METABOLIC ASPECTS OF NIGHT apnea
Mauro Lombardo, Annalisa Del Monte
Division of Human Nutrition, Department of Neuroscience, Faculty of Medicine, University of Rome Tor Vergata.
is defined as obstructive sleep apnea syndrome (OSAS) the occurrence of more than five episodes of apnea per hour of sleep or thirty-five episodes per night, where for apnea means the cessation of airflow at the mouth and nose for more than 10 seconds. The threshold of five episodes per hour distinguishes normality from pathology, in fact, a minimum number of episodes apneic is also observed in normal subjects.
Gastaut and associates described the first three types of apnea: obstructive, central and mixed. The obstructive form is typical of OSAS is characterized by a cessation of air flow and the persistence of the movements of the chest wall.
The central form but is a less common form that affects children who have an immaturity of central control of breathing or adults with cerebrovascular disease or neuromuscular or more often accompanies the breathing of Cheyne-Stokes. In this case, the cessation of airflow is caused by the abolition of the temporary drive to all respiratory muscles, in fact, not observed during apnea the movements of the rib cage instead are present in the obstructive form.
The mixed form is derived from the association of two others: in fact, a patient with central apnea type could also show the characteristics that promote airway collapse and then submit the forms even obstructive.
EPIDEMIOLOGY OSAS
many epidemiological studies have been conducted to determine the prevalence of OSA in the population. The results, however, are often discordant and include broad range of values, because of the different methods used for diagnosis, the definition of the syndrome and referred to the study sample selected.
In a study conducted in England in 2004 the prevalence of subjects who had major daytime sleepiness associated with the need to use the C-PAP was estimated to be around 0.5% in a population of average age (48.2 years) and an average BMI of 24.9 , and reached the 1, 5% in a population of subjects with a mean age of 52 years and a BMI of 27.1. However, this value rose to 24% if they were included in the group of patients with OSAS all those subjects who had more than 5 episodes per hour of apnea or hypopnea during sleep described by polysomnography. Finally the results obtained by considering the association between OSAS more than 5 episodes per hour of apnea or hypopnea and daytime symptoms evident estimated a prevalence of 4% in men and 2% in women.
Several results obtained in other studies in the U.S., these, in fact, the prevalence was estimated to be between 3 and 28% for mild OSAS defined by an AHI> 5 and between 1 and 14 % for moderate degree of OSAS with an AHI> 15.
Obesity, especially visceral fat, may contribute to the development of sleep apnea through different mechanisms. In obesity
serious the diaphragm is pushed upwards and this shift is greater in the supine position, the consequence is a reduced ability of contraction by the muscle associated with a reduction in volumes lung. These factors could also promote a narrowing of the pharynx and then the development of apnea.
Another hypothesis is that visceral fat results in increased activity of respiratory muscles leading to the production of a negative pressure to the point of collapse the upper airway during inspiration.
Finally, the observation that the circumference of the neck was a major factor in predicting the syndrome has been thought that its development was correlated with body fat distribution. In 1997 we conducted a study on 37 patients with primary obesity with a mean BMI of 36.8 + 6.8 kg/m2, with the use of CT has been made an estimate areas of adipose tissue in some districts such as head, thorax, abdomen, forearms, arms, thighs and calves: the area of \u200b\u200bvisceral adipose tissue was found to be higher in 21 patients with OSAS than the others. They were then carried out a series of studies with MRI, which have attributed the reduction in size in the presence of fat deposits around the airways, deposits distributed mainly at the level of the side walls.
Figure I-Influence of obesity in the development of apnea
CLINICAL
syndrome of sleep apnea has a strong impact on the quality and quantity of life of patients who are affected. The mortality of these patients, in fact, has increased compared to that of the general population is due to cardiovascular complications that the syndrome entails, it exposes patients to a high risk of acute events, either due to an increased risk of certain accident onset of the "falling asleep", common in these patients because of the low efficiency of sleep.
