Effects of body composition on the procoagulant imbalance in obese patients.

Obesity is associated with increased thrombotic risk and hypercoagulability whose main driver is an excess of coagulation factor VIII relative to protein C. The aims of this study were to evaluate the association between factor VIII, protein C, factor VIII-to-protein C ratio and bioimpedance parameters of body composition in obese patients. We analysed blood from 69 obese patients and 23 non-obese healthy controls. Plasma levels of factor VIII, protein C, and factor VIII-to-protein C ratio were correlated with total fat, visceral fat, and muscle mass. Compared to controls, obese patients had significantly higher factor VIII (110.5% vs 78.05%, p < 0.001), protein C (120.99% versus 110.51%, p = 0.014), and factor VIII-to-protein C ratio (0.93 versus 0.73, p = 0.002). In obese patients, factor VIII correlated with body-mass index, body fat percentage, muscle mass percentage, and fat-to-muscle ratio, whereas protein C had significant relationships with body fat percentage, muscle mass percentage and fat-to-muscle ratio, but not with body-mass index. Factor VIII-to-protein C ratio > 1 was significantly associated with body-mass index (odds ratio 1.08, 95% CI 1.02 to 1.14) and fat-to-muscle ratio (odds ratio 2.47, 95% CI 1.10 to 5.55). Factor VIII-to-protein C ratio strongly correlated with D-dimer levels in the overall population (rho 0.44, p < 0.001) and obese patients (rho 0.41, p < 0.001). In obese patients, bioimpedance measures of body fat and muscle mass percentage were associated with factor VIII and protein C. Factor VIII-to-protein C ratio was strongly associated with fat-to-muscle ratio and only modestly related to BMI.

From Endothelium to Lipids, Through microRNAs and PCSK9: A Fascinating Travel Across Atherosclerosis.

Lipids and endothelium are pivotal players on the scene of atherosclerosis and their interaction is crucial for the establishment of the pathological processes. The endothelium is not only the border of the arterial wall: it plays a key role in regulating circulating fatty acids and lipoproteins and vice versa it is regulated by these lipidic molecules thereby promoting atherosclerosis. Inflammation is another important element in the relationship between lipids and endothelium. Recently, proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recognized as a fundamental regulator of LDL-C and anti-PCSK9 monoclonal antibodies have been approved for therapeutic use in hypercholesterolemia, with the promise to subvert the natural history of the disease. Moreover, growing experimental and clinical evidence is enlarging our understanding of the mechanisms through which this protein may facilitate the genesis of atherosclerosis, independently of its impact on lipid metabolism. In addition, environmental stimuli may affect the post-transcriptional regulation of genes through micro-RNAs, which in turn play a key role in orchestrating the crosstalk between endothelium and cholesterol. Advances in experimental research, with development of high throughput techniques, have led, over the last century, to a tremendous progress in the understanding and fine tuning of the molecular mechanisms leading to atherosclerosis. Identification of pivotal keystone molecules bridging lipid metabolism, endothelial dysfunction and atherogenesis will provide the mechanistic substrate to test valuable targets for prediction, prevention and treatment of atherosclerosis-related disease.

[What do we know about obesity?]. / Cosa sapere sul problema obesità?

The prevalence of obesity is increasing rapidly in most industrialized countries and it is known that obesity is associated with increased risk of cardiovascular morbidity and mortality. Commonly, obesity is defined by the Body Mass Index (BMI). However, BMI fails to consider body fat distribution. The relationship between the risk of metabolic-cardiovascular diseases and body fat distribution indices, rather than measures of the degree of body fatness as expressed by BMI, has long been recognized. Clinical and epidemiological research has found waist circumference to be the best anthropometric indicator of both total body fat and intra-abdominal fat mass. Android obesity is associated with metabolic syndrome and increased cardiovascular risk through molecular mechanisms possibly linking the metabolic syndrome to hemostatic and vascular abnormalities. Obesity guidelines suggest the need for weight reduction using behavioural change to reduce caloric intake and increasing physical activity. A realistic goal for weight reduction is to reduce body weight by 5% to 10% over a period of 6 to 12 months. Combined intervention of a low calories diet, increased physical activity, and behaviour therapy provides better outcomes for long-term weight reduction and weight maintenance than programs that use only one or two of these modalities. The anorexiant drugs affect neurotransmitters in the brain. The sibutramine has norepinephrine and serotonin effects. Orlistat has a different mechanism of action: the reduction of fat absorption. Recently, the blockade of the endocannabinoid system with rimonabant may be a promising new strategy.

