ABSTRACT
BACKGROUND: Pulse wave velocity (PWV), central pulse pressure and augmentation index are arterial stiffness- related hemodynamic parameters but their associations with renal outcome are still controversial. We hereby aim to study, 1) which hemodynamic parameter is independently associated with progressive chronic kidney disease (CKD), 2) the association of 3-year change in PWV with CKD progression and, 3) the additive predictive value of PWV for progressive CKD. METHODS: Carotid- femoral PWV, central pulse pressure and augmentation index were measured in 1444 participants with type 2 diabetes at baseline and 3 years apart. Progressive CKD was defined as confirmed eGFR decline 40% or greater. RESULTS: In the follow-up, 102 participants experienced progressive CKD. All 3 hemodynamic parameters were significantly associated with progressive CKD In univariable analysis. However, only PWV remained statistically significant after adjustment for known clinical risk factors and the other 2 hemodynamic parameters (OR 1.14 [95% CI 1.01-1.29] per m/s increment). One m/s regression (decrement) in PWV in the 3-year follow-up was associated with 26% lower adjusted- risk of progressive CKD (OR 0.74, 95% CI 0.56-0.97). Adding PWV onto traditional risk factor- based model significantly improved classification (net reclassification improvement 0.25, 95% CI 0.05-0.45, P = 0.01) and positive prediction rate (24.5 to 32.3%). CONCLUSIONS: Of 3 arterial stiffness- related hemodynamic parameters, only PWV is independently associated with progressive CKD. PWV may be a potential intervention target to mitigate risk of CKD progression and also a biomarker to improve risk-stratification of adverse renal outcome in individuals with type 2 diabetes.
Subject(s)
Aorta/physiopathology , Blood Pressure , Diabetes Mellitus, Type 2/physiopathology , Pulse Wave Analysis , Renal Insufficiency, Chronic/physiopathology , Vascular Stiffness , Aged , Diabetes Mellitus, Type 2/complications , Disease Progression , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Prospective Studies , Renal Insufficiency, Chronic/complicationsABSTRACT
OBJECTIVE: Haptoglobin is an acute-phase reactant with pleiotropic functions. We aimed to study whether urine haptoglobin may predict risk of mortality in people with type 2 diabetes. RESEARCH DESIGN AND METHODS: We employed a transethnic approach with a cohort of Asian origin (Singapore) (N = 2,061) and a cohort of European origin (France) (N = 1,438) included in the study. We used survival analyses to study the association of urine haptoglobin with risk of all-cause and cause-specific mortality. RESULTS: A total of 365 and 525 deaths were registered in the Singapore cohort (median follow-up 7.5 years [interquartile range 3.5-12.8]) and French SURDIAGENE cohort (median follow-up 6.8 years [interquartile range 4.3-10.5], respectively. Singapore participants with urine haptoglobin in quartiles 2 to 4 had higher risk for all-cause mortality compared with quartile 1 (unadjusted hazard ratio [HR] 1.47 [95% CI 1.02-2.11], 2.28 [1.62-3.21], and 4.64 [3.39-6.35], respectively). The association remained significant in quartile 4 after multiple adjustments (1.68 [1.15-2.45]). Similarly, participants in the French cohort with haptoglobin in quartile 4 had significantly higher hazards for all-cause mortality compared with quartile 1 (unadjusted HR 2.67 [2.09-3.42] and adjusted HR 1.49 [1.14-1.96]). In both cohorts, participants in quartile 4 had a higher risk of mortality attributable to cardiovascular disease and infection but not malignant tumor. CONCLUSIONS: Urine haptoglobin predicts risk of mortality independent of traditional risk factors, suggesting that it may potentially be a novel biomarker for risk of mortality in patients with type 2 diabetes.
Subject(s)
Diabetes Mellitus, Type 2/ethnology , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/urine , Haptoglobins/urine , Adult , Aged , Biomarkers/urine , Cardiovascular Diseases/complications , Cardiovascular Diseases/ethnology , Cardiovascular Diseases/mortality , Cardiovascular Diseases/urine , Cause of Death , Cohort Studies , Cross-Cultural Comparison , Diabetes Mellitus, Type 2/complications , Diabetic Angiopathies/diagnosis , Diabetic Angiopathies/ethnology , Diabetic Angiopathies/mortality , Diabetic Angiopathies/urine , Female , Follow-Up Studies , France/ethnology , Humans , Male , Middle Aged , Prognosis , Singapore/ethnology , Survival AnalysisABSTRACT
Data on specific causes of mortality in South East Asians with type 2 diabetes mellitus (T2DM) remain scarce. We followed 2061 outpatients with T2DM (Chinese 63%, Malays 20%, and Asian Indians 17%) for an average of 5.5 (standard deviation = 2.9) years and identified 365 death events by data linkage with national death registry. Cardiovascular disease was the main cause of mortality (44%), followed by renal disease (17%), infection (17%), cancer (14%), and others causes (8%). Survival analyses revealed that risks for all-cause and cause-specific mortality vary greatly among ethnic groups. Presence of diabetic kidney disease was an independent risk factor for death attributable to cardiovascular disease, renal disease, and infection, while HbA1c level predicted all major causes of deaths even after accounting for multiple other risk factors. These data reinforce the importance of glycemic control and prevention of diabetic kidney disease for mitigation of mortality burden in multiethnic Asians with T2DM.