Volume 07 · Issue 07 · 2015

diabetic foot (DF) is one of the most serious and expensive chronic complications of diabetic patients. The results of a multi-center survey in China show that about 3% ~5% of hospitalized diabetic patients are DF patients; The annual incidence of DF was 8.1%^[1]Most of the ulcers were combined with infections. diabetic foot infection (DFI) is one of the common causes of amputation in DF patients, and the risk of amputation is 154.5 times that of non-infected patients^[2]。 However, if early diagnosis, rational application of antibiotics and appropriate local treatment of wound can improve the prognosis, save the limbs of patients and restore their motor function to the maximum extent.

The 7th International Diabetic Foot Congress was held at the World Forum Convention Center in The Hague, The Netherlands, from 20 to 23 May 2015, with the participation of 1,425 delegates from more than 100 countries. At this conference, the International Diabetic Foot Working Group issued five clinical guidelines for diabetic foot, among which the Guidelines for the Diagnosis and Treatment of Diabetic Foot Infection (hereinafter referred to as the Guidelines) is of great significance for standardizing the diagnosis and treatment of diabetic foot infection and improving our understanding of foot infection and clinical treatment skills^[1]。

Diabetic foot is one of the most serious and costly chronic complications of diabetes, which can lead to amputation in severe cases^[1]。 According to the data, compared with 2004, in 2012, in 15 tertiary hospitals in 11 provinces and cities in China, patients with diabetic foot disease had more complications and complications, more severe foot ulcers, and a higher total amputation rate, but the large amputation rate was reduced, the healing rate was increased, and the length of hospitalization was shortened^[2]。 The occurrence of diabetic foot disease is mainly related to diabetic lower extremity arterial disease, peripheral neuropathy, foot infection and injury. Compared with other diabetic complications, the management of podiatric complications emphasizes specialized multidisciplinary cooperation and emphasizes prevention^[3]。 Among the multidisciplinary collaborative comprehensive treatment methods, the interventional treatment of diabetic foot uses minimally invasive techniques to reconstruct the peripheral arterial blood flow leading to ulcer and its adjacent tissues, which can improve the microcirculation and oxygen metabolism of ulcer and its adjacent tissues, create favorable conditions for the repair of defective tissues, complement other treatment methods, and can better achieve the treatment goals of ulcer healing and limb saving.

To observe the clinical efficacy and security of high-dose prostaglandin E1 pulse therapy in the diabetic foot patients with peripheral vascular disease.

Based on the same treatment including dressing change, anti-inflammatory and glycemic control, 151 patients with diabetic foot (Wagner grade 1-3) treated from January 2009 to July 2014 in the Sixth People's Hospital in Shanghai were divided into two groups: treatment group (n=85, treated with high-dose prostaglandin E1 (40 μ g/d) for 1 week), and the control group ( n=66, treated with conventional dose of prostaglandin E1 (10 μ g/d) for 2 weeks). Then the healing rate, healing time, amputation rate, ankle-brachial index (ABI), numbness, pain and coldness visual analogue scale (VAS) score and adverse reactions were recorded and analyzed after 3 months of therapy. The t test or Chi-square test was used when data were compared between groups.

The healing rate in Wagner grade 2 and 3 patients in treatment group increased significantly when compared with that in relevant control group (76.0% vs 61.1% and 69.6% vs 42.1%, χ ²=5.21, 15.90, both P<0.05). And the healing time in Wagner grade 2 patients in treatment group was obviously shorter than that in the counterparts in control group ((10.9±4.3) weeks vs (7.7±3.4) weeks,t=2.225,P<0.05). After 3 months of treatment, the ABI increased in the two groups, but only significant difference in ABI was found in Wagner grade 2 patients in treatment group before and after the therapy (0.60±0.21 vs 0.75±0.22,t=2.432,P<0.05). The VAS scores in Wagner grade 1-3 patients in treatment group were all significantly lower than those before the therapy (t=2.292, 2.553, 2.985, all P<0.05), and VAS scores decreased significantly only in Wagner grade 2 and 3 patient in control group (t=2.120, 2.086, both P<0.05). Meanwhile there was no significant differences in the adverse reactions rates between the two groups during the observation period.

