Volume 08 · Issue 07 · 2016

Diabetic foot has a high rate of disability and mortality, which is the main reason for hospitalization of diabetic patients. In China, diabetic foot ulcer has become the main cause of chronic wounds^[1]With an annual incidence of 8.1%, an annual amputation (toe) rate of 5.1% and an annual mortality rate of 14.4%^[2]。 In tertiary hospitals, 27.3% of amputations were due to diabetic foot, accounting for 56.5% of non-traumatic amputations. In addition, diabetic foot costs huge, about twice as much as non-podiatric patients^[1]。 Therefore, diabetic foot imposes a great burden on patients, families and society.

Since 1955 Oakley and Cohen^[1]Since the concept of diabetic foot was first proposed, diabetic foot has now developed into one of the most serious and costly chronic complications of diabetic patients. WHO defines diabetic foot as: foot infections, ulcers, and/or deep tissue destruction associated with distal lower limb nerve abnormalities and varying degrees of peripheral vasculopathy^[2]。 2003 Peking Union Medical College Hospital Guan et al^[3]Multicenter data from seven major cities in China were organized, and 1,397 diabetic patients over 50 years old were included. The survey showed that the incidence of lower extremity arterial lesions in diabetic people in China was 19.47%. The prevalence rate of foot ulcer in diabetic patients is 4% ~10%. Diabetic foot is the main cause of amputation in diabetic patients. In all non-traumatic low amputation operations, diabetic patients account for 40% ~60%^[4]。 The occurrence of diabetic foot is mainly related to diabetic lower extremity arterial disease, peripheral neuropathy, foot infection and injury. It is not only a group of symptoms of diabetes, but a group of foot syndromes caused by diabetes. The treatment should be aimed at its pathophysiological mechanism. It involves internal medicine (vasodilatation, anticoagulation, antiplatelet, regulation of blood sugar, blood pressure, blood lipid, nutritional therapy, immunity enhancement, anti-infection, etc.), surgery (wound treatment, blood supply reconstruction, etc.), basic medicine (molecular biology, cytology) and rehabilitation medicine. It is impossible to rely on a single department, and the concept of multidisciplinary cooperation must be reflected^[5]。 The treatment of diabetic foot vascular disease mainly relies on various therapeutic methods of vascular surgery to reconstruct the blood flow of peripheral arteries leading to ulcer and its adjacent tissues, improve the microcirculation and oxygen metabolism of ulcer and its adjacent tissues, and create favorable conditions for the repair of defective tissues, so as to achieve the therapeutic goals of ulcer healing and limb saving^[6]。 The methods of vascular surgery to reconstruct lower extremity arterial blood flow mainly include arterial bypass grafting, endovascular molding and lower extremity stem cell transplantation.

Hypoglycemia is a common adverse event in the medication of diabetic patients. Its incidence increased significantly in patients treated with intensive hypoglycemic therapy. It has been shown that hypoglycemia can increase the risk of cardiovascular events and death, impair patient cognitive function, reduce patient quality of life and increase medical expenditure. This article discusses the definition, incidence, risk factors, harm and management measures of hypoglycemia in diabetic patients.

To assess the effect of autologous bone marrow stem cell transplantation combined with long balloon angioplasty in treatment of diabetic foot lower extremity vascular disease.

Forty cases of diabetic foot patients admitted in the Department of Endocrinology and Vascular Surgery of Shandong Provential Hospital from July 2008 to August 2013 were recruited. Patients were randomly divided into autologous bone marrow stem cell transplantation combined with long balloon angioplasty treatment group (combined treatment group, n=20) and long balloon angioplasty therapy only group (control group, n=20).Foot skin temperature, arterial pulse, ankle brachial index (ABI) and other markers were compared. Two sample t test was used for continuous data. Before and after surgery comparison with different time points were analyzed using analysis of variance. Categorical data was compared by χ ² test.

