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.