Volume 06 · Issue 08 · 2014

The global prevalence of diabetes has increased rapidly in recent years, which is closely related to the sharp increase in the number of overweight and obese people. There is obvious insulin resistance in obese patients, and islet β cells proliferate compensatingly, secreting a large amount of insulin to maintain blood sugar stability. Diabetes occurs when islet beta cells lose their ability to compensate. There have been a lot of studies on the mechanism of pancreatic beta cell decompensation, including glycotoxicity, lipotoxicity and so on. Obviously, the proliferation of islet beta cells from compensatory proliferation to decompensation is a continuous change process, and the mechanism of compensatory proliferation of islet beta cells under insulin resistance such as obesity is especially unclear. A large amount of adipose tissue accumulated in obese patients, and the metabolic pressure caused by abnormal lipid metabolism, amino acid metabolism and glucose metabolism are also closely related to the proliferation of pancreatic islet β cells. The compensatory proliferation of pancreatic islet β cells under metabolic stress and its mechanism are reviewed.

Type 2 diabetes mellitus (T2DM) is a common metabolic disease, and its occurrence and development are regulated by environmental factors and many genes. Study found that islet beta cell function impairment is a common feature of diabetes^[1]。 Animal model studies have shown that, in most cases, beta cells are sufficiently functional to maintain blood sugar levels by increasing cell populations and insulin secretion, even in obesity and insulin resistance^[2]。 Only when this compensation is inadequate can it develop into diabetes. In diabetic animal models, the expression of originally highly expressed genes, such as insulin, glucose transporter 2 (GLUT2) and pancreaticoduodenal homeobox 1 (PDX-1), is decreased, while the expression of some normally low-expressed genes, such as lactate dehydrogenase A (LDH-A), hexokinase I and glucose-6-phosphatase, is increased^[3,4]。 In order to intuitively study the role of related genes in pancreatic islet β cells, transgenic mice made by transgenic technology have been widely used in the field of diabetes research.

One of the important characteristics of glucotoxicity is the disappearance of glucose-stimulated insulin secretion, however its mechanism remains unclear to date. A large number of experimental evidences suggest that the depolymerization of microfilaments (F-actin) in β cells is a prerequisite for insulin secretion. Microfilaments are one of the components of cytoskeleton, which play an important role in the intracellular transport and exodus of vesicles, the maintenance of cell morphology and cell migration. Under physiological conditions, microfilaments form a dense reticular structure within beta cells, which hinders the docking and exocytosis of insulin vesicles. Glucose stimulation can depolymerize microfilaments and induce insulin secretion. Our recent work suggests that chronic high glucose culture leads to microfilament cytoskeleton aggregation and resists glucose-induced microfilament cytoskeleton depolymerization, suggesting that abnormal microfilament cytoskeleton remodeling may be one of the mechanisms by which glycotoxicity impairs the secretory function of islet β cells.

The Banting Award for Scientific Achievement (hereinafter referred to as the Banting Award) in honor of Frederik Banting, the father of insulin, is the highest scientific award of the American Diabetes Society (ADA). Dr. Daniel J Drucker, who won the Banting Prize at the 74th ADA Annual Science Conference this year, is a professor of medicine at the Banting and Best Diabetes Center of the University of Toronto, Canada, and a senior scientist at the Lunenfeld Tanenbaum Institute of Mount Sinai Hospital. Following the 44th Claude Bernard Prize at the European Diabetes Society (EASD) in Berlin in 2012, this year is his second award for elucidating the fundamentals of the action of intestinal hormones. On the morning of June 15th, Professor Drucker delivered an award-winning speech at Moscone International Convention Center in San Francisco, USA, with the title of "Deciphering Intestinal Metabolic Information and Promoting Treatment Reform and Innovation". In the research field of intestinal hormones, Drucker is not only the reclaimer who pioneered the virgin land in those days, but also the cultivator of today's science experimental park, and the painter of a bright vision for the future. More than 10,000 diabetes scholars from all over the world gathered together, listening to his moving interpretation, telling the memories of deciphering intestinal metabolic information; What is shown in front of us is a long scroll of translational medicine history from laboratory to clinical, and from clinical to laboratory.

To investigate the protective effects and mechanism of cordyceps sinensis(CS) on the islets cells of rats with type 2 diabetes mellitus.

