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Insulin resistance, low-grade inflammation and type 1 diabetes mellitus

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Abstract

To assess the relationships between insulin resistance and low-grade inflammation in subjects with type 1 diabetes mellitus (T1DM) who do not have clinical macrovascular complications. A total of 120 subjects diagnosed with T1DM 14 years before were evaluated for the following: (1) sex, age, body mass index, waist-to-hip ratio (WHR), blood pressure, smoking, alcohol intake, insulin dose, HbA1c and lipid profile; (2) microvascular complications; (3) plasma concentrations of soluble fractions of tumour necrosis factor-α receptors type 1 and 2, interleukin-6, adiponectin, leptin and high-sensitivity C-reactive protein (hs-CRP); and (4) insulin resistance (estimation of the glucose disposal rate—eGDR). Those subjects with an eGDR below the median of the same sex group were classified as insulin resistant and the others as insulin sensitive. Insulin-resistant men, compared to the insulin-sensitive, had higher WHR (0.89 ± 0.08 vs. 0.83 ± 0.05; P < 0.01), higher systolic [121 (118–125) vs. 114 (108–120) mmHg; P = 0.01] and diastolic [73 (66–80) vs. 67 (70–73) mmHg; P = 0.02] blood pressures, higher HbA1c values [8.7 (8.1–9.9) vs. 7.5 (7.2–8.0) %; P < 0.01] and higher hs-CRP concentrations [1.16 (0.61–3.20) vs. 0.49 (0.31–0.82) mg/dl; P = 0.01], but no other significant differences between groups were found. Insulin-resistant women had higher WHR and HbA1c values, compared to the insulin-sensitive, but they did not have any other differences. In men, hs-CRP correlated significantly with WHR and HbA1c (r = 0.363; P = 0.016 and r = 0.317; P = 0.036, respectively), after adjusting for age, alcohol intake, smoking and microvascular complications. Insulin-resistant men with T1DM have an increase in plasma concentrations of hs-CRP. Central obesity and HbA1c are its main determinants.

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References

  1. Pambianco G, Costacou T, Orchard TJ (2007) The prediction of major outcomes of type 1 diabetes: a 12-year prospective evaluation of three separate definitions of the metabolic syndrome and their components and estimated glucose disposal rate: the Pittsburgh Epidemiology of Diabetes Complications Study Experience. Diabetes Care 30(5):1248–1254

    Article  PubMed  Google Scholar 

  2. Thorn LM, Forsblom C, Fagerudd J, Thomas MC, Pettersson-Fernholm K, Saraheimo M, Waden J, Ronnback M, Rosengard-Barlund M, Bjorkesten CG, Taskinen MR, Groop PH (2005) Metabolic syndrome in type 1 diabetes: association with diabetic nephropathy and glycemic control (the FinnDiane study). Diabetes Care 28(8):2019–2024

    Article  PubMed  Google Scholar 

  3. Orchard TJ, Chang YF, Ferrell RE, Petro N, Ellis DE (2002) Nephropathy in type 1 diabetes: a manifestation of insulin resistance and multiple genetic susceptibilities? Further evidence from the Pittsburgh Epidemiology of Diabetes Complication Study. Kidney Int 62(3):963–970

    Article  PubMed  CAS  Google Scholar 

  4. Orchard TJ, Olson JC, Erbey JR, Williams K, Forrest KY, Smithline Kinder L, Ellis D, Becker DJ (2003) Insulin resistance-related factors, but not glycemia, predict coronary artery disease in type 1 diabetes: 10-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetes Care 26(5):1374–1379

    Article  PubMed  Google Scholar 

  5. Kilpatrick ES, Rigby AS, Atkin SL (2007) Insulin resistance, the metabolic syndrome, and complication risk in type 1 diabetes: “double diabetes” in the diabetes control and complications trial. Diabetes Care 30(3):707–712

    Article  PubMed  CAS  Google Scholar 

  6. Schram MT, Chaturvedi N, Schalkwijk CG, Fuller JH, Stehouwer CD (2005) Markers of inflammation are cross-sectionally associated with microvascular complications and cardiovascular disease in type 1 diabetes—the EURODIAB Prospective Complications Study. Diabetologia 48(2):370–378

