ABSTRACT
Aims/Introduction
To investigated the association between serum asprosin and metabolic characteristics in type 2 diabetes mellitus patients with different durations.
Materials and Methods
A total of 436 patients with type 2 diabetes mellitus were enrolled in this study from the community health service center in southeastern Shanxi Province. All the patients were divided into two groups according to their diabetes duration: diabetes duration ≤5 years group (n = 132) and diabetes duration ≥10 years group (n = 304). Fasting blood samples were gathered and serum asprosin was tested. Pearson/Spearman correlation analysis was carried out.
Results
Asprosin was comparable between the two groups. Asprosin was positively correlated with systolic blood pressure (SBP), triglycerides, creatinine, serum uric acid and low‐density lipoprotein cholesterol in the diabetes duration ≤5 years group (P < 0.05). In the diabetes duration ≥10 years group, asprosin was independently correlated with SBP, diastolic blood pressure, body mass index, total cholesterol, triglycerides, low‐density lipoprotein cholesterol, creatinine, serum uric acid, fasting plasma glucose and glycosylated hemoglobin (P < 0.05). Asprosin was associated with alanine aminotransferase and estimated glomerular filtration rate (P < 0.05). Multiple linear regression analysis found that SBP and diastolic blood pressure is an independent factor related to serum asprosin in the group with diabetes duration ≤5 years (P < 0.05). Fasting plasma glucose, SBP, total cholesterol and serum uric acid is an independent factor related to serum asprosin in the group with diabetes duration ≥10 years (P < 0.05).
Conclusions
Serum asprosin was significantly increased in the group with diabetes duration ≥10 years, and glycosylated hemoglobin, blood pressure and estimated glomerular filtration rate were independent risk factors in long‐duration type 2 diabetes mellitus.
Keywords: Asprosin, Diabetes duration, Kidney function
Serum asprosin was significantly increased in the group with diabetes duration ≥10 years, and fasting blood glucose, blood pressure and uric acid were independent risk factors in long‐term type 2 diabetes mellitus.
INTRODUCTION
It was initially found that asprosin is a glucose‐derived protein adipokine, which is very sensitive to the whole body energy status and can be induced by fasting 1 , 2 , and its concentration in the blood is in the nanomolar level. The plasma half‐life of asprosin produced by mammals is approximately 145 min 3 . Fibrillin‐1 messenger ribonucleic acid is widely expressed in multiple tissues in the body; however, the adoption of BCL2 knockout mice in vivo experiments and 3T3‐L1 cells in vitro experiments show white adipose tissue is the main source of plasma asprosin 4 , 5 . Generally, asprosin synthesized by tissues is released into the blood, and transported to peripheral and central target tissues, including hypothalamic neurons, hepatocytes, islet β cells and skeletal muscle, to regulate appetite, glucose release, insulin secretion and insulin sensitivity, respectively 3 . Indeed, in addition to fasting induction, plasma asprosin levels increase with decreasing glucose concentration and vice versa 6 . In addition, exercise might also have a regulatory effect on it 7 . At the same time, circulating asprosin is also a serum marker related to metabolic diseases. Previous studies 8 have shown that asprosin is related to indicators related to obesity, blood lipids and fatty liver, and the relationship between asprosin and various metabolic diseases, such as obesity and diabetes complications, has also attracted attention 9 .
The pathogenesis of type 2 diabetes includes insulin resistance and insulin deficiency. The pathophysiological mechanism of type 2 diabetes is mainly manifested as insulin resistance caused by obesity in the early stage, and insulin deficiency in the later stage. Diabetic microvascular complications and macrovascular complications develop with the prolongation of the course of diabetes 10 . Previous studies 9 have shown that asprosin levels are higher in patients with type 2 diabetes than in healthy people, and elevated asprosin levels in people with normal glucose tolerance can predict the occurrence of type 2 diabetes. As an endocrine factor and blood marker associated with obesity and insulin resistance, whether asprosin evolves with the development of type 2 diabetes is unclear. In the present study, serum asprosin was measured in type 2 diabetes patients with diabetes duration ≤5 years and ≥10 years, and the relationship between serum asprosin and related metabolic parameters was analyzed, to investigate the clinical significance of asprosin in patients with different course of type 2 diabetes.
