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Clinical Studies and Practice

Insulin resistance in obesity can be reliably identified from fasting plasma insulin

International Journal of Obesity volume 39, pages 1703–1709 (2015)Cite this article

Subjects

Abstract

Background/Objectives:

Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables.

Subjects/Methods:

We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6-2H2]glucose as tracer (insulin infusion dose 20 and 60 mU m−2 min−1, respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified.

Results:

Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg−1 min−1, respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd <37.3 μmol kg−1 min−1 did not differ from insulin-sensitive obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol l−1, P<0.001) and homeostasis model assessment of insulin resistance (HOMA-IR) (4.5±2.2 vs 2.7±1.4, P=0.004). Insulin-resistant obese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l−1.

Conclusions:

Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l−1 with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.

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Acknowledgements

No specific funding was received for the present study. KWH, PWG and MJS are supported by an EU grant (FP7-EU 305707). RSK is supported by a TIFN grant (2011 G003). MN is supported by VIDI and CVON grants (016.146.327 and 2012 IN-CONTROL). KWH performed the analysis, contributed to discussions about the results and wrote the manuscript. PWG, KEK, BAW, MB and RSK researched data and reviewed and approved the final manuscript. MTA was responsible for laboratory analyses and reviewed and approved the final manuscript. JAR, MN, MRS and MJS contributed to discussions about the results and reviewed and approved the final manuscript. MJS is the guarantor of this work, had full access to all data and takes responsibility for the integrity of the results.

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, The Netherlands

    K W ter Horst, P W Gilijamse, K E Koopman, B A de Weijer, M Brands, M R Soeters & M J Serlie

  2. Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands

    R S Kootte & M Nieuwdorp

  3. Department of Medicine, Academic Medical Center, Amsterdam, The Netherlands

    J A Romijn

  4. Department of Clinical Chemistry, Laboratory of Endocrinology, Academic Medical Center, Amsterdam, The Netherlands

    M T Ackermans

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  1. K W ter Horst
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Correspondence to M J Serlie.

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ter Horst, K., Gilijamse, P., Koopman, K. et al. Insulin resistance in obesity can be reliably identified from fasting plasma insulin. Int J Obes 39, 1703–1709 (2015). https://doi.org/10.1038/ijo.2015.125

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