Chemokines as risk factors for type 2 diabetes: results from the MONICA/KORA Augsburg study, 1984-2002.
OBJECTIVE
The chemokines monocyte chemoattractant protein-1 (MCP-1), IL-8 and interferon-gamma-inducible protein-10 (IP-10) are released by adipocytes and appear to be involved in atherosclerosis. We hypothesised that these chemokines may be risk factors for the development of type 2 diabetes.


METHODS
Using a case-cohort design based on data from the population-based Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA)/Kooperative Gesundheitsforschung in der Region Augsburg/Cooperative Health Research in the Region of Augsburg (KORA Augsburg) study, chemokine levels at baseline were analysed in 526 individuals with and 1,695 individuals without incident type 2 diabetes. The mean follow-up time was 10.8 years.


RESULTS
MCP-1 was associated with type 2 diabetes, largely independently of classic risk factors, whereas various clinical and metabolic parameters as well as lifestyle factors were major confounders of the association of IL-8 and IP-10 with type 2 diabetes. Further adjustment for C-reactive protein (CRP) and IL-6 had no impact on the observed associations. The hazard ratio (HR) for subjects with systemic concentrations of all three chemokines (MCP-1, IL-8 and IP-10) above the respective median compared with those with all chemokines below or equal to the median was 1.79 (95% CI 1.18-2.72) and was comparable with the HR for elevated CRP and IL-6 together (adjusted for age, sex, survey, BMI, systolic blood pressure, total cholesterol:HDL cholesterol ratio, physical activity, alcohol intake, smoking and parental history of diabetes).


CONCLUSIONS
Elevated concentrations of MCP-1, IL-8 and IP-10 are associated with incident type 2 diabetes. Whereas the association of IL-8 and IP-10 with diabetes was attenuated by multivariable adjustment, high MCP-1 levels contributed to diabetes risk independently of previously described clinical, metabolic and immunological risk factors.
Herder
C
C
German Diabetes Clinic, German Diabetes Centre, Leibniz Centre at Heinrich Heine University, 40225, Düsseldorf, Germany. christian.herder@ddz.uni-duesseldorf.de
Baumert
J
J
Thorand
B
B
Koenig
W
W
de Jager
W
W
Meisinger
C
C
Illig
T
T
Martin
S
S
Kolb
H
H
D001794:Blood Pressure; D015992:Body Mass Index; D049628:Body Size; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000517:prevention & control; D018925:Chemokines / Q000097:blood*; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic; D015995:Prevalence; D012307:Risk Factors
D018925:Chemokines; D002784:Cholesterol