MATERIALS AND METHODS
Study design and participants
From November 2019 to July 2021, a total of 498 patients with type 2 diabetes mellitus who were undergoing physical examinations at community health service stations in the Jindong area of Shanxi Province, China, and who agreed to the retention of their serum samples and the entry of their clinical information into a sample bank, were continuously collected. The inclusion criteria were as follows: (1) age ≥18 years, (2) all type 2 diabetes patients were diagnosed in accordance with the 1999 World Health Organization diagnostic criteria for type 2 diabetes 11 , (3) the patient had complete clinical data, and (4) was able to cooperate with this study. The exclusion criteria included: (1) patients with acute complications of diabetes and poor general conditions; (2) patients with diabetes duration of 5–10 years; (3) patients with unclear diagnosis and classification of diabetes; (4) patients with serum sample loss; and (5) patients with incomplete important clinical information. A total of 436 patients were enrolled and divided into the diabetes duration ≤5 years group (n = 132) and the diabetes duration ≥10 years group (n = 304). This study complied with the ethical guidelines of the Declaration of Helsinki and received approval from the Ethics Committee of the First Hospital of Shanxi Medical University (approval number: 2019[K056]). Informed consent was signed from all patients participating in the study.
Data collection and definition
Demographic and medical details were collected from all patients, including their sex, age, history of previous diseases, and whether they were taking hypoglycemic drugs, insulin, antihypertensive drugs, and lipid‐lowering drugs. Additionally, other general information, the height, weight, abdominal circumference, systolic blood pressure, diastolic blood pressure and so on were collected, and the body mass index (BMI) was calculated. After fasting for 8–10 h the night before the physical examination, 2–3 mL of elbow vein blood was collected in the morning of the next day to detect fasting plasma glucose (FPG), 2 h‐postprandial plasma glucose, serum uric acid, creatinine (CRE), total cholesterol (TC), triglyceride (TG), high‐density lipoprotein‐cholesterol, low‐density lipoprotein‐cholesterol, alanine aminotransferase, aspartate aminotransferase (Beckman automatic biochemical analyzer, BK‐200; Brea, CA, USA). Glycosylated hemoglobin (HbA1c) was measured by high‐pressure liquid chromatography (Roche 501; Basel, Switzerland).
Estimated glomerular filtration rate (eGFR) was calculated according to the Chronic Kidney Disease Epidemiology Collaboration formula. Urine albumin creatine ratio was measured by a Roche C311 biochemical analyzer, and the mean value of three measurements on different days during hospitalization was taken. In addition, diabetes microvascular complications included diabetic kidney disease, diabetic retinopathy and diabetic peripheral neuropathy from the patient's physical examination diagnosis.
Serum asprosin detection
The venous blood sample taken during the physical examination was subjected to centrifugation at 1348 g for 15 min to separate the serum, and the supernatant was subsequently aspirated for determination of serum asprosin levels. All blood samples were stored at −80°C. Serum asprosin levels were measured by enzyme‐linked immunosorbent assay (Hepeng Biotechnology Co., Ltd., Shanghai, China). All samples were tested in double wells, the interassay difference was < 11%, and the intra‐assay difference was <8%. All operations were carried out strictly according to the instructions of the kit and the instrument.
Statistical analysis
SPSS 22.0 software (IBM Corp., Armonk, NY, USA) was used for statistical analysis. Graphs were created using Prism 8.0 (GraphPad Software, San Diego, CA, USA) and SPSS 22.0 software. Measurement data with normal distribution are represented as the mean ± standard deviation, and comparisons between groups were analyzed using the t‐test. Non‐normal distribution measurement data are represented as the median (quartile 1, quartile 3), and comparisons between the two groups were analyzed using the Mann–Whitney rank sum test. Pearson correlation analysis was used to analyze the data with bivariate normal distribution. For data that did not conform to bivariate normal distribution, Pearson/Spearman correlation analysis was used to evaluate the correlation between serum asprosin level and other clinical data. The independent associations between asprosin and metabolism variables were determined using multiple linear regression. We divided the patients into two cohorts according to the different duration of diabetes: the group with diabetes duration ≤5 years (n = 132) and the group with diabetes duration ≥10 years (n = 304). The receiver operator characteristic curve was carried out for the prediction of serum asprosin levels with different duration of diabetes. The Youden index is sensitivity (1 − specificity), and the maximum value of the Youden index is used as the cutoff value. A difference of P < 0.05 was considered statistically significant.