The quality of life is compromised, because patients often report a lack of concentration, reduced work performance and impaired their social life due to the onset of headache and depression. At the base of
disturbances in the clinical picture of OSAS can be identified two main events: the degradation of quality, quantity and structure of sleep, from which psychiatric and neurological disorders, the recurrence of periods of hypoxemia during sleep that cause functional alterations of the system respiratory and cardiovascular system.
endocrine and metabolic syndrome of sleep apnea also seems to have a major impact on metabolic functions, we have seen, in fact, that patients suffering from this disease have a risk of developing insulin resistance and glucose intolerance more than patients only obese.
In a French study conducted on 494 patients, there was a higher prevalence of type-2 diabetes and glucose intolerance (IGT) in patients with OSAS compared with the control group. This study found a correlation between blood glucose after glucose load, insulin sensitivity and the severity of OSAS, in terms of AHI.
assumptions about the possible underlying causes of changes in glucose metabolism are manifold. Dionne and colleagues have suggested that hypoxia may act resulting in a reduction of ATP production in beta cells of the pancreas. Instead, the results obtained in animal studies, insulin resistance is determined by a reduced responsiveness of the receptors action of the hormone insulin and reduced tyrosine kinase activity during hypoxia. The role of hypoxia was also confirmed by another study that found a strong correlation between the degree of hypoxia and insulin sensitivity.
It is assumed that the activity of the sympathetic system is altered in patients with OSAS during the night, could facilitate the development of glucose intolerance and insulin resistance.
The hypothesis about the most recent changes in the levels of leptin, a hormone produced by adipose tissue that has an important role in regulating food intake. The Obese usually high levels of this hormone due to a leptin resistance. People with OSA have even higher levels of leptin than obese subjects, irrespective of fat mass.
Leptin could benefit both the metabolic abnormalities, especially with regard to insulin resistance, and the other could lead to the development of apnea, in fact, in some animal studies it was shown that leptin prevents respiratory depression and that a deficiency can cause hypoventilation.
addition to alterations in hormones involved in the control of glucose metabolism were found in OSAS patients with altered levels of those hypothalamic-pituitary axis.
One of the most studied is the GH, it was noted, that in OSAS as obesity is a reduction in the production of this hormone associated with normal or low levels of IGF-1.
In a more recent study it was shown that in patients with OSAS is also a reduced peripheral sensitivity to the action of GH.
addition, the production of ACTH in response to CRH is increased to a greater extent than in obese subjects. E 'has been suggested that alterations of both GH and ACTH are to be referred to hypoxia or sleep fragmentation, in fact, after three months of treatment with the C-PAP values \u200b\u200breturn to normal even without an obvious weight loss. The changes that affect other hormones of the hypothalamic-pituitary system have reported conflicting results and not yet certain, but there was a reduction in levels of thyroid hormone, LH, testosterone and cortisol and aldosterone in many patients with OSAS .
Finally, OSAS can be considered an independent risk factor for the development of metabolic syndrome. In a study of 104 patients, including 61 with OSAS were measured blood glucose, the plasma insulin, plasma lipids and blood pressure. This study showed that patients with OSAS have higher levels of pressure, high concentration of insulin and triglycerides, increased LDL and reduced HDL independently of obesity. It has also been estimated that metabolic syndrome is 9.1 times more frequent in subjects with OSAS compared to obese.
We propose here an interesting study conducted by the authors concerning the evaluation of resting metabolic rate, body composition and polysomnographic findings in obese patients with OSAS.
CHANGE REPORTS calorimetry obese patients OSAS undergoing treatment DIET AND BEHAVIORAL
Obesity is a condition very common in patients with sleep apnea, and has been shown that the increase in BMI standard deviation implies an increased risk of developing OSAS than four times. While obesity appears to have a strong impact on the development of OSAS, in fact, in many studies there was a marked improvement of the clinical picture after weight loss, and secondly the observation that patients with OSAS have great difficulty weight loss has led to the hypothesis that this syndrome is associated with abnormalities of metabolism that may contribute to the development of obesity and further complicate its management.
Patients with OSAS, but they have a constant supply of oxygen to the tissues, because of apnea and desaturation below may have metabolic abnormalities, especially of the lipid, as fats require a greater amount of oxygen than other nutrients to be oxidized.