Streptozotocin combined with highfat diet was used to induce T2DM rats' model. The rats were randomly divided into three groups: model control group (MOR), low dose group (CS₁, 2 ml·kg^-1·d^-1, i.p.) and high dose group (CS₂, 5 ml·kg^-1·d^-1, i.p.). Two treatment groups (CS₁ and CS₂) were given CS for 12 weeks and a normal control group (NOR) was set to observe the effects of CS on rats' glucose metabolism. The following parameters were measured: the fasting blood glucose (FBG), the fasting insulin level (FINS) and the insulin sensitivity index (ISI). TUNEL was used to detect the islets apoptosis. Immunohistochemistry was used to assess the expression level of islet CHOP and JNK stress proteins.

(1) Rats were given CS for 12 weeks, FBG of CS₁ and CS₂ group,respectively (15.8±2.6), (13.1±2.3) mmol/L, were obviously lower than that of MOR group (20.5±3.7) mmol/L, withq values respectively 8.56, 10.20,P values all below 0.01. ISI of CS₁ and CS₂ group, respectively (-5.43±0.32), (-4.35±0.24), were obviously higher than that of NOR group (-5.94±0.41), withq values: 6.38, 8.52,P<0.01. (2) AI of MOR group (0.583±0.137) was obviously higher than that of NOR group (0.154±0.042), (q=12.02, P<0.01). AI of CS₁ and CS₂, respectively (0.369±0.032), (0.241±0.024), were obviously lower than that of MOR, with q values: 4.58, 9.87,P values below 0.05, 0.01. (3) The expression levels of CHOP and JNK in MOR group, respectively (0.362±0.064), (1.35±0.15), were obviously higher than those of NOR group, respectively (0.063±0.021), (0.12±0.03), with q values: 18.87, 26.28,P<0.01. The expression levels of CHOP and JNK in CS₁ were (0.268±0.038) and (0.56±0.07), obviously lower than those of MOR group, with q values: 4.26, 6.75,P values below 0.05, 0.01. CHOP and JNK expression levels of CS_2, respectively (0.152±0.035) and (0.33±0.06), were obviously lower than those of MOR group, with q values: 7.84, 8.97 (P<0.01).

CS can protect the function of T2DM rats' islet cells; the mechanism may relate to reducing apoptosis, decreasing the level of ERS and the expression level of CHOP and JUN.

To investigate the effect of Jin Lida Granule (JLG) on the oxidative stress and insulin signaling in liver of insulin resistance(IR) rat induced by high-fat diet.

A group of 6-8 weeks male Sprague-Dawley (SD) rats were induced as IR models by high-fat food. Then IR rats were randomly divided into high-fat group (n=8), JLG group (n=9) and metformin group (n=9) by random number table. A paired normal-diet group was set up as a control. After ten weeks' treatment, intraperitoneal glucose tolerance test(IPGTT) was performed to measure the levels of serum glucose and insulin at 0, 60 and 120 min. homeostasis model assessment of IR(HOMA-IR) and insulin sensitive index (ISI) were calculated to evaluate the state of IR in liver and whole body, respectively. The level of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT) in liver tissues were measured; besides, the serine phosphorylation of insulin receptor substrate-1(IRS-1) and c-Jun N-terminal kinase(JNK), and the tyrosine phosphorylation of protein kinase B (Akt) were evaluated by Western blotting. The single factor ANOVA was used for data analysis.

In the IPGTT after 10-week intervene, compared with high-fat group, JLG group, metformin group and control group showed a decreased level of fasting serum glucose, postprandial serum glucose and insulin, with a statistical significance in the serum glucose at 60 min and 120 min, and in the insulin at 0 min and 120 min (t=1.76-5.03, all P<0.05); the HOMA-IR attenuated and ISI increased significantly in the JLG group, metformin group and control group(t=-187.63-5 635.06, all P< 0.05). Compared with those in high-fat group, the SOD increased for 64.9% and 64.4%, the MDA decreased for 36.3% and 28.1%, the CAT increased for 101.0% and 41.5%, the GSH increased for 111.0% and 39.8%, the p-JNK/JNK decreased for 26.3% and 15.0%, the p-IRS-1/IRS-1 decreaed for 23.5% and 29.4% and the p-Akt/Akt increased for 43.7% and 42.3%, respectively in the JLG group and metformin group (t=-0.50,-0.28, all P<0.01). However, there was no significant difference between JLG group and metformin group.

