Volume 08 · Issue 02 · 2016

Obesity and type 2 diabetes often co-occur. The survey shows that the prevalence of type 2 diabetes in overweight and obese people in China is 12.8% and 18.5% respectively; According to the diagnostic criteria of abdominal obesity, abdominal obesity accounts for about 50% of type 2 diabetes patients in China^[1]。 Obesity and type 2 diabetes have a common pathogenic soil. Obesity can cause insulin resistance and chronic inflammatory states. Insulin resistance can lead to the development of type 2 diabetes, as well as hypertension, dyslipidemia, and coagulation/fibrin dysfunction, and eventually atherosclerotic vascular disease.

Obesity is increasingly prevalent all over the world. Metabolic abnormalities, type 2 diabetes, cardiovascular diseases and tumors caused by obesity pose a serious medical burden. Recently, it has been found that some patients have no metabolic abnormalities such as hypertension, hyperglycemia, hyperlipidemia or insulin resistance, although their body mass index (BMI) reaches the standard of obesity, that is, there is "metabolically healthy obesity (MHO)". At present, there are many studies on MHO, but the results are still controversial. This article reviews the definition criteria, influencing factors, mechanism, risk and clinical significance of MHO.

With the increasingly severe situation of diabetes, breakthroughs and innovations in diabetes treatment methods are imminent. In addition to the classical oral hypoglycemic drugs and insulin therapy, many drugs targeting new therapeutic targets, especially molecular biology targets, have also emerged, among which leptin is considered as a potentially effective therapeutic drug. In the early 1990s, studies found that some obese rats lacked an important substance in their blood that could effectively prevent obesity and diabetes in rats. In 1994, this substance was cloned and confirmed to be an adipokine secreted by adipocytes and mainly acts on the central, can regulate appetite, body weight and energy metabolism, so it was named "leptin". Further research found that leptin not only plays an important role in regulating energy intake and consumption, but also has important value in regulating blood sugar. At present, the potential value of leptin in the treatment of diabetes has been increasingly recognized and attracted wide attention. This article will discuss the progress of the mechanism of leptin regulating sugar metabolism.

To assess the endogenous regulation of basic fibroblast growth factor(bFGF) in the foot wound healing response induced by negative pressure wound therapy (NPWT) in diabetic patients.

From January 2010 to December 2014, 40 patients with diabetic foot wounds fitting the inclusion criteria were enrolled in the clinical trial. The subjects were randomly assigned for NPWT or conventional (control group) treatment with a computer randomization algorithm, with 20 cases in each group. Granulated tissue biopsies were collected before(0 day) and 7 days after treatment in both groups. All biopsies were subdivided into two parts. One part was preserved in 4% paraformaldehyde for HE staining, Masson's trichrome staining and immunocytochemical staining for bFGF expression. Another part was stored at -80 ℃ for Western blotting analysis of bFGF protein expression. Differences between two groups were analyzed by using two-samplet test.

Compared with control group, the NPWT-treated wounds developed characteristics of granulated tissue, which presented with intense inflammatory cells, fibroblasts and neoformation of vessels. Masson's trichrome staining showed that the collagen content in the NPWT group was significantly increased compared with that in the control group after treatment(13.4%±5.3% vs 1.1%± 2.6%,t=9.26, P<0.01, α=0.05). The immunohistochemical analysis revealed that the bFGF expression was significantly up-regulated in foot wounds of NPWT-treated groups when compared with that in the control group(0.21 ± 0.06 vs 0.01 ± 0.03, t=12.06, P<0.01, α=0.05). And the protein expression of bFGF in NPWT group with Western blotting analysis was significantly up-regulated when compared with that in the control group (2.30 ± 1.00 vs 0.12 ± 0.07, t=10.43, P<0.01, α=0.05).

NPWT enhances the bFGF expression in granulation tissue in diabetic foot wound and promotes the wound healing.

