The prevalence change of hyperlipidemia and hyperglycemia and the effectiveness of yearly physical examinations: an eight-year study in Southwest China.

BACKGROUND: The aim of this study was to investigate the prevalence changes of hyperlipidemia and hyperglycemia from 2009 to 2016 and the effectiveness of yearly physical examinations to hyperlipidemia and hyperglycemia prevention in Chengdu. METHODS: A total of 794 residents (499 males) who have undergone annual health check-ups for 8 consecutive years (from 2009 to 2016) in Chengdu, a city in southwest China were selected as the follow-up group, 7226 residents in 2009 and 75,068 residents in 2016 who underwent health examinations in the same hospital were chosen to be the contemporary control group. The concentration of fasting serum triglyceride(TG), total cholesterol(TC), low density lipoprotein cholesterol(LDL-C), high density lipoprotein cholesterol (HDL-C) and glucose were measured and compared among these groups. RESULTS: There was a clear rise in the prevalence of hypercholesterolemia and hyperglycemia from 2009 to 2016 (p < 0.05). The follow-up group didn't show difference in levels of serum lipids and glucose compared with the general population after an 8-years' consecutive physical examination (p > 0.05), the follow-up cohort in the 8th year exhibited significant increases in serum total cholesterol and glucose compared with the 1st year (p < 0.05). CONCLUSION: The prevalence of hypercholesterolemia and hyperglycemia were increased significantly from 2009 to 2016. Annual physical examination didn't show a positive effect in the prevention of hypercholesterolemia and hyperglycemia. Health education should be improved to ensure the fulfillment of the preventive objective of yearly physical examination.

[Interference of Exogenous Insulin on Insulin Detection Test by Electrochemiluminescence Immunoassay].

OBJECTIVE: To explore the interference of exogenous insulin therapy on insulin detection test by electrochemical luminescence immunoassay (ECLIA). METHODS: Insulin level was determined by ECLIA. According to the requirements of EP7-A2 of American Society for Clinical Laboratory Standards Institute Standards, paired difference experiment was conducted to evaluate the interference of 8 kinds of exogenous insulin on insulin detection, dose effect experiment was conducted to determine the relationship between exogenous insulin concentration and interference degree. RESULTS: When the interfering substance concentrations were ≤250 µU/mL, Gansulin NⓇ, Gansulin RⓇ, Humulin RⓇ,Novolin RⓇ and LantusⓇ all showed linear positive interference, while LevemirⓇ showed a linear negative interference in high concentrations insulin and non-interfering in low concentrations insulin, HumalogⓇ and Novo RapidⓇ showed non-interference in insulin detection. CONCLUSIONS: The use of different exogenous insulin may have different interference on insulin measurement, which need laboratorians and physicians notice to avoid misdiagnosis.

[Serum Uric Acid and Islet ß-cell Function in Patients with Pre-diabetes and Type 2 Diabetes Mellitus].

OBJECTIVE: To determine the correlation between serum uric acid (SUA) and insulin secretion function in patients with pre-diabetes and type-2 diabetes mellitus (T2DM). METHODS: A total of 4 112 adult people participated in this study. They were divided into three groups according to the results of oral glucose tolerance test (OGTT): 493 with normal glucose regulation (NGR),1 251 with impaired glucose regulation (IGR),and 2 368 with T2DM. Their levels of SUA,fasting insulin (FIns),2 h post-meal insulin (2 h-Ins),and insulin resistance index (HOMA-IR) were determined. Correlations between SUA and insulin secretion and HOMA-IR were estimated. RESULTS: IGR patients had higher levels of SUA and 2 h-Ins compared with those with NGR and T2DM ( P<0.000 1). T2DM patients had higher levels of FIns,glucosylated hemoglobin (HbA1c) and HOMA-IR compared with those with NGR and IGR ( P<0.000 1). In both male and female participants,the highest level of 2 h-Ins appeared in those with IGR,while T2DM had the highest level of HOMA-IA and HbA1c. FIns,2 h-Ins and HOMA-IR increased with SUA in both patients with IGR and T2DM. HbA1c decreased with SUA in T2DM patients. CONCLUSION: High serum SUA is correlated with islet ß-cell dysfunction. It may become an indicator of progression from pre-diabetes to T2DM.

