RU2408287C1 - Method of diagnosing disturbance of tolerance to glucose and diabetes mellitus - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to pulmonology and endocrinology and is intended for early verification if type 2 diabetes mellitus. In the process of type 2 diabetes mellitus diagnostics, chronic obstructive lung disease is estimated as risk factor of type 2 diabetes mellitus and in case of its presence, irrespective of blood sugar indices, obtained on empty stomach, glucose-tolerance test is carried out and by standard criteria disturbance of tolerance to glucose (pre-diabetes) or diabetes is detected.

EFFECT: method allows to increase accuracy of diagnostics of tolerance to glucose and diabetes mellitus, including early stages of development and reduce its terms, therefore reducing economic expenditures on process of diagnostics and treatment.

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Description

The invention relates to medicine, in particular to pulmonology and endocrinology, and can be used for early diagnosis of diabetes mellitus and prediabetic state in patients with bronchopulmonary pathology occurring with irreversible obstruction of the bronchi.

Non-insulin-dependent diabetes mellitus or type 2 diabetes mellitus (T2DM) is one of the most common and socially significant diseases and often significantly complicates the course of another pathological process (1). This disease requires constant treatment, is characterized by frequent complications and manifestations of a systemic nature, leading to disability. Every year in the world 5.5% of patients die from complications of diabetes mellitus, the mortality rate among them is 2-4 times higher than that of people without carbohydrate metabolism disorders, and the life expectancy of such patients is 7-10 years less than that of people without diabetes . It has been established that the key link in the pathogenesis of T2DM is insulin resistance, which is observed in 83.9% of patients with diabetes and occurs in 65.9% of people with impaired glucose tolerance. Along with this, the diagnosis of T2DM and pathological conditions that contribute to and preceding its development, in particular impaired glucose tolerance, is far from an insufficient level, especially in the early stages of the development of the pathological process, when the volume of treatment and its costs are minimal, and the effectiveness is most significant.

A known method for the diagnosis of T2DM, based on the determination of fasting blood sugar and is widely used in clinical practice. At the same time, the sugar content in whole capillary blood is 3.3-5.5 mmol / l. However, impaired glucose tolerance and T2DM can be latent for many years without being diagnosed with this method, which is its drawback.

There is a known method for diagnosing T2DM by assessing glucose tolerance using an oral sugar load or an oral glucose tolerance test, which can detect carbohydrate metabolism disorders where they were not detected by the previous method for assessing fasting blood sugar. Moreover, in accordance with the standard criteria established for this method, when blood sugar is 2 hours after an oral sugar load in the range of 7.8-11.0 mmol / l, glucose tolerance disorders (prediabetes) are diagnosed, more 11.0 mmol / L - diabetes mellitus (2).

However, the known method has certain indications, including the fasting sugar of whole capillary blood up to 5.6-6.1 mmol / L and / or the presence of various risk factors, etc., and does not take into account bronchopulmonary pathology occurring with irreversible obstruction as a risk factor. bronchi, in particular chronic obstructive pulmonary disease (COPD), which is also one of the most common and socially significant diseases. This limits the capabilities of the known method and reduces the accuracy of the diagnosis of disorders of glucose tolerance and diabetes and is a significant drawback.

To eliminate this drawback and significantly improve the accuracy of the diagnosis of impaired glucose and diabetes tolerance disorders according to the claimed method in the presence of obstructive bronchopulmonary pathology, in particular chronic obstructive pulmonary disease (COPD), an oral glucose tolerance test is carried out regardless of fasting blood sugar , and according to the standard criteria reflected above, they diagnose impaired glucose tolerance (prediabetes) or diabetes mellitus. This, allowing to detect latent leaking disorders of carbohydrate metabolism and T2DM in those cases when they are not detected in the usual way, significantly increases the accuracy of the early diagnosis of impaired glucose tolerance and T2DM and is a significant novelty of the claimed method.

This increases the possibility of timely and effective treatment of both type 2 diabetes and obstructive bronchopulmonary pathology, in particular COPD, during which diabetes can significantly complicate it.

A convincing proof of the essence of the claimed method is the study of the mutual prevalence of T2DM and obstructive bronchopulmonary pathology, including COPD and BA. The latter was of a multicenter character. By random sampling by retrospective and current data collection using a blind approach, two patient cohorts were formed. The first cohort is represented by 616 patients with chronic inflammatory obstructive pulmonary diseases, including 280 people with chronic obstructive pulmonary disease (COPD), which proceeded independently (179 people) or in combination with bronchial asthma (BA) (101 people), and 336 - with BA proceeding on its own (247 people) or in combination with COPD (89 people). The second cohort consisted of 300 patients with type 2 diabetes. In the process of their formation, questionnaires were carried out, carried out according to specially developed questionnaires on the basis of questionnaires used in the international consortium (3, 4), and the diagnosis was clarified, primarily of the pulmonological orientation, in the second cohort of patients, for which, if necessary, an additional number of people carried out study.