High-dose prostaglandin E1 pulse therapy can improve the wound healing rate in Wagner grade 2 and 3, shorten the healing time in Wagner grade 2, relieve lower limbs pain with safety for diabetic foot patients.

To investigate the distribution of pathogenic bacteria, sensitive antibiotics, and their association with the severity of diabetic foot ulcers.

From January 2013 to December 2013, clinical materials from 200 patients hospitalized in Ruijin Hospital, Jiaotong University School of Medicine for diabetic foot ulcers with positive microorganism culture results were consecutively collected. The foot ulcers were classified according to Wagner grade and the severity of their infection respectively. The distribution of pathogenic bacterial, sensitive antibiotics were analyzed to investigate their association with the severity of diabetic foot ulcers. And factors that affect the distribution of pathogenic bacterial were also analyzed with Logistic regression.

Gram positive cocci were the main pathogenic bacteria of foot ulcers in Wagner grade 1 and mild infection (100.0% and 53.5% respectively), of which staphylococcus aureus (32.1% in mild infection, 60.0% in Wagner grade 1), enterococcus faecalis (40% in Wagner grade 1), and streptococcus dysgalactiae (21.4% in mild infection) were the most common ones. Sensitive antibiotics to these bacteria included penicillins and vancomycin. Gram negative bacilli were the main pathogenic bacteria in ulcers with moderate or severe infection (83.3% and 75.4% in moderate and severe infection respectively). In foot ulcers of Wagner grade 3 and 4, various kinds of bacteria were found, of which gram negative bacilli were slightly more than gram positive cocci (gram negative bacilli accounted for 53.3% and 78.7% respectively). Gram negative bacilli were the main pathogenic bacteria of foot ulcers of Wagner grade 5(93.6%); among them, proteusbacillus vulgaris (18.5% and 28.8% in moderate and severe infection respectively), escherichia coli (27.8% and 10.2% respectively), and pseudomonas aeruginosa (7.4% and 11.0% respectively) were most common ones; and the sensitive antibiotics included amikacin, imipenem, and ceftazidime. Wagner grade ((odds ratio,OR)=3.43, 95% confident interval (CI): 1.12-5.39), severity of infection (OR=3.17, 95%CI:1.49- 7.81), history of antibiotic use (OR=1.54, 95%CI:1.02- 2.19), hemoglobin (OR: 1.14, 95%CI:1.08-2.10) and albumin (OR=1.54, 95%CI:1.02-2.19) were the factors that affected type of pathogenic bacteria.

Bacteria and sensitive antibiotics varied among different infection levels and depth of foot ulcers in patients with diabetes. Antibiotics could be empirically selected according to the severity of diabetic foot ulcers.

To investigate the effect of different glucose metabolic statuses on the occurrence and severity of breast cancer.

A total of 131 hospitalized female patients with breast cancer from April 2012 to April 2014 were enrolled as breast cancer group, 72 healthy women without breast diseases as the control group. All the subjects without a history of diabetes in the two groups underwent an oral glucose tolerance test (OGTT). Based on the OGTT results the patients were divided into three groups: normal glucose tolerance (NGT group), impaired glucose regulation (IGR group), and diabetes mellitus (DM group). The information of the subjects were collected including age, menopausal status, body mass index (BMI), blood pressure, sugar metabolism, liver and kidney function, blood lipid indicators, and pathology results of breast cancer group. Binary Logistic regression model was used to analyze the OR value of the associated risk factors of breast cancer.

(1) Compared with the control group, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), fasting plasma glucose (FPG), fasting insulin (FINS), and insulin resistance index (HOMA- IR) in breast cancer group were significantly higher, and all the differences were statistically significant (t=2.17- 3.34, P<0.05). (2) The prevalence of breast cancer among NGT, IGR and DM groups showed statistical significance (the prevalence of breast cancer were 54.6%, 85.4% and 78.1%, respectively, χ²=15.94, P<0.001) and pairwise comparisons showed that the prevalence of breast cancer in IGR group was significantly higher than NGT group (χ²=12.51, P<0.001). There was no significant difference between IGR group and DM group (χ²=0.64, P>0.05). (3) Logistic regression analysis showed that adjusted by age, BMI, blood pressure and blood lipids, IGR and DM were independently associated with risk of breast cancer (OR=4.357, 2.778, respectively, P<0.05). (4) All the pathological parameters of breast cancer patients with different glucose metabolic statuses had no significant difference (P>0.05).

