Volume 09 · Issue 07 · 2017

Diabetic foot is a defect of foot tissue far from the ankle joint, with or without foot infection, in diabetic patients due to peripheral neuropathy and/or lower limb vascular disease. Based on this, many clinicians have formed inertial thinking, subconsciously believing that diabetic foot can be diagnosed if foot lesions appear in diabetic patients. In fact, diabetic patients are often associated with other disease states, and there are many other causes of foot lesions in diabetic patients, and their treatment strategies and prognosis are completely different from diabetic foot. If there is a missed diagnosis or misdiagnosis in clinic, it can lead to wrong treatment strategy, eventually leading to treatment failure and even life-threatening. Therefore, we should be alert to its diagnosis traps in clinic, make a correct diagnosis, formulate reasonable treatment strategies, and achieve the purpose of improving the cure rate, reducing the amputation rate and mortality rate.

The factors affecting the healing of diabetic foot ulcer are complex, including diabetic peripheral neuropathy and peripheral vascular disease, infectious factors, systemic poor nutritional status, organ function damage, complications and complications. Local factors of wound, such as tissue necrosis, inflammatory exudation, osteomyelitis, etc. also affect the wound repair process. Therefore, the evaluation and debridement of chronic wounds of diabetic foot have become important steps to affect wound healing. The significance of comprehensive scientific evaluation and reasonable and timely debridement treatment is not only to promote wound healing, but also to shorten the treatment cycle, reduce the treatment cost, and reduce the amputation rate and mortality. In recent years, the treatment of diabetic foot ulcer has been carried out in some specialties, including endocrinology, orthopedics, trauma, vascular surgery and wound clinic. Some irregular treatment methods not only prolong the wound healing time, increase the treatment cost of patients, but also lead to the spread of infection, amputation and disability. Therefore, it is necessary to carry out standardized wound assessment and debridement under the guidance of diabetic foot disease related guidelines. In 2013, the American Diabetic Association issued the "Guidelines for Clinical Diagnosis and Treatment of Hospitalized Diabetic Foot Disease", which proposed that the evaluation and wound management of diabetic foot disease should be completed by the diabetic foot disease prevention and treatment team, which must have the ability to evaluate wounds and stage infection and ischemia^[1]。

The concept of diagnosis and treatment of diabetic retinopathy (DR) has made a breakthrough in the 15 years since the American Diabetes Association (ADA) issued guidelines in 2002^[1]It is manifested in the following aspects: (1) conventional and widely used ocular optical coherence tomography (OCT) as an effective means to assess retinal pathological changes and retinal thickness; (2) fundus camera reveals a larger range of microvascular lesions in the fundus; (3) Anti-vascular endothelial growth factor (VEGF) is not only a first-line choice for the treatment of edema involving the fovea, but also recommended for the treatment of proliferative DR (PDR); (4) Chronic hyperglycemia not only leads to retinal vasculopathy, but also leads to retinal neuronal damage, which are common causes of vision loss. In addition, with the advancement of internal medicine and diagnosis and treatment equipment, patients benefit more from the comprehensive treatment of diabetes. This statement was organized by Professor Thomas Gardner of the Kellogg Eye Center of the University of Michigan, and invited eight famous ophthalmology professors such as Professor Sharon D. Solomon of the John Hopkins Medical Center and Wilmer Eye Institute and Professor Emily Chew of the National Eye Institute to publish the latest position statement on DR diagnosis and treatment in March 2017^[2]The contents of which are applicable to both physicians and patients.

To investigate the prevalence and risk factors of sarcopenia in Wagner grade 2 diabetic foot ulcer (DFU).

A total of 273 patients with Wagner grade 2 DFU were recruited from diabetic foot center of Zhongda Hospital, Southeast University in 2016, and divided into sarcopenia group (n=38) and non-sarcopenia group (n=235) according to bioelectrical impedance analysis, appendicular skeletal mass index, short physical performance battery and handgrip strength. Parameters of fasting plasma glucose, 2-hour postprandial blood glucose, glycosylated hemoglobin (HbA_1c), total cholesterol, triglyceride, ankle brachial index (ABI), nerve conduction velocity (NCV) and transcutaneous oxygen partial pressure (TcPO₂) were compared between these 2 groups;muscle area and density were calculated by computed tomography.

