Volume 05 · Issue 06 · 2013

Professor Michael Edmonds and Chief Podiatrist Ali Foster of the University of London published in 2004A practical manual of diabetic foot careThe foreword of the book points out that the complications of diabetic foot disease are a global public health problem, and the number of diabetic foot disease and resulting amputations is increasing worldwide. There are still many problems in the treatment of podiatry in the existing medical and health system. After presenting typical cases of diabetic foot disease from five continents, they emphasized that the prevention of diabetic foot disease is the most effective among all chronic complications of diabetes, and that early access to specialized diagnosis and treatment (including referral) can effectively save the limbs of patients^[1]。

In China, diabetic foot ulcer has become the main cause of chronic refractory wounds^[1]。 Because diabetic foot ulcer is one of the main causes of hospitalization and non-traumatic amputation in diabetic patients^[2,3], bringing a serious medical burden to diabetic patients^[4]And the treatment of diabetic foot ulcer is extremely difficult, so it should be prevented clinically. Through diabetes education, informing patients about foot care can reduce the incidence of foot ulcer in diabetic patients^[5]。 At the same time, the basic and clinical research on diabetic foot ulcer should be strengthened, and the diagnosis and treatment level of clinicians should be improved, so that it is possible to improve the cure rate of diabetic foot disease in China and reduce the amputation rate.

To investigate the clinical features of the lower extremity artery thrombosis in the type 2 diabetes patients and to evaluate the effect of the catheter directed thrombolysis combined with endovascular intervention.

A total of 46 type 2 diabetes patients with acute lower extremity artery thrombosis who were performed the catheter directed thrombolysis and the endovascular intervention in the PLA 306th Hospital during the period from January, 2008 to December, 2012 were enrolled in the study.The subjects consisted of 8 males and 38 females aged (68±16) years old with the diabetes duration of (8±6) years and the acute limb ischemia duration of (7±4) days. The subjects were divided into three groups according to the location of the lower extremity artery thrombosis relative to the inguinal ligament., which were the central group (8 cases), the peripheral group (22 cases) and the mixed group (16 cases). The treatment process of the catheter directed thrombolysis was compared among the groups and the anke brachial index (ABI) was monitored before and after the treatment. Single factor variance analysis was used for multi-group comparison, and Student-Newman-Keuls test was used for comparison between two groups.

The needed dosage of urokinase was less in the peripheral group than those in the central and mixed groups ((280±40), (350±60), (360±40)×10⁴U, respectively, F=184.47, P<0.05). The required time for thrombolysis treatment was also less in the peripheral group than in the central and mixed groups ((52±12), (76±20), (72±14)h, respectively,F=1203.39, P<0.05). Between the central group and the mixed group, no statistical difference was observed in the needed urokinase dosage or the required thrombolysis time (P>0.05). After the catheter directed thrombolysis, all residual stenoses were treated with the endovascular intervention. The ABI was significantly increased by the endovascular intervention from (0.31±0.15) to (0.95±0.31).

More extensive the thrombosis, much higher dosage of catheter thrombolytic drug and longer treatment time are required. The catheter directed thrombolysis combined with endovascular intervention is a safe and effective treatment to acute lower extremity artery thrombosis in type 2 diabetes patients.

To analyze retrospectively the causes of death, hospital mortalities and mortality risk in hospitalized patients with and without type 2 diabetes mellitus (T2DM).

Informations of all inpatients admitted to PLA General Hospital during 1993 and 2012 were collected and analyzed. Prevalence and mortalities of T2DM among all hospitalized patients and proportion of T2DM patients among total deaths of inpatients each year were calculated. Causes of deaths were analyzed. Logistic regression and stratified analyses of hospital mortalities were performed.

During the study period of 20 years, the proportion of hospitalized patients with T2DM had risen from 4.55% (609/13 395)to 11.97%(11 778/98 402); the proportion of T2DM patients among all deaths had risen from 9.64%(32/332) to 25.47%(149/585), the hospital mortality of patients with T2DM decreased from 5.25%(32/609) to 1.27%(149/11 778). The leading causes of death of patients with T2DM were malignancy (32.02%), respiratory disease (17.13%), ischemic heart disease (15.22%), cerebrovascular disease (9.75%) and organic cardiopathy (5.40%), while the leading causes of death of patients without T2DM were malignancy (48.07%), respiratory disease (13.61%), cerebrovascular disease (5.63%), ischemic heart disease (5.57%) and organic cardiopathy (4.70%). After adjustment for age and sex, T2DM was associated with increased risks of mortality in patients with malignancy (RR 2.03, 95%CI(1.871-2.202)), ischemic heart disease (1.303(1.206-1.409)) and cerebrovascular disease (1.205(1.094-1.327)).

