NOTES
-
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
-
AUTHOR CONTRIBUTIONS
Conception or design: D.H.S., S.H.K.
Acquisition, analysis, or interpretation of data: D.H.S., M.N., M.J., Y.J.S., S.H.A., S.H., S.H.K.
Drafting the work or revising: D.H.S., M.N., M.J., S.H.A., S.H., S.H.K.
Final approval of the manuscript: S.H.K.
Fig. 1Comparison of plasma adipocyte fatty acid-binding protein (A-FABP) levels (µg/L) based on sex (A), the presence of rapid renal function decline (B), or albuminuria (C). The bottom of the box plots indicates the 25th percentile and the top indicates the 75th percentile. The middle line of the box indicates the median. The lower and the upper ends of the whiskers indicate the minimum and the maximum observations below the upper fence (1.5 interquartile range above the 75th percentile), respectively.
Table 1.Baseline characteristics of the study population according to the presence of rapid renal function decline
Characteristic |
All (n=452) |
Non-decliners (n=370) |
Rapid decliners (n=82) |
P value |
Age, yr |
52.6±9.2 |
51.8±9.1 |
55.9±9.3 |
<0.001 |
Male sex |
313 (69.2) |
255 (68.9) |
58 (70.7) |
0.850 |
Diabetes duration, yr |
5.6±5.1 |
5.4±4.9 |
6.4±5.8 |
0.171 |
BMI, kg/m2
|
25.5±3.1 |
25.5±3.2 |
25.6±2.8 |
0.809 |
WC, cm |
88.3±7.5 |
88.2±7.6 |
88.3±7.1 |
0.902 |
SBP, mm Hg |
124.5±14.1 |
124.1±13.6 |
126.4±16.2 |
0.253 |
DBP, mm Hg |
77.5±10.0 |
77.5±9.9 |
77.6±10.6 |
0.893 |
Hypertension |
181 (40.0) |
148 (40.3) |
33 (40.2) |
1.000 |
Dyslipidemia |
128 (28.3) |
107 (29.5) |
21 (25.6) |
0.573 |
CVD |
17 (3.8) |
16 (6.6) |
1 (1.8) |
0.279 |
Diabetic retinopathy |
11 (2.4) |
10 (4.2) |
2 (3.9) |
0.896 |
HbA1c, % |
7.9±1.7 |
7.9±1.7 |
7.9±1.5 |
0.828 |
FPG, mg/dL |
150.0±48.6 |
151.5±49.8 |
143.7±42.3 |
0.189 |
PP2 glucose, mg/dL |
279.6±99.4 |
281.9±100.2 |
269.2±95.9 |
0.434 |
HOMA-IR, unit |
2.9 (1.6 to 4.4) |
2.7 (1.6 to 4.4) |
2.9 (2.0 to 4.1) |
0.537 |
Total cholesterol, mg/dL |
184.6±40.2 |
182.0±38.6 |
196.4±44.9 |
0.003 |
Triglyceride, mg/dL |
168.6±114.5 |
168.1±112.0 |
170.8±125.6 |
0.847 |
HDL-C, mg/dL |
47.1±10.3 |
46.8±10.0 |
48.1±11.8 |
0.349 |
LDL-C, mg/dL |
121.7±36.5 |
120.3±35.1 |
127.8±41.6 |
0.135 |
hs-CRP, mg/dL |
0.09 (0.05 to 0.19) |
0.1 (0.1 to 0.2) |
0.1 (0.1 to 0.2) |
0.953 |
Albuminuria |
|
|
|
0.400 |
Normoalbuminuria |
314 (69.5) |
252 (70.6) |
62 (75.6) |
|
Microalbuminuria |
114 (25.2) |
97 (27.2) |
17 (20.7) |
|
Macroalbuminuria |
11 (2.4) |
8 (2.2) |
3 (3.7) |
|
UACR, mg/g |
17.0 (9.7 to 37) |
18.0 (10.0 to 38.0) |
