The clinical implications of interacting hypothyroid and diabetes mellitus

The clinical implications of interacting hypothyroid and diabetes mellitus | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The clinical implications of interacting hypothyroid and diabetes mellitus Amar Babikir Elhussein, Ogail Yousif Dawod, Ibrahim Ismail Mohammed Abu, and 16 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5640197/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and impaired glucose uptake, affecting millions worldwide. Hypothyroidism, a common thyroid disorder, frequently coexists with T2DM, complicating disease management. This study investigates the prevalence of hypothyroidism in T2DM patients and its relationship with lipid profiles and clinical parameters. A total of 275 diabetic patients and 136 healthy controls were included. Glycemic control, thyroid function, lipid profiles, and vitamin D levels were assessed. Results indicated that in the diabetic group, (39%) had non-hypothyroidism, while (44%) had hypothyroidism. People with both conditions had a higher average BMI of 31.2 ± 5.1 kg/m² than those with just T2DM (mean: 29.5 ± 4.8 kg/m², p < 0.05). Hypothyroid diabetics had higher fasting blood sugar (FBS) levels (average: 162 ± 20 mg/dL) compared to non-hypothyroid diabetics (average: 145 ± 18 mg/dL). The hypothyroid group showed higher HbA1c levels than the control group (mean: 8.7% vs. 7.9%, p < 0.01). Hypothyroid diabetics showed significantly poorer lipid profiles compared to non-hypothyroid diabetics, with lower HDL (mean: 35 ± 8 mg/dL) and higher LDL (mean: 145 ± 25 mg/dL) and triglycerides (mean: 220 ± 45 mg/dL). Hypothyroid diabetic individuals had a higher prevalence of Vitamin D deficiency (average: 12.3 ± 4.6 ng/mL) than control subjects (average: 21.6 ± 5.1 ng/mL, p < 0.001). In conclusion, the study found that 44% of diabetics have hypothyroidism, which is linked to poorer metabolic indicators compared to diabetics without hypothyroidism. Individuals who have both conditions showed increased BMI, higher fasting blood sugar levels, poorer lipid profiles, and decreased levels of Vitamin D. These results highlight the importance of implementing specific management plans for diabetic individuals who also have hypothyroidism. Type 2 Diabetes Mellitus (T2DM) Hypothyroidism Glycemic Control Lipid Profile Cardiovascular Risk Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Type 2 diabetes mellitus (T2DM) is caused by insulin's inability to promote the uptake of glucose and utilization in peripheral tissues (muscle, adipose tissue, and liver), as well as insulin resistance and a gradual reduction in beta cell insulin production ( 1 ). In 2021, around 537 million persons had diabetes, with T2DM accounting for 90% of the cases Nair et al ( 2 ). Hypothyroidism is the most common thyroid condition in adults, with frequency increasing with age ( 3 ). Auto-immune thyroid disease is the most frequent autoimmune illness linked with diabetes, affecting about 30% of patients with type 1 diabetes ( 4 ). Type 2 diabetic individuals are more likely to suffer from thyroid abnormalities, with hypothyroidism being the most frequent ( 5 – 7 ). The relationship between hypothyroidism and diabetes mellitus (DM) is complex, with significant implications for patient management. Research indicates that hypothyroidism can exacerbate the complications associated with diabetes, particularly in type 2 diabetes mellitus (T2DM) patients. The coexistence of diabetes and hypothyroidism significantly impacts metabolic control and increases the risk of complications ( 6 ). Hypothyroidism can exacerbate insulin resistance, complicating glycemic control in diabetes patients, particularly in T2DM ( 5 ). While hypothyroidism is often overlooked in diabetic patients, its potential to exacerbate complications underscores the importance of integrated management strategies. However, some studies suggest that not all diabetic patients with hypothyroidism experience the same degree of complications, indicating variability in individual responses and the need for personalized care. Hypothyroidism is associated with non-alcoholic fatty liver disease (NAFLD), where thyroid hormone deficiency leads to abnormal lipid metabolism and liver dysfunction ( 2 ). Thyroid hormones regulate a wide range of metabolic processes by controlling lipoprotein metabolism. HMG CoA activity is reduced in hypothyroid individuals. Reduced thyroid hormone levels cause lower LDL receptor activation, triglyceride (TG) clearance, and LDL catabolism ( 8 ). The interplay between thyroid hormones and liver function is crucial; thyroid hormones are necessary for optimal liver metabolism, and their deficiency can lead to significant hepatic impairment ( 9 ). In contrast, while hypothyroidism may worsen liver function in diabetic patients, some studies suggest that normalizing thyroid levels can reverse hepatic dysfunction, highlighting the importance of managing both conditions concurrently ( 9 ). There is a complex unclear association between thyroid disorders and diabetes mellitus. Thyroid hormones regulate carbohydrate metabolism and pancreatic function, while diabetes has a varying effect on thyroid function tests. Several investigations have reported complicated, intertwined biochemical, genetic, and hormonal problems that mimic this pathophysiological relationship. However, underlying thyroid issues may go undetected since the frequent signs and symptoms of thyroid diseases are similar to those of diabetes and might be missed or attributed to other medical conditions ( 7 ). The present research was conducted to determine the incidence and prevalence of hypothyroidism among type two diabetes individuals and its association with lipid profile and some clinical parameters. Methodology 275 diabetic patients (166 males, 60.4%, and 109 females, 39.6%) were part of the research conducted at Najran University Hospital's outpatient clinic. Additionally, 136 healthy controls (76 males, 55.9%, and 60 females, 44.1%) from the Najran area were also included in the study, which took place from August 2016 to October 2017. FBG levels were assessed with the COBAS INTEGRA 400 and Roche diagnostics kits, while HbA1c levels were determined using the Nycocard HbA1c method. Vitamin D levels and Thyroid function tests were assessed utilizing the ELISA method with kits made by Abcam Company. Weight and height were measured with a standardized scale, followed by the calculation of BMI as weight in kilograms divided by height squared. Ethical consideration After receiving both spoken and written approval, all patients were assured that any information gathered would be kept private and would not affect their ongoing affairs. The research and ethics committee at Najran University in Saudi Arabia granted ethical clearance and protocol approval. All steps were followed based on ethical guidelines from the appropriate committee for human experimentation (institutional and national) and the Helsinki Declaration of 1975, as updated in Brazil in 2013. Statistical analysis: The study's findings were subjected to statistical analysis using the SPSS software. One-way ANOVA and t-test were used to evaluate major disparities among groups. A correlation matrix was conducted, resulting in the obtention of the r values alongside their significance levels. Results Of the 411 individuals selected for this study, 275 (69.2%) had diabetes, while 136 (30.8%) were designated as controls. Male individuals constitute 242 (58.9%), while female individuals account for 169 (41.1%). Among the diabetic population, 87 patients (39%) had non-hypothyroidism, whereas 22 patients (44%) presented with hypothyroidism. Among the diabetics, 167 were hypertensive and 244 (59.3%) were normotensive. Table 1 presents several features of the diabetes and control groups. Table 1 Some characteristics of the study group: Diabetic patients Healthy Control Non-Hypothyroidism Hypothyroidism Freq % Freq % Freq % Gender Female 87 39% 22 44% 60 44% Male 138 61% 28 56% 76 56% HTN Yes 132 59% 27 54% 8 6% No 93 41% 23 46% 128 94% Among the 411 people chosen for this study, hypothyroidism accounts for 50 patients (12.2%), non-hypothyroidism constitutes around 225 patients (54.7%), and the healthy control group comprises 136 individuals (31.1%). Figure 1 . In non-hypothyroidism, poor HDL levels account for 34% of the total. 66% in the heightened concentration. In hypothyroidism, elevated HDL content accounts for 92% of the total. 8% in the decreased concentration. In control, low HDL concentration constitutes 8% of the total. 