Volume 09 · Issue 02 · 2017

Diabetes brings serious health hazards to our people and leads to huge medical expenses. Type 2 diabetes (T2DM) accounts for approximately 90% of the population. Epidemiological data indicated that 58.3% of T2DM were associated with overweight/obesity^[1]In the overweight/obese population, 18.2% had T2DM^[2]。 Although the research on the pathogenesis of diabetes has made breakthroughs in the past 20 years, and new hypoglycemic drugs have emerged, the control of diabetes is still worrying. The "National Assessment Study on the Risk Factors of Cardiovascular Diseases in Type 2 Diabetic Patients in China-Blood Glucose, Blood Pressure and Blood Lipid" ("3B Study") showed that only 5.6% of T2DM patients achieved the same standard of blood glucose, blood lipid and blood pressure^[1]。 The development of metabolic surgery has opened up new prospects for the treatment of obesity with T2DM. Several clinical studies have shown that metabolic surgery is more effective in weight loss and blood sugar improvement than intensive lifestyle interventions and hypoglycemic drug therapy, and may even achieve long-term remission of T2DM. At the same time, metabolic indicators such as blood lipid and blood pressure can be fully controlled. Therefore, the name of the operation has been renamed from the initial weight-loss operation to metabolic surgery. In a joint statement from the International Diabetes Organization released in May 2016, metabolic surgery was included in the clinical treatment pathway for T2DM for the first time^[3]。 The guideline was jointly drafted by 48 international authoritative experts from 16 countries, 9 disciplines, and jointly formulated by the American Diabetes Society, the International Diabetes Federation, the British Diabetes Society, the Diabetes Branch of Chinese Medical Association and the Indian Diabetes Society. It was recognized by 45 international diabetes organizations. The therapeutic status of metabolic surgery in T2DM is further established. Can obese T2DM really get rid of it with one knife and everything will be fine?

24 May 2016, Official Journal of the American Diabetes SocietyDiabetes CareThe world's first joint statement on metabolic surgery for type 2 diabetes, developed with the participation of several international diabetes organizations, was published online. This statement, based on rigorous evidence-based medical evidence, fully affirms the significance of metabolic surgery for the treatment of diabetes, and states that surgical treatment should be a body mass index (BMI) ≥35 kg/m²One of the standard treatment options for diabetic patients, especially for patients with other serious cardiovascular and metabolic risk factors^[1]。 The statement continues the views of several previous international statements or consensus, pointing out that BMI remains the primary surgical indication, and emphasizing the importance of comprehensive assessment of metabolic risk factors. International Diabetes Federation 2011 Statement on Bariatric Surgery^[2]And "Guidelines for Surgical Treatment of Obesity and Type 2 Diabetes in China"^[3]The difference is that the statement does not explicitly include preoperative islet functional status in the scope of surgical indications. Obviously, there is a consensus on BMI as an indication for surgery in diabetic patients, while there are different views on whether islet functional status can be used as an indication for surgery. However, from the clinical effect of metabolic surgery in diabetes, the immediate hypoglycemic benefit brought by surgery is not accompanied by the corresponding decrease in BMI. Foreign scholars have pointed out that there is an essential difference between bariatric surgery and metabolic surgery. The former emphasizes weight loss to achieve the purpose of improving metabolism, while the latter pays more attention to the improvement of metabolism. Whether there is obesity is not a necessary condition. In response to these contradictory phenomena, the question is whether preoperative BMI or islet functional status can be used as a strong indication for metabolic surgical treatment of diabetes mellitus? Factors associated with metabolic surgery indications as recommended by each statement or consensus are presented inTable 1。

Obese patients are at higher risk and costly for metabolic, cardiovascular, respiratory, reproductive, or oncological complications. Type 2 diabetes mellitus (T2DM) combined with obesity is increasingly prevalent, and its associated macrovascular and microvascular complications are a major health burden. Measures for weight control include diet and exercise intervention, weight loss medication use and weight loss metabolic surgery. Lifestyle interventions combined with weight loss drugs are indeed effective in maintaining weight loss, but whether they can improve the outcome of diabetic complications is a matter of concern.

