Association of nocturnal serum cortisol level with diabetic microvascular complications in overweight/obese type 2 diabetic patients / 中华内分泌代谢杂志

Objective To explore the association of nocturnal serum cortisol levels with diabetic microvascular complications in overweight or obese patients with type 2 diabetes mellitus. Methods Serum cortisol levels of 316 overweight or obese type 2 diabetic patients were tested at midnight by the method of chemiluminescence. Diabetic microvascular complications were compared among various groups according to nocturnal serum cortisol levels. All the patients with nocturnal serum cortisol level > 50 nmol/L were asked to undergo overnight low-dose dexamethasone suppression test to rule out the possibility of subclincal Cushing's syndrome. The incidences of diabetic nephropathy ( DN ) , diabetic retinopathy ( DR ) , and diabetic peripheral neuropathy ( DPN ) were examined in all the patients. Results (1)The incidence of DN was gradually increased from 13.3％to 27.7％and 44.2％in patients with low, medium, and high cortisol level groups, showing a statistical difference among 3 groups ( P<0.05) . The incidences of DR in medium and high cortisol level groups were higher than that in low cortisol level group (40.6％and 47.7％vs 22.7％, both P<0.01). The incidence of DPN in high cortisol level group was higher as compared with low cortisol level group (60.5％ vs 38.7％, P<0.01). (2) Nocturnal serum cortisol level in patients with diabetic microvascular complications was higher than that in patients without complications [ (136.87 ± 105.78 vs 97.55 ± 93.48) nmol/L, P<0.01]. Nocturnal serum cortisol level in patients with multiple diabetic microvascular complications was higher than that in patients with single diabetic microvascular complication [ (151.66±114.54vs117.69±90.26)nmol/L,P<0.05].(3)Singlefactorlogisticregressionanalysisshowedthat higher nocturnal serum cortisol level was a risk factor for diabetic microvascular complications in addition to female, age, longer diabetic duration, higher fasting plasma glucose ( FPG ) . Multivariate logistic regression analysis showed that higher nocturnal serum cortisol level was still a risk factor for diabetic microvascular complications after adjusted by diabetic duration, FPG, HbA1C, and the use of insulin (P=0.013). Conclusion Nocturnal serum cortisol level seems to be a risk factor for diabetic microvascular complications in overweight or obese patients with type 2 diabetes mellitus.

Correlation between polymorphism of estrogen receptor gene and non-alcoholic fatty liver disease in postmenopausal women / 中华内分泌代谢杂志

Genotypes of estrogen receptor gene (ER) α and β in 110 patients with non-alcoholic fatty liver disease (NAFLD) and 100 control subjects were examined by polymerase chain reaction-based restriction fragment length polymorphism.The haplotype analysis was conducted by SHEsis on-line computing platform.The results showed that there were no differences in the genotype frequencies and allele frequencies of ERα at Xba Ⅰ and Pvu Ⅱ enzyme cutting sites between two groups (P ＞ 0.05).There existed significant differences in the genotype frequencies and allele frequencies of ERβ at Rsa Ⅰ and Alu Ⅰ enzyme cutting sites between these two groups (P ＜ 0.05 or P ＜0.01).The risk of NAFLD in postmenopausal women with R or a allele was 1.833 (95％ CI1.209-2.779,P＜0.05)or 1.782 (95％ CI 1.037-3.061,P＜0.05) fold of that with allele r or A.The frequency of r-A haplotype in ERβ was significantly lower in NAFLD group than that in control group (OR =0.529,95％ CI 0.348-0.805).Logistic regression analysis showed the relationship of fasting blood glucose,triglyceride,body mass index,diastolic pressure,Alu Ⅰ genotype with NAFLD (all P＜0.01).The risk of NAFLD in postmenopausal women with Aa/aa genotype was 1.345 (95％ CI 1.028-2.505,P＜0.05) folds of that with AA genotype.

