Panwei Mu

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

Oral anti‐diabetes drugs plus basal insulin (OAD + insulin) therapy in patients with newly diagnosed type 2 diabetes might improve β‐cell function and result in extended glycaemic remission. This randomised trial compared the effect on β‐cell function and diabetes remission rate between oral drug alone or with addition of basal insulin.

Noninferiority Effects on Glycemic Control and β-Cell Function Improvement in Newly Diagnosed Type 2 Diabetes Patients: Basal Insulin Monotherapy Versus Continuous Subcutaneous Insulin Infusion Treatment

AIMS In newly diagnosed type 2 diabetes mellitus (T2DM) patients, short-term insulin therapy might improve β-cell function and glycemic control. This study aimed to compare the effects of basal insulin monotherapy with continuous subcutaneous insulin infusion (CSII) treatment. METHODS Fifty-nine cases of newly diagnosed T2DM patients with fasting plasma glucose of 9.0-16.7 mmol/L were recruited into this study. They were hospitalized and randomly assigned to a basal insulin monotherapy group (n=27) or a CSII group (n=32). Insulin dosage was titrated according to fasting capillary blood glucose levels, and treatment was stopped after 2 weeks. Intravenous glucose tolerance tests were performed, and blood glucose, insulin, C-peptide, and lipid profiles were measured before therapy and 2 days after therapy withdrawal. RESULTS Both treatments reduced fasting and postprandial blood glucose levels (after treatment vs. baseline, both P<0.05). Fasting glycemic control target was achieved in 52 cases (88.14%) with 2 weeks of insulin treatment, and there were no significant differences between the glargine and CSII groups (P=0.059). The time to achieve fasting glycemic target in the CSII group was shorter than that in the glargine group (P<0.01). Plasma lipid profiles such as triglycerides and total cholesterol also decreased significantly after the intervention. Overall β-cell function improved significantly after insulin intervention (P<0.01). Variation did not differ between two groups, nor did the effects on insulin and C-peptide secretion (P>0.05). CONCLUSIONS The effect of basal insulin monotherapy was similar to that of CSII, and thus basal insulin monotherapy might be a reasonable alternative to CSII for initial insulin therapy in newly diagnosed T2DM patients.

Glycemic variability evaluated by continuous glucose monitoring system is associated with the 10-y cardiovascular risk of diabetic patients with well-controlled HbA1c.

BACKGROUND The present study aimed to identify the relationship between glycemic variability (GV) and the 10-y risk of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) patients with good glycemic control. METHODS Two-hundred forty consecutive T2DM patients (HbA1c≤7.0%) without CVD were included to calculate the 10-y CVD risk by Framingham risk score (FRS), and divided into 3 groups: low-risk group (FRS≤10%), intermediate-risk group (>10%, ≤20%) and high-risk group (>20%). Inter-group differences of GV were determined by comparing the SD of blood glucose (SDBG), mean amplitudes of glycemic excursion (MAGE), and mean of daily differences (MODD) gathered from 72-h continuous glucose monitoring system. RESULTS The levels of SDBG and MAGE significantly increased along with the raises of 10-y CVD risk of T2DM patients (p<0.01). FRS was positively correlated with age, systolic blood pressure, SDBG and MAGE (r=0.717, 0.525, 0.509 and 0.485 respectively, p<0.01), while negatively correlated with the level of HDL-C (r=-0.348, p<0.01). Furthermore, multivariate logistic regression analysis confirmed that increased MAGE [OR: 1.623(1.198-2.316), p<0.001] and patients with high urine albumin excretion rates [OR: 1.743(1.247-2.793), p<0.001] were independent predictors for high 10-y CVD risk. CONCLUSION GV predicts independently the 10-y CVD risk of T2DM patients with well-controlled HbA1c.

Gly482Ser mutation impairs the effects of peroxisome proliferator-activated receptor γ coactivator-1α on decreasing fat deposition and stimulating phosphoenolpyruvate carboxykinase expression in hepatocytes.

Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) is a transcriptional coactivator of nuclear receptor peroxisome proliferator-activated receptor γ that critically regulates glucose and fat metabolism. Although clinical evidence suggests that Gly482Ser polymorphism of PGC-1α is associated with an increased incidence of nonalcoholic fatty liver disease, a direct role for Gly482Ser mutation in altering PGC-1α actions on hepatocyte fat deposition remains to be explored. We hypothesized that Gly482Ser mutation impairs the abilities of PGC-1α in ameliorating overnutrition-induced hepatocyte fat deposition and in stimulating hepatocyte expression of cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C; encoded by a key PGC-1α target gene). In the present study, treatment of cultured hepatocytes with palmitate induced fat deposition, serving as a cell model of hepatic steatosis. Upon overexpression of wild-type PGC-1α, H4IIE cells exhibited a significant decrease in palmitate-induced hepatocyte fat deposition compared with control cells and/or cells upon overexpression of mutant PGC-1α (Gly482Ser). Overexpression of wild-type PGC-1α, but not mutant PGC-1α, also caused a significant increase in hepatocyte expression of carnitine palmitoyl transferase 1a, a rate-determining enzyme that transfers long-chain fatty acids into mitochondria for oxidation. In addition, overexpression of mutant PGC-1α did not stimulate PEPCK-C expression as overexpression of wild-type PGC-1α did, likely due to a decrease in the ability of mutant PGC-1α in increasing PEPCK promoter transcription activity. Together, these results suggest that Gly482Ser mutation impairs the abilities of PGC-1α in decreasing fat deposition and in stimulating PEPCK-C expression in cultured hepatocytes.