15.2 (8.9 to 29.0) |
0.164 |
eGFR, mL/min/1.73 m2
|
85.8±14.9 |
84.8±14.9 |
90.2±14.2 |
0.003 |
eGFR slope, %/yr |
–2.0 (–3.5 to –0.6) |
–0.9±1.9 |
–5.8±2.9 |
<0.001 |
Diabetes medications |
|
|
|
|
Metformin |
330 (73.0) |
238 (71.9) |
92 (78.0) |
0.246 |
Sulfonylurea |
207 (45.8) |
267 (72.8) |
63 (76.8) |
0.537 |
TZD |
56 (12.4) |
169 (46.0) |
38 (46.3) |
1.000 |
Insulin |
62 (13.7) |
50 (13.6) |
6 (7.3) |
0.168 |
Use of statin |
148 (32.7) |
96 (31.0) |
52 (37.7) |
0.198 |
Use of ACEi/ARB |
176 (38.9) |
50 (13.6) |
12 (14.6) |
0.950 |
A-FABP, µg/L |
17.72 (11.88 to 25.51) |
17.2 (11.2 to 24.1) |
20.2 (14.1 to 29.9) |
0.005 |
Men |
15.81 (10.82 to 21.40)a
|
15.2 (10.5 to 21.1) |
17.5 (12.2 to 24.4) |
0.037 |
Women |
23.11 (15.72 to 33.09)a
|
22.1 (15.3 to 30.8) |
31.5 (20.7 to 50.7) |
0.007 |
Total adiponectin, µg/mL |
3.9 (2.8 to 6.0) |
3.9 (2.8 to 6.1) |
3.9 (2.8 to 6.3) |
0.876 |
HMW adiponectin, µg/mL |
1.2 (0.6 to 2.4) |
1.3 (0.6 to 2.4) |
1.3 (0.6 to 2.6) |
0.809 |
Interleukin-6, pg/mL |
0.9 (0.5 to 1.5) |
0.9 (0.5 to 1.5) |
0.9 (0.7 to 1.3) |
0.179 |
TNF-α, pg/mL |
1.2 (0.8 to 2.0) |
1.3 (0.8 to 2.0) |
1.2 (0.8 to 2.1) |
0.480 |
PTX3, ng/mL |
1.3 (0.8 to 2.1) |
1.2 (0.8 to 2.2) |
1.4 (0.9 to 2.1) |
0.237 |
Table 2.Association between annual renal function decline (%) and cytokines
Variable |
Unadjusted
|
Adjusteda
|
r
|
P value |
r
|
P value |
A-FABP, µg/L |
–0.055 |
0.24 |
–0.150 |
0.005 |
hs-CRP, mg/dL |
–0.013 |
0.78 |
0.001 |
0.99 |
Fibrinogen, mg/dL |
–0.064 |
0.23 |
–0.046 |
0.39 |
Total adiponectin, µg/mL |
–0.023 |
0.63 |
0.071 |
0.19 |
HMW adiponectin, µg/mL |
–0.039 |
0.40 |
0.055 |
0.31 |
Interleukin-6, pg/mL |
–0.043 |
0.36 |
0.051 |
0.35 |
TNF-α, pg/mL |
0.037 |
0.43 |
–0.045 |
0.40 |
PTX3, ng/mL |
–0.042 |
0.37 |
–0.070 |
0.19 |
Table 3.Characteristics according to A-FABP tertile levels
Characteristic |
Tertiles of A-FABP levels, μg/L
|
P for trend |
1 (<12.25 [men], <18.68 [women]) |
2 (12.25–19.44 [men], 18.68–30.13 [women]) |
3 (>19.44 [men], >30.13[women]) |
Age, yr |
51.2±8.0 |
52.4±8.9 |
54.1±10.5 |
0.005 |
Diabetes duration, yr |
4.8±4.6 |
5.2±4.7 |
6.8±5.6 |
<0.001 |
BMI, kg/m2
|
25.7±3.2 |
25.3±2.8 |
25.5±3.4 |
0.50 |
WC, cm |
88.5 ±7.8 |
87.6±6.8 |
88.6±7.8 |
0.97 |
WHR |
0.9±0.0 |
0.9±0.0 |
0.9±0.1 |
0.65 |
SBP, mm Hg |
125.4±14.2 |
124.8±14.1 |
123.5±14.2 |
0.23 |
DBP, mm Hg |
78.5±9.7 |
77.3±10.3 |
76.7±9.9 |
0.12 |
Hypertension |
60 (40.3) |
52 (34.7) |
69 (46.0) |
0.14 |
Dyslipidemia |
43 (29.3) |
41 (27.5) |
44 (29.5) |
0.92 |
CVD |
5 (5.1) |
4 (3.9) |
