Volume 04 · Issue 11 · 2012

Type 2 diabetes is the result of a combination of genetic and environmental factors. However, in the past 20 years, the prevalence of type 2 diabetes has doubled. The prevalence of type 2 diabetes has reached 4% to 5% in Europe, and 8% to 10% in the United States and China^[1]。 Therefore, the role of environmental factors in the development of type 2 diabetes may be more critical in the context of no obvious changes in genetic factors. Studies show that gut microbes are closely related to the occurrence of type 2 diabetes^[2,3,4]。 The author introduces the relevant progress as follows.

omentin was developed by Yang et al., University of Maryland, USA^[1]The cytokine expressed specifically in omental adipose tissue was first discovered in 2003. In recent years, it has been found that it participates in the regulation of glucose metabolism and vascular endothelial function together with other cytokines secreted by adipose tissue such as leptin, adiponectin and lactin. At the same time, omentin is closely related to obesity, type 2 diabetes, atherosclerosis and inflammation, and its role in the pathogenesis of these diseases has also attracted much attention. The author briefly introduces the research progress of the biological characteristics of omentin.

With the development of economy and the improvement of people's lives, the prevalence of diabetes is increasing rapidly in China^[1]。 In 1999, WHO classified diabetes into two main types, type 1 and type 2, according to etiology. latent autoimmune diabetes in adults (LADA) by Tuomi et al.^[2]It is proposed that subtypes assigned to immune-mediated type 1 diabetes mellitus^[3,4]。 The early clinical manifestations of LADA resemble type 2 diabetes, but are characterized by slow autoimmune damage of islet β cells, and the rate of islet function decline is three times that of type 2 diabetes^[5]。 Early diagnosis and intervention of LADA has practical significance for preserving the residual islet β cell function and delaying the occurrence and development of chronic complications. Given that the diagnosis and treatment of LADA are still difficult and controversial^[4,6,7]The Diabetes Branch of Chinese Medical Association organized experts to discuss, solicit opinions and form consensus on eight aspects of LADA (naming, epidemiology, genetic characteristics, immune response, relationship with other autoimmune diseases, metabolic characteristics and chronic complications, diagnostic criteria and treatment strategies) in Changsha in September and Beijing in November, 2011, in order to raise awareness and promote the translational research and clinical practice level of LADA in China.

To evaluate the effect of thiazolidinediones on the risk of bone fracture in patients with type 2 diabetes.

We searched for randomized controlled trials(RCTs) in the following electronic databases: MedLine, the Cochrane Library, Chinese BioMedical Literature Database(CBM), National Knowledge Infrastructure Database(CNKI), Chongqing VIP Information Database(VIP), Wanfang Data and collect all clinical controlled trials according to selection criteria. Quality assessment and data extraction were conducted by two reviewers independently. Disagreement were resolved through discussion. All data were analyzed by using Review Manager 5.0 software.

Seven studies involving 16 350 participants were selected in this analysis. The main results of meta-analysis showed that: thiazolidinediones significantly increased the risk of bone fractures among women(duration of treatment: three years) compared with that in placebo group(RR=1.99, 95%CI: 1.21-2.37, P<0.05); thiazolidinediones increased the risk of fractures among women(duration of treatment: one to three years) compared with biguanides or sulfonylureas (1.32(0.29-5.87),P>0.05); thiazolidinediones significantly increased the risk of fractures among women(duration of treatment: more than three years) compared with biguanides or sulfonylureas (1.94(1.55-2.43),P<0.05). No significant difference was found in the risk of bone fracture among men treated with thiazolidinediones and men treated with control drugs (P>0.05). Thiazolidinediones significantly increased the risk of fractures of upper limb (1.85(1.33-2.59),P<0.05) and distal lower limb (2.74(1.88-3.97),P<0.05) among women(duration of treatment: more than three years) compared with biguanides or sulfonylureas; but there was no significant differences in the risk of fractures of spine among women treated with thiazolidinediones (duration of treatment: more than three years) compared with biguanides or sulfonylureas(1.72(0.60-4.95),P>0.05).

Based on the current studies, thiazolidinediones might cause bone fracture in female patients with type 2 diabetes mellitus, especially in postmenopausal female patients.

To assess the effects of gender, age and seasonal variation on glycemic control in outpatient diabetics.

The glycosylated hemoglobin A1c (HbA1c) records of 17 857 cases from outpatients in the China-Japan Friendship Hospital enrolled from 2004 to 2011 was analyzed retrospectively, and the blood control status were compared among age groups, genders and seasons. Linear-contrast one-way analysis of variance and Cochran-Armitage analysis were applied to explore annual trend of glycemic control.

