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Disproportionately elevated proinsulinemia is observed at modestly elevated glucose levels within the normoglycemic range

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Abstract

We aimed to evaluate disproportional proinsulinemia in the pre-diabetic state by analyzing the cross-sectional differences between proinsulin (PI) ratios across the entire range of fasting and 2-h plasma glucose. The study sample was 1,016 participants in the insulin resistance atherosclerosis study, who had no previous diagnosis of diabetes. Insulin sensitivity index (SI) and acute insulin response (AIR) were measured by the frequently sampled intravenous glucose tolerance test. Fasting intact and split PI-to-insulin ratios (PI/I, SPI/I), intact and split PI-to-C-peptide ratios (PI/C-pep, SPI/C-pep), and SI-adjusted AIR were assessed as a function of fasting and 2-h glucose levels. SI-adjusted AIR was decreased (fasting glucose 96–98 mg/dl; 2-h glucose 120–131 mg/dl) and SPI/C-pep increased at modestly elevated fasting glucose and 2-h glucose within the normal glucose tolerance range (fasting glucose 96–98 mg/dl; 2-h glucose 132–142 mg/dl). PI/I was not increased until plasma glucose values were in the diabetic range of fasting glucose (>126 mg/dl) or the impaired glucose tolerance range of 2-h glucose (143–156 mg/dl). SPI/I and PI/C-pep as a function of fasting and 2-h glucose were situated between the curves for SPI/C-pep and PI/I. In conclusion, inappropriate amounts of PI and conversion intermediaries are demonstrated at modestly elevated glucose levels within the normoglycemic range. Ratios that use SPI in the numerator or C-pep in the denominator (and especially SPI/C-pep) are more sensitive to early glycemic excursions than PI/I. Disordered processing of PI may accompany derangements in early insulin secretory response.

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Acknowledgments

This study was supported by National Heart, Lung, and Blood Institute Grants HL-47887, HL-47889, HL-47890, HL-47892, and HL-47902 and the General Clinical Research Centers Program (NCRR GCRC, M01 RR431, and M01 RR01346). None of the funding organizations had any role in study design, data collection and analysis, or preparation of the manuscript.

Conflict of interest

Carlos Lorenzo, Anthony J. Hanley, Marian J. Rewers and Steven M. Haffner declare they have no conflict of interest.

Human and Animal Rights

All the procedures were followed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

Informed Consent

The IRAS protocol was approved by local institutional review committees, and all participants provided written informed consent prior to the inclusion in the study.

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Authors and Affiliations

  1. Department of Medicine, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX, 78229, USA

    Carlos Lorenzo & Steven M. Haffner

  2. Department of Nutritional Sciences and Medicine, University of Toronto, Toronto, ON, Canada

    Anthony J. Hanley

  3. Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada

    Anthony J. Hanley

  4. Barbara Davis Center for Childhood Diabetes, University Colorado School of Medicine, Aurora, CO, USA

    Marian J. Rewers

Authors
  1. Carlos Lorenzo
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  2. Anthony J. Hanley
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  3. Marian J. Rewers
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  4. Steven M. Haffner
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Corresponding author

Correspondence to Carlos Lorenzo.

Additional information

Communicated by Massimo Porta.

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Lorenzo, C., Hanley, A.J., Rewers, M.J. et al. Disproportionately elevated proinsulinemia is observed at modestly elevated glucose levels within the normoglycemic range. Acta Diabetol 51, 617–623 (2014). https://doi.org/10.1007/s00592-014-0565-3

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  • DOI: https://doi.org/10.1007/s00592-014-0565-3

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