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The Relationship Between Euthyroid, Hyperthyroid, Hypothyroid, and Type 2 Diabetes

Year 2023, Volume: 3 Issue: 4, 105 - 111, 09.10.2023

Abstract

Diabetes mellitus (DM) and thyroid dysfunction, which have a significant incidence worldwide, are the most common endocrine system disorders that occur together in patients. Our aim is to explain these 2 diseases with high incidence and the relationship between these 2 diseases. Thyroid hormones (TH) are essential hormones that govern body metabolism. Thyroid hormone changes are thought to be effective on the pathogenesis of DM. Diabetes mellitus treatments can be beneficial, as TH changes may contribute to the pathogenesis of DM. However, more research needs to be done. This lack of information limits potential biomarkers and targets for diagnosis, prognosis, and the development of new DM treatments. The limitations of the use of natural THs have led to the development of synthetic hormones called thyromimetics. However, most of the thyromimetics tested so far have been ineffective or toxic.

References

  • 1. Oguntibeju OO. Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links. Int J Physiol Pathophysiol Pharmacol. 2019;11(3):45-63.
  • 2. Cole JB, Florez JC. Genetics of diabetes mellitus and diabetes complications. Nat Rev Nephrol. 2020;16(7):377-390. [CrossRef]
  • 3. Forouhi NG, Wareham NJ. Epidemiology of diabetes. Medicine (Abingdon). 2014;42(12):698-702. [CrossRef]
  • 4. Redondo MJ, Hagopian WA, Oram R, et al. The clinical consequences of heterogeneity within and between different diabetes types. Diabetologia. 2020;63(10):2040-2048. [CrossRef]
  • 5. Ozougwu O. The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus. J Physiol Pathophysiol. 2013;4(4):46-57.
  • 6. Liu YC, Yeh CT, Lin KH. Molecular functions of thyroid hormone signaling in regulation of cancer progression and anti-apoptosis. Int J Mol Sci. 2019;20(20):4986.[CrossRef]
  • 7. Gereben B, Zavacki AM, Ribich S, et al. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr Rev. 2008;29(7):898-938. [CrossRef]
  • 8. Thvilum M, Brandt F, Brix TH, Hegedüs L. A review of the evidence for and against increased mortality in hypothyroidism. Nat Rev Endocrinol. 2012;8(7):417-424. [CrossRef]
  • 9. Pistollato F, Masias M, Agudo P, Giampieri F, Battino M. Effects of phytochemicals on thyroid function and their possible role in thyroid disease. Ann N Y Acad Sci. 2019;1443(1):3-19. [CrossRef]
  • 10. Ragusa F, Fallahi P, Elia G, et al. Hashimotos’ thyroiditis: epidemiology, pathogenesis, clinic and therapy. Best Pract Res Clin Endocrinol Metab. 2019;33(6):101367. [CrossRef]
  • 11. MacFarland SP, Bauer AJ, Adzick NS, et al. Disease burden and outcome in children and young adults with concurrent graves disease and differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2018;103(8):2918-2925. [CrossRef]
  • 12. Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev. 2014;94(2):355-382. [CrossRef]
  • 13. Klieverik LP, Janssen SF, van Riel A, et al. Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver. Proc Natl Acad Sci U S A. 2009;106(14):5966-5971. [CrossRef]
  • 14. López-Noriega L, Cobo-Vuilleumier N, Narbona-Pérez ÁJ, et al. Levothyroxine enhances glucose clearance and blunts the onset of experimental type 1 diabetes mellitus in mice. Br J Pharmacol. 2017;174(21):3795-3810. [CrossRef]
