Skip to main content
Download PDF

Elevated levels of PAI-1 precede the occurrence of type 2 diabetes mellitus

Diabetology & Metabolic Syndrome volume 17, Article number: 61 (2025) Cite this article

Abstract

Aims

Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of the fibrinolytic system and is mainly secreted from adipose tissue. It is associated with cardiovascular disease and has also been considered a possible early risk marker for type 2 diabetes. Here, we present the results of a large prospective study investigating PAI-1 levels in relation to incident type 2 diabetes mellitus.

Methods

We conducted a prospective incident case-referent study within the Västerbotten Intervention Programme (VIP). Data on cardiovascular risk factors, fasting plasma glucose (FPG) and 2-hour plasma glucose (2-hPG) were collected at baseline health examination 1990–2005. Blood samples were collected and stored for future analyses. Participants were followed and 484 cases developed type 2 diabetes. Referents without type 2 diabetes were matched for sex, age, and year of participation, n = 484. Baseline plasma samples were analysed for PAI-1. Subgroup analysis was performed for 201 cases and 201 matched referents with normal baseline glucose levels (FPG < 6.1 and 2hPG < 8.9 mmol/L).

Results

Elevated baseline levels of PAI-1 were associated with incident type 2 diabetes after adjustments for BMI, family history of diabetes, smoking status, hypertension, FPG and 2hPG (PAI-1; OR = 1.87, 95% CI: 1.06–3.29). A similar result was shown in the subgroup analysis with 201 participants who had normal glucose levels at time of the health examination (PAI-1; OR = 2.68, 95% CI: 1.03–6.95).

Conclusions

Elevated PAI-1 levels in non-diabetic persons precede the manifestation of type 2 diabetes and can be detected before an elevation of FPG or 2-hPG is observed.

Introduction

Established risk factors for the development of type 2 diabetes include overweight, smoking, physical inactivity, high blood lipids, high blood pressure, and a family history of type 2 diabetes [1]. Plasminogen activator inhibitor-1 (PAI-1) is the main inhibitor of the fibrinolytic system and is mainly secreted from adipose tissue. PAI-1 is a marker for increased risk of cardiovascular disease. In a previous study, we included 157 diabetes-free participants that later developed type 2 diabetes and found that elevated levels of PAI-1 at baseline preceded the manifestation of type 2 diabetes [2]. In addition, several studies have reported significantly elevated PAI-1 levels in patients with type 2 diabetes compared to controls [3,4,5,6,7]. A systematic review of the epidemiological literature, supports a link between PAI-1 and risk for type 2 diabetes [8]. The conclusion was that elevated PAI-1 levels appear to be associated with incident type 2 diabetes independently of established diabetes risk factors, and that there is a need for investigation of the role of PAI-1 on diabetes risk within cohorts with normal and increased glucose levels at baseline.

The present, larger, study aims to investigate if levels of PAI-1 were associated with incident type 2 diabetes, and secondly, to explore if elevated PAI-1 levels precede the elevation of fasting plasma glucose (FPG) and 2-hour plasma glucose (2-hPG).

Methods

Study population

This is a nested case-referent study within the Västerbotten Intervention Programme (VIP) cohort [9]. Inhabitants in the Västerbotten County in the north of Sweden were invited to their local primary-care centre when they were 40, 50, or 60 years old to participate in a health survey. Health examination included measurement of height, weight, blood pressure, fasting blood glucose, oral glucose tolerance test, and a questionnaire including questions about smoking habits, physical activity and family history of diabetes. The examination was followed by a motivational health promotion dialogue with a trained nurse. Participants were asked to donate a blood sample for future research. The present study included 98 300 subjects who were health examined in VIP between 1990 and 2005, see Fig. 1. The participation rate was high; the total study population represented 70% of the eligible population [10]. A study on selection bias showed that there were small differences between participants and non-participants [11].