8 (8.2) |
0.39 |
Diabetic retinopathy |
32 (25.2) |
30 (24.2) |
34 (27.1) |
0.58 |
HbA1c, % |
7.8±1.5 |
8.1±1.7 |
7.9±1.7 |
0.50 |
FPG, mg/dL |
148.8±46.6 |
151.9±51.1 |
149.4±48.1 |
0.92 |
PP2 glucose, mg/dL |
284.0±99.7 |
272.4±97.7 |
282.4±101.4 |
0.93 |
HOMA-IR, unit |
2.4 (1.5 to 4.0) |
3.0 (1.9 to 4.7) |
2.6 (1.8 to 4.5) |
0.79 |
Total cholesterol, mg/dL |
181.5±42.3 |
190.1±41.2 |
182.3±36.3 |
0.88 |
Triglyceride, mg/dL |
169.9±120.7 |
161.4±95.4 |
174.7±125.6 |
0.72 |
HDL-C, mg/dL |
47.8±10.7 |
46.6±10.4 |
46.8±9.9 |
0.39 |
LDL-C, mg/dL |
118.6±38.9 |
126.3±34.3 |
120.1±35.8 |
0.71 |
hs-CRP, mg/dL |
0.08 (0.04 to 0.18) |
0.10 (0.05 to 0.19) |
0.10 (0.06 to 0.22) |
0.08 |
eGFR, mL/min/1.73 m2
|
87.1±15.3 |
86.6±14.7 |
83.6±14.6 |
0.04 |
eGFR slope, %/yr |
–1.5 (–2.8 to 0.0) |
–2.0 (–3.3 to –0.5) |
–2.1 (–4.0 to –0.4) |
0.03 |
UACR, mg/g |
20.0 (9.1 to 32.5) |
14.0 (8.2 to 30.0) |
19.4 (11.6 to 38.6) |
0.46 |
Albuminuria |
|
|
|
0.35 |
Normoalbuminuria |
107 (74.3) |
109 (74.1) |
98 (66.2) |
|
Microalbuminuria |
34 (23.6) |
36 (24.5) |
44 (29.7) |
|
Macroalbuminuria |
3 (2.1) |
2 (1.4) |
6 (4.1) |
|
Rapid renal function decliners |
19 (12.7) |
25 (16.6) |
38 (25.2) |
0.016 |
Diabetes medications |
|
|
|
|
Metformin |
107 (71.8) |
107 (71.3) |
116 (77.3) |
0.43 |
Sulfonylurea |
65 (43.6) |
73 (48.7) |
69 (46.0) |
0.68 |
TZD |
22 (14.8) |
19 (12.7) |
15 (10.0) |
0.46 |
Insulin |
17 (11.4) |
20 (13.3) |
25 (16.7) |
0.41 |
Use of ACEi/ARB |
64 (43.0) |
47 (31.3) |
65 (43.3) |
0.05 |
A-FABP, µg/L |
9.84 (8.42 to 11.85) |
17.32 (14.36 to 20.45) |
30.36 (22.07 to 38.90) |
< 0.001 |
Total adiponectin, µg/mL |
3.89 (2.84 to 6.17) |
3.68 (2.72 to 5.55) |
3.94 (2.99 to 6.12) |
0.45 |
HMW adiponectin, µg/mL |
1.29 (0.59 to 2.59) |
1.22 (0.60 to 2.39) |
1.35 (0.67 to 2.66) |
0.87 |
Interleukin-6, pg/mL |
0.87 (0.54 to 1.53) |
0.93 (0.57 to 1.47) |
0.87 (0.59 to 1.42) |
1.00 |
TNF-α, pg/mL |
1.31 (0.87 to 2.07) |
1.28 (0.83 to 1.94) |
1.21 (0.76 to 2.16) |
0.57 |
PTX3, ng/mL |
1.31 (0.62 to 2.24) |
1.22 (0.79 to 2.20) |
1.37 (0.91 to 2.13) |
0.25 |
Table 4.OR for rapid renal function decline conferred to the A-FABP levels
Variable |
All
|
Male
|
Female
|
ORa (95% CI) |
P value |
ORa (95% CI) |
P value |
ORa (95% CI) |
P value |
Model 1 |
1.81 (1.17–2.80) |
0.002 |
1.68 (0.97–2.91) |
0.063 |
3.27 (1.31–8.15) |
0.011 |
Model 2 |
3.04 (1.53–6.06) |
0.002 |
2.51 (1.08–5.86) |
0.033 |
5.63 (1.33–23.88) |
0.019 |
Model 3 |
3.10 (1.53–6.29) |
0.002 |
2.65 (1.10–6.38) |
0.030 |
5.65 (1.17–27.19) |
0.031 |