and other cardiovascular risk factors in obese patients

OBJETIVOS: Indivíduos obesos säo mais predispostos à ocorrência de eventos cardiovasculares que indivíduos com peso normal. Para se avaliar o impacto da obesidade e da distribuiçäo de gordura corporal sobre o risco cardiovascular, avaliamos uma populaçäo de indivíduos com sobrepeso ou obesidade. MÉTODOS: Foram feitas medidas do índice de massa corporal (IMC), da relaçäo entre as medidas da cintura e do quadril (RCQ), da pressäo arterial sistólica (PAS) e diastólica (PAD) e dos níveis da glicemia de jejum, colesterol total e triglicérides. RESULTADOS: Altas prevalências de intolerância à glicose ou diabetes (21,8 por cento), hipercolesterolenemia (49,1 por cento), hipertrigliceridemia (21,3 por cento) e hipertensäo arterial (43,8 por cento) foram observadas nesta populaçäo. A prevalência de hipertensäo aumentou de 23 por cento no grupo com sobrepeso (IMC 25-29,9 kg/m²) para 67,1 por cento (p<0.05) em pacientes com obesidade grau 3 (IMC > 40kg/m²). Também a prevalência de hipertensäo aumentou de 35,7 por cento naqueles com RCQ entre 0,73 e 0,88 para 66,6 por cento naqueles com RCQ >0,97 (p<0,05), independente do IMC, e os valores da PAS se correlacionaram com as medidas da circunferência da cintura (r=0,35; p<0,0001). A PAS, entretanto, mostrou aumentos com o IMC apenas entre hipertensos, elevando-se de 150±12 mmHg naqueles com sobrepeso para 161±18mmHg naqueles com IMC > 40kg/m² (p<0,05). CONCLUSÄO: A obesidade favorece a ocorrência dos fatores de risco cardiovascular, sendo que a distribuiçäo central da gordura corporal se destaca especialmente como fator importante no desenvolvimento da hipertensäo arterial

Two-hour insulin determination improves the ability of abdominal fat measurement to identify risk for the metabolic syndrome.

OBJECTIVE: Visceral obesity is shown to be a predictor of morbidity and mortality. We evaluated the association of measurements of generalized adiposity and visceral fat area (VFA), with abnormalities of metabolic syndrome (MS). RESEARCH DESIGN AND METHODS: Seventy-six women (47.9 +/- 9.2 years) with BMI of 38.7 +/- 5.4 kg/m(2) underwent anthropometric measurements, laboratory procedures, bioeletrical impedance, and abdominal computed tomography (CT) scan. Diagnosis of MS was based on the presence of abdominal obesity and at least two of the following components: hypertension, dyslipidemia, and glucose intolerance and/or hyperinsulinemia. RESULTS: BMI was correlated with both components of adipose tissue--subcutaneous (r = 0.66, P < 0.01) and VFA (r = 0.33, P < 0.02)--and leptin levels (r = 0.38, P < 0.01). In contrast, VFA was correlated with 2-h glucose and insulin levels (r = 0.32 and 0.35, P < 0.05, respectively), triglyceride, HDL cholesterol, and uric acid (r = 0.33, -0.34 and 0.24, P < 0.05, respectively). Subjects with high VFA, matched for BMI, showed greater plasma glucose area under the curve (621 +/- 127 vs. 558 +/- 129 mg x h(-1) x dl(-1), P < 0.05), 2-h insulin (804 +/- 599 vs. 579 +/- 347 pmol/l, P < 0.05), and uric acid levels (0.33 +/- 0.07 vs. 0.26 +/- 0.06 mmol/l, P < 0.05) than subjects with low VFA. In logistic regression analysis, waist circumference, VFA, and 2-h insulin were identified as independent predictors of MS. Receiver operating characteristic curve analysis pointed out the values of 104 cm for waist circumference (58.1% specificity, 84.1% sensitivity), 158.5 cm(2) for VFA (78.1% specificity, 52.3% sensitivity), and 559.8 pmol/l for 2-h insulin (71.9% specificity, 69.8% sensitivity); the presence of at least two of the three variables resulted in a degree of concordance of 76%. CONCLUSIONS: While BMI was unable to differentiate between obese people and those at higher risk for MS, abdominal fat was shown to be associated with its metabolic abnormalities. The usefulness of abdominal fat in the identification of high-risk subjects may be improved when combined with 2-h insulin determination.