Shanmei Shen

Autologous hematopoietic stem cell transplantation modulates immunocompetent cells and improves β-cell function in Chinese patients with new onset of type 1 diabetes.

CONTEXT Autologous hematopoietic stem cell transplantation (AHSCT) has the potential to induce clinical remission in patients with newly diagnosed type 1 diabetes. OBJECTIVE The objective of the study was to examine the impact of AHSCT on lymphocytes and pancreatic β-cell function. DESIGN This was a nonrandomized, open-label prospective study. PATIENTS AND INTERVENTIONS Thirteen patients with new onset of type 1 diabetes, 10 of them with diabetic ketoacidosis, were subjected to AHSCT with cryopreserved CD34(+) progenitor cells and followed up for 31-54 months. MAIN OUTCOME MEASURES The numbers of different subsets of lymphocytes and the levels of serum cytokines, islet antibodies, C-peptide, and plasma glycosylated hemoglobin were longitudinally measured. RESULTS The numbers of different subsets of lymphocytes, except for CD8(+) T cells, in the patients before AHSCT were significantly lower than those in controls. However, all lymphocytes gradually recovered after AHSCT, accompanied by decreased levels of serum autoantibodies, IL-1, IL-17, and TNF-α. After AHSCT, 11 of 13 patients required significantly reduced doses of insulin for adequate glycemic control, accompanied by reduced levels of glycosylated hemoglobin but increased C-peptide concentrations. Three patients achieved exogenous insulin independence for 7-54 months. The survival of remaining β-cells was associated positively with the preexisting β-cell function but negatively with preexisting autoantibodies (P < 0.05). The numbers of infused CD34(+) cells were positively correlated with the concentrations of serum IL-10, IL-4, TGF-β, and fasting C-peptide but negatively correlated with the levels of serum TNF-α and insulin doses after AHSCT (P < 0.05). CONCLUSION AHSCT modulated lymphocytes and preserved β-cell function in Chinese patients with new onset of type 1 diabetes and diabetic ketoacidosis.

The status of glycemic control: A cross-sectional study of outpatients with type 2 diabetes mellitus across primary, secondary, and tertiary hospitals in the jiangsu province of China

OBJECTIVES The aims of the study were to determine the following: the status of glycemic control in patients with type 2 diabetes mellitus (DM) at primary, secondary, and tertiary hospitals in the Jiangsu province of China; and the factors associated with achieving glycemic targets. METHODS This study, in which patients were enrolled from July 20 to 31, 2009, at 56 diabetes centers, used a multiple-stage, stratified sampling method to select a representative sample of the population with DM in Jiangsu. The sampling process was stratified by geographic and demographic regions, and by the outpatient numbers in the hospitals. A primary hospital was defined as a community medical institution that provided primary health services; a secondary hospital was a local medical institution that provided comprehensive health services; and a tertiary hospital was a regional medical institution that provided comprehensive and specialist health services. In primary hospitals, patients with DM were treated by general physicians; at secondary and tertiary hospitals, they were seen by specialists. Also, primary and tertiary hospitals treated patients in cities, whereas secondary hospitals treated patients from towns or rural areas. Patients with a medical history of type 2 DM for >6 months and registration at each diabetes center for > or = 6 months, and who were residents of Jiangsu province, were recruited. During the patient enrollment visit, information about DM complications and comorbidities, as well as DM management, was obtained by retrospectively reviewing medical records; basic patient data (eg, date of birth, sex, weight, height) were obtained by patient interview. Blood samples were collected for assessment of glycosylated hemoglobin (HbA1c) at a central laboratory. RESULTS Of 3046 sampled subjects, the analysis was performed in 2966 subjects with complete data. The mean (SD) HbA1c value for analyzed patients was 7.2% (1.6%). The proportion of patients with tight glycemic control was 40.2% (1193/2966) when a threshold of HbA1c <6.5% was used, and 56.1% (1665/2966) when a threshold of HbA1c <7.0% was used. Compared with patients who had inadequate glycemic control, those with tight control were younger (P < 0.001), had shorter duration of DM (P < 0.001), had lower body mass index (BMI) (P = 0.005 for HbA1c <6.5% and P = 0.01 for HbA1c <7.0%), had more education (P < 0.001) and income (P = 0.003 for HbA1c <6.5% and P = 0.008 for HbA1c <7.0%), were more likely to monitor their glucose (P = NS for HbA1c <6.5% and P = 0.043 for HbA1c <7.0%) and attend DM education (P = 0.027 for HbA1c <6.5% and P = 0.002 for HbA1c <7.0%) at least once a month, and were more likely to receive oral antidiabetic drugs (OADs) (P < 0.001). Age, BMI, and DM duration did not differ significantly between hospital types. Compared with primary (36.2%) and secondary hospitals (36.5%), tertiary hospitals (42.2%) had more patients with HbA1c <6.5% (P = 0.043); tertiary hospitals also had more patients with once-monthly glucose self-monitoring (P = 0.001), patients with higher income (P < 0.001) and education (P < 0.001), and those who were more likely to use > or = 2 OADs or insulin with OADs (P < 0.001). CONCLUSION The overall status of glycemic control was unsatisfactory during the study period, although patients at tertiary hospitals appeared to have better control than those at primary or secondary hospitals.