RESULTS
Comparison of general data and biochemical indexes between the two groups
Compared with the diabetes duration ≤5 years group, the proportions of age, hypoglycemic drugs, insulin, antihypertensive drugs, lipid‐lowering drugs, hypertension, coronary heart disease and diabetic microvascular complications were higher in the diabetes duration ≥10 years group (P < 0.05); diastolic blood pressure, BMI, HbA1c, alanine aminotransferase, aspartate aminotransferase, TC, TG, low‐density lipoprotein‐cholesterol and eGFR were decreased (P < 0.05); and SBP, CRE and asprosin were significantly increased (P < 0.05; Table 1).
Table 1.
Comparison of clinical characteristics between the two groups
| Group | Sex, n (male/female) | Duration* (years) | Age (years) | SBP (mmHg) | DBP (mmHg) | BMI (kg/m2) | TC (mmol/L) | TG* (mmol/L) | LDL‐C (mmol/L) |
|---|---|---|---|---|---|---|---|---|---|
| Duration ≤5 years | 132 (86/46) | 2.0 (0.3, 4.0) | 49.6 ± 15.2 | 131.8 ± 18.1 | 81.3 ± 11.5 | 26.8 ± 4.5 | 4.9 ± 1.3 | 1.7 (1.2, 3.4) | 2.8 ± 0.9 |
| Duration ≥10 years | 304 (170/134) | 15.0 (13.0, 20.0) | 62.1 ± 11.1 | 137.3 ± 19.0 | 79.0 ± 10.8 | 25.7 ± 3.8 | 4.5 ± 1.2 | 1.6 (1.0, 2.3) | 2.6 ± 0.9 |
| χ2/z/t | −16.63 | −8.523 | −2.832 | 2.041 | 2.434 | 2.542 | −2.249 | 2.089 | |
| P | <0.001 | <0.001 | 0.005 | 0.042 | 0.016 | 0.011 | 0.024 | 0.037 |
| Group | HDL‐C (mmol/L) | AST* (mmol/L) | ALT* (mmol/L) | CRE* (μmol/L) | eGFR (mL/min) | FPG (mmol/L) | HbA1c (%) | SUA (μmol/L) | Asprosin (pg/mL) |
|---|---|---|---|---|---|---|---|---|---|
| Duration ≤5 years | 0.95 ± 0.24 | 19.0 (14.0, 30.8) | 21.5 (14.0, 39.0) | 62.5 (52.3, 75.8) | 146.3 ± 31.3 | 9.0 ± 3.6 | 9.6 ± 2.4 | 334.0 ± 94.4 | 308.1 ± 85.0 |
| Duration ≥10 years | 0.98 ± 0.25 | 18.0 (14.0, 23.0) | 16.0 (11.0, 24.0) | 67.0 (57.0, 83.0) | 138.6 ± 32.0 | 8.1 ± 2.8 | 9.0 ± 1.9 | 336.2 ± 91.2 | 348.6 ± 97.6 |
| χ2/z/t | −1.414 | −2.523 | −4.563 | −2.337 | 2.313 | 2.362 | 2.579 | −0.230 | −4.366 |
| P | 0.158 | 0.012 | <0.001 | 0.019 | 0.021 | 0.019 | 0.011 | 0.818 | <0.001 |
| Group | Taking metformin, n (%) | Taking glycosidase inhibitors, n (%) | Taking sulfonylureas, n (%) | Taking DPP‐4 enzyme inhibitors, n (%) | Taking thiazolidinedione, n (%) | Using insulin, n (%) |
|---|---|---|---|---|---|---|
| Duration ≤5 years | 44 (33.3) | 27 (20.5) | 18 (13.6) | 0 (0) | 3 (2.3) | 25 (18.9) |
| Duration ≥10 years | 144 (47.4) | 98 (32.2) | 63 (20.7) | 4 (1.3) | 10 (3.3) | 84 (27.6) |
| χ2/z/t‐value | 8.257 | 79.349 | 172.19 | 420.15 | 385.55 | 109.00 |
| P | 0.004 | 0.000 | 0.000 | 0.000 | 0.000 | 0.331 |
| Group | Taking lipid‐lowering drugs, n (%) | Taking antihypertensive drugs, n (%) | Hypertension, n (%) | Coronary heart disease, n (%) | Renal insufficiency, n (%) | DKD, n (%) | DR, n (%) | DPN, n (%) |
|---|---|---|---|---|---|---|---|---|
| Duration ≤5 years | 20 (15.2) | 59 (44.7) | 64 (48) | 6 (4.5) | 7 (5.3) | 69 (52.3) | 13 (9.8) | 58 (43.9) |
