Volume 04 · Issue 10 · 2012

At present, diabetes has been widely prevalent all over the world. In 2011, the number of people with diabetes in the world reached 366 million; With the improvement of people's living standards and the change of lifestyle and the coming of aging population, the incidence of diabetes in China is also increasing year by year. At present, there are 92.4 million diabetic patients, ranking first in the world^[1]。 Diabetes can affect almost all tissues in the eye, and diabetic cataract and diabetic retinopathy (DR) are the most common complications in the eye.

Diabetic retinopathy (DR) is one of the serious complications of microangiopathy in diabetic patients. The macula is the main functional area of the fundus retina, which dominates vision and color vision. Diabetic maculopathy includes macular edema (DME) exudation, macular ischemia and proliferative changes. Among them, DME is the most common cause of vision loss in diabetic people, and it is the main cause of vision loss in working age class in developed countries. DME will occur at different stages of DR, and long-standing macular edema will lead to cystoid macular degeneration with severe and irreversible visual impairment. With the increase of diabetic patients in recent years, the incidence of DME is also increasing. Epidemiological surveys show that the incidence of DME is 3% ~6% in people over 18 years old^[1], up to 14% in the DR population^[2]Relevant surveys in China show that the prevalence of DME is 16.22%, and the DME can reach 27.03% in patients with type II diabetes for more than 10 years^[3]。

Blood glucose monitoring is an important part of diabetes management. The results of blood glucose monitoring are helpful to evaluate the degree of glucose metabolism disorder in diabetic patients, formulate hypoglycemic regimen, reflect the effect of hypoglycemic therapy and guide the adjustment of treatment regimen^[1]。 Patients undergo self-glucose monitoring (SMBG) is the basic form of blood glucose monitoring, while glycosylated hemoglobin (HbA1c) is the gold standard reflecting the level of long-term blood glucose control. However, both HbA1c and SMBG have certain limitations. HbA1c reflects mean blood glucose levels over the past 2 to 3 months, so there is a "delayed effect" on the assessment after adjusted treatment, and HbA1c does not reflect the risk of hypoglycemia, nor does it accurately reflect the characteristics of blood glucose fluctuations. SMBG cannot fully reflect the patient's full-day blood glucose profile, and there is a "blind spot" for monitoring. Therefore, dynamic blood glucose monitoring (CGM) developed in recent years has become an effective supplement to traditional blood glucose monitoring methods, and has gradually been popularized and applied in clinical practice. However, the clinical advantages, indications, accuracy evaluation of monitoring data, interpretation of monitoring results and how to guide clinical practice of this technology are not yet familiar to the majority of clinicians. In December 2009, the Diabetes Branch of the Chinese Medical Association formulated and issued the first "Clinical Application Guidelines for Ambulatory Blood Glucose Monitoring in China", which provided a basis for the standardized application of CGM^[2]。 In recent years, the international CGM field has developed rapidly. In October 2010, the American College of Clinical Endocrinologists (AACE) released the "Expert Consensus on Dynamic Blood Glucose Monitoring Technology"^[3]In October 2011, the American Endocrine Society, the Diabetes Technology Association and the European Endocrine Society formulated the Endocrine Society's clinical application guidelines for ambulatory blood glucose monitoring^[4]。 At the same time, the clinical application and research of CGM in China have also made great progress. Real-time CGM technology has begun to be applied in clinical practice. At the same time, many research results that are recognized by peers and have reference significance have been published, which provides first-hand information for writing guidelines adapting to China's national conditions. In view of this, the Diabetes Branch of Chinese Medical Association once again organized national experts to revise the "Clinical Application Guidelines for Dynamic Blood Glucose Monitoring in China" to adapt to today's ever-changing development trend.

To observe the unbalanced statement of angiogenic growth factors and angiogenesis inhibitors with retinopathy development under insulin treatment in the type 2 diabetics, so as to provide reference for clinical monitoring.