Glucose regulation status has a significantly independent effect on the incidence of breast cancer. In breast cancer risk prediction, the effect of impaired glucose regulation is even greater than that of diabetes.

To observe the efficacy of mesenchymal stem cells (MSCs) transplantation in newly diagnosed patients with ketosis- onset type 1 diabetes mellitus (T1DM), and further evaluate the effects of diabetes duration on the efficacy of MSCs transplantation.

From January 2009 to January 2012, 10 newly diagnosed patients with ketosis-onset T1DM were enrolled in our study and underwent MSCs transplantation in Department of Endocrinology in Drum Tower Hospital Affiliated to Nanjing University Medical School. Of those patients, 4 cases underwent bone marrow MSCs transplantation and 6 cases underwent umbilical cord MSCs transplantation. The insulin dosage, glycated hemoglobin A₁c (HbA_1c) and C-peptide levels in those patients were recorded before/after MSCs transplantation. We divided all patients according to diabetes duration (duration ≤1 month (n=4) and duration>1 month (n=6)) for further analysis. The difference in the recorded values among different time points was determined by one- way ANOVA. The effects of diabetes duration on the efficacy were analyzed by the analysis of stratification and covariance. The survival rate of islet function after transplantation was estimated by survival analysis.

After the transplantation, the insulin dosage and HbA_1c decreased in different degree, and HbA₁c reduced significantly after 6 and 12 months (7.2%±2.1%, 7.2%±1.7% vs 10.3%±3.5%, F=4.435, P<0.05). However, there was no significant improvement in fasting C-peptide (FC-P) and postprandial 2 h C-peptide (2h C-P) levels. Compared with the patients with diabetes duration>1 month, the reduction of insulin dosage was significantly higher after 6 and 12 month (- 0.40±0.64) vs (0.08±0.23) U·kg^-1·d^-1, (- 0.50±0.46) vs (0.08±0.17) U·kg^-1·d^-1,F=7.94, 16.21, both P<0.05) and the increase of 2 h C-P levels was significantly higher after 6 month ((191±258) vs (- 244±276) pmol/L,F=8.69,P<0.05) in the patients with diabetes duration ≤1 month. Moreover, the survival rate of islet function over the course of 12 months was significantly higher in the patients with diabetes duration≤1 month (χ²=3.74, P=0.05).

Allogenic MSCs transplantation can improve glucose homeostasis and reduce insulin dosage in newly diagnosed ketosis- onset T1DM patients. Diabetes duration maybe the key factor affecting the efficacy of MSCs therapy.

To investigate the impact of family history of type 2 diabetes mellitus (T2DM) on pancreatic β-cell function and insulin sensitivity in metabolically healthy overweight/obese individuals.

A total of 435 first-degree relatives of patients with T2DM and 116 spouses without family history of T2DM or impaired glucose tolerance were selected. The individuals were divided into six groups: metabolically healthy normal weight of first-degree relatives (group A), metabolically healthy overweight/obese of first-degree relatives (group B), at-risk overweight/obese of first-degree relatives (group C), metabolically healthy normal weight of spouses (the control group, group A1), metabolically healthy overweight/obese of spouses (group B1), at-risk overweight/obese of spouses (group C1) according to body mass index (BMI) and metabolic status. We used homeostasis model assessment (HOMA-IR) and glucose disposition index (DI1 and DI2) to evaluate insulin sensitivity and pancreatic β-cell function, respectively. T-test was used to measure normal ditribution date, while Mann whitney U test was used to test Skewness distribution data. Covariance analysis was used to exclude the influence of age.