Obesity and its accompanying type 2 diabetes have become a global health problem, and China has become a major country with obesity and diabetes. At present, the number of diabetes patients in China is about 114 million^[1]While the number of overweight and obese people is significantly higher than that of the U.S.^[2]。 The number of obese men in China has risen from 700,000 (2.1% of the world) in 1975 to 43.2 million (16.3% of the world); The number of obese women rose from 1.7 million (2.5% of the world) in 1975 to 46.4 million (12.4% of the world)^[3]。 Generally speaking, compared with other countries, the number of obese and diabetic people in China is still growing rapidly, and the serious situation should not be underestimated.

According to the 2010 National Diabetes Epidemiological Survey, the estimated prevalence of diabetes in adults over 18 years old in China is 11.6%, while only 25.8% of diabetic patients receive treatment, of which only about 39.7% can achieve effective blood sugar control^[1]。 It can be seen that although the prevalence of diabetes in China is high, the blood glucose compliance rate is low. Although there are many factors affecting the achievement of blood glucose standards, the achievement rates of blood glucose standards were only 36.2% and 39.9% in patients who had been treated with insulin at 3 and 6 months^[2]However, patients' lack of mastery of insulin injection technology may be one of the important reasons.

To explore the association between C-reactive protein(CRP) level at baseline and the risk of diabetes mellitus(DM) during follow-up in a community cohort.

Subjects were the residents (35-74 years old) derived from a community-based diabetes prospective cohort study in Pudong New Area in Shanghai, which began in 2009 and followed up in 2012. Baseline non-diabetic population was divided into four groups according to the level of baseline CRP (CRP<1.00 mg/L, 1.00-1.99 mg/L, 2.00-2.99 mg/L or ≥3.00 mg/L). Analysis of variance, Kruskal WallisH nonparametric test and Chi-square test were used to compare the baseline characteristics, and COX regression model was used to analyze the association between baseline CRP level and DM risk during follow-up.

The mean follow-up time was (2.7±0.5) years. For those with CRP<1.00, 1.00-1.99, 2.00-2.99 and ≥3.00 mg/L, the incidence rate of DM was 14.68/1 000, 21.30/1 000, 28.92/1 000 or 46.38/1 000 person-years, respectively; the incidence rate of DM increased with baseline CRP levels (χ_linear²=13.63, P<0.001). After adjusting for family history of diabetes, history of hypertension, age, body mass index, triglycerides, and the baseline blood glucose status, the risk of DM in group with CRP level ≥3.00 mg/L was 3.26 times (95% CI: 1.39-7.64) that of group with CRP level<1.00 mg/L. The areas under the receiver operating characteristic curves of baseline CRP level in predicting the incidence of DM was 0.604 (95%CI:0.522-0.686).

Baseline CRP level is an independent risk factor of diabetes; however, the predict power of CRP is poor. Therefore, combiding CRP with other factors may be a good choice to predict diabetes.

To explore the prevalence and metabolic characteristics of adrenal incidentalomas (AIs) in patients with type 2 diabetes mellitus (T2DM).

A total of 563 patients with T2DM were recruited from August 2014 to July 2015. AIs were screened by adrenal CT scan, their functional types were classified by endocrine function evaluation. Metabolic parameters were compared between the T2DM patients with and without AIs. Unpaired t test or nonparametric test was performed for comparisons between groups.

Of 22 patients who were detected with AIs, 2 had primary aldosteronism (0.36%), 4 had subclinical Cushing's syndrome (0.71%), and 16 had nonfunctional adenomas (2.84%). Compared with the T2DM patients without AIs, levels of plasma glycated hemoglobin A_1c, fasting C peptide, triglyceride, systolic and diastolic blood pressure were significantly increased in the T2DM patients with AIs (z=-2.832, -3.650, -2.661, -3.134, -2.867, respectively, all P<0.05).

The prevalence of AIs in T2DM patients is 3.91%. The incidence rate of metabolic syndrome is much higher in T2DM patients with AIs than in those without AIs.

To investigate the effects of capsaicin (CAP) on coronary endothelium-dependent vasodilation in rats with type 2 diabetes mellitus (T2DM).

