Volume 10 · Issue 12 · 2018

Hierarchical diagnosis and treatment is hierarchical management according to the priority of the disease and the difficulty of treatment. Medical institutions at different levels are responsible for the diagnosis and treatment of different diseases or different stages of the same disease. It gradually realizes the medical process from general practice to specialization through the first diagnosis at the grassroots level, two-way referral, acute and slow treatment, and upper and lower linkage, forming an ideal medical treatment pattern in which minor illnesses are in the community, serious illnesses are admitted to the hospital, and recovery is returned to the community. This model is especially suitable for chronic disease management. The implementation of hierarchical diagnosis and treatment can rationally allocate medical resources in the region and promote the equalization of basic medical and health services. It is an important part of deepening the reform of the medical and health system and establishing a basic medical and health system with Chinese characteristics. It is of great significance to improve people's health level and ensure and improve people's livelihood.

The essence of hierarchical diagnosis and treatment lies in designing integrated, reasonable and efficient medical services according to the needs of patients. The ultimate goal is to build orderly, continuous and homogeneous health services for the people^[1]。 As one of the main chronic diseases, diabetes is the breakthrough of the first pilot of hierarchical diagnosis and treatment in China. According to the needs of residents, combined with management requirements and the provision of existing health resources and services, Shanghai has carried out the exploration and practice of diabetes health management, and vigorously promoted the implementation of the graded diagnosis and treatment system of diabetes.

The prevalence of type 2 diabetes in China is increasing rapidly, and it has become the third major chronic non-communicable disease that seriously endangers people's health^[1]。 The results of the 2010 survey show that the estimated prevalence of diabetes in China has reached 11.6%, and only 10.2% of all patients can achieve good blood sugar control^[2]。 As a long-term chronic disease, the comprehensive management of diabetes mainly has five aspects: diet treatment, exercise, drug treatment, blood sugar monitoring and health education. Inadequate blood sugar management can lead to chronic damage to various tissues, especially eyes, kidneys, heart, blood vessels and nerves. Once chronic complications occur, they are difficult to reverse, so early diagnosis and effective treatment are of great significance. Evidence-based medicine research proves^[3,4,5]Strict control of blood sugar can significantly reduce the risk of acute and chronic complications in diabetic patients; Special interventions for patients with early diabetic nephropathy, retinopathy and diabetic foot can reduce their disability rate and mortality rate, and effectively reduce the disease burden of the state and family. Blood glucose control is the basis for preventing diabetic complications^[1]。 Not only to reduce blood sugar, but more importantly to reduce microvascular complications such as retina and kidney and macrovascular complications such as heart and cerebrovascular, and reduce mortality. Therefore, it is imperative to establish a practical management system and standardized standard management for patients with type 2 diabetes.

The purpose of this paper was to understand the association between the efficacy of acarbose or metformin and the parameters reflected body weight, such as body mass index (BMI), central obesity (COB), magnitude of weight loss.

A total of 788 participants from MARCH database were included in this analysis. After a 4-week run-in period of lifestyle modification, patients were assigned to 48 weeks of therapy with metformin or acarbose as the initial treatment. The participants were divided into four BMI groups (BMI 19.0-23.9, 24.0-25.9, 26.0-27.9, and 28.0-30.0 kg/m²) and two central obesity groups according to IDF criteria (i.e. waist circumference ≥90 cm in male, ≥80 cm in female), respectively. ANCOVA was used to assess the association of the above obesity categories with the changes of glycated hemoglobin A_1c (HbA_1c) from baseline in acarbose group and metformin group respectively, with treatment and center as factors, and baseline HbA_1c as a covariate.

There was no significant difference in change from baseline HbA_1c within the acarbose groups (0.98%±0.09%, 0.95%±0.09%, 1.20%±0.09%, 1.14%±0.10%, F=1.80, P>0.05) as well as the metformin groups (1.08%±0.09%, 1.12%±0.09%, 1.20%±0.10%, 1.32%±0.10%, F=1.25, P>0.05) when patients were stratified by BMI quartile. The reduction in HbA_1c was greater in patients with central obesity than those without in metformin group (1.26%±0.06% vs 0.98%±0.08%, F=7.68, P<0.05), but there was no significant difference among patients with and without central obesity for HbA_1c reduction in acarbose treatment group (1.10%±0.06% vs 0.97%±0.08%, F=1.62, P>0.05).