Glycated haemoglobin A1c for diagnosing diabetes in Chinese subjects over 50 years old: a community‐based cross‐sectional study

Little is known about using glycated haemoglobin A1c (HbA1c) to diagnose diabetes in Chinese subjects over 50 years old. This study aims to evaluate HbA1c in diagnosing diabetes and identify the optimal threshold to be used in Chinese community subjects aged over 50 years.

Dickkopf-1 promotes the differentiation and adipocytokines secretion via canonical Wnt signaling pathway in primary cultured human preadipocytes

OBJECTIVE Dickkopf-1, a newly recognized antagonist for canonical Wnt signaling, is secreted in the early stage of human adipose-derived stem cells (ASCs) adipogenic differentiation. This study was aimed to investigate whether human recombinant DKK-1 (rhDKK-1) could affect the differentiation and metabolism as well as adipocytokines secretion in primary cultured human ASCs. METHODS Human ASCs were isolated from omental adipose tissue and induced to adipogenic differentiation in the absence or presence of Wnt signaling antagonist rhDKK-1 and agonist SB216763, respectively. mRNA and protein expression profiles of adipogenic factors during the differentiation process were analyzed using quantitative RT-PCR and Western blotting. Adipocytokines secretion levels in the culture medium were measured by ELISA method. RESULTS Our results showed that DKK-1 was already expressed during the early stage of adipogenesis and reached the peak on the 9th day. Exogenous rhDKK-1 exposure accelerated the differentiation by up-regulating PPAR-γ and C/EBP-α, down-regulating Wnt3a, Wnt10b and β-catenin, without affecting non-canonical Wnt signaling marker (Wnt5a). In addition, rhDKK-1 treatment increased the secretion of leptin, RBP4, TNF-α and adiponectin during differentiation. rhDKK-1 treatment also significantly increased the intracellular accumulation of lipids and lipolysis. Thus, Wnt signal pathway agonist SB216763 down-regulated DKK-1 transcriptional and secretion levels during adipogenic process. CONCLUSIONS Our results suggest that rhDKK-1 could promote ASCs differentiation and increase adipocytokines secretion via canonical Wnt signaling pathway.

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.

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. 17β-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, ERβ 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 oestrogens inhibitory effect was mimicked by the ERα agonist, but not by the ERβ 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.

Comparison of fasting capillary glucose variability between insulin glargine and NPH

The aim of this study was to compare coefficient of variation of fasting capillary blood glucose (FBG) between insulin glargine and NPH in T2DM with poorly controlled by oral antidiabetic drugs. The results demonstrated that insulin glargine was more potent in improving glycemic control than NPH with stable FBG.

Utility of Neck Circumference for Identifying Metabolic Syndrome by Different Definitions in Chinese Subjects over 50 Years Old: A Community-Based Study

Aims Whether neck circumference (NC) could be used as a valuable tool for identifying metabolic syndrome (MS) by different criteria in Chinese is still unclear. Methods We conducted a cross-sectional survey from October 2010 to January 2011 in Shipai community, Guangzhou, Guangdong Province, China. A total of 1473 subjects aged over 50 years were investigated. We measured height, weight, NC, waist circumference, blood pressure, blood glucose, and lipids in all subjects. MS was identified by criteria of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III), Chinese Diabetes Society (CDS), and International Diabetes Federation (IDF). Results Mean NC was 38.0 ± 2.7 cm in men and 34.2 ± 2.5 cm in women. By using receiver operating characteristic curves, the area under the curve (AUC) of NC for identifying MS (IDF) was 0.823 in men and 0.777 in women, while for identifying MS (CDS), it was 0.788 in men and 0.762 in women. The AUC of NC for diagnosing MS (ATP III) was 0.776 in men and 0.752 in women. The optimal cut points of NC for MS were 38.5 cm by three definitions in men, while those were 34.2 cm, 33.4 cm, and 34.0 cm in women by IDF, ATP III, and CDS definitions, respectively. No significant difference was observed between the AUC of NC and BMI for diagnosing MS by using different criteria (all p > 0.05). Conclusions NC is associated with MS by different definitions in Chinese subjects over 50 years old. It may be a useful tool to identify MS in a community population.