Fig. 1
figure 1

Flow chart showing the selection of cases and referents in the VIP cohort

*All included cases and referents have a complete set of data

Referents are matched for age, sex, and year of health examination

Full size image

Participants were followed between 1990 and 2005 and 484 cases diagnosed with incident type 2 diabetes were included via a local diabetes register (DiabNorth) according to WHO criteria [12]. One referent, without type 2 diabetes according to the registry in 2005, was randomly selected for each case, matched for age, sex, and year of health examination. Complete data sets regarding PAI-1, BMI, fasting and 2-hour glucose levels, total cholesterol, blood pressure, physical activity, smoking and family history of diabetes were found in 484 cases with diagnosed type 2 diabetes during follow-up and 484 matched referents. Participants with known type 2 diabetes or fasting plasma glucose (FPG) levels above 6.9 mmol/L or 2-hour plasma glucose (2hPG) levels above 12.1 mmol/L at baseline were excluded.

Measurements

Participants were instructed to fast from midnight until time of blood sampling. Venous blood samples were drawn with a minimum of stasis in a sitting position into evacuated tubes containing 1/100 volume of 0.5% EDTA. Each tube was centrifuged at 1500 x g; the plasma was immediately frozen at -20 °C and stored at -80 °C until analysis. Oral glucose tolerance tests were performed with a 75-g glucose load according to WHO standards. FPG was measured in venous plasma in a fasting state and in capillary plasma 2 h after glucose intake on a Reflotron bench-top analyser (Boeringer Mannheim GmbH, Mannheim, Germany). Total cholesterol was analysed on thawed frozen samples and performed via routine methods at the Department of Clinical Chemistry at Umeå University Hospital. ELISA reagent kits for PAI-1 were purchased from TrioLab (Gothenburg, Sweden). The inter-assay coefficient of variation for PAI-1 analysis was 4.4%. Samples from cases and their matched referent were analysed together in random order. All reagent kits had identical batch number. Measurements were made in 2016 by laboratory staff unaware of each subject’s disease status.

BMI was calculated as measured weight in kilograms divided by the square of the height in metres (kg/m2). Smoking was categorized into two groups (ever or never smoking). Participants were considered to have a family history of diabetes if they reported having a parent or sibling with type 2 diabetes. Physical activity was categorized into two levels based on the questionnaire: inactive or active. Hypertension was defined as systolic blood pressure of 140 mmHg or more and/or diastolic blood pressure of 90 mmHg or more and/or reported use of antihypertensive medication during the period of 14 days prior to the health examination.

Statistical methods

Data are presented as proportion (%), mean and standard deviation (SD). Significance testing was carried out using independent sample’s t-test for continuous variables and Chi-Squared test for categorical variables.

Univariable conditional logistic regression was used to calculate age- and sex-matched Odds ratios (OR) comparing the risk of incident type 2 diabetes in cases and referents. Multivariable conditional regression analysis was performed to estimate the effects of potential confounders when controlling for factors with p < 0.2 in the univariable analyses. ORs with 95% Confidence Intervals (CI) were calculated per increment of 1 SD for continuous variables. Only case-referent pairs with complete data sets were included.

To investigate whether PAI-1 increases prior to increased levels of plasma glucose we used the subgroup of case-referent pairs where both individuals had normal glucose levels (FPG < 6.1 mmol/L and 2hPG < 8.9 mmol/L) at baseline. Multivariable analysis was again performed for potential confounders as described above.

The Statistical Package for Social Science (SPSS® version 27.0) was used for statistical analysis. A p-value < 0.05 (two-sided) was considered statistically significant.

Ethical considerations

This study protocol was approved by the Research Ethics Committee of Umeå University. All participants provided written informed consent.

Results

During a mean follow-up time of 7.6 years, 484 cases developed type 2 diabetes. The mean age at health examination was 49 years and 48% were women, see Table 1. Cases had higher PAI-1 levels compared to referents as well as higher BMI, systolic blood pressure, FPG and 2hPG. More cases than referents were ever smokers, had hypertension and a family history of type 2 diabetes. PAI-1 levels were correlated to age, BMI, FPG, 2hPG, systolic blood pressure and total cholesterol levels among referents, with the strongest correlation with BMI (rs = 0.46) (Supplemental Table 1).

