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Published on: July 17, 2018
Circulating cellular adhesion molecules and risk of diabetes: the Multi-Ethnic Study of Atherosclerosis (MESA)
J S Pankow1, P A Decker2, C Berardi3
1Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN.
Insights
Elevated levels of certain soluble cellular adhesion molecules, including E-selectin and ICAM-1, are linked to an increased risk of developing diabetes. This suggests microvascular endothelial dysfunction may play a role in diabetes development.
Area of Science:
- Cardiovascular disease and diabetes research
- Endothelial function and metabolic health
Background:
- Cellular adhesion molecules (CAMs) play a role in inflammation and endothelial function.
- Endothelial dysfunction is implicated in the pathogenesis of diabetes.
Purpose of the Study:
- To investigate the association between soluble cellular adhesion molecules and incident diabetes risk.
- To test the hypothesis that soluble CAMs are independently associated with diabetes risk.
Main Methods:
- Prospective cohort study (Multi-Ethnic Study of Atherosclerosis) with up to 10 years of follow-up.
- Measurement of soluble levels of six CAMs: ICAM-1, E-selectin, VCAM-1, E-cadherin, L-selectin, and P-selectin.
- Statistical analysis adjusted for age, sex, race/ethnicity, BMI, and glycemic markers.
Main Results:
- Four CAMs (ICAM-1, E-selectin, VCAM-1, E-cadherin) were positively associated with incident diabetes.
- Significant trends observed across quartiles of these CAMs.
- E-selectin and ICAM-1 showed the largest associations with diabetes risk in fully adjusted models.
Conclusions:
- Significant associations between multiple soluble CAMs and incident diabetes support the role of microvascular endothelial dysfunction in diabetes risk.
- Findings may inform strategies for diabetes prevention and risk assessment.
Aims:
To test the hypothesis that soluble cellular adhesion molecules would be positively and independently associated with risk of diabetes.
Methods:
Soluble levels of six cellular adhesion molecules (ICAM-1, E-selectin, VCAM-1, E-cadherin, L-selectin and P-selectin) were measured in participants in the Multi-Ethnic Study of Atherosclerosis, a prospective cohort study. Participants were then followed for up to 10 years to ascertain incident diabetes.
Results:
Sample sizes ranged from 826 to 2185. After adjusting for age, sex, race/ethnicity, BMI and fasting glucose or HbA1c , four cellular adhesion molecules (ICAM-1, E-selectin, VCAM-1 and E-cadherin) were positively associated with incident diabetes and there was a statistically significant trend across quartiles. Comparing the incidence of diabetes in the highest and lowest quartiles of each cellular adhesion molecule, the magnitude of association was largest for E-selectin (hazard ratio 2.49; 95% CI 1.26-4.93) and ICAM-1 (hazard ratio 1.76; 95% CI 1.22-2.55) in fully adjusted models. Tests of effect modification by racial/ethnic group and sex were not statistically significant for any of the cellular adhesion molecules (P > 0.05).
Conclusions:
The finding of significant associations between multiple cellular adhesion molecules and incident diabetes may lend further support to the hypothesis that microvascular endothelial dysfunction contributes to risk of diabetes.
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