Fig. 1Kaplan-Meier curves for progression of diabetic nephropathy according to serum ceruloplasmin tertile categories.
Table 1Clinical and biochemical characteristics of the study subjects according to serum ceruloplasmin tertile categories at baseline
Characteristic |
Ceruloplasmin tertile categories |
P value |
Q1 (≤219 mg/L) (n=222) |
Q2 (220-249 mg/L) (n=210) |
Q3 (≥250 mg/L) (n=211) |
Baseline data |
|
|
|
|
Age, yr |
56.7±9.9 |
57.4±9.5 |
56.9±11.4 |
0.807 |
BMI, kg/m2
|
25.3±2.8 |
25.3±2.7 |
25.1±3.2 |
0.597 |
Duration of diabetes, yr |
8.0 (4.0-12.0) |
8.0 (5.0-13.0) |
7.0 (3.0-13.0) |
0.209 |
SBP, mm Hg |
126.5±14.1 |
127.3±14.8 |
130.1±16.3 |
0.035 |
DBP, mm Hg |
77.0±9.0 |
76.8±9.6 |
78.1±10.2 |
0.326 |
Current smoker, % |
18.5 |
28.6 |
26.1 |
0.038 |
Past history of CVD, % |
12.6 |
11.0 |
9.0 |
0.484 |
Antidiabetic medication, % |
|
|
|
<0.001 |
None |
6.8 |
8.1 |
7.6 |
OHA |
90.1 |
82.3 |
72.9 |
Insulin |
0.5 |
0 |
6.2 |
OHA+insulin |
2.7 |
9.6 |
13.3 |
ACEi or ARB use, % |
33.3 |
41.0 |
39.3 |
0.225 |
Other HTN medication use, % |
27.9 |
33.8 |
30.3 |
0.413 |
Statin use, % |
36.5 |
35.7 |
37.4 |
0.934 |
Retinopathy, % |
19.8 |
28.6 |
28.0 |
0.064 |
FPG, mmol/L |
7.3 (6.48-8.23) |
7.33 (6.11-8.82) |
7.38 (6.44-8.99) |
0.443 |
HbA1c, % |
7.0 (6.5-7.7) |
7.2 (6.4-8.2) |
7.5 (6.7-8.4) |
0.001 |
HbA1c, mmol/L |
53 (48-61) |
55 (46-66) |
58 (50-68) |
0.001 |
Total cholesterol, mmol/L |
4.42±0.93 |
4.48±0.90 |
4.71±1.06 |
0.005 |
Triglyceride, mmol/L |
1.38 (0.98-1.98) |
1.51 (1.11-2.11) |
1.46 (1.01-2.16) |
0.513 |
LDL-C, mmol/L |
2.54±0.74 |
2.62±0.76 |
2.79±0.81 |
0.004 |
HDL-C, mmol/L |
1.27±0.34 |
1.23±0.30 |
1.21±0.29 |
0.114 |
Uric acid, µmol/L |
321.4±74.1 |
334.3±80.6 |
329.9±87.3 |
0.243 |
hsCRP, mg/L |
0.5 (0.3-0.8) |
0.6 (0.3-1.2) |
1.3 (0.7-2.8) |
<0.001 |
Ceruloplasmin, mg/L |
197.3±17.3 |
233.6±8.4 |
277.8±29.6 |
- |
UACR, mg/g |
5.9 (3.1-13.9) |
9.7 (4.2-39.9) |
11.9 (4.5-46.3) |
<0.001 |
Creatinine, mg/dL |
1.0 (0.9-1.1) |
1.0 (0.9-1.1) |
0.9 (0.8-1.1) |
0.376 |
eGFR, mL/min/1.73 m2
|
87.1±17.1 |
86.0±19.4 |
88.9±23.0 |
0.325 |
Follow-up data |
|
|
|
|
Follow-up mean HbA1c, % |
7.1 (6.6-7.7) |
7.1 (6.5-8.0) |
7.2 (6.5-8.0) |
0.766 |
Follow-up mean HbA1c, mmol/L |
54 (49-61) |
54 (48-63) |
55 (48-64) |
0.766 |
Follow-up mean SBP, mm Hg |
