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Liu S, Ma J, Zhang L, Yang Y, Han Z, Tian L. Circulating leptin levels in thyroid dysfunction: a systematic review and meta-analysis. BMC Endocr Disord 2025; 25:140. [PMID: 40481466 PMCID: PMC12142830 DOI: 10.1186/s12902-025-01943-y] [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: 11/17/2024] [Accepted: 04/17/2025] [Indexed: 06/11/2025] Open
Abstract
PURPOSE Leptin is an important regulator of energy homeostasis, analogous to thyroid hormone (TH). The purpose of this study was to investigate circulating leptin levels in thyroid dysfunction (TD) patients and the role of TH levels. METHODS The electronic databases PubMed, Embase, Cochrane Library, and Web of Science were independently searched by two researchers, from inception until February 3, 2024, and updated on February 15, 2025. Pooled standardized mean difference (SMD) with a 95% confidence interval (CI) was calculated by the random effects model. RESULTS Thirty-eight studies reported circulating leptin levels in TD and control with euthyroidism, 4295 subjects were included in total, of which 1277 were hypothyroidism, 540 were hyperthyroidism, and 2478 were control. Compared to euthyroidism, leptin levels were significantly higher in hypothyroidism, and not significantly altered in hyperthyroidism (SMD [95%CI] = 0.71 [0.38, 1.04] and -0.03 [-0.57, 0.51], respectively). The subgroup analysis indicated that, compared to euthyroidism, leptin levels were significantly higher in subjects regardless of overt and subclinical hypothyroidism (SMD [95%CI] = 0.76 [0.25, 1.26] and 0.41 [0.11, 0.70], respectively), and not significantly different in overt hyperthyroidism (SMD [95%CI] = -0.14 [-0.74, 0.45]). Furthermore, when compared to age-, gender-, and body mass index (BMI)-matched euthyroidism, leptin levels were significantly higher in hypothyroidism and had no significant difference in hyperthyroidism (SMD [95%CI] = 0.66 [0.24, 1.07] and -0.43 [-1.13, 0.27], respectively). A total of 16 studies analyzed the correlations between leptin levels and TH levels in TD, 488 were hypothyroidism and 206 were hyperthyroidism. Following correlation analysis, leptin levels displayed a positive correlation with thyroid-stimulating hormone (TSH) levels (r = 0.19) and a negative correlation with triiodothyronine (T3) levels (r = -0.40) in TD. CONCLUSION Compared to euthyroidism, circulating leptin levels were significantly higher in hypothyroidism, and not significantly altered in hyperthyroidism. Besides, leptin levels in TD may be directly regulated by TSH and T3 levels, independent of BMI. TRIAL REGISTRATION CRD42024561055.
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Affiliation(s)
- Shanshan Liu
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, China
- Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, Gansu, 730000, China
- Clinical Research Center for Metabolic Diseases, Lanzhou, Gansu, 730000, China
| | - Jun Ma
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, China
- Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, Gansu, 730000, China
- Clinical Research Center for Metabolic Diseases, Lanzhou, Gansu, 730000, China
| | - Leyuan Zhang
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, China
- Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, Gansu, 730000, China
- Clinical Research Center for Metabolic Diseases, Lanzhou, Gansu, 730000, China
| | - Yanlong Yang
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou, Gansu, 730000, China
- Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, Gansu, 730000, China
- Clinical Research Center for Metabolic Diseases, Lanzhou, Gansu, 730000, China
| | - Ziqi Han
- Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, Gansu, 730000, China
- Clinical Research Center for Metabolic Diseases, Lanzhou, Gansu, 730000, China
| | - Limin Tian
- Department of Endocrinology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610000, China.
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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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He R, Bi H, He J, Luo Y, Li X, Li Q, Huang R, Tan L. Thyroid hormones and oxidative stress moderated the association between urinary phthalate metabolites and cardiovascular risk factors. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2024; 362:124927. [PMID: 39265773 DOI: 10.1016/j.envpol.2024.124927] [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: 05/31/2024] [Revised: 08/25/2024] [Accepted: 09/07/2024] [Indexed: 09/14/2024]
Abstract
While previous studies suggested that phthalate exposure poses a risk to cardiovascular health, the results are mixed and indicated variability based on population characteristics and health outcomes assessed. Research that simultaneously investigates the association between urinary phthalate metabolites and multiple cardiovascular risk factors within a single study is relatively scarce. This study assessed human exposure to phthalates by determining urinary metabolite concentrations, and applied multiple statistical techniques to systematically evaluate the individual dose-response relationships and joint effects of phthalate exposure on blood lipids, blood pressure, and fasting blood glucose. The results revealed significant negative associations between urinary phthalate metabolites and low-density lipoprotein cholesterol, triglycerides, total cholesterol, diastolic blood pressure, systolic blood pressure, and fasting blood glucose. Significant nonlinear associations were obtained between specific individual metabolites and diastolic blood pressure. The oxidative stress biomarker 8-hydroxydeoxyguanosine levels in urine and thyroid hormone levels in paired serum were measured simultaneously. Then, we examined the indirect roles of thyroid hormones and oxidative stress in the association between urinary phthalate metabolites and cardiovascular risk factors by mediation and moderation analysis. While the mediation effect was not statistically significant, the negative associations of urinary phthalate metabolites with fasting blood glucose, triglyceride, and lipoprotein cholesterol were statistically significant at lower levels of thyroid hormones by moderation analysis. The association was also significant under certain levels of oxidative stress. The results demonstrated that phthalate exposure is associated with several cardiovascular risk factors, and maintaining appropriate oxidative stress levels and ensuring sufficient thyroid hormone levels may attenuate these associations.
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Affiliation(s)
- Rong He
- Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, China
| | - Hua Bi
- Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, China
| | - Jia He
- Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, China
| | - Yangxu Luo
- Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, China
| | - Xiaotong Li
- Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, China
| | - Qin Li
- Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, China
| | - Rende Huang
- Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, China
| | - Lei Tan
- Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, China.
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Abbas W, Elmugabil A, Rayis DA, Adam I, Hamdan HZ. Thyroid functions and insulin resistance in pregnant Sudanese women. BMC Endocr Disord 2024; 24:200. [PMID: 39334080 PMCID: PMC11428568 DOI: 10.1186/s12902-024-01739-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND The thyroid function test (free triiodothyronine [FT3], free thyroxine [FT4], and thyroid-stimulating hormone [TSH]) is one of the key determinant of glucose homeostasis by regulating the balance of insulin. Thyroid dysfunction alters glucose metabolism, leading to insulin resistance (IR). This study aimed to assess the association between thyroid function and IR in pregnant Sudanese women. METHOD A cross-sectional study was conducted in Saad Abuelela Hospital, Khartoum-Sudan, from January to April 2021. Obstetric/sociodemographic characteristics were gathered through questionnaires. Serum TSH, FT3, FT4, fasting plasma glucose (FPG), and fasting insulin levels were measured and evaluated, and IR was estimated using the homeostatic model assessment for insulin resistance (HOMA-IR) equation. RESULTS In total, the study included 127 pregnant women with a median age of 27.0 years (interquartile range [IQR] 23.0‒31.2) and a median gestational (IQR) age of 25.0 (IQR 25.0‒27.0) weeks. The medians (IQRs) of the TSH, FT3, and FT4 were 1.600 (1.162‒2.092) IU/ml, 2.020(1.772‒2.240) nmol/l, and 10.70 (9.60‒11.90) pmol/l, respectively. The median (IQR) of the FPG and fasting blood insulin level was [69.0 (62.00‒78.00) mg/dl] and [5.68(2.99‒11.66) IU/ml], respectively. The median (IQR) of the HOMA-IR level was 0.9407 (0.4356‒2.1410). There was a positive correlation between HOMA -IR and FT3 levels (r = 0.375; P < 0.001) and a negative correlation with FT4 levels (r= -0.312; P < 0.001). Also, a significant positive correlation was found between fasting insulin levels and FT3 levels (r = 0.438; P < 0.001) and a negative correlation with FT4 levels (r= -0.305; P < 0.001). CONCLUSIONS This study indicated that FT3 has positive correlation with HOMA-IR, while FT4 has negative correlation among healthy pregnant women without a history of thyroid dysfunction. This may indicate screening of euthyroid pregnant women for thyroid dysfunction and IR. Further studies are needed.
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Affiliation(s)
- Wisal Abbas
- Faculty of Medicine, Kordofan University, Elobeid, Sudan
| | | | - Duria A Rayis
- Faculty of Medicine, University of Khartoum, P.O. BOX: 102, Khartoum, Sudan.
| | - Ishag Adam
- Department of Obstetrics and Gynecology, College of Medicine, Qassim University, Buraidah, Saudi Arabia
| | - Hamdan Z Hamdan
- Department of Pathology, College of Medicine, Qassim University, Buraidah, Saudi Arabia
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Sotiropoulos C, Giormezis N, Pertsas V, Tsirkas T. Biomarkers and Data Visualization of Insulin Resistance and Metabolic Syndrome: An Applicable Approach. Life (Basel) 2024; 14:1197. [PMID: 39337979 PMCID: PMC11433343 DOI: 10.3390/life14091197] [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: 08/07/2024] [Revised: 09/06/2024] [Accepted: 09/19/2024] [Indexed: 09/30/2024] Open
Abstract
Type 2 diabetes, prediabetes, and insulin resistance (IR) are widespread yet often undetected in their early stages, contributing to a silent epidemic. Metabolic Syndrome (MetS) is also highly prevalent, increasing the chronic disease burden. Annual check-ups are inadequate for early detection due to conventional result formats that lack specific markers and comprehensive visualization. The aim of this study was to evaluate low-budget biochemical and hematological parameters, with data visualization, for identifying IR and MetS in a community-based laboratory. In a cross-sectional study with 1870 participants in Patras, Greece, blood samples were analyzed for key cardiovascular and inflammatory markers. IR diagnostic markers (TyG-Index, TyG-BMI, Triglycerides/HDL ratio, NLR) were compared with HOMA-IR. Innovative data visualization techniques were used to present metabolic profiles. Notable differences in parameters of cardiovascular risk and inflammation were observed between normal-weight and obese people, highlighting BMI as a significant risk factor. Also, the inflammation marker NHR (Neutrophils to HDL-Cholesterol Ratio) Index was successful at distinguishing the obese individuals and those with MetS from normal individuals. Additionally, a new diagnostic index of IR, combining BMI (Body Mass Index) and NHR Index, demonstrated better performance than other well-known indices. Lastly, data visualization significantly helped individuals understand their metabolic health patterns more clearly. BMI and NHR Index could play an essential role in assessing metabolic health patterns. Integrating specific markers and data visualization in routine check-ups enhances the early detection of IR and MetS, aiding in better patient awareness and adherence.
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Affiliation(s)
- Christos Sotiropoulos
- Department of Microbiology, School of Medicine, University of Patras, 26504 Patras, Greece;
| | - Nikolaos Giormezis
- Department of Microbiology, School of Medicine, University of Patras, 26504 Patras, Greece;
| | - Vayianos Pertsas
- Informatics Department, University of Economics and Business, 10434 Athens, Greece;
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Zyoud SH, Hegazi OE, Alalalmeh SO, Shakhshir M, Abushamma F, Khilfeh S, Al-Jabi SW. Mapping the global research landscape on nonalcoholic fatty liver disease and insulin resistance: A visualization and bibliometric study. World J Hepatol 2024; 16:951-965. [PMID: 38948442 PMCID: PMC11212647 DOI: 10.4254/wjh.v16.i6.951] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Revised: 04/29/2024] [Accepted: 06/04/2024] [Indexed: 06/20/2024] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a liver condition that is prevalent worldwide and associated with significant health risks and economic burdens. As it has been linked to insulin resistance (IR), this study aimed to perform a bibliometric analysis and visually represent the scientific literature on IR and NAFLD. AIM To map the research landscape to underscore critical areas of focus, influential studies, and future directions of NAFLD and IR. METHODS This study conducted a bibliometric analysis of the literature on IR and NAFLD indexed in the SciVerse Scopus database from 1999 to 2022. The search strategy used terms from the literature and medical subject headings, focusing on terms related to IR and NAFLD. VOSviewer software was used to visualize research trends, collaborations, and key thematic areas. The analysis examined publication type, annual research output, contributing countries and institutions, funding agencies, journal impact factors, citation patterns, and highly cited references. RESULTS This analysis identified 23124 documents on NAFLD, revealing a significant increase in the number of publications between 1999 and 2022. The search retrieved 715 papers on IR and NAFLD, including 573 (80.14%) articles and 88 (12.31%) reviews. The most productive countries were China (n = 134; 18.74%), the United States (n = 122; 17.06%), Italy (n = 97; 13.57%), and Japan (n = 41; 5.73%). The leading institutions included the Università degli Studi di Torino, Italy (n = 29; 4.06%), and the Consiglio Nazionale delle Ricerche, Italy (n = 19; 2.66%). The top funding agencies were the National Institute of Diabetes and Digestive and Kidney Diseases in the United States (n = 48; 6.71%), and the National Natural Science Foundation of China (n = 37; 5.17%). The most active journals in this field were Hepatology (27 publications), the Journal of Hepatology (17 publications), and the Journal of Clinical Endocrinology and Metabolism (13 publications). The main research hotspots were "therapeutic approaches for IR and NAFLD" and "inflammatory and high-fat diet impacts on NAFLD". CONCLUSION This is the first bibliometric analysis to examine the relationship between IR and NAFLD. In response to the escalating global health challenge of NAFLD, this research highlights an urgent need for a better understanding of this condition and for the development of intervention strategies. Policymakers need to prioritize and address the increasing prevalence of NAFLD.
