Volume 05 · Issue 07 · 2013

Type 1 diabetes has been referred to as "insulin-dependent diabetes", "juvenile onset diabetes", "autoimmune diabetes", etc. These names reflect some of the clinical features of the disease. By 1997 and 1998, the American Diabetes Association (ADA)^[1]And the World Health Organization (world health organization, WHO)^[2]It has been suggested to formally name the disease after "type 1 diabetes" and has gradually been widely accepted by countries all over the world. However, due to the wide heterogeneity of type 1 diabetes (including racial differences), the current major guidelines and consensus statements have not put forward clear diagnosis or classification criteria of type 1 diabetes. From a clinical point of view, with the increase of the age of onset, the difficulty of establishing the diagnosis of "type 1 diabetes" increases exponentially, which is an important reason why many epidemiological studies set the high age limit of onset of type 1 diabetes patients to 15~20 years old. It is due to the lack of clear and objective diagnostic criteria that it is expected that "type 1 or type 2?" will still frequently trouble clinicians and scientific researchers in the future. Based on the current international authoritative guidelines and large-scale studies, this paper tries to explore a way to formulate a suitable reference standard for the diagnosis of type 1 diabetes in China, combined with relevant reports on the characteristics of type 1 diabetes patients in China. In addition, due to the lack of exact large-scale epidemiological data, it is still unclear exactly how many patients with type 1 diabetes are present in China. This article will try to make a preliminary inference on the number of patients with type 1 diabetes in China, in order to provide basis and help for the government health administration department to formulate relevant policies on type 1 diabetes in the future.

polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disease in women of childbearing age. The incidence rate of this population ranges from 8% to 12%^[1]。 PCOS is clinically heterogeneous, and patients can exhibit menstrual disorders, polycystic ovaries, ovulatory disorders, hirsutism, acne, and metabolic abnormalities such as glucose and lipid^[9]。 The cause of PCOS is still unknown, but it is known to be affected by both genetic and environmental factors^[2]。 Hyperandrogenemia, insulin resistance and hyperinsulinemia are important pathophysiological changes of PCOS.

To explore the relationships of human leukocyte antigen (HLA)Ⅰgene frequency with islet function and the four islet autoantibodies(glutamic acid decarboxylase antibody (GADA), zinc transporter 8 antibody (ZnT8A), protein tyrosine phosphatase-2 antibody (IA-2A) and insulin autoantibody (IAA)) in Chinese patients with type 1 diabetes mellitus(T1DM) in Jiangsu Province.

A total of 330 patients with T1DM treated in 26 centers in Jiangsu Province from June 2008 to October 2012 were included in this data set. The HLA-Ⅰ gene was genotyped by the polymerase chain reaction-sequence oligonucleotide probe system method (PCR-SSO), and the four islet antibodies were detected by radioligand assay. HLA-typing control data were drawn from 20 248 individuals in the Chinese Marrow Donor Program with similar genetic backgrounds. The frequencies of HLA alleles and haplotypes were analysed by Arlequin software. The independent sample t test was used in comparison of quantitative data.

Compared with those in controls, the frequencies of HLA-A*24, B*08, B*41, B*54, B*58 were significantly higher (OR=1.250, 2.062, 6.927, 2.472, 1.608, all P<0.05) and that of A*01, B*07, B*27, B*52, B*57 were significantly lower (OR=0.481, 0.464, 0.372, 0.160, 0.315, all P<0.05) in patients with T1DM; the frequency of HLA-A*24-B*54 haplotype was significantly higher (OR=4.128, P< 0.05) in patients with T1DM. The T1DM individuals with the A*02 gene locus had a higher fasting C peptide level than those without A*02((356±249) vs (250±199) pmol/L,t=-3.004, P<0.05). No relationships betweenHLA Ⅰgene and four autoantibodies were found in those patients.

Among T1DM patients in the Jiangsu Han ethnic group, the HLAⅠ loci may affect the their susceptibility to T1DM and the destruction rate of pancreatic β cell.

To analyze the micro-RNA(miRNA) expression profile in pancreas of type 1 diabetes (T1DM) model of NOD mouse and elucidate the association between miRNA and type 1 diabetes.

Twenty NOD mice were raised, and 3 mice sacrificed on 18 weeks, remaining were killed on 25 weeks. Pancreas sample were collected for pathological analysis to classify the insulitis. MicroRNA array were used to analyze miRNA expression profile in 3 samples with different grade of insulitis (0 grade, 2^nd grade, and 3^rd grade insulitis), results were validated by quantitative reverse transcription-PCR in pancreas sample.