JLG obviously improves the insulin sensitivity in rats. The pharmaceutical mechanisms maybe closely associated with the antioxidant capacity, as well as the improvement of insulin signaling transduction in liver including the elevated phosphorylation of Akt, and the reduced phosphorylation of JNK and IRS-1.

To study the role of endoplasmic reticulum stress and c-Jun N-terminal kinase(JNK) pathway in angiotensin Ⅱ (Ang Ⅱ)-caused glomerular podocyte injury and the protection mechanism of resveratrol.

The mouse potocytes were induced differentiation and randomly divided into control group, high AngⅡ group and resveratrol intervention group (AngⅡ +Res group), and the specific inhibitor of JNK pathway SP600125 intervention group (Ang Ⅱ + SP600125 group). Control group was incubated with RPMI1640 medium, the AngⅡ concentration was 10^-8 mol/L, resveratrol concentration was 20 μmol/L, SP600125 concentration was 20 μmol/L. Podocyte morphology in different groups was observed with inverted microscope after treated for 48 hours, and the apoptosis rate was measured with flow cytometer. The mRNA and protein expression of glucose regulated protein 78(GRP78) mRNA and phosphorylated JNK(p-JNK) was messured with real-time quantitative polymerase chain reaction(RT-PCR) and Western blotting. The t test was used for data analysis between group.

Compared with those in the control group, the apoptosis rate and mRNA expression of GRP78 and p-JNK increased significantly in the AngⅡ group(t=9.318, 6.063, 7.160,P<0.05), and the protein expression of GRP78 and p-JNK ascended significantly too(GRP78 protein and p-JNK protein Ⅰ strip, Ⅱ strip,t=4.116, 5.085, 5.117,P<0.05). Compared with those in Ang Ⅱ Group, the apoptosis rate and mRNA and protein expression of GRP78 decreased significantly in Ang Ⅱ + Res group(t=14.328, 4.530, 3.977,P<0.05), the mRNA and protein expression of p-JNK descended significantly too(mRNA and protein Ⅰ strip, Ⅱ strip,t=4.590, 4.990, 4.991, P<0.05). Compared with those in Ang Ⅱ group, apoptosis rate (t=10.756,P<0.05) and the mRNA and protein expression of p-JNK in SP600125 intervention group decreased significantly(mRNA and protein Ⅰ strip, Ⅱ strip,t=5.408, 4.901, 4.886,P<0.05).

Podocyte apoptosis can be induced by Ang Ⅱ in vitro, and it causes apoptosis through endoplasmic reticulum stress and JNK path. However, resveratrol inhibits the apoptosis through inhibition endoplasmic reticulum stress and activation of JNK pathway.

To investigate the effects of 1α,25-Dihydroxyvitamin D₃ on the inflammatory factor and bone metabolism of diabetic rats.

A total of 30 healthy 6-8 weeks old male Sprague Dawley (SD) rats were treated with streptozotocin. The streptozotocin-induced diabetic rats were randomly divided into diabetes group and vitamin D-treated group. Another 10 healthy SD rats were considered as normol control group. The normol control group and diabetes group were fed with 0.05 ml/d nut oil; the vitamin D-treated group was fed with 0.1 μg·kg ^-11·d^-11 1,25(OH)₂D₃, which were dissolved in 0.05 ml nut oil. 12 weeks later, the levels of serum interleukin 17(IL-17), calcium, phosphorus, bone gla protein (BGP) and 24 h urinary calcium, 24 h urine albumin(UAlb) were detected. The expressions of IL-17 were determinated by immunohistochemical staining. The BGP mRNA levels of bone tissue were performed by real-time quantitative reverse transcription polymerase chain reaction assay.

