Volume 05 · Issue 11 · 2013

The advent of insulin has epoch-making historical significance for diabetes treatment. With the development of medical science and technology, while the insulin preparation is constantly changing, the clinical application of insulin has also made great progress. Except that insulin therapy in patients with type 1 diabetes mellitus (T1DM) is an absolute indication, whether patients with type 2 diabetes mellitus (T2DM) need insulin therapy and the choice of insulin therapy mode are very individualized, especially intensive insulin therapy, and its connotation and clinical application value in T2DM patients are very worthy of examination and discussion.

To evaluate the impact of depression on prognosis of Wagner grade 3 diabetic foot ulcer patients by a psychological assessment.

One hundred and sixty-eight patients suffered from Wagner grade 3 diabetic foot ulcers hospitalized in the Tianjin Metabolic Diseases Hospital from June 2010 to May 2011 were included in the study. Their psychological disorders were evaluated by a self-rating depression scale (SDS) to identify depression. Patients complicated with depression or not were divided into two groups accordingly. Unhealing rate and amputation risk of the patients in the two groups were compared using Chi-square test and logistic regression, respectively.

Ninety-five out of 168 patients (56.5%) were identified as depression and the others (73 out of 168, 43.5%) were not. The unhealing rate of the patients complicated with depression was significantly higher than that of the patients without depression analyzed by Chi-square test (18.9% and 6.8% respectively, OR=2.779, 95%CI: 1.120-9.023). Logistic regression analysis indicated that depression was a risk factor of unhealed ulcers (OR=3.569, 95%CI: 1.220-10.442) after the factors related to prognosis of diabetic foot ulcer were adjusted step-by-step, including infection, arterial disease, age, glycosylated hemoglobin A1c and Charlson grading of complications. Healed patients were further analyzed by logistic regression analysis. Healing after amputation rate is higher among the patients complicated with depression than that of the patients without depression after the adjustment mentioned above (OR=2.793, 95%CI: 1.361-5.732).

Depression is common among patients with Wagner grade 3 diabetic foot ulcers and has adverse effects on the prognosis of the patients. It implies that identification of depressed should be a routine process for diabetic foot ulcer patients to improve wound healing and reduce amputation rate.

Cortisol secretion status were analyzed under different conditions of diabetic foot ulcers (DFU) to investigate their relationship and impact on the prognosis of DFU.

Materials from 188 patients with DFU and 173 patients with high risk factors to DFU admitted to Ruijin Hospital during March, 2010 to March, 2012 were collected and all the patients were classified into several groups according to Wagner grade (Wagner 0 to 5) and infection degree (non-, mild, moderate and severe infection) respectively. The relationship of adrenocorticotropin(ACTH), the plasma cortisol of 08∶00, 16∶00, 24∶00 time point and urinary free cortisol (UFC) in 24 hours with severity of DFU and infection were analyzed; All patients were followed up for 3 months to observe the impact of cortisol levels on healing rates of DFU. Linear regression analysis was used to assess the variation trends of all continuous variables.

With Wagner grade stepping up, the plasma cortisol of 08∶00, 16∶00, 24∶00 time point and urinary free cortisol (UFC) in 24 hours were increasing gradually (F=8.47, 19.15, 14.58, 6.23, all P for trend<0.05); These indicators of cortisol secretion also had a gradual augmentation with infection level elevated (F=4.98, 11.26, 5.95, 3.79, all P for trend<0.05). No significant difference were observed among Wagner grades and infection levels when did analysis of ACTH(F=1.79, 1.39, P>0.05). There is a strong association between elevated plasma cortisol levels and low healing rates of DFU, for patients with normal, increasing or remarkably increasing levels of 08∶00 plasma cortisol and urinary free cortisol (UFC) in 24 hours at baseline had significantly different ulcer healing rates (χ²=3.09, 9.56, P<0.05).

Cortisol levels increased when DFU getting worse with ulcer depth and infection, meanwhile ulcer healing rates reduced. These suggested that cortisol level could be used as an indicator to evaluate the severity of DFU.

To investigate the association between the 137A/G polymorphism of SLC2A9 gene and diabetes mellitus(DM) complicated hyperuricemia (HUA).

A total of 102 healthy controls (45 males and 57 females), 103 patients with DM (59 males and 44 females), 105 patients with HUA (86 males and 19 females), and 104 patients with DM complicated HUA (63 males and 41 females) were enrolled in the study from the Affiliated Hospital of Medical College of Qingdao University in 2009-2010.The polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method was used to detect the polymorphism.