Sixty healthy male Sprague Dawley rats (120-140 g) were used in this study. Intraperitoneal injection of streptozotocin and high fat diet were used to establish T2DM in rats. Then all diabetic rats were randomly divided into diabetes mellitus (DM) group, CAP intervention (CAP) group and capsazepine intervention (CAPZ) group with 15 rats in each group. And 15 normal rats were selected as normal control (NC) group. Rats in CAP group and CAPZ group were injected intraperitoneal with CAP (1 mg·kg^-1·d^-1) or CAPZ (1.5 mg·kg^-1·d^-1), respectively. The same volume of saline was injected to rats in NC group and DM group. After 14 weeks, the levels of fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), nitric oxide (NO), endothelial nitric oxide synthase (eNOS), endothelin1 (ET-1) in serum were determined. Endothelium-dependent and endothelium-independent vasodilation were examined in isolated vascular ring by perfusion technique; coronary NO concentration were checked by nitrate reduction assay; levels of coronary transient receptor potential vanilloid 1 (TRPV1), eNOS and phospho-eNOS(p-eNOS) were tested by Western blotting. Paired t test and independent sample t test were used for statistical analysis.

The coronary NO concentration, levels of TRPV1 and p-eNOS were significantly increased in CAP group compared with those in DM group [(105.7±3.9) vs (92.8±8.3) μmol/(mg·pro),(0.41±0.05) vs (0.30±0.05), (0.24 ± 0.03) vs (0.14 ± 0.04), t=-4.47,-2.80,-3.06, all P<0.05]. The endothelium-dependent relaxation induced by different concentrations of acetylcholine were significantly higher in CAP group than in DM group (t=10.42,-5.19,-13.38,-17.46,-20.94, respectively, all P<0.05). The levels of serum FPG, TC, TG and ET-1 were significantly lower in CAP group than those in DM group (t=-13.67,-16.41,-20.39,-42.29, respectively, all P<0.05).

Long-term CAP supplementation prevents the impairment of coronary endothelium-dependent vasodilation in T2DM.

To explore the effects of growth differentiation factor 11 (GDF-11) on mice aorta endothelial cells (MAECs) cultured with palmitate acids (PA) and the possible mechanism involved.

To study the function of endothelial nitric oxide synthase(eNOS) and Smad pathways in GDF-11 protective effect by pre-incubated with inhibitors against eNOS(L-NAME) or Smad3 inhibitor(SIS3). MAECs were divided into five groups: the control group, PA group, PA+GDF-11 group, PA+GDF-11+L-NAME group and PA+GDF-11+SIS3 group, all the cells in the 5 groups were cultured for 24 h. Reactive oxygen species assay kit and reverse transcription polymerase chain reaction(RT-PCR) were used to determine the oxidative stress in MAECs and flow cytometry were used to assess the apoptosis of cells in the 5 groups. And Western blotting was used to measure the expression levels of Bcl-2, Bax and Cleaved-caspase3 protein. To study the effect of GDF-11 on the Smad signal pathway in MAECs. MAECs were divided into three groups: the control group, GDF-11 group and GDF-11+transforming growth factor β(TGF-β) receptor Ⅰ inhibitor (SB431542) group. After cultured for 30 min, the expression levels of phosphorylated Smad2/3 (P-Smad2/3) were measured by immunofluorescence in the three groups. In order to study the effect of GDF-11 on the adenosine monophosphate-activated protein kinase (AMPK)/eNOS pathway in MAECs, MAECs were divided into five groups: the control group, GDF-11 group, GDF-11+AMPK inhibitor (Compound C) group, GDF-11+ L-NAME group and GDF-11+Compound C+L-NAME group. After cultured for 30 min, the expression levels of AMPK, phosphorylated AMPK(P-AMPK), cAMP-dependent protein kinase (PKA), phosphorylated PKA (P-PKA), protein kinase B(Akt), phosphorylated Akt(P-Akt), eNOS and phosphorylated eNOS(P-eNOS) were measured by Western blotting in the 5 groups. Data among multiple groups were compared by using single factor variance analysis and the least significant difference t test.

