[Primary culturing and effects of insulin glargine on proliferation, differentiation of human preadipocytes from subcutaneous and omental adipose tissue].

OBJECTIVE: To compare the morphological and functional differences of human primary preadipocytes from different fat depots and explore the effects of insulin glargine on their proliferation and differentiation. METHODS: Primary preadipocytes isolated from human subcutaneous and omental adipose tissue by collagenase I were passaged in vitro.Inverted phase contrast microscope was used to observe the morphological differences of two kinds of preadipocytes. Then two kinds of preadipocytes were cultured or induced to differentiation with different doses of insulin glargine. The methyl thiazolyl tetrazolium (MTT) assay was used to detect their proliferative differences.Reverse transcription-polymerase chain reaction (RT-PCR) was used to observe the effects of insulin on adipogenic gene expression. RESULTS: (1) Both preadipocytes could be successfully cultured from adipose tissue and amplified in vitro.Subcutaneous preadipocytes were more slender and proliferated more quickly while omental preadipocytes were polygonal and aged easily.(2) MTT results showed that insulin glargine could inhibit the proliferation of omental preadipocytes in a dose-dependent fashion. After 72 h incubation, compared with negative control, the absorbance (A) value of 1000 nmol/L insulin glargine group decreased greatly (0.144 ± 0.021 vs 0.267 ± 0.040, P < 0.01). But it had no effect on subcutaneous preadipocytes (0.305 ± 0.045 vs 0.350 ± 0.037, P > 0.05). (3) Insulin at 500 nmol/L was a suitable concentration for inducing differentiation.RT-PCR analysis showed that, for subcutaneous adipocytes, adipogenic genes such as peroxisome proliferator-activated receptor gamma (PPARγ) (F = 31.31, P < 0.01) and CCAAT enhancer binding protein α (C/EBPα) (F = 9.86, P < 0.05) had the highest mRNA expression while preadipocytes gene Pref-1 had the lowest expression at this concentration. But insulin dose had no obvious effect on PPARγ or C/EBPα mRNA (P > 0.05) for omental adipocytes. CONCLUSION: Insulin glargine could inhibit the proliferation of omental preadipocytes, and enhance the differentiation of subcutaneous and omental preadipocytes.

Effects of a combination of oral anti-diabetes drugs with basal insulin therapy on ß-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes.

BACKGROUND: Oral anti-diabetes drugs plus basal insulin (OAD + insulin) therapy in patients with newly diagnosed type 2 diabetes might improve ß-cell function and result in extended glycaemic remission. This randomised trial compared the effect on ß-cell function and diabetes remission rate between oral drug alone or with addition of basal insulin. METHODS: One hundred and twenty-nine patients, aged 35-50 years, were enrolled between June 2005 and June 2009. For initial correction of hyperglycaemia, patients with fasting plasma glucose ≥9.0 mmol/L and HbA(1c) ≥ 9.0%, were randomly assigned to therapy with oral drugs + insulin or oral drugs alone. Treatment was stopped after normoglycaemia was maintained for 3 months. Patients were then followed-up with diet and physical exercise. Blood glucose, HbA(1c) and insulin were measured prior to treatment and at 1-year follow-up. RESULTS: More patients achieved target glycaemic control in the oral drugs + insulin group [98.3% (58 of 59)] in less time [(10.4 ± 2.5) days] than those in the oral drug group [95.7% (67 of 70) and (12.4 ± 3.4) days]. At 1-year follow-up, more patients maintained target glycaemia without any drugs in the oral drug + insulin group than in the oral drug group [37.9% (22 of 58) vs 20.9% (14 of 67)]. Both treatments improved homeostasis model assessment-ß (HOMA-ß) and homeostasis model assessment-insulin resistance (HOMA-IR) significantly. They had similar effects on insulin resistance [lg(HOMA-IR): (0.50 ± 0.09) vs (0.48 ± 0.09), p = 0.23]. However, oral drugs + insulin could recover ß-cell function much more than OAD alone could [lg(HOMA-ß): (2.17 ± 0.14) vs (2.11 ± 0.13), p = 0.03]. CONCLUSION: In newly diagnosed type 2 diabetes, therapy with oral drugs + insulin has had favourable outcomes on recovery and maintenance of ß-cell function and protracted glycaemic remission compared with treatment with oral drugs alone.

