Activation of the innate immune system as a predictor of cardiovascular mortality in Type 2 diabetes mellitus.
OBJECTIVE
Activation of innate immunity may play a major role in the development and pathophysiology of Type 2 diabetes; we therefore investigated whether a marker of innate immunity (serum sialic acid) predicts cardiovascular disease (CVD) and all-cause mortality in Type 2 diabetes.


METHODS
Type 2 diabetic subjects (n=128, age 31-64 years at outset) participating in the Lewisham Diabetes Survey were followed up for a mean of 12.8 years. Baseline measurements were made of serum sialic acid and known or putative risk factors for CVD. Cause of death was coded from death certificates, post mortem examination and hospital records.


RESULTS
Fifty-six (43%) subjects had died after 12.8 years. The major cause of death was CVD (71.4%), predominantly coronary heart disease (62.5%). Baseline variables significantly associated with CVD mortality were sialic acid and CVD (borderline significance smoking and cholesterol). In multivariate analysis, significant independent predictors of CVD mortality were sialic acid [standardized relative risk (95% confidence interval) 1.53 (1.12, 2.10)], age, male sex and existing CVD.


CONCLUSIONS
Activated innate immunity (low-grade inflammation) is a risk factor for CVD mortality in Type 2 diabetes, independently of other known risk factors, including existing CVD. Since activation of the innate immune system predicts Type 2 diabetes, it may be a common antecedent of both Type 2 diabetes and CVD.
Pickup
J C
JC
Metabolic Unit, Guy's, King's and St Thomas's School of Medicine, Guy's Hospital, London, UK. john.pickup@kcl.ac.uk
Mattock
M B
MB
D000328:Adult; D015415:Biomarkers / Q000097:blood; D002423:Cause of Death; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology* / Q000401:mortality; D003925:Diabetic Angiopathies / Q000097:blood / Q000276:immunology* / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008131:London / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D019158:N-Acetylneuraminic Acid / Q000097:blood; D011446:Prospective Studies; D012307:Risk Factors; D016019:Survival Analysis
D015415:Biomarkers; D019158:N-Acetylneuraminic Acid