Obez Prediyabetiklerde α-klotho, FGF-23 ve İnsülin Direncinin Değerlendirilmesi

Abstract

Amaç: Prediyabet, hiperglisemi ve tip 2 diabetes mellitus (T2DM) gelişme riski olan bir durumdur. Bu çalışmanın amacı, kan basıncı, serum lipoproteinleri, glikoz ve insülin düzeylerinin yanı sıra α-klotho ve FGF-23 parametrelerinin konsantrasyonlarını belirlemektir. Ayrıca obez prediyabetiklerde ve obez normoglisemilerde tüm bu parametreler arasındaki korelasyonu belirlemeyi hedefliyoruz. Gereç yöntemler: Toplam 26 obez normoglisemik (kontrol grubu) ve 25 obez prediyabetik birey bu çalışmaya dahil edildi. Hastanemizin biyokimya laboratuvarlarında rutin prosedür kapsamında glukoz, hemoglobin A1c (HbA1c) ve kolesterol seviyeleri otoanalizör kullanılarak analiz edildi. α-klotho ve fibroblast büyüme faktörü-23 (FGF-23) düzeylerini belirlemek için ELISA yöntemi kullanıldı. Bulgular: Bulgulara göre obez prediyabetik grupta serum LDL-C, TC, HbA1c, glikoz, insülin ve HOMA-IR seviyelerinde kontrol grubuna göre anlamlı artış tespit edildi (p <0.05). Ancak obez prediyabetik grupta serum α-klotho ve FGF-23 düzeyleri kontrol grubuna göre anlamlı olarak düşük bulundu (p <0.05). α-klotho ve FGF-23 değerleri, HOMA-IR değerleri ile ayrı ayrı karşılaştırıldığında güçlü negatif korelasyon gösterdi (p <0.01). Sonuç: Bu bulgular, α-klotho ve / veya FGF-23 parametrelerinin prediyabet için bir belirteç olabileceğini düşündürmektedir. Çalışmamızın sonuçları, ileride yapılacak çalışmalarla birlikte, diyabet polikliniklerinde prediyabet tanı kriterleri olarak literatüre önemli katkı sağlayacaktır.

Keywords

• prediyabet
• insülin direnci
• α-klotho
• fibroblast büyüme faktörü-23 (FGF-23)

Project Number

2018-43085703-03

Evaluation of α-klotho, FGF-23 and Insulin Resistance in Obese Prediabetics

Abstract

Aim: Prediabetes is a condition with hyperglycemia and risk of development type 2 diabetes mellitus (T2DM). The aim of this study is to determine the concentrations of blood pressure, serum lipoproteins, glucose and insulin levels as well as the concentrations of α-klotho and FGF-23 parameters. We also aim at the correlation between all these parameters in obese prediabetics and obese normoglycemics. Material methods: A total of 26 obese normoglycemic (control group) and 25 obese prediabetic individuals were included in this study. Glucose, haemoglobin A1c (HbA1c) and cholesterols levels were analyzed as part of a routine procedure in the biochemistry laboratories of our hospital using an autoanalyzer. In order to determine α-klotho and fibroblast growth factor-23 (FGF-23) levels, ELISA method was used. Result: According to the findings, a significant increase was detected in serum LDL-C, TC, HbA1c, glucose, insulin and HOMA-IR levels in the obese prediabetic group compared to the control group (p <0.05). However, serum α-klotho and FGF-23 levels were found to be significantly lower in the obese prediabetic group compared to the control group (p <0.05). α-klotho and FGF-23 values showed strong negative correlation when compared with HOMA-IR values separately (p <0.01). Conclusion: These findings suggest that α-klotho and / or FGF-23 parameters may be a marker for prediabetes. The results of our study, together with the future studies, will make a significant contribution to the literature, as prediabetes diagnostic criteria in the diabetes outpatient clinics.

Keywords

• Prediabetes
• insulin resistance
• α-klotho
• fibroblast growth factor-23 (FGF-23)

Supporting Institution

Zonguldak Bülent Ecevit University Scientific Research Projects

Project Number

2018-43085703-03

Thanks

The authors would like to thank Safiye ÇATALCAM and Ebru BOZ UZALDI for their valuable contribution in collecting blood and consent forms of patients.

References

1. 1. World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia: report of a WHO/IDF consultation. 1st Edition, WHO; IDF, 2006.
2. 2. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care, 2014;37(1):81-90.
3. 3. World Health Organization (WHO). Obesity and Overweight. (Accessed April 2020, at http://www.who.int/mediacentre/factsheets/fs311/en/)
4. 4. Herder C, Carstensen M, Ouwens DM. Anti-inflammatory cytokines and risk of type 2 diabetes. Diabetes Obes Metab. 2013;15:39-50.
5. 5. Luc K, Schramm-Luc A, Guzik TJ, Mikolajczyk TP. Oxidative stress and inflammatory markers in prediabetes and diabetes. J Physiol Pharmacol. 2019;70(6): 810-824.
6. 6. Hamamcioglu, AC. The Role of Oxidative Stress and Antioxidants in Diabetes Mellitus. Turk J Diab Obes. 2017;1(1):7-13.
7. 7. Sangrós FJ, Torrecilla J, Giráldez-García C, Carrillo L, Mancera J, Mur T, et al. Association of General and Abdominal Obesity With Hypertension, Dyslipidemia and Prediabetes in the PREDAPS Study. Rev Esp Cardiol (Engl Ed). 2018;71(3):170-177.
8. 8. Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature. 1997;390:45-51.

