Early Predictors in the Onset of Type 2 Diabetes at Different Fasting Blood Glucose Levels

Overview

Journal Diabetes Metab Syndr Obes

Publisher Dove Medical Press

Specialty Endocrinology

Date 2021 Apr 9

PMID 33833539

Citations 6

Authors

Xiaomin Xie

Guirong Bai

Huili Liu

Li Zhang

Yanting He

Dan Qiang

Xiaoyan Zou

Affiliations

Soon will be listed here.

Abstract

Purpose: This study investigates the possible roles and potential prediction ability of metabolic parameters in the early development of T2D by detecting their serum levels at different fasting blood glucose (FBG) levels.

Methods: The subjects were included and divided into normal glucose tolerance (NGT), prediabetes (PD), and T2Dsubgroups. Apart from detecting the levels of routine biochemical parameters, fasting serum insulin (FINS), 25(OH)D, thioredoxin-interacting protein (TXNIP), thioredoxin (TRX), and NOD-like receptor family, pyrin domain-containing 3 (NLRP3) were detected. β-cell dysfunction (HOMA-β) and insulin resistance (HOMA-IR) were assessed by homeostasis model assessment. Both univariate and multivariate logistic regression analyses were used to estimate the risk of metabolic parameters, and their optimal cut-off values were obtained in the receiver operating characteristic (ROC) curve analysis and the Youden index.

Results: Among the 207 subjects, aged from 20 to 60 years (44.62+12.92) contain 118 males and 89 females. There was a significantly lower trend of TRX, HOMA-β, and 25(OH)D following the higher FBG level among these three subgroups, while a significantly higher trend of all the other metabolic parameters. The multivariate analysis showed that subjects with higher values of TRX, HOMA-β, and 25(OH)D had a significantly lower risk for patients to be diagnosed as PD (aOR: 0.945, 0.961, and 0.543) and T2D (aOR: 0.912, 0.947, 0.434). Under the reliable 95% CI, TXNIP with a cut-off value of 119.27 showed the highest AUC value, sensitivity, and specificity (AUC: 0.981, 95% CI: 0.8524-0.9839, 91.49%, and 83.33%) to diagnose PD. FINS with a cut-off value of 28.1 also showed the highest ones (AUC=0.9872, 95% CI: 0.9753-0.9992, 100%, and 92.91%) to diagnose T2D.

Conclusion: Early prediction of T2D is vital for timely intervention. Based on the FBG ≥100.8 mg/dl, the results provide evidence that 25(OH)D might be the protective factor in the early development of T2D. Besides, TXNIP and FINS might be the predictor for PD and T2D, respectively.

Citing Articles

The relationship between whole blood iron and fasting blood glucose in community-dwelling elderly people: a cross-sectional study.

Chen S, Pan R, Sun M, He L, Li C J Health Popul Nutr. 2025; 44(1):5.

PMID: 39773371 PMC: 11706085. DOI: 10.1186/s41043-024-00720-2.

Differences and Associations of NLRP3 Inflammasome Levels with Interleukins 1α, 1β, 33 and 37 in Adults with Prediabetes and Type 2 Diabetes Mellitus.

Alfadul H, Sabico S, Ansari M, Alnaami A, Amer O, Hussain S Biomedicines. 2023; 11(5).

PMID: 37238986 PMC: 10216290. DOI: 10.3390/biomedicines11051315.

Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of serum metabolomic characteristics in people with different vitamin D levels.

Li H, Xie X, Zhang L, He Y, Liu H, Qiang D Open Med (Wars). 2023; 18(1):20230658.

PMID: 36874363 PMC: 9979004. DOI: 10.1515/med-2023-0658.

Association of Non-Insulin-Based Insulin Resistance Indices with Risk of Incident Prediabetes and Diabetes in a Chinese Rural Population: A 12-Year Prospective Study.

Li X, Xue Y, Dang Y, Liu W, Wang Q, Zhao Y Diabetes Metab Syndr Obes. 2022; 15:3809-3819.

PMID: 36530590 PMC: 9756794. DOI: 10.2147/DMSO.S385906.

Lipid Accumulation Product Index Predicts New-Onset Type 2 Diabetes Among Non-Obese Koreans: A 12-Year Longitudinal Study.

Yang S, Yoon J, Lee Y, Park B, Jung D Diabetes Metab Syndr Obes. 2022; 15:3729-3737.

PMID: 36474727 PMC: 9719681. DOI: 10.2147/DMSO.S389889.

References

Wilson P, Meigs J, Sullivan L, Fox C, Nathan D, DAgostino Sr R . Prediction of incident diabetes mellitus in middle-aged adults: the Framingham Offspring Study. Arch Intern Med. 2007; 167(10):1068-74. DOI: 10.1001/archinte.167.10.1068. View

Palermo A, Maggi D, Maurizi A, Pozzilli P, Buzzetti R . Prevention of type 2 diabetes mellitus: is it feasible?. Diabetes Metab Res Rev. 2013; 30 Suppl 1:4-12. DOI: 10.1002/dmrr.2513. View

Chou F, Sytwu H . Overexpression of thioredoxin in islets transduced by a lentiviral vector prolongs graft survival in autoimmune diabetic NOD mice. J Biomed Sci. 2009; 16:71. PMC: 2736160. DOI: 10.1186/1423-0127-16-71. View

