Résumé
Objective To evaluate insulin resistance (IR) in patients with systemic lupus erythematosus (SLE) and investigate the effect of glucocorticoids on IR and its clinical significance. Methods Three hundred and one SLE patients and 103 healthy volunteers hospitalized in our hospital from May 2013 to May 2017 were included in this study. Homeostasis model assessment (HOMA) was used to calculate insulin resistance index (HOMA-IR), HOMA-βcell function index (HBCI) and insulin sensitivity index (ISI). The IR grouping was determined by using the upper 1/4 of the HOMA-IR index of 103 healthy volunteers as the cut point. According to the dose of glucocorticoids in the last 3 months, the SLE group was divided into glucocorticoids>7.5 mg/d group,≤7.5 mg/d group and without glucocorticoids group. These parameters were compared with all groups respectively. Furthermore, related factors for HOMA-IR were analyzed by linear correlation. Results Compared with control group, triacylglycerol (TG, P<0.01), fasting insulin (FINS, P<0.01), HOMA-IR (P<0.01), HOMA-HBCI (P<0.05) were significantly increased and high-density lipoprotein cholesterol (HDL-C, P<0.01) and ISI (P<0.01) were significantly lower in SLE group. However, there were no significant differences in TG, FINS, HOMA-IR and ISI between different doses of glucocorticoid groups (P>0.05). The level of HOMA-HBCI was significantly higher in two groups with glucocorticoids than that without glucocorticoid group and normal control group (P<0.05), while there was no significant difference in HOMA-HBCI between without glucocorticoid group and the normal control group ( P>0.05). HOMA-IR was positively correlated with fasting blood glucose (FBG, r=0.566, P<0.01), FINS (r=0.949, P<0.01) and HOMA-HBCI (r=0.280, P<0.01). But there was a negative correlation between TG (r=-0.139, P<0.01) and ISI (r=-0.896, P<0.01). Conclusion Insulin secretion is abnormal and the incidence of IR is elevated in SLE patients. Long term glucocorticoid therapy may be involved in the formation of IR.
Résumé
Objective To explore the effects of dipeptidyl peptidase ( DPP-4 ) inhibitor on proteins expression of Bcl-2 and Bax of islet β-cells through increasing the expression of islet γ amino acid butyric acid ( GABA) . Methods A total of 50 rats of clean grade were studied. Among them, ten rats were randomly selected as normal controls, the remaining forty rats were fed with high-fat diet and then intraperitoneal injection with streptozotocin, the diabetic rats models were then established. Rats were randomly divided into three groups:i. e. diabetic control group, DPP-4 inhibitor group, and antagonist group ( DPP-4 inhibitor and GABA receptor antagonist). Six weeks later, blood glucose, serum insulin, glucagon, and the proteins expression of GABA, Bcl-2, and Bax of islet β-cells were measured. Results ( 1 ) Compared with diabetic control group, serum insulin was increased(P<0.05),bloodglucoseandserumglucagonweredecreasedinDPP-4inhibitorgroup(P<0.05). (2) Compared with DPP-4 inhibitor group, serum insulin was decreased(P<0. 05), blood glucose and serum glucagon were increased(P<0. 05) in antagonist group. (3) Compared with diabetic control group, the expression of GABA was increased(P<0. 05), the expression of Bcl-2 protein was increased (P<0. 05) in pancreatic β-cells in DPP-4 inhibitor group. ( 4 ) Compared with diabetic control group, the expression of GABA in pancreatic β-cells was increased in antagonist group(P<0. 05) . Compared with DPP-4 inhibitor group, the expression of Bax protein in pancreaticβ-cells was increased in antagonist group(P<0. 05) , while the expression of Bcl-2 protein was decreased (P<0. 05). Conclusions DPP-4 inhibitor could increase the secretion of insulin, decrease the secretion of glucagon, up-regulate expression of anti-apoptosis protein Bcl-2, and down-regulate expression of apoptosis protein Bax in pancreatic β-cells through increasing the expression of GABA, inhibiting pancreatic β-cells apoptosis and protecting the damagedβ-cells in type 2 diabetic rats.
Résumé
[Summary] To investigate the association between sleep disorder and ambulatory blood pressure rhythm in patients with type 2 diabetes. 418 patients with type 2 diabetes were divided into two groups according to Pittsburgh sleep quality index ( PSQI):patients without sleep disorder and patients with sleep disorder. Oral glucose tolerance test, insulin releasing test, and C-peptide releasing test were performed to investigate the differences in the β-cell function, the circadian rhythm of blood pressure, and blood pressure variation between the two groups after fasting and glucose-load. The correlation and regression analysis were performed between PSQI and other indicators. (1)The level of HbA1C , fasting plasma insulin, area under curve of insulin, fasting plasma C-peptide, area under curve of C-peptide, and homeostasis model assessment for insulin resistance ( HOMA-IR) were significantly higher in patients withsleepdisordercomparedtothoseinpatientswithoutsleepdisorder[(8.2±2.1)% vs(7.4±1.8)%,(13.42± 4.55vs11.86±4.52)mU/L,(8.51±0.54vs8.38±0.51)mU·L-1·min,(2.42±1.25vs1.79±0.73)ng/ml, (6.59±0.39vs6.49±0.43)μg·L-1·min,4.63±1.12vs3.86±0.97,allP<0.05]. Insulinsensitivityindex (ISI) was lower in patients with sleep disorder than that in patients without sleep disorder(-4. 26 ± 0. 78 vs-4. 05 ± 0.62,P<0.05). (2)Thelevelof24hmeansystolicanddiastolicbloodpressure,nocturalsystolicanddiastolicblood pressure, and systolic blood pressure during daytime and nighttime were significantly higher in patients with type 2 diabetes who were suffering from sleep disorder. The blood pressure variation was more marked in patients with sleep disorder. (3)Multiple stepwise regression analysis showed that PSQI score was positively related to area under curve of C-peptide, HOMA-IR, 24 h mean systolic blood pressure, and noctural systolic blood pressure (β=0. 242, 0. 293, 0. 352, 0. 413, all P<0. 05), and negatively related to ISI and decreasing ratio of noctural systolic blood pressure (β=-0. 124 and -0. 226, both P<0. 05). Sleep disorder may cause abnormal circadian rhythm of blood pressure through various mechanisms. Improving sleep disorder may help to ameliorate insulin resistance and restore normal circadian rhythm of blood pressure.