Obezitenin tiroid fonksiyonu üzerindeki etkisi: Hiperinsülinemi ve inflamasyonun rolleri

Abstract

The impact of obesity on thyroid function: Roles of hyperinsulinemia and inflammation

Abstract

Obesity results from an imbalance between energy intake and expenditure, with thyroid hormones crucial in regulating metabolism and energy balance. A bidirectional relationship between obesity and thyroid hormones exists, but the effect of hyperinsulinemia on the thyroid axis remains unclear This research involved a retrospective evaluation of 486 individuals classified as overweight or obese (BMI ≥25 kg/m² and BMI ≥30 kg/m²), partitioned into groups depending on the presence of hyperinsulinemia. In addition, 42 healthy individuals without obesity or chronic illnesses were enrolled as the control group. Comparisons were made among the groups regarding thyroid-stimulating hormone (TSH), liver function markers, lipid profiles, and CRP levels. Participants were categorized into three groups based on BMI: normal weight (control), overweight, and obese. Higher BMI was associated with significant increases in HbA1c, ALT, LDL, and TG levels (p<0.001, p=0.016, p=0.052, p=0.001, respectively), while HDL levels decreased significantly (p<0.001). TSH levels were significantly higher in obese individuals compared to the overweight and normal-weight groups (p = 0.026). CRP, glucose, and insulin levels were also significantly elevated in the overweight and obese groups (p<0.001 for all). When overweight and obese participants were further classified based on insulin resistance (HOMA-IR>2.5 vs. <2.5), the insulin-resistant group exhibited significantly higher HbA1c, AST, ALT, TG, and CRP levels (p = 0.026, p = 0.036, p = 0.001, p = 0.036, respectively). Additionally, TSH levels were significantly elevated in insulin-resistant individuals (p = 0.023). Higher BMI was associated with metabolic disturbances, including increased 3 HbA1c, ALT, LDL, TG, and TSH levels, along with decreased HDL. Insulin resistance further worsened these parameters, accompanied by significantly higher CRP and TSH levels. The observed CRP elevation suggests that inflammation driven by hyperinsulinemia may contribute to thyroid dysfunction. Clinically, monitoring HOMA-IR and routinely assessing TSH in obese patients may help predict and manage early thyroid abnormalities.

Keywords

• Obesity
• thyroid-stimulating hormone
• insulin resistance
• inflammation
• Body Mass Index

References

1. Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I et al; American Association Of Clinical Endocrinologists And American Thyroid Association Taskforce On Hypothyroidism In Adults. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association ofClinical Endocrinologists and the American Thyroid Association. Thyroid. 2012;22(12):1200-35. Erratum in: Thyroid. 2013;23(2):251. Erratum in: Thyroid.21 2013;23(1):129.
2. Carlé A, Pedersen IB, Knudsen N, Perrild H, Ovesen L et al. Hypothyroid Symptoms Fail to Predict Thyroid Insufficiency in Old People: A Population-Based Case-Control Study. Am J Med. 2016 Oct;129(10):1082-92. doi: 10.1016/j.amjmed.2016.06.013. Epub 2016 Jul 7. PMID: 27393881.3-Garmendia Madariaga A, Santos Palacios S, 1
3. Guillén-Grima F, Galofré JC. The incidence and prevalence of thyroid dysfunction in Europe: a meta-analysis. J Clin Endocrinol Metab 2014; 99: 923–31.
4. Walczak K, Sieminska L. Obesity and Thyroid Axis. Int J Environ Res Public Health. 2021 Sep 7;18(18):9434. doi: 10.3390/ijerph18189434. PMID: 34574358; PMCID: PMC8467528.
5. Gastaldelli A. Measuring and estimating insulin resistance in clinical and research settings. Obesity (Silver Spring). 2022;30(8):1549-1563. doi:10.1002/oby.23503
6. Pacini G, Finegood DT, Bergman RN. A minimal-model-based glucose clamp yielding insulin sensitivity independent of glycemia. Diabetes. 1982;31(5 Pt 1):432-441. doi:10.2337/diab.31.5.432
7. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifyingn insulin secretion and resistance. Am J Physiol 1979;237:E214-23.
8. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004;27(6):1487-1495. doi:10.2337/diacare.27.6.1487