The minor allele frequency of 137A/G was 37.9%. Chi-square test revealed that 137A/G polymorphism was both significantly associated with HUA as well as DM complicated HUA(χ²=4.075, 4.392, both P<0.05), but not with pure DM(χ²=0.942, P>0.05). After adjustment for age and gender, logistic regression analysis showed that people with G allele had higher risk of HUA and DM complicated HUA than those without G allele (OR=1.523, 1.632, both P<0.005), no association with pure DM(OR=1.121, P>0.05).

The 137A/G polymorphism of SLC2A9 gene is closely associated with HUA as well as DM complicated HUA, but not with DM.

To research the current situation of diabetes diet cognition and compliance in patients with type 2diabetes in China.

This questionnaire-based survey was conducted in 50 medical centers in China from April to July in 2010. The selected medical centers covered 21 provinces, 4 municipalities, 4 autonomous regions, and the patients were out-patients and in-patients of 144 secondary, tertiary and community hospitals, the subjects had been diagnosed of type 2 diabetes for more than 1 year. The information of diabetes diet and management was collected by questionnaires. The diabetes attitude scale-3 (DAS-3) formulae, a questionnaire of diabetes knowledge, and summary of diabetes self-care activities (SDSCA) scale were used to assess diabetes diet cognition and compliance of patients. Comparison of data between groups was applied by using t test.

Total of 6043 patients were eligible for the study, and 5961 valid questionnaires were collected. There were 3233 males and 2728 females with an average age of (60±12) years(16-94 years) and a diabetes duration of (9±7) years. The mean body mass index (BMI) 44.04% were normal and 52.21% were overweight or obese. The glycated hemoglobin A1c (HbA1c) was examined in 3048 cases and 32.10% of them reached the standard of <7%. Cognition: 4333(72.69%) cases received diabetic diet education; the average of diet attitudes score was 3.7±1.0; all correct answer rate of the impact of food on glycemia was 1.85%(110/5961), all correct answer rate of the description of food was 0.52%(31/5961); 3669(61.55%) cases treated with insulin, all correct answer rate of diet knowledge was 7.03% (258/3669). Compliance: the average of ordinary diet score was 4.9±2.2 and the average of special diet score was 4.2±1.5 in the SDSCA scale. Total of 4996 cases (83.81%) kept obeying the diet therapy program. And the gender, age, the level of education, BMI, drinking, receive diabetes education, regular follow-up, self-monitoring of blood glucose could influence the patient's compliance with diet therapy.

The mean BMI is high, the rate of HbA1c<7% and the level of diet cognition is low in Chinese patients with type 2 diabetes. And patient educators should consider the factors in diabetic health education, such as gender, age, the level of education, BMI, drinking, receiving diabetes education, regular follow-up, self-monitoring of blood glucose.

To study the change of menopause age in type 2 diabetes mellitus(T2DM) woman and the possible influencing factors.

A random study of residents aged 40 years and over in Zhengzhou city and the surrounding areas was performed by the from of questionnaire.The questionnaire included family composition, past medical history, medication history, smoking and drinking history, physical activity, sleep, mood, menstrual and reproductive history, nursing time and so on.Total of 986 cases of menopause women were contained in this study: 356 cases of non-diabetes women as normal control group (NC), 143 cases of premenopausal diagnosed T2DM women as A1 group (A1) and 487 postmenopausal diagnosed T2DM women as A2 group(A2). The comparison between groups was conducted by using t test or t'test.Multiple stepwise regression analysis was used to evaluate the effect of every indicators on menopause age.

The menopause age of A1 group is (51±3) years old which was significantly higher than that of NC group (t=-5.776, P<0.05). And it had no difference between A2 group(49±4) and NC group(49±4) (t= 0.481, P>0.05). The result of multivariate stepwise regression analysis indicated that menopause age was affected by a variety of factors.T2DM was the most important influence factor of menopause age in the general population as the duration of diabetes was the most important influence factor of menopause age in T2DM woman (P<0.05).

The menopause age of T2DM woman was delayed, which was positively related to the duration of diabetes.

To investigate the effect and mechanism of epidermal growth factor(EGF) nanoparticles on the wounds of diabetic rats.

(1) EGF nanoparticles were prepared by the modified multiple emulsion way with poly lactic-co-glycolic acid(PLGA) as carrier. Drug-loaded rate, encapsulation ratio and release of EGF nanoparticles were measured. (2) Diabetic rats model were made with streptozocin(STZ) through vena caudalis. Skin wound model of diabetic rats were prepared by hole puncher and were divided into 4 groups: EGF nanoparticles group(containing 1 μg/d EGF nanoparticles), EGF group(1 μg/d EGF), empty nanometer particle group(without EGF but the quality was equivalent to the EGF nanoparticles/d) and PBS control group. (3) Photographs and sampling at 3, 7, 14, 21 days were taken and wound healing rate were calculated. The positive cells area of epidermal growth factor receptor were compared by immunohistochemistry.

