Volume 09 · Issue 05 · 2017

Diabetes is a systemic, chronic and progressive disease of the whole body. In recent years, the incidence of diabetes has increased year by year, and it has become a major public health problem faced by the world, especially developing countries. Many chronic complications caused by poor control of diabetes seriously affect the survival and quality of life of patients.

Diabetes mellitus is a long-term chronic lifelong disease, and many chronic complications caused by long-term hyperglycemia and metabolic disorders are often difficult to reverse^[1]It is an important cause of disability and death. In China, with the obvious changes of urbanization, aging, lifestyle and disease spectrum, the incidence of chronic non-communicable diseases has increased rapidly, especially diabetes, which is the third largest non-communicable disease after tumors and cardiovascular diseases. In recent years, the epidemic trend is severe, and health education and behavior management are the top priorities of diabetes prevention and control. Foreign studies have shown that an appropriate health management payment model can not only reduce medical expenses, but also promote people to actively participate in the healthy life of the whole people and disease prevention and control. At present, international health management has developed maturity, but China is still in the primary stage. It is of great significance to discuss the health management and payment mechanism suitable for diabetes in China combining domestic and foreign health management models.

To construct the standardized process of at-risk foot screening, stratification and intervention.

Based on literature review, especially on the International Guideline of Diabetic Foot published by International Working Group of the Diabetic Foot, doctors from diabetic foot multidisciplinary group of a third-grade class-A hospital developed the first draft. Then experts' opinion questionnaire was developed based on the draft. Twenty eight experts from 10 provinces with endocrinology, plastic and repair surgery and endovascular treatment background were recruited, and two rounds of expert consultation were implemented. And finally the standardized process of diagnosis and treatment of diabetic foot with multidisciplinary approach had been constructed.

Through 2 rounds of expert consultation, the response rates were 93.3% and 100%, respectively. The authority coefficients was 0.91±0.02. The coefficients of variation of each item ranged from 0.05-0.20. The final standardized process consisted of 4 first-level indicators and 43 second-level indicators.

We construct a standardized procedure for at-risk foot screening, stratification and intervention, which provides a frame for the comprehensive management of at-risk foot.

To analyze the quality of life (QoL) of residents with normal blood glucose, pre-diabetes mellitus (PDM), newly detected type 2 diabetes mellitus(T2DM) or diagnosed T2DM.

Patients with T2DM or PDM in an epidemiologic survey in Jiangsu Province as well as patients with T2DM in the Basic Public Health Services were included and all received questionnaire. The quality of life scale Euro Qol five-dimensional (EQ-5D) & World Health Organization Well-Being Index (WHO-5) were applied to evaluate the quality of life. Single and multiple statistical methods were used to compare differences between groups.

The score of EQ-5D visual analog scale (VAS) and Well-Being Index of the T2DM were lower than those in residents with normal glucose (75±17 vs 84±17 and 77±22 vs 79±23, χ ²=55.643, 660.489, all P<0.05). There was no difference between PDM and residents with normal glucose in Well-Being Index (80±23 vs 79±23), and there were also no statistical difference between PDM and newly detected T2DM in both the EQ-5D VAS and WHO-5 index (82±16 vs 81±16, 81±22 vs 80±23, all P>0.05). Further analysis showed that the risk factors of high EQ-5D VAS in T2DM were male, low age, high education, and non-farmer occupations (z=3.36, χ ²=31.199, 82.821, 62.708, all P<0.05), while WHO-5 index was influenced by the education, occupation and marital status (χ²=32.964, 66.883 and 9.527, all P<0.05). Multiple factors analysis showed that EQ-5D VAS was influenced by basic diseases, low family income, positive family history, senior and education (B=-5.033-1.409, t=-13.244-10.059, all P<0.05), and WHO-5 Well-Being Index was affected by age, the level of blood glucose, basic diseases and marital status (B=-3.986-1.842, t=-8.288-22.055, all P<0.05).