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Affiliation(s)
- Sa'ed H Zyoud
- Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
- Clinical Research Center, An-Najah National University Hospital, Nablus 44839, Palestine.
| | - Omar E Hegazi
- College of Pharmacy and Health Sciences, Ajman University, Ajman 346, United Arab Emirates
| | - Samer O Alalalmeh
- College of Pharmacy and Health Sciences, Ajman University, Ajman 346, United Arab Emirates
| | - Muna Shakhshir
- Department of Nutrition, An-Najah National University Hospital, Nablus 44839, Palestine
| | - Faris Abushamma
- Department of Medicine, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
- Department of Urology, An-Najah National University Hospital, Nablus 44839, Palestine
| | - Shadi Khilfeh
- Department of Medicine, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
- Department of Gastroenterology, Hepatology and Endoscopy, An-Najah National University Hospital, Nablus 44839, Palestine
| | - Samah W Al-Jabi
- Department of Clinical and Community Pharmacy, College of Medicine and Health Sciences, An-Najah National University, Nablus 44839, Palestine
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Diawara MO, Li S, Zhang M, Bigambo FM, Yang X, Wang X, Dong T, Wu D, Yan C, Xia Y. Evaluation of multiple organophosphate insecticide exposure in relation to altered thyroid hormones in NHANES 2007-2008 adult population. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 273:116139. [PMID: 38428240 DOI: 10.1016/j.ecoenv.2024.116139] [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: 12/26/2023] [Revised: 02/12/2024] [Accepted: 02/19/2024] [Indexed: 03/03/2024]
Abstract
The thyroid gland is susceptible to chemical exposure such as organophosphate insecticides (OPIs). With the ubiquitous nature of these products, humans are simultaneously exposed to a multitude of chemicals. This study aimed to evaluate the association between an individual and a mixture of OPI metabolites and changes in serum thyroid hormone (TH) concentrations. The analyzed data were 1,434 participants from the United States National Health and Nutrition Examination Surveys (NHANES) cycle 2007-2008. Generalized linear model (GLM) regression, weighted quantile sum (WQS), and adaptive least absolute shrinkage and selection operator (adaptive LASSO) regression were used to investigate the associations between urinary OPI metabolites and altered serum THs. In GLM, all of the five urinary OPI metabolites were inversely associated with free triiodothyronine (FT3) among the male subjects; meanwhile, higher thyroglobulin (Tg) was related to dimethylphosphate (DMP). Moreover, in WQS models, the metabolite mixture induced FT3 down-regulation (β = -0.209 (95% CI: -0.310, -0.114)), and caused an increased Tg concentration (β = 0.120 (95% CI: 0.024, 0.212)), however, any significant association was observed among female participants. Consistently, the weighted index and LASSO coefficient demonstrated dimethylthiophosphate (DMTP) as the strongest metabolite in the FT3 model (mean weight= 3.449e-01 and β =-0.022, respectively), and dimethylphosphate (DMP) represented the highest association in the Tg model (mean weight= 9.873e-01 and β =-0.020, respectively). Further research is required to confirm our results and investigate the clinical impacts of these disruptions.
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Affiliation(s)
- Massira Ousseni Diawara
- State Key Laboratory of Reproductive Medicine and Offspring Health, Institute of Toxicology, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Songtao Li
- Department of Clinical Laboratory, Children's Hospital of Nanjing Medical University, Nanjing 210008, China
| | - Mingzhi Zhang
- State Key Laboratory of Reproductive Medicine and Offspring Health, Institute of Toxicology, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Francis Manyori Bigambo
- State Key Laboratory of Reproductive Medicine and Offspring Health, Institute of Toxicology, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Xu Yang
- State Key Laboratory of Reproductive Medicine and Offspring Health, Institute of Toxicology, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Xu Wang
- Department of Endocrinology, Children's Hospital of Nanjing Medical University, Nanjing 210008, China
| | - Tianyu Dong
- State Key Laboratory of Reproductive Medicine and Offspring Health, Institute of Toxicology, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Di Wu
- State Key Laboratory of Reproductive Medicine and Offspring Health, Institute of Toxicology, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
| | - Chenghao Yan
- Department of Engineering, University College London, London WC1E 6BT, UK
| | - Yankai Xia
- State Key Laboratory of Reproductive Medicine and Offspring Health, Institute of Toxicology, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
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Dehghani F, Hajhashemy Z, Keshteli AH, Yazdannik A, Falahi E, Saneei P, Esmaillzadeh A. Nutrient patterns in relation to insulin resistance and endothelial dysfunction in Iranian women. Sci Rep 2024; 14:2857. [PMID: 38310135 PMCID: PMC10838277 DOI: 10.1038/s41598-024-53263-1] [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: 03/27/2023] [Accepted: 01/30/2024] [Indexed: 02/05/2024] Open
Abstract
Prior studies have mainly focused on the association of one specific nutrient with insulin resistance (IR) and endothelial dysfunction and limited studies have assessed the association with different nutrient patterns (NPs). We examined the association between various NPs and IR and endothelial dysfunction among Iranian women. This cross-sectional study was carried out on a sample of 368 female nurses. A 106-items food frequency questionnaire (FFQ) was applied for dietary assessments. Using factor analysis, the relationships between NPs and markers of insulin resistance (HOMA-IR, HOMA-β, and QUICKY), and endothelial dysfunction (E-selectin, sICAM-1, and sVCAM-1) were assessed. Mean age and body mass index of participants were respectively 35.21 years and 24.04 kg/m2. Three major NPs were identified. NP1, named as "dairy, fruits, and vegetables" had high values of potassium, folate, vitamins A and C, magnesium, and beta carotene. No significant association was observed between this NP and insulin resistance or endothelial dysfunction indices. The second NP was full of chromium, selenium, copper, vitamin B6, monounsaturated fatty acid (MUFA), thiamin, vitamin D, and iron. Adherence to NP2 (named "legumes, nuts, and protein foods") was associated with lower values of insulin (6.8 ± 1.1 versus 8.4 ± 1.1, P = 0.01), homeostasis model assessment-Insulin resistance (HOMA-IR) (1.3 ± 0.2 versus 1.7 ± 0.2, P = 0.02), and vascular adhesion molecule 1 (VCAM-1) (444.2 ± 27.9 versus 475.8 ± 28.4, P = 0.03). However, adherence to the third NP, rich in saturated fatty acid (SFA), cholesterol, sodium, zinc, vitamin E, and B12, described as "animal fat and meat + vitamin E", was associated with higher amounts of homeostasis model assessment-β (HOMA-β) (531.3 ± 176.2 versus 48.7 ± 179.8, P = 0.03). In conclusion, following the NP2, correlated with higher intakes of chromium, selenium, copper, vitamin B6, MUFA and thiamin was associated with lower values of insulin, HOMA-IR, and sVCAM-1. Adherence to NP3, rich in SFA, cholesterol, vitamin E, vitamin B12, and zinc was associated with higher levels of HOMA-β.
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Affiliation(s)
- Farimah Dehghani
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, P.O. Box 14155-6117, Tehran, Iran
| | - Zahra Hajhashemy
- Department of Community Nutrition, School of Nutrition and Food Science, Nutrition and Food Security Research Center, Isfahan University of Medical Sciences, PO Box 81745-151, Isfahan, Iran
- Students' Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran
| | | | - Ahmadreza Yazdannik
- Department of Critical Care Nursing, School of Nursing and Midwifery, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Ebrahim Falahi
- Department of Nutrition, School of Health and Nutrition, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Parvane Saneei
- Department of Community Nutrition, School of Nutrition and Food Science, Nutrition and Food Security Research Center, Isfahan University of Medical Sciences, PO Box 81745-151, Isfahan, Iran.
| | - Ahmad Esmaillzadeh
- Department of Community Nutrition, School of Nutritional Sciences and Dietetics, Tehran University of Medical Sciences, P.O. Box 14155-6117, Tehran, Iran.
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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The prevalence of subclinical hypothyroidism in a pre-diabetes population and an analysis of related factors. Ann Med 2023; 55:643-651. [PMID: 37074323 PMCID: PMC9970244 DOI: 10.1080/07853890.2023.2178668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND To investigate the prevalence and related influencing factors of subclinical hypothyroidism (SCH) in a pre-diabetes (PreDM) population. PATIENTS AND METHODS A multi-stage stratified cluster random sampling method was used to select the adult Han population in Gansu Province for investigation. General data and related biochemical indices were recorded and SPSS software was used for statistical analyses. RESULTS This study selected 2876 patients, including 548 with SCH and 433 with PreDM. In the PreDM population, the levels of thyroid stimulating hormone (TSH), serum phosphorus, TPOAb and TgAb in the SCH group were higher than those in the euthyroid group (P < 0.05). The level of TPOAb in females of SCH group was higher than that in males (P < 0.05). The positive rates of TPOAb and TgAb in females were higher than those in males in the total population and SCH population. The prevalence of SCH in the PreDM group under 60 was significantly higher than that in the normal glucose tolerance (NGT) group (26.02% vs. 20.40%, χ2 = 5.150, P < 0.05). We defined SCH as a TSH level of >4.20 mIU/L. Using this criterion, the prevalence of SCH in the total population of PreDM was higher than that in the NGT population (χ2 = 8.611, P < 0.05), the prevalence of SCH in the PreDM population generally showed an upward trend. However, we performed a separate analysis considering the accepted impact of age on TSH redefining SCH as TSH >8.86 mIU/L (for individuals over age 65). However, allowing for the expected rise in TSH levels in individuals over age 65, the prevalence of SCH in the elderly over 65 years of age decreased significantly (NGT population from 27.48% to 9.16%, PreDM population from 34.18% to 6.33%, P < 0.05). Logistic regression analysis showed that the risk factors for SCH in the PreDM population were female gender, fasting plasma glucose and TSH (all P < 0.05). Risk factors for SCH in the impaired fasting glucose (IFG) population were female gender, OGTT 2 h, TSH and TPOAb (all P < 0.05). CONCLUSION The prevalence of SCH in the PreDM population not considering the known physiological increase in age related TSH was relatively high and was significant in female and the IFG population. However, the effect of age on these findings needs to attract more attention.
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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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Skowrońska M, Pawłowski M, Milewski R. A Literature Review and a Proposed Classification of the Relationships between Ovulatory Infertility and Lifestyle Factors Based on the Three Groups of Ovulation Disorders Classified by WHO. J Clin Med 2023; 12:6275. [PMID: 37834919 PMCID: PMC10573907 DOI: 10.3390/jcm12196275] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 09/25/2023] [Accepted: 09/27/2023] [Indexed: 10/15/2023] Open
Abstract
Ovulatory infertility is a serious clinical problem whose direct causes are still largely unknown. In addition to pathologies that make it impossible for a couple to establish a pregnancy, there are a number of other factors that have a bearing on fertility, including lifestyle factors, and particularly diet. Although numerous studies have been performed linking such factors to ovulatory infertility, most of them lack the necessary clinical significance, instead focusing on observational data and suggesting or establishing associative relationships. This article consists of a literature review focusing on connections between lifestyle factors such as diet, physical exercise, oxidative stress, sleep, and supplementation, and ovulatory infertility. Special emphasis was given to issues such as obesity and insulin resistance and their mutual relationship with other factors linked to ovulatory infertility. In addition, based on the conclusions of the literature review, the authors have proposed a classification of relationships between ovulation disorders and lifestyle factors in ovulatory infertility within the framework of the WHO classification of ovulation disorders. Furthermore, areas that merit further research have been indicated as well as those that do not. WHO Group II disorders gained prominence in the results of the study as the number of links with lifestyle factors and ovulatory infertility found in the course of the review greatly exceeded those for Groups I and III. The data presented in the article show that the issues of proper diet and physical exercise are those that could benefit from robust clinical studies focused specifically on ovulation infertility, while studies concerning the relationship between oxidative stress, sleep, and supplementation and ovulatory infertility do not seem to be promising directions as far as clinical significance is concerned.