Association between circulating adiponectin and interleukin-10 levels in android obesity: effects of weight loss.

OBJECTIVE: Adiponectin inhibits vascular inflammation and increases IL-10 mRNA expression in human macrophages. Thus, we investigated the possible relationship between plasma adiponectin and IL-10 levels and the effects of a diet-induced moderate weight loss on both cytokines. PATIENTS AND STUDY DESIGN: Plasma adiponectin and IL-10 levels were analyzed in 64 android [body mass index (BMI), > 28 kg/m2; waist to hip ratio (WHR), > or = 0.86] and 20 gynoid [BMI, > 28 kg/m2; WHR, < 0.86] obese healthy women. Android obese women (49 +/- 14 yr) had a mean BMI of 37.1 +/- 5.3 kg/m2, similar to that of gynoid obese women (49 +/- 11 yr; BMI, 33.4 +/- 2.6 kg/m2). Twenty nonobese control women (46 +/- 11 yr; BMI, 25.2 +/- 2.2 kg/m2) were also studied. In 15 android obese women, measurements were repeated after a 12-wk diet period (1200 kcal/d). RESULTS: Median adiponectin [5.2 (range, 3.3-7.8) vs. 12.1 (9.7-13.9) vs. 15.0 (12.6-18.2) microg/ml; P < 0.0001] and IL-10 [1.8 (1.2-3.3) vs. 3.5 (2.9-4.3) and vs. 4.1 (3.5-4.8) pg/ml; P < 0.0001] levels were lower in android vs. gynoid vs. nonobese women. Among android obese women, low adiponectin levels were independently related (P < 0.0001) to decreased IL-10 levels, independently of BMI, WHR, or insulin resistance. No significant change in either median adiponectin or IL-10 levels was observed after body weight reduction (8 +/- 4 kg; P < 0.01), although percent changes in adiponectin paralleled those in IL-10 (P < 0.05). CONCLUSIONS: Android obesity is associated with a concomitant reduction of IL-10 and adiponectin levels. However, the antiinflammatory status of obesity might require prolonged periods of energy-restricted diets to revert to normal.

Prevalence and severity of airway obstruction in an Italian adult population.

BACKGROUND: This study sets out to estimate the prevalence and the degree of severity of bronchial obstruction in an adult population with three different diagnostic criteria: the European Respiratory Society (ERS), the American Thoracic Society (ATS), and the World Health Organization (WHO) defined as Global Obstructive Lung Disease (GOLD). METHODS: 1514 subjects underwent complete medical evaluation and spirometry. RESULTS: The prevalence of bronchial obstruction was respectively 27.5 % (ERS), 33% (GOLD), and 47.3 % (ATS). The prevalence of bronchial obstruction in the smoker group was 33.4% (ERS), 38.1% (GOLD), and 52.3% (ATS). The prevalence of obstruction in the ex-smoker group was 33% (ERS), 41.4% (GOLD), and 57.1% (ATS). The prevalence of obstruction in the non-smoker group was 21.1% (ERS), 24.9% (GOLD), and 38.6% (ATS). CONCLUSIONS: The results show that the prevalence of airway obstruction increases proportionally with age; the cigarette smoking represents an important conditioning factor. These observations warrant the necessity of a more complete and multi-parametric analysis in the evaluation of patients with airway obstruction using methodologies that explore the functional state and the risk factors that cause the airway obstruction.

Oxidative stress drivers and modulators in obesity and cardiovascular disease: from biomarkers to therapeutic approach.

