Summary
Thyroid hormones have a specific effect on glucose-induced insulin secretion from the pancreas. We aimed to investigate the association between euthyroid hormones and islet beta-cell function in general population and non-treated type 2 diabetes mellitus (T2DM) patients. A total of 5089 euthyroid participants (including 4601 general population and 488 non-treated T2DM patients) were identified from a cross-sectional survey on the prevalence of metabolic diseases and risk factors in East China from February 2014 to June 2016. Anthropometric indices, biochemical parameters, and thyroid hormones were measured. Compared with general population, non-treated T2DM patients exhibited higher total thyroxine (TT4) and free thyroxine (FT4) levels but lower ratio of free triiodothyronine (T3):T4 (P<0.01). HOMA-β had prominently negative correlation with FT4 and positive relationship with free T3:T4 in both groups even after adjusting for age, body mass index (BMI) and smoking. When analyzed by quartiles of FT4 or free T3:T4, there were significantly decreased trend of HOMA-β going with the higher FT4 and lower free T3:T4 in both groups. Linear regression analysis showed that FT4 but not FT3 and free T3:T4 was negatively associated with HOMA-β no matter in general population or T2DM patients, which was independent of age, BMI, smoking, hypertension and lipid profiles. FT4 is independently and negatively associated with islet beta-cell function in euthyroid subjects. Thyroid hormone even in reference range could play an important role in the function of pancreatic islets.
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Teng W, Shan Z, Teng X, et al. Effect of iodine intake on thyroid diseases in China. N Engl J Med, 2006,354(26):2783–2793
Shun CB, Donaghue KC, Phelan H, et al. Thyroid autoimmunity in Type 1 diabetes: systematic review and meta-analysis. Diabet Med, 2014,31(2):126–135
Oda T, Taneichi H, Takahashi K, et al. Positive association of free triiodothyronine with pancreatic beta-cell function in people with prediabetes. Diabet Med, 2015,32(2):213–219
Haluzik M, Nedvidkova J, Bartak V, et al. Effects of hypo- and hyperthyroidism on noradrenergic activity and glycerol concentrations in human subcutaneous abdominal adipose tissue assessed with microdialysis. J Clin Endocrinol Metab, 2003,88(12):5605–5608
Lenzen S. Dose-response studies on the inhibitory effect of thyroid hormones on insulin secretion in the rat. Metabolism, 1978,27(1):81–88
Crunkhorn S, Patti ME. Links between thyroid hormone action, oxidative metabolism, and diabetes risk? Thyroid, 2008,18(2):227–237
Ashwini S, Bobby Z, Joseph M. Mild hypothyroidism improves glucose tolerance in experimental type 2 diabetes. Chem Biol Interact, 2015,235:47–55
Gronich N, Deftereos SN, Lavi I, et al. Hypothyroidism is a Risk Factor for New-Onset Diabetes: A Cohort Study. Diabetes Care, 2015,38(9):1657–1664
Kim MK, Kwon HS, Baek KH, et al. Effects of thyroid hormone on A1C and glycated albumin levels in nondiabetic subjects with overt hypothyroidism. Diabetes Care, 2010,33(12):2546–2548
Saisho Y. Importance of Beta Cell Function for the Treatment of Type 2 Diabetes. J Clin Med, 2014,3(3):923–943
Hollenberg AN, Forrest D. The thyroid and metabolism: the action continues. Cell Metab, 2008,8(1):10–12
Verga Falzacappa C, Mangialardo C, Raffa S, et al. The thyroid hormone T3 improves function and survival of rat pancreatic islets during in vitro culture. Islets, 2010,2(2):96–103
Verga Falzacappa C, Panacchia L, Bucci B, et al. 3,5,3′-triiodothyronine (T3) is a survival factor for pancreatic beta-cells undergoing apoptosis. J Cell Physiol, 2006,206(2):309–321
Mitrou P, Raptis SA, Dimitriadis G. Insulin action in hyperthyroidism: a focus on muscle and adipose tissue. Endocr Rev, 2010,31(5):663–679
Dimitriadis G, Baker B, Marsh H, et al. Effect of thyroid hormone excess on action, secretion, and metabolism of insulin in humans. Am J Physiol, 1985,248(5 Pt 1):E593–601
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
Handisurya A, Pacini G, Tura A, et al. Effects of T4 replacement therapy on glucose metabolism in subjects with subclinical (SH) and overt hypothyroidism (OH). Clin Endocrinol (Oxf), 2008,69(6):963–969
Chaker L, Ligthart S, Korevaar TI, et al. Thyroid function and risk of type 2 diabetes: a population-based prospective cohort study. BMC Med, 2016,14(1):150
Lenzen S, Joost HG, Hasselblatt A. Thyroid function and insulin secretion from the perfused pancreas in the rat. Endocrinology, 1976,99(1):125–129
Jin L, Wang M, Yue J, et al. Association between TSH level and pregnancy outcomes in euthyroid women undergoing IVF/ICSI: A Retrospective Study and Meta-analysis. Curr Med Sci, 2019,39(4):631–637
Xiao E, Mattos M, Vieira GHA, et al. Diabetes Enhances IL-17 Expression and Alters the Oral Microbiome to Increase Its Pathogenicity. Cell Host Microbe, 2017,22(1):120–128.e124
Jun JE, Jin SM, Jee JH, et al. TSH increment and the risk of incident type 2 diabetes mellitus in euthyroid subjects. Endocrine, 2017,55(3):944–953
Jornayvaz FR, Lee HY, Jurczak MJ, et al. Thyroid hormone receptor-alpha gene knockout mice are protected from diet-induced hepatic insulin resistance. Endocrinology, 2012,153(2):583–591