The apoptotic rate of MAECs in PA group was significantly higher than that in control group (28.9% ± 2.2% vs 7.9% ± 1.5%), while it decreased significantly in PA+GDF-11 group (12.6%±1.6% vs 28.9%±2.2%). The apoptotic rate of the cells in PA+GDF-11+L-NAME group and PA+GDF-11+SIS3 group were all significantly higher than that in PA+ GDF-11 group (21.8%±2.0% vs 20.1%±1.8% vs 12.6%±1.6%, F=97.89, P<0.05). Compared with control group, the expression of P-Smad2/3 increased significantly in GDF-11 group, but it decreased significantly in GDF-11 + SB431542 group(F=325.30, P<0.05). The relative P-AMPK/AMPK, P-eNOS/eNOS levels in GDF-11 group were significantly higher than those in control group. The relative P-AMPK/AMPK, P-eNOS/eNOS levels in Compound C, L-NAME and Compound C+L-NAME group were significantly lower than those in GDF-11 group (F=237.65, 281.08, both P<0.05). Whereas the relative P-Akt/Akt, P-PKA/PKA levels showed no difference among those groups (F=1.94, 1.48, both P>0.05).

GDF-11 prevents palmitate acids-induced endothelial oxidative stress and apoptosis, increases the expression of Bcl-2 and decreases the levels of Bax, Cleaved-caspase3 in the MAECs. The possible mechanisms may involve the TGF-β/Smad and the AMPK/eNOS signaling pathways.

A case of type 2 diabetes mellitus(T2DM) with poor glycemic control combined with Cushing's syndrome was reported to remind clinicians' attention. A 52-year-old female has been diagnosed as T2DM for 6 years. Her blood glucose was controlled poorly with insulin therapy and appropriate life style intervention. On the fifth time of admission, this patient was diagnosed as pituitary adrenocorticotropic hormone secreting adenoma. The blood glucose was well-controlled after transsphenoidal pituitary adenoma resection. It indicates that examination for hypercortisolism should be performed in T2DM patients with poor glycemic control, especially in those with a round face, hypertension, dyslipidemia or truncal obesity.

With the aging and lifestyle changes, chronic diseases have gradually become an important issue affecting human health and quality of life^[1]。 Therefore, it is of great significance to construct a prediction model of disease risk and calculate the incidence probability of individual diseases with certain characteristics according to the prediction model for reducing the incidence rate of chronic diseases and reducing the burden of diseases. Disease risk prediction model was mainly applied to cardiovascular diseases in the early stage^[2]In recent years, there has been rapid development in major chronic diseases such as malignant tumors, diabetes, hypertension, metabolic syndrome, blood lipid disorders, and chronic kidney disease^[3,4,5]。 With the rapid progress of computer and the widespread popularization of all kinds of statistical software, the risk prediction model of disease morbidity and death has also entered a period of rapid development^[6]。 From the earlier Logistic regression model and Cox proportional hazard model, the time series model is gradually developed^[7]Grey model^[8]Neural network model^[9]Support Vector Machine Model^[10]And many other methods and models. These models are briefly introduced below.

fulminant type 1 diabetes mellitus (FT1DM) was developed in 2000 by Imagawa et al.^[1]It was reported for the first time that glycosylated hemoglobin (HbA_1c) is characterized by normal or mild elevation, almost complete and irreversible disappearance of islet function, and may be accompanied by serious complications such as rhabdomyolysis^[2], temporarily attributed to idiopathic type 1 diabetes mellitus (type 1B). Japan reported that FT1DM accounts for approximately 19.4% of type 1 diabetes mellitus (T1DM) with ketosis onset^[3], up from 9.1% in China^[4]。

With the development of medical technology, the diagnosis and treatment of diabetes has entered the era of prevention and treatment of diabetic complications. Diabetic foot disease is a chronic complication of diabetes, and its prevalence is increasing year by year. Some data show that the annual incidence of diabetic foot ulcer in China is 8.1%, and the amputation rate is 19.03%^[1]。 The prognosis after amputation is extremely poor, and the 5-year mortality rate of large amputation patients can reach more than 50%^[2,3]It brings serious harm and heavy economic burden to patients and society.