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Association between protein signals and type 2 diabetes incidence

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Abstract

Understanding early determinants of type 2 diabetes is essential for refining disease prevention strategies. Proteomic technology may provide a useful approach to identify novel protein patterns potentially related to pathophysiological changes that lead up to diabetes. In this study, we sought to identify protein signals that are associated with diabetes incidence in a middle-aged population. Serum samples from 519 participants in a nested case–control selection (167 cases and 352 age-, sex- and BMI-matched normoglycemic control subjects, median follow-up 14.0 years) within the Whitehall-II cohort were analyzed by linear matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Nine protein peaks were found to be associated with incident diabetes. Rate ratios for high peak intensity ranged between 0.4 (95% CI, 0.2–0.8) and 4.0 (95% CI, 1.7–9.2) and were robust to adjustment for main potential confounders, including obesity, lipids and C-reactive protein. The proteins associated with these peaks may reflect diabetes pathogenesis. Our study exemplifies the utility of an approach that combines proteomic and epidemiological data.

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Acknowledgments

The Whitehall II study is supported by the Medical Research Council, the British Heart Foundation, the US National Institutes of Health (R01HL36310, R01AG013196, R01AG034454).

Conflict of interest

TMJ, DRW and DV are employed by the Steno Diabetes Center A/S, a research hospital working in the Danish National Health Service and owned by Novo Nordisk A/S. TMJ, DRW and DV hold shares in Novo Nordisk Inc. Remaining authors declare no duality of interest.

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Authors and Affiliations

  1. Steno Diabetes Center A/S, Gentofte, Denmark

    Troels Mygind Jensen, Daniel R. Witte & Dorte Vistisen

  2. Department of Biomedical Sciences, University “G. d’Annunzio” of Chieti-Pescara, Chieti, Italy

    Damiana Pieragostino

  3. Hagedorn Research Institute, Gentofte, Denmark

    James N. McGuire & Ellis D. Schjerning

  4. IRCCS-Santa Lucia Foundation, Rome, Italy

    Chiara Nardi & Andrea Urbani

  5. Department of Internal Medicine, University “Tor Vergata”, Rome, Italy

    Andrea Urbani

  6. Department of Epidemiology & Public Health, University College London, London, UK

    Mika Kivimäki, Eric J. Brunner & Adam G. Tabàk

  7. Semmelweis University Faculty of Medicine, 1st Department of Medicine, Budapest, Hungary

    Adam G. Tabàk

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  1. Troels Mygind Jensen
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  2. Daniel R. Witte
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Correspondence to Troels Mygind Jensen.

Appendix

Appendix

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Table 4 Baseline characteristics of participants with and without MALDI-TOF spectra
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Jensen, T.M., Witte, D.R., Pieragostino, D. et al. Association between protein signals and type 2 diabetes incidence. Acta Diabetol 50, 697–704 (2013). https://doi.org/10.1007/s00592-012-0376-3

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