(1)The average particle diameter of EGF nanoparticles was 193.5 nm. The drug loading ratio was 0.02% and the encapsulation ratio was 85%. The group of EGF nanoparticles released up to 24 h. (2) Healing of wound of EGF nanoparticles group was fast than that of EGF [14 d: (93.8±1.8)% vs(89.3±2.3)%, P<0.05; 21 d: (96.6±1.6)% vs(92.1±4.3)%,P<0.05]. EGF receptor positive cells area of EGF nanoparticles group was more than that of EGF group[7 d: (49.4±6.5)% vs(35.1±2.8)%,P<0.05; 14 d: (80.2±3.8)% vs(73.4±1.7)%,P<0.05].

EGF nanoparticles can upregulate the expression of EGF receptor of cells in wound and accelerate wound healing. The effects are better than that of EGF.

To observe the changes of β/α cells, cell cycle, pocket protein family (retinoblastoma protein (Rb), retinoblastoma-like protein 1 (p107), retinoblastoma-like protein 2 (p130)) and E2F transcription factors of pancreatic islets in mice during neonatal period and to explore their relationship with the proliferation of islet cells.

β/α cell mass, cell size and cell number of mice islets at 1-, 3- to 8-week after birth were detected by immunohistochemistry. Pancreatic islets were digested and isolated by collagenase. Cell cycle was detected by flow cytometry. The expression of mRNA and protein of Rb, p107, p130 and E2F transcription factors was detected by real-time quantitative polymerase chain reaction(PCR) and Western blotting.

(1)Compared with 1 w, β/α cell mass significantly increased at 3 w and 8 w ( P<0.05); cell size didn't change obviously at 3 w, but increased 1.7 times at 8 w (P<0.01); cell number increased nearly 3.5/3.7 times at 3 w (P<0.01), and there's no significant difference between 8 w and 3 w. (2)Compared with 8 w, there were less cells in the G0/G1 phase and more cells in the G2/M phase at 1 w and 3 w (81.3±1.2, 82.8±3.3 vs 92. 6±1.3,F=6.48, P<0.05; 13.4±1.4, 12.2±1.8 vs 5.5±0.5,F=6.25, P<0.05), and the proliferation index were significantly higher at 1 w and 3 w (P<0.05). (3)The mRNA level of Rb at 8 w was much lower than that at 1 w and 3 w (P<0.01); At 3 w and 8 w, the mRNA level of p107 were lower than that at 1 w (P<0.05), whereas the level of p130 were much higher than that at 1 w (P<0.05), and the level of E2F-1 and E2F-2 were significantly lower than that at 1 w (P<0.05), but the mRNA expression of E2F-4 and E2F-5 were increased. Compared with 1 w, the protein level of Rb and p107 were much lower, but the level of p130 was significantly increased at 8 w (P<0.05).

The β/α cell mass increases significantly during neonatal period in mice, primarily in cell numbers and proliferation. Rb, p107, p130 and their related E2F transcription factors dynamically express, which may be involved in the regulation of cell proliferation.

To explore the effect of glucagon-like peptide-1 on the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits p22phox and Nox4 in the heart tissue of type 1 diabetic rats.

Forty-two male Sprague-Dawley(SD) rats were randomly divided into normal control group(group A, n=7) and diabetic model group(n=35) with the random number table. Type 1 diabetic model was established by intraperitoneal injection of streptozotocin. Twenty-nine successfully-induced diabetic rats were randomly divided into diabetic (group DM, n=10), diabetic treated with low-dose of GLP-1 (group DL, n=10) and diabetic treated with high-dose of GLP-1(group DH, n=9) with the random number table method. The rats in group DL were given exenatide in dose of 1 μg/kg twice daily by subcutaneous injection. The rats in group DH were given exenatide in dose of 5 μg/kg twice daily by subcutaneous injection. All rats were sacrificed after exenatide treatment for eight weeks. The mRNA expression of myocardial p22phox and Nox4 in the rats of four groups was detected by real-time fluorescence quantitative polymerase chain reaction(PCR), and the protein expression of myocardial copper-zinc-superoxide dismutase (Cu-Zn-SOD) was detected by immunohistochemical staining. Statistical analysis among groups was performed by using one way ANOVA.

