diaendoСахарный диабетDiabetes mellitus2072-03512072-0378Endocrinology research centre10.14341/DM13311diaendo-13311Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL STUDIESВлияние гиперлипидемии на эндотелиальную дисфункцию и метаболизм аргинина у пациентов с диабетом: нарушение регуляции оксида азота и повышение риска сердечно-сосудистых заболеванийImpact of Hyperlipidemia on Endothelial Dysfunction and Arginine Metabolism in Diabetic Patients: Implications for Nitric Oxide Dysregulation and Increased Cardiovascular Riskhttps://orcid.org/0000-0003-1577-6525БикМ. А.BikM. A.

Бик Мохаммад Ахмад - Медицинский факультет, Кафедра медицинской биохимии.

Конья

Mohammad Ahmad Bik - PhD, Researcher, Faculty of Medicine, Department of Medical Biochemistry.

Konya

mo.bik881@gmail.comhttps://orcid.org/0000-0002-5369-9949АльмагребиЭ.AlmaghrebiE.

Альмагреби Эйса - Медицинский факультет, Кафедра медицинской биохимии.

Конья

Eissa Almaghrebi - PhD, Researcher, Faculty of Medicine, Department of Medical Biochemistry.

Konya

isaahmed9292@gmail.comhttps://orcid.org/0000-0003-3036-4377АкатФ.AkatF.

Акат Фатма - Медицинский факультет, Кафедра медицинской биохимии.

Конья

Fatma Akat - PhD, Researcher, Faculty of Medicine, Department of Medical Biochemistry.

Konya

fatmakat94@gmail.comhttps://orcid.org/0000-0003-4879-3671ГарабК.GharabK.

Гараб Карам.

Багдад

Karam Gharab - PhD, Assistant Lecturer.

Falastin Street, Baghdad

Karammazin@uomustansiriyah.edu.iqhttps://orcid.org/0000-0002-5439-8777СакФ.SakF.

Сак Фирдевс - Медицинский факультет, Кафедра медицинской биохимии.

Конья

Firdevs Sak - PhD, Researcher, Faculty of Medicine, Department of Medical Biochemistry.

Konya

firdevssak92@gmail.comhttps://orcid.org/0000-0002-4728-6355КараманФ.KaramanF.

Караман Фадиме - Медицинский факультет, Кафедра медицинской биохимии.

Конья

Fadime Karaman – MSc, Faculty of Medicine, Department of Medical Biochemistry.

Konya

Fadimekaraman03@gmail.comhttps://orcid.org/0000-0002-9991-3939ЮнлюА.ÜnlüA.

Юнлю Али - Медицинский факультет, Кафедра медицинской биохимии.

Конья

Ali Ünlü - MD, PhD, Professor, Faculty of Medicine, Department of Medical Biochemistry.

Konya

aunlu@selcuk.edu.trУниверситет СельчукТурцияSelcuk UniversityTurkeyУниверситет Мустансирийя, Национальный центр диабетаИракMustansiriyah University, National Diabetes CenterIraq202517012026286568577Copyright © Бик М.А., Альмагреби Э., Акат Ф., Гараб К., Сак Ф., Караман Ф., Юнлю А., 20262026Бик М.А., Альмагреби Э., Акат Ф., Гараб К., Сак Ф., Караман Ф., Юнлю А.Bik M.A., Almaghrebi E., Akat F., Gharab K., Sak F., Karaman F., Ünlü A.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/13311АКТУАЛЬНОСТЬ

АКТУАЛЬНОСТЬ. Сахарный диабет 2 типа (СД2) является одной из основных проблем общественного здравоохранения во всем мире, характеризуется хронической гипергликемией, инсулинорезистентностью и нарушением функции бета-клеток. Эндотелиальная дисфункция является характерным признаком диабета и усугубляется гиперлипидемией.

ЦЕЛЬ

ЦЕЛЬ. Изучить влияние гиперлипидемии на синтез оксида азота, метаболизм аргинина и маркеры сосудистого здоровья при СД2.

МАТЕРИАЛЫ И МЕТОДЫ

МАТЕРИАЛЫ И МЕТОДЫ. В этом перекрестном сравнительном исследовании приняли участие в общей сложности 120 человек. Уровни производных метиларгинина в сыворотке крови (асимметричный диметиларгинин (АДМА), симметричный диметиларгинин (СДМА), L-N-монометиларгинин (L-NMMA)) и связанных метаболитов (аргинин, гомоаргинин, цитруллин, орнитин) измерялись в трех группах: пациенты с диабетом и гиперлипидемией (DM-HL), пациенты с диабетом и нормолипидемией (DM-NL) и здоровые лица из контрольной группы (HC) с использованием методов LC-MS/MS на приборе API SCIEX 3200. Статистическое сравнение между группами проводилось с использованием IBM SPSS 26.0 для оценки влияния гиперлипидемии на эти маркеры.