The mean age of the subjects was (58±13)yrs, the male-female ratio was 1.16∶1; the mean HbA1c level was 7.1%±1.6%, and the HbA1c level in 3465 cases(43.3%) was <6.5%, and was <7.0% in 4914 cases(61.4%). The HbA1c level declined significantly from 2004 to 2011(7.3%±1.7% to 6.8%±1.4%, F=24.17, P<0.01) in those diabetic outpatients. More subjects achieved a HbA1c targets <7.0% in 2011 than in 2004 (69.0% vs 55.3%,Z=4.83, P<0.01). The percentages of subjects reached a HbA1c targets of <7.0% in patients aged ≥40-60 yrs and >60 yrs increased significantly from 2004 to 2011(Z=18.67, 5.58, all P<0.05). The blood glucose control improved significantly in female patients through the years(Z=28.10, P<0.01), but not in male subjects(Z=2.61, P>0.05). The standard-reaching rate of blood glucose in April to September was much lower than those in the other months in 2007.

Glycemic control is improved in the diabetic outpatients through the 8 years, and the blood glucose is controlled better in female patients aged over 40 years. There are seasonal differences in blood glucose control, more attention should be paid to the glycemic control in male patients below 40 years of age, and the therapeutic regimen could be adjusted with the seasons if needed.

To evaluate the association between epicardial fat volume(EFV) and blunted heart rate recovery(HRR) in patients with metabolic syndrome(MS).

Screening subjects in epidemiologic study of metabolic syndrome in Oriental and Qinfeng Community in Taiyuan and health physical examination in Shanxi Province People's Hospital, which was conducted among 486 patients from July to September in 2011, one hundred and nine patients with MS and forty one healthy controls were included in the study. All subjects received a questionnaire survey and physical examination. Laboratory results included fasting blood glucose, glycosylated hemoglobin, triglyceride, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, uria acid and fasting insulin were also collected. Coronary computed tomography angiography(CCTA) was performed to exclude obstructive disease(≥50% luminal narrowing). Then EFV and HRR at 1 min after exercise termination(HRR-1)were measured and compared between two groups.

EFV((159±62) vs (182±50) cm³, t=6.91, P<0.05) was increased and HRR-1((21±8) vs (26±9) time/min,t=-5.74, P<0.05)was significantly reduced in patients with MS compared to those in control group.Among the MS patients, subjects with blunted HRR had increased EFV compared to patients without blunted HRR((197±56) vs (178±62) cm^3,t=7.90, P<0.05). In multivariate analysis, EFV was the only independent predictor of blunted HRR in patients with MS(OR=2.46, P<0.05). Furthermore EFV of equel to or bigger than 163.4 cm³ was associated with the blunted HRR with 86.1% sensitivity and 57.3% specificity(ROC area under curve: 0.74).

EFV is an independent predictor of blunted HRR in patients with MS.

To explore the association between uncoupling protein 2 gene (UCP2) -866G/A polymorphism and type 2 diabetes mellitus (T2DM) and related traits.

A total of 287 eligible T2DM pedigrees were recruited by using the proband-initiated contact method from May 2005 to September 2007 in rural Fangshan district of Beijing. DNA was extracted from blood samples and genotyped by using polymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP) method. Statistical analysis, including non-parametric linkage analysis and family-based association test (FBAT) were implemented to detect the relationship between the variant and the T2DM and related metabolic disorders.

The frequencies of AA, GA and GG genotype of the UCP2-866G/A variant were 19.7%, 52.9% and 27.4%, respectively, as well as the frequencies of A and G allele were 0.461 and 0.539. It was found that both the G allele and AA genotype were significantly associated with metabolic syndrome and central obesity in the FBAT analysis (Z=2.28, 2.01 and -2.22, -2.01, respectively, all P<0.05). However, in the non-parametric linkage analysis, the result did not support the evidence thatUCP2 -866G/A polymorphism had potential linkage relationship with T2DM and related traits.

The UCP2 gene -866G/A polymorphism is related with metabolic syndrome and central obesity, but not with T2DM and dyslipidemia in T2DM families.

To investigate the expression and roles of phosphatidylinositol-3-kinase(PI3K), serine/threonine protein kinase(Akt)1 and Akt2 mRNA in bone of diabetic rats.

Fifty female Wistar rats aged 6-month, were randomly divided into control group (NS group, n=24) and diabetes group (DM group, n=26). The DM group were made by feeding with high-sugar-fat diet 8 weeks and injected small doses of streptozotocin(STZ)(30 mg/kg), while the NS group were fed with normal diet. After 12 weeks, PI3K, Akt1 and Akt2 mRNA in bone were measured respectively by RT-PCR.The t test was used for statistics.