This review article is intended to describe how oxidative stress regulates cardiovascular disease development and progression. Epigenetic mechanisms related to oxidative stress, as well as more reliable biomarkers of oxidative stress, are emerging over the last years as potentially useful tools to design therapeutic approaches aimed at modulating enhanced oxidative stress "in vivo", thereby mitigating the consequent atherosclerotic burden. As a paradigm, we describe the case of obesity, in which the intertwining among oxidative stress, due to caloric overload, chronic low-grade inflammation induced by adipose tissue dysfunction, and platelet activation represents a vicious cycle favoring the progression of atherothrombosis. Oxidative stress is a major player in the pathobiology of cardiovascular disease (CVD). Reactive oxygen species (ROS)- dependent signaling pathways prompt transcriptional and epigenetic dysregulation, inducing chronic low-grade inflammation, platelet activation and endothelial dysfunction. In addition, several oxidative biomarkers have been proposed with the potential to improve current understanding of the mechanisms underlying CVD. These include ROS-generating and/or quenching molecules, and ROS-modified compounds, such as F2-isoprostanes. There is also increasing evidence that noncoding micro- RNA (mi-RNA) are critically involved in post- transcriptional regulation of cell functions, including ROS generation, inflammation, regulation of cell proliferation, adipocyte differentiation, angiogenesis and apoptosis. These molecules have promising translational potential as both markers of disease and site of targeted interventions. Finally, oxidative stress is a critical target of several cardioprotective drugs and nutraceuticals, including antidiabetic agents, statins, renin-angiotensin system blockers, polyphenols and other antioxidants. Further understanding of ROS-generating mechanisms, their biological role as well as potential therapeutic implications would translate into consistent benefits for effective CV prevention.

Leptin increase is associated with markers of the hemostatic system in obese healthy women.

BACKGROUND: Leptin, a hormone secreted by the adipose tissue, might be a link between obesity and increased morbidity for cardiovascular disease. Leptin exerts proinflammatory, pro-angiogenic actions by activating a specific receptor (Ob-Rb) which is expressed in human endothelial cells. Thus, a link may exist between leptin expression and endothelial dysfunction. OBJECTIVES: We sought to determine whether in obese women there is a correlation between leptin levels, endothelial perturbation and coagulative activation. METHODS: Circulating levels of leptin, von Willebrand Factor (VWF), factor (F)VIIa, prothrombin fragment 1 + 2 (F1+2), were measured in 51 non-diabetic, obese women and in 51 normal-weight subjects, using immunoenzymatic assays. RESULTS: Obese women had significantly higher levels of leptin, VWF, FVIIa, F1+2 compared with healthy women. Simple correlation coefficients showed significant correlation between leptin and either VWF, FVIIa, or F1+2 concentrations. A multiple linear regression analysis, performed to quantify further the relationship between leptin levels and the above-mentioned variables as well as the inflammatory marker C-reactive protein (CRP) and including age, body mass index (BMI), waist-hip ratio (WHR) and lipid parameters as potential confounders, revealed that only FVIIa and VWF were independently related to leptin levels. Reduction in adipose tissue after weight loss resulted in a decrease in both circulating leptin and endothelial and coagulative activation markers. CONCLUSIONS: We suggest that leptin might have pro-atherogenic effects in vivo, with a mechanism involving endothelial cell activation.

Ambulatory blood pressure monitoring in evaluating the relationship between obesity and blood pressure.

The relationship of body mass index, body fat, waist to hip ratio, fasting blood glucose and sum of blood glucose levels during oral glucose tolerance test with casual blood pressure (BP) and BP parameters obtained by 24h ambulatory BP monitoring in 97 out-patients moderately obese (66 with android type obesity), normal glucose tolerance and mild hypertension at entry study, has been evaluated. A negative correlation between body mass index and systolic ambulatory BP levels as the 24h mean, daytime and nighttime, has been documented in all of the obese subjects; no correlations between body mass index and casual BP were shown. Only in the group of android type obese was the body mass index correlated positively with the casual DBP. Systolic 24h and nighttime BP values correlated positively with waist to hip ratio; the correlation coefficients improved in the subgroup of android type obese. By using 24h ambulatory BP monitoring, it may be possible to show that waist to hip ratio is a better predictor of systolic hypertension than other parameters such as those derived from weight and height measurements and body fat percentage.

The prevalence of hypertension in gynaecoid and android obese women.

