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.
German Diabetes Clinic, German Diabetes Centre, Leibniz Centre at Heinrich Heine University, 40225, Düsseldorf, Germany. christian.herder@ddz.uni-duesseldorf.de
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C
Herder
J
J
Baumert
B
B
Thorand
W
W
Koenig
W
W
de Jager
C
C
Meisinger
T
T
Illig
S
S
Martin
H
H
Kolb
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