(1) Skin temperature, rest pain and other subjective indicators had improved significantly(χ²=4.710-5.855,P<0.05) in the 2 groups after treatment. (2)The ankle brachial index, walking distance, skin oxygen partial pressure and other objective indicators were significantly improved(t=2.302- 23.643, P<0.05) in the 2 groups after treatment. (3)In the control group, 7 cases were restenosis or occlusion, the restenosis rate was 46.15%(12/26). In the treatment group, 4 cases developed restenosis or occlusion, the restenosis rate was 16.67% (4/24). The restenosis rate of the two groups was statistically significant (χ²= 4.987, P<0.05).

Autologous bone marrow stem cell transplantation combined with prolate spheroidal balloon angioplasty surgery can significantly improve the clinical symptoms of ischaemia in patients with diabetic foot, combined treatment shows greater reduction in the rate of restenosis and overall improvement of clinical therapeutic effect.

To investigate the impact of a previous history of foot ulcers on the plantar pressure distribution in diabetic neuropathy patients.

A total of 119 patients with type 2 diabetes were selected.According to TCSS scores and history of foot ulcers they were divided into diabetic control group(DC), diabetic neuropathy group(DN) and diabetic ulcers group(DFU), at the same time 46 nomal persons were selected as control group(CG). Spatiotemporal parameters of gait were assessed during level barefoot walking using Foot-scan7.

(1)The plantar pressure-time curve of the four groups showed obvious " M" type.DN group showed higher peak-valley plantar pressure difference than CG group((38±16)vs (26±8) N/cm², t=5.389, P<0.05).DFU group showed higher peak-valley plantar pressure difference than CG ((41±16)vs(26±8) N/cm², t=2.964, P<0.05) and DC group((41±16)vs(32±12) N/cm², t=4.070, P<0.05).(2) The peak plantar pressure of CG group, DC group, DN group, DFU grouprose successively at M1, M3-5 and MF, especially at M3(right foot:(34±11), (35±9), (37±14), (49±23) N/cm², F=10.431, P<0.05, leftfoot: (32±8), (37±12), (42±18), (46±17) N/cm², F=8.659, P<0.05). While at HM area, the peak plantar pressure of the four groups decreased successively(right foot:(33±16), (29±10), (28±6), (26±7)N/cm², F=3.878, P<0.05, left foot:(30 ± 8), (28 ± 6), (27 ± 11), (24 ± 8) N/cm², F=3.317, P<0.05).

Diabetic peripheral neuropathy patients presented higher plantar pressure in some local area, leading to the occurence of foot ulcers.

To evaluate the value of early pregnancy fasting plasma glucose(FPG) to predict gestational diabetes mellitus(GDM) in pregnant women with or without GDM risk factors.

From June 2013 to September 2014, 3 223 singleton healthy pregnant women in Peking University First Hospital were recruited and their demographic/medical information were collected using. Based on age, pre-pregnancy body mass index (BMI) and family history of diabetes, participants were grouped into GDM risk factors positive group (n=1 341) and GDM risk factors negative group (n=1 892). T-test and χ ² test were used for between-group comparison. Receiver operating characteristic (ROC) curve was used to evaluate the prediction of early pregnancy FPG for GDM.

(1) Pregnant women with GDM risk factors had significantly higher FPG levels in early pregnancy compared to those without GDM risk factors ((5.1±0.4)vs (5.0±0.4) mmol/L, t=6.44, P<0.001).(2)Compared to women with FPG<4.75 mmol/L and those without GDM risk factors, women with GDM risk factors and with 4.75≤FPG<5.00 mmol/L, 5.00≤FPG<5.25 mmol/L and FPG≥5.25 mmol/L had a significant increased risk of developing GDM, the OR values were 1.84(95%CI 1.26-2.70),2.46 (95%CI 1.71-3.52) and 6.99 (95%CI 5.01-9.77) respectively; while in GDM risk factors negative group, only those with FPG≥5.25 mmol/L had a significant increased risk of developing GDM, and the OR value was 2.55 (95%CI 1.80-3.60). There was approximately a 1.6-fold increase (95%CI 1.45-1.98) in the risk of developing GDM for each 0.5 mmol/L increment in FPG in women without GDM risk factors, while a 2.33-flod increase (95% CI 1.96- 2.61) in women with GDM risk factors. (3) Based on the ROC analysis, the area under the curve of early pregnancy FPG in predicting GDM for women with and without GDM risk factors was 0.694(95%CI 0.661-0.732) and 0.620 (95%CI 0.580-0.662),respectively. The optimal cut off value was 5.17 mmol/L and 5.09 mmol/L respectively.