① 24 h urinary calcium and 24 hUAlb levels of the diabetes group were significantly higher than the normol control group [(0.31±0.18) vs (0.01±0.01) mmol/24 h,(1.15±0.13) vs (0.43±0.09) mg/24 h;t=5.125, 13.948, respectively; both P< 0.05]; 24 hUAlb level of the vitamin D-treated group was significantly lower than the diabetes group[(0.82±0.13)vs (1.15±0.13)mg/24 h,t= -5.798,P<0.05]. ② Compared with the normol control group and the vitamin D-treated group, serum IL-17 level and expressions of IL-17 in kidney cortex of diabetes group were significantly higher [(494±28)vs (137±18), (250±20)pg/ml; (165.0±7.0)vs (81.9±5.6), (119.1±6.6);t= 34.229, -23.263, 29.238, -15.475, respectively; allP<0.05].③Compared with the normol control group and the vitamin D-treated group, serum BGP level and the mRNA expression of BGP diabetes group were significantly lower[(485±123)vs (752±239), (621±161)pg/ml; (19.8±2.9)vs (24.1±2.9), (22.9±3.1);t=-3.147, 2.158, -3.220, 2.265, respectively; all P<0.05]. ④Serum IL-17 was negatively correlated with serum BGP (r=-0.544, P<0.05).

Vitamin D can inhibit the expression of inflammatory cytokines such as IL-17 and promote bone metabolism in diabetic rats.

To investigate the effects and mechanism of glucagon-likepeptide1(GLP-1) analogue liraglutide on glucose transporter 4 (GLUT4) translocation of mouse skeletal muscle cells.

In overexpressing C2C12-GLUT4HA cells, observing the effects and molecular mechanism of liraglutide on GLUT4 translocation. C2C12-GLUT4HA cells were divided into the control group, insulin group(100 nmol/L), liraglutide I group(100 nmol/L), liraglutide II group(1 000 nmol/L), 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) (adenosine 5'-monophosphate (AMP)-activated protein kinase agonist)group (2 mmol/L). The amount of GLUT4HA on the cell surface was measured by enzyme-linked immunosorbent assay(ELISA).The phosphorylation of adenosine 5'-monophosphate (AMP)-activated protein kinase(AMPK), protein kinases B (AKT), and GLUT4 expression were tested by western blotting. Statistical analyses were performed using Student'st test or analysis of variance (ANOVA).

The amount of GLUT4HA on the cell surface in liraglutide groups was more than the amount of GLUT4HA on the cell surface in control group (1.53±0.28 vs 1.41±0.41, F=13.4798,P<0.05). The expression of GLUT4 was not changed in liraglutide groups and the control group.The levels of phosphorylation of AMPK were more in liraglutide groups than that in the control group(1.79±0.31 vs 1.54±0.18, respectively,F=20.0999,P<0.05). But the phosphorylation of AKT was not changed(P>0.05).

This study suggests that Liraglutide may induce GLUT4 translocation of mouse skeletal cells by activation of AMPK.

In order to explore the change of pulmonary angiotensin Ⅱ type 1 receptor (AT1R) in diabetic rats and its effect on expression of transforming growth factor-β1(TGF-β1).

Twenty diabetes mellitus (DM) model rats were established via chain of high sugar and high fat diet in combination with small dose of streptozotocin caudal vein injection. They were randomly divided into DM group (n=10), losartan (LST) group (n=10). Each rat of LST group was fed with 30 mg · kg^-1·d^-1, LST for 12 weeks by gavage.Ten normal rats were established as normal control (NC) group. Immunohistochemistry was used to assay the expression of AT1R in lung of each group rats. RT-PCR and western blotting was performed to compare the expression of AT1R and TGF-β1 between different group. One-way analysis of variance was applied to compare data among groups. LSD anaysis was used for comparision between two groups.

Compared with NC group, the expression of pulmonary AT1R and TGF-β1 in DM group rats increased significantly (AT1R mRNA: 0.04±0.03vs 0.29±0.15, t=5.252; AT1R protein: 0.62±0.05 vc 0.77±0.05, t=6.736 ;TGF-β1 mRNA :0.10±0.05vs 0.73±0.16, t=12.377 ;TGF-β1 protein :0.47±0.05vs 0.70±0.05, t=10.66; all aboveP< 0.05). The expression of pulmonary AT1R and TGF-β1 in LST group rats significantly decresed, compared with DM group (AT1R mRNA: 0.292±0.148vs 0.068±0.024, t=4.741; AT1R protein: 0.77±0.05 vs 0.63±0.04, t=7.396;TGF-β1 mRNA: 0.74±0.16vs 0.19±0.09, t=9.563;TGF-β1 protein: 0.702±0.047vs 0.439±0.018,t=16.601; all aboveP<0.05).

Part of the reninangiotensin system may be activated in lung tissue of DM rats, it promoted the increase of TGF-β1 expression and involved in the change of lung extracellular matrix.