Until now the different epidemiological studies performed have yielded widely different results in terms of the prevalence of hypertension in obese patients. This is mainly due to methodological errors in blood pressure (BP) measurements, including such false positives as white-coat or cuff hypertension, and more recently, to the different distribution in the study population of obese subjects at risk of hypertension (android obesity type). In 803 obese outpatient women (body mass index range: 28-45) randomly selected and subdivided into younger and older groups, and into android and gynaecoid, the casual BP was measured in the morning with a large size cuff. In addition, in 82 obese outpatients casual BP was measured simultaneously with the large and a standard size cuff. Another group of 94 patients was submitted to 24-h ambulatory blood pressure monitoring (ABPM). The aim was to observed if the use of inappropriate cuffs, or the incidence of white-coat hypertension and the prevalence of obese subjects at risk of hypertension, may contribute considerably to overestimating the prevalence of hypertension in obesity. The hypertension prevalence rate was 37.6% for the entire study group. The prevalence rate was 26.2% in women with gynaecoid type of obesity and 47.1% in android obese subjects. We could conclude that the use of inappropriate cuffs, office or white-coat hypertension and the prevalence of obese subjects at risk of hypertension, may contribute considerably to overestimating the prevalence of hypertension in obesity. The number of hypertensive subjects in younger obese subjects with gynaecoid fat distribution is similar to non-obese subjects who are age-adjusted, but our data confirm that the prevalence of hypertension in android type of obesity is significantly higher than in non-obese subjects.

Risk factors for hypertension in obese women. The role of weight cycling.

OBJECTIVE: To study significant factors associated with the risk of hypertension among obese women, with and without a history of weight cycling (WC). DESIGN: Case-control study. SETTING: Obesity Clinic of Chieti University, Italy. SUBJECTS: A group of 258 obese women aged 25-64 y (103 cases with hypertension and 155 controls) were recruited. All obese subjects had the same clinical characteristics, were without a family history for hypertension, were non-smokers, had normal lipidemic profiles and normal glucose tolerance, were not taking any medication and were otherwise healthy. INTERVENTION: In the weight cycling women, the history of WC was established on the basis of at least five weight losses in the previous 5 y due to dieting, with a weight loss of at least 4.5 kg per cycle. A logistic regression model adjusted for confounding variables such as waist-to-hip ratio (WHR) and weight cycling history parameters was used and the odds ratio (OR) with 95% confidence intervals was calculated. RESULTS: The risk of hypertension increases in subjects with larger WHR (OR 7.8; 95% CI 3.4-17.9) and with a positive history for WC (OR 4.1; 95% CI 2.4-6.9). Further, in obese patients with WC, the weight cycling index and the sum of the weight regained are also important risk factors for hypertension. CONCLUSIONS: These findings could support the hypothesis that it is the combined exposure of central-type obesity and WC that strongly raises the risk of hypertension. SPONSORSHIP: This work has been financially supported by a grant of Ministero dell'Università e della Ricerca Scientifica e Tecnologica.

Many factors can affect the prevalence of hypertension in obese patients: role of cuff size and type of obesity.

OBJECTIVE: To determine to what extent methodological errors, including measurements taken with inappropriate cuffs and/or inaccuracies in patient enrollment, can contribute to overestimating the prevalence of hypertension in overweight or obese women. EXPERIMENTAL DESIGN: Randomized and comparative investigation in overweight or obese outpatient women of the Obesity Clinic, Internal Medicine Institute, Chieti University. PATIENTS: In 1,791 overweight or obese women, randomly selected and stratified by age (41-60 years), blood pressure (BP) was taken with casual measurement in the morning. The entire study group was divided into two subgroups. In the first one, causal BP was measured with a standard-size cuff (RCS), while an appropriate large-size cuff was used for the second one (LCS). Patients of the latter subgroup were also divided by type of obesity (android and gynoid), based on their waist-to-hip ratio. RESULTS: In the LCS subgroup, the hypertension prevalence rate was strikingly lower among overweight and obese women, as well as in the younger and older age groups, when compared with the corresponding RCS subgroups (p < 0.001). The hypertension prevalence rate was higher for all android obese subjects (53%), including younger (34%) and older (64%) groups, when compared with gynoid obese patients (29%, 18% and 42%, respectively). CONCLUSIONS: A comparison of different reports on the prevalence of hypertension in obesity reveals considerable differences, due mainly to age, sex, race and income level. Nevertheless, our data seem to indicate that even after adjusting for the above-mentioned variables, two significant confounding factors, cuff hypertension and the prevalence of android obesity in the obese study population, could be responsible for over-estimating the prevalence of hypertension. It should be noted that for certain groups of overweight and obese women, the prevalence of hypertension becomes similar to the rate found among the general population, as reported in many large epidemiological surveys.