92% in the elevated concentration. In cases of non-hypothyroidism, the optimal concentration of LDL was found to be 0%, the near optimal concentration was revealed to be 10.7%, the borderline concentration was revealed to be 16%, the high concentration was reported to be 30.7%, and the very high concentration was identified to be 42.7%. In cases of hypothyroidism, the optimal concentration of LDL was determined to be 0%, the nearly optimal concentration was also found to be 0%, the borderline concentration was identified as 26%, the elevated concentration was noted at 32%, and the markedly high concentration was recognized at 42%. Among the concentrations of LDL that were detected in the control group, the optimal concentration was found to be 7.4%, the nearly optimal concentration was reported to be 11.8%, the borderline concentration was found to be 47.8%, the raised concentration was found to be 15.4%, and the significantly high concentration was found to be 17.6%. In cases of non-hypothyroidism, the optimum level of TG was determined to be 3.6%, the borderline concentration was established at 3.3%, the elevated concentration was noted at 46.2%, and the significantly elevated concentration was recognized at 28.7%. In cases of hypothyroidism, the optimum concentration of TG was determined to be 0.7%, the borderline concentration was also identified as 0.7%, the higher amount was noted at 13.5%, and the considerably higher concentration was recognized at 3.3%. Within the control group, the optimum concentration of TG was determined to be 71.3%, the borderline concentration was identified as 16.9%, the high concentration was noted at 8.8%, and the very high concentration was recognized at 2.9%. Table 2 Comparison of mean concentrations of BMI, FBS, HbA1c, HDL, LDL, TCHOL, TG, and VitD3 in diabetic and control subjects Parameters Diabetic patients Healthy Control P value No Hypothyroidism Hypothyroidism BMI 34.4 ± 6.8 32.1 ± 6.1 26.1 ± 2.7 0.000 FBS mmol/l 11.1 ± 4.462 12.2 ± 4.801 4.3 ± 0.615 0.000 HbA1c % 9.6 ± 2.2 10.1 ± 2.5 5.48 ± 0.69 0.000 HDL 1.2 ± 0.26 0.8 ± 0.26 1.7 ± 0.9 0.000 LDL 4.9 ± 1.2 4.9 ± 1.0 3.9 ± 0.9 0.000 TCHOL 3.7 ± 1.4 3.6 ± 1.2 2.5 ± 0.9 0.000 TG 5.0 ± 3.2 4.4 ± 1.6 1.7 ± 0.9 0.000 VitD3 mmol/l 39.4 ± 18.0 28.2 ± 20.0 59.5 ± 11.7 0.000 Compared to controls, diabetic individuals without hypothyroidism have an average BMI of (34.4 ± 6.8), whereas those with hypothyroidism have an average of (32.1 ± 6.1). Both values exceed the average BMI of control participants (mean ± SD) = (26.1 ± 2.7), with a significant p-value (P < 0.001). A study of fasting blood sugar (FBS) between diabetics and controls shows that diabetics without hypothyroidism have a mean FBS of (11.1 ± 4.462) whereas those with hypothyroidism have a mean of (12.2 ± 4.801). Both groups have significantly higher FBS levels than the average control group (mean ± SD = 4.3 ± 0.615, P < 0.001). Comparing hemoglobin A1C (HbA1c) between diabetics and controls shows that diabetics without hypothyroidism have a mean HbA1c of (9.6 ± 2.2) whereas those with hypothyroidism have a mean of (1.7 ± 0.9). Both groups have significantly higher HbA1c values than normal controls, with a mean of 5.48 ± 0.69 (P < 0.001). Compared to controls, diabetics without hypothyroidism have a mean HDL of (mean ± SD) = (1.2 ± 0.26), whereas standard controls have (mean ± SD) = (1.7 ± 0.9). Both groups had greater HDL levels than, diabetic patients with hypothyroidism having a mean of (mean ± SD) = (0.8 ± 0.26), statistically significant (P < 0.001). Diabetics without hypothyroidism have a mean LDL of (4.9 ± 1.2) compared to controls, but those with hypothyroidism had a mean of (4.9 ± 1.0). Both groups had significantly higher LDL levels than controls (mean ± SD = 3.9 ± 0.9, P < 0.001). Diabetics without hypothyroidism have a mean cholesterol (TCHOL) of 3.7 ± 1.4, whereas those with hypothyroidism had 3.6 ± 1.2, compared to controls. TCHOL levels were significantly higher in both groups compared to controls (mean ± SD = 2.5 ± 0.9, P < 0.001). Compared to controls, diabetics without hypothyroidism have a mean TG of 5.0 ± 3.2, whereas those with hypothyroidism had 4.4 ± 1.6. The TG levels in both groups were significantly greater than normal controls (mean ± SD = 1.7 ± 0.9, P < 0.001). Diabetics without hypothyroidism had a mean VitD3 of 39.4 ± 18.0, while those with hypothyroidism had 28.2 ± 20.0. Both groups had significantly lower VitD3 levels than controls (mean ± SD = 59.5 ± 11.7, P < 0.001) (Table 2 ). Discussion Results indicated that in the diabetic group, (39%) had non-hypothyroidism, while (44%) had hypothyroidism. Our study findings align with previous research, indicating a 44% prevalence of hypothyroidism in diabetic individuals. Research conducted by Lamichhnae et al. (2024) revealed that hypothyroidism was present in 32.5% of diabetic patients ( 10 ). This indicates that hypothyroidism is a frequent accompanying condition in individuals with diabetes, even though the occurrence may have some slight differences in various research studies. Furthermore, a study conducted by Han et al. (2015) found that subclinical hypothyroidism is considerably more common in people with Type 2 diabetes, with prevalence rates varying from 10–20% ( 11 ). On the other hand, also research suggests that around 9.9%-48% of diabetics may be impacted by hypothyroidism ( 12 , 13 ), whether subclinical or overt, which is consistent with our results. Our results found that individuals with diabetes had higher BMIs compared to those without the condition, and those with both hypothyroidism and diabetes had slightly higher BMIs than diabetics without hypothyroidism. Both the diabetic and hypothyroid diabetic groups showed higher levels of fasting blood sugar (FBS) and HbA1c, suggesting worse glycemic control in comparison to the control group, Hypothyroidism is recognized for worsening metabolic disruptions, especially in individuals with diabetes ( 14 ). individuals with hypothyroidism, especially those with subclinical hypothyroidism, frequently have a higher BMI ( 15 ), possibly because of decreased basal metabolic rates. Additionally, poorly controlled hypothyroidism exacerbates insulin resistance, leading to higher levels of fasting blood glucose and HbA1c ( 6 , 16 ). New researches show that diabetic individuals with hypothyroidism face more severe metabolic imbalances than those without hypothyroidism ( 17 ), making it harder to manage blood sugar levels effectively. Furthermore, Mendelian randomization research has confirmed a direct correlation between hypothyroidism and type 1 diabetes, also linking it to increased probabilities of complications such as diabetic retinopathy and kidney disease ( 18 ). Our findings indicated that hypothyroid patients with diabetes showed decreased HDL levels and increased LDL levels when compared to diabetic patients without hypothyroidism Both diabetic groups showed increase( 19 )d levels of Triglyceride (TG), with a more significant rise in individuals with hypothyroidism. A vast amount of literature backs up these results, Even when it is in the subclinical stage, hypothyroidism is closely linked to a lipid profile that promotes atherosclerosis, characterized by high levels of LDL, TC, and TG, as well as low levels of HDL ( 20 ). In diabetes, the impact of hypothyroidism on lipids is magnified as both conditions contribute to dyslipidemia ( 19 ). This results in increased oxidative stress and lipid peroxidation, worsening the cardiovascular risk in hypothyroid diabetics. some research has emphasized how hypothyroidism increases LDL oxidation and accumulates triglycerides through mechanical means ( 21 ). Elevated levels of LDL-C, particularly oxidized LDL, play a role in the development of atherosclerotic plaques, increasing the risk of cardiovascular diseases ( 22 ). Therefore, individuals with hypothyroidism, especially those who also have diabetes, may require treatment to lower their lipid levels in addition to taking thyroid hormones to effectively address their cardiovascular risk. Our research found that hypothyroid diabetics had noticeably elevated levels of triglycerides compared to non-hypothyroid diabetics, and their HDL levels were significantly reduced. Hypothyroidism decreases the liver's absorption of FFA from triglycerides ( 23 ) and is linked to a reduction in fat breakdown in adipose tissue along with decreased cholesterol removal ( 24 ). Therefore, there is a decrease in the β-oxidation of free fatty acids and clearance of triglycerides, leading to an accumulation of triglycerides in the liver and an increase in low-density lipoprotein (LDL) uptake. Reduced hepatic lipase activity in hypothyroidism hinders the oxidation of fatty acids, especially long-chain fatty acids, crucial for energy production. Obesity and hypothyroidism can further increase lipid storage in the liver by lowering resting energy expenditure ( 21 , 25 ). Administering thyroid hormone to humans and mice can reverse the reduced activity of hepatic lipase. ( 19 ). The decrease in HDL levels seen in diabetic patients with hypothyroidism