Fasting Proinsulin Independently Predicts Incident Type 2 Diabetes in the General Population
Fasting proinsulin levels may serve as a marker of β-cell dysfunction and predict type 2 diabetes (T2D) development. Kidneys have been found to be a major site for the degradation of proinsulin. We aimed to evaluate the predictive value of proinsulin for the risk of incident T2D added to a base mode...
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/12/7/1131 |
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| author | Sara Sokooti Wendy A. Dam Tamas Szili-Torok Jolein Gloerich Alain J. van Gool Adrian Post Martin H. de Borst Ron T. Gansevoort Hiddo J. L. Heerspink Robin P. F. Dullaart Stephan J. L. Bakker |
| author_facet | Sara Sokooti Wendy A. Dam Tamas Szili-Torok Jolein Gloerich Alain J. van Gool Adrian Post Martin H. de Borst Ron T. Gansevoort Hiddo J. L. Heerspink Robin P. F. Dullaart Stephan J. L. Bakker |
| author_sort | Sara Sokooti |
| collection | DOAJ |
| description | Fasting proinsulin levels may serve as a marker of β-cell dysfunction and predict type 2 diabetes (T2D) development. Kidneys have been found to be a major site for the degradation of proinsulin. We aimed to evaluate the predictive value of proinsulin for the risk of incident T2D added to a base model of clinical predictors and examined potential effect modification by variables related to kidney function. Proinsulin was measured in plasma with U-PLEX platform using ELISA immunoassay. We included 5001 participants without T2D at baseline and during a median follow up of 7.2 years; 271 participants developed T2D. Higher levels of proinsulin were associated with increased risk of T2D independent of glucose, insulin, C-peptide, and other clinical factors (hazard ratio (HR): 1.28; per 1 SD increase 95% confidence interval (CI): 1.08–1.52). Harrell’s C-index for the Framingham offspring risk score was improved with the addition of proinsulin (<i>p</i> = 0.019). Furthermore, we found effect modification by hypertension (<i>p</i> = 0.019), eGFR (<i>p</i> = 0.020) and urinary albumin excretion (<i>p</i> = 0.034), consistent with an association only present in participants with hypertension or kidney dysfunction. Higher fasting proinsulin level is an independent predictor of incident T2D in the general population, particularly in participants with hypertension or kidney dysfunction. |
| first_indexed | 2024-03-09T03:17:12Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-09T03:17:12Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-ab6cbab09f90457182a0f83e2082b6592023-12-03T15:16:52ZengMDPI AGJournal of Personalized Medicine2075-44262022-07-01127113110.3390/jpm12071131Fasting Proinsulin Independently Predicts Incident Type 2 Diabetes in the General PopulationSara Sokooti0Wendy A. Dam1Tamas Szili-Torok2Jolein Gloerich3Alain J. van Gool4Adrian Post5Martin H. de Borst6Ron T. Gansevoort7Hiddo J. L. Heerspink8Robin P. F. Dullaart9Stephan J. L. Bakker10Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsTranslational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsTranslational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Internal Medicine, Division of Endocrinology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The NetherlandsFasting proinsulin levels may serve as a marker of β-cell dysfunction and predict type 2 diabetes (T2D) development. Kidneys have been found to be a major site for the degradation of proinsulin. We aimed to evaluate the predictive value of proinsulin for the risk of incident T2D added to a base model of clinical predictors and examined potential effect modification by variables related to kidney function. Proinsulin was measured in plasma with U-PLEX platform using ELISA immunoassay. We included 5001 participants without T2D at baseline and during a median follow up of 7.2 years; 271 participants developed T2D. Higher levels of proinsulin were associated with increased risk of T2D independent of glucose, insulin, C-peptide, and other clinical factors (hazard ratio (HR): 1.28; per 1 SD increase 95% confidence interval (CI): 1.08–1.52). Harrell’s C-index for the Framingham offspring risk score was improved with the addition of proinsulin (<i>p</i> = 0.019). Furthermore, we found effect modification by hypertension (<i>p</i> = 0.019), eGFR (<i>p</i> = 0.020) and urinary albumin excretion (<i>p</i> = 0.034), consistent with an association only present in participants with hypertension or kidney dysfunction. Higher fasting proinsulin level is an independent predictor of incident T2D in the general population, particularly in participants with hypertension or kidney dysfunction.https://www.mdpi.com/2075-4426/12/7/1131type 2 diabetesproinsulinkidney dysfunctionhypertensionpredictive value |
| spellingShingle | Sara Sokooti Wendy A. Dam Tamas Szili-Torok Jolein Gloerich Alain J. van Gool Adrian Post Martin H. de Borst Ron T. Gansevoort Hiddo J. L. Heerspink Robin P. F. Dullaart Stephan J. L. Bakker Fasting Proinsulin Independently Predicts Incident Type 2 Diabetes in the General Population Journal of Personalized Medicine type 2 diabetes proinsulin kidney dysfunction hypertension predictive value |
| title | Fasting Proinsulin Independently Predicts Incident Type 2 Diabetes in the General Population |
| title_full | Fasting Proinsulin Independently Predicts Incident Type 2 Diabetes in the General Population |
| title_fullStr | Fasting Proinsulin Independently Predicts Incident Type 2 Diabetes in the General Population |
| title_full_unstemmed | Fasting Proinsulin Independently Predicts Incident Type 2 Diabetes in the General Population |
| title_short | Fasting Proinsulin Independently Predicts Incident Type 2 Diabetes in the General Population |
| title_sort | fasting proinsulin independently predicts incident type 2 diabetes in the general population |
| topic | type 2 diabetes proinsulin kidney dysfunction hypertension predictive value |
| url | https://www.mdpi.com/2075-4426/12/7/1131 |
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