(1) In the group B, HOMA-IR (3.11(1.11, 5.49)) was higher compared to the group A (2.42(0.67, 5.99),P<0.05), and lower compared to the group C (3.80(0.50, 16.02),P<0.05). Simultaneously, DI1(47.17(29.83, 88.93)) was lower compared to the group A (56.07(30.00, 197.90),P<0.05) and higher compared to the group C (38.27(2.46, 225)). DI2(5.02(1.83, 22.51)) was higher significantly when compared to the group C (2.90(0.07, 25.21),P< 0.01), but no statistical significance compared to the group A. (2) When comparing with the B1(2.02(1.44, 6.10)) and A1(2.28(1.07, 7.44)) groups, HOMA-IR in the group B (3.11(1.11, 5.49)) was higher (P<0.05). However, no statistical significance was found in DI2, and DI1(47.17(29.83, 88.93)) was only found significant when comparing with the A1 group (60.00(30.00, 130.81)). Comparing the group A and A1 group, there were no statistical significance in HOMA-IR, DI1 or DI2.

Family history of T2DM may decrease insulin sensitivity of MHO individuals.

To investigate the efficacy of liraglutide in metabolic parameters and pregnancy situations on polycystic ovary syndrome (PCOS) combined with impaired glucose tolerance and obesity.

A total of 177 patients who diagnosed as PCOS combined with impaired glucose tolerance, obesity and infertility were collected in this study from March 2011 to March 2014. They were randomly divided into liraglutide group ((28±7) yrs) and control group ((27±7) yrs). Patients in control group were treated with metformin (0.5 g, tid) and the liraglutide group were treated with metformin (0.5 g, tid) and liraglutide (1.2-1.8 mg/d). The body weight, blood biochemical patametres and sex hormone levels were detected at 0, 12, 24 weeks after treatment. Independent-samples t test and Chi-square were used for statics.

(1) The body weight, waist circumference and BMI were significantly improved in both groups after treatment for 12 and 24 weeks. Compared with the control group, the body weight, waist circumferences, body mass index (BMI) were significantly decreased in liraglutide group (t=10.11-19.97, all P<0.01). (2) Compared with the control group, 2 - hour postprandial blood glucose (2 hPG) and glycated hemoglobin A_1c(HbA_1c) were significantly decreased in Liraglutide-group ((7.5±1.2) vs (8.0±1.1) mmol/L, (5.5±0.8)% vs (6.0±0.3)%,t=31.61, 21.93, both P<0.05). (3) The level of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein-cholesterol (LDL-C) were decreased in Liraglutide group than the control group after 24 weeks (t=13.44- 21.56, all P<0.05). (4) The level of testeserone (T), luteinizing hormone (LH), follicule- stimulating hormone (FSH) were decreased in liaglutide group after 12 weeks and 24 weeks than the control group (at 24 weeks, TSH (4.2±0.4) vs (5.0±0.6) U/L, LH (6.1±1.4) vs (8.2±1.2) U/L,t= 13.72, 204.3, both P< 0.05). (5) The measurements of fasting insulin (FINS), homeostasis model assessment (HOMA) of insulin resistance (HOMA-IR) were decreased while the HOMA-β was increased in liraglutide group after 12 weeks and 24 weeks (t=20.75- 35.78, all P<0.05). (6) In Liraglutide-group, changes of the menstrual cycle, temperature and natural conception odds were significantly increased in comparison to the control group (86.2% (75/87) vs 70.5% (60/85), 78.1% (68/87) vs 50.5% (43/85), 42.5% (37/87) vs 22.3% (19/85), χ ²=10.769, 14.281, 7.97, all P<0.05).

Liraglutide may effectively reduce body weight, improve glucose- lipid metabolism and the level of sex hormones. Furthermore, liraglutide may also promote the natural pregnancy rate.

To assess the concordance rate of lipid risk between non-high density lipoprotein cholesterol (non-HDLC) and apolipoproteinB (ApoB) targets in patients with diabetes.