SLC30A8 polymorphism and type 2 diabetes risk: Evidence from 27 study groups

BACKGROUND AND AIMS Intense research has been performed to identify the genetic risk factors in type 2 diabetes, and a single nucleotide polymorphism (SNP) in SLC30A8 (rs13266634) was reported to be associated with type 2 diabetes mellitus. However, published data on the association between SLC30A8 polymorphism and the risk of type 2 diabetes were inconsistent. Therefore, we conducted this meta-analysis to derive a more precise estimation of the relationship. METHODS AND RESULTS We searched PubMed through October 2009 to identify all relevant papers. Odds ratios (ORs) and 95% confidence intervals (CIs) were extracted under an additive genetic model. In the current meta-analysis, we identified a total of 27 groups including 42,609 cases and 69,564 controls. In analyses of the case-control studies by ethnicity, the results indicated that SLC30A8 polymorphism was related to elevate risks of type 2 diabetes both in Europeans (OR=1.15, 95% CI 1.11-1.18, P<0.001) and Asians (OR=1.15, 95% CI 1.11-1.19, P<0.001). Next, we separated hospital-based case-control studies from population-based case-control studies, however, there was no apparent difference between population-based case-control study groups (OR=1.15, 95% CI 1.12-1.17, P<0.001) and hospital-based case-control study groups (OR=1.16, 95% CI 1.07-1.25, P<0.001). CONCLUSION Our present meta-analysis provided evidence that SLC30A8 (rs13266634) C allele carriers could elevate the risk of type 2 diabetes, especially in Europeans and Asians.

Comparative efficacy of anti‐diabetic agents on nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a systematic review and meta‐analysis of randomized and non‐randomized studies

Nonalcoholic fatty liver disease (NAFLD) has a high prevalence in patients with type 2 diabetes mellitus (T2DM). In this study, we sought to provide a comprehensive assessment regarding the effects of anti‐diabetic agents on NAFLD in patients with T2DM.

Association of β-cell function and insulin sensitivity with fasting and 2-h plasma glucose in a large Chinese population.

Aim: Our aim was to provide a quantitative analysis of the changes in the principal determinants of insulin sensitivity and secretion in relation to fasting plasma glucose (FPG) or 2‐h plasma glucose (2h PG) in a Chinese population with a wide range of glucose tolerance.

Silymarin alleviates hepatic oxidative stress and protects against metabolic disorders in high-fat diet-fed mice

ABSTRACT Silymarin is a potent antioxidant medicine and has been widely used for the treatment of liver diseases over 30 years. Recent studies suggest that silymarin may benefit patients with glucose intolerance. However, the mechanism underlying the action of silymarin is not clarified. The aim of this work was to assess the impact of silymarin on glucose intolerance in high-fat diet (HFD)-fed mice, and explore the potential therapeutic mechanisms. C57BL/6 mice were fed with HFD for 12 weeks, randomized, and treated orally with vehicle saline or silymarin (30 mg/kg) daily for 30 days. We found that silymarin significantly improved HFD-induced body weight gain, glucose intolerance, and insulin resistance in mice. Silymarin treatment reduced HFD-increased oxidative stress indicators (reactive oxygen species, lipid peroxidation, protein oxidation) and restored HFD-down-regulated activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) in the plasma and/or liver of the HFD-fed mice. Furthermore, silymarin decreased HFD-up-regulated hepatic NADPH oxidase expression and NF-κB activation in mice. Additionally, silymarin treatment mitigated HFD-increased plasma IL-1β, TNF-α levels, and HFD-enhanced hepatic NO, TLR4, and iNOS expression in mice. These novel data indicate that silymarin has potent anti-diabetic actions through alleviating oxidative stress and inflammatory response, partially by inhibiting hepatic NADPH oxidase expression and the NF-κB signaling.

