Skip to main content

Advertisement

SpringerLink
Go to cart
  • Log in
  1. Home
  2. Diabetologia
  3. Article
NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X
Download PDF
Your article has downloaded

Similar articles being viewed by others

Slider with three articles shown per slide. Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide.

Clinical investigation of lipopolysaccharide in the persistence of metabolic syndrome (MS) through the activation of GRP78-IRE1α-ASK1 signaling pathway

30 November 2021

Xiangyu Wang, Huaping Zhang, … Xin Zhou

Markers of metabolic endotoxemia as related to metabolic syndrome in an elderly male population at high cardiovascular risk: a cross-sectional study

21 July 2018

Ayodeji Awoyemi, Marius Trøseid, … Ingebjørg Seljeflot

Comparing the inflammatory profiles for incidence of diabetes mellitus and cardiovascular diseases: a prospective study exploring the ‘common soil’ hypothesis

12 June 2018

Xue Bao, Yan Borné, … Gunnar Engström

Correlation between heat shock proteins, adiponectin, and T lymphocyte cytokine expression in type 2 diabetics

11 May 2018

Fadia F. Mahmoud, David Haines, … Fawzia Al-Najjar

A signature of circulating inflammatory proteins and development of end-stage renal disease in diabetes

22 April 2019

Monika A. Niewczas, Meda E. Pavkov, … Andrzej S. Krolewski

The Interconnection Between Immuno-Metabolism, Diabetes, and CKD

19 March 2019

Fabrizia Bonacina, Andrea Baragetti, … Giuseppe Danilo Norata

Increased Plasma Levels of Triglyceride-Enriched Lipoproteins Associate with Systemic Inflammation, Lipopolysaccharides, and Gut Dysbiosis in Common Variable Immunodeficiency

30 March 2023

Magnhild E. Macpherson, Tonje Skarpengland, … Silje F. Jørgensen

Insulin resistance is linked to a specific profile of immune activation in human subjects

10 June 2021

Renaud Cezar, Delphine Desigaud, … Pierre Corbeau

Evaluation of alterations in serum immunoglobulin concentrations in components of metabolic syndrome, obesity, diabetes, and dyslipidemia

30 December 2019

Dee Lin, Mary Barna Bridgeman & Luigi Brunetti

Download PDF
  • Originals
  • Published: November 1997

NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X

  • J. C. Pickup1,
  • M. B. Mattock1,
  • G. D. Chusney1 &
  • …
  • D. Burt2 

Diabetologia volume 40, pages 1286–1292 (1997)Cite this article

  • 3796 Accesses

  • 953 Citations

  • 11 Altmetric

  • Metrics details

Summary

Non-insulin-dependent diabetes mellitus (NIDDM) is commonly associated with hypertrigly-ceridaemia, low serum HDL-cholesterol concentrations, hypertension, obesity and accelerated atherosclerosis (metabolic syndrome X). Since a similar dyslipidaemia occurs with the acute-phase response, we investigated whether elevated acute-phase/stress reactants (the innate immune system’s response to environmental stress) and their major cytokine mediator (interleukin-6, IL-6) are associated with NIDDM and syndrome X, and may thus provide a unifying pathophysiological mechanism for these conditions. Two groups of Caucasian subjects with NIDDM were studied. Those with any 4 or 5 features of syndrome X (n = 19) were compared with a group with 0 or 1 feature of syndrome X (n = 25) but similar age, sex distribution, diabetes duration, glycaemic control and diabetes treatment. Healthy non-diabetic subjects of comparable age and sex acted as controls. Overnight urinary albumin excretion rate, a risk factor for cardiovascular disease, was also assayed in subjects to assess its relationship to the acute-phase response. Serum sialic acid was confirmed as a marker of the acute-phase response since serum concentrations were significantly related to established acute-phase proteins such as α-1 acid glycoprotein (r = 0.82, p < 0.0001). There was a significant graded increase of serum sialic acid, α-1 acid glycoprotein, IL-6 and urinary albumin excretion rate amongst the three groups, with the lowest levels in non-diabetic subjects, intermediate levels in NIDDM patients without syndrome X and highest levels in NIDDM patients with syndrome X. C-reactive protein and cortisol levels were also higher in syndrome X-positive compared to -negative patients and serum amyloid A was higher in both diabetic groups than in the control group. We conclude that NIDDM is associated with an elevated acute-phase response, particularly in those with features of syndrome X. Abnormalities of the innate immune system may be a contributor to the hypertriglyceridaemia, low HDL cholesterol, hypertension, glucose intolerance, insulin resistance and accelerated atherosclerosis of NIDDM. Microalbuminuria may be a component of the acutephase response.

