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El-Eshmawy MM, Barakat AA, El-Baiomy AA, El-Naga MMA, Elbasiony M. Role of serum fasting glucagon in hypothyroidism-related nonalcoholic fatty liver disease. Nutr Metab (Lond) 2025; 22:19. [PMID: 40069760 PMCID: PMC11899932 DOI: 10.1186/s12986-025-00899-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 01/13/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND A bidirectional relationship between hypothyroidism and nonalcoholic fatty liver disease (NAFLD) has been proposed. Fasting hyperglucagonemia in patients with hypothyroidism induced NAFLD needs to be further clarified. The aim of the present study was to determine fasting serum glucagon levels in hypothyroid adults with and without NAFLD. The possible association between fasting glucagon and NAFLD in patients with hypothyroidism was also evaluated. METHODS This study was comprised 60 patients with uncontrolled hypothyroidism and 30 healthy controls matched for age and sex. Patients with hypothyroidism were divided into 2 groups: 30 patients with NAFLD and 30 patients without NAFLD. Diagnosis of NAFLD was based on the combination of hepatic steatosis index (HSI) at a cutoff value of 36 and measurements of steatosis using fibroScan. Anthropometric measurements, lipids profile, homeostasis model assessment of insulin resistance (HOMA-IR), free thyroxine (FT4), triiodothyronine (FT3), thyroid stimulating hormone (TSH) and serum fasting glucagon were assessed. RESULTS Serum fasting glucagon concentration was significantly higher in hypothyroid patients with and without NAFLD than in healthy controls; glucagon was also significantly higher in the hypothyroid patients with NAFLD than in those without NAFLD. Fasting glucagon was significantly correlated with waist circumference (WC), body mass index (BMI), TSH, HSI and fibroScan parameters in hypothyroid patients with NAFLD. Fasting glucagon predicts NAFLD in patients with hypothyroidism at a cutoff value 85 ng/L with 90% sensitivity, 100% specificity and p < 0.001. With multivariable analysis, age, BMI and TSH were significant positive predictors of NAFLD in patients with hypothyroidism. CONCLUSION Fasting glucagon concentration may play a role in the development of NAFLD in patients with hypothyroidism. However, the exact underlying mechanism needs further studies.
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Affiliation(s)
- Mervat M El-Eshmawy
- Internal Medicine Department, Mansoura Specialized Medical Hospital, Faculty of Medicine, Mansoura University, P.O. Box: 35516, Mansoura, Egypt.
| | - Amira A Barakat
- Internal Medicine Department, Mansoura Specialized Medical Hospital, Faculty of Medicine, Mansoura University, P.O. Box: 35516, Mansoura, Egypt
| | - Azza A El-Baiomy
- Clinical Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt
| | - Mohamed M Abo El-Naga
- Internal Medicine Department, Mansoura Specialized Medical Hospital, Faculty of Medicine, Mansoura University, P.O. Box: 35516, Mansoura, Egypt
| | - Mohamed Elbasiony
- Internal Medicine Department, Mansoura Specialized Medical Hospital, Faculty of Medicine, Egyptian Liver Research Institute, Mansoura University, Sherben, Egypt
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Krishnamurthy H, Suresh C, Siriwardhane T, Krishna K, Song Q, Jayaraman V, Wang T, Bei K, Rajasekaran JJ. Association between thyroid dysfunction and insulin resistance: a retrospective cohort study. BMJ Open 2025; 15:e076397. [PMID: 39762110 PMCID: PMC11749310 DOI: 10.1136/bmjopen-2023-076397] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2023] [Accepted: 12/06/2024] [Indexed: 01/23/2025] Open
Abstract
OBJECTIVE To evaluate the association between thyroid disease and diabetes markers. DESIGN Retrospective cohort study. SETTING The study was conducted in a diagnostic setting where the primary care providers recommended the patients to test for thyroid and diabetes panels. PARTICIPANTS The thyroid and diabetes markers were tested in 32 787 subjects with suspected thyroid and related conditions who visited Vibrant America Clinical Laboratory between January 2015 and June 2019. RESULTS Our general prevalence results showed that homeostatic model assessment-insulin resistance (HOMA-IR) was elevated in overt hypothyroid subjects (43.7%) and overt hyperthyroid subjects (42.2%). Glycated hemoglobin (HbA1C) was elevated in subclinical hypothyroid subjects (19.2%), overt hypothyroid subjects (22.3%) and overt hyperthyroid subjects (21.2%). Glucose was significantly elevated in subclinical hypothyroid subjects (24.2%) and overt hyperthyroid subjects (31.0%). Insulin was significantly elevated in overt hypothyroid subjects (15.1%). Interestingly, we found that 70.3% of subjects who had their HOMA-IR score escalated from negative (HOMA-IR<2.7) to positive (HOMA-IR>2.7) during their multiple visits had anti-thyroid peroxidase (anti-TPO) 369 (±242) days prior to the onset of this change. CONCLUSION Our findings showed that anti-TPO levels are elevated before the onset of insulin resistance, indicating its potential use as a predictive marker.
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Affiliation(s)
| | - Chithra Suresh
- Biological, Vibrant America, San Carlos, California, USA
| | | | | | - Qi Song
- Vibrant Sciences LLC, Santa Clara, California, USA
| | | | - Tianhao Wang
- Vibrant Sciences LLC, Santa Clara, California, USA
| | - Kang Bei
- Vibrant Sciences LLC, Santa Clara, California, USA
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Chauhan A, Patel SS. Thyroid Hormone and Diabetes Mellitus Interplay: Making Management of Comorbid Disorders Complicated. Horm Metab Res 2024; 56:845-858. [PMID: 39159661 DOI: 10.1055/a-2374-8756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/21/2024]
Abstract
Insulin and thyroid hormones play important roles in our body. Insulin helps regulate the glucose level while the thyroid hormones affect various cells and tissues, metabolizing protein, lipids, and glucose. Hyperthyroidism and thyrotoxicosis are potential hazards for type 2 diabetes mellitus. There is a high prevalence of hypothyroidism being more common compared to hyperthyroidism coexisting with diabetes mellitus. Thyroid hormones affect glucose metabolism through its action on peripheral tissues (gastrointestinal tract, liver, skeletal muscles, adipose tissue, and pancreas). High-level thyroid hormone causes hyperglycemia, upregulation of glucose transport, and reduction in glycogen storage. The reverse is observed during low levels of thyroid hormone along with insulin clearance. The net result of thyroid disorder is insulin resistance. Type 2 diabetes mellitus can downsize the regulation of thyroid stimulating hormones and impair the conversion of thyroxine to triiodothyronine in peripheral tissues. Furthermore, poorly managed type 2 diabetes mellitus may result in insulin resistance and hyperinsulinemia, contributing to the proliferation of thyroid tissue and an increase in nodule formation and goiter size. Although metformin proves advantageous for both type 2 diabetes mellitus and thyroid disorder patients, other antidiabetics like sulfonylureas, pioglitazone, and thiazolidinediones may have adverse effects on thyroid disorders. Moreover, antithyroid drugs such as methimazole can weaken glycemic control in individuals with diabetes. Thus, an interplay between both endocrinopathies is observed and individualized care and management of the disorder needs to be facilitated.
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Affiliation(s)
- Ayush Chauhan
- Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, India
| | - Snehal S Patel
- Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, India
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Grigoriadis G, Koufakis T, Kotsa K. Epidemiological, Pathophysiological, and Clinical Considerations on the Interplay between Thyroid Disorders and Type 2 Diabetes Mellitus. MEDICINA (KAUNAS, LITHUANIA) 2023; 59:2013. [PMID: 38004062 PMCID: PMC10673571 DOI: 10.3390/medicina59112013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2023] [Revised: 11/12/2023] [Accepted: 11/14/2023] [Indexed: 11/26/2023]
Abstract
Thyroid disorders (TD) and diabetes mellitus (DM) are the two endocrinopathies with the highest prevalence in the general population that frequently coexist. Thyroid dysfunction is more common in people with type 2 diabetes mellitus (T2DM) compared to normoglycemic individuals. Untreated TD can impair glycemic control, increasing the risk of diabetes complications. Hyperinsulinemia can affect the morphology of the thyroid gland by promoting the proliferation of thyroid tissue and increasing the size of thyroid nodules. Metformin can confer benefits in both endocrinopathies, while other antidiabetics, such as sulfonylureas, can negatively affect thyroid function. Animal and human observational data suggest an increased risk of medullary thyroid carcinoma after treatment with glucagon-like peptide-1 receptor agonists. However, randomized trials have so far been reassuring. Furthermore, some observational studies suggest an association between thyroid cancer and T2DM, especially in women. This narrative review aims to shed light on the epidemiological, pathophysiological, and clinical aspects of the interplay between TD and T2DM. Taking into account the important clinical implications of the coexistence of T2DM and TD, proper screening and management strategies are needed for both endocrinopathies to ensure optimal patient care.
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Affiliation(s)
- Gregory Grigoriadis
- Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Theocharis Koufakis
- Second Propaedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
| | - Kalliopi Kotsa
- Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece;
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Cheng H, Hu Y, Zhao H, Zhou G, Wang G, Ma C, Xu Y. Exploring the association between triglyceride-glucose index and thyroid function. Eur J Med Res 2023; 28:508. [PMID: 37946276 PMCID: PMC10636949 DOI: 10.1186/s40001-023-01501-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 11/03/2023] [Indexed: 11/12/2023] Open
Abstract
BACKGROUND Thyroid dysfunction is associated with abnormal glucose-insulin homeostasis, and the triglyceride-glucose (TyG) index has been recommended as a convenient surrogate of insulin resistance (IR). This study aimed to investigate the relationship between TyG and thyroid function in the US population. METHODS We analyzed data from the National Health and Nutrition Examination Survey (NHANES) conducted from 2007 to 2012 in a cross-sectional manner. Aside from conventional thyroid parameters, our study evaluated the central sensitivity to thyroid hormones (THs) using the thyroid feedback quantile-based index (TFQI), thyrotropin resistance index (TT4RI), and thyrotropin index (TSHI). To evaluate peripheral sensitivity to THs, we calculated the ratio of free triiodothyronine (FT3) to free thyroxine (FT4) and the sum activity of peripheral deiodinases (SPINA-GD). In the 1848 adults, multivariable linear regression, subgroup, and interaction analyses were employed to estimate the association between TyG and thyroid parameters. The nonlinear relationship was addressed by smooth curve fittings and generalized additive models. RESULTS After adjusting covariates, we demonstrated a significant negative association between TyG and FT4 (β = - 0.57, p < 0.001), and a positive relationship between TyG and thyroid-stimulating hormone (β = 0.34, p = 0.037), as well as TgAb (β = 17.06, p = 0.005). Subgroup analysis indicated that the association between TyG and TgAb was more pronounced in the female subjects (β = 32.39, p < 0.001, p for interaction = 0.021). We also confirmed an inverse correlation between TyG and central sensitivity to THs, as assessed by TSHI and TT4RI (βTSHI = 0.12, p < 0.001; βTT4RI = 2.54, p = 0.023). In terms of peripheral sensitivity to THs, we found a significant positive correlation between TyG and FT3/FT4 (β = 0.03, p = 0.004), and SPINA-GD (β = 2.93, p = 0.004). CONCLUSION The present study established a noteworthy association between TyG and thyroid parameters, indicating a strong link between IR and thyroid dysfunction. Further investigations are warranted to validate these results.
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Affiliation(s)
- Hui Cheng
- Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, No.155, Hanzhong Road, Qinhuai District, Nanjing, 210029, Jiangsu, People's Republic of China
| | - Yanyan Hu
- Nursing College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Haoran Zhao
- Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, No.155, Hanzhong Road, Qinhuai District, Nanjing, 210029, Jiangsu, People's Republic of China
| | - Guowei Zhou
- Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, No.155, Hanzhong Road, Qinhuai District, Nanjing, 210029, Jiangsu, People's Republic of China
| | - Gaoyuan Wang
- Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, No.155, Hanzhong Road, Qinhuai District, Nanjing, 210029, Jiangsu, People's Republic of China
| | - Chaoqun Ma
- Department of General Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, No.155, Hanzhong Road, Qinhuai District, Nanjing, 210029, Jiangsu, People's Republic of China.
| | - Yan Xu
- Outpatient Department, Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine, The Second Hospital of Nanjing, No.1, Zhongfu Road, Gulou District, Nanjing, 210003, Jiangsu, People's Republic of China.
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Ostadrahimi A, Manzari T, Gohari-Lasaki S, Tutunchi H, Mobasseri M, Sadra V, Najafipour F. Effects of levothyroxine replacement therapy on insulin resistance in patients with untreated primary hypothyroidism. BMC Res Notes 2023; 16:237. [PMID: 37773140 PMCID: PMC10543334 DOI: 10.1186/s13104-023-06516-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Accepted: 09/18/2023] [Indexed: 10/01/2023] Open
Abstract
OBJECTIVES This study investigated the effects of levothyroxine replacement therapy on insulin resistance, lipid profile, and thyroid function in patients with untreated primary hypothyroidism. 105 patients with hypothyroidism with indication for levothyroxine replacement were enrolled in the present study. Insulin, fasting blood glucose and lipid profile were assessed at the beginning of diagnosis and three months after levothyroxine replacement. Insulin resistance was calculated by hemostasis model assessment of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI). RESULTS Our data revealed a significant reduction in body mass index (27.18 ± 4.27 versus 26.81 ± 4.18 kg/m2, p = 0.028), cholesterol (199.79 ± 37.61 versus 178.10 ± 32.25 mg/dl, p < 0.001), triglyceride (160.41 ± 71.86 versus 146 ± 61.11 mg/dl, p = 0.012), low density lipoprotein-cholesterol (123.54 ± 30.7 versus 107.08 ± 26.98 mg/dl, p < 0.001), fasting insulin (8.91 ± 3.92 versus 8.05 ± 2.65 mIU/l, p < 0.001), and thyroid stimulating hormone (47.47 ± 3.4 versus 2.22 ± 1.84 µIU/ml, p < 0.001) levels before and after drug intervention. However, no statistical differences were observed in HOMA-IR, QUICKI, and high density lipoprotein-cholesterol. In conclusion, in patients with untreated primary hypothyroidism, levothyroxine replacement therapy based on HOMA-IR and QUICKI did not improve insulin resistance; however, lipid profile was significantly improved following levothyroxine administration. TRIAL REGISTRATION This study was registered in the Iranian Registry of Clinical Trials (IRCT) with ID number: IRCT20130610013612N10 on the date 2019-09-02.
