Volume 06 · Issue 09 · 2014

Gestational diabetes mellitus (GDM) refers to abnormalities in glucose metabolism that first appear or are found during pregnancy. Although most patients with GDM can return to normal postpartum glucose metabolism disorder, the perinatal and long-term adverse events caused by GDM still deserve our attention^[1]。 Since the middle of last century, a variety of screening methods and diagnostic criteria for GDM have been applied in clinical practice (Table 1), but the previous standards were all based on the risk of long-term diabetes in pregnant women or the statistical data of non-pregnant people, and did not pay attention to perinatal complications. Therefore, there has been a lack of international consensus on GDM diagnosis. In view of this, to investigate the relationship between blood glucose levels and adverse pregnancy outcomes in pregnant women, the National Institutes of Health (NIH) initiated the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study in 2001. According to the results of HAPO, the International Organization for the Study of Pregnancy and Diabetes (IADPSG), the American Diabetes Association (ADA) and the Chinese Medical Association Diabetology Branch (CDS) successively updated the diagnostic criteria for GDM from 2010 to 2012^[2,3,4]。 Although these new criteria have slight differences, they all reduce the diagnostic cut-off point of GDM, and more pregnant women are diagnosed with GDM. However, the results of the HAPO study were not adopted in the GDM diagnostic statement issued by NIH in 2013^[5]It has aroused widespread attention and discussion among scholars at home and abroad, and the applicability of IADPSG and other standards has also been controversial. However, recent studies have shown that stringent standards in clinical application can benefit pregnant women more.

Gestational diabetes mellitus (GDM) refers to different degrees of abnormalities in glucose metabolism that occur or are first detected during pregnancy. GDM is a common perinatal complication with mixed incidence reports due to differences in diagnostic criteria and ethnicity. At present, the American Diabetes Society (ADA) recommends adopting the new standard recommended by the International Diabetes and Pregnancy Research Group (IADPSG), which has been widely accepted globally. According to its standard, the incidence of GDM is 1% ~18%^[1]。

At present, pre-pregnancy diabetes in women of childbearing age accounts for about 13% of pregnant women with diabetes, and the prevalence is increasing^[1,2]。 Lawrence et al.^[3]A retrospective analysis of 175 249 pregnant women showed that the prevalence of pregnancy diabetes increased from 0.81% in 1999 to 1.82% in 2005. Insulin resistance caused by placental hormones, growth factors and cytokines is easy to cause hyperglycemia and harm the fetus. Insulin-related hypoglycemia in the first trimester of pregnancy brings great risks to pregnant women, especially patients with type 1 diabetes (T1DM)^[4]。 Adverse pregnancy outcomes (including miscarriage, congenital malformation, fetal macrosomia, stillbirth, premature birth and preeclampsia) were significantly higher in T1DM women than in general pregnant women^[5]And the incidence of diabetic microangiopathy (such as retinopathy, kidney disease, neuropathy), hypertension, cardiovascular disease and thyroid disease during pregnancy all increased to varying degrees^[6]。 Maintaining normal blood glucose levels is essential to minimize the above adverse events.

To explore the effects of serum triglyceride on islet β cell function and insulin resistance in patients with newly diagnosed gestational diabetes mellitus(GDM).

Total of 439 newly diagnosed GDM patients at 24-30 weeks of gestation from maternity ward in First People's Hospital were recruited from January 2012 to April 2014. The demographic data, lipid profiles were collected and 75 g oral glucose tolerance test(OGTT)and insulin release test were performed. Homeostasis model assessment for β cell function index(HOMA-β), homeostasis model assessment for insulin resistance index(HOMA-IR)and quantitative insulin-sensitivity check index(QUICKI)were calculated respectively. The participants were divided into three groups based on the three tertiles of their fasting serum triglycerides: lowest tertile group(1.25-2.30 mmol/L, Group T1,n=146), medium tertile group(>2.30-3.10 mmol/L, Group T2,n=146)and highest tertile group(>3.10-22.03 mmol/L, Group T3,n=147). The data were analysed by one-way Anova method and multiple stepwise linear regression model was used to explore the risk factors which affected HOMA-IR in newly diagnosed GDM patients.