Download to read the full article text

Working on a manuscript?

Avoid the common mistakes

Abbreviations

VLDL:

Very low density lipoprotein

HDL:

high density lipoprotein

PAI-1:

plasma activator inhibitor-1

NIDDM:

non-insulin-dependent diabetes mellitus

CHD:

coronary heart disease

IL-6:

interleukin-6

TNF-α:

tumour necrosis factor-α

References

  1. Kaplan NM (1989) The deadly quartet: upper-body obesity, glucose intolerance, hypertriglyceridemia and hypertension. Arch Intern Med 149: 1514–1520

    Article  PubMed  CAS  Google Scholar 

  2. Wajchenberg BL, Malerbi DA, Rocha MS, Lerario AC, Santomauro ATMG (1994) Syndrome X: a syndrome of insulin resistance. Diabet Metab Rev 10: 19–29

    CAS  Google Scholar 

  3. Yudkin J (1995) Coronary heart disease in diabetes mellitus: three new risk factors and a unifying hypothesis. J Intern Med 238: 21–30

    Article  PubMed  CAS  Google Scholar 

  4. Reaven GM (1988) Role of insulin resistance in human disease. Diabetes 37: 1595–1607

    Article  PubMed  CAS  Google Scholar 

  5. Zavaroni I, Bonora E, Pagliara M et al. (1989) Risk factors for coronary heart disease in healthy persons with hyperinsulinemia and normal glucose tolerance. N Engl J Med 320: 702–760

    PubMed  CAS  Google Scholar 

  6. Ganda OM, Arkin CF (1992) Hyperfibrinogenemia: an important risk factor for vascular complications in diabetes. Diabetes Care 15: 1245–1250

    Article  PubMed  CAS  Google Scholar 

  7. Barrett-Connor E (1992) Lower endogenous androgen levels and dyslipidemia in men with non-insulin-dependent diabetes mellitus. Ann Intern Med 117: 807–811

    PubMed  CAS  Google Scholar 

  8. Crook M, Tutt P, Pickup JC (1993) Elevated serum sialic acid concentration in non-insulin-dependent diabetes and its relationship to blood pressure and retinopathy. Diabetes Care 16: 57–60

    Article  PubMed  CAS  Google Scholar 

  9. Crook MA, Tutt P, Simpson H, Pickup JC (1993) Serum sialic acid and acute phase proteins in type 1 and 2 diabetes mellitus. Clin Chim Acta 219: 131–138

    Article  PubMed  CAS  Google Scholar 

  10. Taniuchi K, Chifu K, Hayashi N et al. (1981) A new enzymatic method for the determination of sialic acid in serum and its application as a marker of acute phase reactants. Kobe J Med Sci 27: 91–102

    PubMed  CAS  Google Scholar 

  11. Rosenberg A, Schengrund C-L (1976) Circulating sialyl compounds. In: Rosenberg A, Schengrund S (eds) Biological roles of sialic acid. New York, Plenum pp 275–294

    Google Scholar 

  12. Pickup JC, Mattock MB, Crook MA, Chusney GD, Burt D, Fitzgerald AP (1995) Serum sialic acid concentration and coronary heart disease in NIDDM. Diabetes Care 18: 1100–1103

    Article  PubMed  CAS  Google Scholar 

  13. Cabana VG, Siegel JN, Sabesin SM (1989) Effects of the acute phase response on the concentration and density distribution of plasma lipids and apolipoproteins. J Lipid Res 30: 39–49

    PubMed  CAS  Google Scholar 

  14. Blackman JD, Cabana VG, Mazzone T(1993) The acutephase response and associated lipoprotein abnormalities accompanying lymphoma. J Intern Med 233: 201–204

    PubMed  CAS  Google Scholar 

  15. Spiegel RJ, Schaefer EJ, Magrath IT, Edwards B (1982) Plasma lipid alterations in leukemia and lymphoma. Am J Med 72: 775–782

    Article  PubMed  CAS  Google Scholar 

  16. Olsson AG (1991) Non-atherosclerotic disease and lipoproteins. Curr Opin Lipidol 2: 206–210

    Article  CAS  Google Scholar 

  17. Kushner I, Mackiewicz A (1993) The acute phase response: an overview. In: Mackiewicz A, Kushner I, Baumann H (eds) Acute phase proteins: molecular biology, biochemistry and clinical applications. CRC Press Boca Raton, pp 3–19

    Google Scholar 

  18. Steel DM, Whitehead AS (1994) The major acute phase reactants: C-reactive protein, serum amyloid P component and serum amyloid A. Immunol Today 15: 81–87