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Affiliation(s)
- Alireza Ostadrahimi
- Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Taher Manzari
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sahar Gohari-Lasaki
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Helda Tutunchi
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Majid Mobasseri
- Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Vahideh Sadra
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Farzad Najafipour
- Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
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Kruger EM, Shehata SA, Toraih EA, Abdelghany AA, Fawzy MS. Type 2 diabetes and thyroid cancer: Synergized risk with rising air pollution. World J Diabetes 2023; 14:1037-1048. [PMID: 37547591 PMCID: PMC10401455 DOI: 10.4239/wjd.v14.i7.1037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 03/28/2023] [Accepted: 05/30/2023] [Indexed: 07/12/2023] Open
Abstract
Diabetes is a complex condition, and the causes are still not fully understood. However, a growing body of evidence suggests that exposure to air pollution could be linked to an increased risk of diabetes. Specifically, exposure to certain pollutants, such as particulate Matter and Ozone, has been associated with higher rates of diabetes. At the same time, air pollution has also been linked to an increased risk of thyroid cancer. While there is less evidence linking air pollution to thyroid cancer than to diabetes, it is clear that air pollution could have severe implications for thyroid health. Air pollution could increase the risk of diabetes and thyroid cancer through several mechanisms. For example, air pollution could increase inflammation in the body, which is linked to an increased risk of diabetes and thyroid cancer. Air pollution could also increase oxidative stress, which is linked to an increased risk of diabetes and thyroid cancer. Additionally, air pollution could increase the risk of diabetes and thyroid cancer by affecting the endocrine system. This review explores the link between diabetes and air pollution on thyroid cancer. We will discuss the evidence for an association between air pollution exposure and diabetes and thyroid cancer, as well as the potential implications of air pollution for thyroid health. Given the connections between diabetes, air pollution, and thyroid cancer, it is essential to take preventive measures to reduce the risk of developing the condition.
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Affiliation(s)
- Eva M Kruger
- School of Medicine, Tulane University, New Orleans, LA 70112, United States
| | - Shaimaa A Shehata
- Department of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
| | - Eman A Toraih
- Division of Endocrine and Oncologic Surgery, Department of Surgery, School of Medicine, Tulane University, New Orleans, LA 70112, United States
- Genetics Unit, Department of Histology and Cell Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
| | - Ahmed A Abdelghany
- Department of Ophthalmology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
| | - Manal S Fawzy
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia 41522, Egypt
- Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar 1321, Saudi Arabia
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Díez JJ, Iglesias P. Prevalencia de diabetes en personas con disfunción tiroidea. Med Clin (Barc) 2022; 160:333-340. [PMID: 36528402 DOI: 10.1016/j.medcli.2022.09.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 09/05/2022] [Accepted: 09/06/2022] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To describe the prevalence and relative risk of diabetes in the population with hypothyroidism and hyperthyroidism. METHODS A retrospective study was carried out using the Primary Care Clinical Database (BDCAP) of the Ministry of Health. Relative risks (OR) and their 95% confidence intervals (CI) were calculated for type1 (T1D) and type2 (T2D) diabetes. RESULTS In the group of 2,596,041 hypothyroid patients, we found an OR of 1.77 (95%CI: 1.75-1.80) for T1D, and 1.77 (95%CI: 1.76-1.78) for T2D. This elevated risk was observed in both men and women. Hypothyroid people over 65years of age had a near neutral risk of T1D (0.96 [95%CI: 0.94-0.99]) and T2D (0.99 [95%CI: 0.98-0.99]). Hypothyroid patients receiving replacement therapy showed a higher risk of T1D (1.32 [95%CI: 1.28-1.36]) and T2D (1.23 [95%CI: 1.22-1.24]) compared to untreated hypothyroid patients. In the group of 418,772 people with hyperthyroidism, an increased risk of T1D (1.66 [95%CI: 1.60-1.72]) and T2D (1.71 [95%CI: 1.70-1.73]) was also noticed. This risk was observed in both sexes. Those over 65years of age did not present a high risk of T1D (0.89 [95%CI: 0.83-0.95]) and their risk of T2D was close to neutrality (1.03 [95%CI: 1.02-1.05]). Hyperthyroid patients treated with antithyroid agents had a higher risk of T1D (1.26 [95%CI: 1.14-1.40]) and T2D (1.32 [95%CI: 1.28-1.36]) than those without therapy. CONCLUSION People registered in BDCAP of both sexes, under 65years of age, with thyroid dysfunction have an increased risk of suffering from diabetes, especially those on thyroid medication.
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Kim H, Jung DY, Lee S, Cho J, Yim HW, Kim H. Retrospective cohort analysis comparing changes in blood glucose level and body composition according to changes in thyroid-stimulating hormone level. J Diabetes 2022; 14:620-629. [PMID: 36114679 PMCID: PMC9512769 DOI: 10.1111/1753-0407.13315] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2022] [Revised: 08/08/2022] [Accepted: 08/27/2022] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND In the euthyroid state, the risk of developing diabetes according to changes in thyroid-stimulating hormone (TSH) levels remains controversial. Additionally, the correlation of various body indices affecting blood glucose levels according to changes in TSH levels over a certain period is not well known. METHODS Patients who underwent health check-ups twice at a 2 year interval at a tertiary university hospital between 2009 and 2018 were included. By dividing baseline TSH levels into quartiles (TSH_Q1, Q2, Q3, and Q4), various variables were compared, and their changes after 2 years (∆TSH_Q1, Q2, Q3, and Q4) were confirmed. RESULTS Among 15 557 patients, the incidence of diabetes mellitus after 2 years was 2.4% (377/15 557 patients). There was no statistically significant difference in the incidence of diabetes according to TSH_Q (p = 0.243) or ∆TSH_Q (p = 0.131). However, as TSH levels increased, skeletal muscle mass decreased (p < 0.001), and body fat mass and percent body fat significantly increased (p < 0.001). As ∆TSH increased, ∆fasting blood glucose and ∆body mass index also significantly increased (all p < 0.001). The incidence of diabetes decreased significantly as skeletal muscle mass increased (odds ratio 0.734, p < 0.001). CONCLUSIONS Owing to the short study period, it was not possible to prove a statistical relationship between the incidence of diabetes mellitus and TSH levels in the euthyroid state. Significant decreases in skeletal muscle mass and increases in body mass index and body fat mass according to baseline TSH levels were demonstrated. Therefore, a focus on improving physical functions, such as increasing muscle mass and decreasing fat, is required in this case.
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Affiliation(s)
- Hyunah Kim
- College of PharmacySookmyung Women's UniversitySeoulRepublic of Korea
| | - Da Young Jung
- Department of Biostatistics, Clinical Research Coordinating Center, Catholic Medical CenterThe Catholic University of KoreaSeoulRepublic of Korea
| | - Seung‐Hwan Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea
| | - Jae‐Hyoung Cho
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea
| | - Hyeon Woo Yim
- Department of Preventive Medicine, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea
| | - Hun‐Sung Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary's Hospital, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea
- Department of Medical Informatics, College of MedicineThe Catholic University of KoreaSeoulRepublic of Korea
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Rodríguez-Castelán J, Zepeda-Pérez D, Rojas-Juárez R, Aceves C, Castelán F, Cuevas-Romero E. Effects of hypothyroidism on the female pancreas involve the regulation of estrogen receptors. Steroids 2022; 181:108996. [PMID: 35245530 DOI: 10.1016/j.steroids.2022.108996] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Accepted: 02/22/2022] [Indexed: 11/25/2022]
Abstract
This study aimed to investigate the impact of short-time hypothyroidism on the expression of aromatase, estrogen receptors (ERα, β), and GPR30 in the pancreas of female rabbits. The formation of new islets and the expression of insulin, GLUT4, and lactate dehydrogenase (LDH) were also analyzed. This purpose is based on actions that thyroid hormones and estrogens have on β-cells differentiation, acinar cell function, and insulin secretion. Twelve Chinchilla-breed adult virgin female rabbits were divided into control (n = 6) and hypothyroid (n = 6; methimazole 10 mg/kg for 30 days) groups. In the complete pancreas, expressions of aromatase and estrogen receptors, as well as proinsulin, GLUT4, and LDH were determined by western blot. Characteristics of islets were measured in slices of the pancreas with immunohistochemistry for insulin. Islet and acinar cells express aromatase, ERα, ERβ, and GPR30. Hypothyroidism increased the expression of ERα and diminished that for aromatase, ERβ, and GPR30 in the pancreas. It also promoted a high number of extra small islets (new islets) and increased the expression of proinsulin and GLUT4 in the pancreas. Our results show that actions of thyroid hormones and estrogens on β-cells neogenesis, acinar cell function, and synthesis and secretion of insulin are linked. Thus, the effects of hypothyroidism on the pancreas could include summatory actions of thyroid hormones plus estrogens. Our findings indicate the importance of monitoring estrogen levels and actions on the pancreas of hypothyroid women, particularly when serum estrogen concentrations are affected such as menopausal, pregnant, and those with contraceptive use.
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Affiliation(s)
- Julia Rodríguez-Castelán
- Autonomous University of Tlaxcala, Tlaxcala, Tlaxcala, Mexico; Department of Cellular and Molecular Neurobiology, Institute of Neurobiology, Autonomous Nacional University of Mexico, Juriquilla, Querétaro, Mexico
| | | | | | - Carmen Aceves
- Department of Cellular and Molecular Neurobiology, Institute of Neurobiology, Autonomous Nacional University of Mexico, Juriquilla, Querétaro, Mexico
| | - Francisco Castelán
- Department of Cellular and Physiology, Institute of Biomedical Research, Autonomous Nacional University of Mexico, Mexico City, Mexico; Center Tlaxcala of Behavior Biology, Autonomous University of Tlaxcala, Tlaxcala, Tlaxcala, Mexico
| | - Estela Cuevas-Romero
- Center Tlaxcala of Behavior Biology, Autonomous University of Tlaxcala, Tlaxcala, Tlaxcala, Mexico.
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Roh E, Noh E, Hwang SY, Kim JA, Song E, Park M, Choi KM, Baik SH, Cho GJ, Yoo HJ. Increased Risk of Type 2 Diabetes in Patients With Thyroid Cancer After Thyroidectomy: A Nationwide Cohort Study. J Clin Endocrinol Metab 2022; 107:e1047-e1056. [PMID: 34718625 DOI: 10.1210/clinem/dgab776] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Indexed: 11/19/2022]
Abstract
CONTEXT Abnormal thyroid function after thyroidectomy and subsequent thyroid-stimulating hormone suppression can have detrimental effects on glucose homeostasis in patients with thyroid cancer. OBJECTIVE To investigate whether thyroidectomy increases the risk of type 2 diabetes in patients with thyroid cancer and to explore the association between levothyroxine dosage and type 2 diabetes risk. METHODS A retrospective population-based cohort study using the Korean National Health Insurance database. We included 36 377 thyroid cancer patients without known diabetes who underwent thyroidectomy between 2004 and 2013. Matched subjects with nonthyroid cancer were selected using 1:1 propensity score matching. The main outcome measure was newly developed type 2 diabetes mellitus. RESULTS Patients with thyroid cancer who underwent thyroidectomy had a higher risk of developing type 2 diabetes mellitus than the matched controls (hazard ratio [HR] 1.43, 95% CI 1.39-1.47). Among patients with thyroid cancer, when the second quartile group (in terms of the mean levothyroxine dosage; 101-127 μg/day) was considered the reference group, the risk of type 2 diabetes mellitus increased in the first quartile (<101 μg/day; HR 1.45, 95% CI 1.36-1.54) and fourth quartile groups (≥150 μg/day; HR 1.37, 95% CI 1.29-1.45); meanwhile, the risk decreased in the third quartile group (128-149 μg/day; HR 0.91, 95% CI 0.85-0.97). CONCLUSION Patients with thyroid cancer who underwent thyroidectomy were more likely to develop type 2 diabetes mellitus than the matched controls. There was a U-shaped dose-dependent relationship between the levothyroxine dosage and type 2 diabetes mellitus risk.