Compared with group NC, the mRNA expression of myocardial p22phox and Nox4 and the myocardial Cu-Zn-SOD protein expression increased significantly in group DM(t=5.77, 5.36, 59.91, all P<0.05). After exenatide treatment for 8 weeks, the mRNA expression of myocardial p22phox and Nox4 and the myocardial Cu-Zn-SOD protein expression decreased significantly in group DL and DH (t=16.86, 7.66 and 16.11, 7.59 and 56.00, 47.05, and all P<0.05). Compared with group DL, the mRNA expression of myocardial p22phox and Nox4 decreased significantly in group DH (t=10.14, 8.67, both P<0.05). There was no significant difference in the expression of myocardial Cu-Zn-SOD between group DL and group DH (t=81.91, P>0.05).

GLP-1 can dose-dependently down-regulate the over-expression of myocardial Nox4 and p22phox mRNA, and dose-independently up-regulate the expression of myocardial Cu-Zn-SOD in type 1 diabetic rats, which may lessen the myocardial damage induced by oxidative stress.

To study the calcium-independent phospholipase A₂ (iPLA₂)expression of islet microvascular endothelial cells (IMECs) and its relationships with apoptosis in different concentrations of glucose by silencing (iPLA₂) genes of rat pancreatic IMECs using small interference technology.

Rat IMECs are successfully separated and purified, then divided into three groups such as normal glucose, constant high glucose and intermittent high glucose group by the method of random number remainder. Detecting the expression of IMECs iPLA₂ under different concentrations of glucose such as 5 mmol/L, 28 mmol/L and a intermittent one of 5 mmol/L or 28 mmol/L by RT-PCR; synthesizing iPLA₂ RNA interference sequences (siRNA) and transfecting it to IMECs, using RT-PCR to verify the transfection; determining the IMECs apoptosis rate in normal and intermittent high glucose by DNA fragmentation and Annexin V/PI flow cytometry. Differences between groups were compared with LSD test, and ANOVA, single factor randomized block design, was used to analyse the apoptosis rate.

The expression of iPLA₂ significantly weakened under intermittent high glucose from 1.90±0.23 to 0.90±0.05 and 0.23±0.03, compared with under normal glucose and under constant high glucose; successfully synthesized and transfected iPLA₂ siRNA, after silencing iPLA₂ gene, the DNA fragmentation became more apparent and the flow cytometry apoptosis significantly increased under intermittent high glucose conditions(44.9±2.7), compared with under normal glucose (3.1±1.0, P<0.05).

The expression of IMECs iPLA₂ would be suppressed in intermittent high glucose condition. Inhibiting the iPLA₂ gene expression by small interfering technology can promote apoptosis, suggesting that iPLA₂ expression weakening may be involved in the IMECs apoptosis induced by intermittent high glucose.

Hearing loss is divided into two categories: conductive and sensorineural. The most common cause is sensorineural hearing loss, which is mainly caused by abnormal sensitivity or number of sensory hair cells in the cochlea, or abnormal auditory nerves that can transmit sound nerve impulses from the cochlea to the brain. With the increase of age, cochlear auditory hair cells gradually decrease, and neuropathic hearing loss gradually appears after the age of 65, which first affects high-frequency hearing and gradually develops into damage of low-frequency hearing. Since diabetic patients with sensorineural deafness were first reported in 1857, more and more scholars believe that diabetes is related to hearing loss, and the incidence of hearing impairment is directly proportional to age in both type 1 and type 2 diabetes, and high-frequency hearing impairment is the first in middle-aged and elderly patients^[1,2]。 Pudar et al.^[3]The auditory function of 50 patients with type 1 diabetes mellitus was tested by pure tone audiometry and auditory brainstem response. The results showed that 73.04% of patients with diabetes mellitus over 10 years had hearing loss. This article reviews the mechanisms of hearing impairment in diabetic patients.

With the rapid development of economy, the change of people's lifestyle and the increase of life expectancy, the number of diabetic patients is increasing day by day. Its main complication and leading cause of death was cardiovascular disease. Studies have shown that diabetes is an independent risk factor for sudden cardiac death (SCD), but the mechanism is not fully understood. This article briefly reviews the relationship between diabetes mellitus and SCD, and provides scientific basis for studying the mechanism, prevention and treatment of SCD in diabetic patients.