To explore the levels of glucagon-like peptide-1(GLP-1) after oral glucose tolerance test (OGTT) in patients with polycystic ovary syndrome (PCOS).

From June 2013 to August 2014, 33 cases of PCOS patients and 30 healthy women with matched age and body mass index (BMI) were enrolled in this study. The levels of glucose, insulin and GLP-1 were evaluated, the values of homeostasis model assessment for insulin resistance (HOMA-IR), glucose area under curve(AUCGLU), insulin area under curve(AUCINS), GLP-1 area under curve(AUCGLP), early phase glucose change(ΔGLU30), insulin change(ΔINS30) and GLP-1 change(ΔGLP30) were calculated by OGTT in all the subjects. Data were compared with t test between the two groups. Multiple stepwise regression analysis was used to analysize multiple factors of measurement data.

There was no significant difference in age and BMI between the two groups(t=0.280, 1.375, both P>0.05). The fasting glucose and insulin and the levels of 1 hour after OGTT were significantly higher in PCOS group than those in control (GLU 0 h:(5.3±0.6) vs (5.0±0.5) mmol/L, 1 h: (7.8±2.0) vs (7.0±1.0) mmol/L; INS 0 h: (20±14) vs (13±6) mU/L, 1 h: (144±56) vs (114±50) mU/L;t= 2.709, 2.079, 2.457, 2.283, all P<0.05), while, the fasting GLP-1 levels of PCOS group was significantly lower than that in control ((5.0±2.4) vs (6.6±3.0) pmol/L,t=-2.309,P<0.05). There was no significant difference in GLP-1 levels after OGTT between the two groups. The values of HOMA-IR and AUCGLU, ΔGLP30 after glucose load were all significantly higher in PCOS group than those in the control( t=2.712, 2.290, 2.557, all P<0.05). The fasting GLP-1 was positively correlated with fasting glucose and insulin (r=-0.355, -0.552,P<0.05). Multiple regression analysis suggested that the fasting GLP-1 was an important influencing factor of testosterone level(β=0.191,P=0.027).

Abnormal secretion of GLP-1 occurrs in PCOS patients, maily lower in fasting GLP-1, which is associated with insulin resistance, glucose metabolism disorder and testosterone level.

To investigate the influence of lifestyle and social-economic factors on leptin/adiponectin ratio (L/A) among children and adolescents in Beijing.

Total of 3 385 children and adolescents between 6 and 18 years of age were selected from the subjects who were recruited in survey which was conducted by Beijing Children and Adolescent Metabolism Syndrom(BCAMS) cohort study in 2004. Enzyme-linked immunosorbent assay was used to determine serum leptin (LEP) and adiponectin (APN) levels. Self-reported information on lifestyle and social-economic factors were collected by questionnaire.

(1) The age, gender, Tanner stage, lifestyle and social-economic status were different in LEP/APN ratio (L/P) quintile groups(F value: 2.9-58.7,all P<0.05), the metabolic disorder status was more seriously in the high L/A group than the low L/A group (F value: 6.9-999.9,all P<0.05).(2)Multiple linear regression showed that the physical activity, father's education level and sleep duration were independent negative correlated with L/A (unstandardized coefflcients were -0.129,-0.079,-0.060respectively and standardized coefflcients were-0.107,-0.065,-0.046, respectively, allP<0.05) and the unemployed father, mother's education level, unemployed mother and TV-watching time were independent positive with L/A (unstandardized coefflcients were 0.504, 0.156, 0.396, 0.047 respectively and standardized coefflcients were 0.068, 0.122, 0.073, 0.042 respectively, allP<0.05).

We can optimize lifestyle and social-economic factors to improve the adipocytokines profile and prevent metabolic disorder status.

To explore the effects of exenatide on autophagy and occurrence of brown adipocytes for white adipose tissue in obese rats.

