Decreased Uric Acid Excretion Is Risk Factor for CKD in T2D
The clinical characteristics of the subjects grouped according to the UUAE quartiles are presented in Table 1 . The patients were stratified into quartiles based on the UUAE levels with the cutoff limits of <2235, 2235–2848, 2849–3606, and >3606 μmol/24 h. After controlling for age and sex, the diabetics in the higher UUAE quartiles were more likely to be male, younger, smokers and drinkers; have shorter durations of diabetes (DD); have higher DBP, BMI, WHR, FPG, 2 h PPG, FCP, 2 h PCP, HOMA2-IR, TTG, ALT, and eGFR; and have lower HOMA2-%S, HDL-C and Cr.
The associations between UUAE levels and the clinical parameters are shown in Table 2 . After adjusting for age, sex and DD, the partial correlations analyses demonstrated strongly positive correlations of UUAE levels with SBP, DBP, BMI, WHR, FPG, 2 h PPG, FCP, 2 h PCP, HOMA2-IR, TTG, TC, ALT, eGFR, and CRP, and significantly negative correlations between UUAE levels and age (controlling for sex and DD), DD (controlling for age and sex), HOMA2 %S, HDL-C, Cr, and UAE in diabetics.
Figure 1 demonstrates the comparison of CKD among the UUAE quartiles in patients. After controlling for age, sex, and DD, there was a significantly decreasing trend in the prevalence of CKD in patients across the UUAE quartiles (16.9%, 8.5%, 5.9%, and 4.9%, respectively, p < 0.001 for the trend; Figure 1A). Furthermore, the UUAE levels were obviously reduced in the diabetics with CKD compared to those without CKD (p < 0.001) (Figure 1B). Interestingly, the UUAE levels gradually decreased with the decreases in eGFR (p < 0.001; Figure 1C), and the UUAE levels were significantly decreased in the diabetics with UAEs ≥ 300 mg/24 h compared to those with UAEs <30 mg/24 h and those with UAEs in the range of 30–299 mg/24 h (p < 0.001; Figure 1D).
(Enlarge Image)
Figure 1.
Comparison of CKD among the UUAE quartiles. (A) Comparison of the prevalence of CKD among the UUAE quartile groups after adjusting for age, sex, and DD. The P values for the trends were <0.001. (B) Comparison of the UUAE levels between the diabetics with and without CKD after adjusting for age, sex, and DD. The P value was <0.001. (C) Comparison of UUAE levels among the different eGFR levels after adjusting for age, sex, and DD. The P values for the trends were <0.001. (D) Comparison of UUAE levels among the different UAE levels after adjusting for age, sex, and DD. The P values for the trends were <0.001.
A comparison of the atherosclerotic lesions among the UUAE quartile groups after adjustments for age, sex, and DD is shown in Figure 2. There were no statistical associations between the UUAE quartiles and the carotid IMT values (p = 0.736) and the prevalence of carotid plaques (p = 0.938) and stenosis (p = 0.171) in type 2 diabetes (Figure 2A, B and C).
(Enlarge Image)
Figure 2.
Comparison of carotid atherosclerotic lesions among the UUAE quartiles. (A) Comparison of the CIMT values among the UUAE quartile groups after adjusting for age, sex, and DD. (B) Comparison of the prevalence of carotid atherosclerotic plaques among the UUAE quartile groups after adjusting for age, sex, and DD. (C) Comparison of the prevalence of carotid atherosclerotic stenosis among the UUAE quartile groups after adjusting for age, sex, and DD.
Table 3 presents the associations between the UUAE quartiles and the presence of CKD in type 2 diabetes. After controlling for age, sex, DD, HTN, smoking, alcohol drinking, and the use of LLDs and AHAs (model 1), the UUAE quartiles were independently associated with a decreased prevalence of CKD (p < 0.001 for trend). After additional adjustments for SBP, DBP, WHR and BMI (model 2) and for ALT, TC, TTG, LDL-C, HDL-C, CRP, HbA1C, FPG, 2 h PPG, FCP, 2 h PCP, HOMA2-IR, and HOMA %S (model 3) and for SUA (model 4), the UUAE quartiles retained an independent association with a decreased prevalence of CKD (all p <0.001 for the trends in model 2, model 3, and model 4).
The comparisons of carotid atherosclerotic lesions between the diabetics with and without CKD are illustrated in Figure 3. After adjusting for age, sex, and DD, the CIMT values (0.91 ± 0.22 mm for the diabetics with CKD and 0.82 ± 0.20 mm for the diabetics without CKD, p = 0.001) and the prevalence of carotid plaque (62.1% for the diabetics with CKD and 41.8% for the diabetics without CKD, p = 0.025) were significantly higher in the diabetics with CKD than in those without CKD.
(Enlarge Image)
Figure 3.
Comparison of carotid atherosclerotic lesions between the diabetics with and without CKD. (A) Comparison of the CIMT values between the diabetics with and without CKD after adjusting for age, sex, and DD. (B) Comparison of the prevalence of carotid atherosclerotic plaques between the diabetics with and without CKD after adjusting for age, sex, and DD. (C) Comparison of the prevalence of carotid atherosclerotic stenosis between the diabetics with and without CKD after adjusting for age, sex, and DD.
