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0EPIDEMIOLOGY, ETIOPATHOGENESIS, DIAGNOSIS AND TREATMENT STRATEGY FOR OBESITY ASSOCIATED WITH TYPE 2 DIABETES MELLITUS (T2DM) (LITERATURE
REVIEW)
1Abdullajanov B.R., 2Botirov A.K., 3Ibragimov U.Ya., 4Sotiboldiev A.A., 5Madvaliev B.,
6Botirov J.A.
1,2,3,4,5,6Andijan State Medical Institute, Uzbekistan https://doi.org/10.5281/zenodo.13624199
Abstract. Obesity is a chronic disease, heterogeneous in etiology and clinical manifestations, progressing in a natural course, characterized by excessive deposition of fat mass in the body [63]. Morbid obesity is a pathological condition in which the body mass index exceeds 40 kg/m2, i.e., body weight is increased by 45-50% of its normal values, and the risk of death of patients is 10 times higher than that of people with normal weight [3;4;34;63].
Keywords: obesity, chronic disease, diabetes, global epidemic, T2DM, WHO, MO.
The relevance of the problem is determined by the progressive increase in the prevalence of MO in combination with type 2 diabetes mellitus (T2DM). According to WHO, the global epidemic of excess weight currently affects 1.9 billion people, of whom more than 300 million are obese [62]. This increase is 10% of their previous number over a decade [39].
Currently, obesity among the most common non-communicable diseases has taken on the character of a modern pandemic. One of the main metabolic outcomes of obesity is type 2 diabetes mellitus (T2DM) [22], which is the leading cause of disability and mortality in the population [6]. Thus, in the member countries of the Organization for Economic Cooperation and Development (OECD), excess BMI is found in 54% of the population, including 19% suffer from MO [47]. The global epidemic of type 2 diabetes mellitus (T2DM) has already reached 425 million people in 2017. According to experts from the International Diabetes Federation, by 2045 the incidence will be 629 million people [35].
Etiology and pathogenesis. Obesity is a multifactorial disease, in the formation of which, in addition to the imbalance between energy consumption and expenditure, various neurohumoral mechanisms and environmental factors participate [63]. The causes of obesity are mainly changes in people's lifestyle due to urbanization, nutritional patterns, environmental changes, socioeconomic factors, as well as hereditary predisposition [27].
High-calorie diet, sedentary lifestyle and chronic stress are the most important causes of obesity [20]. It has been proven that BMI depends on hereditary factors by 40-70%, many genes have been identified that encode the work of certain links in the regulation of body weight and metabolism [32]. Over the past 30 years, the increase in obesity has been mainly associated with cultural and environmental changes [26].
Obesity is based on hereditary, i.e. genetic causes, but lifestyle, family nutrition traditions, behavioral and psychological factors that are not easy to separate from genetic factors are also important. In general, the pathogenesis of obesity is based on an imbalance between energy intake and expenditure. Currently, a lot of scientific data is emerging on the pathogenetic mechanisms of obesity development. Up to 80% of the predisposition to obesity is a consequence of genetic
disorders that can lead to obesity in combination with type 2 diabetes mellitus (T2DM). There are many risk factors for the development of type 2 diabetes, but in 90% of people, the most important factor in the development of type 2 diabetes mellitus (T2DM) is overweight or obesity [7;43]. People with excess BM have a reduced ability to use insulin to maintain normal blood sugar levels and, as a result, are very likely to develop type 2 diabetes. Lifestyle changes and a 5-10% reduction in BM in obese adults can be a preventative measure for type 2 diabetes mellitus (T2DM) [10;14].
Obesity has a complex pathogenesis, for which no treatment method has yet been found that would provide a satisfactory permanent result. At the same time, weight loss eliminates many problems caused by obesity. Even a modest weight loss of 5-7% leads to an improvement in the general condition [33].
The pathogenesis of obesity includes both external factors (excessive calorie consumption and a sedentary lifestyle) and internal factors in the form of a certain genetic predisposition [48; 51]. A beneficial effect of physical activity on metabolic processes in obesity has been established [45; 61].
Mitsinskaya A.I. et al. (2020) attribute an important role to the disruption of central mechanisms regulating energy intake and expenditure, as well as the influence of adipose tissue itself on the development of obesity, which in turn leads to the development of a number of diseases [12].