Does holiday hypoglycaemia exist?

BACKGROUND: To determine whether an excessive, prolonged and, above all, unusual physical exertion could be associated with episodes of mild hypoglycaemia in non-insulin-dependent diabetes mellitus (NIDDM) patients treated with glibenclamide. EXPERIMENTAL DESIGN: 11 months of observation with retrospective analysis of patient personal diaries to determine the hypoglycaemic risk. SETTING: Diabetic Unit-Department of Medicine and Aging-Chieti University School of Medicine. PATIENTS: We enrolled 340 NIDDM outpatients adjusted for sex, age, body mass index, alcohol intake and oral treatment regimen with glibenclamide. PATIENTS were tested monthly for circadian blood glucose profiles and glycosylated hemoglobin. Mild hypoglycaemia was defined on the basis of blood glucose values < 2.8 mmol/l associated with mild autonomic symptoms, without requiring external assistance. Each diabetic patient filled personal diary indicating the therapy regimen and the characteristics of eventual hypoglycaemic episodes occurring during the observation period. RESULTS: 21.8% of NIDDM patients experienced one or two episodes of mild hypoglycaemia during the observation period. The analysis of the patients' diaries showed that 60% of the hypoglycaemic episodes was associated with excessive, prolonged and unexpected physical exertions. Within this group, about 70% of the episodes occurred during a holiday ("holiday hypoglycaemia"). After analyzing the socio-demographic and clinical characteristics of the diabetic patients reporting hypoglycaemic events, we found a higher risk for "holiday hypoglycaemia" in patients with a lower educational level, with a sedentary occupation or among the ex-farmers. CONCLUSIONS: As resulted in the present study, unexpected physical exertions may represent a relevant cause of mild hypoglycaemia in diabetic patients receiving oral antidiabetic therapy. However, this hypoglycaemic cause may have been underestimated in the literature. Educational programs conducted by general practitioners or diabetologists could be useful for the patients in reducing the number of mild hypoglycaemic episodes.

Circannual rhythm of insulin release and hypoglycemic effect of tolbutamide stimulus in healthy man.

Four healthy non obese young volunteers were observed for a 24-hr period, every other month, over the course of one year. Tolbutamide was injected i.v. each day of the experiment every four hours. Tolbutamide-induced insulin secretion (T.I.I.S.) was evaluated by planimetrically measuring insulin areas above basal levels. Tolbutamide-induced hypoglycemic effect was evaluated by measuring the blood glucose difference between the 5th and 25th minute after the drug injection (delta G5'-25'). The macroscopic evaluation of T.I.I.S. and delta G5'-25' (mean chronograms) permitted the detection of the existence of a circannual variation of both variables. In particular the maximum level of the blood glucose drop (delta G5'-25') was registered in February. Subsequently the quantification of the rhythm of T.I.I.S. was obtained by fitting a sine curve, according to the Cosinor method. The highest insulin release was confirmed in winter. As previously documented, the existence of a statistically significant circadian rhythm of T.I.I.S. was confirmed in the morning, i.e. the same period of the day in which insulin-induced hypoglycemia occurs.

Time-related behaviour of endocrine secretion: circannual variations of FT3, cortisol, HGH and serum basal insulin in healthy subjects.

Four healthy young male volunteers were submitted to the study of circadian and circannual bioperiodicities of several hormones: FT3, FT4, cortisol, HGH, prolactin, PTh and plasma insulin levels. They were observed for a whole year and their blood samples were collected six times a day, every other month. The results were analyzed by two-way ANOVA macroscopic analysis and Student t-test. Our data registered a circannual variation in the mean circadian plasma levels of the following hormones: cortisol (peak in December), HGH (peak in April), FT3 (peak in April), insulin (peak in February). FT4, prolactin and PTH showed no cyclic variation during the period of observation.

Association of body mass index and regional fat distribution with blood pressure investigated by 24-hour ambulatory blood pressure monitoring in android-type obese.

