Circulating metabolomic markers linking diabetic kidney disease and incident cardiovascular disease in type 2 diabetes: analyses from the Hong Kong Diabetes Biobank.

AIMS/HYPOTHESIS: The aim of this study was to describe the metabolome in diabetic kidney disease (DKD) and its association with incident CVD in type 2 diabetes, and identify prognostic biomarkers. METHODS: From a prospective cohort of individuals with type 2 diabetes, baseline sera (N=1991) were quantified for 170 metabolites using NMR spectroscopy with median 5.2 years of follow-up. Associations of chronic kidney disease (CKD, eGFR<60 ml/min per 1.73 m2) or severely increased albuminuria with each metabolite were examined using linear regression, adjusted for confounders and multiplicity. Associations between DKD (CKD or severely increased albuminuria)-related metabolites and incident CVD were examined using Cox regressions. Metabolomic biomarkers were identified and assessed for CVD prediction and replicated in two independent cohorts. RESULTS: At false discovery rate (FDR)<0.05, 156 metabolites were associated with DKD (151 for CKD and 128 for severely increased albuminuria), including apolipoprotein B-containing lipoproteins, HDL, fatty acids, phenylalanine, tyrosine, albumin and glycoprotein acetyls. Over 5.2 years of follow-up, 75 metabolites were associated with incident CVD at FDR<0.05. A model comprising age, sex and three metabolites (albumin, triglycerides in large HDL and phospholipids in small LDL) performed comparably to conventional risk factors (C statistic 0.765 vs 0.762, p=0.893) and adding the three metabolites further improved CVD prediction (C statistic from 0.762 to 0.797, p=0.014) and improved discrimination and reclassification. The 3-metabolite score was validated in independent Chinese and Dutch cohorts. CONCLUSIONS/INTERPRETATION: Altered metabolomic signatures in DKD are associated with incident CVD and improve CVD risk stratification.

Clinical characteristics of local allergic rhinitis sensitized to house dust mites in Asia.

PURPOSE: Local allergic rhinitis (LAR) is characterized by a localized nasal allergic response without evidence of systemic atopy. LAR is an underdiagnosed entity and is a diagnostic and therapeutic challenge for clinicians. This study aimed to investigate the prevalence and clinical characteristics of patients with LAR to house dust mites (LAR-HDM) in Korea. METHODS: We performed a retrospective chart review of 336 adult patients with rhinitis symptoms who visited the Rhinologic Clinic at Korea University Guro Hospital from October 2019 to April 2021. Using results of the skin prick test, serologic test, and nasal provocation test, patients were classified as allergic rhinitis (AR) to HDM (AR-HDM), AR to other allergens, non-allergic rhinitis (NAR), or LAR-HDM. We excluded patients with AR to other allergens and compared the clinical characteristics of the remaining three groups. Patient demographic data were reviewed, and patients' nasal symptoms, olfactory function, serum total IgE, and severity of accompanying rhinosinusitis were evaluated. RESULTS: In total, 336 patients were examined. AR-HDM was diagnosed in 138 (41.1%) patients, AR to other allergens in 36 (10.7%) patients, NAR in 21 (42.0%) patients, and LAR-HDM in 21 (6.3%) patients. The mean age of patients with LAR-HDM was significantly higher than that of patients with AR-HDM. There were no significant differences in sex, smoking history, asthma, and family history of allergic diseases between the groups. Compared to NAR patients, there were significantly more patients with LAR-HDM who had persistent nasal symptoms. The frequency of nasal itching and sneezing was significantly higher in the LAR-HDM group than in the NAR group. The olfactory function score in the LAR-HDM group was significantly worse than that in the AR-HDM group, and the Lund-Mackay score was significantly higher in the LAR-HDM group than in the other groups. CONCLUSION: Clinical history and nasal symptoms are very similar in LAR-HDM and AR-HDM. Clinicians should take more care to differentiate them. LAR-HDM should also be considered in patients with persistent and severe nasal symptoms without systemic atopy.