Twenty 4-week-old male SD rats were randomly divided into 2 groups according to random number table: control group with normal fat diet (n=10)and high fat diet group(HFD group,n=10). The rats in HFD group was fed with high-fat diet for 12 weeks, then they were randomly divided into intervention group(Exe group) and obesity group. The rats in the Exe group were subcutaneously injected with exenatide 10 μg·kg ^-1·d^-1 through abdominal wall for 10 weeks, while the rats in control and obesity group were subcutaneously injected with saline solution. Western blotting and real time polymerase chain reaction (RT-PCR) were used for protein and gene expression assays. One-way analysis of variance and independent-samples t test were used for statistical analysis.

(1) After 4 weeks of high-fat diet feeding, the body weight in the HFD group was increased than that in the control group ((472± 38) vs (420 ± 28) g , t=3.302, P=0.011). After 4 weeks of exenatide treatment, the body weight was significantly decreased in the Exe group than the obesity group ((598 ± 24) vs (696 ± 35) g ,t=4.554, P= 0.002). (2) Compared with the obesity group, the level of autophagy-related protein light chain 3B(LC3B) II/LC3BI was increased in the Exe group(2.17 ± 0.12 vs 1.16±0.08, t=3.584 , P<0.05). The level of uncoupling proteins 1(UCP-1, which represents the occurrence of brown adipocytes for white adipose tissue) was increased than that in the obesity group(1.63 ± 0.09 vs 0.82 ± 0.06, t=8.397, P=0.0014).

Exenatide may reduce the body weight in obesity rats induced by high-fat-diet. The mechanism maybe promotion of the autophagy and converting into brown fat in white adipose tissue.

To explore the distribution of pathogens causing infections in the diabetic foot patients and analyze the drug susceptibility so as to provide guidance for reasonable clinical use of antibiotics.

A retrospective study was carried out on the clinical materials from 580 patients with diabetic foot infections hospitalized in Nanfang Hospital from January 2000 to December 2014. The patients were grouped according to Wagner grading and type of ulcers. Seasons were classified by pentad mean temperature method, then the distribution characteristics of pathogens in different groups was analyzed. And the data were divided into two phases according to the variation trend of drug resistance as follow: from 2000 to 2010, from 2011 to 2014, then analysis was carried out on the change of drug resistance in recent 15 years. The data among groups were compared by using χ ² test.

Among 580 cases, there were 347 males(59.8%) and 233 females(40.2%), mean age was 35-87(62±12) years, duration of diabetes was 0-35(8± 6) years. And 349(46.8%) strains of gram-positive bacteria, 354(47.4%) strains of gram-negative bacteria and 43(5.8%) strains of fungi were isolated from ulcers. With rising Wagner grade, bacterial floras transformed from Gram-positive bacteria (62.3% in Wagner grade≤2) to Gram-negative bacteria (61.7% in Wagner grade≥4) while composite infections increased(χ²=24.645,P<0.05). Gram-positive bacteria were the main pathogens of diabetic foot ulcers in neuropathic ulcers(51.7%) while Gram-negative bacteria were the most frequently isolated in ischemic and neuroischemic ulcers(60.9%, 53.0%). There were significant difference in distribution of pathogens among ulcers with different Wagner grades and different types(χ²= 37.383, 13.045,P<0.05). The distribution of pathogens was influenced by seasons in Wagner grade 3 ulcers. Gram-negative bacteria were the most frequently isolated in summer(55.5%) while gram-positive bacteria were the most common in spring or autumn(60.1%) (χ²=17.740,P<0.05). Among Gram-positive bacteria, Staphylococci were dominating floras, they were totally resistant to penicillin and ampicillin while vancomycin and linezolid were the most effective agents(100%). The resistance rate to amoxicillin/clavulanate was increased from 15.0% to 48.1% in 15 years(χ²=7.499, P<0.05). Among gram-negative bacteria,Enterobacteriaceae was dominating floras, they were highly resistant to ampicillin(91.3%) while meropenem was the most effective agents(99.5%). The resistance rate to cefotaxime is obviously increased from 29.2% to 43.7% in 15 years(χ²=3.899,P<0.05).

