Insulin resistance in multiple tissues in patients with type 1 diabetes mellitus on long-term continuous subcutaneous insulin infusion therapy

Authors

  • Esther Donga,

    Corresponding author
    • Department of Endocrinology and Metabolic Diseases, Leiden University Medical Centre, Leiden, The Netherlands
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    • These authors contributed equally to this work.
  • Marieke van Dijk,

    1. Department of Endocrinology and Metabolic Diseases, Leiden University Medical Centre, Leiden, The Netherlands
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    • These authors contributed equally to this work.
  • Roel P .L. M. Hoogma,

    1. Groene Hart Hospital, Gouda, The Netherlands
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  • Eleonora P. M. Corssmit,

    1. Department of Endocrinology and Metabolic Diseases, Leiden University Medical Centre, Leiden, The Netherlands
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  • Johannes A. Romijn

    1. Department of Endocrinology and Metabolic Diseases, Leiden University Medical Centre, Leiden, The Netherlands
    2. Department of Internal Medicine, Amsterdam Medical Centre, Amsterdam, The Netherlands
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Esther Donga, Department of Endocrinology and Metabolic Diseases C4-R, Leiden University Medical Centre, PO Box 9600, 2300 RC Leiden, The Netherlands.

E-mail: e.donga@lumc.nl

Abstract

Background

The aim of this study was to determine whether insulin resistance is present in lean patients with uncomplicated type 1 diabetes mellitus on long-term continuous subcutaneous insulin infusion (CSII), compared with matched healthy controls.

Methods

We studied eight patients (four men and four women) with type 1 diabetes mellitus on continuous subcutaneous insulin infusion and eight healthy controls, matched for age, gender and body mass index. Insulin sensitivity was measured by hyperinsulinemic euglycemic clamp studies with infusion of [6,6-2H2] glucose.

Results

Endogenous glucose production did not differ in the basal state between patients and controls. However, endogenous glucose production was less suppressed during clamp conditions in patients compared with controls (64% vs 79%, p = 0.01), indicating decreased hepatic insulin sensitivity. During the clamp study, glucose disposal rate was ~38% lower in patients compared with controls (24.4 ± 2.5 vs 39.7 ± 5.6 µmol/kgLBM/min, p = 0.04). Accordingly, the rate of infusion of glucose was ~51% lower in patients (17.7 ± 2.8 vs 39.7 ± 5.7 µmol/kgLBM/min, p = 0.02). Finally, non-esterified fatty acids levels were ~2.5 times higher in patients during steady state clamp conditions (150 ± 26 vs 58 ± 4 pmol/L, p = 0.01), reflecting decreased insulin sensitivity of lipolysis.

Conclusions

Insulin resistance is a prominent feature of lean patients with type 1 diabetes mellitus, despite long term and stable treatment with continuous subcutaneous insulin infusion. Insulin resistance in type 1 diabetes involves both lipolysis, hepatic and peripheral glucose metabolism. Copyright © 2012 John Wiley & Sons, Ltd.

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