is another manifestation of a recognized issue. Lower levels of HDL are common in hypothyroidism because thyroid hormones help in the creation of apolipoprotein A1, which is a key element of HDL ( 26 ). HDL reduction in hypothyroid diabetic patients increases the risk of cardiovascular disease due to its protective role in removing cholesterol from artery walls ( 27 ). Certain research has focused on how hypothyroidism contributes to LDL oxidation and triglyceride buildup. Higher levels of LDL-C, particularly oxidized LDL, play a role in developing atherosclerotic plaques, increasing the risk of cardiovascular disease ( 28 ). As a result, individuals with hypothyroidism, especially those with both diabetes groups, might require lipid-lowering treatment along with thyroid hormone replacement to address their cardiovascular risk properly ( 19 ). Research findings showed that hypothyroid diabetic patients had the lowest levels of vitamin D3 compared to non-hypothyroid diabetics and controls. There is a high prevalence of Vitamin D deficiency in patients with both hypothyroidism and diabetes. Studies have shown a significant negative relationship between thyroid-stimulating hormone (TSH) levels and serum vitamin D levels, where higher TSH levels are frequently associated with lower vitamin D levels, Despite multiple research undertaken to clarify the role of vitamin D in the development of autoimmune thyroid illnesses, it is still unclear if vitamin D insufficiency is an essential element in the etiology or the outcome of autoimmune thyroid diseases ( 29 , 30 ). A lack of vitamin D has been linked to worse metabolic results, especially in individuals with diabetes and hypothyroidism, as it plays a role in regulating insulin sensitivity and lipid metabolism. Recent research indicates that giving vitamin D supplements could enhance insulin sensitivity and lipid profiles, but more clinical trials are necessary to validate these advantages in hypothyroid diabetic individuals ( 31 , 32 ). Conclusion the study found that 44% of diabetics have hypothyroidism, which is linked to poorer metabolic indicators compared to diabetics without hypothyroidism. Individuals with diabetes and hypothyroidism had higher BMIs, poorer glycemic control, and more severe dyslipidemia than those with diabetes alone, according to our findings. Elevated triglyceride and LDL levels, as well as low HDL, raise cardiovascular risk. Hypothyroidism also increases insulin resistance and fat buildup. Furthermore, low vitamin D levels were common among hypothyroid diabetics, indicating the need for additional inquiry. Declarations Authors Contributions: A. E., O. D., I. A., W. B., and A. A. conceptualized and designed the study. A. O., M. B., M. M., N. A., and M. A. analyzed and interpreted the data. B. A., A. A., S. A., and M. E. prepared figures. N. E., H. H., N. E., M. M. F. A., and A. K. wrote the manuscript. All authors have critically evaluated and approved the final text and are responsible for the manuscript's content and similarity index. Conflict of Interest: The authors have disclosed that no conflicts of interest exist. Consent to Participate declaration: Not applicable. Consent to Publish declaration: Not applicable Data Availability The data supporting the findings of this study can be obtained from the corresponding author upon reasonable request. Funding This research is funded by the Deanship of Graduate Studies and Scientific Research, Jazan University, Saudi Arabia, (Project Number: (RG24-L05). Acknowledgements: The authors gratefully acknowledge the funding of the Deanship of Graduate Studies and Scientific Research, Jazan University, Saudi Arabia, through Project Number: (RG24-L05) References Association AD. 6. Glycemic targets: standards of medical care in diabetes—2020. Diabetes care. 2020;43(Supplement_1):S66-S76. Nair A, Jayakumari C, Jabbar P, Jayakumar R, Raizada N, Gopi A, et al. Prevalence and associations of hypothyroidism in Indian patients with type 2 diabetes mellitus. Journal of thyroid research. 2018;2018(1):5386129. Daminov A, Oktamjonov G, Allayorova S, Sanaqulova H, Ergashev S. HYPOTHYROIDIS IS A PROBLEM OF THE XXI ERA. Research and implementation. 2024;2(4):206-14. Touzani A, Imane Z, Kriouile Y, Gaouzi A. Autoimmune and Non-Autoimmune Thyroid Diseases and Type 1 Diabetes. J Med Clin Nurs Stud. 2024;2(1):1-7. Kalra S, Aggarwal S, Khandelwal D. Thyroid dysfunction and type 2 diabetes mellitus: screening strategies and implications for management. Diabetes Therapy. 2019;10(6):2035-44. Biondi B, Kahaly GJ, Robertson RP. Thyroid dysfunction and diabetes mellitus: two closely associated disorders. Endocrine reviews. 2019;40(3):789-824. Ozair M, Noor S, Raghav A, Siddiqi SS, Chugtai AM, Ahmad J. Prevalence of thyroid disorders in North Indian Type 2 diabetic subjects: A cross sectional study. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2018;12(3):301-4. Koyyada A. Clinical evaluation of dyslipidemia among type 2 diabetes and hypothyroidism patients. Current Medicine Research and Practice. 2021;11(5):211-5. Yorke E. Co-Morbid Hypothyroidism and Liver Dysfunction: A Review. Clinical Medicine Insights: Endocrinology and Diabetes. 2024;17:11795514241231533. Lamichhnae A, Pant P, Khadka S, Shrestha R, Pey S. Prevalence and Associated Risk Factors of Hypothyroidism in Patients with Diabetes Mellitus. Diabetes Research. 2024;1(1):1-11. Han C, He X, Xia X, Li Y, Shi X, Shan Z, et al. Subclinical hypothyroidism and type 2 diabetes: a systematic review and meta-analysis. PloS one. 2015;10(8):e0135233. Subekti I, Pramono LA, Dewiasty E, Harbuwono DS. Thyroid dysfunction in type 2 diabetes mellitus patients. Acta Medica Indonesiana. 2018;49(4):314. Fregenal M, D'Urso M, Luciardi H. Prevalence of thyroid dysfunction in patients with type 2 diabetes mellitus. Medicina. 2016;76(6):355-8. Kalra S, Unnikrishnan AG, Sahay R. The hypoglycemic side of hypothyroidism. Medknow; 2014. p. 1-3. Sanyal D, Raychaudhuri M. Hypothyroidism and obesity: An intriguing link. Indian journal of endocrinology and metabolism. 2016;20(4):554-7. Yang W, Jin C, Wang H, Lai Y, Li J, Shan Z. Subclinical hypothyroidism increases insulin resistance in normoglycemic people. Frontiers in Endocrinology. 2023;14:1106968. Vemula SL, Aramadaka S, Mannam R, Sankara Narayanan R, Bansal A, Yanamaladoddi VR, et al. The Impact of Hypothyroidism on Diabetes Mellitus and Its Complications: A Comprehensive Review. Cureus. 2023;15(6):e40447. Zhu X-B, Niu Z-H, Fan W-M, Sheng C-S, Chen Q. Type 2 diabetes mellitus and the risk of male infertility: a Mendelian randomization study. Frontiers in Endocrinology. 2023;14:1279058. Mavromati M, Jornayvaz FR. Hypothyroidism-Associated Dyslipidemia: Potential Molecular Mechanisms Leading to NAFLD. Int J Mol Sci. 2021;22(23). Ghosh A, Kundu D, Rahman F, Zafar ME, Prasad K, Baruah H, et al. Correlation of lipid profile among patients with hypothyroidism and type 2 diabetes mellitus. BLDE University Journal of Health Sciences. 2018;3(1):48-53. Hazlehurst JM, Tomlinson JW. Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders. European Journal of Endocrinology. 2013;169(2):R27-R37. Poznyak AV, Nikiforov NG, Markin AM, Kashirskikh DA, Myasoedova VA, Gerasimova EV, et al. Overview of OxLDL and its impact on cardiovascular health: focus on atherosclerosis. Frontiers in Pharmacology. 2021;11:613780. Klieverik LP, Coomans CP, Endert E, Sauerwein HP, Havekes LM, Voshol PJ, et al. Thyroid hormone effects on whole-body energy homeostasis and tissue-specific fatty acid uptake in vivo. Endocrinology. 2009;150(12):5639-48. Nedvidkova J, Haluzik M, Bartak V, Dostalova I, Vlcek P, Racek P, et al. Changes of noradrenergic activity and lipolysis in the subcutaneous abdominal adipose tissue of hypo‐and hyperthyroid patients: an in vivo microdialysis study. Annals of the New York Academy of Sciences. 2004;1018(1):541-9. D'Ambrosio R, Campi I, Maggioni M, Perbellini R, Giammona E, Stucchi R, et al. The relationship between liver histology and thyroid function tests in patients with non-alcoholic fatty liver disease (NAFLD). PLoS One. 2021;16(4):e0249614. Jung KY, Ahn HY, Han SK, Park YJ, Cho BY, Moon MK. Association between thyroid function and lipid profiles, apolipoproteins, and high-density lipoprotein function. Journal of clinical lipidology. 2017;11(6):1347-53. Wong NKP, Nicholls SJ, Tan JTM, Bursill CA. The Role of High-Density Lipoproteins in Diabetes and Its Vascular Complications. International Journal of Molecular Sciences. 2018;19(6):1680. Gobal FA, Mehta JL. Management of dyslipidemia in the elderly population. Therapeutic advances in cardiovascular disease. 2010;4(6):375-83. Nettore IC, Albano L, Ungaro P, Colao A, Macchia PE. Sunshine vitamin and thyroid. Reviews in endocrine and metabolic disorders. 