РЕЗУЛЬТАТЫ

РЕЗУЛЬТАТЫ. Уровни АДМА и СДМА были значительно повышены в группе DM-HL по сравнению с группами DM-NL и HC (p=0,001 и p=0,000 соответственно), что указывает на усиление эндотелиальной дисфункции и потенциальное нарушение функции почек или сосудов, вызванное дислипидемией. Сниженные уровни аргинина и гомоаргинина в диабетических группах свидетельствуют о нарушении синтеза оксида азота и изменении функции цикла мочевины (p=0,013 и p=0,000 соответственно). Следует отметить, что в группе DM-HL уровни L-NMMA были значительно выше (p=0,001). Это привело к нарушению метаболических соотношений (например, СДМА/АДМА, аргинин/АДМА и гомоаргинин/АДМА), что отражает усиление ингибирования оксида азота и снижение его биодоступности. Гиперлипидемия значительно усугубляла эти нарушения, о чем свидетельствуют измененные соотношения цитруллин/аргинин и цитруллин/АДМА, что подчеркивает ее аддитивное влияние на эндотелиальную дисфункцию.

ВЫВОДЫ

ВЫВОДЫ. Гиперлипидемия усиливает неблагоприятное воздействие диабета на функцию эндотелия, усугубляя ингибирование оксида азота, окислительный стресс и нарушение метаболизма аргинина. Ключевые биомаркеры и метаболические соотношения, особенно индексы, связанные с АДМА и СДМА, дают ценную информацию о сердечно-сосудистом риске в данной популяции. Терапевтические стратегии, направленные на контроль липидов, добавление аргинина и снижение уровня АДМА, могут улучшить здоровье сосудов и снизить риск сердечно-сосудистых осложнений у пациентов с DM-HL.

BACKGROUND

BACKGROUND. Type 2 Diabetes Mellitus (T2DM) is a primary public health concern globally, characterized by chronic hyperglycemia, insulin resistance, impaired beta-cell function. Endothelial dysfunction is a hallmark of diabetes and is exacerbated by hyperlipidemia.

AIM

AIM. This study investigates the impact of hyperlipidemia on nitric oxide synthesis, arginine metabolism, and vascular health markers in T2DM.

MATERIALS AND METHODS

MATERIALS AND METHODS. A total of 120 participants were included in this cross-sectional, comparative study. Serum methylarginine derivatives (Asymmetric dimethyl arginine (ADMA), Symmetric dimethyl arginine (SDMA), L-N Mono-methylarginine (L-NMMA) and related metabolites (arginine, homoarginine, citrulline, ornithine) levels were measured in three groups: diabetes with hyperlipidemia (DM-HL), diabetes with normolipidemia (DM-NL), and healthy controls (HC) using API SCIEX 3200 LC-MS/MS methods. Statistical comparisons between groups were performed using IBM SPSS 26.0 to assess the influence of hyperlipidemia on these markers.

RESULTS

RESULTS. ADMA and SDMA levels were significantly elevated in DM-HL group compared to DM-NL and HC (p=0.001, p=0.000 respectively), indicating increased endothelial dysfunction and potential dyslipidemia-induced renal or vascular impairment. Reduced arginine and homoarginine levels in diabetic groups suggest impaired nitric oxide synthesis and altered urea cycle function (p=0.013, p=0.000 respectively). Notably, the DM-HL group exhibited significantly higher L-NMMA levels (p=0.001). It disrupted metabolic ratios (e.g., SDMA/ADMA, arginine/ADMA, and homoarginine/ADMA), reflecting enhanced nitric oxide inhibition and reduced bioavailability. Hyperlipidemia significantly exacerbated these disruptions, as evidenced by altered citrulline/arginine and citrulline/ADMA ratios, underscoring its additive impact on endothelial dysfunction.

CONCLUSIONS

CONCLUSIONS. Hyperlipidemia amplifies the adverse effects of diabetes on endothelial function by exacerbating nitric oxide inhibition, oxidative stress, and arginine metabolism dysregulation. Key biomarkers and metabolic ratios, particularly ADMA and SDMA-related indices, provide valuable insights into cardiovascular risk in this population. Therapeutic strategies targeting lipid management, arginine supplementation, and ADMA reduction could improve vascular health and mitigate cardiovascular complications in DM-HL.

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