Volume 09 · Issue 12 · 2017

In the past 20 years, the prevalence of diabetes in China has increased sharply^[1,2,3]。 As a major chronic non-communicable disease, the prevention and control of diabetes and its vascular complications has become one of the important contents of the "Healthy China 2030" plan. The epidemiological survey in 2013 showed that the prevalence of adult diabetes in China was 10.9%, and the prevalence of prediabetes was 35.7%^[3]。 In addition, a large observational study showed that in patients with type 2 diabetes in China, blood sugar control [glycosylated hemoglobin (HbA_1c）<7%] was 47.7%, while only 5.6% reached the standard for blood glucose, blood pressure and blood lipid^[4]。 Therefore, the overall situation and management status of diabetes prevention and treatment in China is very severe.

In the last 30 years, the incidence of diabetes in China has increased "explosively". However, the genetic background of Chinese people in the past few decades is unlikely to change greatly, and the great changes in lifestyle are the most important factors affecting the occurrence of diabetes. How does the increase of nutritional intake and changes in environmental factors affect the occurrence of diabetes? Epigenetics plays an important role in mediating environmental factors and gene expression.

The latest survey data shows that the prevalence rate of type 2 diabetes in adults over 18 years old in China is as high as 10.9% ~11.6%^[1,2]。 The incidence of dyslipidemia in type 2 diabetes patients was significantly higher than that in non-diabetic patients^[3]。 Dyslipidemia is also an important risk factor for the increased incidence of atherosclerotic cardiovascular disease (ASCVD, including stroke, coronary heart disease, and peripheral artery disease) in patients with type 2 diabetes^[4,5]。

Epidemiological survey shows that the prevalence of type 2 diabetes in adults in China is 9.7% ~11.6%^[1,2]It has become the country with the largest number of diabetic patients in the world. As a chronic lifelong disease, the improvement of patients' quality of life depends on their own management^[3,4]。 Effective diabetes self-management education/support (DSME/S) is the basis for assisting people with diabetes in managing and maintaining their own health behaviors^[5]。 Diabetes education and management in China started in the mid-1990s. At first, medical staff organized hospitalized diabetic patients to teach, with a single mode and passive learning. With the introduction of successful experiences from abroad, the DSME model, which combines professional group teaching, individualized self-management skills training and patient peer education, begins to emerge^[6]。 However, there are many problems in diabetes education in China at present: such as monotonous content (mainly based on book knowledge), strong randomness of speakers, lack of systematic evaluation and follow-up, disconnection between education and behavior change, disconnection from patient needs, lack of individualized education and diet, exercise plan and DSME plan can not be well implemented, etc^[7,8,9,10]。

To evaluate the risk of pancreatic cancer with incretin drugs in patients with type 2 diabetes mellitus (T2DM).

Pubmed, Embase, Cochrane Central Register and Clininal Trials.gov were used for searching randomized controlled trials of incretin drugs (glucagon-like peptide-1 receptor agonists or dipeptidyl peptidase-4 inhibitors) in the treatment of T2DM from Jan. 2007 to Sept. 2017. Meta-analysis was performed by using RevMan 5.3 to assess the risk of pancreatic cancer.

Of total 12 trials (n=71 942), including 6 cardiovascular outcome trials, 118 pancreatic cancer were identified. Compared with placebo or other antidiabetic drugs, pancreatic cancer was not increased in patients treated with incretin drugs (OR=0.73, 95%CI: 0.51-1.05). Notably, following up for over 104 weeks, pancreatic cancer seemed to be lower in patients with incretin therapy (OR=0.70, 95%CI: 0.48-1.00).

Incretin therapy is not associated with increased risk of pancreatic cancer in patients with T2DM. Instead, it might be a protective factor for pancreatic cancer in T2DM patients treated for over 104 weeks.

To investigate the regulatory role of forkhead box O1 (FoxO1) on differentiation of human embryonic stem cells (hESCs) into insulin producing cells (IPCs).

