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.
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.
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.
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.
M. Knuuti, N. Kartiosuo, K. Pahkala et al.· Cardiovascular Diabetology· 0 citations
BACKGROUND
High body mass index (BMI) in adolescence is associated with accelerated biological aging, which might predict the onset of obesity-related diseases before they develop. Genetic factors may shape both adolescent BMI and weight trajectories.
METHODS
Participants were from the Young Finns Study (n = 3 596, ages 3-18 at baseline), followed from 1980 to 2018-2020. Biological aging was estimated using DNA methylation based epigenetic clocks DunedinPACE (years/calendar year) and PC-GrimAge (years) at three follow-ups (ages 15-56, n = 2045). Genetic predispositions to BMI and childhood body size were quantified using polygenic risk scores (PRSs) (941 and 286 genetic variants). BMI trajectories were modelled from BMI measured at ages 9, 12, 15 and 18 using latent growth curve modelling. Path analysis was used to examine whether genetic liability to BMI is associated with biological aging and if BMI trajectories in adolescence mediate this association. The causal effect of genetically predicted adolescent BMI on biological aging in adulthood was examined with Mendelian randomisation (MR) using individual-level data.
RESULTS
Higher level of adolescent BMI partly mediated the association between higher BMI-PRS and accelerated biological aging from late adolescence to middle adulthood. MR analyses supported a positive causal effect from genetically predicted adolescent BMI on biological aging, and the causal effect was more consistent when DunedinPACE was used to measure biological aging in 2011 (causal estimate = 0.020 [95% CI = 0.008, 0.031]) and 2018 (0.019 [0.003, 0.035]).
CONCLUSIONS
Our findings indicate that high BMI in adolescence may accelerate biological aging, especially in individuals with a genetic predisposition to high BMI. Adolescents with a genetic susceptibility to high BMI and elevated BMI might be prone to obesity-related health risks, highlighting early prevention strategies' importance.
Anni Pitkänen, Anna Kankaanpää, E. Raitoharju et al.· International Journal of Obe...· 0 citations
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