The hypoglycemic efficacy of acarbose was not associated with the obesity status. In contrast, metformin was more effective in diabetic patients with central obesity.

To investigate the clinical characteristics and effective management of type 2 diabetic patients with initiating basal insulin therapy in Shenzhen.

A total of 4 535 patients in 4 hospitals from April 2014 to December 2017 were enrolled in "The Basic Insulin Clinical Standardized Use and Effective Management Program" in Shenzhen (Shenzhen "TRIO" Study). The program was managed by project nurses, patients were providedby standardized education at first day, and followed up with optimized management and supervision for 12 weeks. Fasting blood glucose (FPG) levels were monitored as an optimization evaluation index in the program. At the end of the follow-up, FPG levels from 4 089 patients were examined at least once. We compared our early data (from April 2014 to April 2015) from Shenzhen "TRIO" Study with the data from national "TRIO" Study, and the later data (from May 2015 to December 2017) from Shenzhen "TRIO" Study.

Compared with national "TRIO" Study, the type 2 diabetic patients in early Shenzhen "TRIO" Study had similar age, diabetes duration and baseline FPG (all P>0.05), but there was significantly higher percentage of patients who were treated with oral anti-diabetic drugs only in Shenzhen study (69.6% (335/510) vs 51.6% (38 964/75 467), χ ²=65.612, P<0.05). At the end of follow-up, the average FPG levels in patients were lower in Shenzhen study [(6.5±1.8) vs 6.91 mmol/L, t=5.377, P<0.05], and the FPG control rateswere higher (78.9% (358/454) vs 62.6% (40 334/64 420), χ ²=50.879, P<0.05). Compared with the baseline data in early Shenzhen "TRIO" Study, the patients from late Shenzhen Study hadyounger age [(53.0±13.6) vs (55.6±14.2) years, t=4.094, P<0.05], higher FPG levels and HbA_1c [(12.8±4.8) vs (10.9±4.2) mmol/L, (10.3±2.2)% vs (9.5±2.4)%, t=8.583, 3.661, all P<0.05]. At the end of follow-up, the average FPG levels were lower [(6.2±1.3) vs (6.5±1.8) mmol/L, t=3.661, P<0.05], and the FPG control rates were higher (84.9% (3 085/3 635) vs 78.9% (358/454), χ ²=10.976, P<0.05).

The type 2 diabetic patients in Shenzhen who needed basic insulin initiation treatment had a poor blood glucose control after active oral anti-diabetic treatment. Which indicating clinical inertia the time of initiating insulin was delayed. After the optimized management led by nurses, the FPG control rates were significantly improved. The study suggests that specialist nurses play an active role in the management of type 2 diabetic patients in Shenzhen.

To explore the relationship between cardiovascular autonomic neuropathy (CAN) and nocturnal arrhythmias in patients with type 2 diabetes mellitus (T2DM).

A total of 145 T2DM patients (99 cases for male, 46 cases for female) hospitalized in department of endocrinology of Nanjing Drum Tower Hospital without history of arrhythmias were enrolled from January 2016 to April 2017. CAN was diagnosed based on Ewing tests, which include systolic blood pressure responses to lying-to-standing position, heart rate variation during deep breathing, Valsalva maneuver and lying-to-standing test (30∶15 ratio). According to the scores from Ewing tests, patients were divided into CAN (+) group [scores≥2, n=66, (58±8) yrs] and CAN(-) [scores<2,n=79, (53±12) yrs] group. Ventricular and supraventricular arrhythmic events were recorded with 24h-electrocardiogram. Independent-sample t test, Chi-Square test and Logistics regression were introduced to explore the correlation between nocturnal arrhythmias and CAN.

(1) Patients with CAN had higher incidence of nocturnal (23∶00-6∶00) ventricular arrhythmia [36.4%(24/66) vs 20.3%(16/79), χ ²=4.926, P<0.05]. In addition, patients with higher CAN stages had a higher incidence of nocturnal ventricular arrhythmia [normal group vs early CAN group vs definite CAN group: 16.7%(4/24) vs 21.8%(12/55) vs 36.4%(24/66), χ ²=4.522, P<0.05]. The incidences of ventricular arrhythmia in daytime (6∶00-23∶00) and supraventricular arrhythmia in 24 hours had no difference between two groups. (2)The heart rate variability during deep breathing, valsalva ratio and heart rate response to standing (30∶15 ratio) were all lower in patients with nocturnal ventricular arrhythmias, compared with patients with nocturnal eurhythmia (t=2.072-2.651, all P<0.05). (3)Logistic regression analysis indicated CAN was an independent risk factor of nocturnal ventricular arrhythmias (OR=1.715, 95%CI:1.005-2.927, P<0.05).