[The Preliminary Investigation of GLP-1 Receptor Agonist on Liver Steatosis in Obese Mice].

OBJECTIVES: To investigate the effects of glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, on liver function and steatosis in obese mice. METHODS: Male c57BL/6J mice (8 weeks old) were divided into high-fat-diet group (for obesity model construction) and chow diet group. 12 weeks later, mice of high-fat diet group were randomly divided into high-dose exenatide group [H group, intraperitoneal injection 0.02 µg/ (g·d) , high-fat-diet], low-dose exenatide group [L group, intraperitoneal injection 0.01 µg/ (g·d) , high-fat-diet], saline group (NS group, intraperitoneal injection of saline, high-fat-diet) , diet control group (D group, shifted to chow diet) and high-fat control group (M group, high-fat-diet) for 4-week treatments , respectively. The body mass and serum biochemical indicators of were detected. Liver tissues were stained with HE, and steatosis score was measured. RESULTS: After 4-week treatments, H group showed more body mass loss than L group and D group ( P<0.05). The serum alanine aminotransferase (ALT) level of NG group was higher than that of H, L, M, and NS groups ( P<0.05). Serum cholesterol and triglyceride declined to normal levels by diet intervention or drug treatment. High-dose exenatide treatment ran a risk of increasing serum uric acid level. The serum levels of aspartate aminotransferase (AST), glucose, homeostasis model assessment-insulin resistance (HOMA-IR), lipase, and amylase had no significant differences between groups (P>0.05). Hepatic steatosis score was reduced by diet intervention or drug treatment. CONCLUSIONS: High-dose exenatide treatment can effectively reduce body mass of obese mice, but it has little difference when compared with dietary intervention in improving blood fat and liver steatosis.

[The Targeted Regulating Role of Has-miR-577 and Has-miR-583 on Gene FGF-21 Detected by the Dual Luciferase Reporter System.]

OBJECTIVES: To determine the targeted regulating role of has-miR-577 and has-miR-583 on the expression of fibroblast growth factor 21 (FGF-21) based on a constructed luciferase reporter FGF-21 gene vector. METHODS: The site of has-miR-577 and has-miR-583 target genes FGF-21 were predicted by the bioinformatics analyzing tools online.FGF-21 gene fragments,combined with has-miR-577 or has-miR-583 sequences and mutant sequences,were designed and synthesized.The wild type (psiCHECK2-FGF-21) and mutant (psiCHECK2-FGF-21-mut) luciferase reporter gene carriers were constructed.The relevant plasmids [hsa-miR-577mimics,hsa-miR-583 mimics or miR negative control (miR-NC)] and luciferase reporter gene carrier (wild type or mutant ) were co-transfected into 293T cells.The luciferase reporter system was used to detect the luciferase activity.The effects of has-miR-577 and has-miR-583 on the expression of FGF-21 were observed. RESULTS: The double enzyme electrophoresis and sequencing results showed that the gene fragment size and sequences of the wild type (psiCHECK2-FGF-21) and mutant (psiCHECK2-FGF-21-mut) carriers met expectations of the experiment.The luciferase assays revealed that has-miR-577 and has-miR-583 significantly diminished luciferase activity from the reporter vector containing 3'UTR of FGF-21 (P<0.05),whereas no suppression of luciferase activity was found in the mutant (psiCHECK2-FGF-21-mut). CONCLUSIONS: FGF-21 gene can be targeted by has-miR-577 and has-miR-583.

[Association of Serum Uric Acid with 2-hour Postload Glucose in Predibetic Patients].