Results
Characteristics of the Subjects According to UUAE Quartiles
The clinical characteristics of the subjects grouped according to the UUAE quartiles are presented in Table 1 . The patients were stratified into quartiles based on the UUAE levels with the cutoff limits of <2235, 2235–2848, 2849–3606, and >3606 μmol/24 h. After controlling for age and sex, the diabetics in the higher UUAE quartiles were more likely to be male, younger, smokers and drinkers; have shorter durations of diabetes (DD); have higher DBP, BMI, WHR, FPG, 2 h PPG, FCP, 2 h PCP, HOMA2-IR, TTG, ALT, and eGFR; and have lower HOMA2-%S, HDL-C and Cr.
Associations Between UUAE Levels and Clinical Parameters
The associations between UUAE levels and the clinical parameters are shown in Table 2 . After adjusting for age, sex and DD, the partial correlations analyses demonstrated strongly positive correlations of UUAE levels with SBP, DBP, BMI, WHR, FPG, 2 h PPG, FCP, 2 h PCP, HOMA2-IR, TTG, TC, ALT, eGFR, and CRP, and significantly negative correlations between UUAE levels and age (controlling for sex and DD), DD (controlling for age and sex), HOMA2 %S, HDL-C, Cr, and UAE in diabetics.
Comparison of CKD Among the UUAE Quartiles
Figure 1 demonstrates the comparison of CKD among the UUAE quartiles in patients. After controlling for age, sex, and DD, there was a significantly decreasing trend in the prevalence of CKD in patients across the UUAE quartiles (16.9%, 8.5%, 5.9%, and 4.9%, respectively, p < 0.001 for the trend; Figure 1A). Furthermore, the UUAE levels were obviously reduced in the diabetics with CKD compared to those without CKD (p < 0.001) (Figure 1B). Interestingly, the UUAE levels gradually decreased with the decreases in eGFR (p < 0.001; Figure 1C), and the UUAE levels were significantly decreased in the diabetics with UAEs ≥ 300 mg/24 h compared to those with UAEs <30 mg/24 h and those with UAEs in the range of 30–299 mg/24 h (p < 0.001; Figure 1D).
(Enlarge Image)
Figure 1.
Comparison of CKD among the UUAE quartiles. (A) Comparison of the prevalence of CKD among the UUAE quartile groups after adjusting for age, sex, and DD. The P values for the trends were <0.001. (B) Comparison of the UUAE levels between the diabetics with and without CKD after adjusting for age, sex, and DD. The P value was <0.001. (C) Comparison of UUAE levels among the different eGFR levels after adjusting for age, sex, and DD. The P values for the trends were <0.001. (D) Comparison of UUAE levels among the different UAE levels after adjusting for age, sex, and DD. The P values for the trends were <0.001.
Comparison of the Carotid Atherosclerotic Lesions Among the UUAE Quartiles
A comparison of the atherosclerotic lesions among the UUAE quartile groups after adjustments for age, sex, and DD is shown in Figure 2. There were no statistical associations between the UUAE quartiles and the carotid IMT values (p = 0.736) and the prevalence of carotid plaques (p = 0.938) and stenosis (p = 0.171) in type 2 diabetes (Figure 2A, B and C).
(Enlarge Image)
Figure 2.
Comparison of carotid atherosclerotic lesions among the UUAE quartiles. (A) Comparison of the CIMT values among the UUAE quartile groups after adjusting for age, sex, and DD. (B) Comparison of the prevalence of carotid atherosclerotic plaques among the UUAE quartile groups after adjusting for age, sex, and DD. (C) Comparison of the prevalence of carotid atherosclerotic stenosis among the UUAE quartile groups after adjusting for age, sex, and DD.
Associations of UUAE Quartiles With CKD
Table 3 presents the associations between the UUAE quartiles and the presence of CKD in type 2 diabetes. After controlling for age, sex, DD, HTN, smoking, alcohol drinking, and the use of LLDs and AHAs (model 1), the UUAE quartiles were independently associated with a decreased prevalence of CKD (p < 0.001 for trend). After additional adjustments for SBP, DBP, WHR and BMI (model 2) and for ALT, TC, TTG, LDL-C, HDL-C, CRP, HbA1C, FPG, 2 h PPG, FCP, 2 h PCP, HOMA2-IR, and HOMA %S (model 3) and for SUA (model 4), the UUAE quartiles retained an independent association with a decreased prevalence of CKD (all p <0.001 for the trends in model 2, model 3, and model 4).
Comparisons of Carotid Atherosclerotic Lesions Between the Diabetics With and Without CKD
The comparisons of carotid atherosclerotic lesions between the diabetics with and without CKD are illustrated in Figure 3. After adjusting for age, sex, and DD, the CIMT values (0.91 ± 0.22 mm for the diabetics with CKD and 0.82 ± 0.20 mm for the diabetics without CKD, p = 0.001) and the prevalence of carotid plaque (62.1% for the diabetics with CKD and 41.8% for the diabetics without CKD, p = 0.025) were significantly higher in the diabetics with CKD than in those without CKD.
(Enlarge Image)
Figure 3.
Comparison of carotid atherosclerotic lesions between the diabetics with and without CKD. (A) Comparison of the CIMT values between the diabetics with and without CKD after adjusting for age, sex, and DD. (B) Comparison of the prevalence of carotid atherosclerotic plaques between the diabetics with and without CKD after adjusting for age, sex, and DD. (C) Comparison of the prevalence of carotid atherosclerotic stenosis between the diabetics with and without CKD after adjusting for age, sex, and DD.
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