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Affiliation(s)
| | - Michał Pawłowski
- Department of Biostatistics and Medical Informatics, Medical University of Bialystok, 15-089 Bialystok, Poland;
| | - Robert Milewski
- Department of Biostatistics and Medical Informatics, Medical University of Bialystok, 15-089 Bialystok, Poland;
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Rydberg A, Dodoo CA, Schneekloth TD, Abulseoud OA. No difference in COVID-19 treatment outcomes among current methamphetamine, cannabis and alcohol users. J Cannabis Res 2023; 5:23. [PMID: 37337275 DOI: 10.1186/s42238-023-00193-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Accepted: 06/05/2023] [Indexed: 06/21/2023] Open
Abstract
BACKGROUND Poor outcomes of COVID-19 have been reported in older males with medical comorbidities including substance use disorder. However, it is unknown whether there is a difference in COVID-19 treatment outcomes between patients who are current cannabis users, excessive alcohol drinkers and those who use a known hazardous stimulant such as methamphetamine (METH). METHODS Electronic medical records (EMR) of COVID-19 patients with current METH (n = 32), cannabis (n = 46), and heavy alcohol use (n = 44) were reviewed. COVID-19 infection was confirmed by positive SARS-CoV-2 PCR test, current drug use was confirmed by positive urine drug testing, and alcohol use was identified by a blood alcohol concentration greater than 11 mg/dl. Multivariate linear regression models as well as the firth logistic regression models were used to examine the effect of substance use group (METH, cannabis, or alcohol) on treatment outcome measures. RESULTS A total of 122 patients were included in this analysis. There were no significant differences found between drug groups in regards to key SARS-CoV-2 outcomes of interest including ICU admission, length of stay, interval between SARS-CoV-2 positive test and hospital discharge, delirium, intubation and mortality after adjusting for covariates. About one-fifth (21.9% in METH users, 15.2% in cannabis users, and 20.5% in alcohol users) of all patients required ICU admission. As many as 37.5% of METH users, 23.9% of cannabis users, and 29.5% of alcohol users developed delirium (P = 0.4). There were no significant differences between drug groups in COVID-19 specific medication requirements. Eight patients in total died within 10 months of positive SARS-CoV-2 PCR test. Two patients from the METH group (6.3%), two patients from the cannabis group (4.3%), and four patients from the alcohol group (9.1%) died. DISCUSSION The study outcomes may have been affected by several limitations. These included the methodology of its retrospective design, relatively small sample size, and the absence of a COVID-19 negative control group. In addition, there was no quantification of substance use and many covariates relied on clinical documentation or patient self-report. Finally, it was difficult to control for all potential confounders particularly given the small sample size. CONCLUSION Despite these limitations, our results show that current METH, cannabis, and heavy alcohol users in this study have similar treatment outcomes and suffer from high morbidity including in-hospital delirium and high mortality rates within the first-year post COVID-19. The extent to which co-morbid tobacco smoking contributed to the negative outcomes in METH, cannabis, and alcohol users remains to be investigated.
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Affiliation(s)
- Ann Rydberg
- Alix School of Medicine at Mayo Clinic, Phoenix, AZ, 58054, USA
| | | | - Terry D Schneekloth
- Department of Psychiatry and Psychology, Mayo Clinic Arizona, 5777 E Mayo Blvd, Phoenix, AZ, 58054, USA
| | - Osama A Abulseoud
- Department of Psychiatry and Psychology, Mayo Clinic Arizona, 5777 E Mayo Blvd, Phoenix, AZ, 58054, USA.
- Department of Neuroscience, Mayo Clinic Graduate School of Biomedical Sciences, CRB, Scottsdale, AZ, 85259, USA.
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Krysiak R, Kowalcze K, Madej A, Okopień B. The Effect of Metformin on Plasma Prolactin Levels in Young Women with Autoimmune Thyroiditis. J Clin Med 2023; 12:jcm12113769. [PMID: 37297964 DOI: 10.3390/jcm12113769] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 05/25/2023] [Accepted: 05/27/2023] [Indexed: 06/12/2023] Open
Abstract
Metformin decreases elevated prolactin levels, which are frequently found in patients with thyroid disorders. The aim of this study was to investigate whether thyroid autoimmunity modulates the impact of metformin on lactotrope secretory function. This study compared two matched groups of young women with prediabetes and mild-to-moderate prolactin excess: 28 subjects with coexisting euthyroid autoimmune thyroiditis (group 1) and 28 individuals without thyroid disorders (group 2), treated for six months with metformin (3 g daily). Thyroid antibody titers, glucose homeostasis markers, prolactin, thyrotropin, free thyroid hormones, FSH, LH, ACTH, IGF-1 and hsCRP were assessed at the beginning and at the end of the study. At entry, the study groups differed in antibody titers and hsCRP levels. Although the improvement in glucose homeostasis and the decrease in hsCRP levels were observed in both study groups, they were more pronounced in group 2. Only in group 2 did metformin reduce circulating prolactin levels (both total and monomeric). Prolactin-lowering properties of metformin positively correlated with baseline prolactin levels, baseline antibody titers (in group 1) and with the degree of reduction in hsCRP levels. The obtained results suggest that autoimmune thyroiditis may attenuate the impact of metformin on lactotrope secretory function.
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Affiliation(s)
- Robert Krysiak
- Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, 40-752 Katowice, Poland
| | - Karolina Kowalcze
- Department of Pediatrics in Bytom, School of Health Sciences in Katowice, Medical University of Silesia, Stefana Batorego 15, 41-902 Bytom, Poland
| | - Andrzej Madej
- Department of Pharmacology, Faculty of Medicine, University of Technology, Academy of Silesia, Park Hutniczy 3-5, 41-800 Zabrze, Poland
| | - Bogusław Okopień
- Department of Internal Medicine and Clinical Pharmacology, Medical University of Silesia, 40-752 Katowice, Poland
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ERGENÇ H, KARACA OCAK Ö, AKSOY E, ERGENÇ Z. The effects of pathophysiological changes in Type-2 diabetic patients on thyroid dysfunction and nodular goiter development in Turkey. KONURALP TIP DERGISI 2023. [DOI: 10.18521/ktd.1159387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
Objective: The prevalence of thyroid dysfunction is higher in patients with diabetes, and its diagnosis could cause better diabetes management. The purpose of the present study is to examine the impact of pathophysiological changes in patients with Type-2 diabetes on the frequency of thyroid dysfunction, thyroid autoimmunity, thyroid nodule, and thyroid cancer in Turkey.
Methods: The study was conducted on a total of 3.276 patients with Type-2 diabetes who underwent thyroid tests and thyroid ultrasonography (US). The demographic characteristics, biochemical and hormonal values, thyroid US reports, and histopathology reports were collected from the patient's electronic records.
Results: Thyroid autoimmunity positive TPOab 15.9% (n = 524) and/or positive TGab 9.9% (n = 327), the rate of positivity of both antibodies (TPOab + TGab) in the same patient, and total thyroid autoimmunity was found to be 32.57% (n=1067) in Type-2 diabetic patients. Thyroid dysfunction was detected in 18.3% (n = 602) of these patients. The distribution of thyroid dysfunction was 9.09% (n = 298) subclinical hypothyroidism, 4.1% (n = 135) clinical hypothyroidism, 3.1% (n = 102) subclinical hyperthyroidism, 2.0% (n = 67) clinical hyperthyroidism. Also, 67.9% (n = 2225) thyroid nodules, and 5% (n = 164) thyroid cancer were detected.
Conclusion: Thyroid dysfunction was found to have increased in patients with Type-2 diabetes at significant levels.
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Zhou L, Song K, Luo W. Association between circulating resistin levels and thyroid dysfunction: A systematic review and meta-analysis. Front Endocrinol (Lausanne) 2023; 13:1071922. [PMID: 36686437 PMCID: PMC9845899 DOI: 10.3389/fendo.2022.1071922] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 12/12/2022] [Indexed: 01/05/2023] Open
Abstract
Background As a product of adipose tissue, resistin exceeds other adipokines in its role in regulating appetite, energy expenditure, insulin sensitivity, inflammation, and immunity, similar to thyroid hormones. This study aimed to evaluate the association between resistin levels and thyroid dysfunction and to explore variations in circulating resistin levels before and after treatment for thyroid dysfunction. Methods This study was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. A comprehensive search of PubMed, Embase, and Cochrane databases was conducted until June 15, 2022, with no start date restriction, according to the preregistered protocol (PROSPERO-CRD42022336617). RevMan version 5.4 and R software package version 4.2.0 were used for statistical analyses. Results Fourteen studies with 1716 participants were included in this study. The findings of the meta-analysis confirmed that the resistin levels of patients with thyroid dysfunction were significantly higher than those of the euthyroid function control group (mean difference [MD] = 2.11, 95% confidence interval [CI] = 1.11-3.11, P < 0.00001). Furthermore, the resistin levels of patients with hyperthyroidism (MD = 3.23, 95% CI = 0.68-5.79, P = 0.01) and subclinical hypoidism (MD = 1.37, 95% CI = 0.31-2.42, P = 0.01) were significantly higher than those of euthyroid controls. The resistin levels of patients with thyroid dysfunction after treatment were significantly lower than those before treatment (MD = 1.00, 95% CI = 0.34-1.65, P = 0.003), especially in patients with hyperthyroidism (MD = 2.16, 95% CI = 1.00-3.32, P = 0.0003). Correlation analysis confirmed a positive correlation between resistin levels and free triiodothyronine (FT3) levels in patients with thyroid dysfunction (r = 0.27578, P = 0.001). Conclusions Our meta-analysis demonstrates that resistin levels are significantly higher in patients with thyroid dysfunction, and the resistin levels after treatment in patients with thyroid dysfunction are significantly lower than those before treatment. Correlation analysis shows a positive correlation between resistin levels and FT3 levels in patients with thyroid dysfunction. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022336617.
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Affiliation(s)
- Lin Zhou
- Department of Postgraduate, Qinghai University, Xining, China
- Department of Endocrinology, Qinghai Provincial People’s Hospital, Xining, China
| | - Kang Song
- Department of Endocrinology, Qinghai Provincial People’s Hospital, Xining, China
| | - Wei Luo
- Department of Endocrinology, Qinghai Provincial People’s Hospital, Xining, China
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Li M, Zhang J, Yang G, Zhang J, Han M, Zhang Y, Liu Y. Effects of Anterior Pituitary Adenomas' Hormones on Glucose Metabolism and Its Clinical Implications. Diabetes Metab Syndr Obes 2023; 16:409-424. [PMID: 36816815 PMCID: PMC9937076 DOI: 10.2147/dmso.s397445] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 02/02/2023] [Indexed: 02/17/2023] Open
Abstract
Pituitary adenomas have recently become more common and their incidence is increasing yearly. Functional pituitary tumors commonly secrete prolactin, growth hormones, and adrenocorticotropic hormones, which cause diseases such as prolactinoma, acromegaly, and Cushing's disease, but rarely secrete luteinizing, follicle-stimulating, thyroid-stimulating, and melanocyte-stimulating hormones. In addition to the typical clinical manifestations of functional pituitary tumors caused by excessive hormone levels, some pituitary tumors are also accompanied by abnormal glucose metabolism. The effects of these seven hormones on glucose metabolism are important for the treatment of diabetes secondary to pituitary tumors. This review focuses on the effects of hormones on glucose metabolism, providing important clues for the diagnosis and treatment of related diseases.
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Affiliation(s)
- Mengnan Li
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China
- First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China
| | - Jian Zhang
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China
- First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China
| | - Guimei Yang
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China
- First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China
| | - Jiaxin Zhang
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China
- First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China
| | - Minmin Han
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China
- First Clinical Medical College, Shanxi Medical University, Taiyuan, People’s Republic of China
| | - Yi Zhang
- Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China
- Correspondence: Yi Zhang, Department of Pharmacology, Shanxi Medical University, Taiyuan, People’s Republic of China, Email
| | - Yunfeng Liu
- Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China
- Yunfeng Liu, Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China, Tel +86 18703416196, Email
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Zhang Y, Zhang Y, Zhu L, Yu Z, Lu F, Wang Z, Zhang Q. The Correlation Between Health Risk Factors and Diabesity and Lipid Profile Indicators: The Role Mediator of TSH. Diabetes Metab Syndr Obes 2023; 16:1247-1259. [PMID: 37159748 PMCID: PMC10163876 DOI: 10.2147/dmso.s398124] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2022] [Accepted: 03/02/2023] [Indexed: 05/11/2023] Open
Abstract
Introduction Obesity in adults is a problem, particularly when paired with other metabolic abnormalities. Previous research have linked various screening approaches to diabetes, but additional evidence points to the relevance of combining diabetes screening methods with obesity and its effects. This research examined the impact of thyroid hormones (TSHs) and health risk factors (HRFs) in screening for obesity and diabetes in Chinese populations, and whether age can modulate this association. Methods From March to July 2022, the Hefei Community Health Service Center connected with the First Affiliated Hospital of Anhui Medical University was chosen, and the multi-stage cluster sample approach was utilized to test adults aged 21-90 in each community. Latent category analysis (LCA) was performed to investigate the clustering patterns of HRFs. A one-way ANOVA was used to examine waist circumference (WC), biochemical markers, and general data. Furthermore, multivariate logistic regression analysis was utilized to investigate the relationship between health risk variables and WC. Results A total of 750 individuals without a history of major problems who had a community health physical examination were chosen, with missing data greater than 5% excluded. Finally, 708 samples were included in the study with an effective rate of 94.4%. The average WC was (90.0±10.33) cm, the prevalence in the >P75, P50~P75, P25~P50, and ≤P25 groups were 24.7%, 18.9%, 28.7% and 27.7%, respectively. The average TSH was (2.76±2.0) μIU/mL. Male (β=1.91), HOMA-IR (β=0.06), TyG (β=2.41), SBP (β=0.08), TG (β=0.94) and UA (β=0.03) were more likely to have a higher prevalence of WC level. The analyses revealed significant correlations between HRFs, TSH, age, other metabolic indexes and WC (P < 0.05). Discussion Our findings suggest that the quality of metabolic-related indicators used to successfully decrease diabetes in Chinese individuals with high HRFs levels should be prioritized. Comprehensive indicators might be a useful and practical way for measuring the metabolic evolution of diabetes level levels.
