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Lipid and inflammatory biomarker profiles in early insulin resistance

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Abstract

Aims

To analyze the serum lipid and inflammatory biomarker profile in the early insulin resistance (e-IR).

Methods

Cross-sectional study of 5943 adults without diabetes, stratified into no IR group (C-peptide <third tertile and glucose <100 mg/dL), e-IR group (C-peptide ≥third tertile and glucose <100 mg/dL) and advanced IR group (glucose ≥100 mg/dL).

Results

E-IR showed significant differences with no IR in the serum concentration of triglycerides (P < 0.001), HDL cholesterol (P < 0.001), LDL cholesterol (P < 0.001), sCD40L (P < 0.001), C-reactive protein (P < 0.004), leptin (P < 0.001) and adiponectin (P < 0.001). Adjusting for age, gender and abdominal obesity, corroborated the association of e-IR with highest quintile of triglycerides (OR 3.88 [3.07–4.89]), HDL cholesterol (OR 0.35 [0.28–0.44]), sCD40L (OR 0.47 [0.24–0.94]), C-reactive protein (OR 2.31 [1.29–4.12]), adiponectin (OR 0.11 [0.04–0.32]), PAI-1 (OR 3.29 [1.29–8.40]) and resistin (OR 1.25 [1.01–1.54]); the same biomarkers were associated with advanced IR although resistin was a protective factor (OR 0.73 [0.58–0.93]).

Conclusions

Euglycemic patients with e-IR present an unfavorable serum lipid and inflammatory biomarker profile. Measuring C-peptide in euglycemic patients with elevated triglycerides identifies e-IR.

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References

  1. Pajvani UB, Accili D (2015) The new biology of diabetes. Diabetologia 58:2459–2468

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Muniyappa R, Madan R, Quon MJ (2000) Assessing insulin sensitivity and resistance in humans. In: De Groot LJ, Beck-Peccoz P, Chrousos G, et al. (eds) NCBI Bookshelf. Endotext [Internet]. http://www.ncbi.nlm.nih.gov/books/NBK278954. Last Update: 2 Feb 2015

  3. Weyer C, Tataranni PA, Bogardus C et al(2001) Insulin resistance and insulin secretory dysfunction are independent predictors of worsening of glucose tolerance during each stage of type 2 diabetes development. Diabetes Care 24:89–94

    Article  CAS  PubMed  Google Scholar 

  4. Tabak AG, Jokela M, Akbaraly TN et al (2009) Trajectories of glycemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet 373:2215–2221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Shulman GI (2014) Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med 371:1131–1141

    Article  CAS  PubMed  Google Scholar 

  6. Samuel VT, Shulman GI (2016) The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J Clin Invest 126:12–22

    Article  PubMed  Google Scholar 

  7. Khodabandehloo H, Gorgani-Firuzjaee S, Panahi G, Meshkani R (2016) Molecular and cellular mechanisms linking inflammation to insulin resistance and β-cell dysfunction. Transl Res 167:228–256

    Article  CAS  PubMed  Google Scholar 

  8. Cersosimo E, DeFronzo RA (2006) Insulin resistance and endothelial dysfunction: the road map for cardiovascular diseases. Diabetes Metab Res Rev 22:423–436

    Article  CAS  PubMed  Google Scholar 

  9. Zhan Y, Tang Z, Yu J (2014) Serum ferritin, diabetes, diabetes control, and insulin resistance. Acta Diabetol 51:991–998

    Article  CAS  PubMed  Google Scholar 

  10. Kharroubi I, Ladriere L, Cardozo AK et al (2004) Free fatty acids and cytokines induce pancreatic beta cell apoptosis by different mechanisms: role of NF-kappa B and endoplasmic reticulum stress. Endocrinology 145:5087–5096

    Article  CAS  PubMed  Google Scholar 

  11. Moran A, Steffen LM, Jacobs DR Jr et al (2005) Relation of C-reactive protein to insulin resistance and cardiovascular risk factors in youth. Diabetes Care 28:1763–1768

