Vaspin and adiponectin are two adipocytokines with antidiabetic effects. Some studies reported that levels of adiponectin and vaspin were correlated with decreased glomerular filtration rate (FGR) and increased albuminuria. We therefore evaluated the vaspin and adiponectin levels in renal insufficiency (RI) patients with or without T2DM. Serum vaspin, adiponectin levels were measured in 416 subjects with or without T2DM. Analysis was made between groups divided by these subjects presence or absence of RI. We found that serum adiponectin level was significantly higher in nondiabetic patients with RI than in nondiabetic subjects without RI; however, there were no statistical differences between the diabetic patients with RI and without RI. In all the subjects, the serum adiponectin level was also higher in 50 individuals with RI than that in 366 subjects without RI. The serum vaspin levels showed no significant differences between the diabetic patients or nondiabetics subjects with RI and without RI. Contrary to adiponectin, the serum vaspin level was lower in 169 patients with T2DM than in 247 individuals without T2DM. Our data suggested that both of T2DM and renal insufficiency were correlated with the serum level of adiponectin. However, the serum vaspin levels showed no significant difference between the individuals with renal insufficiency and without renal insufficiency.
Visceral adipose tissue-derived serine proteinase inhibitor (vaspin) was identified in the visceral adipose tissue of OLETF (Otsuka Long-Evans Tokushim a Fatty) rats, an animal model of obesity and type 2 diabetes mellitus (T2DM) [
All subjects were local residents of Han ethnicity in Shanghai and consecutively recruited in Department of Endocrinology and Cardiology, Xinhua Hospital and Shanghai Tenth People’s Hospital from June 2011 to December 2011. The study was approved by the Ethical Committee of Shanghai Tenth People’s Hospital and Xinhua Hospital. Clinical characteristics were recorded with respect to age, sex, body mass index (BMI), risk factors for renal function, and diabetic mellitus (DM). DM was defined as fasting serum glucose level ≥7.0 mmol/L or 2-hour postprandial glucose ≥11.1 mmol/L, or taking hypoglycemic drugs. Those with type 1 diabetes, acute myocardial infarction, systemic inflammatory disorders, severe heart failure (left ventricular ejection fraction <30%), advanced renal insufficiency, and malignant tumor were excluded.
Blood samples were centrifuged at 1000 g for 10 minutes. Plasma specimens were then frozen and stored at −80°C until analysis. Human total Adiponectin (R&D Systems, Minneapolis, American) and Vaspin (Adipogen, Seoul, South Korea) plasma levels were measured with commercially available ELISAs as indicated before [
416 subjects were divided into 4 groups according to the presence or absence of RI and T2DM: 247 individuals without T2DM who had RI (
Renal function was assessed by the estimated creatinine clearance (CrCl) derived from Cockroft-Gault formula, where CrCl (mL/min) = ([140 − age (years)] × weight (kg))/(0.818 × serum creatinine (
Statistical analyses were performed using the PASW Statistics 20 software (IBM Corporation, Armonk, NY, USA). Normality of distribution was evaluated using the Kolmogorov-Smirnov test. Comparisons of variables with a normal distribution were made using Student’s
In the population either with T2DM or without T2DM, patients with RI (Group I or Group III) were older and had lower BMI, higher systolic blood pressure (SBP) than those without RI (Group II or Group IV) (all
Baseline of all subjects divided by T2DM and RI.