The overall quality of life in T2DM is lower than the general population and is affected by many factors. More attention should be paid to the Qol of T2DM and improve their psychological adjusting ability.

To investigate the effects of sitagliptin and glucagon like peptide-1 (GLP-1) on the iron metabolism in human umbilical vein endothelial cells (HUVECs) under normal and high glucose conditions.

HUVECs were treated with sitagliptin (1 μmol/L) and/or GLP-1 (100 nmol/L) under normal (5.5 mmol/L) and high glucose (30.0 mmol/L) conditions, and the corresponding control groups were also included. Cell viability was evaluated. After treatment for 24 h in normal glucose and 48 h in high glucose, mRNA and protein expressions of frataxin (FXN) and aconitase1 (ACO1) were measured by real-time PCR and Western blotting, respectively. Multiple-group comparisons were performed using one-way variance analysis.The two groups were compared using the Bonferroni test (when the variance homogeneity test was performed) or the Dunnett T3 test (when the variance homogeneity test was not satisfied).

(1) Comparing with the control group (assuming its expression level was 1) under normal glucose condition, cell viability had no significance among those groups treated with GLP-1, sitagliptin and the combinations of sitagliptin and GLP-1 (0.99±0.04, 1.07±0.08, 1.06±0.05, F=4.059, all P>0.05); mRNA expressions of FXN were significantly decreased by combinations of sitagliptin and GLP-1 administration (0.68±0.18, t=3.59, P<0.05) and mRNA expressions of ACO1 were significantly decreased by sitagliptin with or without GLP-1 treatment (0.59±0.15, 0.49±0.13, F=10.802, all P<0.05); While protein expressions of FXN and ACO1 were decreased by sitagliptin and/or GLP-1 with no significance (all P>0.05). (2) Comparing with the control group (assuming its expression level was 1) under high glucose condition, mRNA expressions of FXN were significantly increased by combinations of sitagliptin and GLP-1 administration (1.75±0.26, t=-5.71, P<0.05), while mRNA expressions of ACO1 showed no much significance after treatment with sitagliptin and/or GLP-1.

Without affecting cell proliferation in normal state of endothelial conditions, sitagliptin and GLP-1 may affect the intracellular iron metabolism by regulating the expression of FXN and ACO1 in HUVECs in normal or hyperglycemic conditions.

To investigate the expression of transient receptor potential canonical channel-1 (TRPC1) in coronary smooth muscle cells (CSMCs) in diabetic rats and the possible mechanisms of TRPC1 channels on diabetic coronary function.

A total of 160 healthy male Sprague-Dawley (SD) rats with 8-12 weeks of age and weight (200±20) g were randomly divided into normal control group (80 rats) and diabetic group (80 rats). Type 1 diabetes was established by intraperitoneally injection of streptozotocin. Normal and diabetic CSMCs from Sprague-Dawley rats were isolated by enzyme digestion. The protein and gene expressions of TRPC1 channels in normal and diabetic CSMCs were determined by Western blotting and real-time fluorescent quantitative PCR technique, respectively. Cytosolic calcium concentrations before and after incubating with TRPC1 channels blocker SKF96365 in normal and diabetic CSMCs were examined by recording the changes of fluorescence intensity ratios. Vascular reactivity after appliance of SKF96365 on coronary arteries in normal and diabetic rats was detected by using vascular tension measurement. The experimental data were analyzed by t test between two groups.

The protein expressions of TRPC1 channels in diabetic CSMCs were (1.456±0.081) times of the normal groups (t=-2.210, P<0.05). The gene expressions of TRPC1 channels in diabetic CSMCs were (2.198±0.251) times of the normal group(t=-3.864, P<0.05). ΔRatios of normal and diabetic CSMCs were 0.869±0.029 and (1.217±0.043, t=-6.644, P<0.05), respectively. ΔRatios were 0.842±0.020 and 0.067±0.039 before and after the appliance of TRPC1 channels blocker SKF96365 in normal CSMCs ( t=15.726,P<0.05). ΔRatios were 1.217±0.043 and 0.195±0.028 before and after appliance of SKF96365 in diabetic CSMCs ( t=-19.807, P<0.05). When the vascular tension increased to the maximum after application of ET-1, then coronary arteries were exposed to 10 μmol/L SKF96365, and the dilation rate of normal and diabetic coronary arteries were (69.2±6.0)% and (91.6±2.6)%, respectively ( t=-3.529, P<0.05).