Compared with that of Group T1, maternal body mass index(BMI)in Group T2 and T3 were signifcantly higher(both P< 0.05); total cholesterol(TC)level in Group T3 increased obviously and TG levels in Group T2 and Group T3 were significantly higher(allP<0.05); High density lipoprotein-cholesterol(HDL-C)level in Group T3 was lower, fasting plasma glucose(FPG)level and 1 h postprandial plasma glucose(1 hPG)level in Group T3 were higher(allP<0.05); fasting insulin(FINS)level in Group T2 and T3, 1 hINS level in Group T3, 2 h postprandial insulin(2 hINS)level in Group T2 and T3 were all elevated significantly(allP<0.05). Meantime, compared with that of Group T1, maternal HOMA-IR in Group T2 and T3 were elevated obviously (2.0±1.3, 2.7±1.2, 3.3±2.7 respectively,F=16.745, P<0.05), and maternal QUICKI in Group T2 and T3 decreased significantly(1.5±0.5, 1.2±0.4, 1.1±0.4 respectively,F=21.110, P<0.05). However, HOMA-β of three groups were almost at the same level. The multiple stepwise linear regression analysis indicated that BMI(standardized coefficient β =0.210), TG(β =0.135), 2 hINS(β =0.394)and age(β =-0.118)were significantly associated with HOMA-IR in newly diagnosed GDM patients(allP<0.05).

For the newly diagnosed GDM patients, insulin resistance worsens and insulin sensitivity reduces following the elevated fasting serum levels of triglyceride. Except increased BMI, higher 2 hINS level and younger age, higher TG level is independent risk factor for insulin resistance in those patients.

To investigate the relationship between lipoprotein-associated phospholipase (Lp-PLA2) and postpartum abnormal glucose metabolism in patients with gestational diabetes mellitus(GDM).

All of 190 women with GDM and 261 healthy pregnant women who delivered in the Department of Obstetrics in Guangdong Obstetrics and Gynecology Hospital were recruited from January 2009 to August 2012. Laboratory tests included serum activity of Lp-PLA2, blood glucose, serum lipids, etc. The follow-up study(including oral glucose tolerance test(OGTT) and glycated hemoglobin A1c(HbA1c))was performed from November 2012 to April 2013. The selected cases consisted of 172 women with GDM and 249 healthy women as control group.

(1)Postpartum abnormal glucose metabolism in GDM and the normal control group: type 2 diabetes mellitus(T2DM)(4.65%(8/172) vs 0%(0/249)), Pre-DM (39.53%(68/ 172) vs 12.45% (31/249)), the differences were statistically significant (P<0.05). (2)There were significant differences in variables between GDM and the normal control group:postpartum fasting blood glucose((4.5±0.7) vs (4.2±0.3) mmol/L,t=5.6, P<0.01), fasting insulin((9.7±4.9) vs (8.7±4.2) mmol/L,t=2.3, P<0.05), HOMA-IR(2.0±1.3 vs 1.7±1.1,t=2.6, P<0.05). (3) Lp-PLA2 activity: (33±11) vs (24±8) nmol·min^-1·ml^-1. (4) Lp-PLA2 was the risk factor of postpartum abnormal glucose metabolism (P=0.001). Receiver operating characteristic curve(ROC) analysis showed that Lp-PLA2 = 27.96 nmol.min^-1.ml^-1 was a demarcation point to diagnose postpartum abnormal glucose metabolism. The sensitivity and specificity are 71.3% and 82.1%, respectively.

Women with GDM have a higher risk of postpartum abnormal glucose metabolism. Lp-PLA2 is positively correlated with abnormal glucose metabolism in women with previous GDM.

To evaluate the efficacy and safety of Tianmaixiaoke tablet combined with metformin in the treatment of newly diagnosed type 2 diabetes mellitus.

A total of 150 newly diagnosed type 2 diabetics including 83 men and 67 women aged 33-71 years were randomly assigned to two groups. Patients in combination treatment group received Tianmaixiaoke(2 tablet, bid)combined with metformin(500 mg, tid), while patients in the control group received metformin(500 mg, tid) only, and then followed-up for 12 weeks. All patients were required to receive laboratory examination before and after treatment, including glycosylated hemoglobin(HbA1c), fasting plasma glucose(FPG), 2 h postprandial blood glucose(2 hPG), and other related indicators as efficacy endpoints. Safety endpoints included adverse events and hypoglycemia. The independent samples t-test was used to test differences between two groups. A paired t test was used to test differences before and after treatment in the same group. Differences in ratio variables were tested by the χ ² test.