Non-T2DM | T2DM | |||||
---|---|---|---|---|---|---|
RI | Non-RI |
|
RI | Non-RI |
|
|
Gender (male : female) | 9 : 18 | 151 : 69 | 13 : 10 | 75 : 71 | ||
Age (years) |
|
|
<0.001* |
|
|
<0.001* |
BMI (kg/m2) |
|
|
<0.01* |
|
|
<0.01* |
SBP (mmHg) |
|
|
<0.01* |
|
|
<0.05* |
DBP (mmHg) |
|
|
0.227 |
|
|
0.886 |
Vaspin (ng/mL) | 0.55 (0.43–1.14) | 0.52 (0.23–1.32) | 0.402 | 0.50 (0.29–0.91) | 0.38 (0.23–0.74) | 0.245 |
Adiponectin (ng/mL) |
|
|
<0.01* |
|
|
0.349 |
hsCRP (mg/L) | 3.27 (3.10–3.27) | 3.34 (2.93–7.05) | 0.266 | 1.85 (0.05–6.21) | 1.01 (0.06–3.06) | 0.428 |
Crcl (mL/min) |
|
|
<0.001* |
|
|
<0.001* |
Cr ( |
|
|
<0.01* |
|
|
<0.001* |
BUN (mmol/L) |
|
|
0.068 |
|
|
<0.01* |
UA ( |
|
|
<0.01* |
|
|
<0.001* |
FBG (mmol/L) |
|
|
0.576 |
|
|
0.498 |
PG2h (mmol/L) |
|
|
0.974 |
|
|
0.732 |
HbA1c (%) |
|
|
0.342 |
|
|
0.709 |
TC (mmol/L) |
|
|
0.124 |
|
|
0.242 |
TG (mmol/L) |
|
|
0.797 | 1.32 (0.99–1.63) | 1.51 (1.09–2.53) | 0.131 |
HDL-C (mmol/L) |
|
|
0.107 |
|
|
0.387 |
LDL-C (mmol/L) |
|
|
0.326 |
|
|
0.627 |
ApoA (g/L) |
|
|
0.314 |
|
|
0.738 |
ApoB (g/L) |
|
|
0.350 | 0.87 (0.70–1.02) | 0.96 (0.77–1.22) | 0.170 |
LPA (mg/L) |
|
|
0.877 | 5.55 (2.80–53.00) | 5.90 (1.14–19.83) | 0.229 |
FIB (g/L) |
|
|
0.206 |
|
|
0.132 |
The data are presented as the number, mean ± S.D., or median (interquartile range);
BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; vaspin: visceral adipose-tissue-derived serpin; hsCRP: high-sensitive C-reactive protein; Crcl: creatinine clearance; Cr: creatinine; BUN: blood urea nitrogen; UA: uric acid; FBG: fasting blood glucose; PG2h: 2-hour postprandial glucose; HbA1c: hemoglobin A1c; TG: triglyceride; TC: total cholesterol; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; ApoA: apolipoprotein A; ApoB: apolipoprotein B; LPA: lipoprotein A; FIB: fibrinogen.
The serum vaspin showed no significant differences either between non-T2DM patients with RI (Group I) and without RI (Group II) (0.548 (0.428–1.136) ng/mL versus 0.517 (0.232–1.324) ng/mL,
Comparisons of serum vaspin and adiponectin divided by T2DM and RI.
Non-T2DM | T2DM |
|
|
---|---|---|---|
Vaspin | 0.52 (0.18–1.17) | 0.40 (0.22–0.74) | <0.05 |
Adiponectin | 5553.48 (12.10–14225.16) | 7599.07 (4100.63–13827.26) | <0.05 |
|
|||
Non-RI | RI |
|
|
|
|||
Vaspin | 0.43 (0.23–0.93) | 0.54 (0.40–1.02) | 0.141 |
Adiponectin | 6955.13 (2590.05–13533.96) | 10549.71 (5589.72–22429.03) | <0.01 |
Compared with the nondiabetic individuals without RI (Group II), the serum adiponectin was higher in the non-diabetic individuals with RI (Group I) (
Spearmen’s analysis showed that serum vaspin level was only related to Cr in patients without T2DM. In patients with T2DM, serum vaspin levels were related to age, SBP, and UA. In all subjects, serum vaspin levels were related to Crcl, TC, and HbA1c (Tables
Single univariate linear correlations of factors associated with serum vaspin levels.
Non-T2DM | T2DM | All subjects | ||||
---|---|---|---|---|---|---|
|
|
|
|
|
|
|
Age | 0.033 | 0.626 | 0.175 | 0.030* | 0.043 | 0.408 |
BMI | 0.068 | 0.436 | 0.112 | 0.205 | 0.070 | 0.258 |
SBP | 0.009 | 0.899 | 0.195 | 0.016* | 0.068 | 0.189 |
DBP | −0.025 | 0.717 | 0.129 | 0.112 | 0.034 | 0.516 |
Adiponectin | 0.118 | 0.098 | 0.163 | 0.302 | 0.126 | 0.052 |
hsCRP | −0.078 | 0.677 | −0.097 | 0.323 | −0.139 | 0.106 |
Crcl | −0.094 | 0.311 | −0.166 | 0.054 | −0.138 | 0.027* |
Cr | −0.181 | 0.009* | 0.051 | 0.535 | −0.044 | 0.412 |
BUN | 0.017 | 0.810 | 0.067 | 0.411 | 0.029 | 0.574 |
UA | −0.075 | 0.297 | 0.160 | 0.050* | 0.053 | 0.329 |
PG2h | −0.011 | 0.930 | −0.118 | 0.365 | −0.124 | 0.169 |
HbA1c | −0.100 | 0.415 | −0.140 | 0.107 | −0.209 | 0.003* |
TC | 0.105 | 0.127 | 0.100 | 0.233 | 0.105 | 0.047* |
TG | 0.095 | 0.164 | 0.026 | 0.753 | 0.042 | 0.433 |
HDL-C | −0.015 | 0.831 | 0.051 | 0.541 | 0.007 | 0.900 |
LDL-C | 0.125 | 0.084 | 0.007 | 0.931 | 0.075 | 0.170 |
ApoA | 0.122 | 0.344 | −0.009 | 0.921 | 0.022 | 0.770 |
ApoB | 0.152 | 0.238 | 0.010 | 0.915 | 0.051 | 0.496 |
LPA | −0.196 | 0.147 | 0.020 | 0.832 | 0.069 | 0.367 |
FIB | 0.086 | 0.340 | −0.182 | 0.051 | −0.066 | 0.306 |
Single univariate linear correlations of factors associated with serum adiponectin levels.