T2DM is associated with increased risks of mortality in patients with malignancy, ischemic heart disease and cerebrovascular disease. As the proportion of inpatients with T2DM increased, the influence of T2DM on hospital mortality deserves more attention.

To detect multiple islet autoantibodies in patients with type 1 diabetes mellitus (T1DM) and to describe clinical feature of subtype T1DM.

Clinical data of 67 cases of type 1 diabetic patients who admitted in our hospital from November 2010 to November 2011 were retrospectively analyzed. Six islet autoantibodies were screened, including islet cytoplasmic antibody (ICA, detected by immune histochemistry method), insulin autoimmune antibody (IAA, detected by enzyme-linked immunosorbent assay(ELISA)), glutamic decarboxylase antibody (GADA, detected by both ELISA and radio-immune precipitating method(RIP)), protein tyrosine phosphatase-2 antibody and zinc transporter 8 antibody(IA2A and ZnT8A, detected by radio-immune precipitate (RIP)).

Among 67 type 1 diabetic patients, 53 patients were diagnosed as classical T1DM, 12 diagnosed as latent autoimmune diabetes of adults (LADA) and 2 patients fulfilled the criteria for fulminant type 1 diabetes (FT1D). The onset age was between 2 and 77 years, body mass index (BMI) was (22±4) kg/m^2, level of glycated hemoglobin A1c(HbA1c) was 9.7%±2.4%, and level of fasting serum C-peptide was (0.3±0.4) μg/L, respectively. There were 51(76.1%), 35(52.2%), 19(28.3%), 16(23.9%), 16(23.9) and 10 (14.3%) patents positive for GADA (ELISA), GADA (RIP), IA2A, ZnT8A, IAA and ICA, respectively. Fifty-six(83.6%) patients were positive for at least one antibody among four antibodies (GADA(ELISA), GADA(RIP), IA2A, and ZnT8A). Fifty-one GADA-positive patients detected by ELISA included 33 cases of 35 cases with positive GADA detected by RIP, 15 cases among 19 cases with positive IA2A, and 14 cases among 16 cases with positive ZnT8A. Insulin therapy was initiated 3.9 years after onset on average in patients with LADA. The plasma glucose level at onset of the two patients with FT1D was 41.1 and 23.1 mmol/L, respectively. In contrast, the HbA1c level was 7.8% and 6.5%, respectively, at diagnosis. The fasting and postprandial serum C-peptide values were lower than 0.03 μg/L or undetectable in these 2 cases with F1DM.

GADA detected with ELISA shown higher sensitivity than other 5 antibodies screening, and multiple islet antibodies detection has limited value in diagnosing T1DM. FT1D occurs rapidly with serious metabolic disorders.

To investigate the clinical characteristics of immunological hypoglycemia induced by exogenous human insulin or insulin analogues.

The clinical data of 3 new cases from the Peking Union Medical College Hospital and 14 cases from MEDLINE or national core periodical were retrospectively analyzed.

Three patients were admitted in hospital for recurrent hypoglycemia when exogenous insulin had been stopped for at least 1 month. They had blood glucose(BG) wide fluctuation and dissociation between C-peptide(C-P) and insulin or C-P and BG during 5 h oral glucose tolerance test(OGTT). In literature review, 14 cases of this kind of complication had been reported. The overwhelming majority (88.2%) of these 17 patients were Asian people. The lowest BG was 2.2(1.0-3.3)mmol/L, accompanied by high titer of insulin autoantibody (IAA). About half of the patients needed steroid treatment with or without plasmapheresis or cyclophosphamide, while another half would be spontaneous remission in about 2.4(0.5-8.0)months.

(1) Immunological hypoglycemia induced by exogenous human insulin or insulin analogues is a rare complication which easy to be missed and delayed diagnosis for the hypoglycemic effect of insulin itself. (2) The Asian people are most vulnerable to this disease. The episodes of hypoglycemia are irregular and the degree of hypoglycemia can be various, range from mild to severe even unconsciousness. (3) Hypoglycemia can be induced by oral glucose test and in which the tendency of C-P and insulin are separated from each other. (4) The high titer of IAA had a confirmed diagnostic value, however, the choice of therapy option was not related to titer of IAA.

