Neuroinflammation and metabolic dysregulation as predictors of cognitive impairment, depression, and quality of life in type 2 diabetes mellitus patients on SGLT2 inhibitors and sulfonylureas.

IF 4.6 2区医学 Q2 IMMUNOLOGY

Inflammopharmacology Pub Date : 2025-06-27 DOI:10.1007/s10787-025-01824-9

Haya Majid, Sajad Ul Islam, Sunil Kohli, Nidhi

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引用次数: 0

Abstract

Background: Cognitive impairment, depression, and a lower quality of life (QoL) are among the metabolic and neuropsychiatric consequences linked to type 2 diabetes mellitus (T2DM). The pharmacological management of T2DM often involves sodium-glucose co-transporter 2 inhibitors (SGLT2i) and sulfonylureas (SUs), both of which have been shown to influence metabolic control and inflammation. However, their differential effects on neuroinflammatory markers and neuropsychiatric outcomes remain poorly understood. This study aims to compare the effects of SGLT2i and SUs on key metabolic (mTOR, PI3K, AkT), neuroinflammatory (HMGB1, TLR4, ADAM-10, TNF-α, IL-1β, IL-6), and neuroprotective biomarkers (Klotho) associated with cognitive impairment, depression, and QoL in patients with T2DM.

Methods: A case-control study was conducted with 166 participants divided into three groups: healthy controls (n = 55), SGLT2i-treated patients (n = 57), and SUs-treated patients (n = 54). The study assessed anthropometric measurements, biochemical markers, kidney function, serum neuroinflammatory and metabolic biomarkers, cognitive function (MoCA), depression (PHQ-9), and QoL (SF-36) through standard protocols.

Results: Both SGLT2i and SUs significantly increased neuroinflammatory biomarkers (HMGB1, ADAM-10, TNF-α, IL-1β, IL-6) along with mTOR and Klotho compared to the healthy control group (p < 0.001). However, SGLT2i showed a more favourable reduction in these markers. Cognitive impairment and depression were more pronounced in the SUs group (MoCA: 20.03 ± 2.04, PHQ-9: 8.2 ± 1.67) compared to SGLT2i (MoCA: 22.51 ± 4.2, PHQ-9: 6.5 ± 3.8) (p < 0.001).

Conclusion: SGLT2i are more effective than SUs in modulating metabolic and neuroinflammatory biomarkers and may offer better neuropsychiatric outcomes, potentially improving overall QoL in T2DM patients. Further research is needed to explore the long-term effects of these drugs on neurodegeneration and cognitive health.

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神经炎症和代谢失调作为使用SGLT2抑制剂和磺脲类药物的2型糖尿病患者认知障碍、抑郁和生活质量的预测因素

背景：认知障碍、抑郁和较低的生活质量（QoL）是与2型糖尿病（T2DM）相关的代谢和神经精神后果。T2DM的药理学管理通常涉及钠-葡萄糖共转运蛋白2抑制剂（SGLT2i）和磺脲类药物（SUs），这两种药物都被证明可以影响代谢控制和炎症。然而，它们对神经炎症标志物和神经精神预后的不同影响仍然知之甚少。本研究旨在比较SGLT2i和SUs对T2DM患者认知障碍、抑郁和生活质量相关的关键代谢（mTOR、PI3K、AkT）、神经炎症（HMGB1、TLR4、adam10、TNF-α、IL-1β、IL-6）和神经保护生物标志物（Klotho）的影响。方法：对166名受试者进行病例对照研究，将其分为三组：健康对照组（n = 55）、sgltti治疗组（n = 57）和sus治疗组（n = 54）。该研究通过标准方案评估了人体测量、生化指标、肾功能、血清神经炎症和代谢生物标志物、认知功能（MoCA）、抑郁（PHQ-9）和生活质量（SF-36）。结果：与健康对照组相比，SGLT2i和SUs均显著增加了神经炎症生物标志物（HMGB1、adam10、TNF-α、IL-1β、IL-6）以及mTOR和Klotho (p)。结论：SGLT2i在调节代谢和神经炎症生物标志物方面比SUs更有效，可能提供更好的神经精神预后，可能改善T2DM患者的总体生活质量。需要进一步的研究来探索这些药物对神经变性和认知健康的长期影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Inflammopharmacology IMMUNOLOGYTOXICOLOGY-TOXICOLOGY

CiteScore

8.00

自引率

3.40%

发文量

200

期刊介绍： Inflammopharmacology is the official publication of the Gastrointestinal Section of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the Hungarian Experimental and Clinical Pharmacology Society (HECPS). Inflammopharmacology publishes papers on all aspects of inflammation and its pharmacological control emphasizing comparisons of (a) different inflammatory states, and (b) the actions, therapeutic efficacy and safety of drugs employed in the treatment of inflammatory conditions. The comparative aspects of the types of inflammatory conditions include gastrointestinal disease (e.g. ulcerative colitis, Crohn''s disease), parasitic diseases, toxicological manifestations of the effects of drugs and environmental agents, arthritic conditions, and inflammatory effects of injury or aging on skeletal muscle. The journal has seven main interest areas: -Drug-Disease Interactions - Conditional Pharmacology - i.e. where the condition (disease or stress state) influences the therapeutic response and side (adverse) effects from anti-inflammatory drugs. Mechanisms of drug-disease and drug disease interactions and the role of different stress states -Rheumatology - particular emphasis on methods of measurement of clinical response effects of new agents, adverse effects from anti-rheumatic drugs -Gastroenterology - with particular emphasis on animal and human models, mechanisms of mucosal inflammation and ulceration and effects of novel and established anti-ulcer, anti-inflammatory agents, or antiparasitic agents -Neuro-Inflammation and Pain - model systems, pharmacology of new analgesic agents and mechanisms of neuro-inflammation and pain -Novel drugs, natural products and nutraceuticals - and their effects on inflammatory processes, especially where there are indications of novel modes action compared with conventional drugs e.g. NSAIDs -Muscle-immune interactions during inflammation [...]