| Duration ≥10 years | 104 (34.2) | 193 (63.5) | 207 (68) | 37 (12.1) | 26 (8.6) | 216 (71.1) | 142 (46.7) | 233 (76.6) |
| χ2/z/t | 81.06 | 10.61 | 15.042 | 6.020 | 1.389 | 14.338 | 53.770 | 44.352 |
| P | 0.000 | 0.001 | <0.001 | 0.014 | 0.239 | <0.001 | <0.001 | <0.001 |
Mann–Whitney test.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CRE, creatinine; DBP, diastolic blood pressure; DKD, diabetic kidney disease; DPN, diabetic peripheral neuropathy; DPP‐4, dipeptidyl peptidase‐4; DR, diabetic‐retinopathy; eGFR, estimated glomerular filtration rate; FPG, fasting blood glucose; HbA1c, glycosylated hemoglobin; HDL‐C, high‐density lipoprotein cholesterol; LDL‐C, low‐density lipoprotein cholesterol; SBP, systolic blood pressure; SUA, serum uric acid; TC, total cholesterol; TG, triglycerides.
Correlation analysis of serum asprosin and metabolic indexes in diabetes between duration ≤5 years group and duration ≥10 years group
To further investigate the potential relationship between circulating asprosin levels and disease duration, Spearman analysis was carried out. As shown in Figure 1, in type 2 diabetes, circulating asprosin level was remarkably positively correlated with disease duration, the first‐line noninvasive diagnostic method for disease duration (r = 0.243, P < 0.001);
Figure 1.
Spearman correlation analysis between circulating asprosin levels and duration in type 2 diabetes.
Pearson/Spearman correlation analysis showed that asprosin in the diabetes duration ≤5 years group was positively correlated with SBP, TG, CRE and serum uric acid (P < 0.05; Table 2). In the group with diabetes duration ≥10 years, asprosin was positively correlated with SBP, diastolic blood pressure, BMI, TC, TG, low‐density lipoprotein‐cholesterol, CRE, serum uric acid, FPG and HbA1c (P < 0.05), and negatively correlated with alanine aminotransferase and eGFR (P < 0.05; Table 3).
Table 2.
Correlation analysis of the influencing factors for asprosin in diabetes duration ≤5 years group (r)
| Covariates | Item | |
|---|---|---|
| r | P | |
| Age (years) | 0.132 | 0.131 |
| SBP (mmHg) | 0.324 | <0.001 |
| DBP (mmHg) | 0.084 | 0.340 |
| BMI (kg/m2) | 0.161 | 0.065 |
| TC (mmol/L) | 0.101 | 0.252 |
| TG † (mmol/L) | 0.188 | 0.031 |
| LDL‐C (mmol/L) | 0.029 | 0.741 |
| HDL‐C (mmol/L) | −0.064 | 0.464 |
| CRE † (μmol/L) | 0.200 | 0.022 |
| eGFR (mL/min) | −0.128 | 0.143 |
| SUA (μmol/L) | 0.283 | 0.001 |
| FPG (mmol/L) | −0.049 | 0.580 |
| HbA1c (%) | −0.017 | 0.847 |
| AST † (U/L) | 0.083 | 0.346 |
| ALT † (U/L) | 0.032 | 0.716 |
Spearman correlation analysis was used for skewness distribution, Pearson correlation analysis was used for normal distribution.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CRE, creatinine; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FPG, fasting blood glucose; HbA1c, glycosylated hemoglobin; HDL‐C, high‐density lipoprotein cholesterol; LDL‐C, low‐density lipoprotein cholesterol; SBP, systolic blood pressure; SUA, serum uric acid; TC, total cholesterol; TG, triglycerides.