The prevalence of sarcopenia was 13.97% (38/273). Age, body mass index (BMI), HbA_1c, NCV, diabetic course were significantly different between these two groups (P<0.05). Multivariate Logistic regression analysis indicated that age, diabetic course, NCV, TcPO₂ and ABI were risk factors of sarcopenia in patients with Wagner grade 2 DFU (OR=4.281, 6.114, 2.895, 1.093, 5.460, 1.160, 95%CI: 1.751-10.543, 1.202-31.094, 1.185-5.846, 1.012-1.180, 1.793-16.624, 1.020-1.300, all P<0.05).

Sarcopenia tends to present in Wagner grade 2 DFU with advanced age, long diabetic course, long-term poor glucose control and poor vascular and nerval function of extremities.

To evaluate the efficacy and safety of miglitol in type 2 diabetic patients with acarbose as control group.

A multicenter (in 10 hospitals), open, randomized and parallel-controlled clinical trial was carried out from January 2012 to December 2013. A total of newly diagnosed 216 cases of type 2 diabetes [glycosylated hemoglobin A_1c (HbA_1c): 7%~10%] were randomized to treat with miglitol or acarbose. The initial dose of miglitol and acarbose was 50 mg three times daily, and the dose was increased to 100 mg three times daily according to the fasting blood glucose (≥ 7.0 mmol/L). The levels of glycosylated hemoglobin, fasting blood glucose and 2 h postprandial vein blood glucose and insulin were detected at baseline, 12 and 24 weeks after treatment.The incidence of adverse events was observed in both groups, including changes in blood pressure, heart rate, blood, urine, liver and kidney function, electrocardiogram and other indicators. Data were analyzed with t and χ ² test.

The mean decrease of glycosylated hemoglobin [ (6.8±1.1) % vs (6.8±1.0) %], fasting blood glucose [(7.2±1.9) vs (7.0±1.9)mmol/L], postprandial 2 h blood glucose [(9.6±2.9) vs (10.1±3.4) mmol/L] from baseline to study end was no significant for both groups (χ²=0.02, t=0.71, 1.26, all P>0.05) . The serum insulin levels before and after treatment within the group [(10.3±4.2) vs (9.6±3.7) mU/L; (9.8±3.6) vs (9.7±3.8) mU/L], as well as the comparison between the two groups were not statistically significant (t=1.33, 0.55, both P>0.05) . The changes in blood pressure, heart rate, urine routine, liver and kidney function and electrocardiogram from baseline to week 24 after treatment were also not statistically significant between the two groups (all P>0.05). Moreover, the incidences of adverse events were similar between the two groups (both P>0.05).

In type 2 diabetic patients, the efficacy of treatment with miglitol is not inferior to that of acarbose, with a similar safety profile.

To investigate the incidence of hypoglycemia in type 2 diabetic patients with well-controlled glucose levels (HbA_1c<7.0%) by using a continuous glucose monitoring system (CGMS), and evaluate the clinical application value of CGMS.

A total of 102 type 2 diabetic patients with HbA_1c<7.0% were recruited in Xindu District and Longquanyi District of Chengdu between January 2016 and January 2017. Each subject received a continuous glucose monitoring for 3 consecutive days and was instructed to self-monitoring of blood glucose (SMBG) with finger-stick blood glucose 4 times per day. The accuracies of CGMS and SMBG were analyzed by Clarke error grid analysis. The demographic and laboratory data were collected to analyze the incidence of hypoglycemia and its risk factors. The control targets of glucose fluctuation were explored by using receiver operating characteristic curve for avoiding hypoglycemia. T test was used for analyzing measurement data and chi-square test for count data.

(1) Of 102 subjects, 49 patients experienced hypoglycemia including 31 cases with nocturnal hypoglycemia. The mean blood glucose (MBG) was (6.9±1.1) mmol/L and the standard deviation of blood glucose (SDBG) was (1.4±0.7) mmol/L. (2) Taking out 946 pairs of matched glucose measurements from SMBG and CGMS, Clarke error grid analysis showed that 99.05% of the readings from CGMS fell into the clinical acceptable zone A (clinical exactness) and zone B (benign error), further findings presented that 82.05% of the readings from CGMS fell into zone A and zone B when exploring hypoglycemia consistence. (3) MBG, SDBG, continuous overlapping net glycemic action (CONGA), low blood glucose index (LBGI), mean of daily differences (MODD), mean amplitude of glycemic excursions (MAGE), M-value and largest amplitude of glycemic excursion (LAGE) had significant differences between the hypoglycemia and non-hypoglycemia group (t=1.807-33.957, all P<0.05). (4) Forty-nine patients experienced 140 events with a glucose level<3.9 mmol/L recorded in CGMS. The incidence of hypoglycemia presented highest from 22:00pm to 6:00am (45.00%). The duration time of single hypoglycemia event was 35 (P₂₅25.00,P₇₅45.00) min. (5) Episodes of hypoglycemia and LBGI significantly correlated with professional status (r=-0.249,-0.202, P<0.05, respectively) and monthly income (r=-0.295,-0.254, P<0.05, respectively). Logistic regression analysis indicated that LBGI was independently correlated with hypoglycemia (r=2.618, OR=13.712, P<0.05). (6) Control targets analyzed by ROC curve for avoiding hypoglycemic events were MBG<6.93 mmol/L, SDBG<1.38 mmol/L, LBGI<0.84 mmol/L and MODD<1.44 mmol/L, respectively.