    Article  PubMed  CAS  Google Scholar 

  19. Jarrett RJ, Viberti GC, Argyropoulos A, Hill RD, Mahmud U, Murreis TJ (1984) Microalbuminuria predicts mortality in non-insulin-dependent diabetes. Diabet Med 1: 17–19

    PubMed  CAS  Google Scholar 

  20. Mogensen CE (1984) Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes. N Engl J Med 310: 356–360

    PubMed  CAS  Google Scholar 

  21. Groop L, Ekstrand A, Forsblom C et al. (1993) Insulin resistance, hypertension and microalbuminuria in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 36: 642–647

    Article  PubMed  CAS  Google Scholar 

  22. Mattock MB, Keen H, Viberti GC et al. (1988) Coronary heart disease and urinary albumin excretion in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 31: 82–87

    Article  PubMed  CAS  Google Scholar 

  23. Rose G, Blackburn H, Gillum RF, Prineas RJ (1982) Cardiovascular survey methods. WHO Mongr Series 56 pp 162–165

    Google Scholar 

  24. Simpson H, Chusney GD, Crook MA, Pickup JC (1993) Serum sialic acid enzymatic assay based on microtitre plates. Br J Biomed Sci 50: 164–167

    PubMed  CAS  Google Scholar 

  25. Keen H, Clouverakis C (1963) An immunoassay for urinary albumin at low concentration. Lancet ii: 913–916

    Article  Google Scholar 

  26. Havel RJ, Eden HA, Bragdon JH (1955) The distribution and chemical composition of ultracentrifugationally separated lipoproteins in human serum. J Clin Invest 34: 1345–1353

    Article  PubMed  CAS  Google Scholar 

  27. Jonsson A, Wales JK (1976) Blood glycoprotein levels in diabetes mellitus. Diabetologia 12: 245–250

    Article  PubMed  CAS  Google Scholar 

  28. McMillan DE (1989) Increased levels of acute-phase serum proteins in diabetes. Metabolism 38: 1042–1046

    Article  PubMed  CAS  Google Scholar 

  29. Feingold KR, Staprans I, Memon RA et al. (1992) Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production while high doses inhibit clearance. J Lipid Res 33: 1765–1776

    PubMed  CAS  Google Scholar 

  30. Kisilevsky R (1991) Serum amyloid A (SAA), a protein without a function: some suggestions with reference to cholesterol metabolism. Med Hypoth 35: 337–341

    Article  CAS  Google Scholar 

  31. Baumann H, Gauldie J (1994) The acute phase response. Immunol Today 15: 74–80

    Article  PubMed  CAS  Google Scholar 

  32. Dinarello CA (1991) Interleukin-1. In: Thomson AW (ed) The cytokine handbook. Academic Press London, pp 47–82

    Google Scholar 

  33. Akira S, Taga T, Kishimoto T (1993) Interleukin-6 in biology and medicine. Adv Immunol 54: 1–78

    Article  PubMed  CAS  Google Scholar 

  34. Jaattela M (1991) Biological activities and mechanisms of action of tumor necrosis factor α/cachectin. Lab Invest 64: 724–742

    PubMed  CAS  Google Scholar 

  35. Rivier C, Vale W (1984) Influence of corticotrophin-releasing factor on reproductive functions in the rat. Endocrinology 114: 914–921

    PubMed  CAS  Google Scholar 

  36. Brindley DN (1992) Neuroendocrine regulation and obesity. Int J Obes 16 [Suppl 3]: 73–79

    Google Scholar 

  37. Björntorp P (1992) Biochemistry of obesity in relation to diabetes. In: Alberti KGMM, DeFronzo RA, Keen H, Zimmet P (eds) International textbook of diabetes. John Wiley Chichester pp 551–568

    Google Scholar 

  38. Jeanrenaud B (1995) Insulin, corticosterone and the autonomic nervous system in animal obesities: a viewpoint. Diabetologia 38: 998–1002

    Article  PubMed  CAS  Google Scholar 

  39. Figueredo A, Ibarra JL, Bagazgoitia J et al. (1993) Plasma C3d levels and ischemic heart disease in type II diabetes. Diabetes Care 16: 445–449

    Article  PubMed  CAS  Google Scholar 

  40. Feingold KR, Grunfeld C (1992) Role of cytokines in inducing hyperlipidemia. Diabetes 41: [Suppl 2] 97–101

    PubMed  CAS  Google Scholar 

  41. Yokota T, Hansson GK (1995) Immunological mechanisms in atherosclerosis. J Intern Med 238: 479–489

    PubMed  CAS  Google Scholar 

  42. Hotamisligil GS, Spiegelman BM (1994) Tumor necrosis factor a: a key component of the obesity-diabetes link. Diabetes 43: 1271–1278

