Associations of lipoprotein(a) with fasting insulin, fasting glucose, and incident type 2 diabetes: a prospective analysis from the Young Finns Study

Abstract Background Prospective studies have demonstrated an inverse association between lipoprotein(a) [Lp(a)] levels and the risk for type 2 diabetes, although the mechanisms underlying this relationship remain unclear. We examined the associations of Lp(a) with incident type 2 diabetes, fasting serum insulin, and fasting plasma glucose, in the prospective Young Finns Study cohort. Methods Lp(a) measurements were first available in Young Finns Study participants in 1986 (N = 2 464). For type 2 diabetes analyses, the baseline was defined as the 2001 follow-up study (participants aged 24–39 years) when data on both Lp(a) and diabetes status were available (N = 2 263). The association between Lp(a) levels and incident type 2 diabetes was examined using the Fine-Gray model. Associations with fasting insulin and glucose were analyzed using repeated-measures linear regression, utilizing data from 1986, 2001, 2007, 2011, and 2018. Results During the mean follow-up period of 16.6 years from 2001, 144 participants (6.4%) developed type 2 diabetes. 2001 log e -transformed Lp(a) (at 24–39 years of age) was associated with a decreased risk of type 2 diabetes [hazard ratio per one-unit increase in log e -Lp(a): 0.83, 95% confidence interval 0.73–0.96] in the age- and sex-adjusted model. Additionally, longitudinal inverse associations were observed between Lp(a) and fasting insulin levels. Compared to the lowest Lp(a) quartile, mean fasting insulin was 0.079 standard deviation units lower in the highest quartile ( p = 0.019, trend- p = 0.0093). Inverse associations between Lp(a) and fasting glucose were observed in males. Conclusions In the Young Finns Study, higher adult Lp(a) concentrations were prospectively associated with lower risk of incident type 2 diabetes. Longitudinal analyses further showed inverse associations between Lp(a) and fasting insulin, supporting a possible link between Lp(a), insulin metabolism, and diabetes risk.