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Affiliation(s)
- Eun Roh
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul 03803, Korea
| | - Eunjin Noh
- Smart Healthcare Center, Korea University Guro Hospital, Seoul 03803, Korea
| | - Soon Young Hwang
- Department of Biostatistics, Korea University College of Medicine, Seoul 03803, Korea
| | - Jung A Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul 03803, Korea
| | - Eyun Song
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul 03803, Korea
| | - Minjeong Park
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul 03803, Korea
| | - Kyung Mook Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul 03803, Korea
| | - Sei Hyun Baik
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul 03803, Korea
| | - Geum Joon Cho
- Department of Obstetrics and Gynecology, Korea University Guro Hospital, Korea University College of Medicine, Seoul 03803, Korea
| | - Hye Jin Yoo
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Korea University College of Medicine, Seoul 03803, Korea
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12
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Mohammed Hussein SM, AbdElmageed RM. The Relationship Between Type 2 Diabetes Mellitus and Related Thyroid Diseases. Cureus 2021; 13:e20697. [PMID: 35106234 PMCID: PMC8787293 DOI: 10.7759/cureus.20697] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/25/2021] [Indexed: 01/25/2023] Open
Abstract
Diabetes and thyroid diseases are caused by endocrine dysfunction and both have been demonstrated to mutually impact each other. Variation in thyroid hormone levels, even within the normal range, can trigger the onset of type 2 diabetes mellitus (T2DM), particularly in people with prediabetes. However, the available evidence is contradictory. The purpose of this review is to understand the pathological relationship between thyroid-related disorders and T2DM. T2DM in thyroid dysfunction is thought to be caused by altered gene expression of a group of genes, as well as physiological abnormalities that result in decreased glucose uptake increased, splanchnic glucose absorption, disposal in muscles, increased hepatic glucose output. Additionally, both hyperthyroidism and hypothyroidism can cause insulin resistance. Insulin resistance can develop in subclinical hypothyroidism as a result of a reduced rate of insulin-stimulated glucose transfer caused by a translocation of the glucose transporter type 2 (GLUT 2) gene. On the other hand, novel missense variations in (Thr92Ala) can cause insulin resistance. Furthermore insulin resistance and hyperinsulinemia resulting from diabetes can cause culminate in goitrous transformation of the thyroid gland. Thyroid-related diseases and T2DM are closely linked. Type 2 diabetes can be exacerbated by thyroid disorders, and diabetes can worsen thyroid dysfunction. Insulin resistance has been found to play a crucial role in both T2DM and thyroid dysfunction. Therefore, failure to recognize inadequate thyroid hormone levels in diabetes and insulin resistance in both conditions can lead to poor management of patients.
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13
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Al-Sayed HMA, Abdelaleem MA, Shawky HA. Physiochemical and nutritional evaluation of whole kumquat fruits powder and its protective effect on thyroid hormones and blood sugar levels in diabetic rats. BRAZ J BIOL 2021; 83:e247071. [PMID: 34431915 DOI: 10.1590/1519-6984.247071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 03/09/2021] [Indexed: 10/05/2024] Open
Abstract
The present study was conducted to evaluate the chemical composition, antioxidant activity and hypoglycemic effects of whole kumquat (Ku) powder in diabetic rats fed a high-fat-high-cholesterol (HFHC) diet. The antioxidant activities were evaluated using stable 1,1-diphenyl 2-picrylhydrazyl (DPPH) free radical scavenging method, 2,2´-azinobis (3-ethyl benzo thiazoline-6-sulphonic acid) radical cation (ABTS) and Ferric reducing antioxidant power (FRAP). Total phenolic content was (51.85 mg GAE/g) and total flavonoid content was (0.24 mg Cateachin Equivalent, CE/g). DPPH and ABTS values were 3.32 and 3.98 mg Trolox equivalent (TE)/g where FRAP value was 3.00 mM Fe2+/kg dry material. A total of 90 albino rats were used in the present study. Rats group were as follows: normal diet; normal treated (2, 4, and 6% Ku.), diabetic rats (non-treated), diabetic + HFHC diet (non-treated), HFHC (non-treated), Diabetic (treated), HFHC (treated) and Diabetic + HFHC (treated). The diets were followed for 8 weeks. Blood samples were collected at the end of the experiment. Serum glucose was recorded and thyroid hormones (T4, Thyroxine and T3, Triiodothyronine) were conducted. Diet supplemented with Kumquat at different concentrations have a hypoglycemic effect and improve the thyroid hormones of both diabetic rats and HFHC diabetic rats.
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Affiliation(s)
- H M A Al-Sayed
- Ain Shams University, Faculty of Agriculture, Food Science Department, Cairo, Egypt.,Tabuk University, Faculty of Home Economics, Nutrition and Food Science Department, Tabuk, Saudi Arabia
| | - M A Abdelaleem
- Egyptian Atomic Energy Authority, Nuclear Research Center, Plant Research Department, Cairo, Egypt
| | - H A Shawky
- Egyptian Atomic Energy Authority, Nuclear Research Center, Plant Research Department, Cairo, Egypt
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14
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Yu YH, Filion KB, Reynier P, Platt RW, Yu OHY, Grandi SM. Use of levothyroxine among pregnant women with subclinical hypothyroidism in the United Kingdom: A population-based assessment. Pharmacol Res Perspect 2021; 9:e00848. [PMID: 34390215 PMCID: PMC8363773 DOI: 10.1002/prp2.848] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Accepted: 07/10/2021] [Indexed: 12/17/2022] Open
Abstract
Our study aimed to describe levothyroxine prescription patterns and trends over time among pregnant women with subclinical hypothyroidism (SCH) in the United Kingdom. We used data from the Clinical Practice Research Datalink linked to its Pregnancy Register and the Hospital Episode Statistics database from 1998 to 2017. The study population included women with a diagnosis of SCH or an abnormal thyroid‐simulated hormone (TSH) level one year prior to or during pregnancy. We compared characteristics between women who received a prescription for levothyroxine during pregnancy and those who did not. We further described the timing, dose, duration, and temporal trends of levothyroxine prescriptions. Our cohort included 6,757 pregnancies from 6,287 women with SCH, of whom 10% received levothyroxine during pregnancy. Among women who received levothyroxine, most received their first prescription during the first trimester (median gestational age: 7 weeks; interquartile range [IQR]: 0, 16) with a median daily dosage of 50 mcg (IQR: 50, 73). Levothyroxine prescription varied over time, decreasing from 23% of pregnant women in 1998 to 7.5% in 2003, remaining stable until 2014, and increasing to 12.5% in 2016. Smoking, diabetes, polycystic ovary syndrome, infertility, timing of SCH diagnosis, age, TSH level at diagnosis, and general practice regions were associated with prescription. Few women with SCH received levothyroxine during pregnancy, and treatment varied by patient characteristics and geographical regions. These results highlight the need to increase awareness among healthcare providers and will guide future studies that explore barriers to initiating levothyroxine treatment for women with SCH during pregnancy.
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Affiliation(s)
- Ya-Hui Yu
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.,Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
| | - Kristian B Filion
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.,Departments of Medicine and of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
| | - Pauline Reynier
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
| | - Robert W Platt
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.,Departments of Pediatrics and of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada
| | - Oriana H Y Yu
- Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada.,Division of Endocrinology, Jewish General Hospital, Montreal, Quebec, Canada
| | - Sonia M Grandi
- Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.,Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada
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15
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Tang L, Li P, Zhou H, Li L. A longitudinal study of thyroid markers during pregnancy and the risk of gestational diabetes mellitus and post-partum glucose metabolism. Diabetes Metab Res Rev 2021; 37:e3441. [PMID: 33486811 PMCID: PMC8243952 DOI: 10.1002/dmrr.3441] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 12/07/2020] [Accepted: 01/02/2021] [Indexed: 12/11/2022]
Abstract
AIMS To determine the relationship between thyroid markers during pregnancy and gestational diabetes mellitus (GDM) or post-partum glucose metabolism. MATERIALS AND METHODS Based on pregnancy 75-g oral glucose tolerance test (OGTT) results, 1467 subjects were grouped into normal glucose tolerance (NGTp; n = 768) and GDM (n = 699) groups. Furthermore, based on post-partum 75-g OGTT results, 286 GDM subjects, screened for glucose metabolism after delivery, were grouped into NGTd (n = 241) and abnormal glucose tolerance (AGT; n = 45) groups. RESULTS Maternal age, family history of diabetes, acanthosis nigricans, previous adverse pregnancy outcomes and caesarean section incidence, and thyroid positive antibody rates were higher in the GDM group than in the NGTp group. In the first trimester, free triiodothyronine (FT3), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) levels were higher in the GDM group than in the NGTp group. In the second trimester, free thyroxine (FT4) levels were lower and TPOAb and TgAb levels were higher in the GDM group than in the NGTp group. After adjusting for confounding factors, FT3, TPOAb and TgAb (first trimester), and FT4, TPOAb and TgAb (second trimester) were risk factors for GDM. TPOAb and TgAb levels were higher in the AGT group than in the NGTd group and were potential predictors of abnormal post-partum glucose tolerance. CONCLUSIONS GDM risk significantly increased with increased FT3 (first trimester), TPOAb and TgAb (first and second trimesters) or with decreased FT4 (second trimester). Presence of thyroid antibodies predicted post-partum glucose abnormalities in subjects with GDM.
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Affiliation(s)
- Lei Tang
- Department of EndocrinologyShengjing Hospital of China Medical UniversityShenyangLiaoningChina
| | - Ping Li
- Department of EndocrinologyShengjing Hospital of China Medical UniversityShenyangLiaoningChina
| | - Hua Zhou
- Department of NephrologyShengjing Hospital of China Medical UniversityShenyangLiaoningChina
| | - Ling Li
- Department of EndocrinologyShengjing Hospital of China Medical UniversityShenyangLiaoningChina
- Liaoning Province Key Laboratory of Endocrine DiseasesShenyangLiaoningChina
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16
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Kuś A, Marouli E, Del Greco M F, Chaker L, Bednarczuk T, Peeters RP, Teumer A, Medici M, Deloukas P. Variation in Normal Range Thyroid Function Affects Serum Cholesterol Levels, Blood Pressure, and Type 2 Diabetes Risk: A Mendelian Randomization Study. Thyroid 2021; 31:721-731. [PMID: 32746749 DOI: 10.1089/thy.2020.0393] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background: Observational studies have demonstrated that variation in normal range thyroid function is associated with major cardiovascular risk factors, including dyslipidemia, hypertension, type 2 diabetes (T2D), and obesity. As observational studies are prone to residual confounding, reverse causality, and selection bias, we used a Mendelian randomization (MR) approach to investigate whether these associations are causal or not. Methods: Two-sample MR analysis using data from the largest available genome-wide association studies on normal range thyrotropin (TSH) and free thyroxine (fT4) levels, serum lipid levels, blood pressure measurements, T2D, and obesity traits (body mass index [BMI] and waist/hip ratio). Results: A one standard deviation (SD) increase in genetically predicted TSH levels was associated with a 0.037 SD increase in total cholesterol levels (p = 3.0 × 10-4). After excluding pleiotropic instruments, we also observed significant associations between TSH levels and low-density lipoprotein levels (β = 0.026 SD, p = 1.9 × 10-3), pulse pressure (β = -0.477 mmHg, p = 7.5 × 10-10), and T2D risk (odds ratio = 0.95, p = 2.5 × 10-3). While we found no evidence of causal associations between TSH or fT4 levels and obesity traits, we found that a one SD increase in genetically predicted BMI was associated with a 0.075 SD decrease in fT4 levels (p = 3.6 × 10-4). Conclusions: Variation in normal range thyroid function affects serum cholesterol levels, blood pressure, and T2D risk.
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Affiliation(s)
- Aleksander Kuś
- Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
- Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland
| | - Eirini Marouli
- William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
- Centre for Genomic Health, Life Sciences, Queen Mary University of London, London, United Kingdom
| | - Fabiola Del Greco M
- Institute for Biomedicine, Eurac Research, Affiliated Institute of the University of Lubeck, Bolzano, Italy
| | - Layal Chaker
- Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Tomasz Bednarczuk
- Department of Internal Medicine and Endocrinology, Medical University of Warsaw, Warsaw, Poland
| | - Robin P Peeters
- Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
| | - Alexander Teumer
- Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Greifswald, Germany
| | - Marco Medici
- Department of Internal Medicine, Academic Center for Thyroid Diseases, Erasmus Medical Center, Rotterdam, The Netherlands
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands
- Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Panos Deloukas
- William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
- Centre for Genomic Health, Life Sciences, Queen Mary University of London, London, United Kingdom
- Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia
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17
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Chen X, Deng S, Sena C, Zhou C, Thaker VV. Relationship of TSH Levels with Cardiometabolic Risk Factors in US Youth and Reference Percentiles for Thyroid Function. J Clin Endocrinol Metab 2021; 106:e1221-e1230. [PMID: 33274355 PMCID: PMC7947754 DOI: 10.1210/clinem/dgaa900] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2020] [Indexed: 12/12/2022]
Abstract
CONTEXT Thyroid hormones play an important role in metabolic homeostasis, and higher levels have been associated with cardiometabolic risk. OBJECTIVE To examine the association of cardiometabolic risk factors with TSH levels in US youth. METHODS Cross-sectional study of youth aged 12 to 18 years without known thyroid abnormalities from 5 National Health and Nutrition Examination Survey cycles (n = 2818) representing 15.4 million US children. Subclinical hypothyroidism (SH) was defined as thyrotropin (TSH) levels of 4.5 to 10 mIU/L. Assessed cardiometabolic risk factors include abdominal obesity (waist circumference >90th percentile), hypertriglyceridemia (triglyceride ≥130 mg/dL), low high-density lipoprotein cholesterol (<40 mg/dL), elevated blood pressure (systolic and diastolic blood pressure ≥90th percentile), hyperglycemia (fasting blood glucose ≥100 mg/dL, or known diabetes), insulin resistance (homeostatic model for insulin resistance > 3.16), and elevated alanine transferase (≥ 50 for boys and ≥44 U/L for girls). Age and sex- specific percentiles for thyroid parameters were calculated. RESULTS In this cohort of youth (51.3% male), 31.2% had overweight/obesity. The prevalence of SH was 2.0% (95% CI 1.2-3.1). The median TSH levels were higher in youth with overweight/obesity (P < 0.001). Adjusting for age, sex, race/ethnicity, and obesity, youth with TSH in the fourth quantile had higher odds of abdominal obesity (OR 2.53 [1.43-4.46], P = .002), insulin resistance (OR 2.82 [1.42-5.57], P = .003), and ≥2 cardiometabolic risk factors (CMRF) (OR 2.20 [1.23-3.95], P = .009). CONCLUSION The prevalence of SH is low in US youth. The higher odds of insulin resistance and cardiometabolic risk factors in youth with TSH levels >75th percentile requires further study.