The expression of TRPC1 channels in diabetic CMSCs is increased, which increases cytosolic calcium concentrations, leading to vascular constriction and the dysfunction of diabetic coronary arteries. This may be one of the mechanisms that coronary heart diseases are commonly seen in diabetic patients.

To investigate the change of transforming growth factor (TGF) β1/Smad signaling pathway in rat tubular epithelial cell (NRK-52E) under high glucose condition after gene silencing of ubiquitin-ribosomal protein 52 (UBA52).

Firstly, NRK-52E cells were stimulated with 20 mmol/L (normal control group) or 30 mmol/L glucose for 48 hours respectively, while cells cultured with 5.6 mmol/L glucose with or without 24.4 mmol/L of mannitol were set as normal control or hyperosmotic control. Then the mRNA expression of UBA52, TGF-β1 and Smad7 were detected by using real time polymerase chain reaction (PCR) in the 4 groups. After that, three UBA52 small interfering RNA (siRNA) sequences were selected. The transfection efficiency was observed by fluorescence microscope after transfection, and the expression of UBA52 mRNA was detected by real time PCR. The most effective siRNA was selected to be used for subsequent experiments. Then cells stimulated with 30 mmol/L glucose were transfected by UBA52 siRNA for 48 h, those without transfection or being transfected with irrelevant RNA were set as control or negative control. Then the mRNA and protein expression of UBA52, TGF-β1 and Smad7 were detected in the 3 groups. Above mentioned indexes were statistically analyzed by randomized blocks analysis of variance.

In glucose intervention experiment, there were significant differences in the expressions of UBA52, TGF-β1 and Smad mRNA among the 4 groups (normal control group, hypertonic control group, medium concentration glucose and high concentration glucose group) (F=60.914, 65.112, 29.390, P<0.05); expressions of UBA52, TGF-β1 of medium and high concentration glucose group were significantly higher than those in normal control and hypertonic group, but Smad7 were significantly lower the two groups. In transfection experiment, expressions of TGF-β1 mRNA in blank control group, negative control group and transfection group were 1.00±0.04, 0.98±0.04, 0.49±0.14 respectively (F=26.364, P<0.001), it was significantly lower in the transfection group than that in the other two groups; the expressions of Smad7 mRNA in the 3 groups were 1.00±0.12, 1.05±0.17, 2.24±0.31, respectively (F=22.816, P<0.001). The expressions of TGF-β1 protein of the 3 groups were 0.676±0.357, 0.613±0.011, 0.184±0.073, respectively (F=96.433, P<0.01), it was the lowest in transfection group; the expressions of Smad2/3 protein were 0.68±0.10, 0.63±0.05, 0.27±0.15, respectively (F=12.194, P<0.05), it was the lowest in transfection group; the expressions of Smad7 protein were 0.52±0.05, 0.55±0.12, 0.83±0.06 in the 3 groups, respectively (F=12.154, P<0.05), it was the highest in transfection group.

The intervention of TGF-β1/Smad signaling pathway of renal tubular epithelial cells under high glucose by UBA52 gene silence may be a new target for the intervention of renal interstitial fibrosis in diabetic nephropathy.

To explore the effects of glucagon-like peptide-1 (GLP-1) analogue liraglutide on development of steatosis hepatocytes via adipose triglyceride lipase (ATGL) and its mechanism.