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Affiliation(s)
- Yi Zhang
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
| | - Yulin Zhang
- The Second Clinical Medical College, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
| | - Li Zhu
- Department of Endocrinology, Chaohu Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
| | - Zixiang Yu
- The First Clinical Medical College, Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
| | - Fangting Lu
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
| | - Zhen Wang
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
| | - Qiu Zhang
- Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China
- Correspondence: Qiu Zhang, Department of Endocrinology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230022, People’s Republic of China, Email
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Insight into Potential Interactions of Thyroid Hormones, Sex Hormones and Their Stimulating Hormones in the Development of Non-Alcoholic Fatty Liver Disease. Metabolites 2022; 12:metabo12080718. [PMID: 36005590 PMCID: PMC9414490 DOI: 10.3390/metabo12080718] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2022] [Revised: 07/30/2022] [Accepted: 07/31/2022] [Indexed: 02/01/2023] Open
Abstract
Non-Alcoholic Fatty Liver Disease (NAFLD) is a common manifestation of metabolic syndrome. In addition to lifestyle, endocrine hormones play a role in the dysregulation of hepatic metabolism. The most common endocrine hormones contributing to metabolic syndrome are alterations in the levels of thyroid hormones (THs, predominantly in subclinical hypothyroidism) and of sex hormones (in menopause). These hormonal changes influence hepatic lipid and glucose metabolism and may increase hepatic fat accumulation. This review compares the effects of sex hormones, THs and the respective stimulating hormones, Thyroid-Stimulating Hormone (TSH) and Follicle-Stimulating Hormone (FSH), on the development of hepatosteatosis. TSH and FSH may be more relevant to the dysregulation of hepatic metabolism than the peripheral hormones because metabolic changes were identified when only levels of the stimulating hormones were abnormal and the peripheral hormones were still in the reference range. Increased TSH and FSH levels appear to have additive effects on the development of NAFLD and to act independently from each other.
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Fang Y, Wan JP, Zhang RJ, Sun F, Yang L, Zhao SX, Dong M, Song HD. Tpo knockout in zebrafish partially recapitulates clinical manifestations of congenital hypothyroidism and reveals the involvement of TH in proper development of glucose homeostasis. Gen Comp Endocrinol 2022; 323-324:114033. [PMID: 35367205 DOI: 10.1016/j.ygcen.2022.114033] [Citation(s) in RCA: 6] [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: 01/27/2022] [Revised: 03/28/2022] [Accepted: 03/29/2022] [Indexed: 11/26/2022]
Abstract
Congenital hypothyroidism (CH) is a highly prevalent but treatable neonatal endocrine disorder. Thyroid peroxidase (TPO) catalyzes key reactions in thyroid hormone (TH) synthesis. TPO mutations have been found to underlie approximately 5% of congenital hypothyroidism in Chinese patients with more severe phenotypes, the treatment of whom usually requires a higher dose of L-thyroxine. The Tpo gene of zebrafish has 66% homology with the human TPO gene, and synteny analysis has indicated that it is likely a human TPO ortholog. In this study, we generated a tpo-/- mutant zebrafish line through knockout of tpo with CRISPR/Cas9 and investigated the associated phenotypes. Tpo-/- mutant zebrafish displayed growth retardation; an increased number of thyroid follicular cells; and abnormal extrathyroidal phenotypes including pigmentation defects, erythema in the thoracic region, delayed scale development and failure of swim bladder secondary lobe formation. All these abnormal phenotypes were reversed by 30 nM thyroxine (T4) treatment starting at 1 month of age. Tpo-/- mutants also showed increased glucose levels during larval stages, and the increases were induced at least in part by increasing glucagon and decreasing insulin expression. Our work indicates that tpo-mutant zebrafish may serve as a human congenital hypothyroidism model for studying TPO- and TH-related disease mechanisms.
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Affiliation(s)
- Ya Fang
- Department of Molecular Diagnostics & Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Jia-Ping Wan
- Department of Molecular Diagnostics & Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Rui-Jia Zhang
- Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, China
| | - Feng Sun
- Department of Molecular Diagnostics & Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Liu Yang
- Department of Molecular Diagnostics & Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Shuang-Xia Zhao
- Department of Molecular Diagnostics & Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Mei Dong
- Department of Molecular Diagnostics & Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
| | - Huai-Dong Song
- Department of Molecular Diagnostics & Endocrinology, The Core Laboratory in Medical Center of Clinical Research, Shanghai Ninth People's Hospital, State Key Laboratory of Medical Genomics, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
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Fasciolo G, Napolitano G, Aprile M, Cataldi S, Costa V, Ciccodicola A, Di Meo S, Venditti P. Hepatic Insulin Resistance in Hyperthyroid Rat Liver: Vitamin E Supplementation Highlights a Possible Role of ROS. Antioxidants (Basel) 2022; 11:antiox11071295. [PMID: 35883786 PMCID: PMC9311543 DOI: 10.3390/antiox11071295] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 06/26/2022] [Accepted: 06/27/2022] [Indexed: 01/24/2023] Open
Abstract
Thyroid hormones are normally involved in glycaemic control, but their excess can lead to altered glucose metabolism and insulin resistance (IR). Since hyperthyroidism-linked increase in ROS results in tissue oxidative stress that is considered a hallmark of conditions leading to IR, it is conceivable a role of ROS in the onset of IR in hyperthyroidism. To verify this hypothesis, we evaluated the effects of vitamin E on thyroid hormone-induced oxidative damage, insulin resistance, and on gene expression of key molecules involved in IR in the rat liver. The factors involved in oxidative damage, namely the total content of ROS, the mitochondrial production of ROS, the activity of antioxidant enzymes, the in vitro susceptibility to oxidative stress, have been correlated to insulin resistance indices, such as insulin activation of hepatic Akt and plasma level of glucose, insulin and HOMA index. Our results indicate that increased levels of oxidative damage ROS content and production and susceptibility to oxidative damage, parallel increased fasting plasma level of glucose and insulin, reduced activation of Akt and increased activation of JNK. This last result suggests a role for JNK in the insulin resistance induced by hyperthyroidism. Furthermore, the variation of the genes Pparg, Ppara, Cd36 and Slc2a2 could explain, at least in part, the observed metabolic phenotypes.
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Affiliation(s)
- Gianluca Fasciolo
- Dipartimento di Biologia, Università di Napoli Federico II, 80126 Naples, Italy; (G.F.); (S.D.M.)
| | - Gaetana Napolitano
- Dipartimento di Scienze e Tecnologie, Università degli Studi di Napoli Parthenope, Centro Direzionale, Isola C4, 80143 Naples, Italy; (G.N.); (A.C.)
| | - Marianna Aprile
- Institute of Genetics and Biophysics Adriano Buzzati Traverso, National Research Council, Pietro Castellino Street 111, 80131 Naples, Italy; (M.A.); (S.C.); (V.C.)
| | - Simona Cataldi
- Institute of Genetics and Biophysics Adriano Buzzati Traverso, National Research Council, Pietro Castellino Street 111, 80131 Naples, Italy; (M.A.); (S.C.); (V.C.)
| | - Valerio Costa
- Institute of Genetics and Biophysics Adriano Buzzati Traverso, National Research Council, Pietro Castellino Street 111, 80131 Naples, Italy; (M.A.); (S.C.); (V.C.)
| | - Alfredo Ciccodicola
- Dipartimento di Scienze e Tecnologie, Università degli Studi di Napoli Parthenope, Centro Direzionale, Isola C4, 80143 Naples, Italy; (G.N.); (A.C.)
- Institute of Genetics and Biophysics Adriano Buzzati Traverso, National Research Council, Pietro Castellino Street 111, 80131 Naples, Italy; (M.A.); (S.C.); (V.C.)
| | - Sergio Di Meo
- Dipartimento di Biologia, Università di Napoli Federico II, 80126 Naples, Italy; (G.F.); (S.D.M.)
| | - Paola Venditti
- Dipartimento di Biologia, Università di Napoli Federico II, 80126 Naples, Italy; (G.F.); (S.D.M.)
- Correspondence: ; Tel.: +39-081-2535080
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Lubawy M, Formanowicz D. Insulin Resistance and Urolithiasis as a Challenge for a Dietitian. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19127160. [PMID: 35742405 PMCID: PMC9223170 DOI: 10.3390/ijerph19127160] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 06/07/2022] [Accepted: 06/07/2022] [Indexed: 02/01/2023]
Abstract
Many obesity and diet-related diseases have been observed in recent years. Insulin resistance (IR), a state of tissue resistance to insulin due to its impaired function, is a common coexisting condition. The most important predisposing factors are excessive visceral fat and chronic low-grade inflammatory response. However, IR’s pathogenesis is not fully understood. Hence, the diagnosis of IR should be carried out carefully because many different diagnostic paths do not always give equivalent results. An additional disease that is often associated with IR is urolithiasis. The common feature of these two conditions is metabolic acidosis and mild inflammation. A patient diagnosed with IR and urolithiasis is a big challenge for a dietitian. It is necessary to check a thorough dietary history, make an appropriate anthropometric measurement, plan a full-fledged diet, and carry out the correct nutritional treatment. It is also essential to conduct proper laboratory diagnostics to plan nutritional treatment, which is often a big challenge for dietitians. The diet’s basic assumptions are based on the appropriate selection of carbohydrates, healthy fats, and wholesome protein sources. It is also essential to properly compose meals, prepare them, and plan physical activities tailored to the abilities. The study aims to summarise the necessary information on IR with concomitant urolithiasis, which may be helpful in dietary practice.
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El Amrousy D, El-Afify D, Salah S. Insulin resistance, leptin and adiponectin in lean and hypothyroid children and adolescents with obesity. BMC Pediatr 2022; 22:245. [PMID: 35501770 PMCID: PMC9059419 DOI: 10.1186/s12887-022-03318-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 04/25/2022] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Obesity usually complicates hypothyroidism. Adipokines like leptin and adiponectin secreted by adipose tissue modulate insulin resistance (IR), appetite, and obesity. The association between adipokines, IR, and thyroid hormone has not been sufficiently studied in children. We investigated leptin and adiponectin as well as IR and their association with thyroid hormone in both lean and hypothyroid children and adolescents with obesity. METHODS The study included 30 lean hypothyroid, 30 hypothyroid children and adolescents with obesity, and 30 healthy lean children as the control group. Serum thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), fasting blood glucose, fasting insulin, homeostatic model assessment method of insulin resistance (HOMA-IR), leptin, and adiponectin levels were estimated in all participants. RESULTS Fasting insulin, HOMA-IR, and leptin levels were significantly elevated in hypothyroid children compared to the control group; more in hypothyroid children with obesity. In contrast, adiponectin levels were significantly lower in the hypothyroid children with obesity compared to the lean hypothyroid children and controls. HOMA-IR was positively correlated to TSH and BMI but inversely correlated with fT3 and fT4 in hypothyroid children. There was no correlation between IR and either leptin or adiponectin levels. Leptin and adiponectin levels correlated well with BMI in hypothyroid children and adolescents with obesity. CONCLUSION Insulin resistance and leptin levels are increased in hypothyroid children and adolescents; more in those with obesity. IR is not related to leptin and adiponectin levels, however, leptin and adiponectin levels correlate well with BMI in hypothyroid children and adolescents with obesity. IMPACT Insulin resistance (IR) and leptin levels increase in hypothyroid children and adolescent; more with obesity. IR is not related to leptin and adiponectin levels, however leptin and adiponectin levels correlated well with BMI in hypothyroid children and adolescents with obesity.