    Article  PubMed  CAS  Google Scholar 

  7. Saraheimo M, Teppo AM, Forsblom C, Fagerudd J, Groop PH (2003) Diabetic nephropathy is associated with low-grade inflammation in type 1 diabetic patients. Diabetologia 46(10):1402–1407

    Article  PubMed  CAS  Google Scholar 

  8. Gonzalez-Clemente JM, Mauricio D, Richart C, Broch M, Caixas A, Megia A, Gimenez-Palop O, Simon I, Martinez-Riquelme A, Gimenez-Perez G, Vendrell J (2005) Diabetic neuropathy is associated with activation of the TNF-alpha system in subjects with type 1 diabetes mellitus. Clin Endocrinol 63(5):525–529

    Article  CAS  Google Scholar 

  9. Colhoun HM, Schalkwijk C, Rubens MB, Stehouwer CD (2002) C-reactive protein in type 1 diabetes and its relationship to coronary artery calcification. Diabetes Care 25(10):1813–1817

    Article  PubMed  CAS  Google Scholar 

  10. Gonzalez-Clemente JM, Vilardell C, Broch M, Megia A, Caixas A, Gimenez-Palop O, Richart C, Simon I, Martinez-Riquelme A, Arroyo J, Mauricio D, Vendrell J (2007) Lower heart rate variability is associated with higher plasma concentrations of IL-6 in type 1 diabetes. Eur J Endocrinol 157(1):31–38

    Article  PubMed  CAS  Google Scholar 

  11. Laaksonen DE, Niskanen L, Nyyssonen K, Punnonen K, Tuomainen TP, Valkonen VP, Salonen R, Salonen JT (2004) C-reactive protein and the development of the metabolic syndrome and diabetes in middle-aged men. Diabetologia 47(8):1403–1410

    Article  PubMed  CAS  Google Scholar 

  12. Festa A, D’Agostino R Jr, Howard G, Mykkanen L, Tracy RP, Haffner SM (2000) Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 102(1):42–47

    PubMed  CAS  Google Scholar 

  13. Tan KC, Chow WS, Tam S, Bucala R, Betteridge J (2004) Association between acute-phase reactants and advanced glycation end products in type 2 diabetes. Diabetes Care 27(1):223–228

    Article  PubMed  CAS  Google Scholar 

  14. Stehouwer CD, Gall MA, Twisk JW, Knudsen E, Emeis JJ, Parving HH (2002) Increased urinary albumin excretion, endothelial dysfunction, and chronic low-grade inflammation in type 2 diabetes: progressive, interrelated, and independently associated with risk of death. Diabetes 51(4):1157–1165

    Article  PubMed  CAS  Google Scholar 

  15. Fernandez-Real JM, Ricart W (2003) Insulin resistance and chronic cardiovascular inflammatory syndrome. Endocr Rev 24(3):278–301

    Article  PubMed  CAS  Google Scholar 

  16. Su SC, Pei D, Hsieh CH, Hsiao FC, Wu CZ, Hung YJ (2010) Circulating pro-inflammatory cytokines and adiponectin in young men with type 2 diabetes. Acta diabetologica Jan 8 (Epub ahead of print)

  17. Stefan N, Vozarova B, Funahashi T, Matsuzawa Y, Weyer C, Lindsay RS, Youngren JF, Havel PJ, Pratley RE, Bogardus C, Tataranni PA (2002) Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans. Diabetes 51(6):1884–1888

    Article  PubMed  CAS  Google Scholar 

  18. King GA, Deemer SE, Thompson DL (2010) Adiponectin is associated with risk of the metabolic syndrome and insulin resistance in women. Acta diabetologica May 8 (Epub ahead of print)

  19. Ruan W, Lai M (2010) Insulin-like growth factor binding protein: a possible marker for the metabolic syndrome? Acta Diabetol 47(1):5–14

    Article  PubMed  CAS  Google Scholar 

  20. Goday A, Castell C, Tresserras R, Canela J, Taberner JL, Lloveras G (1992) Incidence of type 1 (insulin-dependent) diabetes mellitus in Catalonia, Spain. The Catalan epidemiology diabetes study group. Diabetologia 35(3):267–271

    Article  PubMed  CAS  Google Scholar 

  21. Brun JF, Ghanassia E, Fedou C, Bordenave S, Raynaud de Mauverger E, Mercier J (2010) Assessment of insulin sensitivity (S(I)) and glucose effectiveness (S (G)) from a standardized hyperglucidic breakfast test in type 2 diabetics exhibiting various levels of insulin resistance. Acta diabetologica Oct 28 (Epub ahead of print)