Human HepG2 cells cultured in vitro were randomly divided into: control group(NC group), steatosis model group(M group), liraglutide group (L group), adenosine monophosphate-activated protein kinase (AMPK) inhibitor(Compound C)+liraglutide group(CC group). M group was treated with 0.5 mmol/L mixture of free fatty acids for 24 hours to establish steatosis hepatocyte model; L group (steatosis hepatocyte model) was treated with 100 nmol/L liraglutide for 24 hours; CC group (steatosis hepatocyte model) was treated with 10 mmol/L Compound C (added in advance) and 100 nmol/L liraglutide. Western blotting was performed to detect the protein levels of AMPK, phosphorylated AMPK (p-AMPK), mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR) and ATGL. Differences among groups were compared by one-way analysis of variance, pairwise comparison was conducted by using LSD-t test.

Compared with NC group, the p-AMPK/AMPK and ATGL protein expression was significantly lower and p-mTOR/mTOR increased significantly in M group (0.208±0.069 vs 0.444±0.106, 0.112±0.038 vs 0.333±0.052, 0.421±0.105 vs 0.126±0.041, respectively, t=3.620, 5.900, 5.060, all P<0.05). Compared with M group, ATGL expression and p-AMPK/AMPK increased significantly and p-mTOR/mTOR was significantly inhibited in L group (0.391±0.076 vs 0.208±0.069, 0.233±0.058 vs 0.112±0.038, 0.230±0.066 vs 0.421±0.105, respectively, t=2.810, 3.218, 3.281, all P<0.05). Compared with L group, the p-AMPK/AMPK and ATGL protein expression decreased significantly and p-mTOR/mTOR increased remarkably in CC group (0.234±0.061 vs 0.391±0.076, 0.144±0.03 vs 0.233±0.058, 0.366±0.058 vs 0.230±0.066, respectively, t=2.414, 2.360, 2.334, all P<0.05).

Liraglutide may increase the level of ATGL by activating AMPK-mTOR pathway, it results in the reduction of triglycerides and lipid droplets in steatosis hepatocyte models.

To explore the clinical characteristics of acromegaly patients who had diabetic ketoacidosis (DKA) as their main manifestation.

To report the diagnosis and treatment of a patient with pituitary growth hormone and prolactin mixed tumor complicated with DKA from Peking Union Medical College Hospital in February 2017, and the characteristics of these patients in literature were reviewed.

The patient had DKA and high osmotic status as his first manifestation. His growth hormone (GH) and prolactin (PRL) levels were significantly increased, and imaging results identified a large pituitary mass. The plasma glucose level was high even with insulin treatment at a dose of 90 U/d (0.8 U·kg^-1·d^-1). GH and PRL decreased for more than 50% after bromocriptine treatment. The dose of insulin was reduced to 12 U/d (0.1 U·kg^-1·d^-1), and the blood glucose was controlled. In literature, the prevalence of impaired glucose tolerance and diabetes mellitus was 15%-38%. DKA as the initial clinical condition occurs in 1% acromegaly patients. The main mechanisms are insulin resistance and lipolysis. Plasma glucose level could be controlled with a dose of insulin treatment (50-360 U/d). The dose could be reduced after pituitary adenoma resection and/or somatostatin therapy.

DKA is a rare clinical manifestation of acromegaly. These patients have severe insulin resistance. To control high plasma glucose levels needs insulin treatment as well as the control of primary disease.

fulminant type 1 diabetes mellitus (FT1DM) was first developed by Japanese scholars Imagawa et al.^[1]A new subtype of type 1 diabetes mellitus (T1DM) proposed in 2000, characterized by hyperacute onset, severe metabolic disorders, negative insulin-related antibodies and multiple enzymatic changes, was temporarily classified as idiopathic T1DM by the American Diabetes Society and the World Health Organization^[2]。 Although children and adolescents are the high incidence population of T1DM, the incidence of FT1DM is low, and the cases of FT1DM in children and adolescents are rarely reported at home and abroad. This paper reports a case of FT1DM in children with suspected acute pancreatitis, which is discussed in combination with the literature.