A total of 134 patients were included in the final analysis, including 65 in combination therapy group and 69 in control group.(1)HbA1c: After 12-week treatment, the reduction of HbA1c from baseline in combination therapy group was far more than in control group((1.0±0.8)% vs(0.7±0.6)%; t=-3.205, P<0.05). The HbA1c compliance rate in combination therapy group was higher than control group(44.9% (31/69), 26.2% (17/65), respectively, χ²=5.131, P< 0.05).(2)Blood glucose: The level of FPG (2.7±1.4) and 2 hPG (5.2±2.9) in the combination therapy group was significantly lower than those in the control group (2.0±1.8, 3.8±2.4, respectively,t=-2.675, -2.930, both P<0.01). (3) HOMA-IR: Compared with the control group, the HOMA-IR in the combination therapy group reduced more significantly(2.7±0.8 vs 3.2±0.8, respectively,t=4.62, P< 0.05). There was no statistically significant difference between the both groups in HOMA-β index(t=-2.337, P> 0.05). (4) Adverse reaction: There was not statistically significant difference between the two groups in the incidence of adverse reactions.

Tianmaixiaoke tablet combined with metformin may increase the HbA1c compliance rate, improve insulin resistance, and has a good safety in the treatment of newly diagnosed type 2 diabetic mellitus.

To investigate the association between serum irisin and insulin resistance.

Eighty two subjects with type 2 diabetes mellitus(T2DM) were selected from in-patients in Department of Endocrinology, the First Affiliated Hospital, Zhejiang University School of Medicine (including 48 men and 34 women) as type 2 diabetes group, and 62 control subjects (NC) were selected from healthy people in medical centre (including 33 men and 29 women) as normal control group. Anthropometric indexes, metabolic parameters and serum irisin levels were measured in all subjects. Fasting insulin(FINS), postprandials blood glucose was measured in T2DM group. The data were analyzed using student-t test, Pearson correlation analysis and multiple linear regression analysis.

Serum irisin levels were significantly decreased in T2D group compared with NC group((1.5±0.6)vs (2.6±0.6)ng/L, t=-10.233, P< 0.05). Pearson correlation analysis showed serum irisin levels in T2DM group were inversely associated with waist hip ratio (WHR), 2 hour-postprandial blood glucose and homeostasis model assessment of insulin resistance (HOMA-IR)(r=-0.603,- 0.295,- 0.22,P<0.05). Other clinical parameters, including disease duration, gender, age, smoking habit, diabetic complications, other complications, body mass index (BMI), systolic blood pressure, diastolic blood pressure, fasting blood glucose (FBG), glycated hemoglobin A1c (HbA1c), FINS, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), serum total cholesterol (TC), total triglycerides (TG) and atherosclerosis index (AI), were not correlated with irisin levels(P>0.05 all above). Multiple linear regression analysis showed that after adjusting for gender, age, blood pressure, diabetic complications and other complications, WHR was significantly negatively associated with serum irisin levels, and WHR was the negative independent determinant of serum irisin (standardized regression coefficient =-3.995, P<0.05).

Serum irisin levels are decreased in patients with T2DM and associated with the development of insulin resistance.

To compare the plasma protein expressions of fatty acid binding protein 4 (FABP4)and phosphatase and tensin homolog deleted on chromosome ten(PTEN)in patients with impaired glucose regulation(IGR) and newly-diagnosed type 2 diabetes mellitus(T2DM), and investigate whether they can be the early biochemical markers of glucose metabolism disorders.

From January to December 2013, 65 newly-diagnosed T2DM patients(34 obese patients and 31 non-obese patients), 32 impaired glucose regulation(IGR) patients and 30 healthy subjects were included in this study. Among the IGR and T2DM groups, 48 were male, 49 female and mean age was (47±11) years, while in healthy subjects, 14 were male, 16 female and mean age was (41±11) years. Plasma protein expression levels of FABP4 and PTEN were measured using enzyme-linked immunosorbent assay (ELISA), and other indicators such as fasting glucose and lipids were detected in the meantime. One-way ANOVA was used to compare quantitative data among groups. Pearson correlation analysis was used for correlation analysis between the two variables, and Multiple stepwise regression analysis was used to determine the independent factors of HOMA-IR.