Compared with the NS group, the bone mineral density(BMD) levels of the DM group was significantly decreased ((0.079±0.034) vs (0.060±0.017)g/cm², t= 2.499, P<0.05), and the expression of PI3K, Akt1 and Akt2 mRNA in bone tissue of the DM group was also decreased(0.65±0.05 vs 0.51±0.04, 0.756±0.031 vs 0.694±0.017, 0.77±0.04 vs 0.66±0.04,t=4.969, 3.924 and 4.515, all P<0.01).

Decreased expression of PI3K, Akt1 and Akt2 mRNA in bone may be one of the pathogenesis in type 2 diabetic osteoporosis.

To study the effect and mechanism of forkhead transcription factor O1(FoxO1) on oxidative stress in rat mesangial cells(MCs) cultured under high glucose conditions.

The MCs cultured in normal glucose (5.6 mmol/L) medium were transfected by the plasmid vector of the FoxO1 short hairpin RNAs (FoxO1 shRNA), and then cultured in high glucose (30.0 mmol/L) medium and resveratrol (Resv 20.0 μmol/L). The MCs cultured in normal glucose medium served as normal control group (group NG), and the MCs cultured in high glucose medium were divided into five groups: simple high glucose group (group HG), HG+ Resv group, HG+ FoxO1 shRNA group, HG+ Resv+ FoxO1 shRNA group, HG+ Negative control group (shNC). MCs in each group were cultured for 72 h. The level of reactive oxygen species (ROS) was assessed by fluorescence microplate reader. The mRNA expression of silent information regulator 1(Sirt1), FoxO1, manganese superoxide dismutase (MnSOD) were detected by reverse transcription polymerase chain reaction(RT-RCR). The protein expression of FoxO1 and phosphorylation FoxO1(p-FoxO1) were determined with Western blotting methods. One-way analysis of variance was applied in the data comparisons among the groups.

Compared with group NG, the mRNA expression of Sirt1 and MnSOD were significantly reduced but the p-FoxO1 and ROS were enhanced in group HG (t=12.38, 14.13, 13.27, 8.36, all P<0.05). Compared with group HG, the mRNA expression levels of FoxO1 and MnSOD were obviously inhibited, but the level of ROS was enhanced in group HG+ FoxO1shRNA(t=20.61, 13.61, 10.13, all P<0.05); and the mRNA expression of Sirt1 and MnSOD increased, whereas the level of p-FoxO1 and ROS decreased significantly in group HG+ Resv (t=6.02, 5.39, 10.69, 5.37, all P<0.05). Compared with group HG+ Resv, the mRNA expression of FoxO1 and MnSOD was inhibited but the ROS was enhanced significantly in group HG+ Resv+ FoxO1shRNA (t=22.53, 15.31, 14.63, all P<0.05).

FoxO1 is the important transcription factors to protect MCs against the damage of oxidative stress by activating the expression of downstream antioxidant target gene of MnSOD.

At present, with the improvement of living standards, the phenomenon of type 2 diabetes (T2DM) or metabolic risk factors such as impaired glucose regulation, obesity, dyslipidemia and hypertension based on insulin resistance is increasing in individuals. Among them, obesity and insulin resistance are the central links, and people gradually recognize the importance of fat distribution in cardiovascular and metabolic diseases. 1970 McCully^[1]The theory that hyperhomocysteinemia (Hcy) may be involved in the formation of atherosclerosis was proposed for the first time, and the relationship between serum Hcy level and diabetes and cardiovascular disease has been increasingly paid attention to. This study investigated the characteristics of body fat distribution in patients with coronary atherosclerosis T2DM and observed its relationship with serum Hcy.

Adipocyte-type fatty acid binding protein (A-FABP) is a newly discovered adipokine with a wide range of biological functions. As a member of fatty acid binding protein family, A-FABP not only regulates the differentiation of adipocytes, but also participates in the metabolism of sugar and fat. A-FABP is closely associated with a variety of clinical diseases, such as type 2 diabetes, atherosclerosis, dyslipidemia, obesity, insulin resistance and metabolic syndrome. The relationship between A-FABP and insulin resistance and type 2 diabetes is reviewed as follows.