The expression levels of FoxO1 during IPC differentiation of hESCs in vitro were determined by realtime PCR and Western blotting. The dynamic expression of octamer-binding transcription factor 4 (Oct4), forkhead box a2 (Foxa2), pancreatic and duodenal homeobox 1 (Pdx1) and insulin during the differentiation was analyzed by realtime PCR. The stage-3 cells (pancreatic progenitors) of the differentiation were infected with FoxO1-knockdown and FoxO1-overexprssion lentiviral vectors. The expression levels of Foxa2, Pdx1 and insulin were detected by realtime PCR. The infected cells were induced to differentiate into IPCs, and glucose stimulated insulin secretion was measured by using an ELISA kit. The t test was used to compare the difference between two groups, and one-way ANOVA was used among the groups.

FoxO1 mRNA and protein were invariably expressed during the differentiation of hESCs to IPCs. The expression level of Oct4 dropped significantly with the differentiation progress. The expression level of Foxa2 increased during the differentiation and peaked at stage 3 of the differentiation. The expression levels of Pdx1 and insulin were significantly upregulated during the differentiation. In the infected pancreatic progenitors, the mRNA levels of Foxa2 (4.31±0.74 vs 1.00±0.34, t=7.08, P<0.01), Pdx1 (2.91±0.24 vs 1.00±0.15, t=11.62, P<0.01) and insulin in the FoxO1-knockdown group were significantly increased compared with those in its control group. By contrast, overexpression of FoxO1 downregulated the mRNA level of insulin (0.81±0.07 vs 1.00±0.03, t=4.19, P<0.05), but had no effect on the mRNA levels of Foxa2 and Pdx1. In addition, knockdown of FoxO1 promoted insulin secretion stimulated by both low glucose (2 mmol/L) (7.53±2.02 vs 1.00±0.05, t=3.23, P<0.05) and high glucose (20 mmol/L) (17.39±3.03vs 6.45±1.34, t=3.30, P<0.05). Overexpression of FoxO1 had little effect on insulin secretion under low glucose, but inhibited high glucose stimulated insulin secretion (2.02±0.50vs 4.85±1.42, t=2.61, P<0.05), thus resulting in loss of responsibility to glucose.

FoxO1 negatively regulates the IPC differentiation of hESCs. Inhibition of FoxO1 expression may be a potential strategy for promoting the differentiation and maturation of IPCs from hESCs.

To investigate the association of plasma amino acids and the risk of developing of type 2 diabetes mellitus (T2DM) and their prediction ability of T2DM in a rural Chinese population.

A nested case-control study was carried out in the Handan Eye Study conducted from 2006 to 2013. During follow-up, 209 individuals developed diabetes, and 394 individuals matched for age and gender were identified as controls. Relationship of metabolic biomarkers to incident T2DM was assessed by conditional logistic regression.

After adjusted for age, sex, body mass index (BMI), waist circumference, and family history of diabetes, the plasma concentrations of tyrosine, leucine, valine, alanine and glycine were significantly associated with incident T2DM, and the odds ratios (OR) [95% confidence interval(CI)] were 4.56 (1.77-11.73), 5.73 (1.80-18.25), 6.73 (2.02-22.34), 5.89 (2.26-15.36) and 0.39 (0.17-0.89), respectively (Model 2, all P<0.05). After further adjustment of fasting plasma glucose and triglyceride, only tyrosine and the combination of four-amino acids were still significantly associated with incident rate of T2DM, and the OR (95%CI) were 3.36 (1.10-10.29) and 1.11 (1.02-1.22), respectively (Model 3, both P<0.05). None of these amino acids significantly improved the C-statistics and net reclassification improvement. Only the four-amino acids combination significantly improved the integrated discrimination improvement, but the net changes were not remarkable.

Levels of branched-chain and aromatic amino acids, alanine and glycine, particularly tyrosine, are significantly associated with incident T2DM. However, none of these amino acids significantly improves T2DM risk prediction.