The diagnosis of COPD was made on the basis of modern clinical definitions and international diagnostic criteria, including evidence of incompletely reversible airflow obstruction (5, 6). Based on the fact that COPD is rarely diagnosed before the age of 35, when the presence of incompletely reversible obstruction can occur with genetically determined bronchopulmonary pathology, usually established in childhood, patients with a diagnosis of COPD were excluded from this series of observations was delivered under the age of 35 years. The diagnosis of asthma was made in accordance with international GINA standards (7). Patients with this diagnosis were registered for more than 3 years and received therapy characteristic of this contingent, including theophylline, cromolyn, inhaled and periodically during the exacerbation phase systemic steroids, etc. All patients during the study period were in the phase of clinical remission of the disease.

The prevalence between diseases of each cohort of patients was cross-estimated in comparison with population data (K).

Analysis of the material and the results of the study was carried out using standard statistical processing and student criterion.

The results of the studies showed that in the first cohort, 9 patients with AD and 17 with COPD had type 2 diabetes. The prevalence of T2DM in this cohort of patients with bronchopulmonary pathology, generally exceeding the population indices of 3.0 (1), with COPD was significant (9.49; p <0.01) and more than 2.5 times higher (p <0.05) compared with AD, where the frequency of this disease, amounting to 3.64, did not differ from the control (p> 0.05).

An analysis of the literature indicates that COPD, on the one hand, has a whole range of systemic effects, including metabolic processes that can lead to the development of type 2 diabetes in various ways, and on the other hand, it develops under the influence of a number of factors that play a direct role in the formation of T2DM. It was noted that the level of inflammatory markers that increase with COPD also increases in patients with type 2 diabetes.

The cell composition in COPD is characterized by the presence of mainly neutrophils, macrophages and an increased number of lymphocytes, which are believed to be a helper of type 1 (Th1), CD8 + T-lymphocytes, and a predominance of associated pro-inflammatory cytokines, such as tumor necrosis factor (TNF), interleukins ( IL) - 6 and 8, superoxide radical anion, leukotriene B ₄ , which make a significant contribution to the development of resistance to insulin and type 2 diabetes (8, 9), which indicates a significant role of COPD in the pathogenesis of type 2 diabetes.

It has also been shown that with COPD, the level of C-reactive protein increases, which correlates with the severity of COPD and mortality from various causes in this disease, as well as leptin (10, 11). An increase in the level of C-reactive protein correlates with an increase in the level of inflammatory factors, manifested, in particular, by stimulation of the production of pro-inflammatory cytokines (IL-6 and 8), expression of adhesion molecules, inhibition of transcription of endothelial NO synthase and destabilization of the mRNA of this enzyme, which leads to a decrease basal and stimulated synthesis of nitric oxide by endothelium (10, 12). Along with this, an increase in the level of leptin, accompanied by activation of the function of neutrophils and macrophages, also stimulates the secretion of the same pro-inflammatory cytokines, which play an important role in the pathogenesis of not only COPD, but also T2DM.

The presence of chronic inflammation in patients with COPD is believed to lead to increased energy expenditure at rest. As a result, their weight is reduced in fat-free tissue, which is accompanied by an increase in systemic markers of inflammation (13, 14). A connection has also been shown between systemic inflammation and muscle loss in COPD, even with implicit weight loss (15). It has been established that the level of circulating TNF is elevated in cachectic patients with COPD with chronic hypoxemia, a potential stimulus for activating the pro-inflammatory cytokine system in such patients. TNF, being the central inflammatory mediator in the process of muscle depletion, supports cachexia, reducing the peripheral effect of insulin (16). Loss of muscle mass and a decrease in the oxidative ability of fat along with low physical activity lead to further loss of muscle mass and increase fat. The latter, in turn, is accompanied by an increase in the level of circulating TNF, increasing insulin resistance, which contributes to the development of T2DM, and muscle loss.

Some studies have suggested that decreased lung function may be a risk factor for developing insulin resistance or diabetes (17).

Along with this, oxidative stress, which is one of the key links in the pathogenesis of COPD, leads to damage to the epithelium of the airways, increasing the flow of neutrophils, lymphocytes into the lungs and activating transcription factors, including nuclear factor kV, which stimulates the expression of TNF, IL-8, and other inflammatory genes mediators, contributes to the development of insulin resistance and plays an important role in the pathogenesis of T2DM (18). TNF-α synthesized by macrophages, elastase secreted by neutrophils, and a significant amount of oxygen induced by the latter have a damaging effect on cells, contributing to the development of destruction. This can be facilitated by exposure to active forms of oxygen entering the lungs directly with tobacco smoke or produced in the lungs by inflammation cells, including macrophages, lymphocytes, neutrophils, etc., whose influx increases under the influence of tobacco smoke.