[Depot-specific expression of caveolin-1 in human adipose tissue and their relationship with obesity and insulin resistance].

OBJECTIVE: To explore the depot-specific mRNA and protein expression of caveolin-1 (CAV-1) in human subcutaneous and omental adipose tissues and analyze their relationship with obesity and insulin resistance. METHODS: A total of 41 subjects with normal glucose regulation were recruited. Among them, there were 29 cases with normal body mass index (BMI) and 12 cases with BMI ≥ 24 kg/m(2). All were scheduled to undergone selective abdominal operations. The levels of fasting insulin (FINS) were measured by chemiluminescence enzyme-linked immunosorbent assay (ELISA) kit. Fasting plasma glucose (FPG) was tested by glucose oxidase and home model insulin resistance index (HOMA-IR) calculated. Real-time polymerase chain reaction (RT-PCR) and Western blotting were employed to assess the relative mRNA and protein expression of caveolin-1 in subcutaneous and omental adipose tissues. And the mRNA and protein expression of caveolin-1 from different fat depots were compared and their correlations with BMI and HOMA-IR analyzed. RESULTS: (1) FINS and HOMA-IR were significantly higher in the overweight and obesity group than those in the normal BMI group (FINS: (8.82 ± 3.79) mU/L vs (6.43 ± 4.38) mU/L, P < 0.05, HOMA-1R: 1.91 ± 0.85 vs 1.36 ± 0.72, P < 0.05). (2) The normal BMI group patients had the higher expression levels of caveolin-1 mRNA in omental adipose tissue than overweight counterparts (2.84 ± 0.86 vs 1.02 ± 0.36, P < 0.01). But the difference in subcutaneous adipose tissue was not significant (P > 0.05). (3) The caveolin-1 protein expression in omental adipose tissue of the normal BMI group was higher than that of overweight patients (1.68 ± 0.67 vs 0.73 ± 0.29, P < 0.05). And the difference between two groups was not significant (P > 0.05). (4)The expressions of caveolin-1 mRNA in omental adipose tissue were negatively correlated with BMI, waist circumstance, triglyceride and HOMA-IR (r = -0.441, -0.615, -0.539, -0.688, P < 0.05). No correlations were found between the expressions of caveolin-1 mRNA in subcutaneous adipose tissue with BMI, waist circumstance and HOMA-IR (P > 0.05). CONCLUSION: Differential depot-specific expressions of caveolin-1 are present in human subcutaneous and omental adipose tissues. A low expression of caveolin-1 in omental adipose tissue may contribute to the pathogenesis of obesity and insulin resistance.

[Characteristics of real-life glucose profiles monitored by continuous glucose monitoring system in persons with normal glucose tolerance].

OBJECTIVE: To decipher the characteristics of real-life glucose profiles in normal glucose tolerance (NGT) persons by continuous glucose monitoring system (CGMS). METHODS: Forty NGT subjects confirmed by oral glucose tolerance test (OGTT) completed a 3-day period of glucose monitoring via CGMS. RESULTS: The values of 24 h mean blood glucose (MBG), standard deviation of MBG (SDBG), mean amplitude of glycemic excursions (MAGE), largest amplitude of glycemic excursions (LAGE) and means of daily differences (MODD) were 6.0 ± 0.7, 0.9 ± 0.1, 1.9 ± 0.8, 2.9 ± 1.4 and 1.1 ± 0.1 mmol/L respectively. Two of them experienced asymptomatic hypoglycemia defined as glucose concentration < 2.8 mmol/L. And 72.5% (29/40) subjects reached glucose concentrations > 7.8 mmol/L for 5.2 ± 4.6 hours. In addition to higher glucose concentration (FPG: 5.0 ± 0.4 vs 4.8 ± 0.3 mmol/L, MBG: 6.4 ± 0.7 vs 5.7 ± 0.5 mmol/L), the subjects with glucose concentrations > 7.8 mmol/L showed more dramatic glucose excursion represented by higher SDBG (1.1 ± 0.3 vs 0.6 ± 0.2 mmol/L), MAGE (2.3 ± 1.1 vs 1.1 ± 0.3 mmol/L), LAGE (3.3 ± 1.2 vs 2.0 ± 1.0 mmol/L) and MODD (1.2 ± 0.4 vs 0.9 ± 0.3 mmol/L) versus those with glucose concentrations within 7.8 mmol/L. CONCLUSION: CGMS provides more detailed information of real-life glucose profiles in NGT subjects. And 72.5% NGT subjects in the present study spent a considerable amount of time at pre-diabetic or even diabetic glucose levels characterized by more predominant glucose excursion.

