OBJECTIVE:To investigate the prevalence of sleep breathing disorders, loud snoring and excessive daytime sleepiness in a group of obese subjects, and to identify the predictors of obstructive sleep apnea (OSA) severity in these patients. SUBJECTS: A total of 161 consecutive obese patients (body mass index (BMI) ! 30.0 kgam 2 ), ranging between 30.0 and 67.3, represented by 57 men and 104 women, aged 16 ± 75 y. Forty (15 men and 25 women) age-matched (20 ± 70 y) nonobese (BMI`27 kgam 2 ) volunteers were also recruited for the study. MEASUREMENTS: Respiratory function parameters, nocturnal sleep quality (evaluated by a speci®c questionnaire), nocturnal hypoventilation and OSA (evaluated by night polysomnography) were examined in all subjects. Anthropometric parameters (neck circumference, waist circumference, waist-to-hip ratio) were also investigated. RESULTS: Eighty-three obese patients (51.5% of the obese group) had a respiratory disturbance index (RDI) ! 10, corresponding to a moderate or severe sleep apnea. In particular, 24.8% (40a161), ie a quarter of all obese patients, were affected by severe OSA and this alteration was present in 42.1% of obese men (24a57) and in 15.4% (16a104) of obese women. When a stepwise multiple regression analysis was performed, neck circumference in men and BMI in women were shown to be the strongest predictors of sleep apnea. Twenty-nine percent of all obese subjects (40.3% of men and 23.1% of women) showed nocturnal hypoventilation; however, it was present as a unique breathing alteration in only 5% of the obese population. The percentage of patients having excessive daytime sleepiness was signi®cantly higher than in nonobese subjects, even when only nonapneic obese patients were considered (P`0.001). CONCLUSION: This study shows that OSA is present in more than 50% of a population of obese patients with a mean BMI higher than 40.0, this percentage being much higher than that commonly reported in previous studies, particularly in women. Neck circumference in men and BMI in women seem to be the strongest predictors of the severity of OSA in obese patients. Nocturnal hypoventilation seems to be present in more than 29% of a severe obese population. Moreover, this study indicates that morbid obesity can be associated with excessive daytime sleepiness even in the absence of sleep apnea.

OBJECTIVE:To investigate whether intima-media thickness (IMT) of the common carotid artery (CCA), an early marker of asymptomatic atherosclerosis, is signi®cantly and independently associated with plasma concentrations of leptin, an adipose tissue hormone that has recently been proposed as a cardiovascular risk factor in obese patients. DESIGN: Cross-sectional sample of normal-weight and obese men and women. SUBJECTS: One-hundred and twenty healthy subjects (52 men and 68 women), aged 18 ± 45 y and with a wide range of BMI, were recruited for the study. MEASUREMENTS: Fasting plasma leptin concentrations and the IMT of the CCA were measured in all subjects. Leptin concentrations were measured by radioimmunoassay and the IMT of the CCA was quanti®ed by high resolution B-mode ultrasound imaging. Central fat (measured by waist circumference), smoking habits, blood pressure, insulin sensitivity (measured by the insulin tolerance test), and fasting plasma glucose, insulin and lipid pattern (cholesterol, HDL-cholesterol, triglycerides, LDL-cholesterol) were also measured. RESULTS: IMT of the CCA was positively correlated with log leptin concentrations (P`0.005 in men and P`0.001 in women), body mass index (P`0.001 in men and women), waist circumference (P`0.001 in men and women), age (P`0.001 in men and P`0.05 in women), and negatively associated with insulin sensitivity in both sexes (P`0.05). IMT was also directly correlated with cholesterol (P`0.05), LDL-cholesterol (P`0.01) and systolic blood pressure in men (P`0.05), and with diastolic blood pressure levels in women (P`0.05). When a multiple linear regression model was used without body mass index (BMI), the correlation between leptin and IMT was maintained in both men (P`0.01) and women (P`0.005), independent of age, insulin sensitivity, smoking habits, systolic blood pressure, fasting glucose, triglycerides, cholesterol, LDL-cholesterol and HDL-cholesterol. By contrast, BMI-adjusted leptin concentrations were not signi®cantly associated with IMT (Pc (partial correlation): 0.41 in men and 0.15 in women). Moreover, when BMI was entered into a multiple linear regression model without leptin, the correlation between BMI and IMT was maintained in both men (P`0.005) and women (P`0.01), independent of the same parameters. CONCLUSION: Plasma leptin concentrations are independently associated with the IMT of the CCA, suggesting that the increase of adipose tissue mass (or leptin per se) may have an unfavourable in¯uence on the development of atherosclerosis. However, the association between IMT and leptin seems to be dependent andaor confounded by the relationship between IMT and obesity.

OBJECTIVE:To investigate whether C-reactive protein (CRP) concentrations are influenced by body composition, insulin resistance, and body fat distribution in healthy women. DESIGN: Cross-sectional study of CRP plasma levels in adult women. SUBJECTS: A total of 201 apparently healthy normal weight, overweight, and obese women, aged 18 -60 y. MEASUREMENTS: CRP plasma levels, several fatness and body fat distribution parameters (by bioimpedance analysis and anthropometry), and insulin resistance (HOMA IR ), as calculated by homeostatic model assessment. RESULTS: CRP was positively correlated with age, body mass index (BMI), waist, fasting glucose and insulin, HOMA IR , fat-free mass (FFM) and fat mass (FM). After multivariate analyses, age, HOMA IR , waist and FM maintained their independent association with CRP. CONCLUSION: Our study has shown an independent relationship of central fat accumulation and insulin resistance with CRP plasma levels, thus suggesting that mild, chronic inflammation may be a further component of the metabolic syndrome and a mediator of the atherogenic profile of this syndrome.