Non-T2DM | T2DM | All subjects | ||||
---|---|---|---|---|---|---|
|
|
|
|
|
|
|
Age | 0.614 | <0.001* | 0.183 | 0.245 | 0.589 | <0.001* |
BMI | 0.081 | 0.357 | 0.164 | 0.317 | 0.093 | 0.224 |
SBP | 0.170 | 0.018* | 0.104 | 0.511 | 0.177 | 0.007* |
DBP | −0.057 | 0.432 | −0.074 | 0.641 | −0.052 | 0.432 |
Vaspin | 0.118 | 0.098 | 0.163 | 0.302 | 0.126 | 0.052 |
hsCRP | −0.543 | 0.030* | 0.213 | 0.555 | −0.172 | 0.402 |
Crcl | −0.526 | <0.001* | −0.098 | 0.552 | −0.434 | <0.001* |
Cr | 0.198 | 0.007* | 0.018 | 0.911 | 0.160 | 0.017* |
BUN | 0.140 | 0.054 | 0.202 | 0.206 | 0.157 | 0.017* |
UA | 0.054 | 0.482 | 0.050 | 0.758 | 0.030 | 0.661 |
PG2h | −0.157 | 0.271 | −0.151 | 0.443 | −0.166 | 0.143 |
HbA1c | −0.078 | 0.575 | −0.245 | 0.218 | −0.254 | 0.022* |
TC | −0.106 | 0.147 | 0.318 | 0.055 | −0.049 | 0.467 |
TG | 0.023 | 0.754 | −0.315 | 0.058 | 0.023 | 0.726 |
HDL-C | 0.116 | 0.134 | 0.157 | 0.360 | 0.093 | 0.186 |
LDL-C | −0.014 | 0.852 | 0.339 | 0.040* | 0.036 | 0.613 |
ApoA | 0.186 | 0.173 | −0.138 | 0.519 | 0.102 | 0.372 |
ApoB | −0.016 | 0.906 | 0.223 | 0.305 | 0.033 | 0.773 |
LPA | 0.133 | 0.357 | 0.235 | 0.319 | 0.179 | 0.138 |
FIB | −0.010 | 0.915 | 0.272 | 0.094 | 0.038 | 0.646 |
The serum adiponectin levels were related to age, SBP, hsCRP, Crcl, and Cr in subjects without T2DM. In patients with T2DM, serum adiponectin levels were related to FBG, LDL-C. In all subjects, serum adiponectin levels were related to age, SBP, Crcl, Cr, BUN, and HbA1c (Tables
Multiple regression analyses were performed to test whether any of the following factors influence the serum vaspin and adiponectin concentrations: age, SBP, FBG, UA, Crcl, Cr, TG, TC, HbA1c levels, and so on. When correcting for these variables using stepwise regression analyses after adjustment for age and BMI, the level of HbA1c was found to be independently and significantly associated with the vaspin concentration in 427 total subjects. However, no significant correlations between the serum vaspin level and any parameter were detected in both groups of the subjects with T2DM and without T2DM. The level of Crcl was found to be independently and significantly associated with the adiponectin concentration in all subjects. However, in the groups of the subjects with or without T2DM, no significant correlations were detected between the serum adiponectin level and any parameter (Tables
Multivariate linear regression analyses of all subjects, patients with and without T2DM, using the serum vaspin levels as dependent variables.