[Cross-sectional study of current situation of glycemic control with type 1 diabetes in Guangdong Province].

OBJECTIVE: To investigate the glycemic control and the related factors of type 1 diabetic patients in Guangdong Province. METHODS: Medical records and blood samples of type 1 diabetic patients were collected in 89 tertiary and secondary hospitals from all of the 21 cities in Guangdong Province. The clinical data were analyzed to explore the correlates of glycemic control. HbA1c levels, measured in Guangdong Diabetes Center, were used to assess glycemic control. RESULTS: 851 patients were enrolled from August 6, 2010 to May 25, 2011. There were 408 males and 443 females. The median (interquartile range) age was 29.6 years (20.3 - 41.3 years). The onset age of diabetes was 25.3 years (15.7 - 35.5 years). The disease duration was 3.3 years (1.0 - 7.3 years). The BMI was 19.9 kg/m(2) (17.9 - 21.8 kg/m(2)). HbA1c levels were 8.6% (6.9% - 11.0%) and only 234 (27.50%) patients reached the age-specific target levels. Correlates with poorer glycemic control were 13 - 19 years old (vs 7 - 12 and ≥ 20 years old), lower household income, not on dietary intervention, never accepting diabetic education and shorter diabetic duration. CONCLUSION: The majority of Guangdong type 1 diabetic patients did not achieve target values for glycemic control, indicating an urgent need for comprehensive management to improve glycemic control.

[The effects of early intensive therapy on islet beta cell function and long-term glycemia control in newly diagnosed type 2 diabetic patients with different fasting plasma glucose levels.].

OBJECTIVE: To investigate the effects of early intensive therapy on beta cell function and long-term glycemic control in newly diagnosed type 2 diabetic patients with different recruiting fasting plasma glucose (FPG) levels. METHODS: A total of 382 newly diagnosed type 2 diabetic patients with FPG 7.0 - 16.7 mmol/L were randomly assigned to therapy with insulin in the form of continuous subcutaneous insulin infusion (CSII) or multiple daily injection (MDI) or oral hypoglycemic agents (OHA, by using gliclazide and/or metformin) for initial rapid correction of hyperglycemia. The treatments were stopped after euglycemia had been maintained for 2 weeks. The patients were followed longitudinally on diet alone for 1 year. Intravenous glucose tolerances tests (IVGTTs) were performed and blood glucose, insulin and proinsulin were measured before and after therapy as well as at 1-year follow-up. Homeostasis model assessment (HOMA) of beta cell function and insulin resistance index (HOMA-beta and HOMA-IR) were calculated. All the patients were stratified on the recruiting FPG: stratum A (7.0 mmol/L

[Depot-specific expression of retinol-binding protein 4 in human adipose tissue and their relationship with obesity and insulin resistance].