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Affiliation(s)
- Xinlei Chen
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA
- Department of Biostatistics, University of Pittsburgh, Pittsburgh, PA, USA
| | - Shuliang Deng
- Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA
- Division of Cardiovascular Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Cecilia Sena
- Department of Pediatrics, Columbia University Medical Center, New York, NY, USA
| | - Chuhan Zhou
- Institute of Human Nutrition, Columbia University, New York, NY, USA
| | - Vidhu V Thaker
- Department of Pediatrics, Columbia University Medical Center, New York, NY, USA
- Correspondence: Vidhu V. Thaker, MD, Division of Molecular Genetics, Department of Pediatrics, Columbia University Medical Center, 1150, St. Nicholas Avenue, New York, NY 10032, USA.
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18
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Aravinda Swami P, T. Saravana Kumar R, Babu Sitty M. KAP of Metabolic Disorders in South Indian Population. ASIAN JOURNAL OF PHARMACEUTICAL RESEARCH AND HEALTH CARE 2021. [DOI: 10.18311/ajprhc/2021/26382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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19
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Kozacz A, Assis GGD, Sanocka U, Ziemba AW. Standard hypothyroid treatment did not restore proper metabolic response to carbohydrate. Endocrine 2021; 71:96-103. [PMID: 32405763 PMCID: PMC7835296 DOI: 10.1007/s12020-020-02334-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Accepted: 04/27/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE Hypothyroidism is associated with a lower metabolic rate, impaired glucose tolerance, and increased responsiveness of sympathetic nervous system to glucose ingestion. The Levothyroxine (LT4) monotherapy is the standard treatment for hypothyroidism; however to what extent this treatment restores the patients' metabolism has not been verified. The aim of this study was to test the hypothesis that standard LT4 therapy may not restore proper metabolic response to carbohydrate ingestion. METHODS Energy expenditure, glucose tolerance, and catecholamine response to glucose ingestion were compared in 18 subjects with pharmacologically compensated hypothyroidism (PCH) and controls, at baseline and during oral glucose tolerance test conditions. RESULTS Metabolic rate was significantly lower in PCH (P < 0.0001). Glucose tolerance was decreased in this group with no differences in insulin resistance indicators between both groups. Adrenergic activity (P < 0.05) as well as adrenergic reaction to glucose ingestion (P < 0.001) were stronger in PCH. CONCLUSIONS Standard treatment for hypothyroidism does not restore the normal metabolic reaction to carbohydrate which is observed in healthy people.
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Affiliation(s)
- Agnieszka Kozacz
- Department of Applied Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5 str., 02-106, Warsaw, Poland
| | - Gilmara Gomes de Assis
- Department of Applied Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5 str., 02-106, Warsaw, Poland
| | - Urszula Sanocka
- Endocrinology Outpatient Department, Masovian Hospital Bródno, Kondratowicza 8 str., 03-242, Warsaw, Poland
| | - Andrzej Wojciech Ziemba
- Department of Applied Physiology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5 str., 02-106, Warsaw, Poland.
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20
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Schernthaner-Reiter MH, Wolf P, Vila G, Luger A. The Interaction of Insulin and Pituitary Hormone Syndromes. Front Endocrinol (Lausanne) 2021; 12:626427. [PMID: 33995272 PMCID: PMC8113952 DOI: 10.3389/fendo.2021.626427] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 04/06/2021] [Indexed: 12/21/2022] Open
Abstract
Pituitary hormone axes modulate glucose metabolism and exert direct or indirect effects on insulin secretion and function. Cortisol and growth hormone are potent insulin-antagonistic hormones. Therefore impaired glucose tolerance, elevated fasting glucose concentrations and diabetes mellitus are frequent in Cushing's disease and acromegaly. Also prolactinomas, growth hormone (GH) deficiency, hypogonadism and hypothyroidism might be associated with impaired glucose homeostasis but usually to a lesser extent. Therefore glucose metabolism needs to be closely monitored and treated in patients with pituitary adenomas. Correction of the pituitary dysfunction is frequently followed by improvement of glucose homeostasis.
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21
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Huang X, Zhang X, Zhou X, Han X, Fu Z, Li Y, Ji L. Prevalence of Thyroid Dysfunction in a Chinese Population with Different Glucose Intolerance Status: A Community-Based Cross-Sectional Study. Diabetes Metab Syndr Obes 2020; 13:4361-4368. [PMID: 33235476 PMCID: PMC7678694 DOI: 10.2147/dmso.s271328] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Accepted: 10/27/2020] [Indexed: 12/17/2022] Open
Abstract
AIM Impaired glucose metabolism and thyroid dysfunction (TD) are the two most common chronic metabolic disorders. This study aimed to investigate the epidemiological characteristics of TD in different status of glucose tolerance in a community-based Chinese population and to understand the association between TD and glucose metabolism. METHODS A community-based population study of metabolic disease was conducted from June 2013 to September 2014 in Beijing, China. Residents aged 26-76 years were selected according to gender and age composition using multi-stage stratified random sampling process. All participants underwent serum thyroid function and thyroid-associated antibody tests. The status of glucose tolerance was determined using 75g-oral glucose tolerance test. Chi-square test was used to compare the differences in prevalence. Multivariate logistic regression analysis was used to determine the impact of insulin resistance (IR) on thyroid function. RESULTS By analyzing 3986 participants who were included in the survey, the prevalence of type 2 diabetes (T2DM) and pre-diabetes (pre-DM) was 18.59% and 26.79%, respectively. The prevalence of TD was 8.81%, with overt hyperthyroidism accounting for 0.38%; subclinical hyperthyroidism, 1.86%; overt hypothyroidism, 0.70%; and subclinical hypothyroidism, 5.87%. The prevalence of TD increased with gradually deteriorated glucose tolerance (7.63% in those with normal glucose tolerance, 9.27% in pre-DM, and 11.61% in T2DM) in both men and women. Each unit of higher HOMA-IR was associated with 7% higher likelihood of having subclinical hypothyroidism. CONCLUSION The coexisting of TD with T2DM and pre-DM is high in this community-based Chinese population, suggesting a close relationship between TD and glucose metabolism.
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Affiliation(s)
- Xiuting Huang
- Department of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing100044, People’s Republic of China
| | - Xiuying Zhang
- Department of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing100044, People’s Republic of China
| | - Xianghai Zhou
- Department of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing100044, People’s Republic of China
| | - Xueyao Han
- Department of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing100044, People’s Republic of China
| | - Zuodi Fu
- Department of Endocrinology and Metabolism, Capital Medical University Pinggu Teaching Hospital, Beijing101200, People’s Republic of China
| | - Yufeng Li
- Department of Endocrinology and Metabolism, Capital Medical University Pinggu Teaching Hospital, Beijing101200, People’s Republic of China
| | - Linong Ji
- Department of Endocrinology and Metabolism, Peking University People’s Hospital, Peking University Diabetes Center, Beijing100044, People’s Republic of China
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22
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Pillay S, Pillay D, Singh D, Pillay R. Human immunodeficiency virus, diabetes mellitus and thyroid abnormalities: Should we be screening? South Afr J HIV Med 2020; 21:1116. [PMID: 33240534 PMCID: PMC7670034 DOI: 10.4102/sajhivmed.v21i1.1116] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 09/04/2020] [Indexed: 11/28/2022] Open
Abstract
BACKGROUND Diabetes mellitus (DM) and human immunodeficiency virus (HIV) are associated with thyroid abnormalities. Scarce literature exists on the prevalence of thyroid abnormalities in people living with HIV (PLWH) and DM (PLWHD). Guidelines vary regarding thyroid-stimulating hormone (TSH) screening in PLWH and/or DM. OBJECTIVES This study describes thyroid abnormalities in PLWHD and HIV-uninfected people living with DM (PLWD). METHOD This was a cross-sectional analysis of demographic, clinical and biochemical data including TSH results of first-visit patients to the Edendale Hospital diabetes clinic between January 2016 and December 2017. RESULTS A total of 915 patients were enrolled: 165 PLWHD and 750 PLWD. Overall prevalence of thyroid disorders in PLWD was 8.53% (64/750). The occurrence of 'total' thyroid disorders and of 'subclinical-hypothyroidism' (SCH) was higher in PLWHD than PLWD (23.03% vs. 8.53% and 20.61% vs. 4%, p < 0.001; respectively). People living with HIV and diabetes with thyroid disorders had lower CD4 counts than PLWHD without thyroid disorders (376.08 ± 333.30 vs. 509 ± 341.7 cells/mm3; p = 0.004). Subclinical-hypothyroidism was more common in patients on antiretroviral therapy [ART] (27/136 [19.85%] vs. 4/27 [14.81%], p < 0.001). A significant number of PLWHD acquired HIV before the onset of DM (107/165 [64.85%] vs. 58/165 [35.15%], p < 0.001). Patients on ART were more likely to develop DM, OR 2.66 (95% CI 1.11-6.38). CONCLUSION Our study showed an increased prevalence of thyroid disorders (especially SCH) in PLWD and a higher prevalence in PLWHD. Young, overweight, female PLWHD were at risk of SCH. People living with HIV and DM on ART demonstrated an increased prevalence of thyroid dysfunction and poor lipaemic control. The introduction of combined communicable-non-communicable disease clinics might provide an integrated patient screening option.
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Affiliation(s)
- Somasundram Pillay
- Department of Internal Medicine, King Edward VIII Hospital, Durban, South Africa
- Department of Internal Medicine, University of KwaZulu-Natal, Durban, South Africa
| | | | - Deepak Singh
- Department of Physics, Durban University of Technology, Durban, South Africa
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AKYÜZLÜ ZN, MUTLU HH. Tiroit hastalığı olanlarda trigliserit/glikoz indeksi insülin direnci belirteci olarak kullanılabilir mi? EGE TIP DERGISI 2020. [DOI: 10.19161/etd.790451] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
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Martins VJB, Filgueiras AR, Almeida VBP, de Moraes RCS, Sawaya AL. Changes in Thyroid and Glycemic Status and Food Intake in Children with Excess Weight Who Were Submitted for a Multi-Component School Intervention for 16 Months. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:E3825. [PMID: 32481623 PMCID: PMC7312354 DOI: 10.3390/ijerph17113825] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Revised: 03/20/2020] [Accepted: 04/01/2020] [Indexed: 12/11/2022]
Abstract
We investigated if children with excess weight who submitted to two types of intervention at school for 16 months showed improvements in thyroid and glycemic function and food intake. Children (8-11 years) with a body mass index-for-age (BMI/A) of ≥1 Z score were divided into two groups: Treatment 1 (n = 73) involved motivation to adopt healthier lifestyle; Treatment 2 (n = 103) involved performing weekly nutritional education, motivational, and physical activities at school. A semi-quantitative food frequency questionnaire was used. The delta BMI/A were similar after 16 months; Treatment 1 showed higher decrease in thyroid-stimulating hormone (TSH; median (range)): -0.45 (-3.19 to 2.17) and 0.06 (-4.57 to 1.63) mIU/L, p = 0.001), FreeT3 (-0.46 (-2.92 to 1.54) and -0.15 (-2.46 to 1.38) pmol/L, p = 0.038), and FreeT4 -1.41 (-6.18 to 3.47) and -0.90 (-4.89 to 2.96) pmol/L, p = 0.018), followed by decrease in energy intake (7304 (6806 to 7840) and 8267 (7739 to 8832) kJ, Ptreatment = 0.439, Ptime <0.001, interaction group-time p < 0.001), macronutrients and sugar. A positive correlation between FreeT3 and BMI/A, and a negative correlation with FreeT4 and insulin were found at baseline (r 0.212, p < 0.01; r -0.155, p < 0.01, respectively) and follow-up (r 0.222, p < 0.01; r -0.221, p < 0.01). The decrease in overall diet and particularly sugar intake was accompanied by a greater reduction in TSH and FreeT3 in Treatment 1, demonstrating the impact of dietary intake on thyroid function.
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Affiliation(s)
- Vinicius J. B. Martins
- Department of Physiology and Pathology, Federal University of Paraíba, Health Sciences Center, Campus I, Cidade Universitária, João Pessoa 58051-900, Brazil
| | - Andrea R. Filgueiras
- Department of Physiology, Federal University of São Paulo, Rua Botucatu, 862, Edifício de Ciências Biomédicas, 2 andar, São Paulo 04023-060, Brazil; (A.R.F.); (V.B.P.A.); (A.L.S.)
| | - Viviane B. P. Almeida
- Department of Physiology, Federal University of São Paulo, Rua Botucatu, 862, Edifício de Ciências Biomédicas, 2 andar, São Paulo 04023-060, Brazil; (A.R.F.); (V.B.P.A.); (A.L.S.)
| | - Rúbia C. S. de Moraes
- Department of Nutrition, Federal University of Paraíba, Health Sciences Center, Campus I, Cidade Universitária, João Pessoa 58051-900, Brazil;
| | - Ana L. Sawaya
- Department of Physiology, Federal University of São Paulo, Rua Botucatu, 862, Edifício de Ciências Biomédicas, 2 andar, São Paulo 04023-060, Brazil; (A.R.F.); (V.B.P.A.); (A.L.S.)
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Alemdar S, Yilmaz N, Ozdem S, Sari R. Incretin levels in patients with hypothyroidism and the evaluation of incretin levels alterations with treatment. ASIAN BIOMED 2019. [DOI: 10.1515/abm-2019-0033] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Abstract
Background
Incretin hormones may influence the effects of thyroid hormones on insulin secretion, insulin resistance, and glucose metabolism. Thyroid hormones regulate insulin secretion, and the risk of diabetes was found to be associated with thyroid hormones.