A total of 460 patients from Beijing Chaoyang hospital with newly diagnosed type 2 diabetes without history of cardio-cerebral vascular disease were enrolled in this study during the period from Jan 2013 to Jan 2014. Body height, body weight, body mass index (BMI) and blood lipid were measured.Data from 460 determinations of low density lipoprotein cholesterol (LDL-C), non-HDLC and Apo B in patients were analyzed. To evaluate the relation between Non-HDLC and Apo B in patients with diabetes with triglyceride (TG) 200- 499 mg/dl. Rates of discordance were calculated, based on the currently recommended LDL-C, non-HDLC, and Apo-B goals acknowledged by the American Diabetes Association (ADA) and American Collegeof Cardiology (ACC) panel. Data was analyzed by linear regression and Kappa analysis to show the concordance of LDL-C, non-HDLC and Apo B in T2DM patients.

In patients with diabetes and hypertriglyceridemia, a positive relationship exists between non-HDLC and Apo- B observed by correlated analysis (r=0.86, P<0.001), whereas a weak correlation among the overall diabetes. In patients with non- HDLC goal of<130 mg/dl, there was a discordance with Apo-B level goal of<90 mg/dl in 40% of samples. In patients with non-HDLC goal of<100 mg/dl, 12% of samples had Apo B>80 and 16.9% had Apo B< 80 mg/dl. Using the Apo B goal of<70 mg/dl, these numbers were 24% and 4.4% respectively.

In practice, non-HDLC and ApoB have an obvious correlation in diabetes patients. To some extent, these two parameters have the equivalence in assessment of cardiovascular risks in diabetes with dyslipidemia.

To observe the effect of long noncoding RNA (lncRNA)-urothelial carcinoma associated 1 (UCA-1) on the Ser/Thr protein kinase (Akt) signal pathway in 3T3-L1 adipocyte and glucose uptake activity.

UCA-1 was overexpressed or silenced by plasmids or specific siRNAs transfection into 3T3- L1.Then the effect of UCA-1 on the Akt signal pathway in 3T3- L1 adipocyte was measured by western blotting. And 2-deoxy-³H-D-glucose incorporation assay was performed to measure the glucose uptake activity in 3T3-L1 adipocyte. SPSS12.0 statistical software was used for statistical analysis. Experimental data were showed in average±standard deviation, and t test was performed in comparison between the two groups, while single factor variance analysis for multiple groups comparison.

The mRNA level of UCA-1 was gradually elevated in the differentiation process of 3T3-L1 from pre-adipocyte to mature adipocyte, up to (3.48±0.09) folds, t=12.093,P<0.01 on Day 6, compared to pre-adipocyte. Overexpression of UCA-1 in 3T3- L1 adipocyte could enhance the phosphorylation of Akt and FOXO 1(p- AKT (S473): 1 103±42 vs 2 338±59,t=16.390,P<0.01; p-AKT (T308): 1 524±34 vs 3 565±45,t=13.025,P< 0.01; p- FOXO1: 912±21 vs 2 190±31,t=10.544,P<0.01). Specific siRNA can down- regulate UCA- 1, reverse the phosphorylation of Akt and FOXO1 (p-AKT (S473): 1 090±22 vs 540±34,t=11.045,P<0.01; p- AKT (T308): 1 409±26 vs 805±18,t=9.527,P<0.01; p-FOXO1: 2 444±29 vs 459±31,t=16.899,P<0.01). Overexpression of UCA-1 could also enhance the glucose uptake activity, up to (2.21±0.09) folds,t=5.922, P<0.05, and down-regulation of UCA-1 could reduce the glucose uptake activity by 66%,t=5.557,P<0.05. Overexpression of UCA- 1 could enhance the glucose uptake activity corporately with the stimulation of insulin, up to (3.25±0.12) folds,t=5.709,P<0.05, and down-regulation of UCA-1 could reduce the glucose uptake activity by 77%,t=6.567,P<0.05.

UCA-1 could activate the Akt signal pathway in 3T3-L1 adipocyte and enhance the glucose uptake activity.