To investigate the correlation between pancreatic fat content and type 2 diabetes mellitus (T2DM).

From January to June 2017, 60 patients with newly diagnosed type 2 diabetes mellitus and 64 non-diabetic healthy subjects were enrolled into diabetes group or control group, respectively. Various indexes were measured, including height, weight, body mass index (BMI), fasting plasma glucose (FPG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), glycosylated hemoglobin (HbA_1c) and fasting insulin (FINS). Insulin resistance (IR) index and β cell function index were evaluated with homeostasis model assessment (HOMA). The pancreas was scanned with magnetic resonance imaging Dixon technique, then the pancreatic fat volume fractions (PFVF) was measured and calculated. The data between these two groups were compared with t test, and the correlation analysis was evaluated with Pearson or Spearman test.

The PFVF in diabetic group was higher than that in control group (9.6%±4.1% vs 6.6%±2.8%, t=4.745, P<0.05). The correlation analysis showed that PFVF was positively correlated with BMI (r=0.386, P<0.05), FPG (r=0.358, P<0.05) and TG (r=0.323, P<0.05), meanwhile negatively correlated with HDL-C (r=-0.339, P<0.05). However, PFVF had no correlation with TC, LDL-C, HbA_1c, FINS, HOMA-IR and HOMA-β.

Accumulation of fat content in pancreas may play an important role in the pathogenesis of T2DM.

The correlation between thyroid function and glycated hemoglobin(HbA_1c) in non-diabetic populations with normal thyroid function was studied in cross-sectional way.

Totally 5 428 non-diabetic individuals with normal thyroid function in Dalian were enrolled in Department of Endocrinology of Dalian Municipal Central Hospital from January 2012 to December 2016. The following aspects were examined, including height, weight, blood pressure, thyroid stimulating hormone (TSH), free thyroxine (FT₄), free triiodothyronine (FT₃), fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) 2 h glucose, HbA_1c, blood creatinine, blood uric acid, total cholesterol (TC), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C) and fasting insulin. Homeostasis model assessment insulin resistance (HOMA-IR) was calculated. The population was divided into two subgroups, group A (n=3 691) with serum TSH<2.5 mU/L and group B (n=1 715) with serum TSH≥2.5 mU/L. The correlation between thyroid function and HbA_1c was investigated with Spearman correlation analysis and Logistic regression analysis.

Compared with group A, the levels of blood creatinine, blood uric acid and FT₄ were lower and the levels of LDL-C, TC, TG, HbA_1c, fasting insulin and HOMA-IR were higher in group B (all P<0.05). TSH was positively correlated with HbA_1c (r=0.038, P=0.005) . However, HbA_1c was not related with FT₃ (r=0.022, P=0.101) and FT₄ (r=0.002, P=0.861). With Logistic regression analysis, it was showed that age, gender, body mass index, TC, FPG, OGTT 2 h blood glucose, blood uric acid and TSH were individually risk factors of glycosylated hemoglobin (OR=1.029, 1.845, 1.021, 1.194, 2.853, 1.106, 1.002, 1.147, respectively, all P<0.05). But the systolic blood pressure was an protective factor (OR=0.096, P<0.05).

High TSH level within normal thyroid function was positively correlated with glycosylated hemoglobin in non-diabetic patients and also was an independent risk factor of HbA_1c. It is indicated that the increasing of TSH even within normal range may increase the risk of abnormal glucose metabolism.