We can treat the diabetic foot patients with antibiotics empirically according to the type of ulcers, Wagner grade and seasons. It is essential to pay more attention to pathogen survey and use antibiotics more rationally.

To investigate the relationship of the change of stress hormones with insulin resistance in gestational diabetes mellitus(GDM) patients.

We collected 140 pregnant women diagnosed as GDM in pregnant check-up from January 2014 to May 2015 in Yantai Yuhuangding Hospital. One hundred and forty healthy pregnant women were enrolled as control group. Patients from two groups were matched according to the age stages. Blood glucose, insulin, stress hormone(cortisol, norepinephrine (NE), epinephrine) and oxidative stress level (malnodialdehyde (MDA), superoxide dismutase (SOD)) were detected. Homeostasis model assessment-insulin resistance(HOMA-IR) was used to evaluate insulin resistance status between two groups. We analyzed the correlation between stress hormone, oxidative stressand insulin resistance by multiple liner regression analysis.

HOMA-IR (2.2±0.4 vs 1.7±0.4), NE ((415±102) vs (388±96) ng/L) and epinephrine ((146±40) vs (130±53) ng/L)in GDM group was higher than control group (t=3.153,3.679,2.283, respectively, all P<0.05). There was no significant difference in cortisol level between two groups (t=1.899,P>0.05). Multiple liner regression analysis show that stress hormone (cortisol, epinephrine, NE) were positively correlated with HOMA-IR in both groups (r=0.272, 0.423,0.275, respectively,P<0.05 all above). In oxidative stress indexes, MDA was positively correlated with HOMA-IR in both groups (r=0.355, 0.592, respectively,P<0.05), however SOD was negatively correlated with HOMA-IR in both groups (r=- 0.289,-0.476, respectively,P<0.05).

High level of stress hormone means slightly dysfunction in stress adaptation, suggesting that this dysfunction may be related to hyperglycemia, and is associated with pathogenesis of GDM.

Heart rate variability(HRV) was examined in hospitalized patients with diabetic foot ulcers(DFU) to investigate the characteristics and clinical interrelation of cardiovascular autonomic neuropathy(CAN).

A total of 115 patients with DFU treated in our hospital from January 2011 to December 2013 were included, and there were 59 males and 56 females with an average age of (68 ± 13) years. Another 109 individuals with high risk of DFU(Wagner 0 stage) were selected as the control group, and there were 74 males and 35 females with an average age of (65±14) years. HRV changes were analyzed in two groups, while subgroup analysis was done in DFU group according to Wagner classification. Furthermore, the patients with DFU were divided into two groups according to standard deviation of normal number of intervals(SDNN): patients with SDNN less than 70 ms were considered as HRV abnormal ones. Clinical indexes were compared among HRV abnormal and normal groups. The HRV parameters were tested in patients died in hospital and multi-regression model was used to analyze the association between clinical indexes and HRV parameters. The independence sample t test was implied in data comparison between two groups and variance analysis was used in data comparison among groups.

The CAN of various degree existed in patients with DFU. Patients with abnormal HRV accounted for 51.3% of all the patients. Compared with those in controls, the incidence of peripheral neuropathy and peripheral vascular disease were significantly higher in the HRV abnormal group, which increased from 42.9% to 62.7% and 30.4% to 61.0%, respectively(χ²=4.547, 10.869, both P<0.05). Meanwhile, left ventricle ejection fraction was obviously decreased in the HRV abnormal group(61.9±6.5 vs 64.8±7.2,t= 2. 21,P<0.05). As the stage of Wagner elevated, the average heart rate increased in the DFU group(F=2.750, P<0.05), while SDNN, very low frequency (VLF) and low frequency to high frequency (LF/HF) ratio decreased significantly(F=2.275, 4.349, 3.084, all P<0.05). The VLF index, which reflects the tension of sympathetic nerve, largely decreased in dead patients when compared with that in the survivors(t=1.973,P< 0.05). Multiple regression analysis suggested that SDNN was negatively correlated with glycated hemoglobin A1c(HbA_1c), 24-hour urine trace albumin (β=- 0.208, -0.214, both P<0.05), and the VLF index was also negatively correlated with HbA_1c (β=-0.213,P<0. 05).