Diabetes is a serious and growing global health burden, and the prevalence of diabetes among Chinese adults has reached 11.6%^[1]。 Diabetic patients are prone to various complications or coexisting other diseases and are admitted to non-diabetes specialty. About 10% of non-diabetes specialty hospitalized patients have diabetes at the same time^[2]。 With the deepening of people's understanding that a single professional knowledge cannot meet the different needs of diabetic patients, multidisciplinary collaboration is gradually applied to the management of diabetic patients. The American Diabetic Society believes that multidisciplinary team is the most effective management model for diabetes management, and diabetes education is the foundation of team building. It guides and encourages diabetic patients to actively participate in disease management decisions and develop patient-centered personalized management plans^[3]。 At present, the construction of multidisciplinary diabetes care team (MDCT) in China is in its initial stage, and there is no standardized and unified standard for its establishment, operation, management and evaluation system. The present situation of MDCT construction at home and abroad is summarized as follows, in order to provide reference for better construction and standardized management of MDCT in China.

With the acceleration of the aging of the global population, diabetes and dementia have become diseases affecting many people in the world. According to data released by the International Diabetes Federation (IDF), a total of 415 million adults worldwide suffered from diabetes in 2015, and the number of diabetic patients in China has now exceeded 100 million, making it the country with the largest number of diabetic patients. Epidemiological studies have shown that patients with early diabetes or even pre-diabetes already have mild cognitive impairment (MCI). Elevated blood sugar can accelerate the progression of MCI to dementia and worsen the condition of dementia patients^[1]。 Diabetic complications and poor glycemic control are related to MCI. Early changes in diabetic complication severity index score can predict the risk of dementia in patients with new onset diabetes. Early diagnosis can help delay the process of cognitive decline^[2]。 resting-state functional magnetic resonance imaging (rs-fMRI) is a non-invasive, safe, high spatiotemporal resolution advanced technology to explore global or local brain activity and metabolism. It has been widely used in the research of various neuropsychiatric diseases and cognitive neuroscience, including the study of neurophysiological mechanisms of dementia, schizophrenia, Parkinson's disease, depression, epilepsy, autism and other diseases^[3,4]。 This article reviews the clinical application and progress of rs-fMRI in diabetic patients.

gap junction (GJ) is widely distributed and exists in almost all types of animal cells, including epithelial tissue, cardiac muscle and smooth muscle^[1]。 Gap junctions are direct pathways between two neighboring cells that enable the exchange of information, energy, and matter. The metabolic coupling involved in the exchange of substances between cells and the electrical coupling of electrical signal transmission play an important role in regulating the physiological processes such as metabolism, internal environment stability, proliferation and differentiation of cells. GJ is mainly composed of connexin (Cx), which is widely distributed in many tissues, and is closely related to the occurrence and development of glycolipid metabolism diseases^[2]。

In recent years, type 2 diabetes mellitus (T2DM) has become a major global public health problem. Glucose management in T2DM needs to take into account the overall control of fasting blood glucose and postprandial blood glucose, so that glycosylated hemoglobin (HbA_1c) up to standard. Reducing postprandial blood glucose is important for overall glycemic control, and when HbA_1c<At 8.5%, postprandial blood glucose affected HbA_1cContribution rate exceeds 50%^[1]。 Controlling postprandial blood sugar can be achieved through different mechanisms, such as delaying the absorption of carbohydrates in the intestine and stimulating the secretion of insulin in the first phase. With the launch of a new hypoglycemic drug incretin, the regulatory effect of gastric emptying on postprandial blood glucose has attracted widespread attention. Gastric emptying is the process by which food enters the small intestine from the stomach, and glucose is absorbed into the blood in the small intestine. Therefore, the blood sugar level after eating is affected by the gastric emptying rate, which is regulated by multiple neurohormones such as incretin. In this paper, the research progress of gastric emptying in recent years and its relationship with postprandial blood glucose are reviewed.

Professor Shi Zhongfu, a famous endocrinology and metabolism expert in China, passed away on April 19, 2017 at the age of 95.