13/20 NOD mice developed diabetes by 25 weeks, there were 0-3 grades of insulitis. By microarray analysis, clustering analysis can distinguish insulitis with no insulitis; indicate a different miRNA profile in insulitis. Compared with no insulitis, 2^nd grade insulitis had 2 upregulated miRNA and 19 downregulated miRNA, while 3^rd grade insulitis had 31 downregulated miRNA. For the 7 immune associated miRNA, miR-125b had significant downregulation, miR-125b-5p downregulated for 0.42 and 0.60 folds, miR-125b* and miR-125b-3p downregulated for 0.05 and 0.36 folds, which was validated by qRT-PCR.

Distinct miRNA expression profile is found during insulitis progression, indicating a potential role of miRNA in T1DM development. miR-125b has significant down-regulation effect in T1DM, which indicates its role for islet cell apoptosis.

To analyze the clinical features among 13 cases of neonatal diabetes mellitus (NDM).

Thirteen cases with NDM received treatment in our department between July 2001 and June 2012.The clinical features were reviewed retrospectively.

The age at diagnosis was 0.4-5.0 months, the median age of diagnosis was 3 months. Seven cases were small for gestational age(SGA) infants. Infection presented in 8 cases, 2 cases presented with viscose urine, 2 cases presented with poor reaction, 2 cases presented with poor appetite, 1 case presented with seizure. Seizure was seen in 4 cases. Six cases had diabetic ketoacidosis(DKA). The mean glycated hemoglobin A1c(HbA1c) at onset was 10.0%(7.4%-14.2%). Insulin treatment was started in all 13 patients, the initial dose was 1.0-1.2 U·kg^-1·d^-1, and their blood glucose was well under control. Among the 13 cases followed up, 8 cases were verified as permanent NDM(PNDM), 4 were transient NDM(TNDM), 1 case missed after discharge. One child had skeletal dysplasia and was diagnosed as Wolcott-Rallison syndrome. Six cases were treated with glyburide, only 1 boy who diagnosed as developmental delay, epilepsy and neonatal diabetes syndrome(DEND) got good sugar control, 2 cases stopped glyburide treatment for gastrointestinal side effects. Unfortunately, the patient diagnosed with DEND died at the age of 2.5 years because of DKA, another case died of hepatic and renal failure at the age of 1.5 years. The blood glucose of most patients was well controlled at the follow-up.

The clinical expressions of NDM were atypical and easily miss-diagnosed. Of all the NDM cases, up to 31% was TNDM and relieved automatically. Insulin was the best choice before genetic identification.

To explore the clinical regulation of diabetes education with family members involvement by comparing the influences of different types of family member/patient combination on the long-term therapeutic compliance of patients with type 2 diabetes mellitus.

Total of 300 voluntary pairs of patient-family member treated from March to May in 2010 were sampled and divided into 4 groups according to the relationships between patient and family member: wife supervising husband, husband supervising wife, younger supervising elder and elder supervising younger. The influencing factors on good therapeutic compliance were evaluated in different types of subjects combination after 24-month observation by means of the modified Deborah's diabetes knowledge, self-management skills and self-evaluation table established in previous study. The independent samplet test was implicated in data comparison between two groups and variance analysis in data comparison among groups.

There were more female than male family members(60% vs 40%, χ ²=24.00, P<0.05), and mainly from the group of wife supervising husband (31%). There were significant differences in age of patients and family members, number of active contacting by family members, voluntary participation in diabetic education of family members among the groups(χ²=61.18, 107.77, 35.45, 44.79, all P<0.05). The active contacting came mainly from wives in group of wife supervising husband. Few family members voluntarily attended diabetes education program than expected with less than 3 times during 2 years of observation. Compared with that before observation(33.9%), sustained rising trend of good therapeutic compliance in group of husband supervising wife was observed in following points of observation period (60.3%, 67.9%, 70.9%, 74.1% at the 6th, 12th, 18th, 24th months respectively, χ²=6.762, 9.626, 12.131, 11.707, all P<0.05). Rising but keeping at relatively high level of the good compliance was observed in both groups of younger supervising elder and wife supervising husband but a '∧' -like distribution in group of elder supervising younger. At the end of observation, the total patients' good compliance rate was 52.3%, it was 74.1% in group of husband supervising wife, 60.8% in group of younger supervising elder, 48.3% in group of wife supervising husband and 29.0% in group of elder supervising younger. Logistic analysis showed that gender, age, frequency of active connection and grouping of family members(OR=3.593, 0.251, 2.734, 0.692, all P<0.05) as well as gender, degree of education and grouping of patients(OR=0.497, 2.558, 0.443, all P<0.05) were significant independent influencing factors on the total good therapeutic compliance.