Table 1 Baseline characteristics of 484 cases with incident type 2 diabetes mellitus and their matched referents
Full size table

Elevated levels of PAI-1 were independently associated with incident type 2 diabetes (OR = 1.87, 95% CI: 1.06–3.29) after multivariable analysis including adjustments for BMI, family history of diabetes, smoking status, hypertension, FPG and 2hPG (Table 2).

Table 2 Conditional logistic regression for 484 cases with incident type 2 diabetes compared to their 484 matched referents
Full size table

Likewise, in the subgroup of 201 cases and matched referents with normal glucose levels (FPG < 6.1 mmol/L and 2hPG < 8.9 mmol/L) at baseline, PAI-1 concentrations were independently associated with incident type 2 diabetes in the multivariable model (PAI-1; OR = 2.68, 95% CI: 1.03–6.95), see Table 3.

Table 3 Conditional logistic regression for 201 cases and their 201 matched controls with normal levels of fasting plasma glucose (FPG) and 2-hour plasma glucose (2-hPG) and risk for incident type 2 diabetes mellitus
Full size table

Discussion

In the present study, elevated levels of PAI-1 were associated with incident type 2 diabetes, independently of established diabetes risk factors. This was true also for participants with normal blood glucose levels at health examination. These associations were independent of family history of type 2 diabetes, glucose levels, BMI and other risk factors for diabetes.

We suggest that elevated PAI-1 is an early link in the chain of events leading to type 2 diabetes. Excess visceral adipose tissue has been shown to increase PAI-1 secretion [13, 14], perhaps as a result of the chronic inflammation associated with obesity [15].

Several studies have shown the association of type 2 diabetes and increased levels of PAI-1 [8]. A meta-analysis by Yarmolinsky et al., found a link between PAI-1 and T2DM, independent of established diabetes risk factor. As the association was moderate and there was heterogeneity across the studies further prospective studies were suggested. No individual prospective study in the meta-analysis included more than 182 cases. In the present study we included 484 cases and the association between PAI-1 levels and incident type 2 diabetes remained significant after adjustments for several potential confounders. Furthermore, in participants with normal glucose levels at the health examination only PAI-1 and family history of diabetes were shown to be significantly associated with incident type 2 diabetes.

Alessi et al. have shown that adipose tissue produces PAI-1 [16], but also that insulin stimulates the synthesis of PAI-1 [17]. PAI-1 itself has been shown to inhibit insulin signaling by competing with αvβ-3 integrin for vicronectin binding [18] and by disturbing receptor substrate − 1 activity and expression [19]. Troglitazone treatment in insulin-resistant lean or obese type 2 diabetes patients can lower PAI-1 concentrations and is associated with enhanced fibrinolytic activity linked to lower plasma insulin levels and improved glycemic control [20]. Also, after being fed the same high fat diet, obesity and insulin resistance were completely prevented in mice lacking PAI-1, compared to wild-type mice [21].

In the promoter region of the PAI-1 gene there is a well-known 4G/5G polymorphism [22]. Obese women with the 5G/5G genotype has been shown to have significantly lower levels of plasma PAI-1 than the 4G/4G group [23]. However, in a multivariate analysis including insulin resistance, polymorphisms had a minor contribution to the PAI-1 variability (3% in women and no significant results in men), which indicate that PAI-1 levels depend more on metabolic changes than polymorphisms [24].

Strengths and limitations

This study has a prospective case-referent design with diabetes-free men and women aged 40 to 60 years when participating in an extensive baseline health examination. Participants who developed type 2 diabetes were examined on average 7.6 years before the manifest diagnosis. Diabetic patients were defined according to WHO criteria. Storage time has been shown to have a negligible impact on laboratory PAI-1 measurements of frozen samples [25].