9. 9. Komaba H, Fukagawa M. The role of FGF23 in CKD with or without Klotho. Nat Rev Nephrol. 2012;8:484-490.
10. 10. Kitagawa M, Sugiyama H, Morinaga H, Inoue T, Takiue K, Ogawa A, et al. A decreased level of serum soluble Klotho is an independent biomarker associated with arterial stiffness in patients with chronic kidney disease. PLoS One. 2013;8:e56695.
11. 11. Lin Y, Sun Z. In vivo pancreatic β-cell-specific expression of antiaging gene Klotho: a novel approach for preserving β-cells in type 2 diabetes. Diabetes. 2015;64(4):1444-1458.
12. 12. Kutluturk Y, Akinci A, Ozerol IH, Yologlu S. The relationship between serum FGF-23 concentration and insulin resistance, prediabetes and dyslipidemia in obese children and adolescents. J Pediatr Endocrinol Metab. 2019;32(7):707-714.
13. 13. Antuna-Puente B, Disse E, Rabasa-Lhoret R, Laville M, Capeau J, Bastard JP: How can we measure insulin sensitivity/resistance? Diabetes Metab. 2011;37:179-188.
14. 14. Mojiminiyi OA, Abdella NA. Effect of homeostasis model assessment computational method on the definition and associations of insulin resistance. Clin Chem Lab Med. 2010;48:1629-1634.
15. 15. Boles A, Kandimalla R, Reddy PH. Dynamics of diabetes and obesity: Epidemiological perspective. Biochim Biophys Acta Mol Basis Dis. 2017;1863(5):1026-1036.
16. 16. Mainous AG, Tanner RJ, Baker R, Zayas CE, Harle CA. Prevalence of prediabetes in England from 2003 to 2011: population-based, cross-sectional study. BMJ Open. 2014;4(6):e005002.
17. 17. Dunkley AJ, Bodicoat DH, Greaves CJ, Russell C, Yates T, Davies MJ, Khunti K. Diabetes prevention in the real world: effectiveness of pragmatic lifestyle interventions for the prevention of type 2 diabetes and of the impact of adherence to guideline recommendations: a systematic review and meta-analysis. Diabetes Care. 2014;37(4):922-933.
18. 18. Selph S, Dana T, Blazina I, Bougatsos C, Patel H, Chou R. Screening for type 2 diabetes mellitus: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2015;162(11):765-776. 19. Gopalan A, Lorincz IS, Wirtalla C, Marcus SC, Long JA. Awareness of Prediabetes and Engagement in Diabetes Risk-Reducing Behaviors. Am J Prev Med. 2015;49(4):512-519.
19. 20. Hubbard D, Colantonio LD, Tanner RM, Carson AP, Sakhuja S, Jaeger BC, et al. Prediabetes and Risk for Cardiovascular Disease by Hypertension Status in Black Adults: The Jackson Heart Study. Diabetes Care. 2019;42(12):2322-2329.
20. 21. Liu HH, Cao YX, Li S, Guo YL, Zhu CG, Wu NQ, et al. Impacts of Prediabetes Mellitus Alone or Plus Hypertension on the Coronary Severity and Cardiovascular Outcomes. Hypertension. 2018;71(6):1039-1046.
21. 22. Petrie JR, Guzik TJ, Touyz RM. Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms. Can J Cardiol. 2018;34(5):575-584.
22. 23. Zhang L, Qiao Q, Tuomilehto J, Hammar N, Alberti KG, Eliasson M, et al. Blood lipid levels in relation to glucose status in European men and women without a prior history of diabetes: the DECODE Study. Diabetes Res Clin Pract. 2008;82(3):364-377.
23. 24. Mohieldein AH, Hasan M, Al-Harbi KK, Alodailah SS, Azahrani RM, Al-Mushawwah SA. Dyslipidemia and reduced total antioxidant status in young adult Saudis with prediabetes. Diabetes Metab Syndr. 2015;9(4):287-291.
24. 25. Lin Y, Sun Z. In vivo pancreatic β-cell-specific expression of antiaging gene Klotho: a novel approach for preserving β-cells in type 2 diabetes. Diabetes. 2015;64(4):1444-1458.
25. 26. Silva AP, Mendes F, Pereira L, Fragoso A, Gonçalves RB, Santos N, et al. Klotho levels: association with insulin resistance and albumin-to-creatinine ratio in type 2 diabetic patients. Int Urol Nephrol. 2017;49(10):1809-1814.
26. 27. Gateva A, Assyov Y, Tsakova A, Kamenov Z. Prediabetes is Characterized by Higher FGF23 Levels and Higher Prevalence of Vitamin D Deficiency Compared to Normal Glucose Tolerance Subjects. Horm Metab Res. 2019;51(2):106-111.