Fig. 1Comparison of R-spondin 1 (RSPO1) levels in human in relation to diverse metabolic parameters. (A) Comparison of RSPO1 levels between lean group and obese group. (B) Comparison of RSPO1 levels between insulin-sensitive group and insulin resistant group (IR). (C) Comparison of RSPO1 levels between non-diabetic participants and diabetic participants. BMI, body mass index; DM, diabetes mellitus.
Table 1Characteristics of participants and the association of serum levels of RSPO1 with obesity and DM
Variable |
All participant (n=122) |
Non-DM patients (n=79) |
DM patients (n=43) |
P valuea
|
Non-obese subjects (n=45) |
Obese subjects (n=34) |
DM patients (n=43) |
P valueb
|
Age, yr |
50.6±11.8 |
50.5±12.0 |
50.7±11.6 |
0.912 |
51.3±9.1 |
49.3±15.2 |
50.7±11.6 |
0.767 |
Sex, male/female |
54/68 |
34/45 |
20/23 |
0.712 |
17/28 |
17/17 |
20/23 |
0.520 |
BMI, kg/m2
|
24.9±4.0 |
24.6±3.5 |
25.4±5.0 |
0.329 |
22.3±1.9 |
27.0±2.3c
|
25.4±5.0c
|
<0.001 |
Body weight, kg |
65.9±13.4 |
64.8±12.5 |
67.5±14.7 |
0.319 |
58.8±8.9 |
71.9±11.4c
|
67.5±14.7c
|
<0.001 |
Height, cm |
160.8±17.7 |
159.5±21.7 |
162.7±8.7 |
0.287 |
161.2±7.8 |
158.5±9.9 |
162.7±8.7 |
0.548 |
SBP, mm Hg |
126.2±12.5 |
124.7±13.6 |
128.6±10.3 |
0.124 |
122.5±11.3 |
128.1±16.3 |
128.6±10.3 |
0.070 |
DBP, mm Hg |
77.0±9.0 |
75.4±8.8 |
79.4±8.7 |
0.027 |
73.8±8.3 |
77.8±9.3 |
79.4±8.7c
|
0.018 |
Fasting glucose, mg/dL |
126.5±54.2 |
99.1±10.3 |
176.7±65.4 |
<0.001 |
98.9±10.6 |
99.4±10.0 |
176.7±65.4c,d
|
<0.001 |
Fasting insulin, μIU/mL |
10.6±5.2 |
9.8±4.6 |
12.1±6.0 |
0.034 |
8.1±3.2 |
12.1±5.3c
|
12.1±6.0c
|
<0.001 |
Fasting C-peptide, ng/mL |
0.8±0.4 |
0.7±0.4 |
0.9±0.4 |
0.016 |
0.6±0.3 |
0.9±0.5c
|
0.9±0.4c
|
<0.001 |
Post-load 2-hr glucose, mg/dL |
184.9±119.4 |
119.9±31.8 |
320.1±121.7 |
<0.001 |
117.3±33.9 |
123.4±28.6 |
320.1±121.7c,d
|
<0.001 |
Post-load 2-hr insulin, μIU/mL |
54.1±54.1 |
53.1±55.2 |
56.4±52.3 |
0.755 |
43.9±34.4 |
65.2±73.3 |
56.4±52.3 |
0.216 |
Post-load 2-hr C-peptide, ng/mL |
3.1±1.6 |
3.1±1.4 |
3.0±2.0 |
0.652 |
2.8±1.2 |
3.5±1.6 |
3.0±2.0 |
0.218 |
HbA1c, % |
6.4±2.0 |
5.4±0.3 |
8.1±2.5 |
<0.001 |
5.4±0.4 |
5.4±0.3 |
8.1±2.5c,d
|
<0.001 |
HOMA-IR |
3.3±2.2 |
2.4±1.2 |
5.0±2.5 |
<0.001 |
2.0±0.7 |
3.1±1.2c
|
5.0±2.5c,d
|
<0.001 |
HOMA-β |
29.8±17.6 |