Table 3.
Correlation analysis of the influencing factors for asprosin in diabetes duration ≥10 years group (r)
| Covariates | Item | |
|---|---|---|
| r | P | |
| Age (years) | 0.001 | 0.993 |
| SBP (mmHg) | 0.296 | <0.001 |
| DBP (mmHg) | 0.151 | 0.008 |
| BMI (kg/m2) | 0.129 | 0.025 |
| TC (mmol/L) | 0.201 | <0.001 |
| TG † (mmol/L) | 0.132 | 0.021 |
| LDL‐C (mmol/L) | 0.154 | 0.007 |
| HDL‐C (mmol/L) | 0.046 | 0.421 |
| CRE † (μmol/L) | 0.274 | <0.001 |
| eGFR (mL/min) | −0.291 | <0.001 |
| SUA (μmol/L) | 0.175 | 0.002 |
| FPG (mmol/L) | 0.123 | 0.032 |
| HbA1c (%) | 0.263 | <0.001 |
| AST † (U/L) | −0.074 | 0.198 |
| ALT † (U/L) | −0.135 | 0.018 |
Spearman correlation analysis was used for skewness distribution, Pearson correlation analysis was used for normal distribution.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; CRE, creatinine; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FPG, fasting blood glucose; HbA1c, glycosylated hemoglobin; HDL‐C, high‐density lipoprotein cholesterol; LDL‐C, low‐density lipoprotein cholesterol; SBP, systolic blood pressure; SUA‐serum uric acid; TC, total cholesterol; TG, triglycerides.
Multiple linear regression analysis on the factors related to asprosin among different diabetes duration
Multiple linear regression analysis found that SBP (β = 1.861, P = 0.000), diastolic blood pressure (β = −1.496, P = 0.014) and CRE (β = 1.602, P = 0.010) were independent factors related to serum asprosin in the group with diabetes duration ≤5 years (Table 4). SBP (β = 1.377, P = 0.000), TC (β = 34.009, P = 0.017), HbA1c (β = 14.480, P = 0.000) and eGFR (β = −0.592, P = 0.004) were independent factors related to serum asprosin in the group with diabetes duration ≥10 years (Table 5).
Table 4.
Multiple linear regression analysis on the factors related to asprosin among diabetes duration ≤5 years group
| Variable | β | SE | T | P | 95% CI |
|---|---|---|---|---|---|
| BMI | 2.336 | 1.732 | 1.349 | 0.180 | −1.093 to 5.765 |
| FPG | −0.057 | 2.401 | −0.024 | 0.981 | −4.813 to 4.699 |
| SBP | 1.861 | 0.468 | 3.974 | 0.000 | 0.934–2.788 |
| DBP | −1.496 | 0.743 | −2.014 | 0.046 | −2.967 to −0.025 |
| TC | −15.873 | 13.835 | −1.147 | 0.254 | −43.271 to 11.525 |
| TG | 10.430 | 5.788 | 1.802 | 0.074 | −1.032 to 21.893 |
| LDL‐C | 23.651 | 16.128 | 1.466 | 0.145 | −8.287 to 55.589 |
| HDL‐C | 43.559 | 35.044 | 1.243 | 0.216 | −25.837 to 112.954 |
| SUA | 0.103 | 0.089 | 1.165 | 0.246 | −0.072 to 0.279 |
| HbA1c | 2.654 | 3.464 | 0.766 | 0.445 | −4.206 to 9.514 |
| CRE | 1.602 | 0.608 | 2.635 | 0.010 | 0.398–2.805 |
| eGFR | 0.886 | 0.502 | 1.765 | 0.080 | −0.108 to 1.879 |
BMI, body mass index; CRE, creatinine; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FPG, fasting blood glucose; HbA1c, glycosylated hemoglobin; HDL‐C, high‐density lipoprotein cholesterol; LDL‐C, low‐density lipoprotein cholesterol; SBP, systolic blood pressure; SUA‐serum uric acid; TC, total cholesterol; TG, triglycerides.