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Affiliation(s)
- Doaa El Amrousy
- Pediatric Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Dalia El-Afify
- Department of Clinical Pharmacy, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Shaimaa Salah
- Pediatric Department, Faculty of Medicine, Kafrelsheikh University, Kafrelsheikh, Egypt
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Al-Beltagi M, Bediwy AS, Saeed NK. Insulin-resistance in paediatric age: Its magnitude and implications. World J Diabetes 2022; 13:282-307. [PMID: 35582667 PMCID: PMC9052009 DOI: 10.4239/wjd.v13.i4.282] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 03/12/2022] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
Insulin resistance (IR) is insulin failure in normal plasma levels to adequately stimulate glucose uptake by the peripheral tissues. IR is becoming more common in children and adolescents than before. There is a strong association between obesity in children and adolescents, IR, and the metabolic syndrome components. IR shows marked variation among different races, crucial to understanding the possible cardiovascular risk, specifically in high-risk races or ethnic groups. Genetic causes of IR include insulin receptor mutations, mutations that stimulate autoantibody production against insulin receptors, or mutations that induce the formation of abnormal glucose transporter 4 molecules or plasma cell membrane glycoprotein-1 molecules; all induce abnormal energy pathways and end with the development of IR. The parallel increase of IR syndrome with the dramatic increase in the rate of obesity among children in the last few decades indicates the importance of environmental factors in increasing the rate of IR. Most patients with IR do not develop diabetes mellitus (DM) type-II. However, IR is a crucial risk factor to develop DM type-II in children. Diagnostic standards for IR in children are not yet established due to various causes. Direct measures of insulin sensitivity include the hyperinsulinemia euglycemic glucose clamp and the insulin-suppression test. Minimal model analysis of frequently sampled intravenous glucose tolerance test and oral glucose tolerance test provide an indirect estimate of metabolic insulin sensitivity/resistance. The main aim of the treatment of IR in children is to prevent the progression of compensated IR to decompensated IR, enhance insulin sensitivity, and treat possible complications. There are three main lines for treatment: Lifestyle and behavior modification, pharmacotherapy, and surgery. This review will discuss the magnitude, implications, diagnosis, and treatment of IR in children.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Egypt
- Department of Pediatrics, University Medical Center, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
| | - Adel Salah Bediwy
- Department of Chest Disease, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
- Department of Pulmonology, University Medical Center, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Manama 12, Bahrain
- Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Busaiteen 15503, Bahrain
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Interplay between Fatty Acid Binding Protein 4, Fetuin-A, Retinol Binding Protein 4 and Thyroid Function in Metabolic Dysregulation. Metabolites 2022; 12:metabo12040300. [PMID: 35448487 PMCID: PMC9026429 DOI: 10.3390/metabo12040300] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2022] [Revised: 03/24/2022] [Accepted: 03/27/2022] [Indexed: 12/22/2022] Open
Abstract
Signalling between the tissues integrating synthesis, transformation and utilization of energy substrates and their regulatory hormonal axes play a substantial role in the development of metabolic disorders. Interactions between cytokines, particularly liver derived hepatokines and adipokines, secreted from adipose tissue, constitute one of major areas of current research devoted to metabolic dysregulation. The thyroid exerts crucial influence on the maintenance of basal metabolic rate, thermogenesis, carbohydrate and lipid metabolism, while its dysfunction promotes the development of metabolic disorders. In this review, we discuss the interplay between three adipokines: fatty acid binding protein type 4, fetuin-A, retinol binding protein type 4 and thyroid hormones, that shed a new light onto mechanisms underlying atherosclerosis, cardiovascular complications, obesity, insulin resistance and diabetes accompanying thyroid dysfunction. Furthermore, we summarize clinical findings on those cytokines in the course of thyroid disorders.
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Sun L, Goh HJ, Verma S, Govindharajulu P, Sadananthan SA, Michael N, Henry CJ, Goh JPN, Velan SS, Leow MKS. Brown adipose tissues mediate the metabolism of branched chain amino acids during the transitioning from hyperthyroidism to euthyroidism (TRIBUTE). Sci Rep 2022; 12:3693. [PMID: 35256693 PMCID: PMC8901628 DOI: 10.1038/s41598-022-07701-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Accepted: 02/22/2022] [Indexed: 11/09/2022] Open
Abstract
AbstractBoth hyperthyroidism and elevated plasma branched chain amino acids (BCAA) are associated with insulin resistance. BCAA utilization and clearance relative to thyroid status changes remains unclear. We investigate amino acids changes, specifically BCAA, during the transition from hyperthyroidism to euthyroidism, and the impact of active brown adipose tissue (BAT) on the metabolic effects of BCAA. Newly diagnosed Graves’ disease participants were recruited. Hyperthyroidism was treated via a titration dosing regimen of thionamide anti-thyroid drug to establish euthyroidism over 12–24 weeks. All underwent energy expenditure (EE) measurement within a chamber calorimeter, 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging and plasma amino acids measurement during hyperthyroidism and euthyroidism. PET BAT maximum standardized uptake value (SUVmax), SUVmean and MR supraclavicular fat fraction (FF) quantified BAT activity. Twenty-two patients completed the study. Plasma BCAA level was significantly reduced in BAT-positive but not in BAT-negative patients during the transition from hyperthyroidism to euthyroidism. Plasma valine but not leucine and isoleucine correlated positively with insulin and HOMA-IR in hyperthyroidism. Plasma valine, leucine and isoleucine correlated with insulin and HOMA-IR in euthyroidism. Plasma valine correlated with insulin and HOMA-IR in BAT-negative but not in BAT-positive participants in both hyperthyroid and euthyroid state. However, the change (i.e. decrease) in plasma valine concentration from hyperthyroid to euthyroid state was affected by BAT-status. BAT utilizes and promotes BCAA plasma clearance from hyperthyroid to euthyroid state. Active BAT can potentially reduce circulating BCAA and may help to ameliorate insulin resistance and improve metabolic health.Clinical trial registration: The trial was registered at clinicaltrials.gov as NCT03064542.
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Eom YS, Wilson JR, Bernet VJ. Links between Thyroid Disorders and Glucose Homeostasis. Diabetes Metab J 2022; 46:239-256. [PMID: 35385635 PMCID: PMC8987680 DOI: 10.4093/dmj.2022.0013] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Accepted: 02/21/2022] [Indexed: 12/13/2022] Open
Abstract
Thyroid disorders and diabetes mellitus often coexist and are closely related. Several studies have shown a higher prevalence of thyroid disorders in patients with diabetes mellitus and vice versa. Thyroid hormone affects glucose homeostasis by impacting pancreatic β-cell development and glucose metabolism through several organs such as the liver, gastrointestinal tract, pancreas, adipose tissue, skeletal muscles, and the central nervous system. The present review discusses the effect of thyroid hormone on glucose homeostasis. We also review the relationship between thyroid disease and diabetes mellitus: type 1, type 2, and gestational diabetes, as well as guidelines for screening thyroid function with each disorder. Finally, we provide an overview of the effects of antidiabetic drugs on thyroid hormone and thyroid disorders.
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Affiliation(s)
- Young Sil Eom
- Division of Endocrinology, Department of Internal Medicine, Gachon University Gil Medical Center, Gachon University College of Medicine, Incheon, Korea
| | - Jessica R. Wilson
- Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Jacksonville, FL, USA
| | - Victor J. Bernet
- Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Jacksonville, FL, USA
- Corresponding author: Victor J. Bernet https://orcid.org/0000-0002-2477-5631 Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA E-mail:
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27
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Liu J, Li X, Wu J, Chen Y, Li H, Tian Z. Non-diabetic ketoacidosis: A case of alcoholic ketoacidosis accompanied by hyperglycemia. Am J Emerg Med 2021; 52:270.e5-270.e8. [PMID: 34474943 DOI: 10.1016/j.ajem.2021.08.063] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 07/24/2021] [Accepted: 08/23/2021] [Indexed: 11/19/2022] Open
Abstract
Alcoholic ketoacidosis (AKA) lacks specific clinical presentation. The results of blood testing commonly show hemoconcentration, elevated β-hydroxybutyrate levels, and acidosis in patients with AKA. Herein, we report a case of AKA accompanied by hyperglycemia and review the related literature. Case report: AKA associated with hyperglycemia is rare, and its pathogenesis is similar to that of diabetic ketoacidosis, thereby making differentiation challenging. Accordingly, AKA is easily misdiagnosed by endocrinologists. The main symptoms of a 37-year-old female included hyperglycemia, elevated β-hydroxybutyrate levels, and metabolic acidosis. Primary clinical presentations were severe nausea and vomiting. The patient initially diagnosed with DKA were eventually confirmed as AKA, who recovered after active therapy with rehydration and correction of hyperglycemia, electrolyte imbalance, and ketosis. This study provides a reference for clinicians to reduce missed diagnosis and the misdiagnosis rates of AKA.
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Affiliation(s)
- Jiaojiao Liu
- Department of Endocrinology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China; Department of Graduate School, Yan'an University, Yan'an, Shaanxi 716000, China
| | - Xiangshan Li
- Department of Endocrinology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China; Department of Graduate School, Yan'an University, Yan'an, Shaanxi 716000, China
| | - Jiali Wu
- Department of Endocrinology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China; Department of Graduate School, Yan'an University, Yan'an, Shaanxi 716000, China
| | - Yazhuo Chen
- Department of Endocrinology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China; Department of Graduate School, Yan'an University, Yan'an, Shaanxi 716000, China
| | - Heng Li
- Department of Endocrinology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China
| | - Zhufang Tian
- Department of Endocrinology, Xi'an Central Hospital, Xi'an, Shaanxi 710003, China.
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HbA1c is inversely associated with thyroid cysts in a euthyroid population: A cross-sectional study. PLoS One 2021; 16:e0253841. [PMID: 34191857 PMCID: PMC8244890 DOI: 10.1371/journal.pone.0253841] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Accepted: 06/14/2021] [Indexed: 01/27/2023] Open
Abstract
Anti-thyroid peroxidase antibody (TPO-Ab) is revealed to be inversely associated with thyroid cysts among euthyroid population. TPO-Ab causes autoimmune thyroiditis by bolstering thyroid inflammation. Therefore, at least partly, absence of thyroid cysts could indicate latent thyroid damage. Since participants with subclinical hypothyroidism are reported to have higher HbA1c than normal healthy controls, HbA1c could be inversely associated with thyroid cysts through a mechanism reflecting latent thyroid damage. To investigate the association between HbA1c and thyroid cysts among a euthyroid population, a cross-sectional study was conducted on 1,724 Japanese individuals who were within the normal range of thyroid function [i.e., normal range of free triiodothyronine (T3) and free thyroxine (T4)] and aged 40–74 years. Among this study population, 564 were diagnosed with thyroid cysts. Independently of thyroid related hormones [thyroid stimulating hormone (TSH), free T3, and free T4] and known cardiovascular risk factors, HbA1c was found to be significantly inversely associated with the presence of thyroid cysts. This association remained significant even after this analysis was limited to participants within a normal range of TSH. The fully adjusted odds ratios (ORs) of thyroid cysts for 1 standard deviation (SD) increment of HbA1c were 0.84 (0.74, 0.95) for total participants and 0.80 (0.70, 0.92) for participants within a normal range of TSH. Among participants with normal thyroid function, HbA1c was inversely associated with the presence of thyroid cysts. The absence of thyroid cysts and higher levels of HbA1c could indicate the latent functional damage of the thyroid.
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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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Ha J, Lee J, Lim DJ, Lee JM, Chang SA, Kang MI, Kim MH. Association of serum free thyroxine and glucose homeostasis: Korea National Health and Nutrition Examination Survey. Korean J Intern Med 2021; 36:S170-S179. [PMID: 32506867 PMCID: PMC8009147 DOI: 10.3904/kjim.2019.160] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Accepted: 09/07/2019] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND/AIMS Thyroid hormones are involved in wide range of glucose metabolism functions. Overt thyroid dysfunctions are related to altered glucose homeostasis. However, it is not conclusive as to whether subtle changes in thyroid hormones within normal ranges can induce alterations in glucose homeostasis. The aim of this study was to evaluate the association between thyroid hormone and glucose homeostasis parameters in subjects without overt thyroid dysfunction based on nationwide population data. METHODS In the Sixth Korea National Health and Nutrition Examination Survey 2015 (n = 7,380), data were collected from subjects with insulin and thyroid function measurements who were older than 19-years-old. After the exclusion of 5,837 subjects, a total of 1,543 patients were included in the analysis. Subjects were categorized into the quartiles of the free thyroxine (FT4). Fasting glucose, insulin, homeostatic model assessment of insulin resistance and hemoglobin A1c (HbA1c) levels were considered to be glucose homeostasis parameters. RESULTS Subjects with the highest FT4 quartile showed significantly lower fasting insulin and HbA1c levels. A significant inverse correlation FT4 and HbA1c levels was observed (β = -0.261, p = 0.025). In the logistic regression analysis, the highest quartile of FT4 was demonstrated to lower the risk of HbA1c to a greater degree than the median by approximately 40%, after adjusting for confounders, compared to the lowest quartile (p = 0.028). CONCLUSION We demonstrated subjects with a lower FT4 quartile exhibited high risk of HbA1c levels above the median value in a representative Korean population. Subjects with the lowest FT4 quartile should be cautiously managed in terms of altered glucose homeostasis.
