Aims/hypothesis: There is evidence for a bidirectional association between type 2 diabetes and Alzheimer's disease. Plasma β-amyloid (Aβ) is a potential biomarker for Alzheimer's disease. We aimed to investigate the association of plasma Aβ40 and Aβ42 with risk of type 2 diabetes.
Methods: We performed a case-control study and a nested case-control study within a prospective cohort study. In the case-control study, we included 1063 newly diagnosed individuals with type 2 diabetes and 1063 control participants matched by age (±3 years) and sex. In the nested case-control study, we included 121 individuals with incident type 2 diabetes and 242 matched control individuals. Plasma Aβ40 and Aβ42 concentrations were simultaneously measured with electrochemiluminescence immunoassay. Conditional logistic regression was used to evaluate the association of plasma Aβ40 and Aβ42 concentrations with the likelihood of type 2 diabetes.
Results: In the case-control study, the multivariable-adjusted ORs for type 2 diabetes, comparing the highest with the lowest quartile of plasma Aβ concentrations, were 1.97 (95% CI 1.46, 2.66) for plasma Aβ40 and 2.01 (95% CI 1.50, 2.69) for plasma Aβ42. Each 30 ng/l increment of plasma Aβ40 was associated with 28% (95% CI 15%, 43%) higher odds of type 2 diabetes, and each 5 ng/l increment of plasma Aβ42 was associated with 37% (95% CI 21%, 55%) higher odds of type 2 diabetes. Individuals in the highest tertile for both plasma Aβ40 and Aβ42 concentrations had 2.96-fold greater odds of type 2 diabetes compared with those in the lowest tertile for both plasma Aβ40 and Aβ42 concentrations. In the nested case-control study, the multivariable-adjusted ORs for type 2 diabetes for the highest vs the lowest quartile were 3.79 (95% CI 1.81, 7.94) for plasma Aβ40 and 2.88 (95% CI 1.44, 5.75) for plasma Aβ42. The multivariable-adjusted ORs for type 2 diabetes associated with each 30 ng/l increment in plasma Aβ40 and each 5 ng/l increment in plasma Aβ42 were 1.44 (95% CI 1.18, 1.74) and 1.47 (95% CI 1.15, 1.88), respectively.
Conclusions/interpretation: Our findings suggest positive associations of plasma Aβ40 and Aβ42 concentration with risk of type 2 diabetes. Further studies are warranted to elucidate the underlying mechanisms and explore the potential roles of plasma Aβ in linking type 2 diabetes and Alzheimer's disease.
Keywords: Alzheimer’s disease; Case–control; Nested case–control; Type 2 diabetes; β-amyloid 40; β-amyloid 42.