To determine the current prevalence and risk factors of metabolic syndrome (MS) among adult residents in Guiyang by the four different diagnostic criteria.

Data came from healthy examination of Guiyang community population.Age and sex standardized prevalences of MS were calculated according to the criteria of Chinese Diabetes Society (CDS), US National Cholesterol Education Program Adult Treatment Panel Ⅲ (ATP Ⅲ), International Diabetes Federation (IDF) and Joint Interim Statement (JIS).The four MS diagnostic concordance were compared by the value of Kappa.

The MS prevalence were 43.6 % for JIS, 29.1 %for IDF, 21.7%for CDS and 40.3%for ATPⅢ, respectively. MS was more popular in female than in male by the IDF criterion(31.0% vs 26.2%, P<0.01).While the prevalence was higher in male by JIS criteria (45.1% vs 38.8%,P<0.01). The highest value of kappa was 0.94 between JIS and ATP Ⅲ. The value of kappa was 0.78 between IDF and ATP Ⅲ.

The prevalence rate of MS in Guiyang City was higher than other area in different diagnostic criteria in China. The MS diagnostic criteria of ATPⅢ and JIS are in good accordance.

To investigate the impact of different virulent strains of Helicobacter pylori (Hp) infection on the insulin resistance and glucose level in the type 2 diabetes mellitus (T2DM) patients. A total of 168 T2DM inpatients were recruited and gastrointestinal symptoms were collected from January 2012 to March 2013. Blood glucose, insulin levers, glycated hemoglobin A1c (HbA1c), blood lipids, liver function and kidney function were tested and IR indexs (HOMA-IR) were calculated for all patients. Based on the Hp protein microarray chip test, the patients were divided into type I group, type Ⅱ group and negative group. Patients in each group continued hypoglycemic therapy while Hp eradication therapy were executed in type I group. All indexs were rechecked 6 months later. Multiple sample mean pairwise comparisons using analysis of variance. Results showed before treatment, the cases of the type I group, type Ⅱ group and negative group were 53, 45 and 70, respectively. There had no statistical difference of the blood lipids, liver function, kidney function in the 3 groups, and the positive rate of gastrointestinal symptoms was 67.9%, 28.9% and 11.4%, respectively; HbA1c were (9.1±0.9)%, (8.2±0.8)% and (7.8±0.8)%, respectively; HOMA-IR were 4.6±1.4, 3.9±1.2 and 3.2±0.9, respectively. After eradication therapy for 6 months, gastrointestinal symptoms of type Ⅰ group decreased significantly. The HbA1c in the type Ⅰ group, type Ⅱ group and negative group decreased to (7.3±0.8)%, (7.1±0.9)% and (6.9±0.6)%, respectively; while the HOMA-IR in 3 groups decreased to 3.9±1.3, 3.4±1.1 and 3.1±0.8, respectively. There was largest decline in HbA1c, HOMA-IR in type Ⅰ group. Compared with before treatment, the difference was statistically significant(both P<0.05). We found that insulin resistance was increased in patients with infectedHp infection, especially with virulent type Ⅰ Hp infection, and which caused poor glycemic control. Treatment should be eradicated as soon as possible.

With the development of social economy and the change of lifestyle, the prevalence of type 2 diabetes mellitus (T2DM) is increasing year by year, and it tends to be younger. Its chronic complications can lead to blindness, gangrene of lower limbs and myocardial infarction, and even life-threatening. The occurrence of T2DM is related to genetic and environmental factors, and recent studies have shown that intestinal flora is closely related to the occurrence of T2DM. Intestinal flora can make the host obtain more energy and also regulate the glucose and lipid metabolism of the host; The change of its quantity and structure can lead to changes in the permeability of the host intestinal wall, increase in circulating endotoxin, induce chronic mild inflammation, promote the occurrence of obesity, insulin resistance, and eventually lead to diabetes^[1]。 In this paper, the role and mechanism of intestinal flora in the development of T2DM and its application in treatment are reviewed.

Diabetic retinopathy (diabetic reticulopathy) is one of the most common chronic complications of diabetes, so that retinopathy occurring in almost all diabetic patients is taken for granted as diabetic reticulopathy, but this is not the case. The case presented in this article is a distant retinopathy misdiagnosed as diabetic reticulosis. In addition, the classification of diabetes is often a difficult problem for clinicians. This patient has similarities with type 1, type 2 and special types of diabetes, so how to classify diabetes is also one of the key contents of this article.

