Triglyceride-glucose index is prospectively associated with chronic kidney disease progression in Type 2 diabetes - mediation by pigment epithelium-derived factor.

BACKGROUND: Triglyceride-glucose (TyG) index is a surrogate marker of insulin resistance. Its role in chronic kidney disease (CKD) progression in Type 2 Diabetes Mellitus (T2DM) is unclear. We investigated the association between TyG index and CKD progression, and possible mediation of the association by pigment epithelium-derived factor (PEDF). METHODS: This was a prospective study on 1571 patients with T2DM. CKD progression was defined as worsening across KDIGO estimated glomerular filtration rate (eGFR) categories with ≥25% reduction from baseline. PEDF was quantitated using enzyme-linked immunosorbent assay method. Cox proportional hazards regression model was used to assess the relationship between TyG index and CKD progression. RESULTS: Over a follow-up period of up to 8.6 years (median 4.6 years, IQR 3.0-3.6), 42.7% of subjects had CKD progression. Every unit increase in TyG was associated with hazards of 1.44 (95%CI 1.29-1.61; p < 0.001) in unadjusted analysis and 1.21 (1.06-1.37; p = 0.004) in fully adjusted model. Compared to tertile 1, tertiles 2 and 3 TyG index were positively associated with CKD progression with corresponding hazard ratios HRs 1.24 (1.01-1.52; p = 0.037) and 1.37 (1.11-1.68; p = 0.003) in fully adjusted models. PEDF accounted for 36.0% of relationship between TyG index and CKD progression. CONCLUSIONS: Higher TyG index independently predicted CKD progression in T2DM. PEDF mediated the association between TyG index and CKD progression.

Genetic Risk Score for Plasma Uric Acid Levels Is Associated With Early Rapid Kidney Function Decline in Type 2 Diabetes.

CONTEXT: Observational studies have shown that elevated uric acid (UA) is associated with chronic kidney disease (CKD). However, whether the relationship is causal remains unclear. OBJECTIVE: To determine the association of plasma UA and incident CKD and the causal relationship between plasma UA and rapid decline in kidney function (RDKF) in patients with type 2 diabetes (T2D). METHODS: Multivariable Cox regression was conducted to evaluate the hazard ratio (HR) between plasma UA and incident CKD among 1300 normoalbuminuric patients in 2 T2D study cohorts (DN, n = 402; SMART2D, n = 898). A weighted genetic risk score (wGRS) was calculated based on 10 single nucleotide polymorphism (SNPs) identified in genome-wide association studies of UA in East Asians. Mendelian randomization (MR) analysis was performed among 1146 Chinese T2D patients without CKD (estimated glomerular filtration rate [eGFR] > 60 mL/min/1.73m2) at baseline (DN, 478; SMART2D, 668). The wGRS and individual SNPs were used as genetic instruments and RDKF was defined as eGFR decline of 5 mL/min/1.73m2/year or greater. RESULTS: During mean follow-up of 5.2 and 5.4 years, 81 (9%) and 46 (11%) participants in SMART2D and DN developed CKD, respectively. A 1-SD increment in plasma UA conferred higher risk of incident CKD (DN, adjusted-HR = 1.40 [95% CI, 1.02-1.91], P = 0.036; SMART2D, adjusted-HR = 1.31 [95% CI, 1.04-1.64], P = 0.018). Higher wGRS was associated with increased odds for RDKF (meta-adjusted odds ratio = 1.12 [95% CI, 1.01-1.24], P = 0.030, Phet = 0.606). CONCLUSION: Elevated plasma UA is an independent risk factor for incident CKD. Furthermore, plasma UA potentially has a causal role in early eGFR loss in T2D patients.

Prevalence of Chronic Kidney Disease in Adults with Type 2 Diabetes Mellitus.

INTRODUCTION: Diabetes mellitus (DM) is a major cause of chronic kidney disease (CKD). The epidemiology of CKD secondary to type 2 DM (T2DM) (i.e. diabetic nephropathy (DN)) has not been well studied in Singapore, a multi-ethnic Asian population. We aimed to determine the prevalence of CKD in adult patients with T2DM. MATERIALS AND METHODS: We conducted a cross-sectional study on patients (n = 1861) aged 21 to 89 years with T2DM who had attended the DM centre of a single acute care public hospital or a primary care polyclinic between August 2011 and November 2013. Demographic and clinical data were obtained from patients using a standard questionnaire. Spot urine and fasting blood samples were sent to an accredited hospital laboratory for urinary albumin, serum creatinine, HbA1c and lipid measurement. CKD was defined and classified using the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines and classification. RESULTS: The distribution by risk of adverse CKD outcomes was: low risk, 47%; moderate risk, 27.2%; high risk, 12.8%; and very high risk, 13%. The prevalence of CKD in patients with T2DM was 53%. Variables significantly associated with CKD include neuropathy, blood pressure ≥140/80 mmHg, triglycerides ≥1.7 mmol, body mass index, duration of diabetes, HbA1c ≥8%, age, cardiovascular disease, and proliferative retinopathy. CONCLUSION: CKD was highly prevalent among patients with T2DM in Singapore. Several risk factors for CKD are well recognised and amenable to intervention. Routine rigorous screening for DN and enhanced programme for global risk factors reduction will be critical to stem the tide of DN.