Cross- sectional survey of 90 type 2 diabetic patients in the first people's hospital affiliated to Shanghai Jiaotong university from September of 2010 to March of 2011 (30 cases without retinopathy, 36 cases with mild non-proliferative diabetic retinopathy (NPDR) and 24 cases with moderate and severe NPDR). The level of vascular endothelial growth factor(VEGF) and CXC chemotatic factors, including SDF-1, IL-8, GROα, IP-10 and MIG were measured in those patients. One-way analysis of variance was used between groups compared,t test was used in pairwise comparison. Three ratio of angiogenic growth factors and angiogenesis inhibitors were selected using ROC curve and compared with the area under the curve.

The expression of SDF-1 was significant higher in mild NPDR group than that in no retinal lesion group (t=-2.977, P<0.05, AUC=0.643). And compared with mild NPDR group, the expression of VEGF (t=3.333, P<0.05, AUC=0.952), IP-10 (t=-3.45, P<0.05, AUC=0.857) and IL-8 (t=-3.05, P<0.05, AUC=0.5) was significant higher in the moderate and severe NPDR group. At the early stasge, all the three type of ratio (SI: SDF-1/IP-10; II: IL-8/IP-10; VI: VEGF/IP-10) had diagnostic value (II: AUC=0.561, Sen=62.5%, Spe= 51.5%; SI: AUC=0.625, Sen=12.5%, Spe=100%; VI: AUC=0.655, Sen=87.5%, Spe=57.6%). However, only VI had the diagnostic value in the group of moderate and severe NPDR.

There is an unbalance phenomenon of angiogenic growth factors and angiogenesis inhibitors in the type 2 diabetic, which is relative to the development of diabetic retinopathy. The ratio of VEGF/IP-10 may be a good index for the progressive of DR.

To compare the efficacy of modified-ETDRS with mild macular grid laser photocoagulation for treatment of diabetic macular edema.

72 patients (97 eyes) with mild or moderate non-proliferative diabetic retinopathy (NPDR) and diabetic macular edema (DME) were randomly assigned to receive laser photocoagulation of modified-ETDRS (n=36 patients, 48 eyes) or mild macular grid (MMG) (n=36 patients, 49 eyes) from January 2008 to January 2010. All subjects received 24-month follow-up. General clinical examinations, including blood pressure and glycated hemoglobin, and comprehensive standardized ophthalmic examinations were performed. One-way analysis of variance was used between groups compared.

From baseline to 24 months, there was a significant improvement of best corrected visual acuity (BCVA) both in modified-ETDRS group and MMG group (modified-ETDRS group: baseline 55±21, 24 month 59±21; MMG: baseline 54±11, 24 month 58±13), however, there was no significant difference in BCVA improvement between the two groups. Central macular thickness (CMT) was significantly decreased in both groups within 24 months after treatment (modified-ETDRS group: baseline 395±174, 24 month 204±16; MMG: baseline 464±204, 24 month 241±13, P<0.05), but no significant difference in CMT improvement between the two groups.

After 24 months follow-up, both modified-ETDRS and mild macular grid laser photocoagulation are effective to improve BCVA of patients with diabetic macular edema.

To investigate the risk factors of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus.

Seven hundred and eight hospitalized patients with type 2 diabetes mellitus from August 2008 to December 2011 were enrolled in this study. All subjects in this study were divided into two groups based on the results of fundus examination, non-diabetic retinopathy(NDR) group including 498 cases and diabetic retinopathy(DR) group including 210 cases. The subjects were analyzed according to their age, sex, diabetic duration, blood glucose, blood lipids, blood pressure, liver function, renal function, 24 hour urine albumin excretion rate, complications , insulin usage and so on. The spearman analysis was used to analyze the relationship between the diabetic retinopathy and the diabetic nephropathy.