The study was conducted within a well-defined intervention programme, the VIP, where recommended lifestyle changes, such as weight loss and smoking cessation, may have influenced the incidence of type 2 diabetes [26]. Most participants were of Caucasian origin limiting the possibility of generalizing the results to populations of other ethnicities. The results were based on one single baseline blood sample per participant, which may decrease the estimations of the observed associations.

Conclusions

Elevated PAI-1 levels in non-diabetic persons precede the manifestation of type 2 diabetes and can be detected before an elevation of FPG or 2-hPG is observed.

Data availability

No datasets were generated or analysed during the current study.

Abbreviations

2hPG:

2-hour plasma glucose after oral glucose tolerance test

BMI:

Body mass index

CI:

Confidence interval

FPG:

Fasting plasma glucose

OGTT:

Oral glucose tolerance test

PAI-1:

Plasminogen activator inhibitor-1

SD:

Standard deviation

type 2 diabetes:

Type 2 diabetes mellitus

VIP:

Västerbotten Intervention Programme

References

  1. Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG, et al. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med. 2001;345(11):790–7. PubMed PMID: 11556298.

    Article  CAS  PubMed  Google Scholar 

  2. Hernestål-Boman J, Norberg M, Jansson JH, Eliasson M, Eriksson JW, Lindahl B, et al. Signs of dysregulated fibrinolysis precede the development of type 2 diabetes mellitus in a population-based study. Cardiovasc Diabetol. 2012;11:152. https://doiorg.publicaciones.saludcastillayleon.es/10.1186/1475-2840-11-152. Epub 2012/12/18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Festa A, Williams K, Tracy RP, Wagenknecht LE, Haffner SM. Progression of plasminogen activator inhibitor-1 and fibrinogen levels in relation to incident type 2 diabetes. Circulation. 2006;113(14):1753–9. PubMed PMID: 16585388.

    Article  CAS  PubMed  Google Scholar 

  4. Al-Hamodi Z, Ismail IS, Saif-Ali R, Ahmed KA, Muniandy S. Association of plasminogen activator inhibitor-1 and tissue plasminogen activator with type 2 diabetes and metabolic syndrome in Malaysian subjects. Cardiovasc Diabetol. 2011;10:23. PubMed PMID: 21414238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Thorand B, Baumert J, Chambless L, Meisinger C, Kolb H, Döring A et al. Elevated markers of endothelial dysfunction predict type 2 diabetes mellitus in middle-aged men and women from the general population. Arterioscler Thromb Vasc Biol. 2006;26(2):398–405. Epub 2005/12/01. https://doiorg.publicaciones.saludcastillayleon.es/10.1161/01.ATV.0000198392.05307.aa. PubMed PMID: 16322530.

  6. Festa A, D’Agostino R Jr., Tracy RP, Haffner SM. Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes. 2002;51(4):1131–7. PubMed PMID: 11916936.

    Article  CAS  PubMed  Google Scholar 

  7. Meigs JB, O’donnell CJ, Tofler GH, Benjamin EJ, Fox CS, Lipinska I, et al. Hemostatic markers of endothelial dysfunction and risk of incident type 2 diabetes: the Framingham offspring study. Diabetes. 2006;55(2):530–7. https://doiorg.publicaciones.saludcastillayleon.es/10.2337/diabetes.55.02.06.db05-1041. PubMed PMID: 16443791.

    Article  CAS  PubMed  Google Scholar 

  8. Yarmolinsky J, Bordin Barbieri N, Weinmann T, Ziegelmann PK, Duncan BB, Inês Schmidt M. Plasminogen activator inhibitor-1 and type 2 diabetes: a systematic review and meta-analysis of observational studies. Sci Rep. 2016;6:17714. https://doiorg.publicaciones.saludcastillayleon.es/10.1038/srep17714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Norberg M, Wall S, Boman K, Weinehall L. The Vasterbotten Intervention Programme: background, design and implications. Glob Health Action. 2010;3. PubMed PMID: 20339479.