CAN is an independent risk factor of nocturnal ventricular arrhythmias in patients with T2DM, which suggests early screening of CAN may be important for forecasting adverse cardiovascular events and mortality.

To investigate whether human umbilical cord mesenchymal stem cells (hUC-MSCs) can play a role in the treatment of diabetic retinopathy (DR) by affecting Notch signaling pathway and vascular endothelial growth factor receptor 2 (VEGFR-2).

Eighty female NOD mice aged 6-8 weeks and weighingt of 20-24 g were randomly divided into diabetes group (group DM) group, insulin group (INS) group (insulin glargine subcutaneous injection, group INS) and mesenchymal stem cells (MSC) group (hUC-MSCs + insulin glargine subcutaneous injection, group MSC) according to random number table after adaptive feeding for 1 week. NOD mice without diabetes were compared as normal control (NC) group (group NC). Each group had 10 mice. Random blood glucose was detected regularly. All the mice were sacrificed after 8 weeks. The number of vascular endothelial nuclei beyond the inner limiting membrane of retina were counted. The mRNA expressions of VEGFR-2 and hairy and enhancer of split related 1 (HESR1), as well as the protein expressions of VEGFR-2 and Notch-1 intracellular domain (NICD) of retina were detected. One-way analysis of variance (ANOVA) was used for comparison among multiple groups. The least-significant difference (LSD)-t test was used for comparison between two groups after ANOVA.

(1) The difference in the number of endothelial nuclei beyond the inner limiting membrane of retina among four groups was statistically significant (F=57.247, P<0.001). The number was significantly lower in MSC group (2.8±0.5) than that in DM group (6.4±1.0) (P<0.05). (2) There were significant differences in the expression of NICD protein, HESR1 mRNA, VEGFR-2 mRNA and protein of retina among four groups (F=155.076-562.306, all P<0.05). Compared with NC group, the expression of NICD protein (0.38±0.18 vs 1.74±0.11) and HESR1 mRNA (0.29±0.04 vs 1.00±0.00) decreased significantly, the expression of VEGFR2 mRNA (4.11±0.40 vs 1.00±0.00) and protein (1.40±0.85 vs 0.28±0.02) increased significantly in DM group(all P<0.05). Compared with DM group, the expression of NICD protein (1.36±0.05 vs 0.38±0.18) and HESR1 mRNA (0.80±0.02 vs 0.29±0.04) increased significantly, meanwhile the expression of VEGFR2 mRNA (1.80±0.27 vs 4.11±0.40) and protein (0.92±0.10 vs 1.40±0.85) decreased significantly in MSC group (all P<0.05).

hUC-MSCs may inhibit the formation of retinal neovascularization by activating Notch signaling pathway and inhibiting VEGFR-2, and may be helpful for the treatment of DR.

To investigate the effect of down-regulation fibroblast growth factor 21 (FGF21) expression on atherosclerosis in diabetic apolipoproteins E deficient (ApoE^-/-) mice.

Intraperitoneal injection of streptozotocin (STZ) was used to make diabetic ApoE^-/- animal model. 8-week-old male C57 mice were used as normal control (n=8). ApoE^-/- mice with the same age were randomly divided into 4 groups: ApoE^-/- group, STZ-ApoE^-/- group, STZ-ApoE^-/-+ FGF21 Scramble miRNA (vehicle control) group, STZ-ApoE^-/-+FGF21 miRNA group. FGF21 Scrambled siRNA and FGF21 miRNA were administered to mice by caudal vein at a dose of 3×10⁹ pfu for each injection, once a week for 8 weeks (n=8). Blood glucose and lipid were determined with glucose oxidase method and enzymic method respectively. The serum level of FGF21 was detected by enzyme linked immunosorbent assay. The intima lipid deposit and the area of atherosclerosis plaque of thoracic aorta were detected by oil red O staining and hematoxylin-eosin (HE) staining respectively. Hepatocytes were cultured and treated with high glucose (25 mmol/L). Real-time polymerase chain reaction and western blotting were performed to measure FGF21 expression. All analysis were performed using SPSS 13.0 statistical software. Statistical significances among groups were evaluated by one-way analysis of variance (One-Way ANOVA) and pairwise comparision with LSD-t test.