2017;18:347-54. Babić Leko M, Jureško I, Rozić I, Pleić N, Gunjača I, Zemunik T. Vitamin D and the thyroid: A critical review of the current evidence. International journal of molecular sciences. 2023;24(4):3586. Mohamed OE, Elhussein A, Babikr WG, AlSayed MI. Vitamin D Deficiency Among Type 2 Diabetic Patients in Najran Area, Saudi Arabia. Zagazig University Medical Journal. 2021;27(1):132-9. Argano C, Mirarchi L, Amodeo S, Orlando V, Torres A, Corrao S. The role of vitamin D and its molecular bases in insulin resistance, diabetes, metabolic syndrome, and cardiovascular disease: state of the art. International Journal of Molecular Sciences. 2023;24(20):15485. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5640197","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":394202848,"identity":"791c6c3a-3b74-4b33-b315-a882ed3e25b5","order_by":0,"name":"Amar Babikir Elhussein","email":"","orcid":"","institution":"Nile University","correspondingAuthor":false,"prefix":"","firstName":"Amar","middleName":"Babikir","lastName":"Elhussein","suffix":""},{"id":394202849,"identity":"3585b3ba-990e-4897-8a7d-a4cf07256d63","order_by":1,"name":"Ogail Yousif Dawod","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyUlEQVRIiWNgGAWjYJCCAw//2ciBGQ+I1pLAlmYMYRBtTQLbocQGMIMY1fz8ix8eSOA5kD4/7DCQwWAnp9tAQIvkjGcGBxIk7uRuvJ0GZDAkG5sdIKDF4MYBoEqDZ7kbZyeAtBxI3EZYy/EPBxISDqcbzk7/QKSW8z1Aww8cTpCXziHSFskZPAUHEhvSDDdI5xQAXUiEX/j5j2/+8LHBRl5+dvrmDx8q7OQIamGQSIC6EKzSgJBysDVQQ+UbiFE9CkbBKBgFIxIAACmATyuEYB7bAAAAAElFTkSuQmCC","orcid":"","institution":"Jazan University","correspondingAuthor":true,"prefix":"","firstName":"Ogail","middleName":"Yousif","lastName":"Dawod","suffix":""},{"id":394202850,"identity":"a134c6d9-95b7-4fc8-b0d3-35e0cd654b8e","order_by":2,"name":"Ibrahim Ismail Mohammed Abu","email":"","orcid":"","institution":"King Abdulaziz University","correspondingAuthor":false,"prefix":"","firstName":"Ibrahim","middleName":"Ismail Mohammed","lastName":"Abu","suffix":""},{"id":394202851,"identity":"4e5fb995-2875-40f6-a651-6c023c5d764e","order_by":3,"name":"Walid G babikr","email":"","orcid":"","institution":"Internist-ECNHN","correspondingAuthor":false,"prefix":"","firstName":"Walid","middleName":"G","lastName":"babikr","suffix":""},{"id":394202852,"identity":"6fcf2779-af82-4f6c-8cfb-eba0b90b122a","order_by":4,"name":"Abdulrahman A. Alsayegh","email":"","orcid":"","institution":"Jazan University","correspondingAuthor":false,"prefix":"","firstName":"Abdulrahman","middleName":"A.","lastName":"Alsayegh","suffix":""},{"id":394202853,"identity":"31f32b4e-54fd-4187-8c5a-7a0237bdb7d6","order_by":5,"name":"Abdullah Y. Otayf","email":"","orcid":"","institution":"Jazan University","correspondingAuthor":false,"prefix":"","firstName":"Abdullah","middleName":"Y.","lastName":"Otayf","suffix":""},{"id":394202854,"identity":"45c88f6b-bdb6-45f7-adad-2f467912053b","order_by":6,"name":"Mohammed Bajahzer","email":"","orcid":"","institution":"Jazan University","correspondingAuthor":false,"prefix":"","firstName":"Mohammed","middleName":"","lastName":"Bajahzer","suffix":""},{"id":394202855,"identity":"44966dff-80ac-4055-96b7-9d599e84c97e","order_by":7,"name":"Monami Mukherjee Mondal","email":"","orcid":"","institution":"Jazan University","correspondingAuthor":false,"prefix":"","firstName":"Monami","middleName":"Mukherjee","lastName":"Mondal","suffix":""},{"id":394202856,"identity":"ea630279-3b26-47c5-8b68-54b020d72785","order_by":8,"name":"Nusayba Abdelrhman Alageb","email":"","orcid":"","institution":"Jazan University","correspondingAuthor":false,"prefix":"","firstName":"Nusayba","middleName":"Abdelrhman","lastName":"Alageb","suffix":""},{"id":394202857,"identity":"d98e243e-8fb3-42ab-8b03-f102ad9b9eca","order_by":9,"name":"Mohamed M Almaki","email":"","orcid":"","institution":"Jazan University","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"M","lastName":"Almaki","suffix":""},{"id":394202858,"identity":"c8518514-a8e5-43bf-9853-74f89e5e465b","order_by":10,"name":"Badreldin S. R. Ahmed","email":"","orcid":"","institution":"Jazan University","correspondingAuthor":false,"prefix":"","firstName":"Badreldin","middleName":"S. R.","lastName":"Ahmed","suffix":""},{"id":394202859,"identity":"becf3688-1f4e-469f-98df-33e71c5013ac","order_by":11,"name":"Ammar Abdelmola","email":"","orcid":"","institution":"Jazan University","correspondingAuthor":false,"prefix":"","firstName":"Ammar","middleName":"","lastName":"Abdelmola","suffix":""},{"id":394202860,"identity":"5f30cff0-306a-4cb1-b538-0bcf85ce4a02","order_by":12,"name":"Saif Elden B. Abdalla","email":"","orcid":"","institution":"Jazan University","correspondingAuthor":false,"prefix":"","firstName":"Saif","middleName":"Elden B.","lastName":"Abdalla","suffix":""},{"id":394202861,"identity":"34e84b79-38a7-4cf0-b73c-55873b458375","order_by":13,"name":"Mohamed Eltaib Elmobark","email":"","orcid":"","institution":"Jazan University","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"Eltaib","lastName":"Elmobark","suffix":""},{"id":394202862,"identity":"f72d4276-ba7b-4c0a-bd78-10ca0df3f618","order_by":14,"name":"Nour Eldaim Elnoman Elbadawi","email":"","orcid":"","institution":"University of Shaqra","correspondingAuthor":false,"prefix":"","firstName":"Nour","middleName":"Eldaim Elnoman","lastName":"Elbadawi","suffix":""},{"id":394202863,"identity":"bee39c25-9fb9-4a93-9915-4cbc5b1e64a6","order_by":15,"name":"Husham E. Homeida","email":"","orcid":"","institution":"Jazan University","correspondingAuthor":false,"prefix":"","firstName":"Husham","middleName":"E.","lastName":"Homeida","suffix":""},{"id":394202864,"identity":"7be73156-6e74-4e94-b8ad-2672a5382312","order_by":16,"name":"Nahid Mahmoud Hassan Elamin","email":"","orcid":"","institution":"Jazan University","correspondingAuthor":false,"prefix":"","firstName":"Nahid","middleName":"Mahmoud Hassan","lastName":"Elamin","suffix":""},{"id":394202865,"identity":"83ec74db-d7a7-4e7e-834e-b8bcaf236580","order_by":17,"name":"Muntaser Mohammed Fadoul Alhassen","email":"","orcid":"","institution":"Jazan University","correspondingAuthor":false,"prefix":"","firstName":"Muntaser","middleName":"Mohammed Fadoul","lastName":"Alhassen","suffix":""},{"id":394202866,"identity":"b2e24a19-ba6b-4f8e-9106-5985e6402134","order_by":18,"name":"Asaad Khalid","email":"","orcid":"","institution":"Jazan University","correspondingAuthor":false,"prefix":"","firstName":"Asaad","middleName":"","lastName":"Khalid","suffix":""}],"badges":[],"createdAt":"2024-12-13 19:08:07","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5640197/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5640197/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72643544,"identity":"ba022378-7a80-4f0a-a80b-4e5a244a2375","added_by":"auto","created_at":"2024-12-30 16:38:16","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":20319,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePercentage of non-hypothyroidism, hypothyroidism, and control group\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5640197/v1/a43e4e618cd04a06a84cbaab.png"},{"id":72642398,"identity":"d21bad0e-5236-42f8-86f9-15601b5e3f2d","added_by":"auto","created_at":"2024-12-30 16:30:15","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":17055,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe percentages of HDL among the non-hypothyroidism, hypothyroidism and control subjects\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5640197/v1/5d838cdc2bbf9e816094d60a.png"},{"id":72643543,"identity":"f90fb17e-df1f-4df9-bcda-4784399b1f52","added_by":"auto","created_at":"2024-12-30 16:38:15","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":29338,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe percentages of LDL among the non-hypothyroidism, hypothyroidism, and control subjects\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5640197/v1/e73a6c96d1b304e14804a170.png"},{"id":72642399,"identity":"690ce362-23e7-4d9c-bb4d-5058e1d73fe0","added_by":"auto","created_at":"2024-12-30 16:30:15","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":26048,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe percentages of TG among the non-hypothyroidism, hypothyroidism, and control subjects\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-5640197/v1/bdd9ca2cd68337b2e4fe3f89.png"},{"id":72645894,"identity":"c2069152-0d0b-4633-972f-b32a454942b3","added_by":"auto","created_at":"2024-12-30 16:46:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":610167,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5640197/v1/628811ae-2187-4558-9d7e-f0512b38d6b7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The clinical implications of interacting hypothyroid and diabetes mellitus","fulltext":[{"header":"Introduction","content":"\u003cp\u003eType 2 diabetes mellitus (T2DM) is caused by insulin's inability to promote the uptake of glucose and utilization in peripheral tissues (muscle, adipose tissue, and liver), as well as insulin resistance