Monocyte chemoattractant protein 1–2518 A/G polymorphism and susceptibility to type 2 diabetes in a Chinese population

BACKGROUND Hyperglycemia could accelerate monocyte chemoattractant protein 1 (MCP-1) production in monocytes and vascular endothelial cells. Recently, a genetic polymorphism (-2518 A/G) located in MCP-1 gene promoter has been found that could influence the expression of MCP-1. A large cohort study of Caucasians reported that MCP-1 G-2518 gene variant was negatively correlated with the prevalence of insulin resistance and type 2 diabetes. However, it is unclear whether this polymorphism is associated with type 2 diabetes in Han Chinese. METHODS We conducted a population-based case-control study of 416 type 2 diabetes cases and 416 controls. RESULTS Compared with the wild genotype AA, MCP-1 G-2518 gene variant could significantly decrease the prevalence of type 2 diabetes in Han Chinese (adjusted OR=0.49, 95% CI 0.32-0.77, P<0.0001). The results of stratified analyses indicated that a decreased risk of type 2 diabetes related with variant genotypes was evident in younger participants (age ≤50) (adjusted OR=0.35, 95% CI 0.20-0.61, P<0.0001), and similar results were observed in males (adjusted OR=0.37, 95% CI 0.21-0.66, P=0.001) and urban participants (adjusted OR=0.35, 95% CI 0.21-0.58, P<0.0001). In addition, a statistically significant difference was observed between MCP-1-2518 A/G polymorphism and waist to hip ratio. CONCLUSIONS Our present pilot study indicated that MCP-1 G-2518 gene variant could significantly decrease the risk of type 2 diabetes in a Chinese population.

Role for sterol regulatory element binding protein-1c activation in mediating skeletal muscle insulin resistance via repression of rat insulin receptor substrate-1 transcription

Aims/hypothesisSterol regulatory element binding protein-1c (SREBP-1c) is a master regulator of fatty acid synthase and controls lipogenesis. IRS-1 is the key insulin signalling mediator in skeletal muscle. In the present study, we investigated the role of SREBP-1c in the regulation of IRS-1 in skeletal muscle cells.MethodsL6 muscle cells were treated with palmitic acid (PA) or metformin. Adenovirus vectors expressing Srebp-1c (also known as Srebf1) and small interfering RNA (siRNA) against Srebp-1c were transfected into the L6 cells. Protein–DNA interactions were assessed by luciferase reporter analysis, electrophoretic mobility shift assay and chromatin immunoprecipitation assay.ResultsWe found that both gene and protein expression of SREBP-1c was increased in contrast to IRS-1 expression in PA-treated L6 cells. SREBP-1c overproduction decreased Irs-1 mRNA and IRS-1 protein expression in a dose-dependent manner, and suppressed the resultant insulin signalling, whereas SERBP-1c knockdown by Serbp-1c siRNA blocked the downregulation of IRS-1 induced by PA. Protein–DNA interaction studies demonstrated that SREBP-1c was able to bind to the rat Irs-1 promoter region, thereby repressing its gene transcription. Of particular importance, we found that metformin treatment downregulated Srebp-1c promoter activity, decreased the specific binding of SREBP-1c to Irs-1 promoter and upregulated Irs-1 promoter activity in PA-cultured L6 cells.Conclusions/interpretationOur data indicate for the first time that SREBP-1c activation participates in skeletal muscle insulin resistance through a direct effect of suppressing Irs-1 transcription. These findings imply that SREBP-1c could serve as an attractive therapeutic target for insulin resistance.

Remission induced by autologous hematopoietic stem cell transplantation in one newly diagnosed type 1 diabetes patient with diabetic ketoacidosis: A case report

A 21-year-old man was admitted to hospital on 18 June 2006 with complaints of polydipsia, polyuria, and loss of weight over the previous 1 week, and unconsciousness for 3 h. On 11 June 2006 the patient had contracted an upper respiratory infection, developing polydipsia and polyuria after 2 days. However, these symptoms were not taken seriously until the patient lost consciousness 3 h before presentation to hospital. On admission, the patient was dehydrated, unconscious, with no response to voice commands, and smelled of ketones. His body temperature was increased (37.6 C, axillary) but he had normal blood pressure (100 ⁄ 70 mmHg) with a respiratory rate of 22 ⁄min and pulse rate of 110 ⁄min. No other positive signs were found. On admission, the patient’s blood glucose level was 26.2 mmol ⁄L, accompanied by strong positivity for urine ketone and urine glucose. Arterial blood gas analysis revealed a pH of 6.96. Serum transaminases, creatinine, and electrolytes were within the normal limits. Routine tests, including blood lipids (total cholesterol, low-density lipoprotein–cholesterol, highdensity lipoprotein–cholesterol, and triglycerides), were normal. The patient was positive for protein tyrosine phosphatase antibody (IA-2A), but negative for glutamic acid decarboxylase antibody (GADA), protein tyrosine islet cell antibody (ICA), and insulin autoantibodies (IAAs).

Randomized trial comparing the effects of gliclazide, liraglutide, and metformin on diabetes with non-alcoholic fatty liver disease†

The aim of the present study was to compare the effects of gliclazide, liraglutide, and metformin in type 2 diabetes mellitus (T2DM) patients with non‐alcoholic fatty liver disease (NAFLD).