High glucose contributed to the expression of FGF21 in a time-dependent manner. Compared with ApoE^-/- group, the level of fasting blood glucose, serum FGF21, liver FGF21 mRNA and protein were significantly increased in STZ-ApoE^-/- group [(17.8±2.3) vs (7.5±0.7) mmol/L, t=-10.7, P<0.01; 129.59±15.35 vs 12.85±2.61, t=-18.4, P<0.01; 1.05±0.13 vs 20.36±3.02, t=-15.7, P<0.01; 1.30±0.14 vs 0.33±0.04, t=-16.8, P<0.01]. Compared with STZ-ApoE^-/- group, the levels of liver FGF21 mRNA and protein were significantly decreased in STZ-ApoE^-/-+FGF21 miRNA group (2.15±0.35 vs 20.36±3.02, t=-15.7, P<0.01; 0.36±0.04 vs 1.30±0.14, t=-16.8, P<0.01). Meanwhile, the fasting blood glucose, intima lipid deposit and the area of atherosclerosis plaque of thoracic aorta were significantly increased in STZ-ApoE^-/-+FGF21 miRNA group [(23.2±2.3) vs (17.8±2.3) mmol/L, t=-3.85, P<0.01; 252±20 vs 176±14, t=-8.16, P<0.01].

High glucose increased mRNA and protein levels of FGF21 in hepatocytes. FGF21 miRNA promotes the formation and development of arteriosclerosis in diabetic ApoE^-/- mice, possibly through down-regulation of FGF21 expression.

To investigate the protective effects of oridonin (Ori) on Toll like receptor 4 (TLR-4) mediated immune and inflammatory signaling pathway of kidney in type 2 diabetes and to discuss the intervention role and the possible mechansim of Ori on diabetic nephropathy.

In vivo experiments: 32 male SD rats with 8 weeks of age and weight 180-220 g were divided into normal control group (NC group), normal control with Ori treatment group (NCO group), diabetes group (DM group) and diabetes with Ori treatment group (DMO group) by randomized table method, with 8 rats in each group. In vitro experiments: cells were cultured with high glucose (HG) and treated with TLR-4 inhibitor TAK-242 and Ori. Rats in NCO group and DMO group received intraperitoneal injection of 10 mg·kg^-1·d^-1 Ori for 8 weeks. The biochemical indexes were detected after intervention. Renal histopathological changes were observed under light microscope. The expression of TLR-4 and CD₆₈ were tested by immunoreactivity. The expression of CD₄₊, CD₈₊ T cells in renal tissue were checked by immunofluorescence. The level of tumor necrosis factor(TNF-α), interleukin-6 (IL-6) and IL-1β were detected by ELISA, and the expression of TLR-4 and nuclear factor-κB (NF-κB) were measured by Western blot. The difference between groups were evaluated using analysis of variance (ANOVA).

(1) The infiltrated CD₆₈ positive cells in kidney tissue (glomeruli and tubules interstitium) in DM group were significantly greater than NC group (t=11.56, 13.69, both P<0.05); compared with DM group, the CD₆₈ positive cells in DMO group were significantly decreased (1.87±0.25 vs 2.93±0.31, 0.27±0.04 vs 0.65±0.07, t=8.58, 15.54, both P<0.05). (2) The level of TNF-α, IL-6 and IL-1β in renal tissue of DM group were significantly higher than those of NC group (t=11.01-19.79, all P<0.05), while the levels of TNF-α, IL-6 and IL-1β in DMO group were significantly lower than those in DM group (t=11.72-17.18, all P<0.05). (3) The expression of TLR-4 protein in renal tissue of DMO group was significantly decreased compared with DM group(0.28±0.06 vs 0.55±0.12, t=7.89, P<0.05). Compared with HG group, the expression of TLR-4 protein was significantly decreased after the intervention of Ori and TAK-242 at high glucose level (0.49±0.05 vs 0.79±0.12, 0.42±0.10 vs 0.79±0.12, respectively, t=9.13, 9.63, both P<0.05). (4) Compared with DM group, the expression of p65 protein in renal tissue of DMO group was significantly lower (t=5.90, P<0.05). Compared with HG group, the phosphorylation level of p65 and IκBα were significantly decreased after intervention with Ori and TAK-242 at high glucose level (allP<0.05).