The waist circumference, diabetic duration, systolic blood pressure, diastolic blood pressure, uric acid, uric acid excretion rate, fibrinogen, 24 hour urine albumin excretion rate, blood urine nitrogen, serum creatinine and blood viscosity of patients in DR group were significantly higher than those in NDR group, the difference was statistically significant((95±11), (93±10)cm, (12±7), (7±7)y, (144±23), (135±19) mm Hg(1 mm Hg=0.133 kPa), (83±12), (81±10) mm Hg, (316±87), (300±86) μmol/L, (26±15), (23±11)%, (3.5±1.1), (3.1±0.8) g/L, (125±122), (51±45)mg/24 h, (8±5), (6±3) mmol/L, (110±101), (71±48 )μmol/L, (39/115/44), (57/303/109), t=-2.069, -8.285, -4.807, -2.612, -2.104, -2.883, -4.186, -7.949, -5.132, -4.561, 6.513, respectively P<0.05), the hemoglobin, direct bilirubin, total bilirubin, alanine aminotransferase and creatinine clearance rate of patients in DR group were significantly lower than those in NDR group, the difference was statistically significant((8.9±2.2), (8.1±2.1) g/L, (4.5±2.3), (4.0±2.1) μmol/L, (13±6), (12±6) μmol/L, (27±22), (21±16) U/L, (117±43), (88±50) ml/min,t=-0.067, 2.719, 2.396, 3.220 and 6.548 respectively, P<0.05). Logistic regression analysis showed that diabetic duration, 24 hour urine albumin excretion rate and creatinine clearance rate were selected into the equation(P<0.05). Spearman analysis showed that severity of diabetic nephropathy was positively related to the occurrence and development of diabetic retinopathy(r=0.513, P<0.05).

Diabetic duration more than 5 years, increasing of 24 hour urine albumin excretion rate as well as decreasing of creatinine clearance rate are the independent risk factors of diabetic retinopathy in type 2 diabetic patients.

To evaluate clinical safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in Chinese patients with type 2 diabetes mellitus(T2DM) inadequately controlled on their previous treatments.

A₁chieve study was a prospective, open-label, 24-week observational study in patients with type 2 diabetes initiating insulin analogues therapy in routine clinical practice. From November 2008 to March 2011, eligible patients who had decided to start BIAsp 30 based on physicians' clinical judgments were enrolled into this study from 130 hospitals in China. The overall study population contains 8578 Chinese patients with T2DM who were treated with BIAsp 30. Among the overall study population, a subgroup of 1191 patients was treated with biphasic human insulin before study. The treatment regimen and dosing adjustment were decided at physician's discretion.

The rates of total, major, and nocturnal hypoglyceamia (events/patient/year) of the overall study population were 2.32, 0.15, 0.58 at baseline and 1.54, 0.00, 0.28 at week 24 for the overall population (Fisher exact test P<0.05,P<0.01,P<0.01). Glycaemic control was poor at baseline reflected by HbA1c (9.5±2.3) %. After 24 weeks treatment, HbA1c of the overall study population decreased to (7.0±1.0) % (P<0.01). Fasting plasma glucose (FPG) and post-prandial plasma glucose (PPG) were both improved for the overall population (changes were (-3.5±3.6) mmol/L and (-5.5±5.0) mmol/L, with bothP value <0.01). The rates of total, major, and nocturnal hypoglyceamia (events/patient/year) were 7.20, 0.51, 2.15 at baseline and 2.37, 0.00, 0.43 at week 24 for subgroup patients (all P value <0.01). The HbA1c of these patients decreased from (8.7±2.1) % at baseline to (7.0±1.1) % at week 24 ( P<0.01).

Beginning BIAsp 30 therapy in Chinese patients with T2DM inadequately controlled on previous treatment is associated with marked improvements in glycaemic control, without evidence of clinically significant safety or tolerability concerns, regardless of the previous treatment regimen.

To investigate the prevalence and epidemiologic characteristics of diabetes mellitus and prediabetic state among the adults in Shandong province.

It was a cross-sectional and cluster sampling investigation. From May to July in 2008, a total of 3011 residents( 1328 males and 1683 females), aged 20 years and above(20-76 yrs, mean (51±12) yrs), from 4 regions in Shandong province were enrolled in this study. After an overnight fast, participants underwent an oral glucose-tolerance test. The fasting and 2-hour plasma glucose levels were measured to identify undiagnosed diabetes and prediabetes. Prevalence of diabetes and prediabetes and fat metabolism were compared by subgroups according to sex, age (10 years for an interval). One-way ANOVA was applied to compare differences of continuous variables between subgroups. Rates were compared by using the Chi-Square test.