Helicobacter pylori (Hp) is a gram-negative helicobacter that colonizes and multiplies in gastric epithelial cells. In 1982, Australian scholars Warren and Marshall successfully isolated this bacterium from the gastric mucosa of patients with chronic gastritis. Hp infection is one of the most common chronic infections at present, and about 50% of the population in the world is infected with Hp. Studies have shown that the rate of Hp infection in patients with type 2 diabetes mellitus (T2DM) is higher than that in non-diabetic patients (NDM), and T2DM patients infected with Hp are prone to diabetes-related chronic complications^[1]。 This article summarizes the status of Hp infection, the fluctuation of blood glucose after Hp infection, and the risk of macrovascular and microvascular diseases in T2DM patients as follows.

Congenital hyperinsulinemia (CHI) is a genetically heterogeneous disorder characterized by inappropriate insulin secretion in a hypoglycemic state^[1]。 So far, nine CHI-causing genes have been identified, and eight genetic types have been identified^[2], ATP-sensitive potassium channel type congenital hyperinsulinemia (K_ATP-CHI) is the most common type of congenital hyperinsulinemia due toABCC8AndKCNJ11Caused by a mutation in a gene. According to the different histological characteristics, the pancreas of CHI can be divided into three histological types: diffuse, focal and atypical. WhileABCC8Focal K due to gene mutation_ATP-CHI is rare in China. In this paper, a case ofABCC8Focal K due to gene mutation_ATP-CHI was reported to improve the awareness of focal congenital hyperinsulinemia among pediatricians and endocrinologists.

With the increase of the number of patients with type 2 diabetes mellitus (T2DM) and the prolongation of the disease time, more and more patients need to use insulin. Both fasting blood glucose (FBG) and postprandial blood glucose (PPG) affect the control of overall glycated hemoglobin (HbA1c), so the simultaneous control of FBG and PPG is needed as early as possible^[1]。 The 2010 "Guidelines for the Prevention and Treatment of Type 2 Diabetes in China" pointed out that T2DM patients in China mainly have postprandial blood glucose increase, and the proportion of newly diagnosed diabetic patients with simple postprandial blood glucose increase is close to 50%^[2]It can be seen that postprandial glycemic control is one of the biggest challenges in the prevention and treatment of T2DM in China. At present, premixed insulin containing both prandial and basal insulin components has become the treatment choice for many Chinese T2DM patients because it can meet the body's demand for basal and prandial insulin at the same time. Among them, premixed insulin analogs showed better postprandial glycemic control and less risk of hypoglycemia because their drug mode of action could better mimic the physiological insulin secretion pattern than premixed human insulin^[3]。 Therefore, premixed insulin analogs can better improve postprandial blood glucose on the basis of controlling basal blood glucose, and are more suitable for Chinese T2DM patients. In recent years, premixed insulin analogs with different ratios have been introduced continuously, and they have provided multiple options for individualized treatment of T2DM with different postprandial glycemic challenges.

Obesity-induced inflammation is associated with insulin resistance and is morphologically characterized by macrophage infiltration into adipose tissue. Recent studies have shown that a variety of immune cells, including B cells and T cells, are involved in regulating adipose tissue inflammation during the development of obesity.

Obesity, metabolic syndrome are associated with systemic inflammation and increased perinatal morbidity. Metformin (MET) improves metabolic and inflammatory markers in non-pregnant adults. Researchers at Hofstra North Shore School of Medicine in the United States used in vivo and in vitro models to investigate the effects of MET on maternal and fetal inflammation.

The increase of macrophage in adipose tissue of obese people is closely related to insulin resistance and metabolic dysfunction. However, little is known about changes in other immune cells in adipose tissue and whether they also contribute to the development of insulin resistance in obese people. This study from the University of Washington, USA, explored the characteristics of T cells in adipose tissue of obese individuals with metabolic disorders and insulin resistance (MAO), obese individuals with normal metabolism and insulin sensitivity (MNO), and lean people (lean). The researchers evaluated insulin sensitivity using a high insulin-n-glucose clamp technique.

Recent studies have shown that the composition of intestinal microorganisms causes metabolic disorders by affecting the physiological function and metabolic balance of the host. Metformin is one of the most widely prescribed drugs in the treatment of type 2 diabetes. In this study, researchers from Kyung Hee University in South Korea investigated whether the antidiabetic effects of metformin are related to changes in gut microbial composition.

In obese patients, the gastrointestinal mechanisms involved in suppressing appetite are impaired. Eating stimulates intestinal release of glucagon-like peptide 1 (GLP – 1) that inhibits feeding and plays a role in energy balance regulation. Currently, it is unknown whether obesity-prone (OP) rats have a dysregulation of GLP – 1 signaling that reduces nutrient-induced satiety and leads to excessive appetite.