32.1±16.7 |
25.4±18.6 |
0.053 |
25.9±11.1 |
40.4±19.2c
|
25.4±18.6c,d
|
<0.001 |
TG, mg/dL |
135.6±97.9 |
126.8±94.0 |
151.6±104.0 |
0.202 |
113.4±67.6 |
145.7±120.6 |
151.6±104.0 |
0.152 |
TC, mg/dL |
198.3±40.0 |
195.8±34.9 |
203.1±47.9 |
0.339 |
192.0±35.7 |
200.1±33.6 |
203.1±47.9 |
0.398 |
LDL-C, mg/dL |
124.0±35.9 |
121.0±31.9 |
129.3±42.2 |
0.235 |
116.3±31.7 |
127.8±31.4 |
129.3±42.2 |
0.193 |
HDL-C, mg/dL |
54.2±14.0 |
55.9±13.8 |
51.0±14.0 |
0.075 |
58.1±15.2 |
52.6±11.0 |
51.0±14.0c
|
0.048 |
Apo-lipoprotein A, mg/dL |
131.8±29.2 |
128.8±25.2 |
135.4±33.7 |
0.500 |
130.8±22.3 |
125.9±30.5 |
135.4±33.7 |
0.749 |
Apo-lipoprotein B, mg/dL |
101.2±30.7 |
86.6±21.2 |
118.4±31.6 |
0.001 |
85.6±23.8 |
88.0±17.9 |
118.4±31.6c
|
0.004 |
AST, U/L |
23.2±10.9 |
21.8±7.5 |
25.6±15.1 |
0.069 |
21.3±6.8 |
22.6±8.4 |
25.6±15.1 |
0.169 |
ALT, U/L |
25.8±17.2 |
23.6±16.3 |
30.0±18.4 |
0.063 |
20.8±12.0 |
27.4±20.3 |
30.0±18.4c
|
0.036 |
hsCRP, mg/L |
1.6±4.3 |
1.1±1.8 |
4.0±9.5 |
0.021 |
0.9±1.7 |
1.4±1.8 |
4.0±9.5 |
0.062 |
RSPO1, pg/mL |
51.4±13.2 |
58.0±29.8 |
56.8±16.2 |
0.784 |
51.4±13.0 |
66.8±41.6c
|
56.8±16.2 |
0.030 |
Table 2Correlation analysis between serum RSPO1 level and diverse parameters in relation to obesity and DM
|
All participants (n=123) |
Non-DM subjects (n=79) |
Non-obese subjects (n=45) |
Obese subjects (n=34) |
DM patients (n=43) |
ra
|
P value |
ra
|
P value |
ra
|
P value |
ra
|
P value |
ra
|
P value |
BMI |
0.244 |
0.010b
|
0.343 |
0.005b
|
0.242 |
0.014b
|
0.407 |
0.017b
|
0.084 |
0.593 |
Fasting glucose |
0.108 |
0.237 |
−0.058 |
0.612 |
0.161 |
0.291 |
0.056 |
0.751 |
0.035 |
0.825 |
Fasting insulin |
0.155 |
0.088 |
0.256 |
0.023b
|
0.033 |
0.831 |
0.265 |
0.129 |
−0.156 |
0.319 |
Fasting C-peptide |
0.244 |
0.007c
|
0.266 |
0.019b |
0.062 |
0.688 |
0.347 |
0.048b
|
0.016 |
0.920 |
Post-load 2-hr glucose |
0.194 |
0.039b
|
0.102 |
0.378 |
0.002 |
0.989 |
−0.067 |
0.928 |
0.029 |
0.863 |
Post-load 2-hr insulin |
0.157 |
0.093 |
0.185 |
0.103 |
0.144 |
0.345 |
−0.201 |
0.254 |
0.085 |
0.623 |
Post-load 2-hr C-peptide |
0.167 |
0.079 |
0.175 |
0.131 |
<0.001 |
0.998 |
0.294 |
0.097 |
0.164 |
0.345 |
HbA1c |
0.098 |
0.285 |
0.025 |
0.829 |
0.032 |
0.836 |
0.005 |
0.980 |
−0.165 |
0.634 |
HOMA-IR |
0.311 |
0.001c