(1)The plasma concentration of FABP4 in the normal control group, IGR group, non-obese and obese groups of diabetes was (31±4), (34±5), (34±4) and (34±5)ng/L, respectively. Plasma FABP4 concentrations increased in the IGR group, non-obese and obese group of diabetes compared with the control group(t value was 2.057, 2.369 and 3.094, respectively, all P<0.05). (2) The plasma concentration of PTEN in the normal control group, IGR group, non-obese and obese group of diabetes was (2.9±0.5), (3.8±0.6), (3.7±0.7) and (3.8±0.5)μg/L, respectively. Compared with control group, the plasma concentrations of PTEN increased in IGR group, non-obese and obese groups of diabetes (t value was 6.049, 5.509 and 5.798, respectively, all P<0.05). (3) The levels of FABP4 and PTEN were positively correlated (r=0.361, P<0.01) in all the subjects. Multiple stepwise regression analysis showed that triglyceride, body mass index, FABP4 and PTEN were independent variables of HOMA-IR.

FABP4 and PTEN might be the early biochemical markers of glucose metabolism disorders, and there might be an interaction between FABP4 and PTEN with insulin resistance in type 2 diabetic patients.

To make comparative analysis of the glycated hemoglobin A1c(HbA1c) values obtained by three HbA1c test methods in patients with variant hemoglobins.

Total of 50 blood samples of patients with different types of variant hemoglobin were collected from January 2012 to December 2012; 25 of them (14 males and 11 females) carried hemoglobin D, Q, G, J and E with a mean age of (24±3) years; the other 25 cases (11 males and 14 females) were blood samples with hemoglobin F from newborn infants. Meanwhile, 50 blood samples(25 males and 25 females) from people without variant hemoglobins were also collected as control(mean age (25±5) years). Three methods were used to test HbA1c, which were affinity high performance liquid chromatography (HPLC) method (Ultra 2 of American Primus), ion exchange HPLC method (VariantⅡ of American Bio-Rad and G8 of Japanese Tosoh) and immunization method (DCA Vantage of German Siemens). The statistic analysis were done with variance analysis and correlation analysis.

The HbA1c of the group with normal HbA1c structure was 5.7%±1.1%, 5.7%±1.2%, 5.7%±1.2% and 5.7%±1.1% respectively when it was tested by affinity HPLC method (Ultra2), ion exchange HPLC method (G8), ion exchange HPLC (Variant Ⅱ) and immunization method (DCA Vantage), and there was no significant difference among the groups (F=0.023, P>0.05). In the 25 samples with hemoglobin F, HbA1c could not be detected by ion exchange HPLC or immunoassay method. The fasting blood glucose level correlated with HbA1c level tested by Ultra 2 method (r=0.647, P<0.05), but it didn't correlate with HbA1c level when tested with VariantⅡ and G8 as well as DCA Vantage method. The HbA1c result of affinity HPLC method was free from the disturbance of Hb D, Q, G, J and E, and had a obvious correlation with blood glucose (r=0.823, P<0.05). The HbA1c result of ion exchange HPLC method was disturbed by hemoglobin D, Q, G, J and E in varying degrees. The HbA1c measured by immunization method was associated with blood glucose (r=0.611, P<0.05).

The HbA1c value obtained by affinity HPLC method can accurately reflect the mean blood glucose level. Variant hemoglobins disturb the HbA1c result tested by ion exchange HPLC method, and the immunization test result is only disturbed by hemoglobin F.

This study tested serum retinol-binding protein 4 (RBP4) level in type 2 diabetic mellitus (T2DM) patients with lower limb ischemia (LLI) and non-lower limb ischemia (NLLI) to investigate the relationship between serum retinol-binding protein 4 levels and lower limb ischemia in type 2 diabetic population.

A total of 755 type 2 diabetic in-patients and out-patients in Shanghai Clinical Medical Center from Jul 2011 to Jun 2012 were included in this cross-sectional study. Their clinical and biochemical characteristics, ankle-brachial index (ABI), lower extremity arterial ultrasound were detected. LLI was defined by ABI< 0.9 and lower extremity arterial stenosis>50% by ultrasound examination. According this standard, patients were divided to two groups: LLI group (n=105) and NLLI group (n=650). Body mass index (BMI), waist circumference, blood pressure, RBP4, blood glucose, serum lipid, estimated glomerular filtration rate (eGFR), intima-meida thickness (IMT) were measured to compare the difference of clinical character and RBP4 level between two groups. The patients were grouped by the quartiles of RBP4 to compare the difference of clinical character and the incidence of LLI. Two groups of continuous variables were compared by the t test. Multiple groups of continuous variables were compared by ANOVA test. The association between RBP4 and other variables were evaluated with Spearman correlation.

