by Julio Libman and Jesús Ramón Giraudo
Obesity is defined as a syndrome determined by the presence of an exaggerated amount of adipose tissue in the body, even though it is difficult to determine the exact meaning of the term "excess". Leaving aside aesthetic considerations, the clinical diagnosis of obesity can be considered as the degree of excess adiposity that implies a health risk. An excess of 20% over the ideal, theoretical or desirable weight for age and sex, taking into account physical conformation, implies a health risk. According to this criterion, approximately 20 to 30% of men and 30 to 40% of women in developed countries are obese.
Physiology and pathophysiology .
When dietary intake exceeds caloric expenditure, the difference between the two is accumulated as fatty tissue. Abnormal eating habits, together with reduced physical activity, are the cause of obesity in an appreciable number of patients with primary or idiopathic obesity.
The regulation of eating behavior is only partially known. In the ventromedial hypothalamus there is a satiety center and in the ventrolateral zone there is a feeding center. The cerebral cortex receives positive signals from the latter that stimulate intake, while the satiety center modulates this process through inhibitory impulses directed to the feeding center. Glucose and various neurotransmitters and hormones act on the center of satiety, such as serotonin, catecholamines, cholecystokinin, pancreatic polypeptide, thyrotrophin-releasing hormone (TRH) and insulin. It is interesting to note that there are insulin receptors in the ventromedial area of the hypothalamus. Dopamine, endorphins influence the activity of the feeding center, enkephalins and secretin. Ultimately, the cerebral cortex regulates eating habits, being subject to impulses that come from the hypothalamus. In any case, psychological and social factors also influence eating habits.
It is difficult to assess the genetic influence on human obesity, due to the confluence of social and cultural factors. Physical activity influences the caloric balance, and in this sense obese individuals tend to be less active than thin ones.
In addition to excessive nutrient intake and low energy expenditure due to physical inactivity, other factors may play a role in the genesis of obesity. The idea that a difference in metabolic efficiency, defined as the rate of energy accumulation in the body in relation to food intake, could be the cause of some types of obesity, has been the subject of numerous investigations. The increase in metabolic efficiency implies that a higher percentage of the energy ingested in the form of food is stored as fat. Various mechanisms have been proposed through which increased metabolic efficiency could occur. Firstly, the processing of metabolic fuels may not be coupled to the formation of ATP or other high-energy phosphate bonds, that is, the energy released during metabolic processes may not transfer to high-energy phosphate junctions such as ATP. Second, there would be differences in the speed with which ATP bonds are split; Its increased catabolism could manifest itself in different ways, some of them called futile cycles. Obese individuals would require less energy for protein synthesis, allocating more for storage. There would also be a decrease in the energy consumed in transporting ions through the membranes, as well as a lower energy expenditure in muscle movement to carry out the same amount of work. there would be differences in the speed with which ATP bonds are split; Its increased catabolism could manifest itself in different ways, some of them called futile cycles. Obese individuals would require less energy for protein synthesis, allocating more for storage. There would also be a decrease in the energy consumed in transporting ions through the membranes, as well as a lower energy expenditure in muscle movement to carry out the same amount of work. there would be differences in the speed with which ATP bonds are split; Its increased catabolism could manifest itself in different ways, some of them called futile cycles. Obese individuals would require less energy for protein synthesis, allocating more for storage. There would also be a decrease in the energy consumed in transporting ions through the membranes, as well as a lower energy expenditure in muscle movement to carry out the same amount of work.
Brown adipose tissue gets its name for its vascularity and for its higher content of cytochrome and other oxidative pigments in the mitochondria of its cells. It represents a very small amount of body fat, and is richly innervated by sympathetic fibers.
It has a very high respiratory capacity, plays a very important role in maintaining body temperature at the beginning of extrauterine life, and decreases with age, and may increase with exposure to cold. Brown fat could play an important role in the metabolic efficiency of the genetic forms of obesity. In these circumstances, its heat production is defective, either in response to the injection of norepinephrine or the stimulation of the nerves that supply the tissue.