The role of connective tissue growth factor in bone metabolism / 中华内分泌代谢杂志

It has been demonstrated that connective tissue growth factor(CTGF) may enhance proliferation and differentiation of osteoblasts,inhibit the functions of osteoblasts,increase osteoclastogenesis in patients with Rheumatoid Arthritis,stimulate proliferation and differentiation of chondrocytes,and induce angiogenesis in vivo and vitro.Above all,CTGF plays an important role in sustaining growth of skeleton and cartilage,and thus maintaining bone quantity.

Serum retinol binding protein 4 and bone metabolism in patients with type 2 diabetes / 中南大学学报(医学版)

OBJECTIVE@#To determine the relation between serum concentration of retinol binding protein (RBP) 4 and markers of bone metabolism, bone mineral density (BMD) in patients with type 2 diabetes mellitus (T2DM).@*METHODS@#A total of 82 patients newly diagnosed with T2DM and 46 subjects with normal glucose tolerance (NGT) enrolled in the cross-sectional study. Subset analyses were performed, dividing subjects on the basis of gender into M-T2DM, F-T2DM, M-NGT, and F-NGT. The serum concentrions of RBP4, osteocalcin (OC) and C-terminal telopeptide of collagen type I (CTX) were measured with ELISA. The BMD was measured by dual-energy X-ray absorptiometry (DXA) with a Hologic QDR4500A device.@*RESULTS@#In both the T2DM groups, lnRBP4 showed a positive relationship with lnCTX (M-T2DM, r=0.564, P<0.01; F-T2DM, r=0.386, P=0.018), but no association with lnOC. After adjusting for age, smoking, creatinine clearance rate (CCr), and waist-to-hip ratio (WHR), lnRBP4 still showed a strong association with lnCTX in the M-T2DM group (r'=0.536, P<0.01), but not in F-T2DM (r'=0.317, P=0.072). In the NGT group, there was no relation between lnRBP4 and lnCTX or lnOC. LnRBP4 showed no association with BMD in all groups.@*CONCLUSION@#The level of serum RBP4 may be correlated with the bone metabolism in patients with T2DM.

A cross-sectional study on the association between serum uric acid and non-alcoholic fatty liver disease in health checkup population / 中华内分泌代谢杂志

Objective To evaluate the relationship between hyperuricemia and nonalcoholic fatty liver disease(NAFLD) by observing the prevalence of NAFLD among healthy individuals with different levels of serum uric acid.Methods The data of 5 230 persons from medical centers for health examination were analyzed,such as height,weight,blood pressure,blood lipids,blood sugar, hepatitis-related markers, and abdominal color Doppler ultrasound examination were conducted in the fasting state.The diagnosis of NAFLD was made according to the diagnostic criteria adopted by China Institute of Liver Disease and Alcoholic Liver Disease Group.Results The incidences of overweight or obesity, hypertension,hyperlipidemia, and metabolic syndrome were raised with serum uric acid greater than 333 μmol/L in male and＞233 μmol/L in female subjects(P＜0.05 or P＜0.01). Excluding the metabolic syndrome in male subjects, the incidence of NAFLD was increased with serum uric acid,＞333 μmol/L in males or ＞233 μmol/L in females(P＜0.05 or P＜0.01). In further studies with subjects without any metabolic syndrome, the detection rate of NAFLD was higher in males than in females at the same serum uric acid level(P＜0.01). Logistic regression analysis showed that sex, body mass index, blood glucose, and triglyceride, low-density lipoprotein cholesterol, uric acid grading were risk factors of NAFLD(OR 1.344, 2.500, 1.292, 1.279, 1.244, 1.256 respectively).Conclusion A high serum uric acid level is associated with an increased risk of NAFLD.

Effect of recombinant human connective tissue growth factor on the expression of membrane type-1 matrix metalloproteinase and matrix metalloproteinase 2 in human osteoblasts / 中华内分泌代谢杂志

Human osteoblast was treated with recombinant human connective tissue growth factor (rCTGF). This experiment showed that rCTGF increased membrane type-1 matrix metalloproteinase and matrix metalloproteinase-2 protein expression in a dose- and time-depentent manner in human osteoblasts. rCTGF induced activation of p38 MAPK in human osteoblasts. p38 MAPK inhibitor SB23058 abrogated the effect of rCTGF on the expressions of membrane type-1 matrix metalloproteinase and matrix metalloproteinase-2 in human osteoblasts.