Ori treatment may delay the progression of type 2 diabetic nephropathy by inhibiting TLR-4/NF-κB mediated inflammatory signal, and therefore may decrease the infiltration of inflammatory cell as well as the expression of inflammatory factors.

Helicobacter pylori (Helicobacter pylori, HP) is an important pathogen of gastric injury, which can cause a series of gastrointestinal symptoms^[1]。 HP can induce chronic inflammation and immune response locally and even systemically, leading to metabolic problems such as insulin resistance. Numerous studies have shown that HP infection rate is higher and cure rate is lower in patients with type 2 diabetes compared with non-diabetic people^[2]。

Gestational diabetes mellitus (GDM) refers to the abnormality of glucose metabolism that occurs for the first time during pregnancy, excluding pre-pregnancy diabetes and pregnancy dominant diabetes. With the prevalence of high-calorie diets, low-activity lifestyles, and increasing gestational age, the incidence of GDM is increasing year by year. Map data published by the International Diabetes Federation (IDF) in 2017 shows that the global incidence of GDM is as high as 14.0%. GDM not only leads to an increase in multiple perinatal adverse outcomes, but also leads to long-term development of type 2 diabetes (T2DM), cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), malignant tumors, kidney disease, eye disease, and depression. However, these long-term risks are often overlooked in clinical practice work. Therefore, this article reviews the effects of GDM on maternal long-term health, in order to provide useful reference for individualized postpartum follow-up of GDM patients.

artificial sweeteners (AS), also known AS artificial sweeteners, low-calorie sweeteners, sugar substitutes, etc., are food additives that are synthesized or modified by artificial chemicals and have a sweet taste without providing or providing a small amount of calories. According to China's National Food Safety Standard for the Use of Food Additives (GB2760-2014), there are 18 kinds of non-nutritional sweeteners allowed to be added to food at present, including 11 kinds of AS^[1]。 The Food and Drug Administration (FDA) allows 8 kinds of non-nutritional sweeteners to be added to Food, including 6 kinds of AS [sucralose, aspartame, neotame, saccharin, acesulfame potassium, advantame] and 2 kinds of natural sweeteners [stevia sugar, Luo Han Guo extract], and stipulates the acceptable daily intake (ADI), among which the ADI of commonly used sucralose is 5 mg · kg^-1• d^-1[2]。

Type 1 diabetes (T1DM) has an early onset, long course, common complications, and even life-threatening, which has a huge negative impact on the quality of life, psychology and economy of patients and their families. T1DM is caused by islet-specific and chronic inflammatory response dominated by T-helper (Th) cells that can secrete interferon gamma (IFN-γ). Rational use of immune regulatory mechanisms can slow down the destruction of T cells to pancreatic islets. However, there are few cells that can secrete insulin in patients with T1DM, and a large number of T cells that can attack pancreatic islets have accumulated. Commonly used immune tolerance and regulatory measures have not been able to reverse the dependence of patients on exogenous insulin, so there is no effective treatment for this disease at present. Pancreas or islet transplants require long-term immunosuppressive drugs, which increase the risk of infectious diseases and cancer. Therefore, there is an urgent need for safe and effective treatment in clinical practice. The future treatment direction should still start with immunomodulation, which has the advantage of purposefully eliminating some autoreactive T cells and retaining cells resistant to foreign pathogens. Therefore, basic researchers need to strengthen etiology research, deeply analyze the ways to activate the autoimmune response of pancreatic islets, and find new molecular targeting that can be used for disease diagnosis, prevention and treatment.

Hyperglycemic status in patients with type 2 diabetes mellitus (T2DM) can involve multiple organs in the body, and is an independent risk factor for cardiovascular and cerebrovascular diseases, increasing all-cause mortality of patients^[1]。 The main objectives of T2DM treatment are to reduce all-cause mortality and improve the patients' health-related quality of life (HRQoL). Non-insulin hypoglycemic drugs are widely used, with the characteristics of lowering glucose, low incidence of hypoglycemia, less weight gain, economy and convenient use, so their clinical application is increasing^[2]。 This article reviews the assessment methods of HRQoL in patients with T2DM and the effects of various non-insulin hypoglycemic drugs on HRQoL in patients with T2DM, so that clinicians can provide better treatment options for patients with T2DM and improve HRQoL of patients.