OBJECTIVE: To explore the depot-specific mRNA and protein expression of retinol-binding protein 4 (RBP4) in human subcutaneous and omental adipose tissue and investigate their relationship with the serum RBP4 levels, obesity and insulin resistance. METHODS: A total of 41 subjects with normal glucose regulation were recruited. Among them, there were 29 cases with normal body mass index (BMI) and 12 cases with BMI ≥ 24 kg/m(2). All were prepared to undergone a selective abdominal surgery. The levels of serum RBP4 and fasting insulin (FINS) were measured by ELISA (enzyme-linked immunosorbent assay) and chemiluminescence ELISA kit respectively. Fasting plasma glucose (FPG) was tested by glucose oxidase and the home model insulin resistance index (HOMA-IR) calculated. Real-time PCR (RT-PCR) and Western blot were employed to assess the relative mRNA and protein expression of RBP4 in subcutaneous and omental adipose tissues. The mRNA and protein expression of RBP4 from different fat depots were compared and their correlations with BMI, the serum RBP4 concentrations and HOMA-IR analyzed. RESULTS: (1) The serum concentrations of RBP4, FINS and HOMA-IR were significantly higher in overweight and obesity group than those in the normal BMI group [RBP4: (39.61 ± 1.57) mg/L vs (33.40 ± 1.28) mg/L, P < 0.01; FINS: (8.82 ± 3.79) mU/L vs (6.43 ± 4.38) mU/L, P < 0.05; HOMA-IR: 1.91 ± 0.85 vs 1.36 ± 0.72, P < 0.05]. (2) The expression levels of RBP4 mRNA and protein were significantly higher in omental adipose tissues than those in subcutaneous adipose tissue [mRNA: (5.88 ± 2.37) vs (2.07 ± 1.66), P < 0.01; protein: (0.76 ± 0.18 vs 0.15 ± 0.07, P < 0.05] and these depots difference in both groups (P < 0.05). Moreover, the overweight patients had the higher expression levels of RBP4 mRNA and protein in omental adipose tissue than normal BMI group (mRNA: 7.52 ± 0.58 vs 4.37 ± 0.45, P < 0.01; protein: 0.92 ± 0.23 vs 0.57 ± 0.13, P < 0.05). (3) The expressions of both RBP4 mRNA and protein in the omental adipose tissue were positively correlated with BMI, waist circumstance, serum concentrations of RBP4, FINS and HOMA-IR. The expression of was negatively correlated with HOMA-IR (r = -0.635, P < 0.05) in subcutaneous adipose tissue. No correlations were found between the expressions of RBP4 mRNA and protein in subcutaneous adipose tissue with BMI, waist circumstance, serum RBP4 and FINS concentrations. CONCLUSIONS: There is depot-specific expression of RBP4 in human subcutaneous and omental adipose tissues. A high expression of RBP4 in omental adipose tissue and an elevated level of serum RBP4 may contribute to the pathogenesis of obesity and IR.

Comparison of two regimens for patients with thyroid-associated ophthalmopathy receiving intravenous methyl prednisolone: A single center prospective randomized trial.

Intravenous (i.v.) glucocorticoid is recommended for active moderate-to-severe thyroid-associated ophthalmopathy (TAO). However, the details of the treatment schedule are still debatable. The present prospective randomized trial was performed to compare clinical outcomes and serum cytokines between the two regimens. A cohort of 90 patients with active moderate-to-severe TAO was randomized to receive i.v. methyl prednisolone on a weekly protocol or daily scheme. The response rate was evaluated at the 12-week follow-up visit. Serum interleukin (IL)-2, IL-6 and IL-17 levels were measured in 160 patients with TAO, 60 patients with isolated Graves' disease (GD) and 60 normal control (NC) at baseline, as well as patients with active moderate-to-severe TAO at the 12th week after treatment. The daily scheme had a higher response rate than the weekly protocol without a significant difference (77.8 vs. 63.6%, P>0.05). No major adverse events were recorded under either regimen. Overall, minor events were more common on the daily scheme (11.36 vs. 4.35%, P<0.05)than on the weekly protocol, whereas the deterioration of eye symptoms (two patients) was only reported on the weekly protocol. At baseline, the IL-17 level in the TAO group was higher than that in the isolated GD and NC groups (P<0.05). In addition, the IL-17 level in the active TAO group was higher than that in the inactive TAO group (P<0.05). Furthermore, the IL-17 level had significantly decreased under the two regimens at the 12-week visit (P<0.05). In conclusion, for patients with active moderate-to-severe TAO, daily i.v. glucocorticoid therapy has a relative higher response rate than the weekly protocol with a few more minor adverse events. These two regimens have their own merits with regard to adverse effects. IL-17 has the potential to be a biomarker for evaluating TAO activity and treatment effects.

[A survey of glucose and lipid metabolism and concomitant diseases among inpatients in Guangdong province].