Objectives
To determine whether incretin hormones influence the effects of thyroid hormones on insulin resistance and glucose metabolism.
Methods
A total of 26 patients were included in 2 groups consisting of 13 patients with hypothyroidism and 13 healthy controls. Levels of glucose, insulin, glucagon-like peptide 1 (GLP-1), and gastric inhibitory polypeptide (GIP) levels were measured in 0, 30, 60, 90, and 120th min during the oral glucose tolerance test in the control group and before and after thyroxine treatment in the hypothyroid group.
Results
In the hypothyroid group, waist circumference decreased after the euthyroid state was achieved (P = 0.026). No statistically significant differences were detected in the GLP-1 and GIP levels at baseline and 30, 60, 90, and 120 min between the hypothyroidism and control groups or after ensuring the euthyroid state in patients with hypothyroidism. Peak GLP-1 levels were observed at 30 min in the control group, whereas peak GLP-1 and GIP levels were detected at 90 min in the hypothyroidism group. After achieving the euthyroid state, peak GLP-1 and GIP levels were detected at 30 min as well.
Conclusion
In patients with hypothyroidism, the incretin hormones, especially the peak response of the incretin system, are significantly affected. Significant changes were observed in the incretin system by correcting hypothyroidism.
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Affiliation(s)
- Serkan Alemdar
- Department of Internal Medicine, School of Medicine, Akdeniz University , Antalya 07070 , Turkey
| | - Nusret Yilmaz
- Department of Internal Medicine, School of Medicine, Akdeniz University , Antalya 07070 , Turkey
| | - Sebahat Ozdem
- Department of Biochemistry, Akdeniz University, School of Medicine , Antalya 07070 , Turkey
| | - Ramazan Sari
- Department of Internal Medicine, School of Medicine, Akdeniz University , Antalya 07070 , Turkey
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Lee SA, Choi DW, Kwon J, Lee DW, Park EC. Association between continuity of care and type 2 diabetes development among patients with thyroid disorder. Medicine (Baltimore) 2019; 98:e18537. [PMID: 31876751 PMCID: PMC6946430 DOI: 10.1097/md.0000000000018537] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2019] [Revised: 09/02/2019] [Accepted: 12/02/2019] [Indexed: 02/06/2023] Open
Abstract
Thyroid disorders are associated with blood glucose abnormalities. For rendering the patients euthyroid, routine screening and care are essential. Therefore, the aim of this study was to investigate the association between continuity of care (COC) and type 2 diabetes onset among patients with thyroid disorders.We used the national claim data. Our study population was 4099 patients with hyperthyroidism or hypothyroidism. For calculating COC, the Most Frequent Provider Continuity Index (MFPCI), Modified Modified Continuity Index (MMCI), and COC Index (COCI) were used. The dependent variable was type 2 diabetes onset. The Cox proportional hazard regression model was used.Among 4099 patients with thyroid disorders, 25.3% experienced onset of type 2 diabetes. Thyroid patients who had MFPCI and COCI below the median were more likely to experience onset of type 2 diabetes than who had these indices above the median (MFPCI: hazard ratio [HR] = 1.26, 95% confidence interval [CI] = 1.09-1.46; COCI: HR = 1.22, 95% CI = 1.06-1.41). Our subgroup analysis showed that female patients and those 20 to 34 years of age showed a significant association between COC and onset of type 2 diabetes.Patients with thyroid disorders with low COC showed an increased risk of developing type 2 diabetes. Therefore, efforts to enhance COC among patients with thyroid disorders needs to be encouraged.
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Affiliation(s)
- Sang Ah Lee
- Department of Public Health, Graduate School
- Institute of Health Services Research, Yonsei University, Seoul
- Research and Analysis Team, National Health Insurance Service Ilsan Hospital, Goyang
| | - Dong-Woo Choi
- Department of Public Health, Graduate School
- Institute of Health Services Research, Yonsei University, Seoul
| | - Junhyun Kwon
- Department of Public Health, Graduate School
- Institute of Health Services Research, Yonsei University, Seoul
| | - Doo Woong Lee
- Department of Public Health, Graduate School
- Institute of Health Services Research, Yonsei University, Seoul
| | - Eun-Cheol Park
- Institute of Health Services Research, Yonsei University, Seoul
- Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea
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Abstract
PURPOSE OF REVIEW To summarize recent developments in the association of thyroid function with metabolic syndrome (MetS). RECENT FINDINGS Although thyroid hormones even within low normal range are associated with various metabolic abnormalities, the risk of MetS remains a controversial issue. Hyperthyroid state might be associated only with insulin resistance and dysglycemia. Autoimmune thyroid diseases may be a potential risk factor for metabolic abnormalities even in those with low normal thyroid function. SUMMARY The interrelation between thyroid stimulating hormone, free T3, freeT4 and metabolic parameters is complex and might be affected by age, sex, BMI, insulin resistance, smoking, iodine intake and inflammatory markers.
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Affiliation(s)
- Ladan Mehran
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Biondi B, Kahaly GJ, Robertson RP. Thyroid Dysfunction and Diabetes Mellitus: Two Closely Associated Disorders. Endocr Rev 2019; 40:789-824. [PMID: 30649221 PMCID: PMC6507635 DOI: 10.1210/er.2018-00163] [Citation(s) in RCA: 260] [Impact Index Per Article: 43.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Accepted: 10/15/2018] [Indexed: 12/13/2022]
Abstract
Thyroid dysfunction and diabetes mellitus are closely linked. Several studies have documented the increased prevalence of thyroid disorders in patients with diabetes mellitus and vice versa. This review critically discusses the different underlying mechanisms linking type 1 and 2 diabetes and thyroid dysfunction to demonstrate that the association of these two common disorders is unlikely a simple coincidence. We assess the current state of knowledge on the central and peripheral control of thyroid hormone on food intake and glucose and lipid metabolism in target tissues (such as liver, white and brown adipose tissue, pancreatic β cells, and skeletal muscle) to explain the mechanism linking overt and subclinical hypothyroidism to type 2 diabetes and metabolic syndrome. We also elucidate the common susceptibility genes and the pathogenetic mechanisms contributing to the autoimmune mechanism involved in the onset of type 1 diabetes mellitus and autoimmune thyroid disorders. An untreated thyroid dysfunction can impair the metabolic control of diabetic patients, and this association can have important repercussions on the outcome of both of these disorders. Therefore, we offer recommendations for the diagnosis, management, and screening of thyroid disorders in patients with diabetes mellitus, including the treatment of diabetic patients planning a pregnancy. We also discuss the major causes of failure to achieve an optimal management of thyroid dysfunction in diabetic patients and provide recommendations for assessing and treating these disorders during therapy with antidiabetic drugs. An algorithm for a correct approach of these disorders when linked is also provided.
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Affiliation(s)
- Bernadette Biondi
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - George J Kahaly
- Department of Medicine I, Johannes Gutenberg University Medical Center, Mainz, Germany
| | - R Paul Robertson
- Department of Medicine, Division of Endocrinology and Metabolism, University of Washington School of Medicine, Seattle, Washington.,Department of Pharmacology, University of Washington, Seattle, Washington
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Chen RH, Chen HY, Man KM, Chen SJ, Chen W, Liu PL, Chen YH, Chen WC. Thyroid diseases increased the risk of type 2 diabetes mellitus: A nation-wide cohort study. Medicine (Baltimore) 2019; 98:e15631. [PMID: 31096476 PMCID: PMC6531080 DOI: 10.1097/md.0000000000015631] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Thyroid function may alter carbohydrate metabolism via influence of insulin, which may in terms of derangement of thyroid function and insulin function result in the development of type 2 diabetes mellitus (T2D). We investigated the association of thyroid disorders with T2D by a cohort study of the Taiwan nationwide health insurance database.A sub-dataset of the National Health Insurance Research Database (NHIRD) was used in this study. The thyroid disease (both hyper- and hypo-thyroidism) group was chosen from patients older than 18 years and newly diagnosed between 2000 and 2012. The control group consisted of randomly selected patients who never been diagnosed with thyroid disease and 4-fold size frequency matched with the thyroid disease group. The event of this cohort was T2D (ICD-9-CM 250.x1, 250.x2). Primary analysis was performed by comparing the thyroid disease group to the control group and the second analysis was performed by comparing the hyperthyroidism subgroup, hypothyroidism subgroup, and control group.The occurrence of T2D in the thyroid disease group was higher than the control group with hazard ratio (HR) of 1.23 [95% confidence interval (CI) = 1.16-1.31]. Both hyperthyroidism and hypothyroidism were significantly higher than control. Significantly higher HR was also seen in female patients, age category of 18 to 39-year-old (y/o) and 40 to 64 y/o subgroups. Higher occurrence of T2D was also seen in thyroid disease patients without comorbidity than in the control group with HR of 1.47 (95% CI = 1.34-1.60). The highest HR was found in the half-year follow-up.There was a relatively high risk of T2D development in patients with thyroid dysfunctions, especially in the period of 0.5 to 1 year after presentation of thyroid dysfunctions. The results suggest performing blood sugar tests in patients with thyroid diseases for early detection and treatment of T2D.
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Affiliation(s)
- Rong-Hsing Chen
- Departments of Endocrine and Metabolism, Anesthesiology, Obstetrics and Gynecology, Medical Research, Medical Education, and Urology, China Medical University Hospital
| | - Huey-Yi Chen
- Departments of Endocrine and Metabolism, Anesthesiology, Obstetrics and Gynecology, Medical Research, Medical Education, and Urology, China Medical University Hospital
- Graduate Institute of Integrated Medicine, College of Chinese Medicine, College of Medicine, China Medical University
| | - Kee-Ming Man
- Departments of Endocrine and Metabolism, Anesthesiology, Obstetrics and Gynecology, Medical Research, Medical Education, and Urology, China Medical University Hospital
- Graduate Institute of Integrated Medicine, College of Chinese Medicine, College of Medicine, China Medical University
- Department of Anesthesiology, China Medical University Hsinchu Hospital, Hsinchu
| | - Szu-Ju Chen
- Departments of Endocrine and Metabolism, Anesthesiology, Obstetrics and Gynecology, Medical Research, Medical Education, and Urology, China Medical University Hospital
- Department of Surgery, Taichung Veterans General Hospital, Taichung
| | - Weishan Chen
- Management Office for Health Data, China Medical University Hospital, Taichung
| | - Po-Len Liu
- Department of Respiratory Therapy, College of Medicine, Kaohsiung Medical University, Kaohsiung
| | - Yung-Hsiang Chen
- Departments of Endocrine and Metabolism, Anesthesiology, Obstetrics and Gynecology, Medical Research, Medical Education, and Urology, China Medical University Hospital
- Graduate Institute of Integrated Medicine, College of Chinese Medicine, College of Medicine, China Medical University
- Department of Psychology, College of Medical and Health Science, Asia University, Taichung, Taiwan
| | - Wen-Chi Chen
- Departments of Endocrine and Metabolism, Anesthesiology, Obstetrics and Gynecology, Medical Research, Medical Education, and Urology, China Medical University Hospital
- Graduate Institute of Integrated Medicine, College of Chinese Medicine, College of Medicine, China Medical University
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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. [PMID: 30742573 DOI: 10.4158/ep-2018-0317] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Latin American Thyroid Society (LATS) Hypothyroidism Clinical Practice Guidelines recommend case finding of hypothyroid patients in multiple and different situations that agree with other Society guidelines. However, the detection of hypothyroidism in type 2 diabetes mellitus (T2DM) or metabolic syndrome (MetS) patients is not mentioned in particular. In the recent years, several basic and epidemiologic studies have appeared showing that a lower thyroid function and MetS/T2DM are associated. Hence, the aim of this review is to manifest the LATS position on the diagnosis of hypothyroidism in both MetS and T2DM patients. METHODS A search was made in PubMed using the following terms: "hypothyroidism" AND "diabetes" OR "metabolic syndrome." The most relevant studies describing the prevalence and complications due to hypothyroidism in both MetS and T2DM patients were selected. RESULTS The current document reviews new information from studies that have shown that the prevalence of hypothyroidism is higher in T2DM patients (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.5 to 4.7) and that diabetic complications are more prevalent in subclinical hypothyroidism (ScH). The incidence of T2DM is 1.09-fold higher with each doubling of thyroid-stimulating hormone (TSH) mIU/L (95% CI, 1.06 to 1.12), and the incidence of prediabetes increases 15% (hazard ratio, 1.15; 95% CI, 1.04 to 1.26) in patients with TSH >5 mIU/L. Similarly, MetS is more prevalent in ScH compared to euthyroid individuals (OR, 1.31; 95% CI, 1.08 to 1.60). CONCLUSION Thyroid function is affected in MetS and T2DM, and hypothyroidism is more common in these patients. Diabetic complications are more frequent in ScH patients. Therefore, LATS now recommends aggressive case finding of hypothyroidism in both MetS and T2DM patients. ABBREVIATIONS CI = confidence interval; GLUT4 = glucose transporter 4; HOMA-IR = homeostatic model assessment for insulin resistance; HR = hazard ratio; LATS = Latin American Thyroid Society; MetS = metabolic syndrome; OR = odds ratio; ScH = subclinical hypothyroidism; T2DM = type 2 diabetes mellitus; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.
