Патогенетические предпосылки применения ингибиторов дипептидилпептидазы-4 в управлении сахарным диабетом типа 2

Демидова Т.Ю., Куленок С.Г., Гасанзаде П.А. Патогенетические предпосылки применения ингибиторов дипептидилпептидазы-4 в управлении сахарным диабетом типа 2. Consilium Medicum. 2017; 19 (4): 23–28.

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Demidova T.Yu., Kulenok S.G., Gasanzade P.A. Pathogenetic background of dipeptidyl peptidase-4 inhibitors application in the management of diabetes mellitus type 2. Consilium Medicum. 2017; 19 (4): 23–28.

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Аннотация

Управление сахарным диабетом (СД) типа 2 предполагает как можно более раннее назначение терапии. Отмечается, что у больных СД типа 2 b-клеточная масса снижается более чем на 50%, и ее уменьшение начинается на стадии предиабета. Уже на стадии нарушения толерантности к глюкозе наблюдается снижение инкретинового эффекта, заключающегося в увеличении концентрации инсулина в ответ на пероральный прием глюкозы или пищевые стимулы. Индуцированная глюкагоноподобным пептидом-1 секреция инсулина у больных СД типа 2 снижена по сравнению со здоровыми людьми в результате сокращения функционирующей массы b-клеток. Таким образом, b-клеточная дисфункция не только является предпосылкой для развития СД типа 2, но также определяет неизбежно прогрессирующее течение болезни. Это наблюдение указывает на возможность улучшения инкретинового эффекта на фоне улучшения функционального состояния b-клеток, например в результате устранения глюкозотоксичности. Предпочтение отдается препаратам, одновременно воздействующим на несколько звеньев патогенеза и обладающим при этом высокой степенью безопасности. Ингибиторы дипептидилпептидазы-4 значительно восстанавливают массу b-клеток и морфологию островков поджелудочной железы, тем самым сохраняя функцию секреции инсулина. В данной статье описаны преимущества раннего применения ингибиторов дипептидилпептидазы-4 с целью коррекции патогенетических дефектов, а также сообщается о разработках новых направлений воздействия на инкретиновую систему.

Ключевые слова: ингибиторы дипептидилпептидазы-4, инкретиновый эффект, b-клеточная дисфункция, алоглиптин, сахарный диабет типа 2.

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Management of type 2 diabetes mellitus (DM) suggests the earliest therapy appointment. It is noted that in patients with DM type 2 the b-cell mass is reduced by more than 50%, and this reduction begins at the stage of pre-diabetes. The reducing of incretin effect can be observed at the stage of impaired glucose tolerance in the incensement of insulin concentration in response to oral intake of glucose and nutritional stimulus. Insulin secretion induced by glucagon-like peptide-1 in patients with type 2 DM is reduced in comparison with healthy people as a result of reduced functioning of b-cells mass. Thus, b-cell dysfunction is not only the step to developing type 2 DM, but also determines the continuing progressive course of the disease. This study indicates the possibility of improving incretin effect against the background of improved functional status of b-cells, for example, as a result of a removal of glucotoxicity. Drug preference is given to agents, simultaneously affecting several parts of pathogenesis and with the high level of safety. Dipeptidyl peptidase-4 inhibitors significantly restore b-cell mass and morphology of pancreatic islets, thus such function as insulin secretion has been persisting. This article describes the benefits of early application of dipeptidyl peptidase-4 inhibitors to correct the pathogenetic defects, as well as the development of new approaches to affect the incretin system.

Key words: dipeptidyl peptidase-4 inhibitors, incretin effect, b-cell dysfunction, alogliptin, diabetes mellitus type 2.

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Авторы

Т.Ю.Демидова*, С.Г.Куленок, П.А.Гасанзаде

ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава России. 125993, Россия, Москва, ул. Баррикадная, д. 2/1
*t.y.demidova@gmail.com

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T.Yu.Demidova*, S.G.Kulenok, P.A.Gasanzade

Russian Medical Academy of Continuous Professional Education of the Ministry of Health of the Russian Federation. 125993, Russian Federation, Moscow, ul. Barrikadnaia, d. 2/1
*t.y.demidova@gmail.com

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