A study that supports this hypothesis is to Bonanni and colleagues, who starting from the observation that patients with OSA often complain of intolerance to physical activity and exercise have a greater susceptibility, have suggested a possible altered muscle metabolism. A deterioration of muscle metabolism and a change in lactate concentration during maximal exercise had already been demonstrated in a previous study. While initially an overproduction of milk was attributed to an alteration of the sympathetic nervous system, since the adrenergic stimulation of muscle glycogenolysis is a major factor in its formation, in agreement with some studies had confirmed that the higher levels of epinephrine and norepinephrine in patients with OSAS during exercise, this hypothesis was later disproved as the amount of lactate produced did not correlate with the levels of catecholamines. E 'has been suggested therefore that increased production and decreased removal of lactate is mainly due to a defect of oxidative metabolism in muscles of patients with OSAS, due to the adaptation of these tissues chronic nocturnal hypoxemia. These changes may also explain the mitochondrial changes of skeletal myofibers, similar to those found in subjects exposed to chronic hypoxia due to altitude, and also increased production of reactive oxygen species in neutrophil these patients.
In conclusion these data would suggest that the syndrome of sleep apnea can have such an impact on the metabolism to make it even more difficult weight loss.
Several conclusions Stenlof and associates, who conducted a study of 11 patients by measuring the metabolism before and after treatment with C-PAP. From this study, in fact, showed a higher energy expenditure, particularly during sleep in patients with OSAS before therapy and its normalization after treatment.
The aim of our study was to evaluate through the use of indirect calorimetry basal metabolism of patients before and after weight loss, also related to modifications of other parameters such as the respiratory quotient, body composition, values \u200b\u200band finds antropoplicometrici polysomnography.
PATIENTS AND METHODS
Among the patients referred to Day Hospital Policlinico Tor Vergata Neurophysiopathology of 16 patients were selected, including 12 males and 4 females with a BMI> 25 and with polysomnographic diagnosis of sleep apnea syndrome, mild to severe.
were excluded from the study patients with metabolic and endocrine disorders, cardiovascular disorders, eating disorders, with chronic inflammatory diseases and in drug treatment.
Those thus selected were subjected to a routine diagnostic procedure at the clinic of the Hospital Nutrition Clinic of Tor Vergata, including a thorough medical history examination, with particular attention to history food investigation and enforcement of certain blood chemistry. Blood tests were required to assess the overall status of the patient (complete blood count, blood electrolytes such as Na, K, Ca, Mg, P, serum iron, ferritin and transferrin), the metabolic status (glucose, insulin, Hb1Ac, triglycerides and total and fractionated cholesterol), liver function (GOT, GPT and gamma-GT) and renal function (creatinine, BUN, uric acid and protidogramma).
Before starting a dietary-behavioral therapy, patients underwent an assessment of energy expenditure and body composition.
After being subjected to these investigations, patients who followed a dietary-behavioral therapy for a period of about three months, with the formulation of a plan customized diet therapy.
E 'was used a low-calorie diet and normocomposta, consisting of 55% from carbohydrates, mostly low-glycemic index, 30% from fat and the remaining 15% protein, with the addition of at least 30 g / day of dietary fiber. The particular aspect was represented by the fact that in every meal of the day had to be present all the macronutrients simultaneously. Through a specific balance of macronutrients for each meal, be configured as a ratio of protein and carbohydrates around 0.75, obtained by combining 4 g carbohydrate 3 g each of protein, because it reaches a balance control hormone, both of the values \u200b\u200bof insulin and glucagon both in autocrine and paracrine hormones. Under this hormonal control of obesity through food would result in control of the speed of assimilation of protein and carbohydrates and in optimizing the use of lipids. According to the theoretical assumptions of this diet, the use of fat reserves would reduce the calories out.
behavior therapy combined with diet was intended to bring about a change of lifestyle in order to promote weight loss and above all keep it. The aim of the therapy was to reduce physical inactivity and ensure exercise of moderate intensity aerobic and at least twice a week. Finally
were distributed before the dietary treatment of the Stanford Sleepiness Scale questionnaires, with a re-evaluation at the end of therapy.
RESULTS Of the 16 selected patients 11 completed the study. The comparison between the medians of the variables for two of the group of patients who completed the protocol shows significant changes with regard to weight (p = 0.001), BMI (p = 0.001) and neck circumference (p = 0003) that are reduced.
