NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X.
Non-insulin-dependent diabetes mellitus (NIDDM) is commonly associated with hypertriglyceridaemia, 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 alpha-1 acid glycoprotein (r = 0.82, p < 0.0001). There was a significant graded increase of serum sialic acid, alpha-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 X-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 acute-phase response.
Pickup
J C
JC
Division of Chemical Pathology, UMDS, Guy's Hospital, London, UK.
Mattock
M B
MB
Chusney
G D
GD
Burt
D
D
D000209:Acute-Phase Proteins / Q000032:analysis*; D000328:Adult; D000419:Albuminuria / Q000652:urine; D002097:C-Reactive Protein / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007333:Insulin Resistance / Q000276:immunology*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000097:blood; D009961:Orosomucoid / Q000032:analysis; D000685:Serum Amyloid A Protein / Q000032:analysis
D000209:Acute-Phase Proteins; D015850:Interleukin-6; D009961:Orosomucoid; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein; D019158:N-Acetylneuraminic Acid; D006854:Hydrocortisone