There were significant differences in age ((72±9) vs (57±12) yrs, t=16.48, P<0.05), duration of diabetes ((13 (8-20) vs 8 (4-13) yrs,t=5.84, P<0.05), systolic blood pressure (SBP (140±20) vs (130±18) mmHg,t=3.45 P<0.05), total cholesterol (TC (4.7±1.0) vs (4.5±1.1) mmol/L,t=-2.07,P<0.05), serum RBP4 ((47(37-54) vs 43(37-51) mg/L,t=2.16, P<0.05) and incidence of hypertension (80.0% vs 50.7%,χ²=31.40, P<0.05), coronary artery disease (24.8% vs 10.9%,χ²=15.40,P<0.05), cerebral infarction (22.9% vs 6.8%,χ²= 28.29,P<0.05) between LLI group and NLLI group. After adjusting for age, duration, eGFR and hypertension, Spearman correlation analysis showed that serum RBP4 level was positively correlated with TC, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), fasting C-peptide, 2 h-postprandial C-peptide, IMT (r=0.27, 0.37, 0.12, 0.17, 0.24, 0.10, respectively, P<0.05). Logistic regression analysis showed that age, hypertension, RBP4 were independent associated factors for LLI (OR=1.166, 2.297, 1.023, P<0.05 all above). Comparisons of patients with quartiles of RBP4 revealed that the levels of BMI, waist circumference, SBP, IMT, TC, TG, LDL-C level increased with the increasing of serum RBP4 concentration (F=4.31, 7.44, 8.01, 2.99, 15.81, 28.27, 3.99, P<0.05). There was significant difference in the incidence of LLI between four groups (χ²=11.66 P<0.05).

RBP4 was associated with lower limb ischemia in type 2 diabetic patients. High serum RBP4 concentration predicts the increasing risk of lower limb ischemia in type 2 diabetic patients.

To investigate the effects and mechanism of glucagon-like peptide-1 agonist exenatide on hepatic insulin resistance in high-fat diet and low-dose streptozotocin-induced diabetic rats.

Twenty-two 6-week-old male SD rats were randomly divided into non-diabetic control group (C, n=6), non-diabetic+exenatide group (C+E, n=6), diabetic group (D, n=5) and diabetic+exenatide group (D+ E, n=5). Among them, the diabetic rats were induced by high-fat diet and low-dose streptozotocin. After eight weeks, isotope tracer technology was used to check the rate of appearance of glucose(GRa), glycerol (GRa') and gluconeogenesis following infusion of 3-³H-glucose and U-¹³C-glycerol. Hepatic glucose production (HGP) and the rate of glucose infusion (GIR) were assessed using a hyperinsulinemic-euglycemic clamp with infusion of 3-³H-glucose. Meanwhile, the ultrastructure changes of the rats' liver were further studied. The one-way ANOVAs followed by a Student-Newman-Keuls post hoc test for multiple comparisons were used for statistics.

In the D+E group, fasting blood glucose, triglyceride, total cholesterol, lower density lipoprotein, and homeostasis model assessment for insulin resistance (HOMA-IR) were significantly decreased compared with those in the D group, but still significantly higher than those in the C and C + E group (F=82.827,81.648, 27.613, 26.300, 105.234, all P<0.05). In the D+E group, the GRa, GRa' HGP and GNG parameters (glycerol converted to glucose %, glucose derived from glycerol, gluconeogenesis from glycerol) were also decreased compared with the D group, but still significantly higher than that in the C and C + E group (F=68.424, 41.543, 68.424, 40.223, 17.491, 86.465, all P<0.05), while the exogenous glucose infusion rate were markedly increased compared with the D group, but still significantly lower than those in the C and C + E group (F=49.954, P<0.05). At the same time, ultrastructure observation revealed that exenatide attenuated the swollen mitochondrial and endoplasmic reticulum inside the cells of liver of the diabetic rats.

The glucagon-like peptide-1 agonist, exenatide, can significantly improve hepatic insulin resistance through alleviating the ultrastructure damage of the hepatic cells in the diabetic rats.