Table 5.
Multiple linear regression analysis on the factors related to asprosin among diabetes duration ≥10 years group
| Variable | β | SE | T | P | 95% CI |
|---|---|---|---|---|---|
| BMI | 1.808 | 1.375 | 1.315 | 0.190 | −0.899 to 4.515 |
| FPG | −0.378 | 2.046 | −0.185 | 0.854 | −4.404 to 3.648 |
| SBP | 1.377 | 0.306 | 4.496 | 0.000 | 0.774–1.979 |
| DBP | −0.501 | 0.538 | −0.930 | 0.353 | −1.559 to 0.558 |
| TC | 34.009 | 14.175 | 2.399 | 0.017 | 6.110–61.907 |
| TG | −6.747 | 6.016 | −1.122 | 0.263 | −18.588 to 5.093 |
| LDL‐C | −29.118 | 16.402 | −1.775 | 0.077 | −61.400 to 3.165 |
| HDL‐C | −13.610 | 25.380 | −0.536 | 0.592 | −63.563 to 36.343 |
| SUA | 0.082 | 0.062 | 1.328 | 0.185 | −0.040 to 0.204 |
| HbA1c | 14.480 | 3.112 | 4.653 | 0.000 | 8.355–20.605 |
| CRE | 0.163 | 0.087 | 1.875 | 0.062 | −0.008 to 0.335 |
| eGFR | −0.592 | 0.206 | −2.871 | 0.004 | −0.997 to −0.186 |
BMI, body mass index; CRE, creatinine; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FPG, fasting blood glucose; HbA1c, glycosylated hemoglobin; HDL‐C, high‐density lipoprotein cholesterol; LDL‐C, low‐density lipoprotein cholesterol; SBP, systolic blood pressure; SUA‐serum uric acid; TC, total cholesterol; TG, triglycerides.
Effect of serum asprosin on the incidence of different diabetes duration in type 2 diabetes
Furthermore, the predictive ability of asprosin to detect different durations of diabetes in type 2 diabetes mellitus was tested using receiver operator characteristic curve analysis. The area under the curve for serum asprosin was 0.628 (95% confidence interval 0.573–0.683, P < 0.001) for the prediction of different duration of diabetes. The calculated cutoff value of 357.5 pg/mL yielded a sensitivity of 44.4% and specificity of 78.8% (Figure 2).
Figure 2.
Receiver operating characteristic curve analyses were carried out for the prediction of serum asprosin levels with different duration of diabetes. AUC, area under the curve; T2DM, type 2 diabetes mellitus.
DISCUSSION
Durations of type 2 diabetes in patients are usually based on the natural development of diabetes and assessment of the risk of complications 12 . There are significant differences in clinical manifestations, metabolic parameters and severity of comorbidities between short‐term and long‐term type 2 diabetes patients. The changes of serum adipokines are related to macrovascular and microvascular complications in diabetes. In the present study, type 2 diabetes patients with disease duration ≤5 years and ≥10 years were selected to analyze the clinical significance of serum asprosin, which is helpful to better understand asprosin, an adipokine that regulates metabolism, and its clinical significance as a serum marker in type 2 diabetes patients with different disease duration.
The results of this study showed that the serum asprosin level increased in the group with diabetes duration ≥10 years, and the number of patients with diabetic nephropathy, diabetic retinopathy and diabetic peripheral neuropathy increased. Correlation analysis showed that serum asprosin was related to bodyweight, blood glucose, blood lipids, blood pressure and blood uric acid. Further analysis of the risk factors of serum asprosin in diabetes patients with a duration of ≥10 years showed that HbA1c, SBP, TC and eGFR were independent risk factors, suggesting that in type 2 diabetes patients with duration of diabetes ≥10 years, asprosin might be closely related to the occurrence and development of glucose, and lipid metabolism disorder, renal function and blood pressure. Receiver operator characteristic analysis is a commonly used statistical method to assess the accuracy of a diagnostic test, and it does not rely on a specific threshold to determine its performance. The present study found that serum asprosin levels can predict different diabetes duration.
