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Plasma lactate and leukocyte mitochondrial DNA copy number as biomarkers of insulin sensitivity in non-diabetic women

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Abstract

High plasma lactate levels have been associated with reduced mitochondrial respiratory capacity and increased type 2 diabetes risk, while mitochondrial DNA (mtDNA) copy number has been proposed as a biomarker of mitochondrial function linked to glucose homeostasis. The aim of this study was to evaluate the association between circulating lactate levels and leukocyte mtDNA copy numbers with insulin secretion/sensitivity indexes in 65 Chilean non-diabetic women. mtDNA copy numbers were measured in leukocytes using qPCR and digital-droplet PCR. A 75-g Oral Glucose Tolerance Test (OGTT) was performed to calculate systemic and tissue-specific insulin sensitivity indexes, as well as insulin secretion surrogates based on plasma c-peptide. An intravenous glucose tolerance test (IVGTT; 0.3 g/kg) was also carried out. Disposition indexes were calculated as the product of insulin secretion × sensitivity. Plasma levels of leptin, adiponectin, TNF-α, MCP-1, and non-esterified fatty acids were also determined. Fasting plasma lactate shows a significant association with a wide range of insulin sensitivity/resistance indexes based on fasting plasma samples (HOMA-S, adipose IR index, Revised-QUICKI, leptin-adiponectin ratio, TyG index, McAuley index and TG-to-HDL-C ratio), as well as OGTT-based measures such as the Matsuda index, the hepatic insulin resistance index, and the disposition index. Fasting plasma lactate was also positively associated with the circulating adipokines TNF-α and MCP-1. We also detected a direct association between fasting plasma lactate with leukocyte mtDNA copy numbers. The above results support the use of fasting plasma lactate, and possibly leukocyte mtDNA copy numbers, as biomarkers of reduced oxidative mitochondrial capacity, decreased hepatic insulin sensitivity, and future diabetes risk.

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Funding

This study was supported by the Chilean Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT; projects 1150416 and 1170117), the Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBERobn), Institute of Health Carlos III, Madrid, Spain (CB12/03/30002) and Ministerio de Economía y Competitividad (AGL2013-4554-R).

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Authors and Affiliations

  1. Department of Nutrition, Diabetes and Metabolism, School of Medicine, Pontificia Universidad Católica de Chile, Avenida Libertador Bernardo O’Higgins 340, Santiago, Chile

    José L. Santos, Luis R. Cataldo, Cristián Cortés-Rivera, Carolina Bravo, Luis Díaz-Casanova & José Galgani

  2. Department of Nutrition, Food Sciences and Physiology, Centre for Nutrition Research, University of Navarra, Pamplona, Spain

    J. Alfredo Martínez & Fermín I. Milagro

  3. Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III, Madrid, Spain

    J. Alfredo Martínez & Fermín I. Milagro

  4. IdiSNA, Navarra’s Health Research Institute, Pamplona, Spain

    J. Alfredo Martínez

  5. IMDEA-Food, Madrid, Spain

    J. Alfredo Martínez

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  1. José L. Santos
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  2. Luis R. Cataldo
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  3. Cristián Cortés-Rivera
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  4. Carolina Bravo
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  6. J. Alfredo Martínez
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Correspondence to José L. Santos.

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All participants signed written informed consent and the research protocol was approved by the Ethics Committee of the School of Medicine of the Pontificia Universidad Católica de Chile.

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Santos, J.L., Cataldo, L.R., Cortés-Rivera, C. et al. Plasma lactate and leukocyte mitochondrial DNA copy number as biomarkers of insulin sensitivity in non-diabetic women. J Physiol Biochem 75, 285–297 (2019). https://doi.org/10.1007/s13105-019-00672-w

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