Спектр эффектов ингибиторов дипептидилпептидазы-4: внутри и за пределами гликемического контроля (часть 1)

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.

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