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Affiliation(s)
- Jeonghoon Ha
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jeongmin Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Dong-Jun Lim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jung-Min Lee
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sang-Ah Chang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Moo-Il Kang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Min-Hee Kim
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Correspondence to Min-Hee Kim, M.D. Division of Endocrinology and Metabolism, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 1021 Tongil-ro, Eunpyeong-gu, Seoul 03312, Korea Tel: +82-2-961-4537 Fax: +82-2-968-7250 E-mail:
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Răcătăianu N, Leach NV, Bolboacă SD, Soran ML, Opriş O, Dronca E, Valea A, Ghervan C. Interplay between metabolic and thyroid parameters in obese pubertal children. Does visceral adipose tissue make the first move? Acta Clin Belg 2021; 76:40-48. [PMID: 31448702 DOI: 10.1080/17843286.2019.1660021] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Objectives: The mechanisms of obesity-associated thyroid dysfunction in children are incompletely deciphered. We aimed to evaluate whether visceral adipose tissue (VAT), insulin resistance (IR), inflammation, oxidative stress (OS) are involved in thyroid morpho-functional changes in pubertal obese children. Methods: We recruited 43 obese pubertal children without history of thyroid pathology. Metabolic and thyroid parameters (visceral fat thickness [VFT], waist/hip ratio [WHR], waist/height ratio [WHtR], insulin, glucose, liver parameters, thyroid stimulation hormone [TSH], free thyroxine [FT4], free triiodothyronine [FT3], thyroid and abdominal ultrasonography) were evaluated. Serum monocyte chemoattractant protein-1 (MCP-1) and malondialdehyde (MDA) levels were quantified as markers of inflammation and OS. Results: VFT correlated positively both with WHR (p= 0.034) and the presence of thyroid nodules (p= 0.036). WHR associated with TSH (p= 0.005), FT3/FT4 (p= 0.033) and was independently associated with FT3/FT4 increase (p< 0.001). HOMA-IR increased with visceral obesity (waist circumference, p= 0.001; WHR, p= 0.018; WHtR: p< 0.001), hepatic impairment (alanine aminotransferase, p= 0.019) and hepatic steatosis (HS; p= 0.013) and correlated positively with FT3/FT4 (p= 0.036). TSH was significantly higher in subjects with HS versus those without HS (p= 0.007) and logistic regression analysis identified TSH as a risk factor for HS (p= 0.014). MDA correlated positively with MCP-1 (p= 0.021). Conclusion: VAT and IR may be responsible for changes in thyroid parameters associated with obesity: elevated TSH, FT3/FT4 levels and increased prevalence of thyroid nodules. WHR was predictive of increased FT3/FT4. In obese children, there is an interdependent relationship between HS and thyroid function.
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Affiliation(s)
- Nicoleta Răcătăianu
- Department of Endocrinology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Nicoleta V. Leach
- 5th Department of Internal Medicine, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Sorana D. Bolboacă
- Department of Medical Informatics and Biostatistics, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Maria Loredana Soran
- National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj-Napoca, Romania
| | - Ocsana Opriş
- National Institute for Research and Development of Isotopic and Molecular Technologies, Cluj-Napoca, Romania
| | - Eleonora Dronca
- Molecular Sciences Department, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Ana Valea
- Department of Endocrinology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Cristina Ghervan
- Department of Endocrinology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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Kocatürk E, Kar E, Küskü Kiraz Z, Alataş Ö. Insulin resistance and pancreatic β cell dysfunction are associated with thyroid hormone functions: A cross-sectional hospital-based study in Turkey. Diabetes Metab Syndr 2020; 14:2147-2151. [PMID: 33395774 DOI: 10.1016/j.dsx.2020.11.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 11/06/2020] [Accepted: 11/08/2020] [Indexed: 11/20/2022]
Abstract
BACKGROUND AND AIMS The prevalence of thyroid disease in diabetic patients is significantly higher than the general population. This indicates a possible interaction between thyroid functions and insulin sensitivity. This study aimed to investigate the relationship between insulin resistance (IR), pancreatic β cell function, and thyroid function tests. METHODS This cross-sectional study was conducted with adults who applied to Eskişehir Osmangazi University Hospital for general control. Fasting insulin, glucose, TSH, fT3, and fT4 levels in the serum of 1340 adult (18-60 aged) patients without any chronic diseases were examined retrospectively. The fT3/fT4 ratio, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), and HOMA-β values were calculated. The correlation between HOMA-IR and HOMA-β values with thyroid function tests and differences between hormone levels of patients with and without IR were evaluated. RESULTS There was a positive correlation between HOMA-IR and TSH, negative with fT4. Also, a positive correlation between HOMA-β and fT3, negative correlation with fT4 were observed. In the IR group, fT3 levels were found significantly higher and fT4 levels were significantly lower. TSH levels were higher in the IR group but not statistically significant. The fT3/fT4 ratio was found significantly higher in the IR group and was correlated positively with both HOMA-IR and HOMA-β. CONCLUSION Our results revealed that thyroid dysfunction prevalence is quite high in adults who have not yet been diagnosed with diabetes but have insulin resistance and the onset of pancreatic β cell dysfunction.
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Affiliation(s)
- Evin Kocatürk
- Department of Medical Biochemistry, Faculty of Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey.
| | - Ezgi Kar
- Department of Medical Biochemistry, Faculty of Medicine, Çanakkale Onsekiz Mart University, Çanakkale, Turkey.
| | - Zeynep Küskü Kiraz
- Department of Medical Biochemistry, Faculty of Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey.
| | - Özkan Alataş
- Department of Medical Biochemistry, Faculty of Medicine, Eskişehir Osmangazi University, Eskişehir, Turkey.
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Gauthier BR, Sola‐García A, Cáliz‐Molina MÁ, Lorenzo PI, Cobo‐Vuilleumier N, Capilla‐González V, Martin‐Montalvo A. Thyroid hormones in diabetes, cancer, and aging. Aging Cell 2020; 19:e13260. [PMID: 33048427 PMCID: PMC7681062 DOI: 10.1111/acel.13260] [Citation(s) in RCA: 84] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 07/27/2020] [Accepted: 09/13/2020] [Indexed: 12/18/2022] Open
Abstract
Thyroid function is central in the control of physiological and pathophysiological processes. Studies in animal models and human research have determined that thyroid hormones modulate cellular processes relevant for aging and for the majority of age‐related diseases. While several studies have associated mild reductions on thyroid hormone function with exceptional longevity in animals and humans, alterations in thyroid hormones are serious medical conditions associated with unhealthy aging and premature death. Moreover, both hyperthyroidism and hypothyroidism have been associated with the development of certain types of diabetes and cancers, indicating a great complexity of the molecular mechanisms controlled by thyroid hormones. In this review, we describe the latest findings in thyroid hormone research in the field of aging, diabetes, and cancer, with a special focus on hepatocellular carcinomas. While aging studies indicate that the direct modulation of thyroid hormones is not a viable strategy to promote healthy aging or longevity and the development of thyromimetics is challenging due to inefficacy and potential toxicity, we argue that interventions based on the use of modulators of thyroid hormone function might provide therapeutic benefit in certain types of diabetes and cancers.
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Affiliation(s)
- Benoit R. Gauthier
- Department of Cell Therapy and Regeneration Andalusian Center for Molecular Biology and Regenerative Medicine‐CABIMER Junta de Andalucía‐University of Pablo de Olavide‐University of Seville‐CSIC Seville Spain
- Biomedical Research Network on Diabetes and Related Metabolic Diseases‐CIBERDEM Instituto de Salud Carlos III Madrid Spain
| | - Alejandro Sola‐García
- Department of Cell Therapy and Regeneration Andalusian Center for Molecular Biology and Regenerative Medicine‐CABIMER Junta de Andalucía‐University of Pablo de Olavide‐University of Seville‐CSIC Seville Spain
| | - María Ángeles Cáliz‐Molina
- Department of Cell Therapy and Regeneration Andalusian Center for Molecular Biology and Regenerative Medicine‐CABIMER Junta de Andalucía‐University of Pablo de Olavide‐University of Seville‐CSIC Seville Spain
| | - Petra Isabel Lorenzo
- Department of Cell Therapy and Regeneration Andalusian Center for Molecular Biology and Regenerative Medicine‐CABIMER Junta de Andalucía‐University of Pablo de Olavide‐University of Seville‐CSIC Seville Spain
| | - Nadia Cobo‐Vuilleumier
- Department of Cell Therapy and Regeneration Andalusian Center for Molecular Biology and Regenerative Medicine‐CABIMER Junta de Andalucía‐University of Pablo de Olavide‐University of Seville‐CSIC Seville Spain
| | - Vivian Capilla‐González
- Department of Cell Therapy and Regeneration Andalusian Center for Molecular Biology and Regenerative Medicine‐CABIMER Junta de Andalucía‐University of Pablo de Olavide‐University of Seville‐CSIC Seville Spain
| | - Alejandro Martin‐Montalvo
- Department of Cell Therapy and Regeneration Andalusian Center for Molecular Biology and Regenerative Medicine‐CABIMER Junta de Andalucía‐University of Pablo de Olavide‐University of Seville‐CSIC Seville Spain
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Krysiak R, Kowalcze K, Okopień B. Different effects of metformin on hypothalamic‐pituitary‐thyroid axis activity in levothyroxine‐treated and levothyroxine‐naïve women with non‐autoimmune hypothyroidism. J Clin Pharm Ther 2020; 45:1427-1433. [DOI: 10.1111/jcpt.13247] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Revised: 07/14/2020] [Accepted: 07/15/2020] [Indexed: 02/06/2023]
Affiliation(s)
- Robert Krysiak
- Department of Internal Medicine and Clinical Pharmacology Medical University of Silesia Katowice Poland
| | - Karolina Kowalcze
- Department of Pediatrics in Bytom School of Health Sciences in Katowice Medical University of Silesia Katowice Poland
| | - Bogusław Okopień
- Department of Internal Medicine and Clinical Pharmacology Medical University of Silesia Katowice Poland
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Yang Q, Dong Li W, Yan Wan H, Yi Cao H. Association of thyroid hormones with metabolic syndrome and its components in postmenopausal Chinese women. Gynecol Endocrinol 2020; 36:705-708. [PMID: 32285712 DOI: 10.1080/09513590.2020.1749997] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
To evaluate the association between thyroid hormones (TH) and metabolic syndrome (MS) in postmenopausal women (PmW), a cross-sectional study was conducted with a sample of 1000 participants of PmW (40-65 years). Thyroid stimulating hormone (TSH) and free thyroxine (fT4) were evaluated. The MS was defined using the International Diabetes Federation (IDF) ethnicity-specific definitions for Asian. Participants were classified into three groups according to the TSH reference range: high-TSH (≥4.2 mU/L), low-TSH (<0.1mU/L), and normal-TSH (0.1-4.2 mU/L) group. Serum triglycerides (TG) levels were higher in low-TSH group and high-TSH group compared with normal-TSH group (p < .05). The whole sample was stratified into <60 and ≥60 years subgroups. In the ≥60 years group, fT4 was negatively correlated with waist circumference (WC) (p = .028) and positively correlated with fasting blood glucose (FBG) (p = .043), meanwhile TSH was positively correlated with WC only in the control subjects (p = .014). No difference was found between TH and the number of MS components. It was demonstrated that serum fT4 levels were associated with FBG and WC, while TSH was associated with WC in elderly PmW without MS.
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Affiliation(s)
- Qiu Yang
- Division of Endocrinology and Metabolism, Chengdu Fifth People's Hospital, Chengdu, China
| | - Wei Dong Li
- Division of Endocrinology and Metabolism, Chengdu Fifth People's Hospital, Chengdu, China
| | - Hai Yan Wan
- Division of Endocrinology and Metabolism, Chengdu Fifth People's Hospital, Chengdu, China
| | - Hong Yi Cao
- Division of Endocrinology and Metabolism, Chengdu Fifth People's Hospital, Chengdu, China
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Dubey P, Thakur V, Chattopadhyay M. Role of Minerals and Trace Elements in Diabetes and Insulin Resistance. Nutrients 2020; 12:1864. [PMID: 32585827 PMCID: PMC7353202 DOI: 10.3390/nu12061864] [Citation(s) in RCA: 194] [Impact Index Per Article: 38.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2020] [Revised: 06/17/2020] [Accepted: 06/18/2020] [Indexed: 12/15/2022] Open
Abstract
Minerals and trace elements are micronutrients that are essential to the human body but present only in traceable amounts. Nonetheless, they exhibit well-defined biochemical functions. Deficiencies in these micronutrients are related to widespread human health problems. This review article is focused on some of these minerals and trace element deficiencies and their consequences in diabetes and insulin resistance. The levels of trace elements vary considerably among different populations, contingent on the composition of the diet. In several Asian countries, large proportions of the population are affected by a number of micronutrient deficiencies. Local differences in selenium, zinc, copper, iron, chromium and iodine in the diet occur in both developed and developing countries, largely due to malnutrition and dependence on indigenous nutrition. These overall deficiencies and, in a few cases, excess of essential trace elements may lead to imbalances in glucose homeostasis and insulin resistance. The most extensive problems affecting one billion people or more worldwide are associated with inadequate supply of a number of minerals and trace elements including iodine, selenium, zinc, calcium, chromium, cobalt, iron, boron and magnesium. This review comprises various randomized controlled trials, cohort and case-controlled studies, and observational and laboratory-based studies with substantial outcomes of micronutrient deficiencies on diabetes and insulin resistance in diverse racial inhabitants from parts of Asia, Africa, and North America. Changes in these micronutrient levels in the serum and urine of subjects may indicate the trajectory toward metabolic changes, oxidative stress and provide disease-relevant information.
