Aims/hypothesis Elevated serum ferritin levels are associated with an increased risk of type 2 diabetes, but the nature of this association remains elusive. The aim of this study was to test the hypothesis that an elevated fasting serum ferritin level is associated with an increased risk of type 2 diabetes due to its association with impaired beta cell function and decreased insulin sensitivity. Methods We investigated 6,392 individuals from the Danish general population. Surrogate measures of beta cell function and insulin sensitivity were calculated for approximately 6,100 individuals based on OGTT examinations. ResultsThe ORs for type 2 diabetes were 4.2 (95% CI 2.4, 7.2) for the highest vs the lowest quintile of serum ferritin, and 17 (95% CI 8.9, 33) for serum ferritin levels ≥97.5th percentile vs <20th percentile. Elevated serum ferritin levels were associated with elevated plasma glucose levels at 0, 30 and 120 min ( p<0.001), elevated serum insulin levels at 0 and 120 min ( p=0.02 and p<0.001), decreased beta cell function estimated as the insulinogenic index and corrected insulin response ( p<0.001), and decreased insulin sensitivity estimated by the Matsuda index of insulin sensitivity and HOMA-IR ( p<0.001). Whereas the association with impaired beta cell function was present in both men and women, the association Electronic supplementary material The online version of this article
Objectives There is growing interest in the pre-diagnostic phase of inflammatory bowel disease (IBD) and in the overlap of IBD with other diseases. We described and compared use of any prescription medication between individuals with and without IBD in a ten-year period preceding diagnosis. Methods Based on cross-linked nationwide registers, we identified 29,219 individuals diagnosed with IBD in Denmark between 2005 and 2018 and matched to 292,190 IBD-free individuals. The primary outcome was use of any prescription medication in years 1-10 prior to IBD diagnosis/matching date. Participants were considered as medication users if they redeemed ≥1 prescription for any medication in the WHO anatomical therapeutic classification (ATC) main or subgroups before diagnosis/matching. Results The IBD population had a universally increased use of medications compared to the matched population prior to IBD diagnosis. At ten years before diagnosis, the proportion of users was 1.1- to 1.8-fold higher in the IBD population in 12 of 14 ATC main groups of medication, p-value <0.0001. This applied across age, sex, and IBD subtypes, although most pronounced for Crohn’s disease (CD). Two years prior to diagnosis, the IBD population had a steep increase in medication use for several organ systems. When analyzing therapeutic subgroups of medication, the CD population exhibited 2.7, 2.3, 1.9, and 1.9 times more users of immunosuppressants, antianemic preparations, analgesics, and psycholeptics than the matched population ten years prior to diagnosis (p-value <0.0001). Conclusions Our findings demonstrate universally increased medication use years before IBD, especially CD, and indicates multiorgan involvement in IBD.
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