Diabetologia

, 40:1286

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

  • J. C. Pickup
  • M. B. Mattock
  • G. D. Chusney
  • D. Burt
Originals

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.

Keywords

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

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

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Copyright information

© Springer-Verlag 1997

Authors and Affiliations

  • J. C. Pickup
    • 1
  • M. B. Mattock
    • 1
  • G. D. Chusney
    • 1
  • D. Burt
    • 2
  1. 1.Division of Chemical Pathology UMDSGuy’s HospitalLondonUK
  2. 2.Unit for Metabolic Medicine, UMDSGuy’s HospitalLondonUK

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