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Affiliation(s)
- Pallavi Dubey
- Department of Obstetrics and Gynecology, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA;
| | - Vikram Thakur
- Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA;
| | - Munmun Chattopadhyay
- Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA;
- Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center El Paso, El Paso, TX 79905, USA
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Manolis AA, Manolis TA, Melita H, Manolis AS. Subclinical thyroid dysfunction and cardiovascular consequences: An alarming wake-up call? Trends Cardiovasc Med 2020; 30:57-69. [DOI: 10.1016/j.tcm.2019.02.011] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 02/14/2019] [Accepted: 02/25/2019] [Indexed: 12/12/2022]
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Palui R, Sahoo J, Kamalanathan S, Kar SS, Sridharan K, Durgia H, Raj H, Patil M. Effect of metformin on thyroid function tests in patients with subclinical hypothyroidism: an open-label randomised controlled trial. J Endocrinol Invest 2019; 42:1451-1458. [PMID: 31127593 DOI: 10.1007/s40618-019-01059-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2019] [Accepted: 05/07/2019] [Indexed: 01/07/2023]
Abstract
PURPOSE Though most of the observational studies have shown that metformin can reduce serum thyroid stimulating hormone (TSH) level in patients of hypothyroidism with diabetes or polycystic ovarian disease, randomised controlled trials are sparse. The primary objective of this study was to evaluate the effect of metformin on thyroid function tests (TSH, free T4, and free T3) in patients with subclinical hypothyroidism (SCH). METHODOLOGY In this open label, parallel arm, randomised controlled trial, 60 patients of SCH (TSH 5.5-10 mIU/L) were randomised to either metformin group (1500 mg/day) or control group. RESULT A total of 46 patients (23 in each group) completed the study and no significant difference in serum TSH, free T4 or free T3 was found in between the 2 groups. Neither there was any significant change in serum TSH, free T4 or free T3 (pre and post 6 months) within the individual groups. However, the rate of normalisation of serum TSH in patients with negative thyroid antibody was significantly higher than patients with positive thyroid antibody (71.4% vs. 18.8%; P = 0.026) in metformin group in post hoc analysis. Fasting plasma glucose, serum high-density lipoprotein and indices of insulin sensitivity significantly improved in metformin group. Four patients (17%) had mild gastrointestinal adverse effects in the metformin group. CONCLUSION We did not find any significant change in thyroid function test in patients with SCH with metformin therapy.
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Affiliation(s)
- R Palui
- Department of Endocrinology, JIPMER, Fourth Floor, Superspeciality Block, Puducherry, 605006, India
| | - J Sahoo
- Department of Endocrinology, JIPMER, Fourth Floor, Superspeciality Block, Puducherry, 605006, India
| | - S Kamalanathan
- Department of Endocrinology, JIPMER, Fourth Floor, Superspeciality Block, Puducherry, 605006, India.
| | - S S Kar
- Department of Preventive and Social Medicine, JIPMER, Puducherry, India
| | - K Sridharan
- Department of Endocrinology, JIPMER, Fourth Floor, Superspeciality Block, Puducherry, 605006, India
| | - H Durgia
- Department of Endocrinology, JIPMER, Fourth Floor, Superspeciality Block, Puducherry, 605006, India
| | - H Raj
- Department of Endocrinology, JIPMER, Fourth Floor, Superspeciality Block, Puducherry, 605006, India
| | - M Patil
- Inlaks Budhrani Hospital, Pune, India
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Houbrechts AM, Beckers A, Vancamp P, Sergeys J, Gysemans C, Mathieu C, Darras VM. Age-Dependent Changes in Glucose Homeostasis in Male Deiodinase Type 2 Knockout Zebrafish. Endocrinology 2019; 160:2759-2772. [PMID: 31504428 DOI: 10.1210/en.2019-00445] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2019] [Accepted: 08/28/2019] [Indexed: 12/13/2022]
Abstract
Thyroid hormones (THs) are crucial regulators of glucose metabolism and insulin sensitivity. Moreover, inactivating mutations in type 2 deiodinase (DIO2), the major TH-activating enzyme, have been associated with type 2 diabetes mellitus in both humans and mice. We studied the link between Dio2 deficiency and glucose homeostasis in fasted males of two different Dio2 knockout (KO) zebrafish lines. Young adult Dio2KO zebrafish (6 to 9 months) were hyperglycemic. Both insulin and glucagon expression were increased, whereas β and α cell numbers in the main pancreatic islet were similar to those in wild-types. Insulin receptor expression in skeletal muscle was decreased at 6 months, accompanied by a strong downregulation of hexokinase and pyruvate kinase expression. Blood glucose levels in Dio2KO zebrafish, however, normalized around 1 year of age. Older mutants (18 to 24 months) were normoglycemic, and increased insulin and glucagon expression was accompanied by a prominent increase in pancreatic islet size and β and α cell numbers. Older Dio2KO zebrafish also showed strongly decreased expression of glucagon receptors in the gastrointestinal system as well as decreased expression of glucose transporters GLUT2 and GLUT12, glucose-6-phosphatase, and glycogen synthase 2. This study shows that Dio2KO zebrafish suffer from transient hyperglycemia, which is counteracted with increasing age by a prominent hyperplasia of the endocrine pancreas together with decreases in hepatic glucagon sensitivity and intestinal glucose uptake. Further research on the mechanisms allowing compensation in older Dio2KO zebrafish may help to identify new therapeutic targets for (TH deficiency-related) hyperglycemia.
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Affiliation(s)
- Anne M Houbrechts
- Laboratory of Comparative Endocrinology, Division of Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium
| | - An Beckers
- Laboratory of Neural Circuit Development and Regeneration, Division of Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium
| | - Pieter Vancamp
- Laboratory of Comparative Endocrinology, Division of Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium
| | - Jurgen Sergeys
- Laboratory of Neural Circuit Development and Regeneration, Division of Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium
| | - Conny Gysemans
- Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism, and Aging, KU Leuven, Leuven, Belgium
| | - Chantal Mathieu
- Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism, and Aging, KU Leuven, Leuven, Belgium
| | - Veerle M Darras
- Laboratory of Comparative Endocrinology, Division of Animal Physiology and Neurobiology, Department of Biology, KU Leuven, Leuven, Belgium
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Abstract
The present analysis aims to investigate the prevalence of thyroid nodules in type 2 diabetes mellitus (T2DM) population. We searched PubMed, EMBASE, and Web of Science from inception to the March 1, 2018. The studies were selected to estimate the prevalence of thyroid nodules in T2DM subjects and to compare the prevalence of thyroid nodules in different glucose tolerance status. The random effects model was used, and the outcome was presented as a pooled prevalence proportion with 95% confidence interval (95% CI) or a summary odds ratio (OR) with 95% CI. In the end, 9 studies met the inclusion criteria and were included in the analysis. The pooled prevalence of thyroid nodules was 60% (95% CI: 0.52, 0.68) for T2DM 2 diabetes patients, 50% (95% CI: 0.48, 0.51) for pre-diabetes, and 43% (95% CI: 0.34, 0.52) for normal glucose tolerance population. Compared with patients without diabetes, diabetes subjects are more likely to develop thyroid nodules, adjusted OR for thyroid nodule was 1.78 (95% CI: 1.25, 2.55). Insulin resistance might be involved in thyroid nodule development.
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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: 37] [Impact Index Per Article: 6.2] [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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Suzuki A, Correia-Santos AM, Vicente GC, Velarde LGC, Boaventura GT. Effects of Maternal Flaxseed Supplementation on Female Offspring of Diabetic Rats in Serum Concentration of Glucose, Insulin, and Thyroid Hormones. INT J VITAM NUTR RES 2019; 89:45-54. [PMID: 30957705 DOI: 10.1024/0300-9831/a000259] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
Objective: This study aimed to evaluate the effect of maternal consumption of flaxseed flour and oil on serum concentrations of glucose, insulin, and thyroid hormones of the adult female offspring of diabetic rats. Methods: Wistar rats were induced to diabetes by a high-fat diet (60%) and streptozotocin (35 mg/kg). Rats were mated and once pregnancy was confirmed, were divided into the following groups: Control Group (CG): casein-based diet; High-fat Group (HG): high-fat diet (49%); High-fat Flaxseed Group (HFG): high-fat diet supplemented with 25% flaxseed flour; High-fat Flaxseed Oil group (HOG): high-fat diet, where soya oil was replaced with flaxseed oil. After weaning, female pups (n = 6) from each group were separated, received a commercial rat diet and were sacrificed after 180 days. Serum insulin concentrations were determined by ELISA, the levels of triiodothyronine (T3), thyroxine (T4) and thyroid-stimulating hormone (TSH) were determined by chemiluminescence. Results: There was a significant reduction in body weight at weaning in HG (-31%), HFG (-33%) and HOG (44%) compared to CG (p = 0.002), which became similar by the end of 180 days. Blood glucose levels were reduced in HFG (-10%, p = 0.044) when compared to CG, and there was no significant difference between groups in relation to insulin, T3, T4, and TSH after 180 days. Conclusions: Maternal severe hyperglycemia during pregnancy and lactation resulted in a microsomal offspring. Maternal consumption of flaxseed reduces blood glucose levels in adult offspring without significant effects on insulin levels and thyroid hormones.
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Affiliation(s)
- Akemi Suzuki
- 1Laboratory of Experimental Nutrition, Department of Nutrition and Dietetics, Fluminense Federal University, Rio de Janeiro, Brazil
| | - André Manoel Correia-Santos
- 1Laboratory of Experimental Nutrition, Department of Nutrition and Dietetics, Fluminense Federal University, Rio de Janeiro, Brazil
| | - Gabriela Câmara Vicente
- 1Laboratory of Experimental Nutrition, Department of Nutrition and Dietetics, Fluminense Federal University, Rio de Janeiro, Brazil
| | - Luiz Guillermo Coca Velarde
- 1Laboratory of Experimental Nutrition, Department of Nutrition and Dietetics, Fluminense Federal University, Rio de Janeiro, Brazil
| | - Gilson Teles Boaventura
- 1Laboratory of Experimental Nutrition, Department of Nutrition and Dietetics, Fluminense Federal University, Rio de Janeiro, Brazil
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iTRAQ-Based Proteomics to Reveal the Mechanism of Hypothalamus in Kidney-Yin Deficiency Rats Induced by Levothyroxine. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2019; 2019:3703596. [PMID: 30949216 PMCID: PMC6425355 DOI: 10.1155/2019/3703596] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/05/2018] [Revised: 01/30/2019] [Accepted: 02/20/2019] [Indexed: 01/16/2023]
Abstract
Kidney-yin deficiency syndrome (KYDS) is a typical syndrome encountered in traditional Chinese medicine (TCM) and is characterized by impaired lipid and glucose homeostasis. The hypothalamus acts as an important regulatory organ by controlling lipid and glucose metabolism in the body. Therefore, proteins in the hypothalamus could play important roles in KYDS development; however, the mechanisms responsible for KYDS remain unclear. Herein, iTRAQ-based proteomics was performed to analyze the protein expression in the hypothalamus of KYDS rats induced by levothyroxine (L-T4). Results revealed a total of 44 downregulated and 18 upregulated proteins in KYDS group relative to the control group. Gene Ontology (GO) analysis revealed that the differently expressed proteins (DEPs) were related to single-organism metabolism process under the biological process (BP), extracellular region part and organelle under the cellular component (CC), and oxidoreductase activity under the molecular function (MF). Kyoto Encyclopedia of Gene and Genomes (KEGG) analysis showed that fatty acid degradation and pyruvate metabolism participated in the metabolism regulation in KYDS rats. RT-PCR validation of five distinctly expressed proteins related to the two pathways was consistent with the results of proteomics analysis. Taken together, the inhibition of fatty acid degradation and pyruvate metabolism in hypothalamus could potentially cause the dysfunction of the lipid and glucose metabolism in KYDS rats. This current study identified some novel potential biomarkers of KYDS and provided the basis for further research of KYDS.
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Venditti P, Reed TT, Victor VM, Di Meo S. Insulin resistance and diabetes in hyperthyroidism: a possible role for oxygen and nitrogen reactive species. Free Radic Res 2019; 53:248-268. [PMID: 30843740 DOI: 10.1080/10715762.2019.1590567] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
In addition to insulin, glycemic control involves thyroid hormones. However, an excess of thyroid hormone can disturb the blood glucose equilibrium, leading to alterations of carbohydrate metabolism and, eventually, diabetes. Indeed, experimental and clinical hyperthyroidism is often accompanied by abnormal glucose tolerance. A common characteristic of hyperthyroidism and type 2 diabetes is the altered mitochondrial efficiency caused by the enhanced production of reactive oxygen and nitrogen species. It is known that an excess of thyroid hormone leads to increased oxidant production and mitochondrial oxidative damage. It can be hypothesised that these species represent the link between hyperthyroidism and development of insulin resistance and diabetes, even though direct evidence of this relationship is lacking. In this review, we examine the literature concerning the effects of insulin and thyroid hormones on glucose metabolism and discuss alterations of glucose metabolism in hyperthyroid conditions and the cellular and molecular mechanisms that may underline them.