To investigate the characteristics of hyperuricemia in the type 2 diabetes patients aged over 40 years old.

A total of 3768 type 2 diabetes patient over 40 years old who visit the clinics of the 306 th Hospital during the period from September, 2003 to December, 2011 were enrolled in the study. The subjects were divided into 2 groups based on the blood uric acid (BUA), which were group A with hyperuricemia (> 420 μmol/L in the male and >357 μmol/L in the female) and group B with normal BUA level. The quinquepartite method was used after sorting the BUA level. The subjects were stratified by age into 7 groups with every 5 yrs differences from 40 to 70 years old. The prevalence of hyperuricemia, BMI, WHR(waist-to-hip ratio), BP(blood pressure) and biochemical parameters were compared among these groups. The spearman analysis was used to explore the correlation between BUA and blood glucose, HbA1c and insulin-resistance index. The logistic regression analysis was applied to investigate the related risk factors of hyperuricemia.

BUA was significantly higher in the male than in the female(t=-11.091, P<0.05). In the males, the level of BUA was initially decreased with age followed by an increase when aged over 65 yrs, while the level of BUA kept increasing with age in the female. In group A, the male were younger and with lower level of HDL-C(t=2.526, 2.764, all P<0.05) than the female. Compared with group B, the female had lower fasting and post prandial glucose level(t=2.147, 3.284, all P<0.05), and the male had lower HbA1c (t=2.982, P<0.05) in group A. in Higher fasting and post-prandial insulin level and higher insulin-resistance index were observed in group A than in group B (allP<0.05). In both the male and the female of group A, the levels of blood TG, BUN, and creatinine were higher, while the HDL-C and e-GFR were lower than those in group B (allP<0.05). The urine Alb/Cr ratio was significantly higher in group A than that in group B for the male(t=-3.922; P<0.05), but not for the female. Logistic regression analysis showed that BUA was positively correlated with BMI, TG, and Alb/Cr (OR: 1.128, 1.231, 1.004; all P<0.05), while negatively correlated with HbA1c and e-GFR(OR: 0.811, 0.973; all P<0.05) for the male. In the female, BUA was showed to be positively correlated with BMI, TG, HDL-C (OR: 1.171, 1.179, 0.264; all P<0.05), while negatively correlated with e-GFR(OR: 0.978; P<0.05).

The patients with diabetes and hyperuricemia have more severe insulin resistance, lipids abnormalities and decrease of e-GFR. The level of BUA itself and the impact of age, BMI and blood pressure on the level of BUA differ in the male and in the female.

To explore the effect of Dynamin-related protein 1 (DRP-1) on glucocorticoid-induced β cell apoptosis.

Rat insulinoma cell line INS-1 β cells were exposed to dexamethasone (Dex) and apoptosis was assessed by measuring the percentage of sub-G1 cells. Dex-upregulated expression of DRP-1 was determined by western blot. The inducible wild-type DRP-1 (DRP-1 wt) and dominant-negative mutant (DRP-1 k38A) stable cell lines were established using Tet-on system in INS-1 cells, respectively. The expression of DRP-1 induced by doxycycline (Dox) in the both cell lines was confirmed by immunofluorescence staining and western blot. The effect of DRP-1 wt and DRP-1 k38A expression on Dex-induced β cell apoptosis were analyzed by TUNEL staining. Caspase-3 activity and ROS generation were further investigated to explore the relevant mechanisms of the cell apoptosis. One-way of variance and t-test were used for data analysis.

In the Dex group with different Dex dosage, the apoptotic rates of INS-1 β cells ((15.7±4.2), (30.4±3.3)and(61.6±5.4)%) were higher than those in the control group(3.3±1.3)%( t was 6.44, 14.07 and 30.26; P<0.05); In the Dex group with different exposure time of Dex, the apoptotic rates of INS-1 β cells ((10.6±1.2)%, (15.1±4.6)%and(42.6±9.8)%) were higher than those in the the control group(2.4±1.3)%(t value was 2.99, 4.63 and 14.66, P<0.05). DRP-1 expression was showed to be induced by Dex by western blotting. The induction of DRP-1 expression significantly promoted Dex-induced apoptosis in the DRP-1 wt inducible β cell line ((53.8±7.2)% vs(16.2±3.2)%,t=10.02, P<0.05), but not in the DRP-1 k38A inducible β cell line. It was further demonstrated that induction of DRP-1 wt enhanced Dex-induced caspase-3 activation ((1979±132)vs(921±182),t=11.13, P<0.05) and ROS production in β cells ((772±62)vs(290±56),t=13.66, P<0.05), whereas induction of DRP-1 k38A inhibited Dex-induced caspase-3 activation ((506±47)vs(681±44),t=5.25, P<0.05) and ROS production ((235±14)vs(309±44),t=3.86, P<0.05).