Early pregnancy FPG has greater effect on predicting GDM in women with GDM risk factors. The optimal cut off values of FPG in predicting GDM are different between women with and without GDM risk factors.

To investigate the effect of short-term very low calorie diet (VLCD) on the level of serum sex hormone binding globulin (SHBG) in patients with metabolic syndrome.

Sixty- two inpatients (22 male and 40 female), average age (39±9)yrs with metabolic syndrome were received 9 days VLCD from December 2013 to December 2014. Anthropometric and biochemical parameters were collected before and after VLCD. The level of serum SHBG was measured with chemiluminescent assay. Homeostasis model of assessment for insulin resistance index (HOMA-IR) was employed to evaluate the insulin sensitivity. Pearson correlation analysis was used to test the correlation of variables.

After short-term VLCD, average body weight decreased from (77.2±2.4) kg to (72.6±2.3) kg (t=15.83, P<0.001); waist circumference reduced by 4.94 cm (t=14.90, P<0.001). Blood pressure, total cholesterol, triglycerides, fasting blood glucose, fasting insulin, and HOMA-IR were all reduced significantly after VLCD. The level of serum SHBG was negatively associated with body weight, waist circumference, fasting insulin, HOMA-IR, and triglycerides(r=- 0.447-- 0.271, P<0.057), while it was positively associated with high density lipoprotein cholesterol (HDL - C) (r=0.364, P<0.05). After short-term VLCD, the level of serum SHBG increased significantly from (27.6±2.1) to (46.2±3.3) mmol/L(t=8.134, P<0.001). The variation amplitude of serum SHBG was negatively associated with basal fasting insulin, HOMA-IR, and triglycerides (r=-0.440, -0.317, -0.337, all P<0.05) , while positively associated with basal serum SHBG level(r=0.338, P< 0.05).

Short-term VLCD improves metabolic markers including serum SHBG level in patients with metabolic syndrome. Patients with higher level of baseline serum SHBG benefit more SHBG increment from VLCD, while patients with higher level of baseline fasting insulin, HOMA-IR, triglycerides benefit less.

To summarize the clinical features of autoimmune pancreatitis (AIP) with diabetes as the initial symptom.

The clinical data of one case of AIP with diabetes as the initial symptom were analyzed. The 60-year-old male patient was diagnosed in March 2015 in the Department of Endocrinology in China-Japan Friendship Hospital. A follow-up study focused on the pancreatic endocrine and exocrine functions was conducted.

Based on observation, the insulin secretion function in the patient was poor, whereas the glutamic acid decarboxylase antibody, insulin autoantibody and islet cell autoantibody were found negative. In addition, the lipase level was 801 U/L. The swelling of pancreas was found under magnetic resonance cholangiopancreatography. The patients was treated with prednisone for 4 months, the pancreatic swelling ameliorated and the serum lipase level restored to normal. However, the dosage of insulin treatment was unchanged during the prednisone treatment.

The IgG4 - related diseases should be paid more attention in suspected diabetes cases, especially in those with clinical characteristics between type 1 and type 2 diabetes, with negative autoantibody and without family history of diabetes, or those with other systematic symptoms.

To investigate the relationship between retinal nerve fibre layer (RNFL) thickness and peripheral neuropathy in patients with type 2 diabetes.