OBJECTIVES: To investigate the epidemiological and clinical characteristics of dyslipidemia as well as its treatment and influence on accompanying diseases in impaired glucose status among inpatients. METHODS: A cross-sectional survey was conducted among the inpatients registered in ten university hospitals of Guangdong, China during the week before the Diabetes Day in 2004. The fasting blood glucose (FBG), lipid profiles, BMI, waist to hip ratio (WHR) and concomitant disorders of the first screen during the hospitalization period were recorded. Those who had FBG level from 5.6 to 6.9 mmol/L and not been previously diagnosed diabetes (PDM) underwent oral glucose tolerance test (OGTT). RESULTS: Of the 8753 inpatients investigated, 1067 cases had complete medical records (CMR case) including PDM cases and previously non-diagnosed diabetes ones with FBG > or = 5.6 mmol/L. Of the previously non-diagnosed diabetes cases with FBG levels from 5.6 to 6.9 mmol/L, 65.8% accepted OGTT. Of the CMR cases, 41.9% had PDM, 21.7% was newly diagnosed diabetes mellitus (NDM), 29.1% had impaired glucose regulation (IGR) and only 7.3% had normal glucose tolerance (NGT). The TG levels in NDM and PDM group were higher than those in IGR and NGT group (P < 0.05, respectively). The HDL-C levels in IGR, NDM and PDM group were lower than those in NGT group (P < 0.05, respectively). Sixty-nine point six percent of the diabetes mellitus (DM) inpatients was accompanied with dyslipidemia and the rate was higher than those in NGT (56.4%) and IGR inpatients (52.5%, P < 0.05, respectively). Only 22.8% of the PDM inpatients underwent treatment of dyslipidaemia and just 3.4% achieved the target suggested by the guideline of ATP-III. BMI was higher and waistline longer in the PDM and NDM inpatients than those in the NGT cases (P < 0.05, respectively). Seventy-two point eight percent of the PDM inpatients was complicated with more than one type of vascular diseases. Nine point seven percent and 0.2% of the NDM inpatients were tormented by diabetic nephropathy and diabetic retinopathy respectively. CONCLUSIONS: More inpatients with accompany DM or IGR had concomitant dyslipidemia than those with NGT, which included hypertriglyceridemia, hypo-high-density lipoproteinemia and metabolic syndrome. Concomitant vascular diseases were more frequently found in PDM inpatients than in the others. Some of the NDM and IGT inpatients were complicated with microvascular diseases.

Inadequate glycaemic control and antidiabetic therapy among inpatients with type 2 diabetes in Guangdong Province of China.

BACKGROUND: Diabetes mellitus has become epidemic in recent years in China. We investigated the prevalence of hyperglycaemia and inadequate glycaemic control among type 2 diabetic inpatients from ten university teaching hospitals in Guangdong Province, China. METHODS: Inadequate glycaemic control in diabetic patients was defined as HbA1c = 6.5%. Therapeutic regimens included no-intervention, lifestyle only, oral antiglycemic agents (OA), insulin plus OA (insulin + OA), or insulin only. Antidiabetic managements included monotherapy, double therapy, triple or quadruple therapy. RESULTS: Among 493 diabetic inpatients with known history, 75% had HbA1c = 6.5%. Inadequate glucose control rates were more frequently seen in patients on insulin + OA regimen (97%) than on OA regimen (71%) (P < 0.001), and more frequent in patients on combination therapy (81% - 96%) than monotherapy (75%) (P < 0.05). Patients on insulin differed significantly from patients on OA by mean HbA1c, glycemic control rate, diabetes duration, microvascular complications, and BMI (P < 0.01). CONCLUSIONS: This study showed that glycaemic control of type 2 diabetic patients deteriorated for patients who received insulin and initiation time of insulin was usually delayed. It is up to clinicians to move from the traditional stepwise therapy to a more active and early combination antidiabetic therapy to provide better glucose control.

The Postprandial-to-Fasting Serum C-Peptide Ratio is a Predictor of Response to Basal Insulin-Supported Oral Antidiabetic Drug(s) Therapy: A Retrospective Analysis.

