Metabolic Syndrome and Neurotrophins: Effects of Metformin and Non-Steroidal Antiinflammatory Drug Treatment

Abstract

Objective: Metabolic syndrome (MS) presents with central obesity, impaired glucose metabolism, dyslipidemia and hypertension. Our aim was to examine the effect of metformin treatment either alone or in combination with non-steroidal anti-inflammatory drugs (NSAID) on plasma levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in patients with early stage MS (MS-es) and generalized MS (MS-ge). Materials and Methods:The study compared 35 female patients with MS-es (mean age of 43.39±1.54 years) and 40 patients with MSge (mean age of 45.69±2.18 years) to 10 age-matched controls each. Patients with MS-es were administered 850 mg metformin twice daily. The patients with MS-ge were divided into two groups of 20 patients per group. One group received metformin alone, while the other group received metformin in combination with 500 mg aspirin and 150 mg Diclac daily. Plasma NGF and BDNF levels were measured by ELISA. Statistical data analysis was performed using ANOVA.Results: Plasma NGF and BDNF levels were significantly higher in MS-es patients and lower in MS-ge patients than in controls. NGF levels were decreased in both groups after treatment with metformin. NGF levels were significantly higher in MS-ge patients on combined therapy than in those on metformin only. Conclusion:The combination of metformin and NSAID treatment is more effective than metformin alone on NGF and BDNF production as well as on metabolism-related anthropometric and laboratory features. This represents a pathogenetic therapeutic mechanism in MS due to its strong anti-inflammatory effect and improves MS-ge symptoms.Key Words: Brain-derived neurotrophic factor, Early stage metabolic syndrome, Generalized metabolic syndrome, Inflammation, Nerve growth factor Özet Amaç: Metabolik sendrom (MS), santral obezite, bozulmuş glukoz metabolizması, dislipidemi ve hipertansiyon ile kendini göstermek-tedir. Hedefimiz, tek başına metformin tedavisinin ve erken evre MS'li hastalarda (MS -es) ve generalize MS (MS-ge) sinir büyüme faktörü (NGF) ve beyin kaynaklı nörotrofik faktör (BDNF) plazma düzeyleri üzerine non-steroid antienflamatuar ilaçlar (NSAID) ile birlikte etkisini araştırmaktır. Gereç ve Yöntem:Çalışma, MS-es'li 35 kadın hasta (yaş ortalaması 43.39±1.54 yıl) ve 40 MS-ge'li kadın hasta (yaş ortalaması 45.69±2.18 yıl) ve her biri ile yaş olarak eşleştirilmiş 10 hastadan oluşan kontrol grubu ile yapılmıştır. MS-es ile hastalar günde iki kez 850 mg dozda metformin verilmiştir. MS-ge ile hastalar, her biri 20 hasta iki gruba ayrıldı. Bunlar, 150 mg günlük doz 500 mg ve Diclac (Diklofenak Na) bir doz aspirin ile ya tek başına veya kombine olarak metformin almıştır. Plazma NGF ve BDNF düzeyleri ELISA yöntemi ile ölçüldü. İsta-tistik veri işleme, ANOVA yöntemi ile yapıldı. Bulgular: Plazma NGF ve BDNF MS-es hastalarda önemli ölçüde daha yüksek ve MS-ge olanlar kontrollere göre daha düşüktü. NGF düzeyleri metformin ile tedavi sonrasında her iki grupta da azalmıştır. NGF seviyeleri sadece bu on metformin kombine tedavi MS-...

Serum Brain-Derived Neurotrophic Factor is Related to Platelet Reactivity and Metformin Treatment in Adult Patients With Type 2 Diabetes Mellitus

“…Another study showed significantly increased BDNF levels in the metformin-treated group than in both the control group and the group with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinsonism in mice (11). In a human study, nonsignificantly higher plasma BDNF levels were observed in patients with metabolic syndrome after treatment with metformin (9). It was also shown that metformin treatment ameliorated the decreased mRNA of BDNF levels in Schwann cells under conditions of hypoxia.…”

“…A limited amount of research has shown the alteration of BDNF levels to be due to antidiabetes drug treatment in vitro, in animal models and in studies in humans (9)(10)(11)(12). In our study, we found increased BDNF levels in patients who were taking metformin treatment.…”

“…Some research has shown alterations in BDNF levels due to metformin treatment in vitro, in animal models and in human studies. However, the research was performed in persons with neurodegenerative disease and metabolic syndrome but not in those with type 2 diabetes (9)(10)(11)(12).…”

Metabolic Syndrome in School Children in Mardin, South-Eastern of Turkey

“…And, another study found that the rate of MES was at 33% based on the IDF criteria [31]. New pathophysiological data imply that MS is a real disease and its prevalence is increasing worldwide [32]. Childhood obesity is increasing the likelihood of MES in children.…”

Nerve Growth Factor in Patients With Arterial Hypertension: Neuropsychical, Hemodynamic, Metabolic Relationships

“…В то же время в многочисленных исследованиях подчеркивается потенциальная роль ФРН в патогенезе кардиометаболических заболеваний, таких как атеросклероз, артериальная гипертензия (АГ), сахарный диабет (СД), хроническая сердечная недостаточность (ХСН), метаболический синдром (МС), а также возможность применения нейротрофических факторов в терапии данных заболеваний [6,[15][16][17].…”