DRP-1 may be involved in the process of glucocorticoid-induced pancreatic β cell apoptosis.

To investigate the effects of exenatide, one of the glucagon-like peptide-1(GLP-1) receptor agonist, on TGF-β1/Smad signaling pathway and myocardial fibrosis.

A total of 36 male Wistar rats with the weight of 170-200 g were randomly divided into the normal control group(n=10) and the model group(n=26). STZ was injected into caudal vein to induce type 2 diabetes mellitus in the model group. The 22 alive rats in the model group were then randomly divided into the exenatide intervention group (EX group, n=11) and the diabetic group (DM group, n=11). Exenatide was subcutaneously injected in the EX group(1.0 nmol·kg^-1·d^-1), while the same amount of saline was injected in the other two groups. In the alive rats at the end of the study, 10 in each group, the structural change of the heart tissue and the collagen aggradation were observed by HE staining and Masson staining and the expression of transforming growth factor 1 (TGF-β1), Smad2, Smad3, Smad7, collagenⅠ(ColⅠ) and peroxisome proliferator-activated receptor α (PPARα) were detected by Western Blot or Real-Time PCR. One-way of variance and rectilinear correlation analysis were used to analyse the data.

Compared to the normal control group, scattered and rearranged collagen was observed in the diabetic group with the ratio of heart weight to body weight increased. After the intervention of exenatide, there was less collagen aggradation and the ratio of heart weight to body weight was decreased(F=44.456, P<0.05). The expression of TGF-β1, Smad2, Smad3, COLI were also increased in the diabetic group compared to the normal control group and those after the intervention of exenatide(F=20.005, 57.902, 14.206, 144.807, P<0.05). Both Smad7 and PPARα were showed to be decreased in the diabetic group compared to the normal control group and those after the intervention of exenatide(F=22.318, 39.142, P<0.05).

Exenatide may suppress the expression of TGF-β1/Smad signaling pathway and alleviate myocardial fibrosis, which may relate to the activation of PPARα.

Periodontitis is a chronic infectious disease of periodontal support tissue caused by microorganisms in dental plaque, which leads to inflammation and destruction of periodontal support tissue, mainly manifested by periodontal pocket formation, progressive attachment loss and alveolar bone resorption. According to statistics, the prevalence rate of periodontitis among adults in China reaches more than 80%, among which 10% ~15% of adults suffer from severe periodontitis and seriously affect the quality of life^[1]。 Diabetes is a major risk factor for periodontitis, research suggests^[1]。 The risk of periodontitis in diabetic people is nearly 3-fold higher than that in non-diabetic people^[2]。 Poor glycemic control is a major factor in the increased risk of periodontitis. The results of the Third National Health and Nutrition Survey showed that the prevalence of periodontitis was significantly higher in adults with glycosylated hemoglobin (HbA1c)>9% than in non-diabetic people after adjusting for influencing factors such as age, race, education, gender, and smoking (OR2.90，95%CI1.40～6.03)^[3]。 Therefore, some scholars list periodontitis as "the sixth major complication of diabetes". More studies show that diabetes and periodontitis have a two-way influence relationship^[4]。 Not only is diabetes a risk factor for periodontitis, but periodontitis is also a negative influencing factor on blood sugar control. The first study to support this view was in 1996 by Taylor et al.^[5]Individual study of the Sheila River community in India. Severe periodontitis resulted in poor glycemic control (HbA1c>9%) at at least 2 years of follow-up. Another meta-analysis, which included five studies, showed that 485 patients with diabetes complicated with periodontitis were treated for periodontitis, and HbA1c decreased by 0.4% at 3 to 9 months of follow-up^[6]。 In addition, periodontitis severity is associated with the severity of non-oral complications associated with diabetes, such as diabetic retinopathy, diabetic neuropathy, diabetic nephropathy, and cardiovascular complications, among others.