The American Diabetes Society (ADA) and the European Diabetes Society (EASD) on April 19, 2012 atDiabetes CareMagazine^[1]AndDiabetologiaMagazine^[2]The online version jointly released a position statement on "Glucose Management in Type 2 Diabetes Mellitus (T2DM) – Patient-Centered". ADA presented the statement at its annual meeting held in June 2012. This statement is an important document to guide the treatment of T2DM. Compared with previous guidelines or position statements, it has distinct characteristics. Understanding and mastering these characteristics will help to improve the efficacy and safety of diabetes treatment.

gestational diabetes mellitus (GDM) refers to different degrees of glucose metabolism abnormalities that first occur during pregnancy. In recent years, the prevalence of GDM has continued to increase, which may have adverse effects on mothers and infants. Recent complications such as cesarean section, shoulder dystocia, preeclampsia, and long-term adverse outcomes such as the chance of pregnant women developing type 2 diabetes in the future are significantly increased, and the risk of obesity and metabolic syndrome in offspring is increased. Therefore, the management of GDM is essential for the health of mother and child. In 2011, the American Diabetes Association (ADA) and the Industry Standards Committee of the Ministry of Health of China both updated the diagnostic criteria of pregnancy complicated by diabetes, and proposed stricter management of hyperglycemia during pregnancy; The 2012 ADA guidelines are supplemented on this basis. However, in the practical clinical work in China, there are still many challenges in the management of GDM, such as how to determine the appropriate blood glucose control target during pregnancy, which time point of blood glucose monitoring and treatment can benefit better, how to avoid the occurrence of hypoglycemia and how to choose the appropriate blood glucose management plan. Therefore, this article reviews the results of a large number of clinical studies to provide useful references for the clinical practice of GDM management.

Diabetes mellitus is an independent risk factor for cardiovascular disease, and cardiovascular disease is a major health threat and cause of death in diabetic patients. Prospective population studies showed that the 8-year survival rate of patients who survived the first episode of myocardial infarction without diabetes was similar to that of patients with diabetes without myocardial infarction, so diabetes is also called the isocoronary disease^[1]。 Clinical evidence shows that strict glycemic control has limited effect on reducing the risk of macrovascular disease and death in type 2 diabetes mellitus (T2DM), especially in patients with long course of disease, older age, and pre-existing cardiovascular disease or multiple cardiovascular risk factors^[2]。 2010 Guidelines for the Prevention and Treatment of Type 2 Diabetes in China^[3](hereinafter referred to as the new edition of the guidelines) emphasized the importance of comprehensive treatment, and put forward the "ABC strategy of standard drug treatment of diabetic cardiovascular disease", namely antiplatelet therapy (A), blood pressure control (B), and intervention of dyslipidemia (C). This article shares the understanding and experience of ABC strategies in combination with clinical practice, with reference to current guidelines for cardiovascular disease prevention and treatment and evidence-based medical evidence.

Type 1 diabetes and adult occult autoimmune diabetes (LADA) are caused by the destruction of pancreatic islet beta cell immunity. LADA is partially similar to the genetic characteristics of patients with type 1 and type 2 diabetes, and is mainly genetically associated with type 1 diabetes. LADA has a similar immunological profile to patients with type 1 diabetes and is clinically similar to type 2 diabetes. LADA is clinically milder than type 1 diabetes, but its mechanism remains unclear. This study aimed to compare the response of T cells to the pro-inflammatory cytokine interferon-gamma (IFN-gamma) and the anti-inflammatory cytokine interleukin-13 (IL-13) in patients with LADA and type 1 diabetes.

Adult occult autoimmune diabetes mellitus (LADA) is a special type of diabetes mellitus characterized by both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). LADA patients develop antibodies against islet autoantigens but do not rely on insulin therapy in the short term. The Diabetic Immunology Society (IDS) proposes diagnostic criteria for LADA: (1) age ≥35 years; (2) at least one common islet autoantibody is positive, including islet cell autoantibody (ICA), glutamate decarboxylase antibody (GADA), protein tyrosine phosphatase 2 antibody (IA-2A), insulin autoantibody IAA; (3) Insulin therapy is not dependent within six months of onset.

The etiology of latent autoimmune diabetes mellitus (LADA) in adults has not been fully understood. At present, LADA is mainly evaluated by autoimmune markers. Through a cross-sectional study, researchers from Norway compared the positive rates of glutamate decarboxylase antibody (GADA), protein tyrosine phosphatase 2 antibody (IA-2A) and zinc transporter 8 antibody (ZnT8A) in pre-diabetes and confirmed diabetes in type 1 diabetes mellitus (T1DM) and LADA, respectively.

Type 1 diabetes mellitus (T1DM) is highly selective autoimmune diabetes mediated by T cells. Its occurrence and development are determined by genetic factors and environmental factors. The progression to T1DM in people at high risk of diabetes is associated with a progressive decline in the ability of regulatory T cells (Treg) to maintain immune tolerance. Studies have shown that Treg plays an important role in peripheral immune tolerance against islet autoantigens. Recent evidence suggests that this deficiency in immune tolerance is due to a decrease in antigen presenting cells (APCs) that maintain Treg function, rather than T cell defects themselves. Because of this, therapies aimed at correcting Treg dysfunction have become research hotspots.