    Article  CAS  PubMed  Google Scholar 

  12. Kajimoto Y, Matsuoka T, Kaneto H et al (1999) Induction of glycation suppresses glucokinase gene expression in HIT-T15 cells. Diabetologia 42:1417–1424

    Article  CAS  PubMed  Google Scholar 

  13. Daniele G, Guardado-Mendoza R, Winnier D et al (2014) The inflammatory status score including IL-6, TNF-α, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus. Acta Diabetol 51:123–131

    Article  CAS  PubMed  Google Scholar 

  14. Nwaneri C, Cooper H, Bowen-Jones D (2013) Screening for type 2 diabetes and population mortality over 10 years. Lancet 381:901–912

    Article  PubMed  Google Scholar 

  15. Salazar MR, Carbajal HA, Espeche WG et al (2016) Insulin resistance: the linchpin between prediabetes and cardiovascular disease. Diabetes Vasc Dis Res 13:157–163

    Article  Google Scholar 

  16. Ariel D, Reaven G (2014) Modulation of coronary heart disease risk by insulin resistance in subjects with normal glucose tolerance or prediabetes. Acta Diabetol 51:1033–1039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cabrera de León A, Oliva García JG, Marcelino Rodríguez I et al (2015) C-peptide as a risk factor of coronary artery disease in the general population. Diabetes Vasc Dis Res 12:199–207

    Article  CAS  Google Scholar 

  18. Cabrera de León A, Rodríguez Pérez MC, Almeida González D et al (2008) Presentation of the “CDC de Canarias” cohort: objectives, design and preliminary results. Rev Esp Salud Publica 82:519–534

    Article  PubMed  Google Scholar 

  19. Fernández-Bergés D, Consuegra-Sánchez L, Peñafiel J et al (2014) Perfil inflamatorio y metabólico. Estudio DARIOS Inflamatorio. Rev Esp Cardiol (Engl Ed) 67:624–631

    Article  Google Scholar 

  20. Ashwell M, Gunn P, Gibson S (2012) Waist-to-height ratio is a better screening tool than waist circumference and BMI for adult cardiometabolic risk factors: systematic review and meta-analysis. Obes Rev 13:275–286

    Article  CAS  PubMed  Google Scholar 

  21. Bo S, Gentile L, Castiglione A et al (2012) C-peptide and the risk for incident complications and mortality in type 2 diabetic patients: a retrospective cohort study after a 14-year follow-up. Eur J Endocrinol 167:173–180

    CAS  PubMed  Google Scholar 

  22. Kim ST, Kim BJ, Lim DM et al (2011) Basal C-peptide level as a surrogate marker of subclinical atherosclerosis in type 2 diabetic patients. Diabetes Metab J 35:41–49

    Article  PubMed  PubMed Central  Google Scholar 

  23. Marx N, Silbernagel G, Brandenburg V et al (2013) C-peptide levels are associated with mortality and cardiovascular mortality in patients undergoing angiography: the LURIC study. Diabetes Care 36:708–714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Marx N, Walcher D, Raichle C et al (2004) C-peptide colocalizes with macrophages in early arteriosclerotic lesions of diabetic subjects and induces monocyte chemotaxis in vitro. Arterioscler Thromb Vasc Biol 24:540–545

    Article  CAS  PubMed  Google Scholar 

  25. Kappert K, Meyborg H, Clemenz M et al (2008) Insulin facilitates monocyte migration: a possible link to tissue inflammation in insulin-resistance. Biochem Biophys Res Commun 365:503–508

    Article  CAS  PubMed  Google Scholar 

  26. Kadowaki T, Yamauchi T, Kubota N et al (2006) Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 116:1784–1792

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Schwartz DR, Lazar MA (2011) Human resistin: found in translation from mouse to man. Trends Endocrinol Metab 22:259–265

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Iqbal N, Seshadri P, Stern L et al (2005) Serum resistin is not associated with obesity or insulin resistance in humans. Eur Rev Med Pharmacol Sci 9:161–165

