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The effects of diet- and RYGB-induced weight loss on insulin sensitivity in obese patients with and without type 2 diabetes

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Abstract

Aims

The impact of diet-induced weight loss and weight loss due to RYGB in patients with (T2DM, N = 16) and without (OB, N = 27) type 2 diabetes was studied.

Methods

At inclusion (A), after diet-induced weight loss (B), 4 months post-surgery (C) and 18 months post-surgery (D) body composition, hepatic glucose production (HGP), insulin-mediated glucose uptake (GIR), respiratory exchange ratio, hepatic insulin sensitivity and clearance were determined. GLUT4, intramuscular triglycerides (IMTG) and glycogen content were measured in skeletal muscle.

Results

Weight loss was 35–40 kg, and approximately one-third of the total improvement in GIR in T2DM was observed after the diet-induced weight loss of only ~6 kg (B). Insulin clearance, visceral fat and fasting plasma insulin also improved significantly after the diet (P < 0.05). Throughout the study, HGP, GLUT4 and glycogen content did not change significantly, but IMTG decreased significantly consistent with significant increases in GIR. Metabolic flexibility and hepatic insulin sensitivity improved after RYGB.

Conclusions

Metabolic improvements of RYGB are present already after the diet-induced weight loss prior to surgery. GLUT4 content in skeletal muscle cannot and IMTG content can only partly explain increases in GIR after RYGB.

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Abbreviations

GIR:

Glucose infusion rate

HGP:

Hepatic glucose production

HISI:

Hepatic insulin sensitivity index

IMTG:

Intramuscular triglyceride

OB:

Patients without type 2 diabetes

RER:

Respiratory exchange ratio

RYGB:

Roux-en-Y gastric bypass

T2DM:

Patients with type 2 diabetes

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Acknowledgments

Technical assistance from Jeppe Bach, Thomas Bech, Christina Neigaard Hansen, Katrine Qvist and Regitze Kraunsøe (Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen) is gratefully acknowledged. Sina Dalby, Emilie Hansen, Lærke Taudorf and Stinna Skaaby (Xlab, Center for Healthy Aging, Department of Biomedical Sciences, University of Copenhagen) are thanked for helping with recruitment and test days. The nurses Lisette Lind Larsen and Anne-Lise Mortensen (Department of Surgery, Koege Hospital) are thanked for their help. Annette Svenningsen, MD, and surgeon Andrea Karen Floyd (Koege Hospital) are thanked for the recruitment of the first patients. Lene Foged (Clinical Metabolism, Department of Biomedical Sciences, University of Copenhagen) is acknowledged for isotope analysis. We thank all the subjects who participated in the study for their cooperation.

Funding

The financial support from the Innovation Fund Denmark (0603-00381B), the Nordea Foundation, Kathrine and Vigo Skovgaards Foundation and Simon Fougner Hartmann Family Foundation is gratefully acknowledged.

Contribution statement

M.H. performed clinical study, researched data and wrote the manuscript. M.T.L. performed clinical study, researched data and reviewed the manuscript. A.L.J./M.P. performed clinical study. G.v.H. advised on isotopes and contributed to results and discussion. J.W.H. researched data and reviewed/edited the manuscript. F.D. designed the study, researched data and reviewed/edited the manuscript. M.H. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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Authors and Affiliations

  1. Xlab, Center for Healthy Aging, Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark

    Merethe Hansen, Michael Taulo Lund, Anne Line Kjærholm Jørgensen, Marie Kroman Palsøe, Jørn Wulff Helge & Flemming Dela

  2. Department of Surgery, Koege University Hospital, Lykkebaekvej 1, 4600, Koege, Denmark

    Michael Taulo Lund

  3. Clinical Metabolism, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark

    Gerrit van Hall

Authors
  1. Merethe Hansen
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  2. Michael Taulo Lund
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Correspondence to Merethe Hansen.

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The authors declare that they have no conflict of interest.

Human and animal rights statement

All procedures were followed in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and were carried out in accordance with the Declaration of Helsinki as revised in 2008 and approved by the local ethics committee of Copenhagen (Protocol: H-C-2009-050).

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All patients gave informed written consent.

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Hansen, M., Lund, M.T., Jørgensen, A.L.K. et al. The effects of diet- and RYGB-induced weight loss on insulin sensitivity in obese patients with and without type 2 diabetes. Acta Diabetol 53, 423–432 (2016). https://doi.org/10.1007/s00592-015-0812-2

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  • DOI: https://doi.org/10.1007/s00592-015-0812-2

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