  • 15. Celani MF, Bonati ME, Stucci N. Prevalence of abnormal thyrotropin concentrations measured by a sensitive assay in patients with type 2 diabetes mellitus. Diabetes Res. 1994;27(1):15-25.
  • 16. Maratou E, Hadjidakis DJ, Kollias A, et al. Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur J Endocrinol. 2009;160(5):785-790. [CrossRef]
  • 17. Shun CB, Donaghue KC, Phelan H, Twigg SM, Craig ME. Thyroid autoimmunity in Type 1 diabetes: systematic review and meta-analysis. Diabet Med. 2014;31(2):126-135. [CrossRef]
  • 18. Seely EW, Solomon CG. Insulin resistance and its potential role in pregnancy induced hypertension. J Clin Endocrinol Metab. 2003;88(6):2393-2398. [CrossRef]
  • 19. Kühl C. Insulin secretion and insulin resistance in pregnancy and GDM. Implications for diagnosis and management. Diabetes. 1991;40(suppl 2):18-24. [CrossRef]
  • 20. Karbalaei N, Ghasemi A, Faraji F, Zahediasl S. Comparison of the effect of maternal hypothyroidism on carbohydrate metabolism in young and aged male offspring in rats. Scand J Clin Lab Investig. 2013;73(1):87-94. [CrossRef]
  • 21. Martin-Montalvo A, López-Noriega L, Jiménez-Moreno C, et al. Transient PAX8 expression in islets during pregnancy correlates with β-cell survival, revealing a novel candidate gene in gestational diabetes mellitus. Diabetes. 2019;68(1):109-118 [CrossRef]
  • 22. Mastracci TL, Evans-Molina C. Pancreatic and islet development andfunction: the role of thyroid hormone. J Endocrinol Diabetes Obes. 2014;2(3):1044.
  • 23. Aguayo-Mazzucato C, Zavacki AM, Marinelarena A, et al. Thyroid hormone promotes postnatal rat pancreatic β-cell development and glucose-responsive insulin secretion through MAFA. Diabetes. 2013;62(5):1569-1580. [CrossRef]
  • 24. López-Noriega L, Capilla-González V, Cobo-Vuilleumier N, et al. Inadequate control of thyroid hormones sensitizes to hepatocarcinogenesis and unhealthy aging. Aging (Albany NY). 2019;11(18):7746-7779. [CrossRef]
  • 25. Supale S, Li N, Brun T, Maechler P. Mitochondrial dysfunction in pancreatic β cells. Trends Endocrinol Metab. 2012;23(9):477-487. [CrossRef]
  • 26. Klieverik LP, Sauerwein HP, Ackermans MT, Boelen A, Kalsbeek A, Fliers E. Effects of thyrotoxicosis and selective hepatic autonomic denervation on hepatic glucose metabolism in rats. Am J Physiol Endocrinol Metab. 2008;294(3):E513-E520 [CrossRef]
  • 27. Gierach M, Gierach J, Junik R. Insulin resistance and thyroid disorders. Endokrynol Pol. 2014;65(1):70-76. [CrossRef]
  • 28. Hatting M, Tavares CDJ, Sharabi K, Rines AK, Puigserver P. Insulin regulation of gluconeogenesis. Ann N Y Acad Sci. 2018;1411(1):21-35. [CrossRef]
  • 29. Martin U, Davies C, Hayavi S, Hartland A, Dunne F. Is normal pregnancy atherogenic? Clin Sci (Lond). 1999;96(4):421-425. [CrossRef]
  • 30. Waring AC, Arnold AM, Newman AB, Bùzková P, Hirsch C, Cappola AR. Longitudinal changes in thyroid function in the oldest old and survival: the cardiovascular health study all-stars study. J Clin Endocrinol Metab. 2012;97(11):3944-3950. [CrossRef]
  • 31. Ludwig U, Holzner D, Denzer C, et al. Subclinical and clinical hypothyroidism and non-alcoholic fatty liver disease: a cross-sectional study of a random population sample aged 18 to 65 years. BMC Endocr Disord. 2015;15:41. [CrossRef]