The best long term good therapeutic compliance is found in group of husband supervising wife. As supervisor, female is better than male and the younger generation is better than the elder.

To observe the effect of tripterygium and irbesartan on nephrin and podocin expression in the podocyte of diabetic nephropathy rats.

Fifty SD rats(weight 200-260 g) were randomly divided into control group(group C) and model group. Rats in model group were then divided into diabetic nephropathy group (group DN), Irbesartan group ( group I) , Tripterygium group ( group T) and combined treatment group(group T+ I ) after being given streptozotocin (STZ) (60 mg/kg) by a single intraperitoneal injection to establish animal model of diabetes. After 8 weeks, blood and Urine index were measured. The renal cortical tissues were obtained and used for HE staining to determine pathological changes. The expression of nephrin and podocin in renal cortices were semiquantitatively measured with RT-PCR.

Compared to group DN, the mRNA expressions of nephrin and podocin were higher in the cortex of renal in group (T+ I) compared to group DN (0.507±0.024 vs 0.276±0.015, P<0.01 and 0.533±0.024 vs 0.463±0.022,P<0.01). The expressions of nephrin and podocin protein were higher in the cortex of renal in group (T+ I) compared to group DN (0.738±0.029 vs 0.199±0.012,P<0.01 and 0.811±0.032 vs 0.227±0.014,P<0.01). HE and Masson staining showed that the glomerular volume became bigger, messegium increased, mesangial cells proliferation, basement-membrane thickening and lymphocytes and mononuclear cell infiltration in group DN, which reduced in Irbesartan group and Tripterygium group, and further reducing in combined treatment group.

Tripterygium combined irbesartan play a protective role on the podocytes in diabetic nephropathy rats. The mechanism may be partly through the up-regulated expression of nephrin and podocin in kidney.

To investigate the effects of telmisartan on insulin sensitivity and adiponectinexpression in primary cultured human preadipocytes and adipose tissue of spontaneously type 2 diabetic OLETF rats fed with high-fat diet.

Human subcutaneous and visceral preadipocytes were differentiated for 14 days in serum-free medium, in the presence of 10 μmol/L telmisartan (group H-T), or pioglitazone (group H-P), or vehicle (group H-N). Insulin sensitivity of preadipocytes was detected by glucose consumption test. Radioimmunoassay was employed to determine the concentration of adiponectin in the culture medium. The mRNA expression of adiponectin was measured by real-time fluorescence quantitative polymerase chain reaction(real-time PCR) with TaqMan probe. From 22 weeks of age, the pre-diabetic OLETF rats, which were fed with high-fat diet from 8 weeks old, were divided into group O-HFD, O-T (treated with telmisartan 5 mg·kg ^-1·day^-1), or O-P (treated with pioglitazone 10 mg·kg^-1·day^-1). The insulin resistance of OLETF rats were determined by euglycaemic-hyperinsulinaemic clamp test and oral glucose tolerance test (OGTT). The mRNA and protein expression of adiponectin in the subcutaneous and visceral adipose tissue were measured by real-time PCR and Western blot. The statistical analyses were performed using the SPSS 13.0 software package, and the significance of differences between groups was analyzed by one-way ANOVA.

The glucose consumption of human visceral preadipocytes in group H-T ((5.6±1.6) mmol/L) and H-P ((4.4±1.6) mmol/L) were higher than that in group H-N ((2.0±0.8) mmol/L). The 60-120 min glucose infusion rates in euglycaemic-hyperinsulinaemic clamp test were (18±5) and (20±4) mg·kg^-1·min^-1 in group O-T and O-P, Prespectively, which were both higher than that of group O-HFD((10±3) mg·kg^-1·min^-1, F=8.136, P<0.05). That improvement was also manifested with the HOMA index of insulin resistance in OGTT of OLETF rats (F=5.784, P<0.05). Telmisartan reduced the abdominal circumference((24.0±2.0) vs (26.5 ± 2.7) cm), visceral fat tissue coefficient (5.8%±2.4% vs 8.6%±2.4%), serum free fatty acids ((2.8±0.7) vs (5.3±1.8) μg/L) and the fasting plasma glucose ((10±6)vs(15±7) mmol/L) in high-fat-diet OLETF rats(P<0.05). The mRNA and proteinexpression of adiponectin in human preadipocytes and the adipose tissue in OLETF rats were up-regulated significantly by telmisartan (P<0.05). The especially important result was that the mRNA and protein expression of adiponectin in the human visceral preadipocytes and the OLEFT rats visceral adipose tissue were higher in group H-T and group O-T than those in group H-P and O-P(59.9±2.0 vs 6.0±1.6, 1.807±0.297 vs 1.332±0.112, 4.43±2.57 vs 1.71±0.57, 2.6±0.9 vs 1.9±0.5, with allP<0.05).