Patients with DFU are always complicated with CAN, and poor glycemic control is a significant cause of CAN. Thus, maintain the reasonable level of blood glucose along with combined therapy, is helpful to prevent the development of CAN in the long-term management of diabetic patients.

Diabetic nonketotic hemichorea is a group of reversible clinical syndromes, and correction of hyperglycemia can significantly improve its symptoms, but clinically such patients are rarer. One such patient was admitted to the author's hospital from August 23 to September 10, 2015. The characteristics of the case and the literature review are analyzed as follows.

In recent decades, the prevalence of obesity and type 2 diabetes (T2DM) in China has increased significantly due to the westernized diet structure and urbanized lifestyle. A series of large and long-term follow-up studies abroad have shown that the risk of T2DM significantly increases with the increase of body mass index (BMI), especially in women^[1,2,3]。 On the contrary, the incidence of obesity in T2DM patients is also significantly increased. Data from the 2013 study of the Chinese National Diabetes and Metabolic Diseases Research Group showed that compared with the overall population, the proportion of obesity in T2DM population increased by nearly 2 times^[4]。 From these studies, we can see that the risk of T2DM in obese people is significantly increased, and people with T2DM or abnormal blood sugar are also more likely to develop obesity, and both are high risk factors for cardiovascular events. Therefore, it leads to a thought: obesity and T2DM are a similar process, or is there a significant difference? What is the connection between the two pathogenesis processes?

diabetic kidney disease (DKD) is one of the most common microvascular complications of diabetes. Globally, it has become the most common cause of end-stage renal disease (ESRD), accounting for 30% ~40% of ESRD^[1]。 However, the pathogenesis of DKD is still not fully understood. It was found that mesangial hyperplasia, basement membrane thickening, podocyte reduction, renal tubular injury and other pathological changes appeared in the early stage of DKD, which eventually caused glomerular sclerosis and renal interstitial fibrosis. Among them, podocyte injury and apoptosis are directly related to proteinuria, and are also one of the main factors affecting the prognosis of DKD patients^[2]。 Although current aggressive treatments can delay disease progression, approximately 1/3 of diabetic patients progress to ESRD and require renal replacement therapy^[1]。 Therefore, finding a new treatment option is a hot topic in DKD research. In recent years, some progress has been made in the research of immunosuppressive agents in the field of DKD^[3]。 Studies have shown that tacrolimus, a novel calcineurin (CaN) -specific inhibitor, has obvious protective effects on DKD podocyte damage and apoptosis, CaN reduce proteinuria and delay renal dysfunction^[4]。

With the advancement of electronic technology, micro-forming manufacturing technology, material science and sensor technology, blood glucose monitoring technology has made rapid development. Accurate, continuous, long-term, minimally invasive and non-invasive blood glucose monitoring technologies are coming out continuously, and blood is no longer the only medium for blood glucose monitoring. In order to better serve the blood glucose management of diabetic patients, this paper introduces the application and research progress of blood glucose monitoring technology.

The latest edition of the International Diabetes Federation (IDF) diabetes map in 2015 shows that diabetes is spreading globally, and the number of diabetes patients in China still ranks first, reaching 109.6 million people. This means that in the future, the challenges faced by diabetes management in my country are increasing day by day, and diabetes medical expenses will also show a straight-line upward trend. However, the status of diabetes control in China is not satisfactory. A 2010 survey showed that only 25.8% of diabetic patients received treatment; Only 39.7% of treated patients achieved glycemic control targets^[1]。 Poor blood sugar control can bring long-term complications and increase the risk of death, further aggravating the health and economic burden of patients.