|
0.367 |
0.001b
|
0.203 |
0.180 |
0.274 |
0.117 |
0.001 |
0.995 |
HOMA-β |
0.100 |
0.271 |
0.238 |
0.035b
|
0.087 |
0.568 |
0.184 |
0.298 |
−0.087 |
0.579 |
TG |
0.198 |
0.031b
|
0.205 |
0.074 |
0.013 |
0.934 |
0.295 |
0.102 |
0.052 |
0.745 |
TC |
0.115 |
0.213 |
0.096 |
0.406 |
0.039 |
0.799 |
0.002 |
0.991 |
0.048 |
0.762 |
LDL-C |
0.153 |
0.099 |
0.119 |
0.306 |
0.074 |
0.630 |
0.011 |
0.953 |
0.107 |
0.501 |
HDL-C |
−0.199 |
0.032b
|
−0.253 |
0.027b
|
−0.153 |
0.315 |
−0.306 |
0.094 |
0.106 |
0.509 |
Apo-lipoprotein A |
−0.222 |
0.187 |
−0.134 |
0.573 |
−0.366 |
0.244 |
−0.024 |
0.955 |
−0.405 |
0.107 |
Apo-lipoprotein B |
0.456 |
0.005c
|
0.374 |
0.104 |
0.200 |
0.534 |
0.714 |
0.047b
|
0.171 |
0.513 |
AST |
0.106 |
0.248 |
0.214 |
0.060 |
−0.001 |
0.995 |
0.327 |
0.064 |
−0.187 |
0.236 |
ALT |
0.234 |
0.010b
|
0.268 |
0.018b
|
0.052 |
0.708 |
0.377 |
0.031b
|
−0.050 |
0.755 |
hsCRP |
0.320 |
0.004c
|
0.300 |
0.015b
|
0.505 |
0.104 |
0.354 |
0.044b
|
−0.155 |
0.614 |
Table 3Comparison of metabolic parameters of study population by serum RSPO1 levels in non-DM participants
Variable |
Low RSPO1 group (n=39) |
High RSPO1 group (n=40) |
P value |
Age, yr |
51.9±12.0 |
49.2±12.1 |
0.327 |
BMI, kg/m2
|
23.3±2.7 |
25.6±3.4 |
0.003 |
Body weight, kg |
63.0±11.3 |
67.3±13.4 |
0.159 |
Height, cm |
162.4±8.2 |
157.9±29.4 |
0.421 |
SBP, mm Hg |
124.0±12.8 |
125.4±14.7 |
0.691 |
DBP, mm Hg |
75.1±8.2 |
75.7±9.6 |
0.813 |
Fasting glucose, mg/dL |
99.9±9.8 |
98.4±10.9 |
0.516 |
Fasting insulin, μIU/mL |
9.4±4.9 |
10.3±4.5 |
0.390 |
Fasting C-peptide, ng/mL |
0.6±0.3 |
0.8±0.4 |
0.128 |
Post-load 2-hr glucose, mg/dL |
119.0±32.2 |
120.7±31.7 |
0.816 |
Post-load 2-hr insulin, μIU/mL |
48.5±57.6 |
57.5±53.2 |
0.476 |
Post-load 2-hr C-peptide, ng/mL |
2.9±1.4 |
3.3±1.4 |
0.249 |
HbA1c, % |
5.4±0.4 |
5.4±0.3 |
0.842 |
HOMA-IR |
2.1±0.9 |
2.8±1.2 |
0.007 |
HOMA-β |
30.3±17.7 |
33.9±15.6 |
0.335 |
TG, mg/dL |
110.3±64.5 |
142.9±114.3 |
0.127 |
TC, mg/dL |
190.2±30.7 |
201.2±38.1 |
0.169 |
LDL-C, mg/dL |
115.8±28.6 |
126.3±34.4 |
0.154 |
HDL-C, mg/dL |
58.1±12.3 |
23.7±15.1 |
0.166 |
AST, U/L |
20.3±5.2 |
23.4±9.1 |
0.063 |
ALT, U/L |
19.2±9.0 |
28.0±20.4 |
0.017 |
hsCRP, mg/L |
2.9±1.4 |
3.3±1.4 |
0.387 |
RSPO1, pg/mL |
44.6 ±3.6 |
71.0±37.6 |
<0.001 |