G. De Pergola

Sleep-related breathing disorders, loud snoring and excessive daytime sleepiness in obese subjects.

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 kg/m2), 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 kg/m2) volunteers were also recruited for the study.MEASUREMENTS: Respiratory function parameters, nocturnal sleep quality (evaluated by a specific 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% (40/161), ie a quarter of all obese patients, were affected by severe OSA and this alteration was present in 42.1% of obese men (24/57) and in 15.4% (16/104) 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 significantly 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.

Effect of shift work on body mass index: results of a study performed in 319 glucose-tolerant men working in a Southern Italian industry

OBJECTIVE: To examine the influence of shift work on metabolic and cardiovascular risk factors in subjects working in an industry sited in Apulia, Southern Italy.DESIGN: Cross-sectional study of metabolic effects of shift work in glucose tolerant workers in a chemical industry in southern Italy.SUBJECTS: The subjects included 319 glucose tolerant male individuals, aged 35–60 y.MEASUREMENTS: Anthropometric parameters (body mass index (BMI) and waist-to-hip ratio (WHR)), fasting concentrations of glucose, insulin, and lipids (total cholesterol, HDL-cholesterol, triglycerides), the sum of glucose levels during 75 g-oral glucose tolerance test (Σ-OGTT), and systolic and diastolic blood pressure (SBP and DBP, respectively).RESULTS: The prevalence of obesity was higher among shift workers compared to day workers, whereas body fat distribution was not different between the two groups. Shift workers had higher BMI than day workers, and shift working was associated with BMI, independently of age and work duration. Shift workers had significantly higher SBP levels, which were independently influenced by BMI, but not by shift work, thus suggesting that the difference in SBP may well be mediated by the increased body fatness.CONCLUSION: In workers of an industry sited in Southern Italy, shift work may be directly responsible for increased body fatness and is indirectly associated with higher blood pressure levels and some features of metabolic syndrome.

C-reactive protein is independently associated with total body fat, central fat, and insulin resistance in adult women

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 (HOMAIR), as calculated by homeostatic model assessment.RESULTS: CRP was positively correlated with age, body mass index (BMI), waist, fasting glucose and insulin, HOMAIR, fat-free mass (FFM) and fat mass (FM). After multivariate analyses, age, HOMAIR, 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.

Plasma leptin is independently associated with the intima-media thickness of the common carotid artery

OBJECTIVE: To investigate whether intima-media thickness (IMT) of the common carotid artery (CCA), an early marker of asymptomatic atherosclerosis, is significantly 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 quantified 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 significantly 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 influence on the development of atherosclerosis. However, the association between IMT and leptin seems to be dependent and/or confounded by the relationship between IMT and obesity.

Low sleep quality and daytime sleepiness in obese patients without obstructive sleep apnoea syndrome

Abstract.  Resta O, Foschino‐Barbaro MP, Bonfitto P, Giliberti T, Depalo A, Pannacciulli N, De Pergola G (Respiratory Pathophysiology, University of Bari, School of Medicine, Bari, Italy; University of Foggia, School of Medicine, Foggia, Italy; and Internal Medicine, Endocrinology, and Metabolic Diseases, University of Bari, Bari, Italy). Low sleep quality and daytime sleepiness in obese patients without obstructive sleep apnoea syndrome. J Intern Med 2003; 253: 536–543.

The adipose tissue metabolism : role of testosterone and dehydroepiandrosterone

Testosterone (T) and dehydroepiandrosterone (DHEA) are fat-reducing hormones, even though they exert this effect by different mechanisms. In particular, T inhibits lipid uptake and lipoprotein-lipase (LDL) activity in adipocytes, and stimulates lipolysis by increasing the number of lipolytic β-adrenergic receptors. An indirect sign of these effects is the decrease of adipocyte leptin production. Lastly, T inhibits differentiation of adipocyte precursor cells. Concerning DHEA, this hormone does not seen to have any of T effects; however, DHEA stimulates resting metabolic rate (RMR) and lipid oxidation, and enhances glucose disposal, by increasing the expression of GLUT-1 and GLUT-4 on fat cell plasma membrane. The insulin-like effect of DHEA would be associated to a decrease of plasma insulin concentrations and, thus, to an increase of the molar ratio between lipolytic hormones and insulin. Noteworthy, the fat-reducing effect of both T and DHEA seems to be more evident at the level of visceral adipose tissue.Testosterone (T) and dehydroepiandrosterone (DHEA) are fat-reducing hormones, even though they exert this effect by different mechanisms. In particular, T inhibits lipid uptake and lipoprotein-lipase (LDL) activity in adipocytes, and stimulates lipolysis by increasing the number of lipolytic β-adrenergic receptors. An indirect sign of these effects is the decrease of adipocyte leptin production. Lastly, T inhibits differentiation of adipocyte precursor cells. Concerning DHEA, this hormone does not seen to have any of T effects; however, DHEA stimulates resting metabolic rate (RMR) and lipid oxidation, and enhances glucose disposal, by increasing the expression of GLUT-1 and GLUT-4 on fat cell plasma membrane. The insulin-like effect of DHEA would be associated to a decrease of plasma insulin concentrations and, thus, to an increase of the molar ratio between lipolytic hormones and insulin. Noteworthy, the fat-reducing effect of both T and DHEA seems to be more evident at the level of visceral adipose tissue.