Effects of recombinant human connective tissue growth factor on the expression of osteoprotegerin and receptor activator of NF-κB ligand in human osteoblasts / 中华内分泌代谢杂志

Objective To investigate the effects of recombinant human connective tissue growth factor (rCTGF) on the expression of osteoprotegerin (OPG) and RANKL ( receptor activator of NF-κB ligand ) in human osteoblasts, as well as the mechanisms involved. Methods Human osteoblasts were treated with rCTGF. The expressions of OPG and RANKL were assessed by Western blotting. The expressions of focal adhesion kinase ( FAK), mitogen-activated protein kinase (MAPK) were also observed. Results rCTGF inhibited RANKL protein expression in a dose-and time-depentent manner in human osteoblasts, while the expression of OPG kept unchanged. rCTGF induced activation of p38MAPK and dephosphorylation of FAK in human osteoblasts, but had no effect on ERK and JNK phosphorylation. p38MAPK inhibitor SB23058 abrogated the inhibitory effect of rCTGF on RANKL in human osteoblasts. Conclusion rCTGF inhibits the expression of RANKL in human osteoblasts via activation of p38MAPK and dephosphorylation of FAK.

Effect of body composition on bone mineral density in males with different glucose tolerance / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of body composition on bone mineral density (BMD) in males with different glucose tolerance.@*METHODS@#A total of 87 male subjects aged 35~64 years were divided into 2 groups by glucose tolerance test, 57 diagnosed T2DM and 30 with normal glucose tolerance(NGT). BMDs of anteroposterior lumbar vertebrae (AP), left femur neck (FN), total hip (T-hip), and total bone mineral density(TBMD)were measured by dual-energy-X-ray absorptiometry (DEXA). Body composition was also measured by DEXA, while fat tissue mass(FTM), lean tissue mass(LTM), percentage of truncal fat (Tru-fat%) and total fat (Fat%) were computed. The effect of body composition on the BMD of the 2 groups was analyzed.@*RESULTS@#LTM and FN-BMD had a positive correlation in the NGT group, but no correlation in the T2DM group. The percentage of fat showed a negative relationship with the BMD of AP in the T2DM group, but not in the NGT group. The percentage of fat and total BMD had a negative association in both the NGT and the T2DM groups. In the NGT group, LTM was the independent predictor of BMD of AP,FN and hip (b=0.509, 0.411, and 0.585; P<0.01 or 0.05; R2=0.169~0.342). In the T2DM group, LTM was the independent predictor of BMD of AP (b=0.330, P<0.05, R2=0.109) and hip (b=0.462, P<0.01,R2=0.213), but not FN.@*CONCLUSION@#LTM has an attenuated effect on the BMD in male patients with T2DM compared with patients with NGT. An increased percent of fat percent is harmful to preserve bone mass in male adults, regardless of normal glucose tolerance or T2DM.

The relationship between serum retinol binding protein 4 and the parameters of inflammatory, lipid metabolism, insulin resistance in patients with type 2 diabetes / 中国医师杂志