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de Vries TI, Kappelle LJ, van der Graaf Y, de Valk HW, de Borst GJ, Nathoe HM, Visseren FLJ, Westerink J. Thyroid-stimulating hormone levels in the normal range and incident type 2 diabetes mellitus. Acta Diabetol 2019; 56:431-440. [PMID: 30259116 PMCID: PMC6420678 DOI: 10.1007/s00592-018-1231-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Accepted: 09/17/2018] [Indexed: 11/27/2022]
Abstract
AIM To evaluate the relationship between thyroid-stimulating hormone (TSH) levels within the normal range and the risk of type 2 diabetes mellitus (T2DM) in a cohort of patients at high cardiovascular risk, and to perform a systematic review and meta-analysis of previous studies. METHODS We included 5542 patients without T2DM from the prospective Secondary Manifestations of ARTerial disease study with TSH levels between 0.35 and 5.0 mIU/L without anti-thyroid medication or thyroid-hormone replacement therapy. Cox regression was used to investigate the relationship between baseline plasma TSH levels and incident T2DM. MEDLINE, EMBASE, and Cochrane were searched for prospective cohorts assessing TSH and incident T2DM. Hazard ratios (HR) from included prospective cohort studies were pooled using a random-effects model. RESULTS In patients at high cardiovascular risk, higher plasma TSH levels in the normal range were not associated [HR 1.07 per mIU/L increase in TSH (95% confidence interval (95% CI) 0.95-1.22)] with an increased risk of T2DM, adjusted for age, sex, smoking, total and HDL cholesterol, and triglycerides. In the meta-analysis involving three prospective cohort studies, including the present study, including 29,791 participants with 1930 incident events, there was no relation between plasma TSH levels in the normal range and incident T2DM [pooled HR 1.06 (95% CI 0.99-1.14)]. CONCLUSION There is no apparent relation between plasma TSH levels in the normal range and incident T2DM in patients at high cardiovascular risk.
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Affiliation(s)
- T I de Vries
- Department of Vascular Medicine, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands
| | - L J Kappelle
- Department of Neurology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Y van der Graaf
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - H W de Valk
- Department of Internal Medicine, University Medical Center Utrecht, Utrecht, The Netherlands
| | - G J de Borst
- Department of Vascular Surgery, University Medical Center Utrecht, Utrecht, The Netherlands
| | - H M Nathoe
- Department of Cardiology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - F L J Visseren
- Department of Vascular Medicine, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands
| | - Jan Westerink
- Department of Vascular Medicine, University Medical Center Utrecht, P.O. Box 85500, 3508 GA, Utrecht, The Netherlands.
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Jayanthi R, Srinivasan AR. Biochemical isthmus [nexus] between type 2 diabetes mellitus and thyroid status-an update. Diabetes Metab Syndr 2019; 13:1173-1177. [PMID: 31336461 DOI: 10.1016/j.dsx.2019.01.037] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Accepted: 01/18/2019] [Indexed: 11/29/2022]
Abstract
Both Type 1 [T1DM] and Type 2 diabetes mellitus [T2DM] share a nexus with altered thyroid status. In recent times, evidences point to the link between thyroid hormones andT2DM in particular. Several lines of evidences suggest an array of biochemical and molecular events. Gene polymorphism, disturbances in gene expression and regulation, enhanced and bizarre absorption of dietary glucose from intestine, decreased utilization of glucose by tissues and aberrations in hepatic handling of glucose with the onus on Gluconeogenesis are some of the projected mechanisms. Insulin resistance, a progressive condition is the hallmark in T2DM. Hypothyroidism as well as hyperthyroidism have been associated with insulin resistance which are synonymous with impaired glucose metabolism in T2DM. A multitude of basic, clinical and molecular studies provide an insight into thyroid comorbidity in T2DM, though there are a few instances to suggest equivocal link denoting cause-effect relationship. In biochemical pharmacology, as fortified by pharmacogenomics, modalities have now been proposed, through drug trials, to underline the utility of specifically designed thyroid hormone analogues in addressing metabolic syndrome, DM and associated cardiovascular pathology. A thorough understanding of the physiological, biochemical and molecular mechanisms would certainly open newer vistas in the perspectives of T2DM with special reference to alterations in thyroid status.
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Affiliation(s)
- Rajendran Jayanthi
- Department of Biochemistry, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth, Pillaiyarkuppam, Pondicherry, 607 402, India
| | - Abu Raghavan Srinivasan
- Department of Biochemistry, Mahatma Gandhi Medical College and Research Institute, Sri Balaji Vidyapeeth, Pillaiyarkuppam, Pondicherry, 607 402, India.
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Ahn N, Kim HS, Kim K. Exercise training-induced changes in metabolic syndrome parameters, carotid wall thickness, and thyroid function in middle-aged women with subclinical hypothyroidism. Pflugers Arch 2019; 471:479-489. [PMID: 30656407 DOI: 10.1007/s00424-019-02254-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Accepted: 01/03/2019] [Indexed: 12/19/2022]
Abstract
This study analyzed the differences in effects of a 12-week combination of exercise training program with resistance training and aerobic exercises on the risk factors of metabolic syndrome, carotid wall thickness, and thyroid function, between subclinical hypothyroidism patients and obese groups, in middle-aged women. Subjects consisted of either 20 middle-aged women in the subclinical hypothyroidism (SCH) group or 20 obese (body mass indices [BMI], ≥ 25 kg/m2) women without hypothyroidism in the obese (OB) group. The body composition, blood lipid factors, hormones associated with thyroid functions, blood pressure (BP), and carotid intima-media thickness were measured, while physical fitness was ascertained. In the SCH group, waist circumference (WC) and high-density lipoprotein cholesterol values were outside the normal ranges, while WC and systolic BP (SBP) were outside the normal ranges in the OB group. Following the 12-week training program, significantly positive changes occurred in body fat percentage, sit and reach test results, and SBP (p < 0.05) in the SCH group, while in the OB group, significantly positive changes in BMI, WC, sit and reach test results, SBP, and diastolic BP (DBP, p < 0.05) were observed. In addition, both groups showed significant decreases in intima-media thickness of the right carotid bifurcation (p < 0.05). However, in the two groups, the 12-week exercise training program did not have similar significant impact on the hormones related to thyroid functions and blood lipids. Therefore, further research on exercise training that can effectively induce changes in the hormones associated with thyroid functions in patients with subclinical hypothyroidism is necessary.
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Affiliation(s)
- Nayoung Ahn
- Department of Physical Education, College of Physical Education, Keimyung University, 1095 Dalgubeuldaero, Dalseo-gu, Daegu, 42601, South Korea
| | - Hye Soon Kim
- Department of Internal Medicine, School of Medicine, Keimyung University, Jung-gu, Daegu, South Korea
| | - Kijin Kim
- Department of Physical Education, College of Physical Education, Keimyung University, 1095 Dalgubeuldaero, Dalseo-gu, Daegu, 42601, South Korea.
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Ittermann T, Schipf S, Dörr M, Thuesen BH, Jørgensen T, Völzke H, Markus MRP. Hyperthyroxinemia is positively associated with prevalent and incident type 2 diabetes mellitus in two population-based samples from Northeast Germany and Denmark. Nutr Metab Cardiovasc Dis 2018; 28:173-179. [PMID: 29239740 DOI: 10.1016/j.numecd.2017.10.016] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/20/2017] [Revised: 10/06/2017] [Accepted: 10/13/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS A potential causal relationship between thyroid function and type 2 diabetes mellitus is currently under debate, but the current state of research is limited. Our aim was to investigate the association of thyroid hormone levels with prevalent and incident type 2 diabetes mellitus (T2DM) in two representative studies. METHODS AND RESULTS Analyses are based on data from the Study of Health in Pomerania (SHIP), a German population based cohort with 4308 individuals at baseline and 3300 individuals at a five-year follow-up, and from INTER99, a Danish population-based randomized controlled trial with 6784 individuals at baseline and 4516 individuals at the five-year-follow-up. Serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) concentrations were measured in both studies, while free triiodothyronine was measured in SHIP only. T2DM was defined by self report or intake of anti-diabetic medication. Neither in SHIP nor in INTER99 we detected significant associations of serum TSH levels with prevalent or incident T2DM. Serum fT4 levels were significantly positively associated with prevalent T2DM in SHIP and INTER99. In longitudinal analyses baseline levels of fT4 were significantly positively associated with incident T2DM in SHIP (RR per pmol/L = 1.07; 95%-CI = 1.05-1.10), while this association barely missed statistical significance in INTER99 (RR per pmol/L = 1.03; 95%-CI = 0.99-1.06). In SHIP baseline fT3 levels were significantly associated with incident T2DM (RR per pmol/L = 1.21; 95%-CI = 1.16-1.27). CONCLUSION We demonstrated positive associations of thyroid hormones with prevalent and incident type 2 diabetes mellitus suggesting that hyperthyroxinemia may contribute to the pathogenesis of this condition.
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Affiliation(s)
- T Ittermann
- Institute for Community Medicine, University Medicine Greifswald, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Germany.
| | - S Schipf
- Institute for Community Medicine, University Medicine Greifswald, Germany; DZD (German Center for Diabetes Research), Site Greifswald, Germany
| | - M Dörr
- DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Germany; Department of Internal Medicine B - Cardiology, Intensive Care, Pulmonary Medicine and Infectious Diseases, University Medicine Greifswald, Germany
| | - B H Thuesen
- Research Centre for Prevention and Health, the Capital Region, Glostrup, Denmark
| | - T Jørgensen
- Research Centre for Prevention and Health, the Capital Region, Glostrup, Denmark
| | - H Völzke
- Institute for Community Medicine, University Medicine Greifswald, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Germany
| | - M R P Markus
- Institute for Community Medicine, University Medicine Greifswald, Germany; DZHK (German Center for Cardiovascular Research), Partner Site Greifswald, Germany; DZD (German Center for Diabetes Research), Site Greifswald, Germany
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Chang CH, Yeh YC, Shih SR, Lin JW, Chuang LM, Caffrey JL, Tu YK. Association between thyroid dysfunction and dysglycaemia: a prospective cohort study. Diabet Med 2017; 34:1584-1590. [PMID: 28710779 DOI: 10.1111/dme.13420] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 07/10/2017] [Indexed: 12/19/2022]
Abstract
AIMS To compare the incidence of hyperglycaemia among participants with low, elevated and normal serum thyroid-stimulating hormone concentration, as well as the incidence of abnormal thyroid function test results among participants with normal blood glucose and those with hyperglycaemia. METHODS In a prospective study, a cohort of 72 003 participants with normal, low and elevated serum thyroid-stimulating hormone concentration were followed from the study beginning to the first report of diabetes and prediabetes. A proportional hazards regression model was used to calculate the hazard ratios and 95% CIs for each outcome, adjusting for age, sex, education level, smoking, alcohol consumption and obesity. Analyses for the association between dysglycaemia and incident abnormal thyroid function test were also conducted. RESULTS During a median 2.6 year follow-up, the incident rates for dysglycaemia, particularly prediabetes, were substantially higher in participants with elevated thyroid-stimulating hormone concentrations at baseline, while the rates for participants with normal and low thyroid-stimulating hormone were similar. After controlling for risk factors, participants with elevated thyroid-stimulating hormone retained a 15% increase in risk of prediabetes (adjusted hazard ratio 1.15, 95% CI 1.04-1.26), but were not at greater risk of diabetes (adjusted hazard ratio 0.96, 95% CI 0.64-1.44). By contrast, participants with normal and low thyroid-stimulating hormone concentrations had similar dysglycaemia risks. Participants with diabetes and prediabetes were not at greater risks of developing abnormal thyroid function test results when compared with participants with euglycaemia. CONCLUSIONS People with elevated serum thyroid-stimulating hormone concentration are at greater risk of developing prediabetes. Whether this includes a greater risk of developing frank diabetes may require an extended period of follow-up to clarify.
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Affiliation(s)
- C-H Chang
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei
- Department of Medicine, College of Medicine, National Taiwan University, Taipei
| | - Y-C Yeh
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei
| | - S-R Shih
- Department of Internal Medicine, National Taiwan University Hospital, Taipei
- Department of Medicine, College of Medicine, National Taiwan University, Taipei
| | - J-W Lin
- Department of Internal Medicine, National Taiwan University Hospital, Taipei
- Department of Medicine, College of Medicine, National Taiwan University, Taipei
- Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Dou-Liou City, Yun-Lin County, Taiwan
| | - L-M Chuang
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei
- Department of Medicine, College of Medicine, National Taiwan University, Taipei
| | - J L Caffrey
- Institute for Cardiovascular and Metabolic Disease, University of North Texas Health Science Center, Fort Worth, TX, USA
| | - Y-K Tu
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei
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Shpakov AO. [Pharmacological approaches for correction of thyroid dysfunctions in diabetes mellitus]. BIOMEDIT︠S︡INSKAI︠A︡ KHIMII︠A︡ 2017; 63:219-231. [PMID: 28781255 DOI: 10.18097/pbmc20176303219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
Thyroid diseases are closely associated with the development of types 1 and 2 diabetes mellitus (DM), and as a consequence, the development of effective approaches for their treatment is one of the urgent problems of endocrinology. Traditionally, thyroid hormones (TH) are used to correct functions of the thyroid system. However, they are characterized by many side effects, such as their negative effect on the cardiovascular system as well as the ability of TH to enhance insulin resistance and to disturb insulin-producing function of pancreas, exacerbating thereby diabetic pathology. Therefore, the analogues of TH, selective for certain types of TH receptors, that do not have these side effects, are being developed. The peptide and low-molecular weight regulators of thyroid-stimulating hormone receptor, which regulate the activity of the thyroid axis at the stage of TH synthesis and secretion in thyrocytes, are being created. Systemic and intranasal administration of insulin, metformin therapy and drugs with antioxidant activity are effective for the treatment of thyroid pathology in types 1 and 2 DM. In the review, the literature data and the results of own investigations on pharmacological approaches for the treatment and prevention of thyroid diseases in patients with types 1 and 2 DM are summarized and analyzed.
