diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM13342diaendo-13342Research ArticleОБЗОРЫREVIEWSСпектр эффектов ингибиторов дипептидилпептидазы-4: внутри и за пределами гликемического контроля (часть 1)Spectrum of effects of dipeptidyl peptidase-4 inhibitors: within and beyond glycemic control (part 1)https://orcid.org/0000-0002-6762-5238РуяткинаЛ. А.RuyatkinaL. A.

 

Руяткина Людмила Александровна - д.м.н., профессор.

630091, Новосибирск, Красный проспект, д. 52

Lyudmila A. Ruyatkina - MD, PhD, Professor.

52 Krasny prospect, 630091 Novosibirsk

larut@list.ruhttps://orcid.org/0000-0003-3431-5943РуяткинД. С.RuyatkinD. S.

Руяткин Дмитрий Сергеевич - к.м.н., доцент.

Новосибирск

Dmitry S. Ruyatkin - MD, PhD, Associate Professor.

Novosibirsk

larut@list.ruНовосибирский государственный медицинский университетРоссияNovosibirsk State Medical UniversityRussian Federation202509102025284404412Copyright © Руяткина Л.А., Руяткин Д.С., 20252025Руяткина Л.А., Руяткин Д.С.Ruyatkina L.A., Ruyatkin D.S.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.dia-endojournals.ru/jour/article/view/13342

Современные акценты контроля сахарного диабета 2 типа (СД2) сместились с HbA1c на вариабельность гликемии (ВГ) вследствие ее ключевого значения в ускоренном развитии диабетических осложнений, помимо хронической гипергликемии. Центральным звеном ранней стадии дисгликемии служит дисфункция β-клеток с последующей потерей их массы при важной роли гиперглюкагонемии на всех этапах диабетического континуума. Решающее значение для поддержания гомеостаза глюкозы имеет скоординированная работа α и β-клеток с помощью двух эндогенных инкретинов: глюкагоноподобного пептида-1 (ГПП-1) и глюкозозависимого инсулинотропного полипептида (ГИП). Способность ингибиторов дипептидилпептидазы-4 (иДПП-4) за счет сохранения биоактивных ГПП-1 и ГИП интактными не только поддерживать массу β-клеток и способствовать высвобождению инсулина, а также одновременно корректировать секрецию глюкагона из α-клеток, предотвращая гипогликемии, привлекает к препаратам особое внимание.

Рассматривается место иДПП-4 среди различных фармакологических вариантов лечения СД2: уточняются детали гликемического контроля и роль в снижении ВГ с безопасностью в отношении риска сердечно-сосудистых заболеваний (ССЗ). Представлены новые данные о механизмах действия дипептидазы-4, которая, как новый адипокин с системной активностью и клеточной специфичностью в регуляции не только метаболического гомеостаза, но и воспалительных процессов, может представлять собой ключевое звено между центральным ожирением, инсулинорезистентностью (ИР) и атеросклерозом. Соответственно, патофизиологическая связь СД2 и ССЗ через ИР и низкоуровневое воспаление определила смещение целей терапии с контроля уровня глюкозы крови на общее управление факторами риска, в котором уточняется роль и место иДПП-4.

The current focus of type 2 diabetes mellitus (T2DM) control has shifted from HbA1c to glycemic variability (GV) due to its key role in the accelerated development of diabetic complications, in addition to chronic hyperglycemia. The central link in the early stage of dysglycemia is β-cell dysfunction with subsequent loss of their mass with an important role of hyperglucagonemia at all stages of the diabetic continuum. Coordinated work of α and β-cells with the help of two endogenous incretins: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) is of decisive importance for maintaining glucose homeostasis. The ability of dipeptidyl peptidase-4 (DPP-4) inhibitors to not only maintain β-cell mass and promote insulin release, but also simultaneously correct glucagon secretion from α-cells, preventing hypoglycemia, by preserving bioactive GLP-1 and GIP intact, attracts special attention to these drugs.

The place of DPP-4 inhibitors among various pharmacological treatment options for T2DM is considered: details of glycemic control and the role in reducing GV with safety in relation to the risk of cardiovascular diseases (CVD) are clarified. New data on the mechanisms of action of dipeptidase-4 are presented, which, as a new adipokine with systemic activity and cellular specificity in the regulation of not only metabolic homeostasis, but also inflammatory processes, may represent a key link between central obesity, insulin resistance (IR) and atherosclerosis. Accordingly, the pathophysiological relationship between T2DM and CVD through IR and low-level inflammation has determined a shift in therapy goals from blood glucose control to general risk factor management, which clarifies the role and place of DPP-4 inhibitors.

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The authors declare that there are no conflicts of interest present.