Lai Y, Brandhorst H, Hossain H, Bierhaus A, Chen C, Bretzel R . Activation of NFκB dependent apoptotic pathway in pancreatic islet cells by hypoxia. Islets. 2010; 1(1):19-25. DOI: 10.4161/isl.1.1.8530. View

Lerner A, Upton J, Praveen P, Ghosh R, Nakagawa Y, Igbaria A . IRE1α induces thioredoxin-interacting protein to activate the NLRP3 inflammasome and promote programmed cell death under irremediable ER stress. Cell Metab. 2012; 16(2):250-64. PMC: 4014071. DOI: 10.1016/j.cmet.2012.07.007. View

Minn A, Hafele C, Shalev A . Thioredoxin-interacting protein is stimulated by glucose through a carbohydrate response element and induces beta-cell apoptosis. Endocrinology. 2005; 146(5):2397-405. DOI: 10.1210/en.2004-1378. View

Zhou R, Tardivel A, Thorens B, Choi I, Tschopp J . Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol. 2009; 11(2):136-40. DOI: 10.1038/ni.1831. View

Ishida M, Shima M, Seino Y . 1,25(OH)2D and 24,25(OH)2D production in the developing kidney. Pediatr Nephrol. 1988; 2(1):166-70. DOI: 10.1007/BF00870399. View

Hanschmann E, Godoy J, Berndt C, Hudemann C, Lillig C . Thioredoxins, glutaredoxins, and peroxiredoxins--molecular mechanisms and health significance: from cofactors to antioxidants to redox signaling. Antioxid Redox Signal. 2013; 19(13):1539-605. PMC: 3797455. DOI: 10.1089/ars.2012.4599. View

10.

Park S, Garland C, Gorham E, BuDoff L, Barrett-Connor E . Plasma 25-hydroxyvitamin D concentration and risk of type 2 diabetes and pre-diabetes: 12-year cohort study. PLoS One. 2018; 13(4):e0193070. PMC: 5908083. DOI: 10.1371/journal.pone.0193070. View

11.

Jiang H, He H, Chen Y, Huang W, Cheng J, Ye J . Identification of a selective and direct NLRP3 inhibitor to treat inflammatory disorders. J Exp Med. 2017; 214(11):3219-3238. PMC: 5679172. DOI: 10.1084/jem.20171419. View

12.

Zhao Y, Zhu J, Song G, Li X . Relationship between thioredoxin-interacting protein (TXNIP) and islet β-cell dysfunction in patients with impaired glucose tolerance and hypertriglyceridemia. Int J Clin Exp Med. 2015; 8(3):4363-8. PMC: 4443188. View

13.

Chai T, Hong S, He H, Zheng L, Hagen T, Luo Y . A potential mechanism of metformin-mediated regulation of glucose homeostasis: inhibition of Thioredoxin-interacting protein (Txnip) gene expression. Cell Signal. 2012; 24(8):1700-5. DOI: 10.1016/j.cellsig.2012.04.017. View

14.

Luo B, Li B, Wang W, Liu X, Liu X, Xia Y . Rosuvastatin alleviates diabetic cardiomyopathy by inhibiting NLRP3 inflammasome and MAPK pathways in a type 2 diabetes rat model. Cardiovasc Drugs Ther. 2013; 28(1):33-43. DOI: 10.1007/s10557-013-6498-1. View

15.

Di Camillo B, Hakaste L, Sambo F, Gabriel R, Kravic J, Isomaa B . HAPT2D: high accuracy of prediction of T2D with a model combining basic and advanced data depending on availability. Eur J Endocrinol. 2018; 178(4):331-341. DOI: 10.1530/EJE-17-0921. View

16.

Gallwitz B, Kazda C, Kraus P, Nicolay C, Schernthaner G . Contribution of insulin deficiency and insulin resistance to the development of type 2 diabetes: nature of early stage diabetes. Acta Diabetol. 2011; 50(1):39-45. DOI: 10.1007/s00592-011-0319-4. View

17.

Oslowski C, Hara T, OSullivan-Murphy B, Kanekura K, Lu S, Hara M . Thioredoxin-interacting protein mediates ER stress-induced β cell death through initiation of the inflammasome. Cell Metab. 2012; 16(2):265-73. PMC: 3418541. DOI: 10.1016/j.cmet.2012.07.005. View

18.

Parikh H, Carlsson E, Chutkow W, Johansson L, Storgaard H, Poulsen P . TXNIP regulates peripheral glucose metabolism in humans. PLoS Med. 2007; 4(5):e158. PMC: 1858708. DOI: 10.1371/journal.pmed.0040158. View

19.

Tang Q, Li X, Song P, Xu L . Optimal cut-off values for the homeostasis model assessment of insulin resistance (HOMA-IR) and pre-diabetes screening: Developments in research and prospects for the future. Drug Discov Ther. 2016; 9(6):380-5. DOI: 10.5582/ddt.2015.01207. View

20.

Shao W, Yu Z, Fantus I, Jin T . Cyclic AMP signaling stimulates proteasome degradation of thioredoxin interacting protein (TxNIP) in pancreatic beta-cells. Cell Signal. 2010; 22(8):1240-6. DOI: 10.1016/j.cellsig.2010.04.001. View