  22. Williams KV, Erbey JR, Becker D, Arslanian S, Orchard TJ (2000) Can clinical factors estimate insulin resistance in type 1 diabetes? Diabetes 49(4):626–632

    Article  PubMed  CAS  Google Scholar 

  23. Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18(6):499–502

    PubMed  CAS  Google Scholar 

  24. Feldman EL, Stevens MJ, Thomas PK, Brown MB, Canal N, Greene DA (1994) A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy. Diabetes Care 17(11):1281–1289

    Article  PubMed  CAS  Google Scholar 

  25. Saltevo J, Vanhala M, Kautiainen H, Kumpusalo E, Laakso M (2008) Gender differences in C-reactive protein, interleukin-1 receptor antagonist and adiponectin levels in the metabolic syndrome: a population-based study. Diabet Med 25(6):747–750

    Article  PubMed  CAS  Google Scholar 

  26. Saraheimo M, Forsblom C, Fagerudd J, Teppo AM, Pettersson-Fernholm K, Frystyk J, Flyvbjerg A, Groop PH (2005) Serum adiponectin is increased in type 1 diabetic patients with nephropathy. Diabetes Care 28(6):1410–1414

    Article  PubMed  CAS  Google Scholar 

  27. Jenkins AJ, Rothen M, Klein RL, Moller K, Eldridge L, Zheng D, Durazo-Arvizu R, McGee D, Lackland D, Thorpe SR, Garvey WT, Lyons TJ (2008) Cross-sectional associations of C-reactive protein with vascular risk factors and vascular complications in the DCCT/EDIC cohort. J Diabetes Complicat 22(3):153–163

    Article  PubMed  Google Scholar 

  28. Mackness B, Hine D, McElduff P, Mackness M (2006) High C-reactive protein and low paraoxonase1 in diabetes as risk factors for coronary heart disease. Atherosclerosis 186(2):396–401

    Article  PubMed  CAS  Google Scholar 

  29. Hayaishi-Okano R, Yamasaki Y, Katakami N, Ohtoshi K, Gorogawa S, Kuroda A, Matsuhisa M, Kosugi K, Nishikawa N, Kajimoto Y, Hori M (2002) Elevated C-reactive protein associates with early-stage carotid atherosclerosis in young subjects with type 1 diabetes. Diabetes Care 25(8):1432–1438

    Article  PubMed  CAS  Google Scholar 

  30. Schram MT, Chaturvedi N, Schalkwijk C, Giorgino F, Ebeling P, Fuller JH, Stehouwer CD (2003) Vascular risk factors and markers of endothelial function as determinants of inflammatory markers in type 1 diabetes: the EURODIAB Prospective Complications Study. Diabetes Care 26(7):2165–2173

    Article  PubMed  Google Scholar 

  31. Kilpatrick ES, Keevil BG, Jagger C, Spooner RJ, Small M (2000) Determinants of raised C-reactive protein concentration in type 1 diabetes. QJM 93(4):231–236

    Article  PubMed  CAS  Google Scholar 

  32. Schalkwijk CG, Poland DC, van Dijk W, Kok A, Emeis JJ, Drager AM, Doni A, van Hinsbergh VW, Stehouwer CD (1999) Plasma concentration of C-reactive protein is increased in type I diabetic patients without clinical macroangiopathy and correlates with markers of endothelial dysfunction: evidence for chronic inflammation. Diabetologia 42(3):351–357

    Article  PubMed  CAS  Google Scholar 

  33. Willerson JT, Ridker PM (2004) Inflammation as a cardiovascular risk factor. Circulation 109(21 Suppl 1):II2–10

    Google Scholar 

  34. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95(5):2409–2415

    Article  PubMed  CAS  Google Scholar 

  35. Picardi A, Valorani MG, Vespasiani Gentilucci U, Manfrini S, Ciofini O, Cappa M, Guglielmi C, Pozzilli P (2007) Raised C-reactive protein levels in patients with recent onset type 1 diabetes. Diabetes Metab Res Rev 23(3):211–214