and a gradual reduction in beta cell insulin production (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). In 2021, around 537\u0026nbsp;million persons had diabetes, with T2DM accounting for 90% of the cases Nair et al (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eHypothyroidism is the most common thyroid condition in adults, with frequency increasing with age (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Auto-immune thyroid disease is the most frequent autoimmune illness linked with diabetes, affecting about 30% of patients with type 1 diabetes (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Type 2 diabetic individuals are more likely to suffer from thyroid abnormalities, with hypothyroidism being the most frequent (\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe relationship between hypothyroidism and diabetes mellitus (DM) is complex, with significant implications for patient management. Research indicates that hypothyroidism can exacerbate the complications associated with diabetes, particularly in type 2 diabetes mellitus (T2DM) patients. The coexistence of diabetes and hypothyroidism significantly impacts metabolic control and increases the risk of complications (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Hypothyroidism can exacerbate insulin resistance, complicating glycemic control in diabetes patients, particularly in T2DM (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWhile hypothyroidism is often overlooked in diabetic patients, its potential to exacerbate complications underscores the importance of integrated management strategies. However, some studies suggest that not all diabetic patients with hypothyroidism experience the same degree of complications, indicating variability in individual responses and the need for personalized care.\u003c/p\u003e \u003cp\u003eHypothyroidism is associated with non-alcoholic fatty liver disease (NAFLD), where thyroid hormone deficiency leads to abnormal lipid metabolism and liver dysfunction (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThyroid hormones regulate a wide range of metabolic processes by controlling lipoprotein metabolism. HMG CoA activity is reduced in hypothyroid individuals. Reduced thyroid hormone levels cause lower LDL receptor activation, triglyceride (TG) clearance, and LDL catabolism (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe interplay between thyroid hormones and liver function is crucial; thyroid hormones are necessary for optimal liver metabolism, and their deficiency can lead to significant hepatic impairment (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). In contrast, while hypothyroidism may worsen liver function in diabetic patients, some studies suggest that normalizing thyroid levels can reverse hepatic dysfunction, highlighting the importance of managing both conditions concurrently (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere is a complex unclear association between thyroid disorders and diabetes mellitus. Thyroid hormones regulate carbohydrate metabolism and pancreatic function, while diabetes has a varying effect on thyroid function tests. Several investigations have reported complicated, intertwined biochemical, genetic, and hormonal problems that mimic this pathophysiological relationship. However, underlying thyroid issues may go undetected since the frequent signs and symptoms of thyroid diseases are similar to those of diabetes and might be missed or attributed to other medical conditions (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe present research was conducted to determine the incidence and prevalence of hypothyroidism among type two diabetes individuals and its association with lipid profile and some clinical parameters.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cp\u003e275 diabetic patients (166 males, 60.4%, and 109 females, 39.6%) were part of the research conducted at Najran University Hospital's outpatient clinic. Additionally, 136 healthy controls (76 males, 55.9%, and 60 females, 44.1%) from the Najran area were also included in the study, which took place from August 2016 to October 2017. FBG levels were assessed with the COBAS INTEGRA 400 and Roche diagnostics kits, while HbA1c levels were determined using the Nycocard HbA1c method. Vitamin D levels and Thyroid function tests were assessed utilizing the ELISA method with kits made by Abcam Company. Weight and height were measured with a standardized scale, followed by the calculation of BMI as weight in kilograms divided by height squared.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eEthical consideration\u003c/h2\u003e \u003cp\u003eAfter receiving both spoken and written approval, all patients were assured that any information gathered would be kept private and would not affect their ongoing affairs. The research and ethics committee at Najran University in Saudi Arabia granted ethical clearance and protocol approval. All steps were followed based on ethical guidelines from the appropriate committee for human experimentation (institutional and national) and the Helsinki Declaration of 1975, as updated in Brazil in 2013.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis:\u003c/h2\u003e \u003cp\u003eThe study's findings were subjected to statistical analysis using the SPSS software. One-way ANOVA and t-test were used to evaluate major disparities among groups. A correlation matrix was conducted, resulting in the obtention of the r values alongside their significance levels.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOf the 411 individuals selected for this study, 275 (69.2%) had diabetes, while 136 (30.8%) were designated as controls. Male individuals constitute 242 (58.9%), while female individuals account for 169 (41.1%). Among the diabetic population, 87 patients (39%) had non-hypothyroidism, whereas 22 patients (44%) presented with hypothyroidism. Among the diabetics, 167 were hypertensive and 244 (59.3%) were normotensive. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents several features of the diabetes and control groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSome characteristics of the study group:\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"2\" nameend=\"c2\" namest=\"c1\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c6\" namest=\"c3\"\u003e \u003cp\u003eDiabetic patients\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c8\" namest=\"c7\" rowspan=\"2\"\u003e \u003cp\u003eHealthy Control\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eNon-Hypothyroidism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eHypothyroidism\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eFreq\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFreq\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFreq\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eFemale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e44%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e44%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eMale\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e138\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e61%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e56%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e56%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cb\u003eHTN\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eYes\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e59%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e54%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003eNo\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e93\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e41%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e46%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e94%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAmong the 411 people chosen for this study, hypothyroidism accounts for 50 patients (12.2%), non-hypothyroidism constitutes around 225 patients (54.7%), and the healthy control group comprises 136 individuals (31.1%). Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn non-hypothyroidism, poor HDL levels account for 34% of the total. 66% in the heightened concentration. In hypothyroidism, elevated HDL content accounts for 92% of the total. 8% in the decreased concentration. In control, low HDL concentration constitutes 8% of the total. 92% in the elevated concentration.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn cases of non-hypothyroidism, the optimal concentration of LDL was found to be 0%, the near optimal concentration was revealed to be 10.7%, the borderline concentration was revealed to be 16%, the high concentration was reported to be 30.7%, and the very high concentration was identified to be 42.7%.