9. Radziuk J. Insulin sensitivity and its measurement: structural commonalities among the methods. J Clin Endocrinol Metab 2000;85:4426-33.
10. Brenta G. Why can insulin resistance be a natural consequence of thyroid dysfunction? J Thyroid Res. 2011;2011:152850. doi:10.4061/2011/152850
11. Clément K, Viguerie N, Diehn M, Alizadeh A, Barbe P et al. In vivo regulation of human skeletal muscle gene expression by thyroid hormone. Genome Res. 2002 Feb;12(2):281-91. doi: 10.1101/gr.207702. PMID: 11827947; PMCID: PMC155277.12-Douyon L, Schteingart
12. DE. Effect of obesity and starvation 1 on thyroid hormone, growth hormone, and cortisol secretion. Endocrinol Metab Clin North Am 2002; 31: 173-189.
13. Kokkoris P, Pi-Sunyer FX. Obesity and endocrine disease. Endocrinol Metab Clin North Am 2003; 32: 895-914.
14. Reinehr T. Obesity and thyroid function. Mol Cell Endocrinol 2010; 316: 165- 171.25Biondi B. Thyroid and obesity: an intriguing relationship. J Clin Endocrinol Metab 2010; 95: 3614-3617.
15. Pasquali R., Casanueva F., Haluzik M., van Hulsteijn L., Ledoux S. et al. European Society of Endocrinology Clinical Practice Guideline: Endocrine work-up in obesity. Eur. J. Endocrinol. 2020;182:G1–G32. doi: 10.1530/EJE-19-0893.
16. Abdi H., Faam B., Gharibzadeh S., Mehran L., Tohidi M. et al. Determination of age and sex specific TSH and FT4 reference limits in overweight and obese individuals in an iodine replete region: Tehran Thyroid Study (TTS) Endocr. Res. 2021;46:37–43. doi: 10.1080/07435800.2020.1854778.
17. Michalaki MA, Vagenakis AG, Leonardou AS, Argentou MN, Habeos IG, Makri MG et al. Thyroid function in humans with morbid obesity. Thyroid.2006;16(1):73-8.
18. Brenta G, Caballero AS, Nunes MT. Case finding for hypothyroidism should include type 2 diabetes and metabolic syndrome patients: a Latin American Thyroid Society (LATS) position statement. Endocr Pract 2019; 25: 101–105
19. Teixeira PFDS, Dos Santos PB, Pazos-Moura CC. The role of thyroid hormone in metabolism and metabolic syndrome. Ther Adv Endocrinol Metab. 2020 May 13;11:2042018820917869. doi: 10.1177/2042018820917869. PMID: 32489580; PMCID: PMC7238803.
20. Ambrosi B, Masserini B, Iorio L, Delnevo A, Malavazos AE et al. Relationship of thyroid function with body mass index and insulin-resistance in euthyroid obese subjects. J Endocrinol Invest. 2010 Oct;33(9):640-3. doi: 10.1007/BF03346663. Epub 2010 Mar 25. PMID: 20339314.
21. Baskol G, Baskol M, Kocer D. Oxidative stress and antioxidant defenses in serum of patientswith non-alcoholic steatohepatitis. Clin Biochem. 2007;40(11):776-780.doi:10.1016/j.clinbiochem.2007.02.006
22. Sheth SG, Gordon FD, Chopra S. Nonalcoholic steatohepatitis [published correction appears in Ann Intern Med 1997 Oct 15;127(8 Pt 1):658]. Ann Intern Med. 1997;126(2):137-145. doi:10.7326/0003-4819-126-2-199701150-00008
23. Singh Y, Garg MK, Tandon N, Marwaha RK. A study of insulin resistance by HOMA-IR and its cut-off value to identify metabolic syndrome in urban Indian adolescents. J Clin Res Pediatr Endocrinol. 2013; 5:245-251
24. Longo M, Zatterale F, Naderi J, Parrillo L, Formisano P et al. Adipose Tissue Dysfunction as Determinant of Obesity- Associated Metabolic Complications. International Journal of Molecular Sciences. 2019; 20(9):2358. https://doi.org/10.3390/ijms20092358
25. Festa A, D'Agostino R, Jr, Howard G, Mykkanen L, Tracy RP et al. Chronic subclinical treatment as part of insulin resistance surgery: Circulation Insulin Resistance Atherosclerosis Study (IRAS). 2000;102:42–47. doi: 10.1161/01.cir.102.1.42.
26. Keaney JF, Jr, Larson MG, Vasan RS, Wilson 1 PWF, Lipinska I. et al. Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscle Thromb Vasc Biol. 2003;23:434–439. doi:
27. Ahmed B, Sultana R, Greene MW. Adipose tissue and insulin resistance in obese. Biomed Pharmacother.2021;137:111315. doi:10.1016/j.biopha.2021.111
28. Nayak SS, Hashemi SM, Patel M, et al. The impact of weight loss interventions on thyroid function: a systematic review and meta-analysis. Ann Med Surg (Lond). 2025;87(7):4484-4497. Published 2025 May 26. doi:10.1097/MS9.000000000000342829. Sutkowska E, Kisiel M,
29. Zubkiewicz-Kucharska A. When Should the Treatment of Obesity in Thyroid Disease Begin?. Biomedicines. 2025;13(1):157. Published 2025 Jan 10. doi:10.3390/biomedicines13010157