E 'result also significantly reduced the score of the Stanford Sleepiness Scale (p = 0.003), the amount of fat mass (0036), the basal metabolic rate (p = 0.008) and basal metabolism in relation to lean body mass (P = 0.008).
There were no significant changes instead of the required amount of water and intracellular values \u200b\u200bof blood pressure and respiratory quotient.
E 'also found a significant association between the weight and circumference of the neck (0668, p = 0.025), between the weight and the score of the Stanford Sleepiness Scale (0841, p = 0.001) and between the basal metabolic rate and quantity fat mass (-0.69, p = 0.019).
DISCUSSION The results of our study, in agreement with previous work, confirming the importance of weight loss in the treatment of OSAS.
All patients, in fact, showed a significant association between body weight and circumference of the neck, particularly in patients who have lost much weight have played an important variation: the case 5 which had a weight loss of 22.4 kg is gone from a neck circumference of 50.6 cm to 46 cm, then a change of 4.6 cm, while the case 8, who lost only 2.6 kg showed a change in neck circumference of 0.3 cm. The variation of the circumference of the neck can be considered an important indicator of improvement, as evidenced by previous studies as a major factor in pathogenesis of sleep apnea is the deposition adipose tissue around the upper airway. This was also confirmed in our study, since the reduction of neck circumference was positively associated with the Stanford Sleepiness Scale score, an indicator of quality of life of the patient. The results of the questionnaire showed, in fact, the average reduction of 1 point after weight loss, particularly in combination with neck circumference.
Figure 7 - Multivariate linear regression (neck Δ / Δ SDS).
As regards the calorimetric data the results show a median reduction of basal metabolism of 400 calories after the dietary treatment, although the BIA has not revealed a significant change in lean body mass (Figure 8). This figure could be interpreted by some as simply a body's response to a low-calorie diet, it could support the hypothesis of Stenlof and associates, according to which patients with OSAS show a higher resting energy expenditure, which decreases with the improvement of the syndrome.
Figure 8 - Changes in weight (p = 0.001) and metabolism (p = 0.008) after dietary-behavioral therapy
The respiratory quotient instead showed no significant changes, remaining around a value 0.8 and not decreasing as might be expected to improve lipid oxidation.
In fact, this result could be altered by a false start value of QR due to the peculiarities of the syndrome of sleep apnea: in fact in the supine position, which is what the patient takes during calorimetry, you can have a collapse of the airways and then the occurrence of episodes of apnea and ipoapnee, resulting in hypoventilation. Since the QR is the ratio between carbon dioxide and oxygen, it is clear that the work by reducing hypoventilation in a fictitious way. It can therefore be assumed that any improvement of lipid oxidation, resulting in a reduction in QR, is covered by an improvement respiration, due to weight loss, which leads to an increase of QR and that the result of two effects is not precisely that of the variation of QR. In fact, if we evaluate the QR for each patient is noted that in 5 of 11 subjects there was even an increase, probably due to a prevalence of respiratory mechanism, while in 4 patients was reduced, as has prevailed 's effect of improving lipid metabolism and in two patients did not change Figure 9).
Figure 9 - Changes in QR in each patient.
CONCLUSIONS The magnitude of the selected sample and the short time of follow-up does not allow to draw conclusions Ultimately, however from this study revealed some interesting data.
First there was a significant association between weight and symptoms assessed with the Stanford Sleepiness Scale, especially in relation to the circumference of the neck, confirming the hypothesis that one of the main pathogenetic factors of sleep apnea in obese subjects is the deposition of tissue fat around the upper airway.
Also, although the basal metabolism of patients has decreased after the dietary treatment, the non-reduction of respiratory quotient has opened new questions about possible changes of lipid oxidation. The episodes of apnea and hypopnea during that patients exhibit indirect calorimetry, in fact, might affect the result and then give the initial values \u200b\u200bof QR lower than they were in reality. Calorimetry does not prove so effective in measuring changes in lipid metabolism in these patients, which would result in a reduction of QR, are still needed for this study to assess whether weight loss by reducing the number of apnea and nocturnal desaturation can then also help improve metabolism.