  • 32. Xu C, Xu L, Yu C, Miao M, Li Y. Association between thyroid function and nonalcoholic fatty liver disease in euthyroid elderly Chinese. Clin Endocrinol (Oxf). 2011;75(2):240-246. [CrossRef]
  • 33. Pagadala MR, Zein CO, Dasarathy S, Yerian LM, Lopez R, McCullough AJ. Prevalence of hypothyroidism in nonalcoholic fatty liver disease. Dig Dis Sci. 2012;57(2):528-534. [CrossRef]
  • 34. Kim D, Kim W, Joo SK, Bae JM, Kim JH, Ahmed A. Subclinical hypothyroidism and low-normal thyroid function are associated with nonalcoholic steatohepatitis and fibrosis. Clin Gastroenterol Hepatol. 2018;16(1):123-131.e1. [CrossRef]
  • 35. Bano A, Chaker L, Plompen EP, et al. Thyroid function and the risk of nonalcoholic fatty liver disease: the Rotterdam study. J Clin Endocrinol Metab. 2016;101(8):3204 3211. [CrossRef]
  • 36. Pearce EN. Hypothyroidism and dyslipidemia: modern concepts and approaches. Curr Cardiol Rep. 2004;6(6):451-456. [CrossRef]
  • 37. Rochon C, Tauveron I, Dejax C, et al. Response of glucose disposal to hyperinsulinaemia in human hypothyroidism and hyperthyroidism. Clin Sci (Lond). 2003;104(1):7-15. [CrossRef]
  • 38. Lahesmaa M, Orava J, Schalin-Jäntti C, et al. Hyperthyroidism increases brown fat metabolism in humans. J Clin Endocrinol Metab. 2014;99(1):E28-E35. [CrossRef]
  • 39. Gavrila A, Hasselgren PO, Glasgow A, et al. Variable cold-induced brown adipose tissue response to thyroid hormone status. Thyroid. 2017;27(1):1-10. [CrossRef]
  • 40. Torrance CJ, Usala SJ, Pessin JE, Dohm GL. Characterization of a low affinity thyroid hormone receptor binding site within the rat GLUT4 gene promoter. Endocrinology. 1997;138(3):1215-1223. [CrossRef]
  • 41. Marsili A, Aguayo-Mazzucato C, Chen T, et al. Mice with a targeted deletion of the type 2 deiodinase are insulin resistant and susceptible to diet induced obesity. PLoS One. 2011;6(6):e20832. [CrossRef]
  • 42. Lin Y, Sun Z. Thyroid hormone potentiates insulin signaling and attenuates hyperglycemia and insulin resistance in a mouse model of type 2 diabetes. Br J Pharmacol. 2011;162(3):597-610. [CrossRef]
  • 43. Verga Falzacappa C, Patriarca V, Bucci B, et al. The TRbeta1 is essential in mediating T3 action on Akt pathway in human pancreatic insulinoma cells. J Cell Biochem. 2009;106(5):835-848. [CrossRef]
  • 44. Ochs N, Auer R, Bauer DC, et al. Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med. 2008;148(11):832-845. [CrossRef]
  • 45. Finan B, Clemmensen C, Zhu Z, et al. Chemical hybridization of glucagon and thyroid hormone optimizes therapeutic impact for metabolic disease. Cell. 2016;167(3):843-857.e14. [CrossRef]
  • 46. Cable EE, Finn PD, Stebbins JW, et al. Reduction of hepatic steatosis in rats and mice after treatment with a liver-targeted thyroid hormone receptor agonist. Hepatology. 2009;49(2):407- 417. [CrossRef]
  • 47. Ladenson PW, McCarren M, Morkin E, et al. Effects of the thyromimetic agent diiodothyropropionic acid on body weight, body mass index, and serum lipoproteins: a pilot prospective, randomized, controlled study. J Clin Endocrinol Metab. 2010;95(3):1349-1354. [CrossRef]
  • 48. Sinha RA, Bruinstroop E, Singh BK, Yen PM. Nonalcoholic fatty liver disease and hypercholesterolemia: roles of thyroid hormones, metabolites, and agonists. Thyroid. 2019;29(9):1173-1191. [CrossRef]
Year 2023, Volume: 3 Issue: 4, 105 - 111, 09.10.2023