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Affiliation(s)
- Paola Venditti
- a Dipartimento di Biologia , Università di Napoli Federico II , Napoli , Italy
| | - Tanea T Reed
- b Department of Chemistry , Eastern Kentucky University , Richmond , KY , USA
| | - Victor M Victor
- c Service of Endocrinology, Dr. Peset University Hospital, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO) , Valencia , Spain.,d Department of Physiology , University of Valencia , Valencia , Spain
| | - Sergio Di Meo
- a Dipartimento di Biologia , Università di Napoli Federico II , Napoli , Italy
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Helaleh M, Diboun I, Al-Tamimi N, Al-Sulaiti H, Al-Emadi M, Madani A, Mazloum NA, Latiff A, Elrayess MA. Association of polybrominated diphenyl ethers in two fat compartments with increased risk of insulin resistance in obese individuals. CHEMOSPHERE 2018; 209:268-276. [PMID: 29933163 DOI: 10.1016/j.chemosphere.2018.06.108] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/03/2018] [Revised: 06/06/2018] [Accepted: 06/15/2018] [Indexed: 06/08/2023]
Abstract
BACKGROUND Polybrominated diphenyl ethers (PBDEs), a widely utilized class of flame retardants in various commercial products, represent a prominent source of environmental contaminants. PBDEs tend to accumulate in adipose tissue, potentially altering the function of this endocrine organ and increasing risk of insulin resistance. The aim of this study was to compare levels of PBDEs in adipose tissues from two metabolically distinct obese groups; the insulin sensitive (IS) and the insulin resistant (IR). METHODS Levels of 28 PBDE congeners were assessed in subcutaneous and omental adipose tissues from 34 obese Qatari individuals (11 IS and 23 IR) using gas chromatography (Trace GC Ultra) coupled to a TSQ Quantum triple Quadrupole mass spectrometer. Correlations of identified PBDEs and mediators of metabolic disease were established and effects of PBDEs treatment on insulin signaling in primary omental preadipocytes were determined. RESULTS Out of 22 detectable PBDEs in subcutaneous and omental adipose tissues, PBDEs 28, 47, 99 and 153 were predominant in omental adipose tissues from obese Qatari subjects. PBDEs 99, 28, and 47 were significantly higher in IR individuals compared to their IS counterparts. Significant positive correlations were identified between PBDEs 28 and 99 in the omental tissues and with fasting insulin levels. When considering PBDEs congeners, penta congeners were also higher in IR compared to IS individuals, while no significant differences were detected in mono, tri, tertra, hexa, hepta and octa congeners between the two studied groups. Treatment of human omental preadipocytes from insulin sensitive individuals with PBDE28 caused inhibition of phosphorylation of GSK3 α/β (Ser21/Ser9), mTOR (Ser2448), p70 S6 kinase (Thr389) and S6 ribosomal protein (Ser235/Ser236) and activation of PTEN (Ser380) phosphorylation, suggesting inhibition of insulin signaling. CONCLUSION This pilot data suggests that accumulation of specific PBDEs in human adipose tissues is associated with insulin resistance in obese individuals. Further investigation of the functional role of PBDEs in the pathology of insulin resistance should help developing therapeutic strategies targeting obese individuals at higher risk.
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Affiliation(s)
- Murad Helaleh
- Anti Doping Laboratory Qatar, Sports City, Doha, Qatar.
| | - Ilhame Diboun
- Department of Economics, Mathematics and Statistics, Birkbeck, University of London, London WC1E 7HX, UK.
| | | | | | | | - Aishah Madani
- Microbiology and Immunology, Weill Cornell Medicine-Qatar, Doha, Qatar.
| | - Nayef A Mazloum
- Microbiology and Immunology, Weill Cornell Medicine-Qatar, Doha, Qatar.
| | - Aishah Latiff
- Anti Doping Laboratory Qatar, Sports City, Doha, Qatar.
| | - Mohamed A Elrayess
- Anti Doping Laboratory Qatar, Sports City, Doha, Qatar; Division of Medicine, University College London, London, UK.
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Hussein MA, Fawzi M, Ibrahim A, Saif A. Thyroid dysfunction and insulin resistance in patients with nonalcoholic fatty liver disease. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2018. [DOI: 10.4103/ejim.ejim_3_18] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Wang CY, Yu TY, Shih SR, Huang KC, Chang TC. Low total and free triiodothyronine levels are associated with insulin resistance in non-diabetic individuals. Sci Rep 2018; 8:10685. [PMID: 30013028 PMCID: PMC6048097 DOI: 10.1038/s41598-018-29087-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2017] [Accepted: 07/05/2018] [Indexed: 01/12/2023] Open
Abstract
This study examined associations of thyroid hormone levels and insulin resistance (IR) in non-diabetic individuals. Using a cross-sectional design, 2007-2008 data from the National Health and Nutrition Examination Survey (NHANES) were analyzed. NHANES participants ≥20 years of age with complete data of interest were included. The homeostatic model assessment (HOMA) was used to quantify IR, and treated as a continuous variable. Self-reported diabetes or a fasting glucose ≥7 mmol/L were used as criteria to exclude diabetic subjects. Race, liver function, obesity, hypertension, dyslipidemia, smoking, physical activity, vigorous recreational activity, 2-hour glucose, hemoglobin A1C (HbA1C), high-density lipoprotein, triglyceride, vitamin D and C-reactive protein were covariates significantly associated with HOMA-IR. A total of 1,560 non-diabetic subjects were included in the analysis. When adjusted for all factors significant in the univariate analysis (race, liver function, obesity, hypertension, dyslipidemia, smoking, physical activity, vigorous recreational activity, 2-hour glucose, HbA1C, high-density lipoprotein, triglyceride, vitamin D, and CRP) low total triiodothyronine (TT3) and low free T3 (FT3) were significantly associated with decreased HOMA-IR (adjusted coefficient = -0.486, 95% confidence interval [CI]: -0.936, -0.036; adjusted coefficient = -1.151, 95% CI: -1.952, -0.350, respectively). Insulin resistance is associated with low thyroid hormone levels in non-diabetic individuals.
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Affiliation(s)
- Chih-Yuan Wang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan.
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, 100, Taiwan.
| | - Tse-Ya Yu
- Health Management Center, Far-Eastern Memorial Hospital, New Taipei City, 222, Taiwan
| | - Shyang-Rong Shih
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, 100, Taiwan
| | - Kuo-Chin Huang
- Department of Family Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan
| | - Tien-Chun Chang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, 100, Taiwan
- Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, 100, Taiwan
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Effect of maternal hypothyroidism during pregnancy on insulin resistance, lipid accumulation, and mitochondrial dysfunction in skeletal muscle of fetal rats. Biosci Rep 2018; 38:BSR20171731. [PMID: 29784871 PMCID: PMC6028760 DOI: 10.1042/bsr20171731] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2017] [Revised: 05/06/2018] [Accepted: 05/21/2018] [Indexed: 01/09/2023] Open
Abstract
The present study aimed to investigate the effect of maternal hypothyroidism during pregnancy on thyroid function of the fetal rat. Female Sprague–Dawley rats were randomized into two groups. Propylthiouracil (PTU) group received PTU in drinking water for 6 weeks (n=90), normal group received normal drinking water (n=50). The pregnant rats were obtained and had a cesarean-section to get at gestational ages of 8.5, 13, and 21 days, following blood samples and skeletal muscle were obtained from fetal rats. Levels of thyroid hormone, insulin, mitochondrial protein, and adipokines were detected using ELISA. Western blotting was performed to analyze mitochondria and insulin signal transduction-related protein in fetal rat skeletal muscle. Immunostaining of Periodic Acid-Schiff (PAS) and Oil Red O was used to observe the accumulation of muscle glycogen and lipid in the fetal rat. The results showed that the levels of thyroid hormone, insulin, insulin signal transduction-related protein, mitochondrial, and adipokines increased with the fetus developed, but had no statistical differences in the PTU group compared with the normal group. In conclusion, pregnant rats with hypothyroidism had no influence on insulin resistance (IR), lipid accumulation, and mitochondrial dysfunction in skeletal muscle of the fetal rats.
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Suga H, Asakura K, Kobayashi S, Nojima M, Sasaki S. Association between habitual tryptophan intake and depressive symptoms in young and middle-aged women. J Affect Disord 2018; 231:44-50. [PMID: 29438897 DOI: 10.1016/j.jad.2018.01.029] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Revised: 12/31/2017] [Accepted: 01/29/2018] [Indexed: 12/17/2022]
Abstract
BACKGROUND The intake of tryptophan, the precursor of serotonin, is assumed to affect serotonin availability and depression onset. Nevertheless, a definitive relationship between dietary tryptophan intake and depressive symptoms has not been established. We examined the association between tryptophan intake and depressive symptoms screened in a group of 4272 first-year female dietetic students and 3651 their mothers. METHODS Dietary tryptophan intake during the preceding month was assessed with a validated, self-administered diet history questionnaire. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D) using two cutoff scores: CES-D score ≥ 16 and CES-D score ≥ 19 (the optimal cutoff score for Japanese people). The multivariate adjusted prevalence ratio (PR) and 95% confidence interval (CI) for depressive symptoms were calculated using Poisson regression analysis. RESULTS The prevalence of depressive symptoms (CES-D score ≥ 16) was 50.0% for young women and 26.5% for middle-aged women. The adjusted PR (95% CI) for depressive symptoms in the highest versus lowest quintile of tryptophan intake was 0.84 (0.75, 0.93) in young women (P for trend < 0.0001) and 0.83 (0.64, 1.01) in middle-aged women (P for trend < 0.0001). These associations were stable even when depressive symptoms were defined as a CES-D score ≥ 19. LIMITATIONS This is a cross-sectional study. Depressive symptoms were assessed using a self-reported questionnaire. CONCLUSIONS This cross-sectional study showed that a higher tryptophan intake was independently associated with a lower prevalence of depressive symptoms in young Japanese women.
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Affiliation(s)
- Hitomi Suga
- Department of Social and Preventive Epidemiology, School of Public Health, The University of Tokyo, Tokyo, Japan.
| | - Keiko Asakura
- Department of Environmental and Occupational Health, School of Medicine, Toho University, Tokyo, Japan
| | - Satomi Kobayashi
- Department of Social and Preventive Epidemiology, School of Public Health, The University of Tokyo, Tokyo, Japan
| | - Masanori Nojima
- Division of Advanced Medicine Promotion, The Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Satoshi Sasaki
- Department of Social and Preventive Epidemiology, School of Public Health, The University of Tokyo, Tokyo, Japan
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Niaz K, Maqbool F, Khan F, Hassan FI, Momtaz S, Abdollahi M. Comparative occurrence of diabetes in canine, feline, and few wild animals and their association with pancreatic diseases and ketoacidosis with therapeutic approach. Vet World 2018; 11:410-422. [PMID: 29805204 PMCID: PMC5960778 DOI: 10.14202/vetworld.2018.410-422] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2017] [Accepted: 02/26/2018] [Indexed: 12/20/2022] Open
Abstract
Diabetes mellitus (DM) is a chronic metabolic disorder in which blood glucose level raises that can result in severe complications. However, the incidence increased mostly by obesity, pregnancy, persistent corpus luteum, and diestrus phase in humans and animals. This review has focused on addressing the possible understanding and pathogenesis of spontaneous DM in canine, feline, and few wild animals. Furthermore, pancreatic associated disorders, diabetic ketoacidosis, hormonal and drug interaction with diabetes, and herbal remedies associated with DM are elucidated. Bibliographic search for the present review was done using PubMed, Scopus, and Google Scholar for articles on concurrent DM in small and wild animals. Persistent corpus luteal and pseudopregnancy in female dogs generate gestational DM (GDM). GDM can also be caused by extensive use of drugs/hormones such as glucocorticosteroids. Although many similarities are present between diabetic cats and diabetic humans which present islet amyloidosis, there was a progressive loss of β- and α-cells and the normal number of δ-cells. The most prominent similarity is the occurrence of islet amyloidosis in all cases of diabetic cat and over 90% of human non-insulin dependent DM Type-2. Acute pancreatic necrosis (APN) occurs due to predisposing factors such as insulin antagonism, insulin resistance, alteration in glucose tolerance, obesity, hyperadrenocorticism, and persistent usage of glucocorticoids, as these play a vital role in the progression of APN. To manage such conditions, it is important to deal with the etiological agent, risk factors, diagnosis of diabetes, and hormonal and drug interaction along with its termination with suitable therapy (herbal) protocols. It should be noted that the protocols used for the diagnosis and treatment of human DM are not appropriate for animals. Further investigations regarding diabetic conditions of pets and wild animals are required, which will benefit the health status of all animals health worldwide.
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Affiliation(s)
- Kamal Niaz
- Department of Toxicology and Pharmacology, International Campus, Tehran University of Medical Sciences, Tehran, Iran
- The Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Faheem Maqbool
- Department of Toxicology and Pharmacology, International Campus, Tehran University of Medical Sciences, Tehran, Iran
- The Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Fazlullah Khan
- Department of Toxicology and Pharmacology, International Campus, Tehran University of Medical Sciences, Tehran, Iran
- The Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatima Ismail Hassan
- Department of Toxicology and Pharmacology, International Campus, Tehran University of Medical Sciences, Tehran, Iran
- The Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Saeideh Momtaz
- Department of Toxicology and Pharmacology, International Campus, Tehran University of Medical Sciences, Tehran, Iran
- The Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Abdollahi
- Department of Toxicology and Pharmacology, International Campus, Tehran University of Medical Sciences, Tehran, Iran
- The Institute of Pharmaceutical Sciences, Tehran University of Medical Sciences, Tehran, Iran
- Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
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