INTRODUCTION: Basal insulin is widely recommended for the treatment of type 2 diabetes mellitus (T2DM) patients who are unable to achieve glycemic control with oral antidiabetic drug(s) (OADs). However, some patients are still unable to control their blood glucose levels even when on basal insulin-supported OAD(s) therapy (BOT). The aim of this study was to investigate the factor(s) predicting patient response to BOT. METHODS: A total of 212 patients with T2DM, ranging in age from 18 to 65 years, admitted to the university hospital of Sun Yat-sen University, Guangzhou, China, were enrolled in the study between January 2013 and July 2016. All patients had fasting blood glucose levels of ≥ 10.0 mmol/L despite receiving OAD(s) treatment. According to study design, these patients first received intensive insulin therapy for 2 weeks to attain and maintain their glycemic goals and then were switched to BOT. Responders were defined as subjects who maintained their glycemic targets with BOT for at least 3 months; all others were considered to be non-responders. The characteristics between responders and non-responders were compared. RESULTS: Compared with non-responders, responders had a shorter duration of diabetes (5.1 ± 5.0 vs. and 10.1 ± 3.2 years; P  < 0.001) and a higher 2-h postprandial C-peptide-to-fasting C-peptide ratio (2 h-PCP/FCP: 1.95 ± 0.51 vs. 1.67 ± 0.32; P  < 0.01). Responders showed a lower proportion of previous treatment with insulin (69/100 vs 40/3; P  < 0.001) and sulfonlureas or glinides (116/50 vs 40/0; P <0.001) than non-responders. Multivariate logistic regression analysis showed that previous insulin treatment (odds ratio [OR] 17.677, 95% confidence interval [CI] 5.205-60.027; P  < 0.001) and the 2 h-PCP/FCP ratio (OR 0.241, 95% CI 0.058-0.679; P  = 0.007) had predictive value. CONCLUSIONS: A higher 2 h-PCP/FCP ratio and a lack of previous insulin treatment increase the likelihood of BOT success.

[Characteristics of dysfunction of islet beta-cell in newly diagnosed type 2 diabetic patients].

OBJECTIVE: To investigate the characteristics of the dysfunction of islet beta-cell in newly diagnosed type 2 diabetic patients. METHODS: Intravenous glucose tolerance test (IVGTT) was carried out on 352 newly diagnosed type 2 diabetic patients and 48 subjects with normal glucose tolerance (NGT) and then blood samples were collected 1, 2, 4, 6, and 10 minutes later to measure the plasma glucose and insulin to calculate the acute insulin response (AIR) and the area under the curve of insulin (AUC of insulin), homeostasis model assessment beta-cell (Homabeta), and Homa IR (insulin resistance). RESULTS: The median AIR of the type 2 diabetic patients was -33.7 pmol/L, significantly lower than that of the NGT subjects (6962.0 pmol/L, P < 0.001). The median AUC of the type 2 diabetic patients was 834.2 pmol/L, significantly lower than that of the NGT subjects (7934.7 pmol/L, P < 0.001). When the fasting plasma glucose (FPG) of the type 2 diabetic patients was above 7.0 mmol/L, the AIR value was remarkably reduced with a median level of 317.3 pmol/L, and then subsequently disappeared when the FPG was above 9.0 mmol/L. After adjustment of the insulin resistance assessed by HOMA IR, the Homabeta of the type 2 diabetic patients was reduced to be 30% that of the NGT subjects (3.7 +/- 0.9 vs 5.9 +/- 0.9, P < 0.001). Both the fasting proinsulin concentration and the ratio of fasting proinsulin to fasting insulin of the type 2 diabetic patients were significantly higher those of the NGT subjects (22.6 pmol/L +/- 14.7 pmol/L vs 11.5 pmol/L +/- 7.1 pmol/L, P < 0.001; and 30.1% +/- 20.5% vs. 12.1% +/- 9.6%, P < 0.001). CONCLUSION: The dysfunction of islet beta-cell in newly diagnosed type 2 diabetic patients is mainly represented by the disappearance of AIR and the evident decline of AUC and HOMA B, and the decrease of quality of insulin secretion.

Oestrogen exerts anti-inflammation via p38 MAPK/NF-κB cascade in adipocytes.