OBJECTIVE: To investigate whether serum uric acid (SUA) is associated with 2-hour postload glucose (2-h PG) in predibetic patients. METHODS: There were 3 588 subjects enrolled in this study from May 2014 to March 2015 in the department of physical examination center and outpatient clinic of West China Hospital of Sichuan University. All the subjects received a 75-g oral glucose tolerance test (OGTT) and measurements of serum uric acid (SUA), Creatinine, Cystatin (Cys-C), serum lipid and glycosylated hemoglobin (HbAlc). According to the results of glucose and HbAlc, the subjects were divided into three groups, including normal glucose regulation (NGT), impaired glucose regulation (IGR) and Type 2 Diabetes Mellitus (T2DM) group. The correlation between 2-h PG and serum uric acid in each group was analyzed. RESULTS: Based on the exam results, there were 556 cases of NGT, 1 019 cases of IGR, 2 013 cases of T2DM. There were statistically significant differences of glucose, serum insulin, triglycerides, high density lipoprotein, HbAlc, SUA, Creatinine, Cys-C levels among the three groups (P<0. 05). Multiple linear regression analysis showed that SUA level was positively correlated to 2-h PG level (P<0. 05) in NGT and IGR groups, but there was no correlation in T2DM group (P=0. 156). In the entire study population, levels of HbAlc and FPG were positive to 2-h PG correlated (P<0. 05). Positive correlation existed between FPG and 2-h PG in NGT group (P=0. 031). In IGR and T2DM group, HbAlc and 2-h PG were positively correlated (P<0. 05). HbAlc, FPG and SUA levels were independent risk factors for 2-h PG. CONCLUSION: In prediabetes, 2-h PG is associated with SUA and independent of FPG, HbAlc and other known risk factors. SUA may play a key role in the prediabetic condition as a risk indicator of T2DM.

[Changes of bone mineral density and bone metabolic marker in patients with subclinical hypothyroidism].

OBJECTIVE: To investigate the change of bone mineral density and bone metabolism biochemical markers in subclinical hypothyroidism. METHODS: This study included total 122 patients with subclinical hypothyroidism and 153 healthy age and gender matched people as control. All the patients and controls were subjected to the measurements of bone density by dual energy X-ray absorptiometry (DEXA), and serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), Ca2+, PO4(3+), alkaline phosphatase (ALP) levels. All the data was analyzed statistically with the stratification of gender and menopause status. RESULTS: Compared to the control, the patients with subclinical hypothyroidism had significantly higher incidence of bone mass loss (P < 0.005) and lower level of Serum Ca2+ (P < 0.05) and higher levels of serum PO4(3+), T-value and Z-value (P < 0.05). Furthermore, premenopausal women had higher Z-value (P < 0.01) , but no significantly differences of T-value, serum PO4(3+) was found either in pre-menopause or post-menopause women when compared to the control. Multiple linear regression analysis showed gender (B = 0.543, P < 0.0001) was positive correlation with T value, female had lower T values. Moreover, T value was negative correlated to menopausal status (B = -0.274, P = 0.001), age (B = -0.161, P < 0.0001) and TSH (B = -0.108, P < 0.0001). CONCLUSION: Subclinical hypothyroism appears decreased serum calcium and low bone density.

[Risk stratification of diabetic chronic kidney disease using eGFR equations].

OBJECTIVE: To compare different eGFR equations for risk stratification of diabetic chronic kidney disease. METHODS: A total of 601 diabetic patients participated in the study. Data about the patient serum cystatin C (Cys-C), blood urea nitrogen (BUN), creatinine (Scr), uric acid (UA), glycosylated hemoglobin (HbAlc), and urinary albumin creatinine ratio (ACR) were extracted. Simplified MDRD formula were used for calculating glomerular filtration rate (eGFR) using eGFR-EPlcrea, eGFR-EPIcys and eGFR-EPIcrea-cys. The patients were divided into three groups according to their urine ACR. Comparisons were made between the groups of patients in Cys-C, BUN, UA, eGFR and Scr. RESULTS: There were significant differences (P < 0.05) in Cys-C, eGFR-MDRD, eGFR EPIcrea, eGFR-EPIcys, and eGFR-EPIcrea-cys among the groups of patients. The different equations for risk stratification produced different distributions of patients among the three groups. Significant differences appeared among the groups in the distribution of patients using eGFR-MDRD (P < 0.05), eGFR-EPIcrea (P = 0.000) and eGFR-EPIcys (P < 0.05) and indication for stratification. No significant differences were found in the distribution of patient among the three groups (P > 0.05) using GFR-MDRD, eGFR-EPIcrea and eGFR-EPIcrea-cys as an indication for stratification. In low risk patients, eGFR-MDRD was higher than other eGFR (P < 0.05). In medium and high-risk patients, eGFR-MDRD and eGFR-EPIcrea were higher than eGFR-EPIcys and eGFR-EPIcrea-cys. In very high-risk patients, the four eGFR did not show differences. CONCLUSION: The performance of different eGFR equations differs in risk stratification of diabetic chronic kidney disease. In low-risk patients, MDRD equation may overestimate GFR level.

