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Background  Recent studies suggest an association between Lipoprotein(a) [Lp(a)] and the development of diabetes mellitus. We analyzed the association between baseline Lp(a) levels and diabetes development after 4 years of follow-up, in a population of apparently healthy Korean subjects.    Methods  A total of 2,536 non-diabetic participants (mean age: 41 years, men: 92%) of a health checkup program were included in the study. Diabetes development was defined by fasting blood glucose ≥126 mg/dL, HbA1c ≥6.5%, and self-reported treatment of diabetes. Homeostasis model assessment (HOMA) indices were used to assess insulin resistance (IR) and insulin secretion (IS). Presence of IR and impaired IS was defined by being in the highest quartile of HOMA-IR and in the lowest quartile HOMA-IS.    Results  After four years, 3.4% of the participants developed diabetes. The odds ratio (OR) of developing diabetes was lowest in the 4 th  quartile group of baseline Lp(a) (0.323 [95% CI 0.153–0.685])with the 1 st  quartile group as the reference. The subjects with both IR & impaired IS plus baseline Lp(a)<50 mg/dL showed the higher OR for diabetes development compared with those without IR and normal IS as the reference (67.277 [20.218–223.871], and those with IR plus Lp(a)<50 mg/dL showed higher OR for diabetes than in those with impaired IS and Lp(a)<50 mg/dL (3.811 [1.938–7.495] vs. 3.452 [1.620–7.353]).    Conclusions  The subjects with low baseline Lp(a) level showed higher risk for development of diabetes compared with high baseline Lp(a) level, and this was prominent in those with IR than in those with impaired IS.

Insulin resistance contributes more to the increased risk for diabetes development in subjects with low lipoprotein(a) level than insulin secretion