    CAS  PubMed  Google Scholar 

  29. Coello Domínguez S, Cabrera de León A, Almeida González D et al (2008) Inverse association between serum resistin and insulin resistance in humans. Diabetes Res Clin Pract 82:256–261

    Article  CAS  Google Scholar 

  30. Abbasi F, Okeke Q, Reaven GM (2014) Evaluation of fasting plasma insulin concentration as an estimate of insulin action in nondiabetic individuals: comparison with the homeostasis model assessment of insulin resistance (HOMA-IR). Acta Diabetol 51:193–197

    Article  CAS  PubMed  Google Scholar 

  31. Noctor E, Crowe C, Carmody LA et al (2015) ATLANTIC-DIP: prevalence of metabolic syndrome and insulin resistance in women with previous gestational diabetes mellitus by International Association of Diabetes in Pregnancy Study Groups criteria. Acta Diabetol 52:153–160

    Article  CAS  PubMed  Google Scholar 

  32. Hivert MF, Christophi CA, Franks PW et al (2016) Lifestyle and metformin ameliorate insulin sensitivity independently of the genetic burden of established insulin resistance variants in diabetes prevention program participants. Diabetes 65:520–526

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Karen Shashok for translation of the manuscript into English.

Funding

Canary Islands Health Service. Spanish Government (Instituto de Salud Carlos III, Projects 0901314, PI12/01855, and RD12/0042/0031 and 0013. FEDER).

Author information

Authors and Affiliations

  1. Research Unit, University Hospital Nuestra Señora de la Candelaria, Carretera de El Rosario 145, 38010, Santa Cruz de Tenerife, Canary Islands, Spain

    Itahisa Marcelino Rodríguez, José Juan Alemán Sánchez, Buenaventura Brito Díaz, María del Cristo Rodríguez Pérez  & Antonio Cabrera de León

  2. Cardiovascular Research Network of the Carlos III Institute of Health, Santa Cruz de Tenerife, Spain

    Itahisa Marcelino Rodríguez, José Juan Alemán Sánchez, Delia Almeida González, Santiago Domínguez Coello & Roberto Elosua

  3. Research Unit, University Hospital Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Spain

    José Oliva García

  4. Primary Care Authority, Santa Cruz de Tenerife, Spain

    José Juan Alemán Sánchez, Santiago Domínguez Coello, Buenaventura Brito Díaz & María del Cristo Rodríguez Pérez

  5. Immunology Unit, University Hospital Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, Spain

    Delia Almeida González

  6. Faculty of Sciences of Bizerte, Carthage University, Tunis, Tunisia

    Fadoua Gannar

  7. Cardiovascular Epidemiology and Genetics, IMIM, Barcelona, Spain

    Roberto Elosua

  8. Área de medicina preventiva y salud pública, Universidad de La Laguna, La Laguna, Spain

    Antonio Cabrera de León

Authors
  1. Itahisa Marcelino Rodríguez
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  2. José Oliva García
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  3. José Juan Alemán Sánchez
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  4. Delia Almeida González
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  5. Santiago Domínguez Coello
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  6. Buenaventura Brito Díaz
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  7. Fadoua Gannar
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  8. María del Cristo Rodríguez Pérez
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  9. Roberto Elosua
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  10. Antonio Cabrera de León
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Corresponding author

Correspondence to Antonio Cabrera de León.

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Conflict interests

The authors declare that they have no conflict of interest.

Ethical standard

This study was approved by the Bioethics Committee of Nuestra Señora de la Candelaria University Hospital, and all participants provided their informed consent in writing.

Human and animal rights

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5).

Informed consent

Informed consent was obtained from all patients for being included in the study.

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Managed by Antonio Secchi.

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Marcelino Rodríguez, I., Oliva García, J., Alemán Sánchez, J.J. et al. Lipid and inflammatory biomarker profiles in early insulin resistance. Acta Diabetol 53, 905–913 (2016). https://doi.org/10.1007/s00592-016-0885-6

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  • DOI: https://doi.org/10.1007/s00592-016-0885-6

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