Adela Brahimaj1, Symen Ligthart1, M Arfan Ikram1,2,3, Albert Hofman1,4, Oscar H Franco1, Eric J G Sijbrands5, Maryam Kavousi1, Abbas Dehghan6. 1. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands. 2. Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands. 3. Department of Radiology, Erasmus University Medical Center, Rotterdam, the Netherlands. 4. Harvard School of Public Health, Boston, MA. 5. Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands. 6. Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands a.dehghan@erasmusmc.nl.
Abstract
OBJECTIVE: We aimed to investigate the role of serum levels of various apolipoproteins on the risk for type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We used data from 971 individuals from the prospective population-based Rotterdam Study. We studied the association of HDL cholesterol (HDL-C), apoA1, apoCIII, apoD, and apoE as well as the ratios of apolipoproteins with apoA1 with the risk of T2D. All apolipoproteins, ratios, and HDL-C levels were naturally log-transformed to reach normal distribution. First, their cross-sectional associations with fasting glucose and insulin were investigated by using linear regression. Second, Cox proportional hazard models were used to examine whether apolipoproteins predict the risk for T2D among individuals free of diabetes at baseline. We also studied the apolipoproteins jointly by calculating the apolipoproteinic score from the first step and then performing Cox regression with it. RESULTS: During a median follow-up of 13.5 years, diabetes developed in 110 individuals. After adjustment for age, sex, BMI, parental history of diabetes, hypertension, alcohol use, smoking, prevalent cardiovascular disease, and serum lipid-reducing agents, HDL-C (per 1 SD naturally log-transformed hazard ratio 0.74 [95% CI 0.57, 0.97], apoCIII (1.65 [1.42, 1.91]), apoE (1.36 [1.18, 1.55]), apoCIII-to-apoA1 ratio (1.72 [1.51, 1.95]), apoE-to-apoA1 ratio (1.28 [1.13, 1.45]), and apolipoproteinic score (1.60 [1.39, 1.83]) remained significant. Only apoCIII (1.42 [1.03, 1.96]) and apoCIII-to-apoA1 ratio (1.56 [1.04, 2.36]) survived the adjustment for triglycerides in the last model. CONCLUSIONS: Serum apoCIII levels as well as apoCIII-to-apoA1 ratio are associated with incident T2D. They are associated independent of known risk factors and stronger than HDL-C levels.
OBJECTIVE: We aimed to investigate the role of serum levels of various apolipoproteins on the risk for type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We used data from 971 individuals from the prospective population-based Rotterdam Study. We studied the association of HDL cholesterol (HDL-C), apoA1, apoCIII, apoD, and apoE as well as the ratios of apolipoproteins with apoA1 with the risk of T2D. All apolipoproteins, ratios, and HDL-C levels were naturally log-transformed to reach normal distribution. First, their cross-sectional associations with fasting glucose and insulin were investigated by using linear regression. Second, Cox proportional hazard models were used to examine whether apolipoproteins predict the risk for T2D among individuals free of diabetes at baseline. We also studied the apolipoproteins jointly by calculating the apolipoproteinic score from the first step and then performing Cox regression with it. RESULTS: During a median follow-up of 13.5 years, diabetes developed in 110 individuals. After adjustment for age, sex, BMI, parental history of diabetes, hypertension, alcohol use, smoking, prevalent cardiovascular disease, and serum lipid-reducing agents, HDL-C (per 1 SD naturally log-transformed hazard ratio 0.74 [95% CI 0.57, 0.97], apoCIII (1.65 [1.42, 1.91]), apoE (1.36 [1.18, 1.55]), apoCIII-to-apoA1 ratio (1.72 [1.51, 1.95]), apoE-to-apoA1 ratio (1.28 [1.13, 1.45]), and apolipoproteinic score (1.60 [1.39, 1.83]) remained significant. Only apoCIII (1.42 [1.03, 1.96]) and apoCIII-to-apoA1 ratio (1.56 [1.04, 2.36]) survived the adjustment for triglycerides in the last model. CONCLUSIONS: Serum apoCIII levels as well as apoCIII-to-apoA1 ratio are associated with incident T2D. They are associated independent of known risk factors and stronger than HDL-C levels.
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