In 46 female outpatients with android-type obesity, body mass index (BMI) 36.6 +/- 1.0, waist to hip ratio (WHR) > 0.86, and normal glucose tolerance (NGT) who were hypertensive at entry study [blood pressure (BP) > 140/90 mm Hg] and in 10 clinically healthy, nonobese, normotensive women, we evaluated the relationship between BMI, fat mass, WHR, fasting blood glucose, sum of blood glucose levels during oral glucose tolerance test and casual BP levels, 24-h ambulatory BP monitoring (ABP) parameters as the 24-hour mean, day-time mean, night-time mean and, by using a periodic model of cosine regression, MESOR (midline estimating statistic of rhythm), amplitude, acrophase, and baric impact. In android obese women, a negative correlation between ABP levels (day-/night-time, MESOR, and baric impact of systolic BP; night-time and MESOR of diastolic BP) and BMI has been documented. A positive correlation between systolic BP (casual, night-time mean, MESOR, amplitude, and baric impact), diastolic baric impact, and the WHR has been found. No correlation has been demonstrated between ABP monitoring parameters, and BMI, body fat, and WHR in the control group. Our data could suggest that, when enrolling obese subjects, it must be taken into account that obesity is a heterogeneous disorder. There are in fact obese subjects with normal or impaired glucose tolerance, as well as diabetics with moderate to severe obesity and with gynecoid or android-type obesity. In our android obese subjects with NGT, the WHR rather than the BMI was found to be a better predictor of hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

[Relationship between eating behavior and distribution of body fat]. / Relazione tra comportamento alimentare e distribuzione del grasso corporeo.

In these recent few years the study of the pathogenesis of obesity include the observation of the difference in eating behaviour between obese and non obese subjects. Therefore, current therapies now take into account, among others, also a program of behavioural therapy. On the other hand, recent studies have revealed the role of different body fat distribution on the obesity prognosis, especially considering cardiovascular risk factors. To this purpose much attention has been focused on the measurement of waist and hips circumferences and their ratio (WHR) considered important predictors of risk associated with obesity. Aim of this study was the observation of some differences in eating habits and psychological status during a 24-hr period in relationship with the android or gynecoid type of obesity. 102 outpatients were divided in two groups: 1) with WHR less than 0.85; 2) with WHR greater than or equal to 0.85. All subjects were given a questionnaire in which by a scale from 0 to 3 they expressed their appetite sensation during different hours of the day. In addition, they indicated their motivation to loose body weight. Our results demonstrated that subjects with WHR greater than or equal to 0.85 showed higher appetite sensation, during the whole day, with a peak at lunch, in comparison with subjects with WHR less than 0.85. Subjects with gynecoid type of obesity seemed to pay much attention to their body image than subjects with android type of obesity and complained less physical disorders than subjects of the second group. These preliminary data seem to suggest a non-secondary role of behavioural pattern in obesity also by affecting the different regional fat distribution.

Long-term treatment with fenfluramine in obese subjects.

The effect of fenfluramine, an anorectical drug, given for nine months to a group of 156 obese subjects, on body-weight and adipose mass reduction as well as on glucose tolerance, has been studied. Subjects were divided in four different groups according to various protocols of therapy: the first group took the drug once a day in a single 60 mg dose in the morning; the second group received the drug once a day in a single 40 mg dose in the morning; the third group took the drug divided in three equal daily doses and the last group was treated with diet alone. During the first three months of treatment, fenfluramine 60 mg, given both in a single dose in the morning and divided in three equal daily doses, combined with diet, produces a significant body-weight reduction in comparison with the group of obese subjects treated with diet alone. In the following three months, it was possible to document a further body weight loss in all subjects, whatever the group to which they were assigned. At the end of the sixth month of observation, only slight differences could be demonstrated among the groups as regards the body-weight and adipose mass decrease. In addition the results failed to demonstrate a statistically different weight loss when the drug as administered in a single dose in the morning, compared with the conventional treatment of three times a day. No significant improvement of glucose tolerance was documented. In conclusion, in long-term treatment with fenfluramine, in contrast with short-term studies, no direct effect of this drug on body-weight and adipose mass decrease was demonstrated.

Hyperinsulinaemia in hypertension and diabetes mellitus: a chronobiological approach.

