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Objective: Fibroblast growth factor 21 (FGF21) is a peptide hormone synthesized by several organs and regulates, among others, energy homeostasis. In obesity, insulin resistance and type 2 diabetes (T2D), higher circulating FGF21 concentrations have been found. Temporal analyses in murine studies demonstrate that FGF21 increases before insulin resistance occurs. The current study aims to investigate in timeto- event analyses whether FGF21 may be an early biomarker in the development of T2D. Research Design and Methods: Circulating FGF21 was measured using an immunoassay of the Mesoscale U-PLEX assay platform. The study outcome was incident T2D. Associations of circulating FGF21 concentration with T2D were quantified using Cox proportional hazards models with adjustments for potential confounders. Results: We included 5244 participants aged 52± 12 years, of whom 50% were male. Median [interquartile range] circulating FGF21 concentration was 860 [525-1329] pg/mL. During 7.3 [6.1-7.7] years of follow-up, 299 (5.7%) participants developed T2D. In fully adjusted analyses, higher circulating FGF21 concentration was associated with an increased risk of incident T2D (hazard ratio per doubling: 1.26 [95% CI, 1.06-1.51]; P= 0.008), with effect modification by fasting plasma glucose, consistent with strengthening of the association at lower fasting glucose (interaction coefficient: -0.12; P= 0.022). Conclusion: Higher circulating FGF21 concentrations are independently associated with an increased risk of incident T2D in participants with a low fasting plasma glucose, making circulating FGF21 concentration a potential early biomarker for type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Posttransplantation diabetes mellitus (PTDM) effects up to 30% of all kidney transplant recipients (KTR). Recent studies in mice found that sufficient androgen levels are necessary for β-cell health and adequate insulin secretion. This raises the question whether a similar relationship might be present in KTR. Hence, we hypothesized that dihydrotestosterone and testosterone are associated with the development of PTDM in male KTR.Research Design and Methods: We conducted a post hoc analyses of a prospective single-center cohort study including adult male KTR with a functioning graft ≥1 year posttransplantation. Androgen levels were assessed by liquid chromatography-tandem mass spectrometry. Development of PTDM was defined according to the American Diabetes Association's criteria.Results: We included 243 male KTR (aged 51 ± 14 years), with a median dihydrotestosterone 0.9 (0.7-1.3) nmol/L and testosterone of 12.1 (9.4-15.8) nmol/L. During 5.3 (3.7-5.8) years of follow-up, 28 KTR (11.5%) developed PTDM. A clear association was observed, as 15 (19%), 10 (12%), and 3 (4%) male KTR developed PTDM in the respective tertiles of dihydrotestosterone (P = 0.008). In Cox regression analyses, both dihydrotestosterone and testosterone as continuous variables were inversely associated with the risk to development PTDM, independent of glucose and HbA1c (hazard ratio [HR] 0.31 [95% CI 0.16-0.59], P < 0.001; and HR 0.32 [95% CI 0.15-0.68], P = 0.003, respectively).Conclusions: Our results suggest that low androgen levels are a novel potential modifiable risk factor for the development of PTDM in male KTR. [ABSTRACT FROM AUTHOR]