The crude prevalence estimates of diabetes and prediabetes in this survey was 12.6%(378/3011) and 8.8%(266/3011), respectively. When adjusted for age and sex, the prevalence was 9.9% (10.9% for men and 8.8% for women) for diabetes and 7.3% for prediabetes (7.6% for men and 6.9% for women). There was no significant differences in prevalence of diabetes and prediabetes between males and females (χ²=0.225, 0.184, both P>0.05). The prevalence of diabetes increased with age in men and women (χ²=57.296, 109.882, both P<0.05). The newly-diagnosed diabetes (n=276) accounted for 41.3% of the total diabetes. The prevalence of isolated impaired glucose tolerance was higher than that of isolated impaired fasting glucose(74.1% vs 16.9%). The prevalence of diabetes was higher in urban residents than that in rural residents (13.5% vs 10.9%, χ ²=4.25, P<0.05). The multivariable analysis showed that age, family history of diabetes, central obesity, systolic blood pressure, heart rate, triglyceride and low density lipoprotein cholesterol were the risk factors for development of glucose metabolism disorder (OR=1.623, 2.150, 1.758, 1.132, 1.214, 1.130, 1.171, respectively, all P<0.05), and high density lipoprotein cholesterol was the protective factor (OR=0.617, P<0.05).

The prevalence of diabetes and prediabetes is 9.9% and 7.3 respectively in Shandong. More effective measures should be taken for the prevention, early diagnosis and treatment of diabetes and prediabetes.

To explore the relationship between glucose variability and vascular complications in type 2 diabetic patients, and analysis the related factors.

Data were obtained from 712 type 2 diabetic patients hospitalized in the Endocrinology department from Sep 2005 to Mar 2011, and with full evaluation of diabetic complications, β cell function detection, liver and kidney function, lipid profile and at least two complete 7-point blood glucose profile. Within-day blood glucose fluctuation was evaluated by standard deviation (SD), and patients were separated into four groups according to the SD quartiles(Q1 sd-Q4 sd). Day-to-day blood glucose fluctuation was evaluated by MBS-coeffecient of variance (CV), and patients were separated into four groups according to MBS-CV quartiles(Q1 mc-Q4 mc)Further analyze the comparisons of variant indexes among different within-day and day-to-day blood glucose fluctuation groups.Quantitative data were use independent t test or ANOVA analysis. Count data were use χ ² analysis. Binary variables were use binary logistic regression analysis to evaluate the related risk factors for vascular complications.

(1) Patients in Q1 sd-Q4 sd groups have significant in the course of disease(average in four groups were 4.5, 6.1, 6.7 and 6.8 years. F=4.683, P<0.05), blood glucose control(average HbA1c in four groups were 8.7%, 9.2%, 8.9% and 9.9%,F=5.043, P<0.05)and the β cell function(average HOMA-β in four groups were 2.1, 7.4, 5.2, and 1.5,F=3.462, P<0.05; average CIR in four groups were 4.2, 5.0, 3.1 and 1.2,F=5.308, P<0.05; average IGI in four groups were 2.3, 0.8, 0.6 and 1.0,F=2.963, P<0.05; average AUCINS in four groups were 101.2, 86.9, 72.0 and 47.1,F=2.835, P<0.05). Patients in Q1 mc-Q4 mc groups have significant in the blood glucose control (Average HbA1c in four groups were 8.1%, 8.9%, 9.3% and 10.9%,F=23.669, P<0.05)and the β cell function(average HOMA-β in four groups were 1.4, 1.6, 2.2 and 2.4,F=4.884, P=0.05; average CIR in four groups were 3.3, 3.4, 4.4 and 1.1, F=8.083, P<0.05; average IGI in four groups were 2.1, 2.4, 0.3 and 0.2,F=5.433, P<0.05; average AUCINS in four groups were 103.3, 92.7, 68.8 and 56.6,F=4.148, P<0.05). (2) The incidence of diabetic complications were increased with the increase of within-day blood glucose fluctuation and day-to-day blood glucose fluctuation. But analysis shown no significant difference among Q1 sd-Q4 sd groups (χ²=4.115, P>0.05) and Q1 mc-Q4 mc groups (χ²=2.365, P>0.05). Proportions of patients with 1 or over 2 kinds of diabetic complications were increased with the increase of within-day blood glucose fluctuation and day-to-day blood glucose fluctuation. But analysis shown no significant difference among Q1 sd-Q4 sd groups (χ²=12.286, P>0.05) and Q1 mc-Q4 mc groups (χ²=10.543, P>0.05). (3) Regression analysis shows that SD is the related factor for diabetic retinopathy (P<0.05), MBS-CV is the related factor for macrovascular complications (P<0.05).