Adipose tissue, as an endocrine organ with active function, secretes adipokines that can enhance or weaken insulin action 13 , Injection of asprosin antibody to mice can reduce their plasma asprosin levels and improve insulin sensitivity 14 . Asprosin, which is mainly derived from white adipose tissue, is abnormally increased in people with insulin resistance. Type 2 diabetes patients are affected by obesity. Compared with type 2 diabetes patients with normal body fat, there are a large number of free fatty acids and adipocytokines released and deposited in the liver in obese patients, which not only block insulin signal transduction, but also affect liver lipid transport, stimulate the increase of TG and TC concentration in peripheral blood, and participate in insulin antagonism. It can cause pancreatic secretion dysfunction, inhibit pancreatic β‐cells to secrete insulin and destroy blood glucose balance 14 .
The present study found that patients with diabetes duration ≥10 years were older and had lower levels of blood lipids and blood glucose, whereas HbA1c and TC were independent risk factors for patients with diabetes duration ≥10 years. Analysis of the reasons was related to more patients taking hypoglycemic and lipid‐lowering drugs. Furthermore, animal research has found that asprosin activates the G protein–cyclic adenosine monophosphate–protein kinase A signaling axis, which promotes the release of hepatic glycogen and the extensive accumulation of excessive lipid metabolites 1 . This exacerbates metabolic disorders, induces atherosclerotic changes in the arteries and leads to an increase in blood pressure. This study found that blood pressure was an independent risk factor for patients with diabetes duration ≤5 years and diabetes duration ≥10 years.
As a serum marker, asprosin serum in patients with type 2 diabetes and multiple sclerosis is higher than that of healthy people 15 , 16 . However, the reported results on the changes of asprosin levels in obese patients are not consistent. Some studies observed increased serum asprosin levels in obese individuals 17 , and asprosin levels are positively correlated with waist circumference. However, a clinical observation of obese children found that fasting asprosin levels in obese children were significantly lower than those in the control group, and decreased with the increase of BMI, without a significant relationship with insulin resistance 18 . The present study found that BMI decreased and asprosin levels increased in patients with diabetes duration ≥10 years. On the one hand, the reason for the inconsistent results is related to the differences in the participants and expression sites of asprosin. Studies have found that liver, heart, lung, muscle, brain and other tissues can also secrete asprosin 1 . On the other hand, BMI might not directly reflect the deposition characteristics of adipose tissue in different parts.
Previous studies 19 showed that the level of asprosin in patients with chronic kidney disease, diabetic kidney disease and end‐stage kidney disease increased, and high asprosin content in type 2 diabetes patients was associated with lower eGFR. In the present study, the correlation between asprosin and eGFR was reflected in patients with diabetes duration ≥10 years. It is speculated that type 2 diabetes patients with short duration experience acute metabolic stress due to poor blood glucose control, and eGFR is influenced by more factors, which masks the correlation between asprosin and chronic kidney disease.
The present study had several limitations. First, this study was a cross‐sectional analysis, which can only observe associations and cannot determine causality. Second, the age and blood glucose levels of the two groups could not be completely matched, which precluded the execution of a case–control study. Third, the precise onset time of type 2 diabetes is difficult to determine, leading us to categorize the disease duration based solely on medical records. This approach inevitably introduces some degree of overlap between the two groups. In addition, we cannot discount the possibility that asprosin levels might be influenced by DM treatment drugs, lipid‐lowering drugs and so on.
In conclusion, serum asprosin was significantly increased in the group with diabetes duration ≥10 years, and HbA1c, blood pressure, TC and eGFR were independent risk factors in long‐duration type 2 diabetes.
FUNDING
This study was supported by the China Diabetes Research Fund, China Foundation for International Medical Exchanges (Z‐2017‐26‐2202‐4). Shanxi Academy of Social Sciences (Development Research Center of Shanxi Provincial People's Government) 2024 Shanxi Province High Quality Development Research Project (Project Number: SXGZL202482)
DISCLOSURE
The authors declare no conflict of interest.
Approval of the research protocol: The research protocol is applicable by the ethics committee of the First Hospital of Shanxi Medical University (approval number: 2019[K056]).
Informed consent: All study participants provided informed written consent. The study kept patient data confidential and complied with the Declaration of Helsinki.
Registry and the registration no. of the study/trial: N/A.
Animal studies: N/A.
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