\u003c/p\u003e \u003cp\u003eIn cases of hypothyroidism, the optimal concentration of LDL was determined to be 0%, the nearly optimal concentration was also found to be 0%, the borderline concentration was identified as 26%, the elevated concentration was noted at 32%, and the markedly high concentration was recognized at 42%.\u003c/p\u003e \u003cp\u003eAmong the concentrations of LDL that were detected in the control group, the optimal concentration was found to be 7.4%, the nearly optimal concentration was reported to be 11.8%, the borderline concentration was found to be 47.8%, the raised concentration was found to be 15.4%, and the significantly high concentration was found to be 17.6%.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn cases of non-hypothyroidism, the optimum level of TG was determined to be 3.6%, the borderline concentration was established at 3.3%, the elevated concentration was noted at 46.2%, and the significantly elevated concentration was recognized at 28.7%.\u003c/p\u003e \u003cp\u003eIn cases of hypothyroidism, the optimum concentration of TG was determined to be 0.7%, the borderline concentration was also identified as 0.7%, the higher amount was noted at 13.5%, and the considerably higher concentration was recognized at 3.3%.\u003c/p\u003e \u003cp\u003eWithin the control group, the optimum concentration of TG was determined to be 71.3%, the borderline concentration was identified as 16.9%, the high concentration was noted at 8.8%, and the very high concentration was recognized at 2.9%.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of mean concentrations of BMI, FBS, HbA1c, HDL, LDL, TCHOL, TG, and VitD3 in diabetic and control subjects\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eParameters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eDiabetic patients\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHealthy Control\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo Hypothyroidism\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHypothyroidism\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBMI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e34.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e32.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e26.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFBS mmol/l\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e11.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.462\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e12.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.801\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.615\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHbA1c %\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e5.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHDL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLDL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTCHOL\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTG\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eVitD3 mmol/l\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e39.4\u0026thinsp;\u0026plusmn;\u0026thinsp;18.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e28.2\u0026thinsp;\u0026plusmn;\u0026thinsp;20.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e59.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCompared to controls, diabetic individuals without hypothyroidism have an average BMI of (34.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8), whereas those with hypothyroidism have an average of (32.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.1). Both values exceed the average BMI of control participants (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) = (26.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.7), with a significant p-value (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eA study of fasting blood sugar (FBS) between diabetics and controls shows that diabetics without hypothyroidism have a mean FBS of (11.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.462) whereas those with hypothyroidism have a mean of (12.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.801). Both groups have significantly higher FBS levels than the average control group (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u0026thinsp;=\u0026thinsp;4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.615, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eComparing hemoglobin A1C (HbA1c) between diabetics and controls shows that diabetics without hypothyroidism have a mean HbA1c of (9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2) whereas those with hypothyroidism have a mean of (1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9). Both groups have significantly higher HbA1c values than normal controls, with a mean of 5.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69 (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eCompared to controls, diabetics without hypothyroidism have a mean HDL of (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) = (1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26), whereas standard controls have (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) = (1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9). Both groups had greater HDL levels than, diabetic patients with hypothyroidism having a mean of (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) = (0.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26), statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eDiabetics without hypothyroidism have a mean LDL of (4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2) compared to controls, but those with hypothyroidism had a mean of (4.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0). Both groups had significantly higher LDL levels than controls (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u0026thinsp;=\u0026thinsp;3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eDiabetics without hypothyroidism have a mean cholesterol (TCHOL) of 3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4, whereas those with hypothyroidism had 3.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2, compared to controls. TCHOL levels were significantly higher in both groups compared to controls (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u0026thinsp;=\u0026thinsp;2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eCompared to controls, diabetics without hypothyroidism have a mean TG of 5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2, whereas those with hypothyroidism had 4.4\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6. The TG levels in both groups were significantly greater than normal controls (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u0026thinsp;=\u0026thinsp;1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eDiabetics without hypothyroidism had a mean VitD3 of 39.4\u0026thinsp;\u0026plusmn;\u0026thinsp;18.0, while those with hypothyroidism had 28.2\u0026thinsp;\u0026plusmn;\u0026thinsp;20.0. Both groups had significantly lower VitD3 levels than controls (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u0026thinsp;=\u0026thinsp;59.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.7, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eResults indicated that in the diabetic group, (39%) had non-hypothyroidism, while (44%) had hypothyroidism. Our study findings align with previous research, indicating a 44% prevalence of hypothyroidism in diabetic individuals. Research conducted by Lamichhnae et al. (2024) revealed that hypothyroidism was present in 32.5% of diabetic patients (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). This indicates that hypothyroidism is a frequent accompanying condition in individuals with diabetes, even though the occurrence may have some slight differences in various research studies. Furthermore, a study conducted by Han et al. (2015) found that subclinical hypothyroidism is considerably more common in people with Type 2 diabetes, with prevalence rates varying from 10\u0026ndash;20% (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). On the other hand, also research suggests that around 9.9%-48% of diabetics may be impacted by hypothyroidism (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e), whether subclinical or overt, which is consistent with our results.