Objective To investigate the relationships between serum concentration of RBP-4 and the parameters of inflammatory, lipid metabolism, insulin resistance in patients with T2DM. Methods 71 patients newly diagnosed with T2DM and 34 subjects with normal glucose tolerance (NGT) were enrolled in this cross-sectional study. Additionally, another subset analysis was performed. Subjects were divided into normal weight (NW) and overweight or obesity (OW/OB) group on the basis of BMI. Serum RBP-4 was measured with ELISA. Serum concentrations of hs-CRP, free fatty acids (FFA), triglyceride (TG), total cholesterol (TC) and insulin were measured in fasting status. Insulin resistance was assessed by HOMA-IR. Results Ln (HOMA-IR) and the concentrations of TG, FFA, In(hs-CRP) in T2DM were significant-ly higher than that of NGR group[1.20±0.38 vs 0.76±0.34,(2.74±2. 20)mmol/L vs (1.88±1.41),(0. 80±0. 29)mmol/L vs (0.61±0.22)retool/L,0.62±1.00 vs -0. 17±1.07] . InRBP-4 showed a positive relationship with In (HOMA-IR) ( r =0. 382, P <0. 05), but no association with TC, TG, FFA and In(hs-CRP). In the group of T2DM, InRBP-4 showed a positive relationship with FFA ( r =0. 242, P <0.05) and In (hs-CRP) ( r =0.346, P <0.01), but no association with TC, TG and In (HOMA-IR). There were no relationships between InRBP-4 and In (HOMA-IR), TC, TG, FFA and In (hs-CRP)in NW, while in OW/OB group, InRBP-4 showed a positive relationship with In (HOMA-IR) ( r =0. 290,P < 0. 05 ) and In (hs-CRP) ( r = 0. 295, P <0.05 ), but no association with TC, TG and FFA. In a mul-tiple linear regression analysis, In( hs-CRP), TC, TG, FFA or In(HOMA-IR) was not the independent de-terminant of InRBP-4 in any group. Conclusion In patients with T2DM, InRBP-4 is positively correlatedwith In (hs-CRP) and FFA, and it may be a new marker of inflammation.

Relationship of age-related serum transforming growth factor (TGF)-β1 and TGF-β2 with osteoprotegerin and leptin in women / 中华内分泌代谢杂志

-β2 was positively correlated with OPG (r=0. 432,P<0. 01). Conclusions The reference ranges of serum TGF-β1 and TGF-β2 in healthy adult females are established. Both TGF-β1 and TGF-β2 of them are correlated with OPG and ieptin.

Effect of cyclic mechanical stimulation on expression of connective tissue growth factor in MG63 osteoblast-like cells / 中华内分泌代谢杂志

Objective To investigate cyclic mechanical stimulation on expression of connective tissue growth factor (CTGF) in osteoblast-like cells (MG63) and to explore the rote of MAPK involved in the process.Methods Expressions of CTGF protein and mRNA in MG63 cells were detected by Western blot and RT-PCR,respectively. Phosphorylation levels of p38, ERK, JNK were examined by Western blot. Results Cyclic mechanical stimulation upregulated expressions of CTGF protein and mRNA. The levels reached a maximal response of 2-3 fold after 3-6 h. ERK and JNK signal pathways were activated by cyclic mechanical stimulation, the phosphorylated proteins increased within 10 min of stretch, phosphorylated ERK reached maximal levels by 60 min of stretch, phosphorylated JNK reached maximal levels by 15-30 min of stretch, but not for p38 signal pathway.Only the inhibitior of JNK signal pathway (SP600125) markedly suppressed stretch-induced CTGF expression,meanwhile the inhibitors of ERK (PD98059) and p38 (SB203580) did not show such effect. Conclusion Cyclic mechanical stimulation upregulates CTGF expression via JNK-dependent pathway in MG63 cells.

Effects of recombinant human connective tissue growth factor on proliferation, differentiation, and apoptosis in human osteoblasts / 中华内分泌代谢杂志

Objective To investigate the effects of recombinant human connective tissue growth factor (rCTGF) on the proliferation, differentiation and apoptosis in human osteoblasts. Methods Human osteoblasts were treated with rCTGF, cell proliferation was measured by [3 H] -thymidine ([3 H] -TdR) incorporation method,the activity of alkaline phosphatase (ALP) was determined using α-nitrophenyl phosphate as a substrate, the expression of type Ⅰ collagen was determined by Western blotting, osteocalcin in conditioned media was measured by radioimmune assay, and cell apoptosis was assayed by flow cytometry. Results rCTGF promoted proliferation and differentiation of human osteoblasts in a dose-depentent manner, rCTGF increased ALP activity, osteocalcin and type I collagen secretion in a dose-depentent manner, rCTGF inhibited human osteoblastic apoptosis induced by serum deprivation. Conclusion rCTGF can promote osteoblastic proliferation, and differentiation and protect osteoblast against apoptosis, suggesting that CTGF plays an essential role in bone metabolism.