Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
Copyright © 2015 Korean Diabetes Association
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICTS OF INTEREST: No potential conflict of interest relevant to this article was reported.
Values are presented as mean±standard deviation, median (range) unless otherwise indicated.
BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; CVD, cardiovascular disease; OHA, oral hypoglycemic agent; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; HTN, hypertension; FPG, fasting plasma glucose; HbA1c, glycosylated hemoglobin; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; hsCRP, high sensitivity C-reactive protein; UACR, urinary albumin-to-creatinine ratio; eGFR, estimated glomerular filtration rate.
aLast UACR represent UACR in spot urine sample at last follow-up or at the time of event occurrence.
Values are presented as mean±standard deviation, median (range) unless otherwise indicated.
BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; CVD, cardiovascular disease; OHA, oral hypoglycemic agent; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; HTN, hypertension; FPG, fasting plasma glucose; HbA1c, glycosylated hemoglobin; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; hsCRP, high sensitivity C-reactive protein; UACR, urinary albumin-to-creatinine ratio; eGFR, estimated glomerular filtration rate.
aLast UACR represent UACR in spot urine sample at last follow-up or at the time of event occurrence.
Model 1: adjusted for conventional diabetic nephropathy risk factors (age, body mass index, duration of diabetes, current smoker, angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) use, other hypertension medication, high sensitivity C-reactive protein, baseline urinary albumin-to-creatinine ratio (UACR), baseline creatinine, follow-up mean glycosylated hemoglobin (HbA1c), follow-up mean systolic blood pressure (SBP), follow-up mean diastolic blood pressure). Model 2: adjusted for factors that showed a statistically significant (P<0.05, i.e., antidiabetic medication, ACEi or ARB use, fasting plasma glucose, total cholesterol, uric acid, baseline UACR, baseline creatinine, follow-up mean HbA1c) or borderline significant (P<0.10, i.e., duration of diabetes, baseline SBP, past history of cardiovascular disease, retinopathy) association in the univariate analysis. Model 3: adjusted for all the variables in models 1 and 2.
HR, hazard ratio; CI, confidence interval.
HR, hazard ratio; CI, confidence interval; UACR, urinary albumin-to-creatinine ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; HTN, hypertension; HbA1c, glycosylated hemoglobin; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; hsCRP, high sensitivity C-reactive protein.
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 |
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 |
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 |
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 |
Values are presented as mean±standard deviation, median (range) unless otherwise indicated. BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; CVD, cardiovascular disease; OHA, oral hypoglycemic agent; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; HTN, hypertension; FPG, fasting plasma glucose; HbA1c, glycosylated hemoglobin; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; hsCRP, high sensitivity C-reactive protein; UACR, urinary albumin-to-creatinine ratio; eGFR, estimated glomerular filtration rate. aLast UACR represent UACR in spot urine sample at last follow-up or at the time of event occurrence.
Values are presented as mean±standard deviation, median (range) unless otherwise indicated. BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; CVD, cardiovascular disease; OHA, oral hypoglycemic agent; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; HTN, hypertension; FPG, fasting plasma glucose; HbA1c, glycosylated hemoglobin; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; hsCRP, high sensitivity C-reactive protein; UACR, urinary albumin-to-creatinine ratio; eGFR, estimated glomerular filtration rate. aLast UACR represent UACR in spot urine sample at last follow-up or at the time of event occurrence.
Model 1: adjusted for conventional diabetic nephropathy risk factors (age, body mass index, duration of diabetes, current smoker, angiotensin-converting enzyme inhibitor (ACEi) or angiotensin II receptor blocker (ARB) use, other hypertension medication, high sensitivity C-reactive protein, baseline urinary albumin-to-creatinine ratio (UACR), baseline creatinine, follow-up mean glycosylated hemoglobin (HbA1c), follow-up mean systolic blood pressure (SBP), follow-up mean diastolic blood pressure). Model 2: adjusted for factors that showed a statistically significant ( HR, hazard ratio; CI, confidence interval.
HR, hazard ratio; CI, confidence interval; UACR, urinary albumin-to-creatinine ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; HTN, hypertension; HbA1c, glycosylated hemoglobin; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; hsCRP, high sensitivity C-reactive protein.