Abstract

References

  • 1. Oguntibeju OO. Type 2 diabetes mellitus, oxidative stress and inflammation: examining the links. Int J Physiol Pathophysiol Pharmacol. 2019;11(3):45-63.
  • 2. Cole JB, Florez JC. Genetics of diabetes mellitus and diabetes complications. Nat Rev Nephrol. 2020;16(7):377-390. [CrossRef]
  • 3. Forouhi NG, Wareham NJ. Epidemiology of diabetes. Medicine (Abingdon). 2014;42(12):698-702. [CrossRef]
  • 4. Redondo MJ, Hagopian WA, Oram R, et al. The clinical consequences of heterogeneity within and between different diabetes types. Diabetologia. 2020;63(10):2040-2048. [CrossRef]
  • 5. Ozougwu O. The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus. J Physiol Pathophysiol. 2013;4(4):46-57.
  • 6. Liu YC, Yeh CT, Lin KH. Molecular functions of thyroid hormone signaling in regulation of cancer progression and anti-apoptosis. Int J Mol Sci. 2019;20(20):4986.[CrossRef]
  • 7. Gereben B, Zavacki AM, Ribich S, et al. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr Rev. 2008;29(7):898-938. [CrossRef]
  • 8. Thvilum M, Brandt F, Brix TH, Hegedüs L. A review of the evidence for and against increased mortality in hypothyroidism. Nat Rev Endocrinol. 2012;8(7):417-424. [CrossRef]
  • 9. Pistollato F, Masias M, Agudo P, Giampieri F, Battino M. Effects of phytochemicals on thyroid function and their possible role in thyroid disease. Ann N Y Acad Sci. 2019;1443(1):3-19. [CrossRef]
  • 10. Ragusa F, Fallahi P, Elia G, et al. Hashimotos’ thyroiditis: epidemiology, pathogenesis, clinic and therapy. Best Pract Res Clin Endocrinol Metab. 2019;33(6):101367. [CrossRef]
  • 11. MacFarland SP, Bauer AJ, Adzick NS, et al. Disease burden and outcome in children and young adults with concurrent graves disease and differentiated thyroid carcinoma. J Clin Endocrinol Metab. 2018;103(8):2918-2925. [CrossRef]
  • 12. Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev. 2014;94(2):355-382. [CrossRef]
  • 13. Klieverik LP, Janssen SF, van Riel A, et al. Thyroid hormone modulates glucose production via a sympathetic pathway from the hypothalamic paraventricular nucleus to the liver. Proc Natl Acad Sci U S A. 2009;106(14):5966-5971. [CrossRef]
  • 14. López-Noriega L, Cobo-Vuilleumier N, Narbona-Pérez ÁJ, et al. Levothyroxine enhances glucose clearance and blunts the onset of experimental type 1 diabetes mellitus in mice. Br J Pharmacol. 2017;174(21):3795-3810. [CrossRef]
  • 15. Celani MF, Bonati ME, Stucci N. Prevalence of abnormal thyrotropin concentrations measured by a sensitive assay in patients with type 2 diabetes mellitus. Diabetes Res. 1994;27(1):15-25.
  • 16. Maratou E, Hadjidakis DJ, Kollias A, et al. Studies of insulin resistance in patients with clinical and subclinical hypothyroidism. Eur J Endocrinol. 2009;160(5):785-790. [CrossRef]
  • 17. Shun CB, Donaghue KC, Phelan H, Twigg SM, Craig ME. Thyroid autoimmunity in Type 1 diabetes: systematic review and meta-analysis. Diabet Med. 2014;31(2):126-135. [CrossRef]
  • 18. Seely EW, Solomon CG. Insulin resistance and its potential role in pregnancy induced hypertension. J Clin Endocrinol Metab. 2003;88(6):2393-2398. [CrossRef]