126.0±23.0 |
126.0±20.0 |
129.7±17.9 |
0.123 |
Follow-up mean DBP, mm Hg |
70.9±13.3 |
70.4±11.2 |
72.5±10.6 |
0.192 |
Last UACR, mg/ga
|
7.6 (3.7-17.5) |
9.1 (4.4-44.0) |
12.0 (5.0-71.8) |
<0.001 |
Last creatinine, mg/dL |
0.9 (0.8-1.0) |
0.9 (0.8-1.1) |
0.9 (0.8-1.1) |
0.542 |
Last eGFR, mL/min/1.73 m2
|
89.5±18.3 |
88.1±24.1 |
90.9±29.6 |
0.488 |
Progression of diabetic nephropathy, n (%) |
6 (2.7) |
12 (5.7) |
31 (14.7) |
<0.001 |
Table 2Baseline and follow-up clinical and biochemical characteristics of progressors and nonprogressors of diabetic nephropathy
Characteristic |
Nonprogressors (n=594) |
Progressors (n=49) |
P value |
Overall |
Baseline data |
|
|
|
|
Age, yr |
56.8±10.2 |
59.1±10.7 |
0.131 |
57.0±10.25 |
BMI, kg/m2
|
25.2±2.9 |
25.1±3.0 |
0.842 |
25.2±2.9 |
Duration of diabetes, yr |
8.0 (3-12) |
10.0 (6.0-16.5) |
0.018 |
8.0 (4.0-13.0) |
SBP, mm Hg |
127.6±14.6 |
131.4±20.2 |
0.206 |
127.9±15.1 |
DBP, mm Hg |
77.2±9.6 |
78.1±10.3 |
0.533 |
77.3±9.6 |
Current smoker, % |
23.9 |
28.6 |
0.464 |
24.3 |
Past history of CVD, % |
11.4 |
4.1 |
0.112 |
10.9 |
Antidiabetic medication, % |
|
|
0.001 |
|
None |
8.1 |
0 |
7.5 |
OHA |
82.4 |
75.5 |
81.9 |
Insulin |
1.7 |
8.2 |
2.2 |
OHA+insulin |
7.8 |
16.3 |
8.4 |
ACEi or ARB use, % |
35.5 |
65.3 |
<0.001 |
37.8 |
Other HTN medication use, % |
29.6 |
42.9 |
0.054 |
30.6 |
Statin use, % |
36.0 |
42.9 |
0.340 |
36.5 |
Retinopathy, % |
24.6 |
34.7 |
0.118 |
25.3 |
FPG, mmol/L |
7.33 (6.38-8.60) |
7.33 (6.19-9.32) |
0.680 |
7.33 (6.38-8.60) |
HbA1c, % |
7.2 (6.5-8.1) |
7.2 (6.5-8.6) |
0.587 |
7.2 (6.5-8.1) |
HbA1c, mmol/L |
55 (48-65) |
55 (47-70) |
0.587 |
55 (48-65) |
Total cholesterol, mmol/L |
4.51±0.94 |
4.87±1.27 |
0.058 |
4.53±0.97 |
Triglyceride, mmol/L |
1.42 (1.01-2.05) |
1.72 (1.20-2.42) |
0.056 |
1.46 (1.02-2.08) |
LDL-C, mmol/L |
2.64±0.77 |
2.74±0.80 |
0.392 |
2.65±0.77 |
HDL-C, mmol/L |
1.24±0.31 |
1.28±0.36 |
0.441 |
1.24±0.32 |
Uric acid, µmol/L |
324.3±78.2 |
378.1±95.4 |
<0.001 |
328.4±80.8 |
hsCRP, mg/L |
0.6 (0.4-1.4) |
1.1 (0.6-3.0) |
0.004 |
0.7 (0.4-1.5) |
Ceruloplasmin, mg/L |
233.3±37.8 |
262.6±40.9 |
<0.001 |
235.6±38.8 |
UACR, mg/g |
7.8 (3.7-25.4) |
27 (14.3-265.2) |
<0.001 |
8.5 (3.8-30.8) |
Baseline creatinine, mg/dL |
0.9 (0.9-1.1) |
1.1 (0.9-1.4) |
<0.001 |
0.9 (0.9-1.1) |