Models | Independent variables |
|
Beta |
|
|
Model |
---|---|---|---|---|---|---|
1 | All subjects | |||||
Age | −0.023 | −0.024 | −0.286 | 0.775 | 0.044 | |
BMI | −0.046 | −0.047 | −0.573 | 0.568 | ||
Crcl | −0.061 | −0.061 | −0.738 | 0.461 | ||
TC | 0.071 | 0.072 | 0.883 | 0.379 | ||
HbA1c | −0.235 | −0.209 | −2.612 | 0.010* | ||
|
||||||
2 | Non-T2DM | |||||
Age | 0.026 | 0.121 | 1.194 | 0.235 | 0.017 | |
BMI | −0.024 | −0.022 | −0.225 | 0.823 | ||
Cr | −0.019 | −0.102 | −1.027 | 0.307 | ||
|
||||||
3 | T2DM | |||||
Age | 0.008 | 0.110 | 0.949 | 0.346 | 0.066 | |
BMI | 0.025 | 0.141 | 1.224 | 0.224 | ||
FBG | −0.042 | −0.149 | −1.308 | 0.194 | ||
UA | 0.001 | 0.133 | 1.172 | 0.244 |
Multivariate linear regression analyses of all subjects, patients with and without T2DM, using the serum adiponectin levels as dependent variables.
Models | Independent variables |
|
Beta |
|
|
Model |
---|---|---|---|---|---|---|
1 | All subjects | |||||
Age | 0.196 | 0.154 | 1.226 | 0.225 | 0.132 | |
BMI | −0.154 | −0.141 | −1.120 | 0.267 | ||
SBP | −0.070 | −0.074 | −0.582 | 0.563 | ||
Crcl | −86.311 | −0.363 | −3.089 | 0.003* | ||
Cr | −0.248 | −0.220 | −1.779 | 0.080 | ||
BUN | −0.106 | −0.107 | −0.848 | 0.400 | ||
HbA1c | −0.175 | −0.184 | −1.475 | 0.145 | ||
|
||||||
2 | Non-T2DM | |||||
Age | 79.928 | 0.203 | 0.215 | 0.837 | 0.384 | |
BMI | −810.955 | −0.320 | −0.471 | 0.654 | ||
SBP | −190.316 | −0.475 | −1.088 | 0.318 | ||
Crcl | −93.939 | −0.353 | −0.353 | 0.736 | ||
Cr | −89.348 | −0.248 | −0.364 | 0.728 | ||
hsCRP | 12.961 | 0.085 | 0.211 | 0.840 | ||
|
||||||
3 | T2DM | |||||
Age | 231.786 | 0.215 | 1.204 | 0.239 | 0.121 | |
BMI | 151.377 | 0.066 | 0.323 | 0.749 | ||
FBG | −611.036 | −0.190 | −0.925 | 0.363 | ||
LDL-C | 1778.647 | 0.186 | 1.012 | 0.320 |
Mann-Whitney
Comparisons of serum vaspin and adiponectin levels divided by gender.
Models | Men | Women |
|
---|---|---|---|
Vaspin | 1.07 | 1.72 | <0.01 |
Adiponectin | 7063.03 | 11866.85 | <0.01 |
Comparisons of serum vaspin and adiponectin levels divided by gender and T2DM.
Models | T2DM | Non-T2DM | ||||
---|---|---|---|---|---|---|
Men | Women |
|
Men | Women |
|
|
Vaspin | 0.51 | 0.74 | <0.01 | 1.38 | 2.73 | <0.01 |
Adiponectin | 7367.09 | 12419.30 | 0.021 | 7015.52 | 11695.67 | <0.01 |
Adipose tissue is a highly active endocrine organ secreting a number of bioactive molecules called adipokines [
In patients with CKD, the levels of adipokines appear to increase in association with declines in the GFR. This is most likely due to reduced renal metabolism of adipokines, which may not increase vascular risks in patients with a reduced renal function [
Previous studies have shown that, in the diabetic patients, serum vaspin level is higher than that in normal glucose tolerance subjects in women [
Adiponectin is a fat-derived hormone whose reduction plays central roles in obesity-linked diseases including insulin resistance, type 2 diabetes, and atherosclerosis. Adiponectin multimers are secreted by white adipose tissue [
Both of T2DM and renal insufficiency were correlated with the serum level of adiponectin. Although the serum vaspin levels showed no significant difference between the patients with renal insufficiency which did not required treatment by chronic hemodialysis and subjects without renal insufficiency, we have found that the serum vaspin level was lower in 169 diabetic patients than in 247 individuals without T2DM.
The authors declare that they have no conflict of interests.
The authors thank all patients and normal individuals for participating in this study. This work was supported in part by the National Natural Science Foundation of China (Grants nos. 81101444 and 81370391). Meiyu Yan and Bin Su are cofirst authors.