Glucose variability is probably related with blood control, course of disease, β cell function and insulin resistance. The risk and categories of diabetic complications might increased with the increase of glucose variability. Glucose variability might by related to the process of diabetic retinopathy and macrovascular complications.

To investigate the relationship between serum sex hormone-binding globulin (SHBG) and macrovascular complications in patients with type 2 diabetes mellitus (T2DM).

A total of 80 T2DM patients (male 48, female 32, average age (61±8) y) who were admitted to our hospital during January 2010 and December 2011 were assigned to the macrovascular complication group (group C, n=40, male 25, female 15, average age (63±11) y) and non-macrovascular complication group (group B, n=40, male 23, female 17, average age (60±11) y). Another 40 healthy controls were recruited from health check-up populations (group A, male 25, female 15, average age (58±10) y). Serum SHBG, body mass index (BMI), waist/hip ratio (WHR), fasting and postprandial plasma glucose, serum insulin, hemoglobin A1c (HbA1c), lipids, blood pressure, urinary albumin to creatinine ratio (ACR), and insulin resistance were measured. Student'st test or Analysis of variance was used for data analysis.

Serum level of SHBG in group C ((31±6) μg/L) was significantly lower than that in group B ((46±17) μg/L) and group A ((56±14) μg/L) ( F=9.763, P<0.01). In Spearman correlation analysis, serum SHBG was negatively correlated with WHR, triglyceride (TG), fasting and postprandial serum insulin, insulin resistance index (IRI) and ACR (r values were -0.216, -0.156, -0.144, -0.108, -0.263 and -0.126, respectively; all P<0.05). Multiple stepwise regression analysis showed that TG, WHR and IRI were independent variables of serum SHBG (r² values were -1.132, -0.862 and -2.650, respectively; all P<0.05).

Serum SHBG seems to play an important role in the development of type 2 diabetic macrovascular complications.

To study the role of L-type and P/Q-type calcium channels in insulin secretion of rat islet β cell.

Healthy SD rats were randomly divided into control group (n=8), L-type channel blocking group (n=8) and P/Q-type channel blocking group (n=8). Sodium pentobarbital was injected into abdominal cavity of the rat. Then a slice was made in its abdomen and separated the pancreas from spleen, stomach, colon and other organs. Finally the silicone catheters were inserted into the abdominal aorta and portal vein on the proper position. The pancreas of rats of the three groups were first perfused with 3.3 mmol/L glucose solution for 10 minutes and then with 16.7 mmol/L glucose solution for 25 minutes. The glucose solution for L-type channel blocking group and P/Q-type channel blocking group contains 50 nmol/L isradipine and 10 nmol/Lω-Agatoxin IVA respectively. Collect the fluid from the portal vein per minute to detect the insulin level by radioimmunoassay. Using SPSS-statistical software package, the experimental data were analyzed through the method of Student Newman Keuls of One-Way-ANOVA.