Hypoglycemia presents high in type 2 diabetes mellitus patients with good glycemic control. CGMS has good accuracy and can monitor hypoglycemia which is not easily to be detected by SMBG. It can be used to provide a more reasonable treatment plan for type 2 diabetes mellitus patients.

To investigate the parafoveal and perifoveal vessel density and the area of foveal avascular zone (FAZ) by optical coherence tomography angiography (OCTA) in diabetic patients with early diabetic retinopathy.

Clinical data of in-patients and out-patients with diabetes in Department of Endocrinology of Beijing Hospital from October 2015 to November 2016 were collected. All of the participants underwent examination with OCTA, and were examined for the condition of fundus according to Early Treatment Diabetic Retinopathy Study (ETDRS) international DR staging criteria. Total of 85 eyes from patients without diabetic retinopathy (NDR group) and 23 eyes with diabetic retinopathy (DR group) were checked in the study. Ninety eight eyes from healthy subjects were set as normal control. Differences of vessel density in macular region and the area of FAZ among the three groups were analyzed by analysis of variance and pairwise comparison was done by using LSD method.

The difference in mean vessel density between the control and patients with diabetes was statistically significant (51%±4% vs 50%±5%, F=5.828, P=0.017). Vessel densities in fovea beside macula lutea, upper part of macula lutea,upward margin of central fovea, temporal margin of central fovea, nasal margin of central fovea of normal control group were all significantly higher than those in patients with diabetes (F=4.794, 6.677, 6.117, 7.294, 4.656, P<0.05). The size of FAZ of control group was significantly smaller than that in patients with diabetes [(0.29±0.08) vs (0.33±0.09) mm², F=12.30, P=0.001]. Mean vessel densities of control group, NDR group and DR group were tapering off (51%±4% vs 50%±5% vs 47%±4%, F=10.605, P=0.000), and area of FAZ of the three groups increased instead [(0.29±0.08) vs (0.33±0.07) vs (0.38±0.10) mm², F=10.892, P=0.000]. Therewas significant difference in vessel density in the macular region between the normal control and DR group [mean deviation (I-J value) 4.422, P=0.000], while no significant differences between the normal control and NDR group was found (I-J value 1.196, P=0.051). Significant difference in FAZ area between the normal control and NDR group, and between normal control and DR group were found with LSD method (I-J value 0.043, 0.091, both P<0.05). Similarly, significant differences in mean vessel densities in macular region and FAZ area were found between the NDR group and DR group (I-J value 3.227, 0.048, both P<0.05).

OCTA can detect early ischemia changes in macular region such as lower vessel density, greater size of FAZ, thus is helpful for early intervention.

To investigate the prognosis of impaired glucose regulation (IGR) in military officers and its risk factors.

Subjects with IGR was identified from 1 429 military officers who underwent physical examination from June to September 2012, and were followed up by repeating glucose tolerance test in 2015. Variance, Chi-square test, rank sum test and Logistic regression were used for data analysis.