  10. Norberg M, Eriksson JW, Lindahl B, Andersson C, Rolandsson O, Stenlund H, et al. A combination of HbA1c, fasting glucose and BMI is effective in screening for individuals at risk of future type 2 diabetes: OGTT is not needed. J Intern Med. 2006;260(3):263–71. PubMed PMID: 16918824.

    Article  CAS  PubMed  Google Scholar 

  11. Weinehall L, Hallgren CG, Westman G, Janlert U, Wall S. Reduction of selection bias in primary prevention of cardiovascular disease through involvement of primary health care. Scand J Prim Health Care. 1998;16(3):171–6. PubMed PMID: 9800231.

    Article  CAS  PubMed  Google Scholar 

  12. World Health Organisation. Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a WHO consultation Part 1: Diagnosis and classification of diabetes mellitus. 1999.

  13. Sawdey MS, Loskutoff DJ. Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo. Tissue specificity and induction by lipopolysaccharide, tumor necrosis factor-alpha, and transforming growth factor-beta. J Clin Invest. 1991;88(4):1346–53. https://doiorg.publicaciones.saludcastillayleon.es/10.1172/JCI115440. PubMed PMID: 1918385; PubMed Central PMCID: PMC295605.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Shimomura I, Funahashi T, Takahashi M, Maeda K, Kotani K, Nakamura T, et al. Enhanced expression of PAI-1 in visceral fat: possible contributor to vascular disease in obesity. Nat Med. 1996;2(7):800–3. PubMed PMID: 8673927.

    Article  CAS  PubMed  Google Scholar 

  15. Samad F, Loskutoff DJ. Tissue distribution and regulation of plasminogen activator inhibitor-1 in obese mice. Mol Med. 1996;2(5):568–82. PubMed PMID: 8898373; PubMed Central PMCID: PMC2230189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Alessi MC, Peiretti F, Morange P, Henry M, Nalbone G, Juhan-Vague I. Production of plasminogen activator inhibitor 1 by human adipose tissue: possible link between visceral fat accumulation and vascular disease. Diabetes. 1997;46(5):860–7. https://doiorg.publicaciones.saludcastillayleon.es/10.2337/diab.46.5.860. Epub 1997/05/01.

    Article  CAS  PubMed  Google Scholar 

  17. Alessi MC, Juhan-Vague I, Kooistra T, Declerck PJ, Collen D. Insulin stimulates the synthesis of plasminogen activator inhibitor 1 by the human hepatocellular cell line hep G2. Thromb Haemost. 1988;60(3):491–4. Epub 1988/12/22. PubMed PMID: 3149048.

    Article  CAS  PubMed  Google Scholar 

  18. Lopez-Alemany R, Redondo JM, Nagamine Y, Munoz-Canoves P. Plasminogen activator inhibitor type-1 inhibits insulin signaling by competing with alphavbeta3 integrin for vitronectin binding. Eur J Biochem. 2003;270(5):814–21. https://doiorg.publicaciones.saludcastillayleon.es/10.1046/j.1432-1033.2003.03453.x. Epub 2003/02/27. PubMed PMID: 12603314.

    Article  CAS  PubMed  Google Scholar 

  19. Gerrits AJ, Gitz E, Koekman CA, Visseren FL, van Haeften TW, Akkerman JW. Induction of insulin resistance by the adipokines resistin, leptin, plasminogen activator inhibitor-1 and retinol binding protein 4 in human megakaryocytes. Haematologica. 2012;97(8):1149–57. PubMed PMID: 22491740; PubMed Central PMCID: PMCPMC3409811.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kruszynska YT, Yu JG, Olefsky JM, Sobel BE. Effects of troglitazone on blood concentrations of plasminogen activator inhibitor 1 in patients with type 2 diabetes and in lean and obese normal subjects. Diabetes. 2000;49(4):633–9. https://doiorg.publicaciones.saludcastillayleon.es/10.2337/diabetes.49.4.633. Epub 2000/06/28.