Normally stimulated by overfeeding, food-induced thermogenesis is a process by which excess ingested energy is preferably dissipated in the form of heat rather than stored as fat. The sympathetic nervous system and brown adipose tissue play an important role in the regulation of diet-induced thermogenesis, and defects in this mechanism have been observed in obese rodents.
Interestingly, catecholamines may have opposite actions on lipolysis in humans, actions that are mediated by alpha-inhibitory and beta-stimulatory adrenoceptors. Alterations in this regulatory mechanism could explain certain types of human obesity.
According to the number and size of adipocytes, obesity can be hypertrophic or hyperplastic. The ability to increase the number of fat cells exists for a limited period during the first years of life. Thus, overfeeding in the years prior to adulthood leads to an increase in their number and size, while subsequent overfeeding influences only size. Patients with severe obesity have an increase in the number and size of adipocytes, with a tendency to start obesity early in life (hyperplastic form). Patients with moderate obesity show only cellular hypertrophy and its onset in adulthood. From the above it follows that the so-called primary obesity is not a single disease, but a complex group of alterations with genetic factors,
Causes of obesity
In the vast majority of obese patients, it is impossible to detect a determining cause, constituting primary or idiopathic obesity. Secondary causes include:
- Hypothyroidism . Obesity can result, in these cases, from a decreased caloric requirement. However, only a minority of hypothyroid patients are truly obese, and an even smaller proportion of obese patients are hypothyroid.
- Insulinoma . It can produce marked weight gain due to the lipogenic and anabolic action of insulin and the fact that patients soon learn that episodes of hypoglycemia subside by ingesting carbohydrates.
- Overinsulinization . Overinsulinized diabetic patients gain excess weight for the reasons stated.
- Cushing's syndrome . Obesity presents special characteristics, of the centripetal type, prevailing in the trunk, with a prominent abdomen and thin extremities, a round face with a full moon and cervical (buffalo dorsum) and supraclavicular fat deposits.
- Hypothalamic and genetic alterations . Sometimes hypothalamic tumors can cause obesity. Other rare pathologies include Laurence-Moon-Biedi syndrome, characterized by retinitis pigmentosa, mental retardation, cranial deformations, poly and syndactyly, and Prader Wilii syndrome, which has hypotonia, mental retardation, and increased frequency of diabetes mellitus. Both pictures are also associated with obesity and hypogonadism of probable hypothalamic origin. Pseudohypoparathyroidism, in turn, is an inherited disorder due to a lack of response of peripheral tissues to parathyroid hormone, whose levels are high. Patients present with signs of litany, round facies, picnic habit, and brachydactyly.
- Hypogonadism . Primary hypogonadism and polycystic ovarian syndrome are frequently associated with obesity. Lo
Clinical manifestations. Metabolic sequelae and complications
There are difficulties in accurately evaluating the amount of adipose tissue in an organism. In practice, two procedures are used: a) the weight-height-age-sex-physical complexion relationship, and b) the body mass index, which is calculated by dividing the weight in kilos by the square of the height in meters. It is accepted that obesity exists when the actual weight is 20% higher than the theoretical or desirable weight stipulated in relationship tables, or when the body mass index is greater than 25 in women and 27 in men.
As a complementary evaluation method, the thickness measurement of the triceps, subscapular and abdominal folds is used. In men the average does not exceed 2 cm and in women 3 cm.
Massive obesity produces a mechanical overload that aggravates pre-existing disorders such as osteoarthritis, varicose veins, thromboembolism, and diaphragmatic and anterior hernia of the abdomen. Gallbladder lithiasis is more frequent in obese patients, as is hypertension associated with hypervolemia. In this sense, it is important to remember the need to use a cuff larger than usual to determine blood pressure, given the possibility of obtaining falsely elevated readings. Obesity is a risk factor for the development of coronary arteriosclerotic disease, through hypertension, hyperlipidemia and associated diabetes.