Charcot foot, also known as Charcot neuroarthropathy, is an inflammatory disease involving the bones, joints and soft tissues of the foot and ankle, often accompanied by varying degrees of bone destruction, joint subluxation or dislocation, and the collapse of the middle of the foot in a "navicular" deformity as its characteristic change^[1]； The disease was named after Charcot after it was first reported in 1868. It can be caused by diseases with combined nerve damage such as leprosy, poisoning (ethanol, drugs), spinal disease and radiculopathy. In 1936 Jordan first discovered that diabetes was closely related to it. At present, diabetic neuropathy has become the most common cause of Charcot foot, which is also known as diabetic Charcot neuroarthropathy. Because its incidence is not high, and it only manifests as local redness and swelling in the early stage, it is easy to misdiagnose and misdiagnose in clinic. Therefore, strengthening the understanding of Xia Ke foot is of great significance for reducing the occurrence of ulcers and preserving the lower limbs.

Bile acids are the main components of bile, which are converted and synthesized by cholesterol in liver cells, and discharged into the intestine through the biliary system, mediating the digestion and absorption of lipids, fat-soluble vitamins and other substances. Recent studies have found that bile acids are not only important substances in food digestion and absorption, but also can be used as signaling molecules to regulate the metabolism of glycolipid and energy in the body through signaling pathways mediated by farnesol X receptor (FXR) and G protein coupled bile acid receptor (TGR5)^[1]。 Bariatric surgery is one of the most effective methods for treating obesity and its comorbidity type 2 diabetes mellitus (T2DM)^[2]But its mechanism of action has not been fully defined. Studies have shown that bile acids may play an important role in the alleviation of T2DM in bariatric surgery. The mechanism of bile acids in bariatric surgery is reviewed.

Angiogenesis refers to the biological process of proliferation and migration from the original vascular endothelial cells, forming new vascular network, and growing new blood vessels on the original vascular structure. Angiogenesis is involved in the development of many important physiological and pathological processes in the body. Under normal circumstances, angiogenesis only occurs in the embryonic development period (early embryonic development involves angiogenesis, that is, the process of blood vessels from scratch), the wound healing period and the physiological cycle of women, etc. Abnormal angiogenesis will occur under pathological conditions, such as diabetic vascular disease and tumor, which are accompanied by abnormal angiogenesis. In vivo, angiogenesis needs to undergo a multi-step fine regulation process. Studies have shown that the signaling cascade mediated by vascular endothelial growth factor (VEGF) and its receptor (VEGFR) is a key regulatory pathway, which plays an important role in regulating both physiological and pathological angiogenesis^[1]。 In-depth understanding of the mechanism of action of VEGF/VEGFR signaling pathway is helpful for the research of related diseases and the development of new drugs. The research on vascular endothelial growth factor receptor 1 (VRGFR-1, Flt-1) and its soluble receptor subtype (sFlt-1) is very necessary for the study of the pathophysiological mechanism of angiogenesis, and it is also the hot and difficult research at present.

The diagnosis and treatment of osteomyelitis became a central issue at the 7th World Congress on Diabetic Foot Disease, held in The Hague from 20 to 23 May 2015. Dr. Bonnie Hurwitz, entitled "Microadvances, New Technologies and New Ideas in Diabetic Foot Disease", states that about 63% of patients with diabetic foot infection are complicated with osteomyelitis and may have soft tissue infections. When diabetic foot osteomyelitis reaches a moderate or higher degree of infection, urgent and early debridement surgery is needed. At this time, antibiotics can't play a role. Early surgery can remove necrotic soft tissue, reduce the pressure on the infected site, and eliminate local microcirculation abnormalities caused by infection. In addition, since the level of amputation is related to the time of tissue infection, early debridement surgery can also avoid large amputations. The success of surgery depends on the surgeon's familiarity with the knowledge of podiatric anatomy, the physician's expertise and the seriousness of management. At the same time, a good prognosis also depends on the presence of at least one patent blood vessel at the debridement site. Studies have found that the patency of blood vessels can cure more than 95% of osteomyelitis patients after conservative and small amputation treatment.

1. Diabetic foot infection must be diagnosed clinically, based on local or systemic signs or symptoms of inflammation (strong/low).