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Affiliation(s)
- A O Shpakov
- I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences
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Dityrosine administration induces dysfunction of insulin secretion accompanied by diminished thyroid hormones T3 function in pancreas of mice. Amino Acids 2017. [DOI: 10.1007/s00726-017-2442-1] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Yang M, Du C, Wang Y, Liu J. Increased CD19+CD24+CD27+ B regulatory cells are associated with insulin resistance in patients with type I Hashimoto's thyroiditis. Mol Med Rep 2017; 15:4338-4345. [DOI: 10.3892/mmr.2017.6507] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2016] [Accepted: 02/03/2017] [Indexed: 11/05/2022] Open
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Ding YY, Tang X, Cheng XR, Wang FF, Li ZQ, Wu SJ, Kou XR, Shi Y, Le G. Effects of dietary oxidized tyrosine products on insulin secretion via the thyroid hormone T3-regulated TRβ1–Akt–mTOR pathway in the pancreas. RSC Adv 2017. [DOI: 10.1039/c7ra10435a] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Oxidized tyrosine products (OTPs) have been detected in commercial foods with high protein content.
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Affiliation(s)
- Yin-Yi Ding
- The State Key Laboratory of Food Science and Technology
- School of Food Science and Technology
- Jiangnan University
- Wuxi
- China
| | - Xue Tang
- The State Key Laboratory of Food Science and Technology
- School of Food Science and Technology
- Jiangnan University
- Wuxi
- China
| | - Xiang-Rong Cheng
- The State Key Laboratory of Food Science and Technology
- School of Food Science and Technology
- Jiangnan University
- Wuxi
- China
| | - Fang-Fang Wang
- The State Key Laboratory of Food Science and Technology
- School of Food Science and Technology
- Jiangnan University
- Wuxi
- China
| | - Zhu-Qing Li
- The State Key Laboratory of Food Science and Technology
- School of Food Science and Technology
- Jiangnan University
- Wuxi
- China
| | - Sha-Ji Wu
- The State Key Laboratory of Food Science and Technology
- School of Food Science and Technology
- Jiangnan University
- Wuxi
- China
| | - Xing-Ran Kou
- The State Key Laboratory of Food Science and Technology
- School of Food Science and Technology
- Jiangnan University
- Wuxi
- China
| | - Yonghui Shi
- The State Key Laboratory of Food Science and Technology
- School of Food Science and Technology
- Jiangnan University
- Wuxi
- China
| | - Guowei Le
- The State Key Laboratory of Food Science and Technology
- School of Food Science and Technology
- Jiangnan University
- Wuxi
- China
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Sirigiri S, Vaikkakara S, Sachan A, Srinivasarao P, Epuri S, Anantarapu S, Mukka A, Chokkapu SR, Venkatanarasu A, Poojari R. Correction of Hypothyroidism Leads to Change in Lean Body Mass without Altering Insulin Resistance. Eur Thyroid J 2016; 5:247-252. [PMID: 28101489 PMCID: PMC5216684 DOI: 10.1159/000448889] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2016] [Revised: 07/21/2016] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Hypothyroidism is associated with insulin resistance, dyslipidemia, and abnormal body composition. This study assessed changes in body composition and insulin resistance after thyroxine (T4) replacement in overt hypothyroidism. METHODS In this prospective longitudinal study carried out in a tertiary care center, adult nondiabetic patients with overt hypothyroidism were rendered euthyroid on T4. Anthropometry including skinfold thickness (SFT) at the triceps and subscapularis was recorded. Patients underwent testing for fasting plasma glucose, creatinine, serum insulin, T4, thyrotropin (TSH) and body composition analysis by dual-energy X-ray absorptiometry (DEXA) both before and at 2 months after restoration to the euthyroid state. RESULTS Twenty-seven patients (20 female and 7 male) aged 35.3 ± 11.0 years (min-max: 17-59 years) with overt hypothyroidism were recruited. Serum T4 at the time of recruitment was 48.9 ± 24.6 nmol/l (normal range = 64.4-142 nmol/l). All patients had TSH ≥50 µIU/l. Following treatment, there was a mean body weight reduction of 1.7 kg (p = 0.01). Waist circumference as well as triceps and subscapularis SFT decreased significantly (p < 0.001). There was no change in fat mass (FM), percentage of fat (%FM) or bone mineral content in any of the specified regions or in the body as a whole. In contrast, mean lean body mass (LBM) decreased significantly by 0.8 kg (p < 0.01) in the trunk and 1.3 kg (p < 0.01) in the whole body. Insulin resistance and level of glycemia were not affected by treatment with T4. CONCLUSION LBM decreases significantly without affecting FM after correction of hypothyroidism. Insulin resistance was not influenced by T4 treatment.
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Affiliation(s)
| | - Suresh Vaikkakara
- Department of Endocrinology, Tirupati, India
- *Prof. Suresh Vaikkakara, MD, DM, Department of Endocrinology, Sri Venkateswara Institute of Medical Sciences, Alipiri Road, Tirupati 517 507 (India), E-Mail
| | - Alok Sachan
- Department of Endocrinology, Tirupati, India
| | - P.V.L.N. Srinivasarao
- Department of Biochemistry, Sri Venkateswara Institute of Medical Sciences, Tirupati, India
| | - Sunil Epuri
- Department of Endocrinology, Tirupati, India
| | | | - Arun Mukka
- Department of Endocrinology, Tirupati, India
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Chaker L, Ligthart S, Korevaar TIM, Hofman A, Franco OH, Peeters RP, Dehghan A. Thyroid function and risk of type 2 diabetes: a population-based prospective cohort study. BMC Med 2016; 14:150. [PMID: 27686165 PMCID: PMC5043536 DOI: 10.1186/s12916-016-0693-4] [Citation(s) in RCA: 103] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2016] [Accepted: 09/13/2016] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND The association of thyroid function with risk of type 2 diabetes remains elusive. We aimed to investigate the association of thyroid function with incident diabetes and progression from prediabetes to diabetes in a population-based prospective cohort study. METHODS We included 8452 participants (mean age 65 years) with thyroid function measurement, defined by thyroid-stimulating hormone (TSH) and free thyroxine (FT4), and longitudinal assessment of diabetes incidence. Cox-models were used to investigate the association of TSH and FT4 with diabetes and progression from prediabetes to diabetes. Multivariable models were adjusted for age, sex, high-density lipoprotein cholesterol, and glucose at baseline, amongst others. RESULTS During a mean follow-up of 7.9 years, 798 diabetes cases occurred. Higher TSH levels were associated with a higher diabetes risk (hazard ratio [HR] 1.13; 95 % confidence interval [CI], 1.08-1.18, per logTSH), even within the reference range of thyroid function (HR 1.24; 95 % CI, 1.06-1.45). Higher FT4 levels were associated with a lower diabetes risk amongst all participants (HR 0.96; 95 % CI, 0.93-0.99, per 1 pmol/L) and in participants within the reference range of thyroid function (HR 0.96; 95 % CI, 0.92-0.99). The risk of progression from prediabetes to diabetes was higher with low-normal thyroid function (HR 1.32; 95 % CI, 1.06-1.64 for TSH and HR 0.91; 95 % CI, 0.86-0.97 for FT4). Absolute risk of developing diabetes type 2 in participants with prediabetes decreased from 35 % to almost 15 % with higher FT4 levels within the normal range. CONCLUSIONS Low and low-normal thyroid function are risk factors for incident diabetes, especially in individuals with prediabetes. Future studies should investigate whether screening for and treatment of (subclinical) hypothyroidism is beneficial in subjects at risk of developing diabetes.
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Affiliation(s)
- Layal Chaker
- Rotterdam Thyroid Center, Erasmus University Medical Center, Rotterdam, The Netherlands.,Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.,Department of Epidemiology, Erasmus University Medical Center, Room NA-2828, 3000CA, Rotterdam, The Netherlands
| | - Symen Ligthart
- Department of Epidemiology, Erasmus University Medical Center, Room NA-2828, 3000CA, Rotterdam, The Netherlands
| | - Tim I M Korevaar
- Rotterdam Thyroid Center, Erasmus University Medical Center, Rotterdam, The Netherlands.,Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.,Department of Epidemiology, Erasmus University Medical Center, Room NA-2828, 3000CA, Rotterdam, The Netherlands
| | - Albert Hofman
- Department of Epidemiology, Erasmus University Medical Center, Room NA-2828, 3000CA, Rotterdam, The Netherlands.,Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Oscar H Franco
- Department of Epidemiology, Erasmus University Medical Center, Room NA-2828, 3000CA, Rotterdam, The Netherlands
| | - Robin P Peeters
- Rotterdam Thyroid Center, Erasmus University Medical Center, Rotterdam, The Netherlands. .,Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. .,Department of Epidemiology, Erasmus University Medical Center, Room NA-2828, 3000CA, Rotterdam, The Netherlands.
| | - Abbas Dehghan
- Department of Epidemiology, Erasmus University Medical Center, Room NA-2828, 3000CA, Rotterdam, The Netherlands
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Safayee S, Karbalaei N, Noorafshan A, Nadimi E. Induction of oxidative stress, suppression of glucose-induced insulin release, ATP production, glucokinase activity, and histomorphometric changes in pancreatic islets of hypothyroid rat. Eur J Pharmacol 2016; 791:147-156. [PMID: 27568837 DOI: 10.1016/j.ejphar.2016.08.024] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2016] [Revised: 08/24/2016] [Accepted: 08/25/2016] [Indexed: 12/12/2022]
Abstract
Thyroid hormones have important role in metabolism and impairment of glucose metabolism and insulin secretion has been shown in hypothyroid rats but the exact mechanisms for this defect are poorly understood. The aim of this study was to investigate the effect of hypothyroidism on oxidative stress parameters, insulin secretory pathway and histomorphometric changes of pancreas. In the isolated islets of the control and methimazole -treated hypothyroid insulin secretion and content, ATP production, Glucokinase, and hexokinase specific activity and kATP and L-type channels sensitivity were assayed. In order to determine oxidative stress parameters, antioxidant enzymes and lipid peroxidation were measured in pancreatic homogenates. Histomorphometric changes and histochemistry of the islet in both groups were compared. Results showed that plasma glucose and insulin concentration and their area under the curve during IPGTT in hypothyroid group were respectively higher and lower than the controls. In the hypothyroid islets, glucose stimulated insulin secretion, ATP production, hexokinase and glucokinase activities were decreased. Hypothyroid induced a significant increased lipid peroxidation, and decreased the antioxidant enzyme activity. Compared with the control group, insulin antibody positivity, the total volume of the pancreas, islets, and the total number as well as the mean volume of the beta cells were also significantly decreased in the hypothyroid group. These findings indicate that oxidative stress produced under hypothyroidism could have a role in progression of pancreatic β-cell dysfunction, reduced beta cell mass and decreased glucokinase activity, impairing glucose tolerance and insulin secretion.
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Affiliation(s)
- Sepideh Safayee
- Department of Physiology, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Narges Karbalaei
- Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Physiology, Faculty of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Ali Noorafshan
- Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Elham Nadimi
- Histomorphometry and Stereology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
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Javed Z, Sathyapalan T. Levothyroxine treatment of mild subclinical hypothyroidism: a review of potential risks and benefits. Ther Adv Endocrinol Metab 2016; 7:12-23. [PMID: 26885359 PMCID: PMC4740939 DOI: 10.1177/2042018815616543] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Subclinical hypothyroidism (SCH) is defined as elevated thyroid stimulating hormone (TSH) with normal levels of free triiodothyronine (FT3) and free thyroxine (FT4). SCH is further classified into a milder condition with TSH levels between 4.0 and 10.0 milli-international units (mIU)/l (mild-SCH) and a severe form with TSH >10.0 mIU/l (severe-SCH). SCH is a common problem (prevalence is greater in women than men), which increases further with increasing age and TSH levels. Even though the risk of progression to overt hypothyroidism is higher in patients with severe-SCH, the risk is also significant in patients having mild-SCH; it has been suggested that every twofold rise in serum TSH would increase the risk from 1 to 4%, which further increases to 38% if thyroid antibodies are positive. Current data have shown increased cardiovascular risk in patients with mild-SCH and have demonstrated some benefits of levothyroxine treatment in reducing these events. However, evidence on the association of mild-SCH and musculoskeletal system, cognitive dysfunction, mood disorders, dyslipidaemia, diabetes and goitre is conflicting. Similarly, the discussion regarding the exact upper limit of normal for serum TSH remains controversial. The data have also shown increased risk of adverse pregnancy outcomes in patient with mild-SCH, with some benefits of thyroxine treatment. The recent available guidelines related to management of patients with serum TSH <10 mIU/l have suggested decisions should be made taking into account the age of the patient, associated risk factors and comorbid conditions. This chronicle review assesses current evidence regarding the risks associated and the recommendations related to benefits of levothyroxine treatment in patients having mild-SCH.