\u003c/p\u003e \u003cp\u003eOur results found that individuals with diabetes had higher BMIs compared to those without the condition, and those with both hypothyroidism and diabetes had slightly higher BMIs than diabetics without hypothyroidism. Both the diabetic and hypothyroid diabetic groups showed higher levels of fasting blood sugar (FBS) and HbA1c, suggesting worse glycemic control in comparison to the control group, Hypothyroidism is recognized for worsening metabolic disruptions, especially in individuals with diabetes (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). individuals with hypothyroidism, especially those with subclinical hypothyroidism, frequently have a higher BMI (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), possibly because of decreased basal metabolic rates. Additionally, poorly controlled hypothyroidism exacerbates insulin resistance, leading to higher levels of fasting blood glucose and HbA1c (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). New researches show that diabetic individuals with hypothyroidism face more severe metabolic imbalances than those without hypothyroidism (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), making it harder to manage blood sugar levels effectively. Furthermore, Mendelian randomization research has confirmed a direct correlation between hypothyroidism and type 1 diabetes, also linking it to increased probabilities of complications such as diabetic retinopathy and kidney disease (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eOur findings indicated that hypothyroid patients with diabetes showed decreased HDL levels and increased LDL levels when compared to diabetic patients without hypothyroidism Both diabetic groups showed increase(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e)d levels of Triglyceride (TG), with a more significant rise in individuals with hypothyroidism. A vast amount of literature backs up these results, Even when it is in the subclinical stage, hypothyroidism is closely linked to a lipid profile that promotes atherosclerosis, characterized by high levels of LDL, TC, and TG, as well as low levels of HDL (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). In diabetes, the impact of hypothyroidism on lipids is magnified as both conditions contribute to dyslipidemia (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). This results in increased oxidative stress and lipid peroxidation, worsening the cardiovascular risk in hypothyroid diabetics. some research has emphasized how hypothyroidism increases LDL oxidation and accumulates triglycerides through mechanical means (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Elevated levels of LDL-C, particularly oxidized LDL, play a role in the development of atherosclerotic plaques, increasing the risk of cardiovascular diseases (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Therefore, individuals with hypothyroidism, especially those who also have diabetes, may require treatment to lower their lipid levels in addition to taking thyroid hormones to effectively address their cardiovascular risk.\u003c/p\u003e \u003cp\u003eOur research found that hypothyroid diabetics had noticeably elevated levels of triglycerides compared to non-hypothyroid diabetics, and their HDL levels were significantly reduced. Hypothyroidism decreases the liver's absorption of FFA from triglycerides (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e) and is linked to a reduction in fat breakdown in adipose tissue along with decreased cholesterol removal (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Therefore, there is a decrease in the β-oxidation of free fatty acids and clearance of triglycerides, leading to an accumulation of triglycerides in the liver and an increase in low-density lipoprotein (LDL) uptake. Reduced hepatic lipase activity in hypothyroidism hinders the oxidation of fatty acids, especially long-chain fatty acids, crucial for energy production. Obesity and hypothyroidism can further increase lipid storage in the liver by lowering resting energy expenditure (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Administering thyroid hormone to humans and mice can reverse the reduced activity of hepatic lipase. (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe decrease in HDL levels seen in diabetic patients with hypothyroidism is another manifestation of a recognized issue. Lower levels of HDL are common in hypothyroidism because thyroid hormones help in the creation of apolipoprotein A1, which is a key element of HDL (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). HDL reduction in hypothyroid diabetic patients increases the risk of cardiovascular disease due to its protective role in removing cholesterol from artery walls (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e). Certain research has focused on how hypothyroidism contributes to LDL oxidation and triglyceride buildup. Higher levels of LDL-C, particularly oxidized LDL, play a role in developing atherosclerotic plaques, increasing the risk of cardiovascular disease (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). As a result, individuals with hypothyroidism, especially those with both diabetes groups, might require lipid-lowering treatment along with thyroid hormone replacement to address their cardiovascular risk properly (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eResearch findings showed that hypothyroid diabetic patients had the lowest levels of vitamin D3 compared to non-hypothyroid diabetics and controls. There is a high prevalence of Vitamin D deficiency in patients with both hypothyroidism and diabetes. Studies have shown a significant negative relationship between thyroid-stimulating hormone (TSH) levels and serum vitamin D levels, where higher TSH levels are frequently associated with lower vitamin D levels, Despite multiple research undertaken to clarify the role of vitamin D in the development of autoimmune thyroid illnesses, it is still unclear if vitamin D insufficiency is an essential element in the etiology or the outcome of autoimmune thyroid diseases (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA lack of vitamin D has been linked to worse metabolic results, especially in individuals with diabetes and hypothyroidism, as it plays a role in regulating insulin sensitivity and lipid metabolism. Recent research indicates that giving vitamin D supplements could enhance insulin sensitivity and lipid profiles, but more clinical trials are necessary to validate these advantages in hypothyroid diabetic individuals (\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003ethe study found that 44% of diabetics have hypothyroidism, which is linked to poorer metabolic indicators compared to diabetics without hypothyroidism. Individuals with diabetes and hypothyroidism had higher BMIs, poorer glycemic control, and more severe dyslipidemia than those with diabetes alone, according to our findings. Elevated triglyceride and LDL levels, as well as low HDL, raise cardiovascular risk. Hypothyroidism also increases insulin resistance and fat buildup. Furthermore, low vitamin D levels were common among hypothyroid diabetics, indicating the need for additional inquiry.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA. E., O. D., I. A., W. B., and A. A. conceptualized and designed the study. A. O., M. B., M. M., N. A., and M. A. analyzed and interpreted the data. B. A., A. A., S. A., and M. E. prepared figures. N. E., H. H., N. E., M. M. F. A., and A. K. wrote the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll authors have critically evaluated and approved the final text and are responsible for the manuscript's content and similarity index.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have disclosed that no conflicts of interest exist.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate declaration:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish declaration:\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this study can be obtained from the corresponding author upon reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research is funded by the Deanship of Graduate Studies and Scientific Research, Jazan University, Saudi Arabia, (Project Number: (RG24-L05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors gratefully acknowledge the funding of the Deanship of Graduate Studies and Scientific Research, Jazan University, Saudi Arabia, through Project Number: (RG24-L05)\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eAssociation AD. 6. Glycemic targets: standards of medical care in diabetes\u0026mdash;2020. Diabetes care. 2020;43(Supplement_1):S66-S76.\u003c/li\u003e\n \u003cli\u003eNair A, Jayakumari C, Jabbar P, Jayakumar R, Raizada N, Gopi A, et al. Prevalence and associations of hypothyroidism in Indian patients with type 2 diabetes mellitus. Journal of thyroid research. 2018;2018(1):5386129.\u003c/li\u003e\n \u003cli\u003eDaminov A, Oktamjonov G, Allayorova S, Sanaqulova H, Ergashev S. HYPOTHYROIDIS IS A PROBLEM OF THE XXI ERA. Research and implementation. 2024;2(4):206-14.\u003c/li\u003e\n \u003cli\u003eTouzani A, Imane Z, Kriouile Y, Gaouzi A. Autoimmune and Non-Autoimmune Thyroid Diseases and Type 1 Diabetes. J Med Clin Nurs Stud. 2024;2(1):1-7.\u003c/li\u003e\n \u003cli\u003eKalra S, Aggarwal S, Khandelwal D. Thyroid dysfunction and type 2 diabetes mellitus: screening strategies and implications for management. Diabetes Therapy. 