Ortega E, Pannacciulli N, Bogardus C, et al. Plasma concentrations of free triiodothyronine predict weight change in euthyroid persons. Am J Clin Nutr, 2007,85(2):440–445
Amouzegar A, Kazemian E, Gharibzadeh S, et al. Association between thyroid hormones, thyroid antibodies and insulin resistance in euthyroid individuals: A population-based cohort. Diabetes Metab, 2015,41(6):480–488
Furuya F, Shimura H, Yamashita S, et al. Liganded thyroid hormone receptor-alpha enhances proliferation of pancreatic beta-cells. J Biol Chem, 2010,285(32):24 477–24 486
Wang N, Wang X, Han B, et al. Is Exposure to Famine in Childhood and Economic Development in Adulthood Associated With Diabetes? J Clin Endocrinol Metab, 2015,100(12):4514–4523
Nie X, Wang N, Chen Y, et al. Blood cadmium in Chinese adults and its relationships with diabetes and obesity. Environ Sci Pollut Res Int, 2016,23(18):18 714–18 723
Chen Y, Chen Y, Xia F, et al. A Higher Ratio of Estradiol to Testosterone Is Associated with Autoimmune Thyroid Disease in Males. Thyroid, 2017,27(7):960–966
Wang N, Chen Y, Ning Z, et al. Exposure to Famine in Early Life and Nonalcoholic Fatty Liver Disease in Adulthood. J Clin Endocrinol Metab, 2016,101(5):2218–2225
Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 1985,28(7):412–419
Association TAD. Standards of Medical Care in Diabetes-2017: Summary of Revisions. Diabetes Care, 2017,40(Suppl 1):S4–s5
Lambadiari V, Mitrou P, Maratou E, et al. Thyroid hormones are positively associated with insulin resistance early in the development of type 2 diabetes. Endocrine, 2011,39(1):28–32
Ortega E, Koska J, Pannacciulli N, et al. Free triiodothyronine plasma concentrations are positively associated with insulin secretion in euthyroid individuals. Eur J Endocrinol, 2008,158(2):217–221
Bakker SJ, ter Maaten JC, Popp-Snijders C, et al. Triiodothyronine: a link between the insulin resistance syndrome and blood pressure? J Hypertens, 1999,17(12 Pt 1):1725–1730
Bianco AC, Salvatore D, Gereben B, et al. Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases. Endocr Rev, 2002,23(1):38–89
Yen PM. Physiological and molecular basis of thyroid hormone action. Physiol Rev, 2001,81(3):1097–1142
Mouradian M, Abourizk N. Diabetes mellitus and thyroid disease. Diabetes Care, 1983,6(5):512–520
Aguayo-Mazzucato C, Zavacki AM, Marinelarena A, et al. Thyroid hormone promotes postnatal rat pancreatic beta-cell development and glucose-responsive insulin secretion through MAFA. Diabetes, 2013,62(5):1569–1580
Furuya F, Shimura H, Asami K, et al. Ligand-bound thyroid hormone receptor contributes to reprogramming of pancreatic acinar cells into insulin-producing cells. J Biol Chem, 2013,288(22):16 155–16 166
Medina MC, Molina J, Gadea Y, et al. The thyroid hormone-inactivating type III deiodinase is expressed in mouse and human beta-cells and its targeted inactivation impairs insulin secretion. Endocrinology, 2011,152(10):3717–3727
Misiti S, Anastasi E, Sciacchitano S, et al. 3,5,3′-Triiodo-L-thyronine enhances the differentiation of a human pancreatic duct cell line (hPANC-1) towards a beta-cell-like phenotype. J Cell Physiol, 2005,204(1):286–296
Chin KY, Ima-Nirwana S, Mohamed IN, et al. The relationships between thyroid hormones and thyroid-stimulating hormone with lipid profile in euthyroid men. Int J Med Sci, 2014,11(4):349–355
Acknowledgments
The authors thank all team members and participants from Institute and Department of Endocrinology and Metabolism, Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine (Shanghai, China), Shangyu People’s Hospital (Zhejiang, China), Fengcheng Hospital (Shanghai, China), the Third Affiliated Hospital of Nanchang University (Jiangxi, China), Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School (Jiangsu, China), the First Affiliated Hospital of Anhui Medical University (Anhui, China) in the SPECT-China study 2014–2016.
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The authors declare that there are no conflicts of interest or financial interests associated with this manuscript.
This study was supported by grants from the National Natural Science Foundation of China (No. 81270885, No. 81570726 and No. 81600609), Shanghai Jiao Tong University School of Medicine (2014), the Ministry of Science and Technology in China (No. 2012CB524906), and the Science and Technology Commission of Shanghai Municipality (No. 14495810700 and No. 16410723200), Three-year Action Plan for Public Health System Construction in Shanghai by Shanghai Municipal Commission of Health and Family Planning (2015–2017), Clinical Potential Subject Construction of Shanghai Jiao Tong University School of Medicine (2014), Shanghai Municipal Health Bureau of China (No. 20124262), and Seed Founding of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine (No. JYZZ032).
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Li, Q., Lu, M., Wang, Nj. et al. Relationship between Free Thyroxine and Islet Beta-cell Function in Euthyroid Subjects. CURR MED SCI 40, 69–77 (2020). https://doi.org/10.1007/s11596-020-2148-6
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DOI: https://doi.org/10.1007/s11596-020-2148-6