    Article  CAS  PubMed  Google Scholar 

  21. Ma LJ, Mao SL, Taylor KL, Kanjanabuch T, Guan Y, Zhang Y, et al. Prevention of obesity and insulin resistance in mice lacking plasminogen activator inhibitor 1. Diabetes. 2004;53(2):336–46. https://doiorg.publicaciones.saludcastillayleon.es/10.2337/diabetes.53.2.336. Epub 2004/01/30.

    Article  CAS  PubMed  Google Scholar 

  22. Humphries SE, Lane A, Dawson S, Green FR. The study of gene-environment interactions that influence thrombosis and fibrinolysis. Genetic variation at the loci for factor VII and plasminogen activator inhibitor-1. Arch Pathol Lab Med. 1992;116(12):1322–9. PubMed PMID: 1456879.

    CAS  PubMed  Google Scholar 

  23. de Paula Sabino A, Ribeiro DD, Domingueti CP, Dos Santos MS, Gadelha T, Dusse LM, et al. Plasminogen activator inhibitor-1 4G/5G promoter polymorphism and PAI-1 plasma levels in young patients with ischemic stroke. Mol Biol Rep. 2011;38(8):5355–60. https://doiorg.publicaciones.saludcastillayleon.es/10.1007/s11033-011-0687-4. PubMed PMID: 21373825.

    Article  CAS  PubMed  Google Scholar 

  24. Henry M, Tregouet DA, Alessi MC, Aillaud MF, Visvikis S, Siest G, et al. Metabolic determinants are much more important than genetic polymorphisms in determining the PAI-1 activity and antigen plasma concentrations: a family study with part of the Stanislas Cohort. Arterioscler Thromb Vasc Biol. 1998;18(1):84–91. PubMed PMID: 9445260.

    Article  CAS  PubMed  Google Scholar 

  25. Hernestal-Boman J, Jansson JH, Nilsson TK, Eliasson M, Johansson L. Long-term stability of fibrinolytic factors stored at -80 degrees C. Thromb Res. 2010;125(5):451–6. PubMed PMID: 20053424.

    Article  PubMed  Google Scholar 

  26. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, et al. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med. 2001;344(18):1343–50. PubMed PMID: 11333990.

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

Open access funding provided by Umea University.

We thank the Biobank Research Unit at Umeå University, Västerbotten Intervention Programme, and the County Council of Västerbotten for providing data and samples. This study received grants from the Visare Norr Fund, the Foundation of Medical Research in Skellefteå and the County Council of Västerbotten. Study sponsors were not involved in the interpretation of data, writing of manuscript or decision of publication.

Author information

Authors and Affiliations

  1. Department of Laboratory Medicine, University Hospital of Umeå, Umeå, Sweden

    Jenny Hernestål-Boman

  2. Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden

    Tina Öhman, Jan-Håkan Jansson, Marcus M. Lind, Olov Rolandsson, Ingvar A. Bergdahl & Lars Johansson

  3. Department of Medicine, Skellefteå Lasarett, Skellefteå, S-931 86, Sweden

    Lars Johansson

Authors
  1. Jenny Hernestål-Boman
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Tina Öhman
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Jan-Håkan Jansson
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Marcus M. Lind
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Olov Rolandsson
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Ingvar A. Bergdahl
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Lars Johansson
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

All authors reviewed and approved the manuscript. JHB: basic study design, data handling, statistical analysis and wrote initial manuscript. TÖ: data handling, statistical analysis. JHJ: initiated the study, basic stydy design, collection of study population. MML: interpretation of data, completion of manuscript. OR: collection of study population and validation of cases. IAB: collection of study population and validation of cases. LJ: initiated the study, basic study design, statistical analysis.

Corresponding author

Correspondence to Lars Johansson.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Supplementary Material 2

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hernestål-Boman, J., Öhman, T., Jansson, JH. et al. Elevated levels of PAI-1 precede the occurrence of type 2 diabetes mellitus. Diabetol Metab Syndr 17, 61 (2025). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13098-025-01629-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s13098-025-01629-4

Keywords

Diabetology & Metabolic Syndrome

ISSN: 1758-5996

Contact us