Telmisartan can increase the insulin sensitivity in the high-fat-diet OLETF rats and the human preadipocytes, ameliorate the visceral obesity and improve the glucose and lipid metabolism in the OLETF rats Those effects might via the upregulation of adiponectin expression in the adipose tissue, especially in the visceral adipose tissue.

To investigate the inhibitory effect of adiponectin on the human breast carcinoma cell line MCF7 and to explore the potential mechanism.

MCF7 cells were grown in RPMI 1640.The expression of adiponectin receptors in MCF7 cells, including adiponectin receptor 1 and adiponectin receptor 2, was detected by the RT-PCR assay.The total cell count and the percentage of cells at different stages of cell cycle were measured after the exposure to human adiponectin at 20 μg/ml or 40 μg/ml for 48 hours.The expression of phospho-AMPK (THr172)/AMPK, phospho-Akt (Ser473)/Akt, cyclin D1 and cyclin E2 was determined by Western blotting.Comparisons between groups were performed using one-way ANOVA.

(1) MCF7 cells express both adipo-R1 and adipo-R2.(2) Treatment of the cultured MCF7 cells with human adiponectin resulted in a dosage-dependent suppressive effect on the cell proliferation.At 20 μg/ml and 40 μg/ml, human adiponectin inhibited the growth of MCF7 cells by 13.3% and 27.1%, respectively ( F=20.438, P<0.05). (3) Adiponectin treatment leads to suppression of cell proliferation, which is primarily due to the significant increase of cell populations at G₁/G₀ phase (control group 45.1%±0.7%, 20 μg/ml adiponectin group 49.1%±1.3%, 40 μg/ml adiponectin group 50.1%±1.1%, F=17.339, P<0.05), concomitant with these changes, the percentage of MCF7 cells in S phase was decreased (control group 39.9%±1.2%, 20 μg/ml adiponectin group 36.4%±1.5%, 40 μg/ml adiponectin group 36.0%±2.1%,F=9.715, P<0.05). (4) Adiponectin treatment markedly increases the phosphorylation (Thr172) of AMPK in MCF7 cells within 30 min.The expression of phospho-AMPK-α was 0.44±0.01, 0.67±0.02 and 0.72±0.03 in the control group, the 20 μg/ml adiponectin group and the 40 μg/ml adiponectin group, respectively (F=91.07, P<0.05). Prolonged exposure to adiponectin for 24 hours resulted in the expression reduction of cyclin D1.The expression of cylcin D1 was 0.81±0.03, 0.70±0.03 and 0.59±0.03 in the control group, the 20 μg/ml adiponectin group and the 40 μg/ml adiponectin group, respectively (F=30.25, P<0.05). The treatment of adiponectin for 48 hours markedly decreased the expression of cyclin E2.The expression of cylcin E2 was 0.83±0.04, 0.72±0.02 and 0.64±0.02 in the control group, the 20 μg/ml adiponectin group, and the 40 μg/ml adiponectin group, respectively (F=21.17, P<0.05).

Direct anti-proliferative effect has been shown in the MCF7 cells, which may be mediated by the activation of AMPK pathway and the reduction in the expression of cyclin D1 and cyclin E2.

To analyze a rare case of pulmonary mucormycosis in a 14-year-old type 1 diabetes child and review the literatures of pulmonary mucormycosis in diabetes. The child was new onset type 1 diabetes and ketoacidosis combination with pulmonary mucormycosis. There was poor efficacy of treatment with amphotericin B liposome after admission 2 weeks and no effect of fibreoptic bronchoscopy. She died from severe haemoptysis due to no lung surgery. The literatures suggest that mucormycosis mostly occurs in poor glycemic control in adults with type 2 diabetes, rarely occurs in children new-onset type 1 diabetes. Current international recommendations on pulmonary mucormycosis diabetes requires early diagnosis, active treatment of primary disease, surgical debridement and liposomal amphotericin B.