A total of 214 subjects (15.0%) with IGR were identified from 1 429 military officers, in which 52(24.3%) were found with impaired fasting glucose (IFG), 113(52.8%) with impaired glucose tolerance (IGT), and 49(22.9%) with IFG+IGT. After 3 years, 78(36.4%) subjects with IGR turned out to be normal, 105(49.1%) subjects remained to be IGR and 31(14.5%) subjects developed diabetes. The cumulative incidence rates of diabetes mellitus in subjects with IFG, IGT, IFG+IGT was 11.5%, 8.8%, and 30.6%, respectively (χ²=13.55, P=0.001). The risk of developing diabetes in subjects with IFG+IGT was 1.8 times higher than that in those with IFG (OR=1.84, 95%CI:1.090-3.102, P=0.022) and 4.5 times higher than that in those with IGT (OR=4.54, 95%CI:1.868-11.056,P=0.001). Fasting blood glucose (OR=4.21, 95%CI:1.937-9.155, P<0.001), postprandial 2 hours blood glucose (OR=1.41, 95%CI:1.024-2.027,P=0.036) and glycosylated hemoglobin A_1c (OR=10.30, 95%CI:2.831-37.489,P<0.001) were the independent risk factors for IGR to develop into diabetes. In the subjects with a glycosylated hemoglobin A_1c≥5.7%, the risk of developing diabetes in 3 years would be 5 times higher than that in the subjects with a glycosylated hemoglobin A_1c<5.7% (OR=4.99, 95%CI:1.837-13.538, P=0.002).

The prevalence of IGR among military officers is lower than that in the general population. The risk of developing diabetes in subjects with IFG+IGT is the highest. Glycosylated hemoglobin A_1c may be a predictor for prognosis of IGR.

To investigate the therapeutic effects of dynamic 3C therapy in patients with pituitary growth hormone tumor complicated with diabetes during the perioperative period.

A total of 60 inpatients with pituitary growth hormone tumor complicated with diabetes hospitalized in Liaocheng People's Hospital from June 2013 to June 2016 were enrolled in this study. The patients were divided into control group and treatment group according to the random number table with 30 cases in each group. Basic-meal insulin therapy was used in the control group while 3C program monitoring therapy was applied in the treatment group. The blood glucose control, glucose fluctuation range, insulin dosage, hypoglycemia incidence, standard time of preoperative glucose and glycosylated serum protein (GSP) were compared during the whole perioperative period between the two groups. Double independent-samplet test was adopted for data comparisons between groups.

The glycemic control in the treatment group was superior to control group in the whole perioperative period. Fasting blood-glucose (FPG) and 2 hours postprandial blood glucose (2hPG) in treatment group reduced significantly when compared with those in control group (t=8.688, 5.016, both P<0.05). The time needed to return the set level of FPG was shorter [(4.7±1.3)vs(8.1±2.2)d], the GSP was significantly lower [(152±31) vs (186±51)μmol/L] and the insulin dosage was remarkably lower [(36±9) vs (40±13)U/d] in the treatment group when compared with those in the control group (t=4.823, 10.523, 4.461, all P<0.05). And the incidence of hypoglycemia was also markedly lower in the treatment group (5.2%±1.2% vs 9.1%±2.3%, t=5.333, P<0.05). Particularly on the operation day and during the postoperative days with descending growth hormone, the glucose fluctuation and the incidence of hypoglycemia were both much milder in treatment group than those in control group(t=4.590-9.519, all P<0.05) in the treatment group.

Real-time dynamic glucose monitoring in 3C therapy system reflects the trend of glucose changes and controls the glucose safely, rapidly and effectively. It has unique advantages in glucose management in the perioperative period of pituitary growth hormone tumor.

To investigate the effects of growth and differentiation factor 11 (GDF-11) on injury of MIN6 cells induced by high glucose and its possible mechanisms.

MIN6 cells were cultured in vitro and divided into the following groups: normal glucose (NG) group, NG+GDF-11 group, high glucose (HG) group, HG+GDF-11 group, HG+GDF-11+phosphatidylinositol-3-kinase (PI3K) inhibitor LY492002 group, and HG+GDF-11+transforming growth factor β (TGF-β) receptor Ⅰ inhibitor SB431542 group. Apoptosis of MIN6 cells were stained with Annexin V-FITC and propidium iodide (PI), and assessed by flow cytometry. The expression levels of B cell lymphoma 2 (Bcl-2), Bcl-2 associated X protein (Bax), cleaved-caspase3 and protein kinase B (Akt), phosphorylated Akt (p-Akt), forkhead box o1 (FoxO1), phosphorylated FoxO1 (p-FoxO1), ribosomal protein S6 kinase 1 (S6k1) and phosphorylated S6k1 (p-S6k1) were measured by western blotting. The phosphorylation of Smad were assessed by immunofluorescence. Data among multiple groups were compared by using one-way ANOVA and the least significant difference t test.

