RESUMEN
BACKGROUND: Some studies have assessed the predictive role of the atherogenic index of plasma (AIP) for macrovascular diseases. This prospective investigation aimed to elucidate whether AIP is associated with diabetic kidney disease (DKD) and diabetic retinopathy (DR) incidence. METHODS: The data were extracted from 4831 participants, of whom 2943 and 3360 participants with type 2 diabetes (T2D) were included in the DKD and DR follow-up analyses, respectively. Cox regression models were performed to test the relationships of AIP value at baseline with the risk of incident DKD and DR. Group-based trajectory modelling was utilized to discern AIP trajectories during the follow-up period. Subsequently, logistic regressions were applied to ascertain the influence of AIP trajectories on the incidence of DKD and DR. RESULTS: During the follow-up period, 709 (24.1%) and 193 (5.7%) participants developed DKD and DR, respectively. The median (interquartile range) follow-up time was 24.2 (26.3) months for DKD and 25.7 (27.0) months for DR. According to the multivariate Cox regression models, baseline AIP was positively and linearly related to the occurrence of DKD, with a hazard ratio of 1.75 (95% confidence interval [CI] 1.36-2.26). Three distinct trajectories of AIP were identified throughout the follow-up time: Low (31.4%), Median (50.2%), and High (18.3%). Compared to participants with the Low AIP trajectory, those with High and Median AIP trajectories presented 117% (95% CI: 1.62-2.91) and 84% (95% CI 1.46-2.32) greater odds of developing DKD, respectively. However, neither baseline levels nor trajectories of AIP were shown to be related to DR after adjusting for confounding factors. CONCLUSIONS: Baseline levels and trajectories of AIP were independently related to elevated DKD risk, indicating that AIP could be used as a predictor for identifying T2D participants at higher risk of DKD. No association between AIP and DR was detected.
Asunto(s)
Aterosclerosis , Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Retinopatía Diabética , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/epidemiología , Estudios Longitudinales , Estudios Prospectivos , Estudios de Cohortes , Retinopatía Diabética/epidemiología , Aterosclerosis/complicaciones , Factores de RiesgoRESUMEN
AIMS: Current evidence regarding iron status and mortality risk among patients with diabetes is limited. This study aimed to evaluate association of iron indices with all-cause and cause-specific mortality risk among patients with diabetes. METHODS: The current study included 2080 (with ferritin data), 1974 (with transferrin saturation (Tsat) data), and 1106 (with soluble transferrin receptor (sTfR) data) adults with diabetes from NHANES 1999-2018. Death outcomes were obtained from National Death Index through December 31, 2019. Cox proportional hazards models were employed to calculate hazard ratios and 95% confidence intervals for mortality. RESULTS: Association with all-cause mortality was demonstrated to be J-shaped for serum ferritin (Pnonlinearity < 0.01), U-shaped for Tsat (Pnonlinearity < 0.01) and linear for sTfR (Plinearity < 0.01). Ferritin 300-500 ng/mL possessed lower all-cause mortality risk than ferritin ≤ 100 ng/mL, 100-300 ng/mL, and > 500 ng/mL. Tsat 25-32 % showed a protective effect on all-cause mortality risk compared with Tsat ≤ 20 %, 20-25 %, and > 32 %. Individuals with sTfR < 4 mg/L were associated with a lower risk of all-cause mortality than those with higher sTfR. CONCLUSIONS: Moderate levels of serum ferritin (300-500 ng/mL), Tsat (25 %-32 %) and a lower concentration of sTfR (< 4 mg/L) identified adults with diabetes with lower all-cause mortality risk, adding novel modifiers to diabetes management.
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Diabetes Mellitus , Hierro , Adulto , Humanos , Hierro/metabolismo , Causas de Muerte , Encuestas Nutricionales , FerritinasRESUMEN
CONTEXT: Cushing syndrome (CS) is a severe endocrine disease characterized by excessive secretion of cortisol with multiple metabolic disorders. While gut microbial dysbiosis plays a vital role in metabolic disorders, the role of gut microbiota in CS remains unclear. OBJECTIVE: The objective of this work is to examine the alteration of gut microbiota in patients with CS. METHODS: We performed shotgun metagenomic sequencing of fecal samples from 78 patients with CS and 78 healthy controls matched for age and body mass index. Furthermore, we verify the cortisol degradation capacity of Ruminococcus gnavus in vitro and identify the potential metabolite by LC-MC/MS. RESULTS: We observed significant differences in microbial composition between CS and controls in both sexes, with CS showing reduced Bacteroidetes (Bacteroides vulgatus) and elevated Firmicutes (Erysipelotrichaceae_bacterium_6_1_45) and Proteobacteria (Enterobacter cloacae). Despite distinct causes of hypercortisolism in ACTH-dependent and ACTH-independent CS, we found no significant differences in metabolic profiles or gut microbiota between the 2 subgroups. Furthermore, we identified a group of gut species, including R. gnavus, that were positively correlated with cortisol levels in CS. These bacteria were found to harbor cortisol-degrading desAB genes and were consistently enriched in CS. Moreover, we demonstrated the efficient capacity of R. gnavus to degrade cortisol to 11-oxygenated androgens in vitro. CONCLUSION: This study provides evidence of gut microbial dysbiosis in patients with CS and identifies a group of CS-enriched bacteria capable of degrading cortisol. These findings highlight the potential role of gut microbiota in regulating host steroid hormone levels, and consequently host health.
Asunto(s)
Síndrome de Cushing , Disbiosis , Heces , Microbioma Gastrointestinal , Hidrocortisona , Humanos , Disbiosis/microbiología , Disbiosis/metabolismo , Masculino , Femenino , Microbioma Gastrointestinal/fisiología , Síndrome de Cushing/microbiología , Síndrome de Cushing/metabolismo , Hidrocortisona/metabolismo , Persona de Mediana Edad , Adulto , Heces/microbiología , Estudios de Casos y Controles , Clostridiales/aislamiento & purificación , Clostridiales/metabolismoRESUMEN
Numerous studies have reported critical roles for the gut microbiota in obesity. However, the specific microbes that causally contribute to obesity and the underlying mechanisms remain undetermined. Here, we conducted shotgun metagenomic sequencing in a Chinese cohort of 631 obese subjects and 374 normal-weight controls and identified a Megamonas-dominated, enterotype-like cluster enriched in obese subjects. Among this cohort, the presence of Megamonas and polygenic risk exhibited an additive impact on obesity. Megamonas rupellensis possessed genes for myo-inositol degradation, as demonstrated in vitro and in vivo, and the addition of myo-inositol effectively inhibited fatty acid absorption in intestinal organoids. Furthermore, mice colonized with M. rupellensis or E. coli heterologously expressing the myo-inositol-degrading iolG gene exhibited enhanced intestinal lipid absorption, thereby leading to obesity. Altogether, our findings uncover roles for M. rupellensis as a myo-inositol degrader that enhances lipid absorption and obesity, suggesting potential strategies for future obesity management.