To explore the effect of liraglutide on function of human umbilical vein endothelial cells (HUVECs) and its underlying mechanism in high glucose environment.

HUVECs were cultured in high glucose environment (glucose concenrtration 25 mmol/L), and treated with different concentrations of liraglutide (0,10,100,1 000 μg/L, respectively). Real-time polymerase chain reaction(RT-PCR) and Western blotting were used to measure the mRNA and protein expressions of endothelial nitric oxide synthase (eNOS), induced nitric oxide synthase(iNOS) and phosphate nuclear factor kappa B p65 (p-NF-κB p65). Tumor necrosis factor-α(TNF-α) was used to incubate HUVECs after liraglutide treatment, before the measurements for eNOS, iNOS, NF-κB p65 on mRNA and protein levels. One-way ANOVA was used to analyze multiple means and SLD analysis for comparison between two groups.

Compared with normal medium (glucose concenrtrations for 7 mmol/L), both the mRNA and the protein expressions of eNOS in HUVECs were significantly decreased in high glucose medium, while those of iNOS and p-NF-κB p65 protein were significantly increased (t=2.79, 5.75, 4.32, 4.85, 7.12, P<0.05). Compared group treated with 0 μg/L of liraglutide, 1 000 μg/L of liraglutide significantly increased mRNA and protein expressions of eNOS, while significantly decreased those of iNOS and p-NF-κB p65 protein (t= 5.12, 9.34, 6.70, 5.50, 8.94, P<0.05). Compared with liraglutide alone treated HUVECs, both the mRNA and the protein expressions of eNOS were significantly decreased in HUVECs treated with TNF-α and liraglutide, while those of iNOS and p-NF-κB p65 protein expression increased significantly(t=3.33-7.87, P< 0.05).

Liraglutide enhances eNOS, represses iNOS expressions at the level of transcription and translation through inhibiting NF-κB p65 phosphorylation in HUVECs in high glucose environment. This may contribute to the improvement of endothelial function and prevention of subsequent atherogenesis.

To explore the effect of spironolactone to NRK-52E's senescence in high glucose culture.

NRK-52E cells was divided into five groups, which were a,b,c,d and e group. Group a: cells were in only high glucose culture(25.6 mmol/L glucose). Group b was interfered with aldosterone(10^-5 mmol/L), while the other groups were treated by different dose of spironolactone(group c: low dose with 10^-7 mmol/L spironolactone, group d:medium dose with 10^-6 mmol/L spironolactone, and group e: high dose with 10^-5 mmol/L spironolactone) before aldosterone was added into high glucose culture. After these interventions, cell aging would be tested by β-galactosidase while mRNA and protein expression of Klotho, p53, p21 and β-actin would be detected by qPCR and Western Blot.

(1) After different exposure as above for 72 hours, the senescent cells proportion of group a, b, c, d and e were (47.9±4.7)%, (49.0±5.2)%, (38.2±4.1)%, (39.7±3.8)%, (42.1±3.9)%, respectively. Comparing the aging cells positive rate of each group in 72 hour, the chi-square was 45.850. The aging cells ratio increased despending the time. Compared with group a and b, the ratio of group c,d and e decreased followed by different doses of spironolactone(P<0.01). (2) Compared with group a, the Klotho mRNA expression of group b decreased while the p53 mRNA and p21 mRNA increased obviously(P<0.05). The Klotho mRNA levels of each group were 1.13±0.09, 0.85±0.02, 1.42±0.11, 1.37±0.08 and 1.14±0.06, respectively(F= 8.134, P<0.01). The expression of p53 mRNA of each group were 0.62±0.13, 0.93±0.15, 0.45±0.06, 0.51±0.09 and 0.61±0.09, respectively(F= 9.629, P<0.05). As p21 mRNA, they were 0.74±0.06, 1.05±0.05, 0.42±0.02, 0.61±0.07, 0.72±0.03, respectively(F= 5.450, P<0.05).(3)Comparison with group b, Klotho of group c, d and e, Whatever mRNA or protein expression, increased at different level, while p53, p21 had the opposite results. Klotho protein expression had the negative correlation with p53 and p21(r=-0.744, r=-0.627, P<0.05).

Aldosterone may accelerate NRK-52E aging, while spironolactone can prevent it through MR/ Klotho/p53/p21 signal way.