Blood pressure was continuously recorded for 24 h in 31 non-insulin-dependent diabetic men with borderline, mild, or moderate systolic and/or diastolic hypertension. A 2-h oral glucose tolerance test was also performed with blood glucose, serum insulin and C-peptide determination at 30-min intervals. Significant correlations were found between fasting and post-glucose integrated area of blood glucose, insulin and C-peptide concentrations versus blood pressure measures. Total insulin area appeared to correlate significantly with diastolic measures [casual, daytime, night-time, mean computational (mesor), hyperbaric impact and percent time elevation], mean blood pressure, and mesor and hyperbaric impact systolic measures. It is concluded that the more accurate assessment of the circadian pattern of blood pressure by a chronobiological procedure allowed the existence of close correlations between metabolic and blood pressure measures to be established, confirming the importance of hyperinsulinaemia in the pathophysiology of arterial hypertension.

Chronobiology in endocrinology.

Temporal endocrine structure (TES). It can be defined as a combination of predictable hormonal changes that are time-related. Regarding their frequency, endocrine rhythms may be circadian, ultradian and infradian. In this context, the endocrine circadian time structure (ECTS), that is closely dependent of some areas of the hypothalamus, is of particular interest. Long and short loop feedback link together the various components: central nervous system (CNS), hypothalamus and anterior pituitary with target glands and tissues. The hypothalamic neuropeptides (releasing hormones or factors - RH or RF - or inhibiting hormones or factors IH or IF) presently known are: thyrotropin releasing hormone (TRH); luteinizing releasing hormone (LH RH); prolactin releasing factor (PRF); Prolactin Inhibiting Factor (PIF); Corticotropin Releasing Factor (CRF); Growth Releasing hormone (GH RH). Some general remarks on endocrine rhythms should be noted: the circadian changes in hormones may depend on each other; even an apparently subordinate rhythm should be considered a true independent rhythm; accurate studies have shown that hormonal secretion occurs in all cases according to a rhythmic organization at many levels; these rhythms may not be evident at a first analysis. The hormone secretion is basically pulsating which makes it difficult to draw standard reference values. Although an ECTS is present at the cell level, in organs etc., it is evident that a rhythm hierarchy exists. Hormonal secretion and sleep-wake cycle. Although several reports state that no rhythm is totally dependent on the sleep-wake cycle, from a general point of view the hormone secretion rhythms can be divided in: sleep-dependent rhythms and sleep-independent rhythms. Meal-timing and hormonal secretion. In animals, meal-timing is a powerful synchronizer; however, there are no definitive and conclusive data to prove that meal-timing is a true synchronizer also in humans, although there have been some reports suggesting it. Endocrine rhythms. Data regarding the endocrine rhythms (circadian-ultradian-infradian) of the numerous hormones as GH; prolactin; aspects of temporal pattern of CRF-ACTH-corticosteroid and of hypothalamic - pituitary - thyroids axis; hypothalamic - pituitary - ovaric steroid and testosterone axis are reported. The study of a possible rhythmic pattern of insulin has been approached from many points of view as the basal rhythmicity of insulin; the diurnal variation of efficacy of injected insulin and of insulin responsiveness to insulinogenic stimuli.

[Role of leptin in anorexia nervosa]. / Il ruolo della leptina nell'anoressia nervosa.

Anorexia and bulimia nervosa are the main psychiatric disorders characterised by abnormal models of feeding and perception of people's personal physical appearance and weight. These symptoms are associated with a severe psychosocial uneasiness that leads to severe medical complications and this, to its turn, has a big impact on morbidity and sick rate of general population. Although researchers have made big improvements in individualising some likely pathogenic mechanisms that include different factors (genetic, neurochemical and sociocultural) and psychological development, the pathogenesis of these kinds of feeding disorders is still unknown. Leptina is a neurochemical factor particularly relevant. It is a 17 KD hormone, produced by adipocytes. At hypothalamic level, it is essential for regulating body weight and body development. Recent studies have identified some factors responsible for the production and the secretion of leptina. They are micro and macronurishing factors, hormones and the sympatic neurotic system that is the most important among them. It plays a very important role for some disorders of feeding behaviour, specifically for the anorexia nervosa, where we notice a reduction of leptina levels strictly correlated to a reduction of the fat component. Since anorexia nervosa is associated to medical, nourishing and psychological components, it involves different areas and needs complete measurement and administration. Therefore the approach to this kind of pathology has necessarily to predict a multidisciplinary administration of patients. The aim of our work has been to point out the possible interactions between leptina and the development and progression of anorexia nervosa, on the basis of recent works and reviews in medical literature.