Patients with diabetic foot disease often need amputation (toe amputation) and debridement surgery because of severe infection and ischemia. Most of these patients are complicated with acute and chronic diseases such as hypertension and coronary heart disease^[1]。 Long-term diabetes and its chronic complications can make them suffer from anemia and hypoalbuminemia, resulting in poor general condition, increased operation difficulty and difficulty in recovery after operation; The perioperative period is often life-threatening due to sudden cardiac events. Four typical cases are reported below.

Diabetic foot disease has been widely concerned by diabetic patients and their related professionals because of its complex etiology, difficult treatment and poor prognosis. Diabetes is also associated with other foot skin diseases, some of which are unique to diabetic patients, such as eruptive xanthomas, collagen deposition, waxy skin, lipid progressive necrosis, and skin changes caused by oral sulfonylureas. Mold infection, eczema, itchy skin, etc. are also common in diabetic patients, which are the inducing causes of foot ulcers and infections. Some rare skin diseases and systemic diseases have different treatments and prognosis in the feet. Therefore, the differentiation between diabetic foot disease and non-specific foot skin lesions has important clinical significance. This article will discuss the skin lesions of the foot that need to be identified.

The proportion of patients with diabetic foot ulcer in clinical practice is relatively small, and every patient is very precious to clinical researchers. The shapes of diabetic foot ulcer wounds are varied, with different manifestations in size, shape, color, depth, location, etc. Moreover, the wound shape is constantly changing during the treatment process, so it is difficult to express the characteristics of the wound accurately by simple text description. If there are no accurate records at different stages, the records will be blurred at the final evaluation of efficacy, and comparisons cannot be made. On the contrary, if the wound is photographed and retained, the original appearance of the wound can be restored to a greater extent, making up for the shortage of text description, and it can also be displayed repeatedly for convenient comparison.

The first plenary meeting of the second editorial committee of Chinese Diabetes Journal was successfully held in Nanjing on May 26, 2013. Luo Ling, Deputy Secretary-General of Chinese Medical Association, Wei Junmin, Vice President of Chinese Medical Association Magazine, and more than 70 editorial members from all over the country attended the meeting.

Professor Caravaggi first introduced some information about diabetic foot disease: worldwide, every 30 seconds, a diabetic patient is amputated; 15% of diabetic patients will have diabetic foot disease in their lifetime; 50% of non-traumatic amputations occur in diabetic patients; Critical limb ischemia (CLI) is the main cause of amputation in diabetic patients.

Insulin plays an extremely important regulatory role in liver lipid synthesis, metabolism and export. Considering the three factors of local obesity and insulin sensitivity to regulation of glucose metabolism and anti-lipolysis, the researchers hypothesized that intrahepatic insulin exposure is an important determinant of intrahepatic cellular lipid content (IHCL).

Dietary copper deficiency has been associated with a variety of clinical manifestations of metabolic syndrome, including hyperlipidemia as well as fatty liver. Fructose feeding has been reported to worsen some of the complications associated with copper deficiency. This study explored whether copper deficiency plays an important role in the induction of fatty liver by fructose feeding, and further clarified the possible mechanisms.

Epidemiological studies have found obesity and diabetes to be independent risk factors for nonalcoholic steatohepatitis (NASH) and liver cancer. However, there is still debate as to whether insulin resistance is directly related to NASH and liver tumors. It is hypothesized that hepatic steatosis (rather than insulin resistance) may be associated with NASH and the pathophysiology of liver tumors. Study to observe knockout insulin receptor substrate 1 (IRS1) in long-term high-fat (HF) feeding^-/-Incidence of NASH and liver tumors in mice.

Data on non-alcoholic fatty liver disease (NAFLD) incidence, remission rates and their predictors are insufficient. This study aimed to evaluate the epidemiological characteristics of NAFLD through prospective observational follow-up based on the general population.

Patients with polycystic ovary syndrome (PCOS) are often associated with non-alcoholic fatty liver disease (NAFLD), both of which are associated with obesity and insulin resistance. Few studies have explored in depth the causes of the high prevalence of obesity in patients with PCOS. The study aimed to determine whether PCOS was independently associated with hepatic steatosis compared to healthy controls with similar age, body mass index (BMI); Whether hepatic steatosis is associated with hyperandrogenism.