The fasting blood glucose and body weight were no significant difference among three groups (F=0.377, 1.224, P>0.05). The basal insulin secretion rates were no significant difference among three groups (F=0.095, P>0.05). Glucose-evoked insulin secretion rate of the first phase and the second phase, secretion peak value of insulin in L-type channel blocking group were significantly lower than those in the control group respectively[(402±24) vs (744±32) vs (728±42)μU/min,F=163.879, P<0.01; (323±29)vs(568±40)vs (563±19) μU/min,F=95.043, P<0.01; (521±43)vs(1134±146)vs (1083±199) μU/min,F=27.713, P<0.01]. Glucose-evoked insulin secretion rate of the first phase and the second phase, secretion peak value of insulin were no significantly differences between the P/Q-type channel blocking group and the control group (P>0.05).

Blocking L-type calcium channel significantly inhibited the biphasic insulin secretion of rat islets β cells. Blocking P/Q-type calcium channel doesn't affect the function of the insulin secretion of the rat islet β cells. It showed that L-type calcium channels of rat islets cells play an important role in biphasic secretion of insulin, but P/Q-type calcium channels are not found to play a role in insulin secretion at any stage.

Diabetic Retinopathy (DR) is a disease characterized by microcirculation disorders. The pathological changes in the non-proliferative stage include selective loss of retinal capillary pericytes, thickening of endothelial cells and basement membrane, destruction of blood-brain barrier (BBB), capillary occlusion, and formation of microangioma. In the late stage, a large number of microvascular abnormalities and the presence of non-perfusion areas lead to the formation of retinal neovascularization, which seriously affects the visual acuity of patients^[1]。 In addition, diabetic retinopathy is accompanied by significant nerve cell damage, which even predates the appearance of microcirculatory disorders^[2]。 The mechanisms of neuroretinal injury caused by DR include not only apoptosis of ganglion cells, amacrine cells, photoreceptor cells and pigment epithelial cells, but also excitatory injury caused by Müller cell activation and inflammatory injury caused by microglia activation^[3]。 It can be seen that the neuroretinal damage effect in DR is very complicated, and the neuroprotective effect on DR should also be multi-faceted. erythropoietin (EPO) has attracted more and more attention in the study of many factors of neuroprotection in DR.

Certain cytotoxic mechanisms have been suggested to be important causes of T cell involvement in beta cell death in patients with type 1 diabetes. However, it is possible that the sensitivity of beta cells to these mechanisms differs between in vivo and in vitro environments. CD4^＋T cells and CD8^＋T cells are important for the development of type 1 diabetes, and CD4^＋T cells and CD8^＋It is possible that T cells cause beta cell death through an independent mechanism that may involve the activation of a third class of cytotoxic cells.

Type 1 diabetes is caused by immune-mediated destruction of insulin-producing cells, islet beta cells. T cells directly mediated the destruction of beta cells. However, clinical trials have shown the important role of B cells in type 1 diabetes. For newly diagnosed patients with type 1 diabetes, elimination of total B cells maintains pancreatic islet function and has a tendency to interfere with insulin autoantibody formation. For the treatment of type 1 diabetes, the elimination of total B cells by the elimination of autoantigen-specific B cells is a remarkable update.

Studies have confirmed that type 2 diabetes mellitus (T2DM) is associated with a preclinical chronic inflammatory state caused by abnormalities in the innate immune pathway. Serum pro-inflammatory cytokines and acute phase proteins, collectively referred to as "inflammatory networks", are elevated as the disease progresses during the pre-, early and disease course of type 2 diabetes. Genetic variation can affect how innate immune responses respond to certain environmental factors, which may determine an individual's lifetime risk of disease.

The remaining beta cells at the onset of type 1 diabetes will be sufficient to control hyperglycemia if they are protected from progressive autoimmune destruction. Much research has been devoted to the development of immunotherapies that can both directly tolerate or eliminate pathological T-cell immune effectors and increase the number of regulatory T cells (Treg). The current challenge is how to find an immunotherapy that can not only selectively inhibit the diabetogenic immune response and effectively reverse diabetes, but also establish long-term β-cell-specific immune tolerance to alleviate the disease.