  • 19. Kühl C. Insulin secretion and insulin resistance in pregnancy and GDM. Implications for diagnosis and management. Diabetes. 1991;40(suppl 2):18-24. [CrossRef]
  • 20. Karbalaei N, Ghasemi A, Faraji F, Zahediasl S. Comparison of the effect of maternal hypothyroidism on carbohydrate metabolism in young and aged male offspring in rats. Scand J Clin Lab Investig. 2013;73(1):87-94. [CrossRef]
  • 21. Martin-Montalvo A, López-Noriega L, Jiménez-Moreno C, et al. Transient PAX8 expression in islets during pregnancy correlates with β-cell survival, revealing a novel candidate gene in gestational diabetes mellitus. Diabetes. 2019;68(1):109-118 [CrossRef]
  • 22. Mastracci TL, Evans-Molina C. Pancreatic and islet development andfunction: the role of thyroid hormone. J Endocrinol Diabetes Obes. 2014;2(3):1044.
  • 23. Aguayo-Mazzucato C, Zavacki AM, Marinelarena A, et al. Thyroid hormone promotes postnatal rat pancreatic β-cell development and glucose-responsive insulin secretion through MAFA. Diabetes. 2013;62(5):1569-1580. [CrossRef]
  • 24. López-Noriega L, Capilla-González V, Cobo-Vuilleumier N, et al. Inadequate control of thyroid hormones sensitizes to hepatocarcinogenesis and unhealthy aging. Aging (Albany NY). 2019;11(18):7746-7779. [CrossRef]
  • 25. Supale S, Li N, Brun T, Maechler P. Mitochondrial dysfunction in pancreatic β cells. Trends Endocrinol Metab. 2012;23(9):477-487. [CrossRef]
  • 26. Klieverik LP, Sauerwein HP, Ackermans MT, Boelen A, Kalsbeek A, Fliers E. Effects of thyrotoxicosis and selective hepatic autonomic denervation on hepatic glucose metabolism in rats. Am J Physiol Endocrinol Metab. 2008;294(3):E513-E520 [CrossRef]
  • 27. Gierach M, Gierach J, Junik R. Insulin resistance and thyroid disorders. Endokrynol Pol. 2014;65(1):70-76. [CrossRef]
  • 28. Hatting M, Tavares CDJ, Sharabi K, Rines AK, Puigserver P. Insulin regulation of gluconeogenesis. Ann N Y Acad Sci. 2018;1411(1):21-35. [CrossRef]
  • 29. Martin U, Davies C, Hayavi S, Hartland A, Dunne F. Is normal pregnancy atherogenic? Clin Sci (Lond). 1999;96(4):421-425. [CrossRef]
  • 30. Waring AC, Arnold AM, Newman AB, Bùzková P, Hirsch C, Cappola AR. Longitudinal changes in thyroid function in the oldest old and survival: the cardiovascular health study all-stars study. J Clin Endocrinol Metab. 2012;97(11):3944-3950. [CrossRef]
  • 31. Ludwig U, Holzner D, Denzer C, et al. Subclinical and clinical hypothyroidism and non-alcoholic fatty liver disease: a cross-sectional study of a random population sample aged 18 to 65 years. BMC Endocr Disord. 2015;15:41. [CrossRef]
  • 32. Xu C, Xu L, Yu C, Miao M, Li Y. Association between thyroid function and nonalcoholic fatty liver disease in euthyroid elderly Chinese. Clin Endocrinol (Oxf). 2011;75(2):240-246. [CrossRef]
  • 33. Pagadala MR, Zein CO, Dasarathy S, Yerian LM, Lopez R, McCullough AJ. Prevalence of hypothyroidism in nonalcoholic fatty liver disease. Dig Dis Sci. 2012;57(2):528-534. [CrossRef]
  • 34. Kim D, Kim W, Joo SK, Bae JM, Kim JH, Ahmed A. Subclinical hypothyroidism and low-normal thyroid function are associated with nonalcoholic steatohepatitis and fibrosis. Clin Gastroenterol Hepatol. 2018;16(1):123-131.e1. [CrossRef]