    Article  PubMed  CAS  Google Scholar 

  36. Blum CA, Muller B, Huber P, Kraenzlin M, Schindler C, De Geyter C, Keller U, Puder JJ (2005) Low-grade inflammation and estimates of insulin resistance during the menstrual cycle in lean and overweight women. J Clin Endocrinol Metab 90(6):3230–3235

    Article  PubMed  CAS  Google Scholar 

  37. Carlson CS, Aldred SF, Lee PK, Tracy RP, Schwartz SM, Rieder M, Liu K, Williams OD, Iribarren C, Lewis EC, Fornage M, Boerwinkle E, Gross M, Jaquish C, Nickerson DA, Myers RM, Siscovick DS, Reiner AP (2005) Polymorphisms within the C-reactive protein (CRP) promoter region are associated with plasma CRP levels. Am J Hum Genet 77(1):64–77

    Article  PubMed  CAS  Google Scholar 

  38. Eklund C, Kivimaki M, Islam MS, Juonala M, Kahonen M, Marniemi J, Lehtimaki T, Viikari J, Raitakari OT, Hurme M (2008) C-reactive protein genetics is associated with carotid artery compliance in men in the cardiovascular risk in young finns study. Atherosclerosis 196(2):841–848

    Article  PubMed  CAS  Google Scholar 

  39. Lange LA, Carlson CS, Hindorff LA, Lange EM, Walston J, Durda JP, Cushman M, Bis JC, Zeng D, Lin D, Kuller LH, Nickerson DA, Psaty BM, Tracy RP, Reiner AP (2006) Association of polymorphisms in the CRP gene with circulating C-reactive protein levels and cardiovascular events. JAMA 296(22):2703–2711

    Article  PubMed  CAS  Google Scholar 

  40. Szalai AJ, Wu J, Lange EM, McCrory MA, Langefeld CD, Williams A, Zakharkin SO, George V, Allison DB, Cooper GS, Xie F, Fan Z, Edberg JC, Kimberly RP (2005) Single-nucleotide polymorphisms in the C-reactive protein (CRP) gene promoter that affect transcription factor binding, alter transcriptional activity, and associate with differences in baseline serum CRP level. J Mol Med (Berlin, Germany) 83(6):440–447

    Article  CAS  Google Scholar 

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Acknowledgments

Financial support was provided by: (1) Fondo de Investigaciones Sanitarias (CIBERDEM; 2008 Intensification Grant to José Miguel González-Clemente), Instituto de Salud Carlos III. Ministerio de Sanidad y Consumo, Spain; (2) Associació Catalana de Diabetis (Beca Gonçal Lloveras 2008); (3) Fundació la Marató de TV3-2008 (081410); and (4) Intensification Grant from the Comité Institucional de Recerca i Innovació (Corporació Parc Taulí) (2008–2009).

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Authors and Affiliations

  1. Department of Diabetes, Endocrinology and Nutrition, Hospital de Sabadell, Corporació Sanitària i Institut Universitari Parc Taulí (UAB), Parc Taulí s/n, 08208, Sabadell, Spain

    G. Llauradó, R. Tirado, A. Caixàs, O. Giménez-Palop & J. M. González-Clemente

  2. Centro de Investigación Biomédica en Red de Diabetes y enfermedades metabólicas asociadas (CIBERDEM), University Hospital of Tarragona Joan XXIII, Pere Virgili Institute, Universitat Rovira i Virgili, Dr. Mallafré Guasch 4, 43007, Tarragona, Spain

    L. Gallart, A. Megia, I. Simón & J. Vendrell

  3. Biochemistry Department, UDIAT, Corporació Sanitària i Institut Universitari Parc Taulí (UAB), Parc Taulí s/n, 08208, Sabadell, Spain

    E. Berlanga

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  1. G. Llauradó
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  2. L. Gallart
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  3. R. Tirado
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  4. A. Megia
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  6. A. Caixàs
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  8. E. Berlanga
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  9. J. Vendrell
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  10. J. M. González-Clemente
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Correspondence to G. Llauradó.

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Llauradó, G., Gallart, L., Tirado, R. et al. Insulin resistance, low-grade inflammation and type 1 diabetes mellitus. Acta Diabetol 49, 33–39 (2012). https://doi.org/10.1007/s00592-011-0257-1

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  • DOI: https://doi.org/10.1007/s00592-011-0257-1

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