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Affiliation(s)
- Zeeshan Javed
- Department of Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, University of Hull, Hull and East Yorkshire NHS Trust, Brocklehurst Building, Hull Royal Infirmary, Hull, HU3 2RW, UK
| | - Thozhukat Sathyapalan
- Department of Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, University of Hull, Hull and East Yorkshire NHS Trust, Hull, UK
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Martinez B, Soñanez-Organis JG, Viscarra JA, Jaques JT, MacKenzie DS, Crocker DE, Ortiz RM. Glucose delays the insulin-induced increase in thyroid hormone-mediated signaling in adipose of prolong-fasted elephant seal pups. Am J Physiol Regul Integr Comp Physiol 2016; 310:R502-12. [PMID: 26739649 DOI: 10.1152/ajpregu.00054.2015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2015] [Accepted: 01/04/2016] [Indexed: 12/14/2022]
Abstract
Prolonged food deprivation in mammals typically reduces glucose, insulin, and thyroid hormone (TH) concentrations, as well as tissue deiodinase (DI) content and activity, which, collectively, suppress metabolism. However, in elephant seal pups, prolonged fasting does not suppress TH levels; it is associated with upregulation of adipose TH-mediated cellular mechanisms and adipose-specific insulin resistance. The functional relevance of this apparent paradox and the effects of glucose and insulin on TH-mediated signaling in an insulin-resistant tissue are not well defined. To address our hypothesis that insulin increases adipose TH signaling in pups during extended fasting, we assessed the changes in TH-associated genes in response to an insulin infusion in early- and late-fasted pups. In late fasting, insulin increased DI1, DI2, and THrβ-1 mRNA expression by 566%, 44%, and 267% at 60 min postinfusion, respectively, with levels decreasing by 120 min. Additionally, we performed a glucose challenge in late-fasted pups to differentiate between insulin- and glucose-mediated effects on TH signaling. In contrast to the insulin-induced effects, glucose infusion did not increase the expressions of DI1, DI2, and THrβ-1 until 120 min, suggesting that glucose delays the onset of the insulin-induced effects. The data also suggest that fasting duration increases the sensitivity of adipose TH-mediated mechanisms to insulin, some of which may be mediated by increased glucose. These responses appear to be unique among mammals and to have evolved in elephant seals to facilitate their adaptation to tolerate an extreme physiological condition.
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Affiliation(s)
- Bridget Martinez
- Department of Molecular & Cellular Biology, University of California, Merced, California;
| | - José G Soñanez-Organis
- Departamento de Ciencias Químico Biológicas y Agropecuarias, Universidad de Sonora, Navojoa, Sonora, México
| | - Jose A Viscarra
- Department of Molecular & Cellular Biology, University of California, Merced, California
| | - John T Jaques
- Veterinary Medical Diagnostic Laboratory, Texas A&M University, College Station, Texas
| | - Duncan S MacKenzie
- Department of Biology, Texas A&M University, College Station, Texas; and
| | - Daniel E Crocker
- Department of Biology, Sonoma State University, Rohnert Park, California
| | - Rudy M Ortiz
- Department of Molecular & Cellular Biology, University of California, Merced, California
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Association between thyroid hormones, thyroid antibodies and insulin resistance in euthyroid individuals: A population-based cohort. DIABETES & METABOLISM 2015; 41:480-8. [PMID: 26049821 DOI: 10.1016/j.diabet.2015.04.004] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2014] [Revised: 04/26/2015] [Accepted: 04/27/2015] [Indexed: 02/08/2023]
Abstract
AIM The association between insulin resistance and thyroid function in euthyroid subjects has not yet been clarified. This study aimed to investigate the association between thyroid function within the normal reference range and insulin resistance in participants of the Tehran Thyroid Study (TTS). METHODS This cross-sectional study was conducted within the framework of the TTS. Of 5786 subjects aged ≥ 20 years, 2758 euthyroid subjects free of thyroid disorders, diabetes, chronic kidney disease and cardiovascular disease, and not taking steroids and lipid-lowering agents, were included. Serum concentrations of free thyroxine (FT4) and TSH were measured. The homoeostasis model assessment index for insulin resistance (HOMA-IR) was used to evaluate IR. RESULTS On linear regression analysis, a negative association was found between serum FT4 levels and HOMA-IR in the model with age, smoking and physical activity (B = -0.09, P < 0.001) and in the WC-adjusted model with age, smoking and physical activity for men (B = -0.06, P < 0.01). In addition, there was a positive association between serum TSH levels and HOMA-IR in both models [with age, smoking and physical activity (B = 0.07, P = 0.006), and age, smoking, physical activity and adjusted for WC (B = 0.05, P = 0.01)] that was not more significant on logistic regression analysis. In women, neither serum FT4 nor TSH levels were associated with HOMA-IR; the prevalence of IR decreased from 27.2 to 19.1 with increasing tertiles of FT4 only in men (P = 0.01). No significant differences were observed in HOMA-IR and its components between thyroid peroxidase antibody (TPOAb)-negative and -positive groups. Also, it was found that metabolically healthy but obese (MHO) subjects had higher levels of TSH than individuals who were MONW (metabolically obese but normal weight; P < 0.01). CONCLUSION Low FT4 was independently associated with IR in healthy euthyroid Iranian men.
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Ashwini S, Bobby Z, Joseph M. Mild hypothyroidism improves glucose tolerance in experimental type 2 diabetes. Chem Biol Interact 2015; 235:47-55. [DOI: 10.1016/j.cbi.2015.04.007] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2014] [Revised: 04/01/2015] [Accepted: 04/07/2015] [Indexed: 02/07/2023]
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van Tienhoven-Wind LJN, Dullaart RPF. Low-normal thyroid function and the pathogenesis of common cardio-metabolic disorders. Eur J Clin Invest 2015; 45:494-503. [PMID: 25690560 DOI: 10.1111/eci.12423] [Citation(s) in RCA: 38] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Accepted: 02/12/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND Subclinical hypothyroidism may adversely affect the development of cardiovascular disease (CVD). Less is known about the role of low-normal thyroid function, that is higher thyroid-stimulating hormone and/or lower free thyroxine levels within the euthyroid reference range, in the development of cardio-metabolic disorders. This review is focused on the relationship of low-normal thyroid function with CVD, plasma lipids and lipoprotein function, as well as with metabolic syndrome (MetS), chronic kidney disease (CKD) and nonalcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS This narrative review, which includes results from previously published systematic reviews and meta-analyses, is based on clinical and basic research papers, obtained via MEDLINE and PubMed up to November 2014. RESULTS Low-normal thyroid function could adversely affect the development of (subclinical) atherosclerotic manifestations. It is likely that low-normal thyroid function relates to modest increases in plasma total cholesterol, LDL cholesterol and triglycerides, and may convey pro-atherogenic changes in lipoprotein metabolism and in HDL function. Most available data support the concept that low-normal thyroid function is associated with MetS, insulin resistance and CKD, but not with high blood pressure. Inconsistent effects of low-normal thyroid function on NAFLD have been reported so far. CONCLUSIONS Observational studies suggest that low-normal thyroid function may be implicated in the pathogenesis of CVD. Low-normal thyroid function could also play a role in the development of MetS, insulin resistance and CKD, but the relationship with NAFLD is uncertain. The extent to which low-normal thyroid function prospectively predicts cardio-metabolic disorders has been insufficiently established so far.
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Affiliation(s)
- Lynnda J N van Tienhoven-Wind
- Department of Endocrinology, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands
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Relationship between high normal TSH levels and metabolic syndrome components in type 2 diabetic subjects with euthyroidism. JOURNAL OF CLINICAL AND TRANSLATIONAL ENDOCRINOLOGY 2015; 2:110-113. [PMID: 29204374 PMCID: PMC5685047 DOI: 10.1016/j.jcte.2015.02.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Revised: 01/23/2015] [Accepted: 02/12/2015] [Indexed: 11/09/2022]
Abstract
Objective Thyroid hormones as modulators of adaptive thermogenesis can potentially contribute to development of obesity. The purpose of our study is to observe a relationship between TSH and BMI, blood lipids, BP and HbA1c in type 2 diabetic subjects with euthyroidism. Methods A total of 120 subjects with type 2 diabetes were recruited for this study from November 2012 to June 2014. Subjects were included in the study with TSH values between 0.4 and 4.5 mU/l, who did not take any thyroid medication and had a similar iodine diet. Subjects were weighed and anthropometric indices, lipid parameters, fasting plasma glucose, HbA1c, eGFR, blood pressure (BP) were documented. TSH was measured by an electrochemiluminescence immunoassay. Statistical analysis was performed by using SPSS 18(P value <0.05 was considered significant). Results The mean age of the participants was 60.6 ± 11.6 years with a BMI of 25.3 ± 3.1 kg/m2. Serum TSH levels were significantly and positively associated with BMI, systolic and diastolic BP, serum triglyceride and HbA1c levels, whereas negatively with eGFR. Subjects with a TSH in a higher normal range (2.5–4.5 mU/I, n = 58) had a significantly higher BMI (26.7 ± 3 vs. 24.1 ± 2.7) and this relation remained significant adjusted for age and sex (P < 0.001). When TSH was in low normal range, the number of patients with glycemic goal (HbA1c > 7%) decreased from 27.5% to 12.5% (P = 0.02, adjusted for age and sex). Conclusion In type 2 diabetic subjects with biochemical euthyroidism we found significant association between high normal TSH levels and components of metabolic syndrome. High normal TSH levels were associated with more number of subjects with glycemic goal (HbA1c >7%).
We report TSH levels association with MetS components in type 2 diabetic subjects. Diabetes control was somehow complicated in subjects with high-normal TSH levels. We suggest low normal TSH concentrations in insulin-resistant subjects.
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Key Words
- BMI, body mass index
- Body mass index
- DBP, diastolic blood pressure
- FPG, fasting plasma glucose
- FT3, free triiodothyronine
- HDL-c, high-density lipoprotein cholesterol
- HbA1c, glycated hemoglobin
- Insulin resistance
- LDL-c, low-density lipoprotein cholesterol
- MetS, metabolic syndrome
- Metabolic syndrome
- Obesity
- SBP, systolic blood pressure
- TG, triglyceride
- Thyroid hormones
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van Tienhoven-Wind LJN, Dullaart RPF. Low-normal thyroid function and novel cardiometabolic biomarkers. Nutrients 2015; 7:1352-77. [PMID: 25690422 PMCID: PMC4344592 DOI: 10.3390/nu7021352] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2014] [Revised: 01/16/2015] [Accepted: 02/04/2015] [Indexed: 12/14/2022] Open
Abstract
The concept is emerging that low-normal thyroid function, i.e., either higher thyroid-stimulating hormone or lower free thyroxine levels within the euthyroid reference range, could contribute to the development of atherosclerotic cardiovascular disease. It is possible that adverse effects of low-normal thyroid function on cardiovascular outcome may be particularly relevant for specific populations, such as younger people and subjects with high cardiovascular risk. Low-normal thyroid function probably relates to modest increases in plasma total cholesterol, low density lipoprotein cholesterol, triglycerides and insulin resistance, but effects on high density lipoprotein (HDL) cholesterol and non-alcoholic fatty liver disease are inconsistent. Low-normal thyroid function may enhance plasma cholesteryl ester transfer, and contribute to an impaired ability of HDL to inhibit oxidative modification of LDL, reflecting pro-atherogenic alterations in lipoprotein metabolism and HDL function, respectively. Low-normal thyroid function also confers lower levels of bilirubin, a strong natural anti-oxidant. Remarkably, all these effects of low-normal thyroid functional status appear to be more outspoken in the context of chronic hyperglycemia and/or insulin resistance. Collectively, these data support the concept that low-normal thyroid function may adversely affect several processes which conceivably contribute to the pathogenesis of atherosclerotic cardiovascular disease, beyond effects on conventional lipoprotein measures.
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Affiliation(s)
- Lynnda J N van Tienhoven-Wind
- Department of Endocrinology, University of Groningen and University Medical Center Groningen, Groningen, AV Groningen 19713, The Netherlands.
| | - Robin P F Dullaart
- Department of Endocrinology, University of Groningen and University Medical Center Groningen, Groningen, AV Groningen 19713, The Netherlands.
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Ozdemir D, Dagdelen S, Usman A. Serum Adiponectin Levels and Changes in Glucose Metabolism before and after Treatment for Thyroid Dysfunction. Intern Med 2015; 54:1849-57. [PMID: 26234224 DOI: 10.2169/internalmedicine.54.0668] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVE Adiponectin is an adipokine which is known to decrease in individuals associated with obesity and insulin resistance. In this study, we aimed to investigate the serum adiponectin levels and glucose metabolism in patients with thyroid dysfunction before and after treatment. METHODS Newly diagnosed overt hypothyroid (n=20) and thyrotoxic (n=23) patients and healthy controls (n=20) with a body mass index of <30 kg/m(2) were evaluated prospectively. Patients with a known state of insulin resistance, including prediabetes and overt diabetes, and individuals with chronic diseases were excluded. Thyroid function and fasting plasma glucose (FPG), insulin, homeostatic model assessment (HOMA) insulin resistance (HOMA-IR) and HOMA-beta cell function (HOMA-beta), lipid and adiponectin levels were investigated in the basal state and after the restoration of euthyroidism. RESULTS The basal fasting FPG levels were lower in the hypothyroid patients than the control subjects (p=0.02) and similar between the thyrotoxic patients and control subjects (p=0.127). The basal HOMA-beta levels were higher in the patients with hypothyroidism than in those with thyrotoxicosis (p=0.015). Following the restoration of euthyroidism, the FPG levels significantly increased in the hypothyroid patients (p=0.002) and decreased in the thyrotoxic (p=0.001) patients. The basal plasma adiponectin levels were 14.55±8.4 mcg/mL, 13.79±9.13 mcg/mL and 11.68±6.0 mcg/mL in the hypothyroid and thyrotoxic patients and healthy controls, respectively (p=0.503). The adiponectin levels decreased significantly in the patients with hypothyroidism (p=0.047), whereas they did not change in the patients with thyrotoxicosis (p=0.770) after achieving euthyroidism. CONCLUSION In this study, following the restoration of euthyroidism, the FPG levels increased in the hypothyroidism patients and decreased in the thyrotoxicosis patients, despite the lack of changes in the HOMA-IR and HOMA-beta levels. Meanwhile, the hypothyroid, thyrotoxic and euthyroid subjects had similar basal adiponectin levels, and a significant decrease in the adiponectin levels was observed after treatment for hypothyroidism, despite the absence of changes after treatment for thyrotoxicosis, indicating the need for further studies with a larger sample size.
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Affiliation(s)
- Didem Ozdemir
- Department of Endocrinology and Metabolism, Hacettepe University School of Medicine, Turkey
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