Compared with the vehicle control groups, Bcl-2/Bax ratio decreased, the protein levels of cleaved-caspase 3 increased and the percentage of apoptotic MIN6 cells elevated in those groups cultured with HG (0.39±0.03 vs 3.82±0.26, 0.83±0.04 vs 0.17±0.02, 26.1%±3.0% vs 7.9%±0.8%, t=23.12,-27.60,-10.11, P<0.01, respectively). However, the effects were blocked by pretreatment with recombinant GDF-11 (rGDF-11) (t=-44.110, 19.530, 6.535,P<0.01, respectively). Treatment of MIN6 cells with TGF-β receptor Ⅰ inhibitor SB431542 or PI3K inhibitor LY294002 partially abolished the anti-apoptotic effects of rGDF-11 (allP<0.05). Immunofluorescence analyses showed that Smad 2 phosphorylation (p-Smad 2) decreased in high glucose culturing, whereas Smad 3 phosphorylation increased (t=4.830, 5.760, P<0.01, respectively). Pre-incubation with rGDF-11 restored p-Smad 2 expression, however, rGDF-11-mediated Smad 2 activation was partially blocked by SB431542 (t=5.550, 3.040, P<0.05, respectively). High glucose decreased Akt, FoxO1 and S6k1 phosphorylation in MIN6 cells, but pretreatment with rGDF-11 partly rescued these defects (P<0.01, respectively). The PI3K inhibitor LY294002 exerted a suppressive effect on rGDF-11-mediated Akt and FoxO1 phosphorylation (all P<0.05).

GDF-11 may prevent apoptosis in high glucose-induced MIN6 cells through activation of TGF-β/Smad 2 and PI3K-Akt-FoxO1 signaling pathway.

Charcot joint disease is a rare clinical disease, which can be caused by a variety of pathogenic factors. It often occurs in large joints, and the main clinical manifestations are painless joint destruction and instability. Diabetic Charcot arthropathy is more common with foot and ankle lesions, and knee joint lesions are less common. A recent adult case of occult autoimmune diabetes complicated by Charcot knee arthropathy is presented as follows, and the relevant literature is reviewed.

Among the hospitalized patients with type 2 diabetes in China, about 5.2% are complicated with diabetic foot^[1]The 5-year mortality rate of diabetic foot patients is 43% to 55%, and the amputation rate is as high as 26.4%^[2]This difficult and severe illness has brought great pain and heavy economic burden to patients, their families and society. Adipose tissue contains abundant multi-potential elements. Transplanting it into ulcer wounds can repair damaged blood vessels, improve and restore blood flow in lower limbs, and promote tissue regeneration, thus achieving the purpose of ulcer healing. Recently, the diabetic foot prevention and treatment center of our hospital used autologous adipose tissue functional microfragment transplantation to treat a patient with diabetic foot, and obtained good results, which provided new ideas and methods for the clinical treatment of diabetic foot.

Diabetic foot is one of the serious chronic complications of diabetes, which has the characteristics of high incidence, high disability/death rate and high cost. The annual incidence rate of diabetic foot is about 2%, and the lifetime incidence rate may be as high as 15% to 25%^[1]。 Increased plantar pressure is an important cause of diabetic foot ulcer (especially neuropathic ulcer), but the threshold of plantar pressure is still controversial^[2]。 Effective decompression of the ulcer site is an important part of the treatment of ulcers, especially neuropathic ulcers^[3]。 Therefore, decompression therapy not only can effectively promote the healing of diabetic foot ulcer, but also has great significance for preventing the occurrence and recurrence of ulcer.

In the past, the understanding of vitamin D (VitD) was only limited to regulating calcium and phosphorus metabolism. However, since 1970s, with the deepening of various studies, especially gene receptor analysis, people have gradually discovered that VitD, as a fat-soluble vitamin, plays an important role in glucose and lipid metabolism, immunity and inflammatory response. Among them, type 2 diabetes mellitus (T2DM), which is mainly characterized by insulin resistance and pancreatic islet β cell damage, is particularly closely related to VitD. In this paper, the research progress of VitD and T2DM in recent years is reviewed.

Studies show that 2% ~10% of pregnant women will suffer from gestational diabetes mellitus (GDM). Because it is related to maternal and fetal health, the management of GDM has attracted special attention from doctors and patients. When lifestyle adjustments still fail to achieve blood sugar standards, drug treatment needs to be initiated. Compared with insulin, oral hypoglycemic drugs are convenient to use and have an ideal hypoglycemic effect. Glibenclamide and metformin are commonly used abroad. Oral hypoglycemic drugs are not included in the registration indication of GDM in China, so their clinical use experience is limited. This article will briefly review the use of the above two oral hypoglycemic drugs in GDM.