Due to the disorder of glucose and lipid metabolism, gestational diabetes mellitus (GDM) not only increases the complications of perinatal mothers and offspring, such as gestational hypertension, high cesarean section rate, macrosomia and neonatal hypoglycemia, but also causes the fetus to be in a high nutritional state in the uterus, which in turn leads to fetal metabolic disorders, even abortion and stillbirth^[1]。 Professor Barker, a British environmental epidemiologist, put forward the hypothesis of fetal origin of chronic diseases in adults in 1986^[2]Since then, several studies have shown that early-life nutritional status is closely related to the incidence of hypertension, coronary heart disease, stroke, type 2 diabetes, obesity, and metabolic syndrome in adulthood^[3,4]。 At present, the research on nutritional status in early life has involved birth weight, birth size, food intake and growth and development status of fetus. In 2006, the Executive Committee on Nutrition of the World Health Organization proposed that "the period from pregnancy to two years after birth is the window of opportunity to prevent chronic diseases in adulthood through nutritional interventions". The nutritional metabolism status of newborns has been widely concerned. Dyslipidemia is an important component of metabolic disorders in neonates with GDM, and the offspring of GDM have an increased risk of long-term metabolic diseases such as obesity and type 2 diabetes in adulthood^[5,6]。 This article reviews the influence of GDM on neonatal lipid metabolism, which is of great significance for clinical prevention of adverse pregnancy outcome, ensuring healthy growth and development of perinatal infants and preventing metabolic diseases in adulthood.

Islet β-cell dysfunction and insulin resistance are important pathogenesis of type 2 diabetes mellitus (T2DM). In the natural course of the disease, the function of β cells has begun to decline several years before the onset of diabetes. With the progression of the disease, the total amount of β cells gradually decreases, and its function is not enough to maintain the homeostatic regulation of blood sugar in the body, thus causing hyperglycemia. The decline of β-cell function is a prerequisite for the development of diabetes and a central link in its development. The British Diabetes Prospective Study (UKPDS) revealed that at least 50% of beta cell function was lost when patients were diagnosed with T2DM, and it worsened with the course of the disease. Therefore, preventing or reversing the progressive decline in the total amount and function of beta cells is an important strategy for the treatment of T2DM.

Bile acid (BA) is synthesized and secreted by liver cells and constitutes an important component of bile. The synthesis of bile acid is the main pathway of cholesterol catabolism in the body, and plays an important role in lipid absorption and cholesterol metabolism balance. Recent studies have shown that bile acid also plays an important role in sugar metabolism balance. Colevilon, a bile acid chelator, was approved in 2008 to control blood glucose levels in patients with type 2 diabetes mellitus (T2DM)^[1]Phase III clinical trials have shown that colevilon can improve blood glucose and low-density lipoprotein cholesterol (LDL-C) levels in T2DM patients with poor glycemic control after receiving metformin, sulfonylurea or insulin-based therapy^[2]。 In addition, INT-777, a semi-synthetic bile acid derivative, can stimulate glucagon-like peptide 1 (GLP-1) secretion through the G protein-coupled bile acid receptor, the Gpbar1 (TGR5) signaling pathway, thereby increasing insulin secretion and improving glucose tolerance^[3]。 Holst and Mcgill^[4]It is further reported that colevilon can increase intestinal secretion of GLP-1 and improve glucose metabolism in patients with T2DM. Bile acid analogs and bile acid chelators may become new options for the treatment of T2DM in the future. Meanwhile, Patti et al.^[5]Increased bile acid concentrations were also found in obese patients after Rouxen-Y gastric bypass (RYGBP) surgery, and there was an inverse correlation between plasma bile acids and 2 h postprandial blood glucose concentrations, and a positive correlation with adiponectin and peak postprandial GLP-1 concentrations. These studies suggest that changes in glucose metabolism after gastric bypass are closely related to bile acid levels. This paper reviews the biological effects of bile acids in the regulation of farnesate derivative x receptor (FXR) and TGR5-signaling pathway of glucose metabolism in vivo and after Roux-en-Y surgery.