BACKGROUND: Oestrogen has anti-inflammatory property in obesity. However, the mechanism is still not defined. OBJECTIVE: To investigate the effect of oestrogen on LPS-induced monocyte chemoattractant protein-1 (MCP-1) production in adipocytes. METHODS: Lipopolysaccharides (LPS) was used to imitate inflammatory responses and monocyte chemotactic protein-1 (MCP-1) was selected as an inflammatory marker to observe. 17ß-Estradiol (E2), SB203580 (SB), pyrrolidine dithiocarbamate (PDTC), pertussis toxin (PTX), wortmannin (WM), p65 siRNA and p38 MAPK siRNA were pre-treated respectively or together in LPS-induced MCP-1. Then p38 MAPK and NF-κB cascade were silenced successively to observe the change of each other. Lastly, oestrogen receptor (ER) α agonist, ERß agonist and ER antagonist were utilised. RESULTS: LPS-induced MCP-1 largely impaired by pre-treatment with E2, SB, PDTC or silencing NF-κB subunit. E2 inhibited LPS-induced MCP-1 in a time- and dose-dependent manner, which was related to the suppression of p65 translocation to nucleus. Furthermore, LPS rapidly activated p38 MAPK, while E2 markedly inhibited this activation. It markedly attenuated LPS-stimulated p65 translocation to nucleus and MCP-1 production by transfecting with p38 MAPK siRNA or using p38 MAPK inhibitor. The oestrogen's inhibitory effect was mimicked by the ERα agonist, but not by the ERß agonist. The inhibition of E2 on p38 MAPK phosphorylation was prevented by ER antagonist. CONCLUSIONS: E2 inhibits LPS-stimulated MCP-1 in adipocytes. This effect is related to the inhibition of p38 MAPK/NF-κB cascade, and ERα appears to be the dominant ER subtype in these events.

Saxagliptin is similar in glycaemic variability more effective in metabolic control than acarbose in aged type 2 diabetes inadequately controlled with metformin.

This study compared the effects on glycaemic variability and glucose control between saxagliptin and acarbose as add-on therapies for aged T2DM inadequately controlled with metformin alone. The results showed that compared with acarbose-metformin, saxagliptin-metformin was more effective in glucose control with similar glycaemic variability.

[Association of diabetes mellitus with biological behaviors of colorectal cancer].

OBJECTIVE: To evaluate the association of diabetes mellitus(DM) with colorectal cancer. METHODS: Case-control study was performed to compare 486 patients with colorectal cancer (study group) and 533 patients without colorectal cancer (control group) in the Affiliated Nanhai Hospital of Southern Medical University between 2006 and 2009. RESULTS: The incidence of DM was 12.1% in study group and 7.1% in the control group, and the difference was significant(P<0.01). On multivariate analysis, DM was independently associated with colorectal cancer (OR=1.886,95% CI:1.450~3.571). Colorectal cancer risk was increased in DM patients with a duration of 5-20 years(P<0.05), while colorectal cancer risk in those with a duration less than 5 years or more than 20 years did not change(P>0.05). No significant differences in tumor differentiation, invasion depth, lymph node involvement, distant metastasis and lymphovascular invasion were found between colorectal cancer patients with and without DM(all P>0.05). CONCLUSION: Diabetes mellitus increases the risk of colorectal cancer, however, biological behaviors of colorectal cancer is not associated with diabetes mellitus.

[Effects of leptin on RAAS and nitric oxide production in isolated rat glomeruli].

OBJECTIVE: To investigate the changes in angiotensinogen (AGT), angiotensin II type 1 receptor (AT(1)R), endothelial nitric oxide synthase (eNOS) mRNA and protein expressions and nitric oxide (NO) content in the rat glomeruli in response to leptin stimulation. METHODS: The glomeruli isolated from male SD rats were stimulated with 3 nmol/L leptin for 2 h. Real-time PCR and Western blotting were performed to analyze the mRNA and protein expressions of AGT, AT(1)R and eNOS in the glomeruli, and nitrite concentration in the glomeruli was measured by nitrate reductase assay. RESULTS: In comparison with the control group, exposure to leptin increased the mRNA levels of AGT, ATR(1) and eNOS in the isolated glomeruli by 2.69-/+0.17, 3.77-/+0.16 and 2.56-/+0.29 folds (P=0.024, 0.018 and 0.044), and their protein levels by 2.06-/+0.10, 2.67-/+0.08 and 1.61-/+0.13 folds (P=0.021, 0.015 and 0.032), respectively. The NO production in the glomeruli was also increased by 2.77-/+0.14 folds (P=0.000) following leptin exposure. CONCLUSION: Leptin exposure of isolated rat glomeruli directly causes activation of the internal renal renin-angiotensin system and enhanced NO production, suggesting that leptin plays a role in the pathogenesis of maladaptation in renal hemodynamics in obesity.

[Cost-effectiveness analysis on continuous subcutaneous insulin infusion and multi-point daily insulin injections in the treatment program of type 2 diabetes].