Conflicting results have been reported regarding whether the PPAR␥2 Pro12Ala polymorphism plays a role in the risk of type 2 diabetes (T2D), suggesting genetic heterogeneity. To investigate this issue, a meta-analysis of 41 published and 2 unpublished studies (a total of 42,910 subjects) was conducted. Ala12 carriers had a 19% T2D risk reduction, but this association was highly heterogeneous (p ϭ 0.005). A great proportion (48%) of heterogeneity was explained by the controls' BMI, with risk reduction being greater when BMI was lower. Risk reduction of Ala12 carriers in Asia (35%) was higher than in Europe (15%, p ϭ 0.02) and tended to be higher than in North America (18%, p ϭ 0.10). Difference between Asians and Europeans was no longer significant (p ϭ 0.15) after adjusting for the controls' BMI. Studies from Europe were still heterogeneous (p ϭ 0.02) with risk reduction in Ala12 carriers being progressively smaller (test for trend in the odds ratios, p ϭ 0.02) from Northern (26% reduction, p Ͻ 0.0001) to Central (10%, p ϭ 0.04) and Southern (0%, p ϭ 0.94) Europe. In conclusion, in our meta-analysis, the reduced risk of T2D in Ala12 carriers is not homogeneous. It is greater in Asia than in Europe and, among Europeans, it is higher in Northern Europe, barely significant in Central Europe, and nonexistent in Southern Europe. Key words: peroxisome proliferator-activated receptor, genetic susceptibility, candidate genes, type 2 diabetesThe peroxisome proliferator-activated receptor ␥2 (PPAR␥2) 1 is a key modulator of adipogenesis and insulin signaling (1). A single nucleotide polymorphism (SNP) in the PPAR␥2 gene, giving a Pro12Ala substitution, has been described (2). Although most studies have shown a statistically significant type 2 diabetes (T2D) risk reduction given by the Ala12 variant (3-11), some others have not (10 -36), thus suggesting variability in the contribution of this variant to the risk of T2D. To investigate this issue, a comprehensive meta-analysis of 41 published studies (3-36) and two unpublished Italian studies was conducted for a total of 42,910 individuals, which, to the best of our knowledge, is the largest one so far conducted (6,37,38). An additional aim of this study was to investigate the effect of covariates on genetic heterogeneity by meta-regression analysis.

It is well known that obstructive sleep apnoea is especially frequent in the morbidly obese. In these subjects diurnal chronic hypercapnia, whose mechanism is still debated, may be present. Our study was performed to evaluate the prevalence and the mechanism of diurnal hypercapnia in the morbidly obese affected by obstructive sleep apnoea. From a population referred to our centre because of suspicion of sleep related breathing disorders, we selected 285 subjects without cardiopulmonary, neuromuscular or endocrinological diseases: 89 (36 M and 53 F, aged 46+/-13 years) had body mass index (BMI) > or = 40 kg m(-2) (MO group: morbidly obese subjects) and 196 (99 M and 97 F, aged 48+/-16 years) had BMI <40 kg m(-2) (NMO group: non-morbidly obese subjects). Then the MO group was divided into three subgroups: normocapnic subjects without obstructive sleep apnoea, normocapnic subjects with obstructive sleep apnoea, hypercapnic subjects with obstructive sleep apnoea; while we found no hypercapnic subject without obstructive sleep apnoea. All subjects underwent anthropometric evaluations and bioelectrical impedance analyses, respiratory function tests and arterial blood gas analysis, a modified version of the Sleep and Healthy questionnaire and a full night polysomnography. Our results showed that hypercapnia (PaCO2 > or = 45 mm Hg) associated with obstructive sleep apnoea [respiratory disturbance index (RDI) > or = 10 h(-1)] was found in 27% of the morbidly obese subjects, but only in 11% of the nonmorbidly obese ones (P<0.01). The comparison among the three subgroups, in which we divided the morbidly obese subjects, shows that those with hypercapnia and obstructive sleep apnoea had significantly more important ventilatory restrictive defects [forced vital capacity (FVC)% of pred 73.27+/-14 81 vs. 82.37+/-16.93 vs. 87.25+/-18.14 respectively; total lung capacity (TLC)% of pred 63.83+/-16.35 vs. 79.11+/-14.15 vs. 87.01+/-10.5], a significantly higher respiratory disturbance index (RDI 46.34+/-26.90 vs. 31.79+/-22.47 vs. 4.98+/-3.29) a longer total sleep time with oxyhaemoglobin saturation<90% [total sleeptime (TST)SaO2<90% 63.40+/-33.86 vs. 25.95+/-29.34 vs. 8.22+/-22.12] and a lower rapid eye movement (REM) stage (9.5+/-1.2 vs. 14.0+/-0.9 vs. 17.05+/-1.2) than normocapnic subjects with obstructive sleep apnoea or subjects without obstructive sleep apnoea. The best model to predict PaCO2 resulted from a combination of TSTSaO2<90% (r2 = 0.22, P<0.001), forced expiratory volume in 1 sec (FEV1)% of pred (r2 = 0.09, P<0.01), FVC % of pred (r2 = 0.075, P<0.01). In conclusion our study suggests that diurnal hypercapnia is frequently associated with obstructive sleep apnoea in the morbidly obese without chronic obstructive pulmonary disorder (COPD) and that ventilatory restriction and sleep related respiratory disturbances correlate to diurnal hypercapnia.