Gender differences in serum leptin in obese people: relationships with testosterone, body fat distribution and insulin sensitivity

Testosterone levels are decreased in obese men but increased in obese women. The interplay between gonadal steroids and leptin is, at present, far from being elucidated. This study was carried out to investigate the relationship between serum leptin, plasma insulin, insulin sensitivity and free testosterone in 46 men (29 obese and 17 lean) and 65 premenopausal women (42 obese and 23 lean). In all subjects, anthropometric parameters and serum levels of insulin, leptin, free testosterone (T), dehydroepiandrosterone sulphate and sex hormone‐binding globulin were measured. An oral glucose tolerance test (OGTT) and an insulin tolerance test were also performed to determine the insulin sensitivity index. Our results show a significant difference in serum leptin between lean and obese men (3.19 ± 0.71 vs. 20.28 ± 0.26 ng mL−1; P < 0.0005) as well as between lean and obese women (10.78 ± 2.14 vs. 34.79 ± 2.26 ng mL−1; P < 0.00001). Basal T concentration in the obese men was significantly lower than in the control group (18.6 ± 1.3 vs. 23.3 ± 1.4 ng L−1; P < 0.01), whereas in the obese women it was significantly higher than in the control group (2.0 ± 0.2 vs. 1.3 ± 0.1 ng L−1; P < 0.05). When multiple linear regression was performed without body mass index (BMI) in the statistical model, leptin was correlated with basal insulin (P < 0.0001), insulin sensitivity (P < 0.0001) and T (P < 0.0001) in both men and women. When BMI was included in the model as an independent variable, leptin was significantly correlated only with BMI (P < 0.0001), the degree of insulin resistance (P < 0.05) and T (only in men, P < 0.05). This study confirms that serum leptin is strongly correlated with the degree of obesity and female sex. The negative correlation between leptin and T in men, independent of BMI, is consistent with the hypothesis that T may possess an inhibitory effect on adipocyte ob gene transcription.

Increase in both pro-thrombotic and anti-thrombotic factors in obese premenopausal women : relationship with body fat distribution

OBJECTIVE: To examine the relationship of obesity, body fat distribution, and fasting plasma insulin concentrations with the plasma levels of both pro-thrombotic and anti-thrombotic factors in premenopausal women. SUBJECTS: 32 obese women with BMI>28 and 33 age-matched non-obese=women with BMI<25. MEASUREMENTS: (i) plasma concentrations of plasminogen activator inhibitor-1 antigen (PAI-1 Ag), plasminogen activator inhibitor-1 activity (PAI-1 activity), fibrinogen, von Willebrand factor antigen (vWF Ag), von Willebrand factor activity (vWF activity), and factor VII activity as pro-thrombotic factors; (ii) plasma concentrations of tissue plasminogen activator antigen (t-PA Ag), protein C, and antithrombin III as anti-thrombotic factors; (iii) fasting plasma insulin and glucose concentrations, and the lipid pattern (triglycerides, total and HDL-cholesterol) as metabolic parameters. The body fat distribution was evaluated by measuring the waist circumference and the waist-to-hip ratio (WHR). RESULTS: Obese subjects had higher plasma concentrations of all pro-thrombotic factors as compared to non-obese controls (PAI-1 Ag, P<0.001; PAI-1 activity, P<0.05; fibrinogen, P<0.001; vWF Ag, P<0.001; vWF activity, P<0.05; factor VII, P<0.05). The plasma concentrations of PAI-1 Ag and vWF Ag were directly correlated with the waist circumference independently of other metabolic and non-metabolic variables (P<0.05). Obese women were also characterized by higher plasma concentrations of anti-thrombotic factors such as t-PA Ag and protein C as compared to non-obese controls (P<0.001 and P<0.001, respectively), although these factors were not independently correlated with the waist circumference or the WHR. CONCLUSION: Plasma concentrations of the pro-thrombotic factors are increased in obese women as compared to non-obese controls, and plasma levels of PAI-1 Ag and vWF Ag correlate with central fat accumulation specifically. Plasma concentrations of anti-thrombotic factors (namely protein C and t-PA Ag) are also raised in obese women, but they are not correlated with parameters of body fat distribution. The increase in protein C levels may represent a protective response partly counteracting the increase in pro-thrombotic factors in these individuals.

Gender, age and menopause effects on the prevalence and the characteristics of obstructive sleep apnea in obesity

Background  In the 1970s and 80s it was believed that obstructive sleep apnea (OSA) was primarily a disease of men. The present study was addressed to evaluate the effect of gender and menopause on the prevalence and the characteristics of OSA and on anthropometric, clinical, respiratory and polysomnographic data in a population of obese individuals.

Interrelationships between weight loss, body fat distribution and sex hormones in pre‐ and postmenopausal obese women

Objectives. Relationships between regional body fat distribution and sex hormones as well as changes in sex hormones after weight loss were evaluated.