[Study of glycated albumin cut-off point in diabetes mellitus and impaired glucose regulation].

OBJECTIVE: To investigate the cut-off point of glycated albumin (GA) in the detection of diabetes mellitus (DM) and impaired glucose regulation (IGR). METHODS: This study was conducted in 20-84 years-old adults who had risk factors of diabetes but no previously diagnosed diabetes. There were finally 392 individuals included and received the measurement of GA and HbA1c. Receiver operating characteristic curve (ROC) was plotted to determine the performance of GA. RESULTS: (1) Based on the diabetes diagnosis criteria of WHO (1999), the subjects were divided into DM group (n = 131), IGR group (n = 126), and normal glucose tolerance (NGT) group (n = 135). The GA level in the three groups tended to increase (P < 0.05). (2) Spearman correlation analysis demonstrated that GA was positively correlated with glycated haemoglobin A1c (HbA1c) (r = 0.942 1, P < 0.05), fasting plasma glucose (FPG) (r = 0.856 6, P < 0.05) and 2 h post-load plasma glucose (2-hPG) (r = 0.813 7, P < 0.05). (3) The mean levels of serum GA/HbA1c were 2.58 +/- 0.37, 2.44 +/- 0.37 and 2.17 +/- 0.25 for DM, IGR and NGT respectively. (4) The optimal cut-off points for detecting diabetes were 16.6% in GA [area under the carve (AUC) = 0.888], producing the sensitivity of 71.8% and the specificity of 87.4%. CONCLUSION: GA as a single screening test shows adequate to detect newly diagnosed DM, and the optimal GA cut-off point was 16.6% in this study.

[Blood lipid, glucose and uric acid in people with subclinical hypothyroidism].

OBJECTIVE: To investigate the changes of blood lipid, fasting blood glucose and blood uric acid and its clinical significance in people with subclinical hypothyroidism. METHODS: Body mass index (BMI), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free tetraiodothyronine (FT4), total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), fasting blood glucose (FBG) and uric acid (UA) were measured and compared in 356 people with subclinical hypothyroidism and 331 health people (controls). RESULTS: Compared to the control group, people with subclinical hypothyroidism had higher levels of BMI, TSH, TC, LDL-C, TG, FBG, UA (P < 0.05) and non-significant decrease of HDL-C (P > 0.05). The level of TSH was positively correlated with TC (r = 0.254), LDL-C (r = 0.110), TG (r = 0.218), BMI (r = 0.119) and FBG (r = 0.210) (P < 0.05). The level of HDL-C was not correlated with TSH (P > 0.05). CONCLUSION: Thyroid dysfunction may have an effect on the metabolism of blood lipid, FBG and UA.

[Application of glomerular filtration rate prediction formulae in diabetic patients].

OBJECTIVE: To compare the predictive performances of glomerular filtration rate (GFR) prediction formulae based on serum crea level in diabetic patients and to determine their clinical application values. METHODS: Fasting serum crea of 125 diabetic patients in Chengdu were detected. 99mTc-DTPA clearance rate was used as the reference test (rGFR). The eGFR was obtained using different formulae (aMDRD and CKD-EPI formula in this study). The bias, precision, accuracy and diagnostic sensitivity of the two formulae were compared. ROC curve analyses were performed with different diagnostic boundary points [rGFR < S90 or < 60 mL/(min x 1.73(2))]. RESULTS: Significant differences between eGFR and rGFR were found with both formulae (P < 0.05). There were no significant differences in the predict performance between the two formulae in terms of bias, precision and accuracy within 30% and 50%. Two cases with higher than 90 mL/(min x 1.732) rGFR were identified as outliers using aMDRD formula according to the eGFR-rGFR scatterplot analysis. The ROC curve analysis showed that the AUC were in the range between 0.8 and 0.9. The AUC approached 0.9 when proteinuria was taken into consideration for both formulae, and this involved a significant improvement (P < 0.05). CONCLUSION: Both aMDRD and CKD-EPI formulae predict eGFR accurately in diabetic patients. However, the CKD-EPI formula may have better stability in predicting eGFR in patients at an early stage of renal injury. Combined use of proteinuria may improve the diagnostic performance of eGFR prediction formulae. [Key words] Diabetes Glomerular filtration rate aMDRD CKD-EPI