It has been proven that both hormonal and neurotransmitter disturbances in the functioning of the gut-brain axis and intestinal microbiota play an important role in the pathogenesis of obesity [64]. The above factors contribute to structural changes in adipose tissue (hypertrophy and hyperplasia of adipocytes, development of chronic inflammation) and changes in its secretory function (for example, in the production of adipokines) [36]. In turn, chronic inflammation of adipose tissue underlies the pathogenesis of insulin resistance [21]. The role of brown adipose tissue thermogenesis and its contribution to energy expenditure are studied mainly from the standpoint of developing strategies to stimulate the growth and activation of brown adipocytes as a preventive and therapeutic measure for weight control in obesity [29].
Endocrine causes of obesity are less common [42;60]. According to the recommendations of the endocrinology society, patients with obesity are recommended to undergo thyroid stimulating hormone (TSH) testing [49]. Normal testosterone levels maintain optimal muscle mass and limit the accumulation of adipose tissue, where its deficiency reduces insulin sensitivity, disrupts glucose tolerance and dyslipidemia [37].
Currently, the number of hormones involved in appetite regulation is growing [41], where an important role is given to glucagon, which can reduce appetite, which is important when creating drugs [55]. Ghrelin, a peptide hormone produced mainly by the etheric endocrine cells of the fundus of the stomach and a "hunger hormone," also affects the diet [16]. Ghrelin acts at the level of the central nervous system and the periphery [50]. At the periphery, ghrelin stimulates gastric emptying, which leads to faster entry of food into the small intestine; signals from the small intestine about the beginning of nutrient absorption by the negative feedback mechanism inhibit ghrelin secretion. In obese individuals, ghrelin concentration decreases, which is apparently associated with the suppression of its secretion under the influence of high-fat foods [9]. One of the most compelling arguments in favor of the important role of ghrelin in weight gain is the effectiveness of bariatric interventions. Operations accompanied by gastric resection (during which the ghrelin-producing zone is removed) [31;54].
It is known that the main role in the pathogenesis of type 2 diabetes mellitus (T2DM) belongs to insulin resistance associated with obesity and lipid metabolism disorders. It is noted that the prevention and treatment of obesity lead to a decrease in the number of cases of developing type 2 diabetes mellitus (T2DM), and in the case of an already identified disease - to an improvement in metabolic parameters [25;28].
Insulin resistance and hyperinsulinism are usually observed in obesity and are pathogenetically associated with the severity of excess body weight [2;38]. It has been established that obesity has a significant effect on lipoprotein metabolism in the form of an increase in the level of triglycerides, low-density lipoproteins and a decrease in the level of high-density lipoproteins. With a decrease in body weight, an inverse effect is observed not only on the level of lipoproteins, but also on the level of sensitivity of insulin receptors in type 2 diabetes mellitus (T2DM) [13].
Insulin resistance associated with obesity and lipid metabolism disorders plays a significant role in the pathogenesis of type 2 diabetes mellitus (T2DM) [59]. It is more difficult for patients with type 2 diabetes mellitus (T2DM) to lose weight than those without diabetes. In most patients with type 2 diabetes mellitus (T2DM), insulin resistance causes the muscles and liver to fail to utilize glucose in the required amount, while lipolysis is suppressed, leading to an increase in adipose tissue [40].
Improvement in glycemia against the background of weight loss is most noticeable at the beginning of the pathogenetic path of development of type 2 diabetes mellitus (T2DM), when obesity-associated insulin resistance has already led to reversible dysfunction of P-cells, but the secretory function of the pancreas is still relatively preserved [52].
Currently, one of the most effective ways to reduce body weight is bariatric (from the Greek baros - heavy, obese) surgical interventions (BSI). BSI includes restrictive (aimed at reducing the size of the stomach), bypass (malabsorptive) operations, which are based on the creation of an additional path bypassing some parts of the small intestine, which allows to significantly reduce the absorption surface of the gastrointestinal tract (GIT), as well as combined (restrictive + bypass) operations [17;57].