Hypoventilation syndrome (Pickwick syndrome). It presents diverse manifestations. Sleepiness is an expression of nighttime apnea. Once sleep begins, obstruction of the upper airways due to tissue flaccidity leads to hypoxemia and hypercapnia, causing awakening and the reappearance of normal breathing. Repeating these episodes results in lack of nighttime sleep and daytime sleepiness. Obesity and sleep-induced relaxation of the pharyngeal musculature are thought to be the cause of intermittent obstruction of the upper airways. When intense enough, these episodes can cause cardiac arrhythmias. Similarly, daytime hypoventilation is common. Occasionally polycythemia, pulmonary hypertension, and cor pulmonale develop.
Adrenal function There is an increase in urinary 17-OH corticosteroids, due to the increased production of cortisol by the adrenals to maintain normal cortisolysis due to the greater body volume. Plasma cortisol, circadian rhythm, urinary free cortisol, and dexamethasone suppressibility are normal. Implicit in the increased production of cortisol is the increase in some androgenic precursors, responsible for menstrual disturbances and the increased production of estrogens by peripheral aromatization in adipose tissue. Hyperestrogenism would be responsible for the increased incidence of endometrial cancer in obese women.
Somatotrophin . A decrease in the somatotrophic response to various stimuli is observed, such as hypoglycemia, arginine, etc. This fact must be taken into account in the interpretation of studies in obese children of short stature.
Hyperinsulinemia and insulin resistance . There is basal hyperinsulinemia and post glucid overload. We discuss whether the primary event is peripheral resistance increased by alterations at the receptor and / or post-receptor insulin level, with secondary hyperinsulinemia, or if this is the primary alteration with secondary decrease (down regulation) of the receptors and consecutive resistance.
Diabetes mellitus . Even though a minority of obese patients are diabetic, 80% of non-insulin dependent diabetics are obese. The cause would be the aforementioned decrease in peripheral sensitivity with an inability of the pancreas to produce adequate amounts of insulin to the highest demand.
Hypertipoproteinemia . There is a certain correlation between obesity and LDL (low-density lipoprotein) levels, the fraction in which most of the plasma cholesterol circulates. Obesity has a marked effect on the metabolism of VLDL (very low density lipoproteins). Hypertriglyceridaemia is frequent and is related to the degree of obesity. Hypertriglyceridemia is due to increased VLDL secretion from the liver due to hyperinsulinemia and increased availability of free fatty acids.
- Gout. Hyperuricemia appears to be related to increased production and decreased urinary excretion of uric acid.
Interrogation and study methodology
In the presence of an obese patient, it is first of all necessary to rule out infrequent cases of secondary obesity, such as hypothyroidism (infiltrated appearance, asthenia, constipation, dry and cold skin, low T4 and T3 with elevated TSH), Cushing's disease (centripetal obesity, vergetures, ecchymosis, muscle atrophy, flushing, osteoporosis, elevated cortisol that is not suppressed with dexamethasone and abolition of the circadian rhythm), insulinoma (episodes of hypoglycemia, psychic disturbances, hyperinsulinemia with hypoglycemia), polycystic ovarian (oligohyphenorrheal, hirsurgical, hirsus, clinically or sonographically enlarged, elevated luteinizing hormone, 17-ketosteroids, and upper or somewhat elevated testosterone) and the rare cases of hypothalamic and genetic lesions.
Once the existence of primary obesity is established, it is necessary to evaluate the degree of obesity, eating habits, physical activity and the psychological state of the patient, and to determine the existence of any of the clinical and metabolic manifestations that may accompany excess weight through the general and cardiovascular clinical examination, evaluation of hydrocarbon metabolism (glycemia and oral test of carbohydrate tolerance) and lipid (total cholesterol and high-density lipids or HDL, triglycerides and serum appearance).