Ninety-eight cases diagnosed with type 2 diabetes in the Department of Endocrinology in Beijing Hospital from March 2014 to June 2015 were enrolled in this study. Global and sectoral RNFL thicknesses were measured at 3.45 mm diameter around the optic nerve head using optical coherence tomography(OCT), and conduction velocity of peripheral nerve was measured in all cases. According to the diagnosis of diabetic neuropathies, participants were divided into 3 groups: non-diabetic peripheral neuropathy group(NDPN, n=36), subclinical diabetic peripheral neuropathy group(SDPN, n=37) and define diabetic peripheral neuropathy group(DDPN, n=25). RNFL thickness in different group was compared by analysis of variance and least-significant difference pairwise comparison.

All sectoral RNFL thickness was thinning from NDPN group, SDPN group to DDPN group, specially inferior quadrant RNFL thickness, and there was significant difference among the three groups((132±19), (124±18) vs (116±17)μm,F=5.848, P=0.004). And significant difference was found in inferior quadrant RNFL thickness between NDPN and SDPN group(mean difference=8.67 μm, t=1.975, P=0.048), NDPN and DDPN group (mean differenc=16.59 μm, t=3.412, P=0.001). No significant difference was found in inferior quadrant RNFL thickness between SDPN and DDPN group(mean difference=7.93 μm, t=1.661, P=0.104). Covariance analysis showed that age and diabetes duration had no significant influence on RNFL thickness.

RNFL thickness maybe associated with diabetic peripheral neuropathy in patients with type 2 diabetes, especially in serious cases.

To compare the effects of islet-like cells originated from different generations of rat bone marrow-derived mesenchymal stem cells (BMSCs) with pancreatic and duodenal homeobox 1(PDX-1) induction in treating type 1 diabetic SD rats.

The third (P3) and fifth (P5) generation of BMSCs were transfected with PDX-1 and induced to islet-like cells. Dithizone staining was used to detect insulin secretion. Streptozotocin was intraperitoneally injected into SD rats to induce type 1 diabetic model. The 45 established diabetic SD rat models were divided into three groups with random number table(15 rats in each group): transplantation group A, transplantation group B and model control group, the three groups were injected with islet-like cells derived from P3BMSCs+PDX-1, P5 BMSCs+PDX-1 and saline through tail-vain, respectively. Another 15 healthy SD rats with tail-vein injection of equal volume of saline were set as normal controls. Blood glucose, fasting insulin and C-peptide levels were measured at 0, 7, 14, 21 and 28 days after transplantation. Intraperitoneal glucose tolerance test (IPGTT) was conducted at the 21st day after transplantation. Rats were euthanized at day 28 and pancreatic tissues were collected and tested by immunohistochemistry. One-way analysis of variance was applied to do statistic analysis.

From the 14th day of transplantation on, blood glucose levels significantly decreased in rats from group A and group B when compared with those in model control group. Fasting insulin and C - peptide levels in transplantation groups increased, although the difference was not statistically significant. The blood glucose levels in group B on the 21th and 28th day were all significantly lower than those in group A ((21.90±0.26) vs (23.60±1.49) mmol/L, (21.80±1.32) vs (24.20±2.06) mmol/L, t=9.65, 12.73, both P<0.05). Consistently, plasma insulin and C-peptide levels were higher in group B than those in group A at the corresponding time points(t=8.73, 12.51, 18.36, 25.12, all P<0.05). IPGTT showed that the area under curve in group B was significantly lower than that in group A ((1 809.0±2.6) vs (2 301.0±6.8) mmol·L^-1·min, t=5.241, P<0.05). Pancreatic immunohistochemistry showed that insulin positive cells were detected in both transplantation group A and B; and the percentage of insulin positive cells were higher in group B than that in Group A(48.0% ± 1.3% vs 32.8% ± 3.2%, t=8.38, P<0.05).

Islet-like cells originated from the 5th generation of BMSCs with PDX-1 induction have better effects than the 3rd generation in treating type 1 diabetic rats.