To investigate the current work and barrier of diabetes educators who had the certifications of Chinese Medical Association-Chinese Center for Disease Control-Johnson & Johnson Diabetes Institute. Cross-sectional investigating method was used in this study, 197 educators and 55 managers were questioned for the implementation and problems in the diabetes patient education following the training in Chinese Medical Association-Chinese Center for Disease Control-Johnson & Johnson Diabetes Institute. The questionnaires were send and retrieved by email. The diabetes educators were required to fill in the questionnaire for diabetes educator and the managers were required to fill in the questionnaire for education leader. In these diabetes educators, 89% satisfied with the training class, 28% were the full-time diabetes educators in their department, 78% had no enough time to educate patient. For managers, 91% were satisfied with the work of patients education carried out by these educators. Although project of diabetes educator training is successful, many department have no full-time educators. The post-training assessment and certification system and full-time education posts should be established as soon as possible.

The main pathogenesis of type 2 diabetes mellitus (T2DM) includes insulin resistance and islet dysfunction. Insulin resistance is manifested by the decrease of insulin-mediated glucose uptake and increase of liver glucose output in peripheral tissues such as muscle and fat. Pancreatic islet dysfunction is characterized by a decrease in glucose-stimulated insulin secretion by beta cells and inappropriate secretion of glucagon by alpha cells. Metformin has been widely recommended as a first-line drug, and its main mechanism of hypoglycemic effect is to improve insulin resistance. In recent years, dipeptidyl peptidase-4 (DPP-4) inhibitors have received extensive attention as novel oral hypoglycemic drugs, which mainly improve blood glucose control by improving pancreatic islet dysfunction. Clinical studies have shown that combination therapy with DPP-4 inhibitors and metformin can bring more benefits to patients with T2DM. This article will discuss the combination therapy from the two aspects of efficacy and safety.

The majority of patients with type 2 diabetes eventually require insulin replacement therapy due to declining islet beta cell function. The 2012 American Diabetes Society (ADA) /European Association for Diabetes Research (EASD) Joint Statement states: Ideally, individualized insulin therapy regimens should be developed according to different patients, so as to match the patient's diet, exercise and blood sugar status^[1]。 Among the different types of insulin therapy regimens, the basal-meal insulin regimen can provide fine and flexible meal insulin coverage. This article illustrates a "patient-centered" treatment strategy for multiple types of diabetes in conjunction with this guideline.

The effect of the combined regimen of insulin glargine and insulin glulain on blood glucose during exercise and strategies for how to protect against exercise-induced hypoglycemia in such patients have been rarely reported. Intermittent high-intensity exercise has been reported to prevent the development of hypoglycemia, but the effect in patients with type 1 diabetes with insulin glargine and insulin glulain is still unknown. This was studied by the Weisnagel research team at Laval Medical Center in Canada.

Physical exercise is an important component in diabetes treatment and poses challenges while providing health benefits. Adolfsson et al., Institute of Health Sciences, University of Gothenburg, Sweden, explored the difference of maximum exercise power and hormonal response to different intensity physical exercise among adolescent men and women with type 1 diabetes and healthy controls.

For patients with type 1 diabetes, patients who are physically active in leisure time have a higher and more severe incidence of diabetic complications than patients with high activity levels. It is still unclear whether exercise is beneficial to the control of blood sugar in patients with type 1 diabetes. However, aerobic exercise had little effect on glycosylated hemoglobin (HbA1c). In contrast, studies have evaluated resistance exercise (weightlifting) and found that it reduces HbA1c levels compared with aerobic exercise. Resistance exercise is a type of high-intensity activity performed over a relatively short period of time. It has many potential benefits for patients with type 1 diabetes, such as increased muscle strength, improved blood lipid levels, reduced insulin dosage, and reduced self-monitored blood sugar levels, but these benefits have not been proven.

It is an indisputable fact that appropriate exercise can bring benefits to diabetic patients, but the definition of reasonable amount of exercise has been inconclusive, especially for gestational diabetes patients. Kumareswaran and others from the Biomedical Research Center of Cambridge University in England described the exercise patterns of pregnant women with type 1 diabetes, and evaluated the effect of increasing regular physical activity on blood glucose control.