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.

Medical costs associated with chronic kidney disease progression in an Asian population with type 2 diabetes mellitus.

AIM: We aim to examine difference in incremental direct medical costs between non-progressive and progressive chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM) in Singapore. METHODS: This was a prospective study on 676 patients with T2DM attending a diabetes centre in a regional hospital. Annual direct medical costs were extracted from the administrative database. Ordinary least squares regression was used to estimate contribution of CKD progression to annual costs, adjusting for demographics and baseline clinical covariates. RESULTS: Over mean follow-up period of 2.8 ± 0.4 years, 266 (39.3%) had CKD progression. The excess total follow-up medical costs from baseline was S$4243 higher in progressors compared to non-progressors (P = 0.002). The mean cost differential between the two groups increased from S$2799 in Stages G1-G2 to S$11180 in Stage G4. Inpatient cost accounted for 63.4% of total cost of progression. When stratified by glomerular filtration rate stages, the respective total mean annual costs at stages glomerular filtration rate Stages G3a-G3b and G4 were S$3290 (132%; P = 0.001) and S$4416 (135%; P = 0.011) higher post-progression. CONCLUSION: Chronic kidney disease progression in T2DM is associated with high medical costs. The cost of progression is higher with higher severity of CKD stage at baseline and could be largely driven by inpatient admission.

Impact of haemoglobin A1c trajectories on chronic kidney disease progression in type 2 diabetes.

AIM: To characterize haemoglobin A1c (HbA1c) trajectories and examine their associations with chronic kidney disease (CKD) progression. METHODS: This was a prospective cohort study on 770 patients with type 2 diabetes mellitus (T2DM) attending a diabetes centre in 2002-2017. Group-based trajectory modelling was used to identify HbA1c trajectories. Cox proportional hazards models were used to examine association between the trajectories and CKD progression which was defined as deterioration across the Kidney Disease: Improving Global Outcomes estimated glomerular filtration rate categories with ≥25% drop from baseline. RESULTS: We identified four HbA1c trajectories: 'near-optimal stable' (49.1%), 'moderate stable' (37.9%), 'moderate-increasing' (6.0%) and 'high-decreasing' (7.0%). Over a median follow-up period of 4.6 years (interquartile range 2.5-5.6), CKD progression occurred in 35.6% of patients. The risk of CKD progression was significantly higher in the moderate-increasing with adjusted hazard ratios (HR) 2.23 (95% confidence interval (CI) 1.09-4.57). After additional adjustment for mean HbA1c, the association between the moderate-increasing subgroup and CKD progression remained significant at HR 3.07 (95% CI 1.08-8.77). CONCLUSION: Moderate-increasing HbA1c trajectory is associated with renal disease progression in patients with T2DM, independent of mean HbA1c. The deleterious effects of deteriorating HbA1c trajectory highlight the importance of achieving sustained good glycaemic control in diabetes management.

Effect of long-term glycemic variability on estimated glomerular filtration rate decline among patients with type 2 diabetes mellitus: Insights from the Diabetic Nephropathy Cohort in Singapore.

BACKGROUND: In the present study, we examined the association between HbA1c variability and renal disease progression based on estimated glomerular filtration rate (eGFR) decline in patients with type 2 diabetes mellitus (T2DM) in Singapore. METHODS: Glycemic burden and renal function were retrospectively assessed in 1628 patients in 2002-2014. Multivariable logistic regression was used to assess the relationships between HbA1c variability (expressed as HbA1c coefficient of variation [HbA1c-CV] in quartiles), HbA1c intrapersonal mean (HbA1c-IM), and eGFR decline, adjusted for baseline covariates. RESULTS: Among patients with relatively good glycemic control (i.e. HbA1c-IM below the median cohort value [8.0%]), HbA1c-CV Quartile 4 was associated with eGFR decline (odds ratio [OR] 1.88; 95% confidence interval [CI] 1.10-3.25). The OR for HbA1c-CV Quartile 4 was 2.20 (95% CI 1.24-3.89) after additional adjustment for HbA1c-IM. Where HbA1c-IM was above the median cohort value, HbA1c-CV Quartiles 3 and 4 were associated with eGFR decline, with ORs of 2.60 (95% CI 1.48-4.55) and 3.29 (95% CI 1.89-5.76) respectively. After further adjusting for HbA1c-IM, the ORs for Quartiles 3 and 4 were 2.69 (95% CI 1.53-4.74) and 3.51 (95% CI 1.98-6.21), respectively. CONCLUSIONS: Variability in HbA1c is strongly and independently associated with eGFR decline in patients with T2DM independent of mean HbA1c. The findings may highlight the importance of sustained stable glycemic control in management of diabetes mellitus.