The introduction of complex bypass operations (gastric bypass and biliopancreatic bypass) into practice has shown that a decrease in MT is the most important factor determining the improvement of carbohydrate metabolism [19]. At the same time, in patients with type 2 diabetes mellitus (T2DM), the normalization of its indicators depends on the type of bariatric surgery [24]. Thus, the reconstruction of the gastrointestinal tract, carried out during bariatric operations, leads to an additional "antidiabetic" effect. The "low small intestine hypothesis" is that the accelerated movement of the food bolus into the distal small intestine results in stimulation of L-cells and rapid release of the antidiabetogenic and anorexigenic factor [23]. The alternative "high small intestine or anti-incretin hypothesis" is that isolation of the duodenum and the proximal jejunum in animals with type 2 diabetes mellitus (T2DM) can prevent the secretion of a hypothetical "anti-incretin" that stimulates the development of insulin resistance and type 2 diabetes mellitus (T2DM), which has an antidiabetic effect and improves glucose tolerance [18;53]. Thus, both hypotheses are based on an understanding of the special role of the incretin system in obese patients with type 2 diabetes mellitus (T2DM) [18].
Against the background of a decrease in BM as a result of gastric bypass, suppression of ghrelin, a hormone stimulating appetite, which remained high during a decrease in BM caused by
a diet, was established [19]. After gastric bypass operations, a consistent decrease in the level of leptin in the blood plasma, which correlates with insulin resistance, as well as an increase in the activity of adiponectin and peptide YY in the blood, was established, which also confirms the hypothesis of the "endocrine efficiency" of these operations. In addition, intestinal malabsorption caused by gastric bypass operations leads to a decrease in the intensity of glucose absorption, which minimizes P-cell stress, and a decrease in fat absorption reduces the circulation of free fatty acids, which leads to an increase in tissue sensitivity to insulin [44].
Diagnostics. Clinical diagnosis of obesity is established based on physical examination data - body mass index (BMI) > 30 kg/m2, as well as assessment of the characteristics of the medical history and lifestyle. To diagnose obesity and assess its severity, it is recommended to measure body weight, height and determine the body mass index (BMI) [63]. To diagnose abdominal (visceral) obesity, it is recommended to measure waist circumference: waist circumference >94 cm in men and >80 cm in women is a diagnostic criterion for abdominal obesity [63].
The examination algorithm for patients with obesity, including morbid obesity, is determined individually. Along with laboratory diagnostics, ultrasound of the liver, gallbladder and bile ducts plays an important role [4]. Nocturnal pulse oximetry is used as a screening method for obstructive sleep apnea syndrome [56].
Clinical evaluation of the obese patient undergoing surgical treatment is recommended to be performed by a multidisciplinary team, including specialists with experience in bariatric surgery [11;46]. Patients with MO are prescribed a standard preoperative examination, with special attention to the basal metabolic rate [46].
Treatment strategy for MO in combination with type 2 diabetes mellitus (T2DM). Currently, the treatment strategy for MO in combination with type 2 diabetes mellitus (T2DM) includes: psychotherapy of eating behavior, drug therapy, bariatric surgery and liposuction [8]. When planning the treatment of MO in combination with type 2 diabetes mellitus (T2DM), it is necessary to take into account the progression of the disease, which is not always possible due to a violation of the diet [1;15].
Body mass index is calculated by dividing weight in kilograms by height in meters squared
[14].
Treatment of MO in combination with type 2 diabetes mellitus (T2DM) should begin with dietary counseling, education, and lifestyle changes [58]. Recommendations of the American Association of Clinical Endocrinologists focus on the quality of glycemic control and BM gain [30]. The consensus of the Russian Association of Endocrinologists recommends starting combination therapy with drugs with a low risk of hypoglycemia and BM gain [5].
Conclusion. Thus, obesity and associated metabolic disorders are a pressing problem of modern medicine, as they lead to the development of a number of severe diseases. Obesity and type 2 diabetes mellitus (T2DM) are a global medical problem of a pandemic nature and associated with a significantly increased risk of morbidity and mortality. Guidelines for the management of type 2 diabetes mellitus (T2DM) and the treatment of obesity are unanimous in that therapy for MO and diabetes should begin with intensive lifestyle change programs. Pharmacotherapy of obesity is indicated in addition to these programs in order to enhance their effectiveness. The effectiveness of conservative therapy is 5-10%. Therefore, surgical methods have become widely
used throughout the world, which, due to a significant reduction in body weight, affect the course
of diseases associated with obesity, which requires further research.
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