ABSTRACT
BACKGROUND & AIMS: It is well-known that high protein intake is associated with renal hyperfiltration and faster renal function decline, but the association of other macronutrients, carbohydrate and fat, with development of chronic kidney disease (CKD) is still inconclusive. Therefore, we aimed to examine the relationship between fat-to-carbohydrate intake ratio (F/C ratio) and incident CKD. METHODS: We included 9226 subjects from the Korean Genome and Epidemiology Study. The subjects were divided into two groups depending on 1 g protein intake per ideal body weight per day. Primary exposure was the F/C ratio defined as calorie intake of fat/calorie intake of fat and carbohydrate. The primary outcome was the development of CKD, which was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 and/or proteinuria (≥1+). RESULTS: During a median follow-up duration of 11.4 years, 778 (8.4%) CKD events occurred. Subjects in the lowest F/C ratio tertile had faster eGFR decline rate than other tertiles. In multivariable Cox analysis, a significantly higher CKD risk was observed in the lowest tertile when protein intake > 1 g/kg/day (hazard ratio [HR] for T1 (<16.1%) vs. T3 (>21.5%), 1.38; 95% confidence interval [CI], 1.03-1.84; P = 0.031). In sensitivity analysis, subjects maintained low F/C ratio diet (<16.1%) during 4 years showed higher risk of subsequent CKD development than those maintained high F/C ratio diet (≥16.1%; HR, 1.70; 95% CI, 1.10-2.63; P = 0.018). In cubic spline analysis, CKD risk was sharply increased in F/C ratio <16.1%, but the risk was nearly constant in F/C ratio ≥16.1%. CONCLUSIONS: A diet with a low F/C ratio was associated with increased risk of CKD in the general population. Therefore, it is necessary to limit excessive high carbohydrate and low fat intake to prevent CKD development in this population.
Subject(s)
Dietary Carbohydrates/administration & dosage , Dietary Fats/administration & dosage , Dietary Proteins/administration & dosage , Energy Intake , Renal Insufficiency, Chronic/epidemiology , Adult , Cohort Studies , Diet, Carbohydrate Loading/adverse effects , Diet, Fat-Restricted/adverse effects , Female , Glomerular Filtration Rate/drug effects , Humans , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Proteinuria/epidemiology , Republic of Korea/epidemiologyABSTRACT
INTRODUCTION: Obesity is a risk factor for type 2 diabetes mellitus (T2DM) and cardiovascular disease. T2DM increases the risk of cardiovascular-related death. We investigated changes in circulating exosomal microRNA (miRNA) profiles in patients with DM with obesity compared with patients without DM with obesity. RESEARCH DESIGN AND METHODS: This prospective study involved 29 patients with obesity (patients without DM=16, patients with DM=13) and healthy volunteers (HVs) (n=18). We measured circulating levels of exosomal miRNAs by next-generation sequencing and compared miRNA levels across the three groups. RESULTS: The expression levels of 25 miRNAs (upregulated=14, downregulated=11) differed between patients with obesity with DM and patients with obesity without DM. Compared with HV, patients with DM with obesity had 53 dysregulated miRNAs. Additionally, moving stepwise from HV to patients with obesity without DM to patients with obesity with DM, there was a consistent increase in expression levels of miR-23a-5p and miR-6087 and a consistent decrease in expressions levels of miR-6751-3p. CONCLUSIONS: Our data show that the exosomal miRNAs is altered by dysregulated glucose metabolism in patients with obesity. This circulating exosomal miRNA signature in patients with obesity with or without DM is a potential biomarker and therapeutic target in these patients.