2019;10(6):2035-44.\u003c/li\u003e\n \u003cli\u003eBiondi B, Kahaly GJ, Robertson RP. Thyroid dysfunction and diabetes mellitus: two closely associated disorders. Endocrine reviews. 2019;40(3):789-824.\u003c/li\u003e\n \u003cli\u003eOzair M, Noor S, Raghav A, Siddiqi SS, Chugtai AM, Ahmad J. Prevalence of thyroid disorders in North Indian Type 2 diabetic subjects: A cross sectional study. Diabetes \u0026amp; Metabolic Syndrome: Clinical Research \u0026amp; Reviews. 2018;12(3):301-4.\u003c/li\u003e\n \u003cli\u003eKoyyada A. Clinical evaluation of dyslipidemia among type 2 diabetes and hypothyroidism patients. Current Medicine Research and Practice. 2021;11(5):211-5.\u003c/li\u003e\n \u003cli\u003eYorke E. Co-Morbid Hypothyroidism and Liver Dysfunction: A Review. Clinical Medicine Insights: Endocrinology and Diabetes. 2024;17:11795514241231533.\u003c/li\u003e\n \u003cli\u003eLamichhnae A, Pant P, Khadka S, Shrestha R, Pey S. Prevalence and Associated Risk Factors of Hypothyroidism in Patients with Diabetes Mellitus. Diabetes Research. 2024;1(1):1-11.\u003c/li\u003e\n \u003cli\u003eHan C, He X, Xia X, Li Y, Shi X, Shan Z, et al. Subclinical hypothyroidism and type 2 diabetes: a systematic review and meta-analysis. PloS one. 2015;10(8):e0135233.\u003c/li\u003e\n \u003cli\u003eSubekti I, Pramono LA, Dewiasty E, Harbuwono DS. Thyroid dysfunction in type 2 diabetes mellitus patients. Acta Medica Indonesiana. 2018;49(4):314.\u003c/li\u003e\n \u003cli\u003eFregenal M, D\u0026apos;Urso M, Luciardi H. Prevalence of thyroid dysfunction in patients with type 2 diabetes mellitus. Medicina. 2016;76(6):355-8.\u003c/li\u003e\n \u003cli\u003eKalra S, Unnikrishnan AG, Sahay R. The hypoglycemic side of hypothyroidism. Medknow; 2014. p. 1-3.\u003c/li\u003e\n \u003cli\u003eSanyal D, Raychaudhuri M. Hypothyroidism and obesity: An intriguing link. Indian journal of endocrinology and metabolism. 2016;20(4):554-7.\u003c/li\u003e\n \u003cli\u003eYang W, Jin C, Wang H, Lai Y, Li J, Shan Z. Subclinical hypothyroidism increases insulin resistance in normoglycemic people. Frontiers in Endocrinology. 2023;14:1106968.\u003c/li\u003e\n \u003cli\u003eVemula SL, Aramadaka S, Mannam R, Sankara Narayanan R, Bansal A, Yanamaladoddi VR, et al. The Impact of Hypothyroidism on Diabetes Mellitus and Its Complications: A Comprehensive Review. Cureus. 2023;15(6):e40447.\u003c/li\u003e\n \u003cli\u003eZhu X-B, Niu Z-H, Fan W-M, Sheng C-S, Chen Q. Type 2 diabetes mellitus and the risk of male infertility: a Mendelian randomization study. Frontiers in Endocrinology. 2023;14:1279058.\u003c/li\u003e\n \u003cli\u003eMavromati M, Jornayvaz FR. Hypothyroidism-Associated Dyslipidemia: Potential Molecular Mechanisms Leading to NAFLD. Int J Mol Sci. 2021;22(23).\u003c/li\u003e\n \u003cli\u003eGhosh A, Kundu D, Rahman F, Zafar ME, Prasad K, Baruah H, et al. Correlation of lipid profile among patients with hypothyroidism and type 2 diabetes mellitus. BLDE University Journal of Health Sciences. 2018;3(1):48-53.\u003c/li\u003e\n \u003cli\u003eHazlehurst JM, Tomlinson JW. Mechanisms in endocrinology: Non-alcoholic fatty liver disease in common endocrine disorders. European Journal of Endocrinology. 2013;169(2):R27-R37.\u003c/li\u003e\n \u003cli\u003ePoznyak AV, Nikiforov NG, Markin AM, Kashirskikh DA, Myasoedova VA, Gerasimova EV, et al. Overview of OxLDL and its impact on cardiovascular health: focus on atherosclerosis. Frontiers in Pharmacology. 2021;11:613780.\u003c/li\u003e\n \u003cli\u003eKlieverik LP, Coomans CP, Endert E, Sauerwein HP, Havekes LM, Voshol PJ, et al. Thyroid hormone effects on whole-body energy homeostasis and tissue-specific fatty acid uptake in vivo. Endocrinology. 2009;150(12):5639-48.\u003c/li\u003e\n \u003cli\u003eNedvidkova J, Haluzik M, Bartak V, Dostalova I, Vlcek P, Racek P, et al. Changes of noradrenergic activity and lipolysis in the subcutaneous abdominal adipose tissue of hypo‐and hyperthyroid patients: an in vivo microdialysis study. Annals of the New York Academy of Sciences. 2004;1018(1):541-9.\u003c/li\u003e\n \u003cli\u003eD\u0026apos;Ambrosio R, Campi I, Maggioni M, Perbellini R, Giammona E, Stucchi R, et al. The relationship between liver histology and thyroid function tests in patients with non-alcoholic fatty liver disease (NAFLD). PLoS One. 2021;16(4):e0249614.\u003c/li\u003e\n \u003cli\u003eJung KY, Ahn HY, Han SK, Park YJ, Cho BY, Moon MK. Association between thyroid function and lipid profiles, apolipoproteins, and high-density lipoprotein function. Journal of clinical lipidology. 2017;11(6):1347-53.\u003c/li\u003e\n \u003cli\u003eWong NKP, Nicholls SJ, Tan JTM, Bursill CA. The Role of High-Density Lipoproteins in Diabetes and Its Vascular Complications. International Journal of Molecular Sciences. 2018;19(6):1680.\u003c/li\u003e\n \u003cli\u003eGobal FA, Mehta JL. Management of dyslipidemia in the elderly population. Therapeutic advances in cardiovascular disease. 2010;4(6):375-83.\u003c/li\u003e\n \u003cli\u003eNettore IC, Albano L, Ungaro P, Colao A, Macchia PE. Sunshine vitamin and thyroid. Reviews in endocrine and metabolic disorders. 2017;18:347-54.\u003c/li\u003e\n \u003cli\u003eBabić Leko M, Jure\u0026scaron;ko I, Rozić I, Pleić N, Gunjača I, Zemunik T. Vitamin D and the thyroid: A critical review of the current evidence. International journal of molecular sciences. 2023;24(4):3586.\u003c/li\u003e\n \u003cli\u003eMohamed OE, Elhussein A, Babikr WG, AlSayed MI. Vitamin D Deficiency Among Type 2 Diabetic Patients in Najran Area, Saudi Arabia. Zagazig University Medical Journal. 2021;27(1):132-9.\u003c/li\u003e\n \u003cli\u003eArgano C, Mirarchi L, Amodeo S, Orlando V, Torres A, Corrao S. The role of vitamin D and its molecular bases in insulin resistance, diabetes, metabolic syndrome, and cardiovascular disease: state of the art. International Journal of Molecular Sciences. 2023;24(20):15485.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Type 2 Diabetes Mellitus (T2DM), Hypothyroidism, Glycemic Control, Lipid Profile, Cardiovascular Risk","lastPublishedDoi":"10.21203/rs.3.rs-5640197/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5640197/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eType 2 diabetes mellitus (T2DM) is characterized by insulin resistance and impaired glucose uptake, affecting millions worldwide. Hypothyroidism, a common thyroid disorder, frequently coexists with T2DM, complicating disease management. This study investigates the prevalence of hypothyroidism in T2DM patients and its relationship with lipid profiles and clinical parameters. A total of 275 diabetic patients and 136 healthy controls were included. Glycemic control, thyroid function, lipid profiles, and vitamin D levels were assessed.\u003c/p\u003e\n\u003cp\u003eResults indicated that in the diabetic group, (39%) had non-hypothyroidism, while (44%) had hypothyroidism. People with both conditions had a higher average BMI of 31.2 ± 5.1 kg/m² than those with just T2DM (mean: 29.5 ± 4.8 kg/m², p \u0026lt; 0.05). Hypothyroid diabetics had higher fasting blood sugar (FBS) levels (average: 162 ± 20 mg/dL) compared to non-hypothyroid diabetics (average: 145 ± 18 mg/dL). The hypothyroid group showed higher HbA1c levels than the control group (mean: 8.7% vs. 7.9%, p \u0026lt; 0.01). Hypothyroid diabetics showed significantly poorer lipid profiles compared to non-hypothyroid diabetics, with lower HDL (mean: 35 ± 8 mg/dL) and higher LDL (mean: 145 ± 25 mg/dL) and triglycerides (mean: 220 ± 45 mg/dL). Hypothyroid diabetic individuals had a higher prevalence of Vitamin D deficiency (average: 12.3 ± 4.6 ng/mL) than control subjects (average: 21.6 ± 5.1 ng/mL, p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003eIn conclusion, the study found that 44% of diabetics have hypothyroidism, which is linked to poorer metabolic indicators compared to diabetics without hypothyroidism. Individuals who have both conditions showed increased BMI, higher fasting blood sugar levels, poorer lipid profiles, and decreased levels of Vitamin D. These results highlight the importance of implementing specific management plans for diabetic individuals who also have hypothyroidism.\u003c/p\u003e","manuscriptTitle":"The clinical implications of interacting hypothyroid and diabetes mellitus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-30 16:30:11","doi":"10.21203/rs.3.rs-5640197/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"41c2797c-8ab8-4540-a463-b90b4262f977","owner":[],"postedDate":"December 30th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-01-22T04:08:15+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-30 16:30:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5640197","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5640197","identity":"rs-5640197","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}