  • 35. Bano A, Chaker L, Plompen EP, et al. Thyroid function and the risk of nonalcoholic fatty liver disease: the Rotterdam study. J Clin Endocrinol Metab. 2016;101(8):3204 3211. [CrossRef]
  • 36. Pearce EN. Hypothyroidism and dyslipidemia: modern concepts and approaches. Curr Cardiol Rep. 2004;6(6):451-456. [CrossRef]
  • 37. Rochon C, Tauveron I, Dejax C, et al. Response of glucose disposal to hyperinsulinaemia in human hypothyroidism and hyperthyroidism. Clin Sci (Lond). 2003;104(1):7-15. [CrossRef]
  • 38. Lahesmaa M, Orava J, Schalin-Jäntti C, et al. Hyperthyroidism increases brown fat metabolism in humans. J Clin Endocrinol Metab. 2014;99(1):E28-E35. [CrossRef]
  • 39. Gavrila A, Hasselgren PO, Glasgow A, et al. Variable cold-induced brown adipose tissue response to thyroid hormone status. Thyroid. 2017;27(1):1-10. [CrossRef]
  • 40. Torrance CJ, Usala SJ, Pessin JE, Dohm GL. Characterization of a low affinity thyroid hormone receptor binding site within the rat GLUT4 gene promoter. Endocrinology. 1997;138(3):1215-1223. [CrossRef]
  • 41. Marsili A, Aguayo-Mazzucato C, Chen T, et al. Mice with a targeted deletion of the type 2 deiodinase are insulin resistant and susceptible to diet induced obesity. PLoS One. 2011;6(6):e20832. [CrossRef]
  • 42. Lin Y, Sun Z. Thyroid hormone potentiates insulin signaling and attenuates hyperglycemia and insulin resistance in a mouse model of type 2 diabetes. Br J Pharmacol. 2011;162(3):597-610. [CrossRef]
  • 43. Verga Falzacappa C, Patriarca V, Bucci B, et al. The TRbeta1 is essential in mediating T3 action on Akt pathway in human pancreatic insulinoma cells. J Cell Biochem. 2009;106(5):835-848. [CrossRef]
  • 44. Ochs N, Auer R, Bauer DC, et al. Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med. 2008;148(11):832-845. [CrossRef]
  • 45. Finan B, Clemmensen C, Zhu Z, et al. Chemical hybridization of glucagon and thyroid hormone optimizes therapeutic impact for metabolic disease. Cell. 2016;167(3):843-857.e14. [CrossRef]
  • 46. Cable EE, Finn PD, Stebbins JW, et al. Reduction of hepatic steatosis in rats and mice after treatment with a liver-targeted thyroid hormone receptor agonist. Hepatology. 2009;49(2):407- 417. [CrossRef]
  • 47. Ladenson PW, McCarren M, Morkin E, et al. Effects of the thyromimetic agent diiodothyropropionic acid on body weight, body mass index, and serum lipoproteins: a pilot prospective, randomized, controlled study. J Clin Endocrinol Metab. 2010;95(3):1349-1354. [CrossRef]
  • 48. Sinha RA, Bruinstroop E, Singh BK, Yen PM. Nonalcoholic fatty liver disease and hypercholesterolemia: roles of thyroid hormones, metabolites, and agonists. Thyroid. 2019;29(9):1173-1191. [CrossRef]

Details

Primary Language Turkish
Subjects Pharmacology and Pharmaceutical Sciences (Other)
Journal Section Reviews
Authors

Zerrin KUTLU 0000-0002-6279-9810

Afra Dilay KAMACI This is me 0009-0006-5587-8621

Publication Date October 9, 2023
Published in Issue Year 2023 Volume: 3 Issue: 4

Cite

EndNote KUTLU Z, KAMACI AD (October 1, 2023) The Relationship Between Euthyroid, Hyperthyroid, Hypothyroid, and Type 2 Diabetes. Pharmata 3 4 105–111.

Content of this journal is licensed under a Creative Commons Attribution NonCommercial 4.0 International License

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