The key to diabetes treatment is to keep blood sugar within the normal range as much as possible and avoid the occurrence of hypoglycemia. Due to the characteristics of progressive development of type 2 diabetes, patients will enter insulin therapy sooner or later. Basal insulin once daily is one of the commonly used insulin initiation therapy regimens. Traditional intermediate-acting human insulin may have more risk of hypoglycemia due to its fluctuating blood concentration, and its action time is less than 24 hours. At present, it has been gradually replaced by insulin analogs with more gentle action and longer duration. Insulin detemir is one of the commonly used long-acting insulin analogs. The insulin has low risk of hypoglycemia, reduces weight gain, is applicable to a wide range of people, and is widely used in basal insulin treatment. In this paper, the evidence of the above characteristics of insulin detemir in clinical studies is reviewed.

In recent years, with the continuous improvement of people's diagnosis and prevention of diabetes, the life span of diabetic patients has been gradually extended, but at the same time, various chronic complications of diabetic patients have also increased correspondingly. Among them, diabetic foot is one of the main causes of disability and death of diabetic patients. Researchers from Baoding, China measured the serum levels of matrix metalloproteinases 9 and 2 (MMP-9, MMP-2) and metalloproteinase tissue inhibitors 1 and 2 (TIMP-1, TIMP-2) in 94 patients with diabetic foot, and observed the relationship between them and the healing of diabetic foot ulcers. The researchers measured the serum levels of MMP-9, MMP-2, TIMP-1 and TIMP-2 at the initial visit, after 4 weeks of treatment, and at 12 weeks of follow-up, respectively. According to the healing rate of the foot ulcer area at week 4, the patients were divided into groups with better and poor ulcer healing. Through statistical analysis, the relationship between MMP-9, MMP-2, TIMP-1 and TIMP-2 and the degree of ulcer healing was looked for.

The risk of lower limb amputation is significantly increased when diabetic foot ulcer infection is particularly accompanied by osteomyelitis. An accurate diagnosis and identification of its pathogenic bacteria can increase the likelihood of osteomyelitis being cured. Imaging-guided bone biopsy is the key link to achieve the above goals. A study from Paris, France, explored a simpler bedside method for confirming the diagnosis of osteomyelitis. For 2 years, 55 patients with diabetic foot disease with foot ulcer and suspected osteomyelitis but no signs of soft tissue infection were selected⁶⁷Ga single photon emission computed tomography and CT (SPECT/CT) examination, patients with positive scan underwent bedside percutaneous bone biopsy. Patients with positive bone biopsy cultures were diagnosed with osteomyelitis and treated with antibiotics under culture guidance. However, patients with negative SPECT/CT results or positive SPECT/CT but negative bone biopsy culture do not need antibiotic therapy.

Diabetic foot osteomyelitis is a major risk factor for amputation in diabetic patients, but the knowledge of its early infection is very limited at present, which affects the diagnosis and treatment of limb salvage in patients. In order to deeply understand the early pathophysiological characteristics of diabetic osteomyelitis, a research team from the Department of Internal Medicine, Department of Rheumatology and Immunology, University of Michigan School of Medicine measured the bone composition in the early stage of diabetic foot osteomyelitis, aiming at deeply understanding the early pathophysiological changes of diabetic foot osteomyelitis.

Recurrent foot ulcers are often long-standing and accompanied by deterioration of the patient's health and may negatively affect the patient's quality of life and adherence to recommended self-management. In addition, recurrent ulcers can increase the long-term cost of diabetic foot ulcer (DFU) treatment, especially for those patients who require home care services or amputation. Since a history of DFU is the biggest risk factor for ulcer recurrence, the International Diabetic Foot Treatment Guidelines recommend that patients go to a specialist for a foot examination every 1 to 3 months. Patients with a lower risk of recurrence may not need such intensive follow-up. Few studies have investigated factors associated with recurrence of diabetic foot ulcers.

Type 1 diabetes is an organ-specific autoimmune disease with genetic basis and induced by environmental factors. Recent studies have shown that the changes of intestinal flora and viral infection may play an important role in the pathogenesis of diabetes mellitus. Enterovirus (EVs) infection may be related to the early clinical stage of type 1 diabetes. The presence of EVs in the blood may act as a biomarker of type 1 diabetes.