    Article  PubMed  CAS  Google Scholar 

  43. Bendtzen K, Buschard K, Diamant M, Horn T, Svenson M (1989) Possible role of IL-1, TNFα and IL-6 in insulin-dependent diabetes mellitus and autoimmune thyroid disease. Lymphokine Res 8: 335–341

    PubMed  CAS  Google Scholar 

  44. Rabinovitch A (1994) Immunoregulatory and cytokine imbalances in the pathogenesis of IDDM. Diabetes 43: 613–621

    Article  PubMed  CAS  Google Scholar 

  45. Pickup JC, Day CD, Bailey C et al. (1995) Plasma sialic acid in animal models of diabetes mellitus: evidence for modulation of sialic acid concentrations by insulin deficiency. Life Sci 57: 1383–1391

    Article  PubMed  CAS  Google Scholar 

  46. Thompson D, Harrison SP, Evans SW, Whicher JT (1991) Insulin modulation of acute-phase protein production in a human hepatoma cell line. Cytokine 3: 619–626

    Article  PubMed  CAS  Google Scholar 

  47. Campos SP, Baumann H (1992) Insulin is a prominent modulator of the cytokine-stimulated expression of acutephase plasma protein genes. Mol Cell Biol 12: 1789–1797

    PubMed  CAS  Google Scholar 

  48. Stuart J, George AJ, Davies AJ, Aukland A, Hurlow RA (1981) Haematological stress syndrome in atherosclerosis. J Clin Pathol 34: 464–467

    Article  PubMed  CAS  Google Scholar 

  49. Mendall MA, Patel P, Ballam L, Strachan D, Northfield TC (1996) C-reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study. Br Med J 312: 1061–1065

    CAS  Google Scholar 

  50. Vlassara H, Brownlee M, Manogue KR, Dinarello C, Pasagian A (1988) Cachectin/TNF and IL-1 induced by glucose modified proteins: role in normal tissue modelling. Science 240: 1546–1548

    Article  PubMed  CAS  Google Scholar 

  51. Imani F, Horii Y, Suthanthiran M et al. (1993) Advanced glycosylation endproduct-specific receptors on human and rat T-lymphocytes mediate synthesis of interferon y: role in tissue remodelling. J Exp Med 178: 2165–2172

    Article  PubMed  CAS  Google Scholar 

  52. Barker DJP, Hales CN, Fall CHD, Osmond C, Phipps K, Clark PMS (1993) Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 36: 62–67

    Article  PubMed  CAS  Google Scholar 

  53. Caswell M, Pike LA, Bull BS, Stuart J (1993) Effect of age on tests of the acute-phase response. Arch Pathol Lab Med 117: 906–910

    PubMed  CAS  Google Scholar 

  54. Fagiolo U, Cossarizza A, Scala E et al. (1993) Increased cytokine production in mononuclear cells of healthy elderly people. Eur J Immunol 23: 2375–2378

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Chemical Pathology UMDS, Guy’s Hospital, SE1 9RT, London, UK

    J. C. Pickup, M. B. Mattock & G. D. Chusney

  2. Unit for Metabolic Medicine, UMDS, Guy’s Hospital, London, UK

    D. Burt

Authors
  1. J. C. Pickup
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. B. Mattock
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. D. Chusney
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Burt
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Pickup, J.C., Mattock, M.B., Chusney, G.D. et al. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 40, 1286–1292 (1997). https://doi.org/10.1007/s001250050822

Download citation

  • Received: 17 April 1997

  • Revised: 06 June 1997

  • Issue Date: November 1997

  • DOI: https://doi.org/10.1007/s001250050822

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Keywords

  • NIDDM
  • acute-phase response
  • cytokines
  • interleukin-6
  • innate immune system
  • insulin resistance
  • syndrome
Download PDF

Working on a manuscript?

Avoid the common mistakes

Advertisement

Over 10 million scientific documents at your fingertips

Switch Edition
  • Academic Edition
  • Corporate Edition
  • Home
  • Impressum
  • Legal information
  • Privacy statement
  • California Privacy Statement
  • How we use cookies
  • Manage cookies/Do not sell my data
  • Accessibility
  • FAQ
  • Contact us
  • Affiliate program

Not logged in - 95.216.99.153

Not affiliated

Springer Nature

© 2023 Springer Nature Switzerland AG. Part of Springer Nature.