OBJECTIVE: To observe the cost-effectiveness of using continuous subcutaneous insulin infusion (CS II) and multi-point daily insulin injections (MDI) in controlling blood sugar in the newly hospitalized type 2 diabetes patients. METHODS: Retrospective analysis on 86 cases taking CS II and 103 cases using MDI on a 'blood sugar control program' among the newly hospitalized patients with type 2 diabetes. The period for observation was 2 weeks, using cost-effectiveness analysis methods to evaluate the two treatment programs. RESULTS: After two weeks of treatment, the effectiveness in the control of blood sugar in CS II group was similar to the MDI group, with no significant difference (P<0.05) and the adverse reactions were similar. Costs in the CS II program (Yuan/person) was less than in the MDI program (1478.34 vs. 1620.46), with significant differences (P< 0.05). The cost-effectiveness ratios (C/E) were 15.07 in the CS II group, and 16.34 in the MDI group, with no significant difference (P>0.05). In order to further reduce the cost of CS II group as a reference, the incremental cost-effectiveness ratio (DeltaC/DeltaE) of the MDI group was 129.20. CONCLUSION: Costs-effective of the CS II program was better than the MDI one in treating the newly hospitalized patients with type 2 diabetes, suggesting that CS II program might be a better choice for hospitals to carry on an intensive insulin therapy program.

[Renal protective effects of sulodexide in diabetic rats and its anti-oxidative mechanism].

OBJECTIVE: To investigate the renal protective effects of sulodexide and its anti-oxidative stress mechanism in diabetic rats. METHOD: Thirty male SD rats were randomized into 3 equal groups, namely the control group, diabetic group, and sulodexide treatment group. Twelve weeks after establishment of rat diabetic models and administration of sulodexide, the rats were sacrificed for measurement of the urine volume, body mass, kidney mass/body weight ratio, plasma glucose, and glycosylated hemoglobin (HbA1c). Malondialdehyde (MDA) levels and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX) activities in the renal tissue or serum were tested. Electron microscopy was performed to observe the pathological changes in the kidneys. RESULTS: The urine volume, renal mass/body mass ratio, serum glucose, HbA1C, and serum and renal MDA levels all significantly increased in the diabetic rats in comparison with the normal controls (P<0.05). But the body weight and activities of SOD, CAT, and GSH-PX in the renal tissue in the normal control group were significantly higher than those in the diabetic and sulodexide group. After 12 weeks of sulodexide treatment, SOD, CAT, and GSH-PX activities in the renal tissue of rats were significantly increased in comparison with those in the diabetic rats (P<0.05). Electron microscopy showed obvious irregular thickening of the glomerular capillary basement membrane in the diabetic group with vacuolization in the mitochondria in the epithelial cells, and such pathological changes were significantly alleviated in the sulodexide treatment group. CONCLUSIONS: Sulodexide can effectively lower the urinary albumin excretion rate, improve the ultrastructural renal pathologies and prevent glomerular basement membrane thickening in diabetic rats, probably in association with the reduction of the MDA levels and enhancement of SOD, CAT, and GSH-PX activities.

[Comparison of continuous and discontinuous density gradient centrifugation for purification of human pancreatic islets].

OBJECTIVE: To compare the effect of continuous and discontinuous density gradient centrifugation for purification of human pancreatic islets with COBE 2991 cell processor. METHODS: Human pancreases were obtained from brain-dead donors and stored in cold UW solution. The connective tissues were removed from the pancreases, and the pancreatic ducts were perfused with a cold enzyme (Liberase). The islets were then separated by gentle mechanical dissociation and purified with discontinuous (10 pancreases) or continuous (8 pancreases) gradients of HCA-Ficoll in COBE 2991 cell processor. Samples were collected in duplicate for determination of the quantity of islets, islet equivalents (IEQ), and the purity. RESULTS: The weights of the pancreases before and after connective tissue removal and pancreas duct perfusion, and the quantity of islets obtained (including islets quantity of different diameters and total IEQ) after dissociation were not significantly different. Continuous gradient of HCA-Ficoll, compared with discontinuous gradient, resulted in significantly greater final islet quantity (55,000 IEQ vs 206,000 IEQ, P=0.000) and islet purity (58.0%-/+8.0% vs 33.5%-/+10.3%, P=0.000) and also greater number of islets with a diameter lager than 200 microm (P<0.01). CONCLUSION: Continuous density gradient centrifugation can be more effective than discontinuous gradient in islet purification.