Hydroxyurea is a nucleoside diphosphate reductase inhibitor, which is commonly used in the treatment of myeloproliferative diseases at present. Its mechanism of action is to prevent the reduction of ribonucleotides to deoxyribonucleotides, interfere with the biosynthesis of purine and pyrimidine bases, selectively hinder DNA synthesis, and lead to the death of S-phase cells^[1]。 Skin ulcers caused by hydroxyurea are extremely rare and were first developed by Stahl and Silber in 1985^[2]Lower extremity ulcers were found in patients treated with hydroxyurea for chronic myeloid leukemia. In January 2006, the U.S. Food and Drug Administration issued a statement formally adding a warning of skin vascular toxicity to the hydroxyurea instructions^[3]。 There are no relevant reports on the diagnosis and treatment of lower limb ulcers in diabetic patients who have been administered hydroxyurea for a long time. The Department of Endocrinology of our hospital recently diagnosed and treated a patient with ankle ulcer misdiagnosed as diabetic foot due to taking hydroxyurea to treat thrombocythemia, which is now reported in combination with the literature as follows.

Diabetic foot refers to lower limb infection, ulcer formation and/or deep tissue destruction in diabetic patients due to neuropathy and various peripheral vascular diseases of different degrees. It is one of the serious complications that lead to disability and death in diabetic patients. As the prevalence of diabetes increases, the incidence of diabetic foot also increases year by year. The pathogenesis, clinical and pathological characteristics of diabetic foot wounds are special and complex. Different from general surgical wounds, they are often prolonged and easy to relapse. In severe cases, amputation (toe) will occur. The amputation rate of diabetic patients is 10 times or higher than that of non-diabetic patients^[1]。 At the same time, compared with non-diabetic patients, diabetic foot patients have a higher incidence of cardiovascular and cerebrovascular diseases^[2]。 At present, the incidence of diabetes is close to 10%, and diabetic patients have a 15% ~25% chance of developing diabetic foot in their lifetime, and the 5-year recurrence rate is as high as 50% ~70%^[3]。 It can be seen that the treatment and nursing of diabetic foot has become a prominent public health problem, which brings a heavy economic and psychological burden to patients.

In recent years, the incidence of diabetes is increasing worldwide, but the age of onset is decreasing year by year, which has become a health problem that cannot be ignored. Long-term hyperglycemia can induce various diabetic complications, and diabetic foot disease is one of the most serious complications.

With the development of society and economy, the ageing trend of population, the prevalence of obesity and metabolic syndrome, the prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing. At present, NAFLD has become the most common chronic liver disease in China^[1]。 NAFLD is a hepatic manifestation of metabolic syndrome, and has a common pathogenesis basis with obesity, type 2 diabetes, cardiovascular disease and other metabolic diseases^[2]Insulin resistance and oxidative stress. In recent years, the role of cytokines in the pathogenesis of NAFLD has attracted much attention, among which the members of lipocalin family are closely related to NAFLD, which is reviewed in this article.

Diabetes mellitus is one of the most common metabolic diseases in China, and its pathogenesis mainly includes progressive islet β cell failure and insulin resistance. Recent studies suggest that abnormal microcirculation function may also be involved in the pathogenesis of diabetes^[1,2]。 Microvascular endothelial cells, as the main component of microcirculation, are directly involved in the occurrence and development of diabetes and its complications. The author reviews the research progress in the fields of microvascular endothelial cells and their functions, their relationship with target organs and tissues, metabolic and molecular mechanisms of diabetic microvascular endothelial cell injury, and related therapeutic drugs.

Diabetic foot is the leading cause of non-traumatic amputation in diabetic patients due to combined neuropathy and various degrees of peripheral vascular disease, which leads to infection, ulcer and/or deep tissue destruction of lower limbs. Diabetic foot with Wagner grade 3 or above may be accompanied by skin, muscle, tendon, fascia and bone involvement and defects.

sodium-glucose co-transporter 2 (SGLT-2) inhibitors (SGLT-2i) are a new type of oral hypoglycemic drugs. These drugs reduce blood glucose by inhibiting the reabsorption of glucose in the proximal convoluted tubules of the kidney and promoting the excretion of urinary glucose. The target organ of these drugs is the kidney, so their renal safety has attracted much attention. This article reviews the clinical research evidence since the development of SGLT-2i, and expounds the renal safety and potential renal protective effect of SGLT-2i treatment.