eGFR, mL/min/1.73 m2
|
88.5±19.1 |
72.4±23.5 |
<0.001 |
87.3±19.9 |
Follow-up data |
|
|
|
|
Follow-up mean HbA1c, % |
7.1 (6.5-7.8) |
7.4 (6.8-8.7) |
0.014 |
7.1 (6.5-7.8) |
Follow-up mean HbA1c, mmol/L |
54.1 (47.5-61.8) |
57.4 (50.8-71.0) |
0.014 |
54.1 (47.5-62.0) |
Follow-up mean SBP, mm Hg |
127.0±20.1 |
130.0±24.2 |
0.330 |
127.2±20.5 |
Follow-up mean DBP, mm Hg |
71.2±11.7 |
71.7±13.1 |
0.805 |
71.3±11.8 |
Last UACR, mg/ga
|
8.0 (3.9-21.1) |
279.6 (51.5-667.1) |
<0.001 |
9.0 (4.1-30.5) |
Last creatinine, mg/dL |
0.9 (0.8-1.0) |
1.1 (0.9-2.1) |
<0.001 |
0.9 (0.8-1.1) |
Last eGFR, mL/min/1.73 m2
|
91.0±21.8 |
71.0±41.1 |
0.001 |
89.5±24.3 |
Table 3HRs and 95% CI for progression of diabetic nephropathy based on serum ceruloplasmin tertile categories
|
HR (95% CI) |
P value |
Q1 (≤219 mg/L) (n=222) |
Q2 (220-249 mg/L) (n=210) |
Q3 (≥250 mg/L) (n=211) |
Subjects, progressor/total, n (%) |
6/222 (2.7) |
12/210 (5.7) |
31/211 (14.7) |
|
HRs for progression of diabetic nephropathy |
|
|
|
|
Unadjusted |
1 |
1.95 (0.73-5.19) |
5.41 (2.30-12.96) |
<0.001 |
Model 1 |
1 |
1.20 (0.42-3.45) |
4.10 (1.64-10.24) |
<0.001 |
Model 2 |
1 |
1.25 (0.44-3.52) |
3.45 (1.37-8.71) |
0.003 |
Model 3 |
1 |
1.14 (0.38-3.40) |
3.14 (1.21-8.10) |
0.010 |
Table 4Other risk factors for progression of diabetic nephropathy demonstrated by multivariate Cox regression analysis
Variable |
HR |
95% CI |
P value |
Age, yr |
1.00 |
0.96-1.04 |
0.807 |
Baseline creatinine, mg/dL |
2.72 |
1.28-5.76 |
0.009 |
Baseline UACR (per 100 mg/g) |
1.04 |
1.00-1.07 |
0.031 |
Follow-up mean SBP, mm Hg |
1.02 |
0.97-1.07 |
0.444 |
Follow-up mean DBP, mm Hg |
0.95 |
0.87-1.04 |
0.288 |
ACEi or ARB use, % |
2.17 |
0.97-1.07 |
0.059 |
Other HTN medication use, % |
0.62 |
0.29-1.32 |
0.214 |
Follow-up mean HbA1c, % |
1.42 |
1.06-1.91 |
0.018 |
Duration of diabetes, yr |
1.00 |
0.95-1.04 |
0.912 |
Fasting plasma glucose, mmol/L |
1.05 |
0.93-1.19 |
0.421 |
Body mass index, kg/m2
|
0.93 |
0.82-1.06 |
0.294 |
Triglyceride, mmol/L |
1.12 |
0.88-1.42 |
0.353 |
LDL-C, mmol/L |
1.17 |
0.78-1.75 |
0.451 |
HDL-C, mmol/L |
0.75 |
0.60-0.96 |
0.360 |
Retinopathy, % |
0.78 |
0.35-1.77 |
0.552 |
Current smoker, % |
1.42 |
0.68-2.97 |
0.350 |
Uric acid, µmol/L |
1.01 |
1.00-1.01 |
0.017 |
hsCRP, mg/L |
0.98 |
0.90-1.06 |
0.590 |