[Preliminary study on the expression of cystatin C in primary liver cancer].

OBJECTIVE: To preliminarily investigate the expression of cysteine proteinase inhibitors C (cystatin C) in primary hepatic carcinoma. METHODS: Hepatic tissue samples and peripheral blood samples were collected from 41 cases of primary hepatic carcinoma, 24 cases of cirrhosis and 40 cases of normal control. To primary hepatic carcinoma, three kinds of hepatic tissue samples were harvested, including carcinoma tissue, adjacent non-tumor tissue, and distant normal tissue. The expression levels of cystatin C in hepatic samples and blood samples were measured by immunohistochemistry method and latex enhanced immune turbidimetric method respectively, and the differences of cystatin C expressions were compared in primary hepatic cancer, cirrhosis, and normal control. Furthermore, the relationships of cystatin C expression with tumor size, intrahepatic metastasis, serum AFP level were studied with correlation analysis. RESULTS: The expression of cystatin C was positive, in primary hepatic carcinoma. Part of adjacent non-tumor tissue, and distant normal tissue and cirrhosis tissues had some degree of cyctatin C expression. Wilcoxon test showed that the differences of cyctatin C expression in different hepatic tissues were statistics significance (P < 0.01). The proportion of positive cell, staining intensity, and the product of these two was: carcinoma tissues > adjacent non-tumor tissues> cirrhosis tissues > distant normal tissue. Compared with normal control, primary hepatic carcinoma and cirrhosis both had higher serum cystatin C level (P < 0.001), but there was no difference between hepatic carcinoma and cirrhosis (P = 0.769). The correlation analysis showed that the level of serum cystatin C was not related to serum AFP, tumor size, or intrahepatic metastasis. CONCLUSION: The expression of cystatin C in primary hepatic carcinoma is higher than that of adjacent non-tumor tissue, distant normal tissue, and cirrohsis tissue. The serum cystatin C level of primary hepatic carcinoma is higher than that of normal control.

[Estimating glomerular filtration rate based on serum cystatin C].

OBJECTIVE: To develop an estimating formula for glomerular filtration Rate (GFR) based on serum cystatin C in patients with chronic kidney disease (CKD). METHODS: Clinical characteristics of 242 CKD patients were collected. The patients were randomly divided into modeling group and model validation group. The rGFR obtained from 99mTc-DTPA clearance rate was used as a reference value of GFR. s-cystatin C was detected by latex enhanced immunoturbidimetric method. Preliminary linear regression analysis followed by multiple linear regression were performed to investigate the association between s-cystatin C and rGFR. The validity of the estimation formula was tested in the model validation group in comparison with Hoek formula and Orebro formula. RESULTS: With standardised countdown conversion, s-cystatin showed linear correlation with rGFR, with a correlation coefficient of 0.773. The multiple correlation coefficient, determination coefficient, adjusted R square and std. error of the estimation model were 0.863, 0.745, 0.742, and 0.207, respectively. The residuals P-P probability plot analysis showed that the model residuals fitted into normal distribution with homogeneity of variance. Theeformula was: eGFR = 67/s-cystatin C +3. No significant difference was found between the distribution of eGFR and rGFR. Our formula had an accuracy of 30% and 50%, which were no less than those obtained from Hoek formula and Orebro formula. The new formula also had acceptable bias and high precision. The Bland-Altman analysis and ROC curve analysis showed good applicability of the new formula. CONCLUSION: The GFR prediction formula we established has a good prediction performance as comparised with other formulae, which could be used in measuring GFR in CKD patients.