At the same time, the contribution of tobacco smoking to the development of T2DM is also known, which also reflects the community of these diseases (19). In turn, an increase in insulin or glucose levels further increases the production of reactive oxygen species and oxidative stress, disrupting both the action of insulin and its secretion and accelerating the development of overt diabetes. In this case, free radical oxidation processes are associated with protease activity due to the fact that under the influence of oxidants antiproteases can be inactivated and the balance of the protease-inhibitory system can occur (towards an increase in protease activity), which play a significant role in the pathogenesis of COPD and T2DM (20). Bacterial products have a significant effect on this (21).

The combination of COPD and asthma is a fairly common phenomenon that contributes to the formation of severe asthma and is comparable to the latter in prevalence, comprising 9-25% of cases of asthma in general (22). According to our results, the combination of COPD and AD is accompanied by prevalence of T2DM (4, 14), significantly exceeding not only the control values (p <0.001) and similar indicators for COPD (p <0.05) and AD (p <0, 01), but also by 23.4%, the sum of the values for these diseases. This indicates a negative effect with this mixed pathology, which increases the risk of developing T2DM. A similar effect against the background of its severe course may be that “extra drop” that contributes to a sharp deterioration of the pathological process up to a fatal outcome. This, obviously, is largely associated with the interdependent effect of AD and COPD, which increases the likelihood of infectious episodes during these diseases, is accompanied by a change in the nature of the inflammatory process in the mucous membrane of the respiratory tract towards its protracted course, the appearance of purulent elements, increased intoxication, as well as hypoxia and exacerbation of oxidative stress, whose contribution to the pathogenesis of COPD is significant.

Therefore, early diagnosis of diabetes, the identification of predisposition to it and prevention are important in patients with COPD, especially with its severe course and combination with AD. This is ensured by the claimed method, namely, the purposeful conduct of a glucose tolerance test in this contingent of patients, along with the fact that it is usually not carried out and is not recommended for routine clinical use, including in these patients, without an increase in blood sugar above standard values defined using the usual standard method.

The proposed approach for the diagnosis of T2DM with its high information content is simple, economically low-cost and affordable at all levels of medical support and can be used in wide medical practice.

Possible illustrations of the use of the method are given as an illustration.

Example 1. The patient. X. was observed and treated for COPD for more than 15 years, in accordance with existing standards. Periodically, treatment was carried out in a hospital. Hormonal systemic drugs were not included in the therapy. A history of hypertension. The hereditary history is not burdened.

An objective examination: the physique is somewhat hypersthenic. The number of breaths in 1 min is 24. The percussion sound over the lungs is not changed. Excursion of the lungs within normal limits. Auscultatory - hard breathing, isolated scattered dry rales. From other organs and systems without features. The phenomena of decompensation in the large and small circle of blood circulation are not determined.

General analysis of blood and urine without features. Fasting blood sugar 5.1 mmol / L.

On chest x-ray signs of emphysema and pulmonary pneumosclerosis.

When spirographic examination - signs of a significant violation of patency of the bronchi obstructive type. Bronchodilator test is negative.

Due to the presence of COPD in a patient, blood sugar was examined using a glucose tolerance test. As a result of the latter, an increase in blood sugar to 9.4 mmol / L was detected despite its normal values obtained in the usual way on an empty stomach and reflected above. This, in accordance with standard criteria, made it possible to diagnose a patient with impaired glucose tolerance (prediabetes) and promptly prescribe an appropriate treatment correction for both carbohydrate metabolism and COPD disorders.

Example 2. Patient U. has been suffering from COPD for about 20 years. He is constantly being treated on this issue on an outpatient basis and periodically in the hospital due to exacerbations of the disease. Periodically received only inhaled glucocorticosteroids. The data of the clinical examination and laboratory and instrumental studies were consistent with the diagnosis. An elevated fasting blood glucose level was not recorded. Given that the patient was suffering from COPD, he had a glucose tolerance test, with which he had twice revealed elevated blood sugar values of 11.4 mmol / L, 11.6 mmol / L and a diagnosis of T2DM was established. In this regard, the patient underwent a corresponding correction of treatment.

Claims (1)

A method for the diagnosis of type 2 diabetes mellitus, including a glucose tolerance test, characterized in that chronic obstructive pulmonary disease is regarded as a risk factor for type 2 diabetes mellitus and, if there is any, regardless of fasting blood sugar parameters, glucose tolerance is performed test and establish by standard criteria impaired glucose tolerance (prediabetes) or diabetes.