Islet cell transplantation is an ideal treatment for type 1 diabetes mellitus (T1DM). Since the development of islet transplantation, new progress has been made in islet cell transplantation technology^[1]However, the scarcity of donors and the need for lifelong use of immunosuppressants after surgery restrict its extensive clinical development. Immunosuppressants are a class of drugs that have an inhibitory effect on the body's immune response. By inhibiting the proliferation and function of cells related to immune response (T lymphocytes, B lymphocytes and macrophages, etc.), they reduce the body's immune response. Immunosuppressants are the most commonly used and important therapeutic drugs to ensure the success of pancreatic islet transplantation, but they have side effects such as liver and kidney toxicity, and long-term use will also increase the risk of infection and tumor. This article will review the representative immunosuppressive agents used in the field of pancreatic islet transplantation, and review the application progress of immunosuppressive regimen in the field of pancreatic islet transplantation.

Patients with type 2 diabetes mellitus (T2DM) have increased risk of cardiovascular disease and cardiovascular mortality^[1,2]It is estimated that 70% to 75% of patients with T2DM die from cardiovascular complications^[3]。 At the end of 2008, the U.S. Food and Drug Administration (FDA) required clinical trial data of the new drug to be provided when submitting a new drug application for T2DM to confirm that the new drug does not increase cardiovascular risk. Subsequently, the European Medicines Agency (EMA) and the Chinese Food and Drug Administration (SFDA) also required that clinical trials should have sufficient time and sample size to detect cardiovascular adverse events to demonstrate no drug-induced cardiovascular risk. In this paper, the cardiovascular effects of linagliptin, a novel dipeptidyl peptidase IV (DPP-4) inhibitor, will be reviewed.

The logical sequential treatment of type 2 diabetes mellitus (T2DM) needs to take into account both the early stage of the disease (insulin resistance, early β-cell dysfunction and risk of microvascular and macrovascular lesions) and the advanced and late stages of the disease (severe β-cell dysfunction and microvascular and macrovascular lesions). Treatment strategies mainly include active treatment with early oral hypoglycemic drugs, followed by the activation of basal insulin when oral drugs are not well controlled, and further treatment upgrades include basal insulin + preprandial insulin therapy to comprehensively control hyperglycemia and postprandial blood glucose fluctuations.

Diabetic foot is one of the common chronic complications of diabetes. Foot ulcer can aggravate the personal, family, social and economic burden of diabetic patients. Diabetic foot needs timely and correct diagnosis and treatment. In order to evaluate the relationship between endothelial progenitor cells, cytokines and ulcer healing in diabetic foot patients, a research team from the United States followed up healthy people, low-risk diabetic foot ulcer patients, high-risk diabetic foot ulcer patients and active diabetic foot ulcer patients for 12 weeks to observe the changes of endothelial progenitor cells and cytokines, and also observed the changes of the above indexes in ulcer healing in diabetic rabbit and mouse models.

Chronic unhealed wounds in diabetic patients are extremely difficult to manage and bring a serious medical burden to these patients and society as a whole. Negative pressure wound therapy (NPWT) is widely used in the treatment of various refractory wounds, and the effect is remarkable. However, the mechanism of the therapy has not been fully elucidated.

Diabetic foot is a common chronic complication of diabetes in clinical practice, and it is the main cause of amputation in diabetic patients. Studies have confirmed that wearing customized diabetic foot orthopedic shoes can prevent foot ulcers in diabetic patients. However, the current high recurrence rate of foot ulcers in diabetic patients makes people have to consider the following questions: Is the recurrence of diabetic foot ulcers related to the patient's compliance with wearing diabetic orthopedic shoes?

Treatment options for diabetic foot osteomyelitis are often based on the site of infection, local blood supply, degree of soft tissue and bone destruction, presence or absence of necrosis, presence or absence of systemic infection, and patient and clinician preferences. Surgery has always been the primary treatment, but the use of antibiotics avoids surgical costs and potential complications. Both approaches have their own advantages, so the best treatment options are currently debated.

The American Society of Infectious Diseases (IDSA) classifies diabetic foot infections (DFI) into three categories: mild, moderate and severe according to the manifestations of local and systemic infections in patients with diabetic foot. It has been previously documented that the more severe DFI, the higher the risk of amputation and hospitalization. In the past, the distinction between moderate and severe DFI mainly depends on systemic toxemia symptoms or metabolic imbalance (chills and fever, tachycardia, hypotension, confusion, white blood cell elevation, acidosis, severe hyperglycemia or azotemia). At present, IDSA has put forward a new view, that is, systemic inflammatory response (SIRS) is used to distinguish between moderate and severe DFI.