suppressors of cytokine signaling 3 (SOCS3) can regulate cytokine signaling by inhibiting signal transduction and abnormal activation of signal transducer and activator of transcription3 (STAT3), and play an important role in maintaining the balance of the internal environment^[1]。 Studies have shown that STAT3-SOCS3 signaling is involved in the formation of insulin resistance and plays an important role in the pathogenesis of type 2 diabetes mellitus (T2DM)^[2,3,4]。 The results of previous studies of our research group showed that the upregulation of SOCS3 gene expression in T2DM rats may lead to insulin resistance by increasing the degradation of insulin receptor substrate (IRS) and promoting its serine phosphorylation level^[5,6]。 RNAi (RNAi) is a post-transcriptional horizontal gene silencing technique mediated by the degradation of homologous mRNA in cells induced by small interfering RNA (siRNA)^[7], lentivirus-mediated RNAi technology, has been widely used in the treatment and research of diseases^[8]。 In this study, lentiviral vector-mediated RNAi was used to down-regulate SOCS3 gene in T2DM rats, to observe the changes of insulin signaling pathway related molecules, and to investigate the effect of silencing SOCS3 gene on insulin signaling pathway.

fulminant type 1 diabetes mellitus (FT1DM), a new subtype of type 1 diabetes mellitus, belongs to idiopathic type 1 diabetes mellitus (type 1B), and there is still no confirmed etiology and autoimmune evidence. FT1DM by Japanese scholars Imagawa et al.^[1]It was first put forward in 2000, and gradually attracted the attention of scholars at home and abroad. pregnancy-associated FT1DM (PF) refers to FT1DM occurring during pregnancy or postpartum, which is mostly combined with severe ketoacidosis. The disease progresses rapidly, and it is easy to misdiagnose or misdiagnose in clinic. If it is not diagnosed and treated in time, it will endanger the life of mother and child. The author now reports a case of FT1DM recently diagnosed and treated in our hospital, and analyzes its onset characteristics, clinical manifestations, laboratory auxiliary examination and treatment combined with relevant literatures to improve the understanding of this disease.

Metformin is the most commonly used oral hypoglycemic agent and is also used for the treatment of polycystic ovary syndrome (PCOS)^[1]。 Metformin reduces serum testosterone levels in PCOS patients, studies have shown^[2,3], but does metformin also reduce serum testosterone levels in men with diabetes? Are there effects on the hypothalamus-pituitary-gonadal axis (HPGA) and sexual function? These problems are often overlooked by clinicians. In this paper, the effects of metformin on HPGA and sexual function are briefly reviewed based on the existing research data.

Type 2 diabetes mellitus (T2DM) is a major chronic metabolic disease characterized by excessive glucose levels in the blood. The prevalence of diabetes in adults was 6.4%^[1]And increasing year by year, it has become one of the major diseases that endanger global health. At present, T2DM is considered to be a complex polygenic hereditary disease caused by the combination of genetic and environmental factors. It is characterized by insulin resistance, insufficient insulin secretion and increased hepatic glycogen export, but its main pathophysiological mechanism is still unknown^[2]。 Epigenetic changes, particularly DNA methylation, play a role in the pathogenesis and progression of linking genetic and environmental factors^[3]。 This paper discusses the role of DNA methylation in the pathogenesis of high risk factors of T2DM and the molecular mechanisms in the development of T2DM, and reviews the research progress of epigenetics of T2DM.

diabetic retinopathy (DR) is one of the most common chronic ocular complications of diabetes^[1]It is one of the important factors causing blindness among adults in China. In the past few decades, human beings have made important progress in the treatment of this disease. At present, traditional treatment methods include drug therapy, retinal laser photocoagulation, vitrectomy, etc^[1]。 However, the effect of drug treatment is limited, there are many complications after laser or surgery treatment, and the pathogenesis of DR is complex. Traditional treatment methods cannot fundamentally inhibit the progression of the disease. Stem cells have multidirectional differentiation potential and can play a therapeutic role in retinopathy. Related research is gradually being carried out. Previous studies have shown the presence of stem cells in mammalian retina, but this result is still controversial^[2]mesenchymal stem cells (MSCs) can differentiate into retinal cells, thereby replacing diseased cells and playing a therapeutic role. Therefore, in recent years, the treatment of DR by MSCs has gradually become a research hotspot. This article will review the potential mechanism of action of MSCs in DR treatment.