Volume 08 · Issue 12 · 2016

In the past hundred years, human society has gradually entered the information age, and the influence of information on social progress is becoming more and more important. The amount of information we face every day, the speed of information dissemination, processing and application are increasing in geometric progressions. How to master as much valuable information as possible and efficiently transform and apply it to practical work is a problem that we need to constantly think about, and it is also one of the ways to achieve remarkable results in diabetes prevention and treatment. Continuous glucose monitoring (CGM) technology, usually referred to as dynamic blood glucose monitoring technology in clinic, refers to a monitoring technology that reflects blood glucose levels by monitoring glucose concentration in subcutaneous intertissue fluid through glucose sensors. More blood glucose information can be obtained through CGM, which helps to make blood glucose management more refined and scientific. In order to better guide clinicians to effectively transform the information science obtained by CGM into clinical practice, various societies at home and abroad have successively issued relevant consensus and guidelines. In December 2009, the Diabetes Branch of Chinese Medical Association released the first "Clinical Application Guidelines for Dynamic Blood Glucose Monitoring in China (2009 Edition)"^[1]and updated in 2012^[2]。 In 2011, the American Endocrinology Society, together with the Diabetes Technology Association and the European Endocrinology Society, formulated the Endocrinology Society's clinical application guidelines for ambulatory blood glucose monitoring.^[3]。 In February 2016, the American College of Clinical Endocrinologists and the American Society of Endocrinology published the "Consensus on Clinical Application of Dynamic Blood Glucose Monitoring"^[4]。

Blood glucose monitoring is an important part of diabetes management. It runs through the whole process of diabetes treatment and efficacy evaluation, and plays an important role in the prevention and treatment of acute and chronic complications of diabetes^[1]。 According to the relevant guidelines and research progress at home and abroad, this paper introduces the blood glucose monitoring of diabetic patients in special populations, including children and adolescents, gestational diabetes mellitus, perioperative patients and elderly diabetes mellitus.

It is widely recognized that persistent hyperglycemia causes damage to cardiovascular and target organs. Recent studies have found that fluctuating hyperglycemia is closely related to the occurrence and development of chronic complications of diabetes. The so-called blood sugar fluctuation refers to the fluctuation of blood sugar in the body between high and low values. The body's blood glucose level is not constant. The postprandial blood glucose of people with normal glucose tolerance is higher than the basal blood glucose level, but the increase is small, and they can return to the basal state before the next meal. The insulin secretion function of diabetic patients gradually declines with the progression of the disease, and irregular diet and exercise, treatment compliance and other reasons can lead to increased blood sugar fluctuations. There is evidence that blood glucose fluctuations can activate oxidative stress in the body, impairing vascular endothelial function and leading to chronic complications of diabetes. Therefore, in the treatment of diabetes, blood sugar fluctuations have received increasing attention.

To investigate blood glucose profiles of patients with type 2 diabetes mellitus during short-term intensive insulin therapy and to analyze the relationship between blood glucose levels and glycemic remission.

A total of 266 patients with newly diagnosed type 2 diabetes who accepted short-term insulin pump therapy in the Department of Endocrinology in the First Affiliated Hospital of Sun Yat-sen University during 2001 to 2014 were included in this study. All patients accepted 2- 3 weeks of short-term insulin pump therapy after diagnosis. They were followed-up for 1 year after the cessation of the pump. Subjects were divided into instant remission group (187 patients, 127 men and 60 women) and instant non-remission group(79 patients, 47 men and 32 women) according to whether they could be relieved immediately after the treatment. According to the follow-up one year, subjects were divided into long-term remission group (127 patients, 89 men and 38 women) and non-remission group(139 patients, 85 men and 54 women). The capillary blood glucose profiles were recorded, relationship between blood glucose levels, standard deviation of blood glucose level and glycemic remission was analyzed. Difference between two groups was analyzed by t test. Logistics regression analysis and Cox regression analysis were used to analyze the influencing factors of glycemic remission.

Mean blood glucose (MBG) after achieving glycemic targets was (6.2±0.6) mmol/L in all subjects. Instant glycemic remission rate after the cessation of the pump was 70.3% (187/266), one year remission rate was 47.7% (127/266). Compared with instant non-remission group, MBG was lower in instant remission group [(6.1±0.6)vs (6.6±0.7) mmol/L, t= 6.026, P<0.05]. Multivariate logistics regression analysis showed that immediate glycemic remission rate was reduced by 65% (OR=0.350, 95% CI:0.192- 0.638, P<0.05) for every 1 mmol/L increase in MBG. Compared with non-remission group, MBG was lower in one-year remission group [(6.0 ± 0.5)vs(6.5 ± 0.7) mmol/L,t=6.147, P<0.05]. Multivariate regression analysis showed that MBG [OR=0.388, 95% CI(0.224- 0.670), P<0.05] was a predictor of 1-year remission. The risk of recurrence of hyperglycemia in one year increased by 0.814 fold [HR=1.814, 95%CI(1.333-2.469), P<0.05] for every 1 mmol/L increase in MBG. If mean 2-hour postprandial blood glucose and mean fasting blood glucose were substituted for MBG in the analysis, mean 2-hour postprandial blood glucose [OR=0.530, 95%CI(0.368-0.753), P<0.05], but not mean fasting blood glucose was an independent predictor of one year glycemic remission.

Stricter glycemic control during maintenance phase of short-term intensive insulin therapy in newly diagnosed type 2 diabetes mellitus patients is associated with higher remission rate after treatment.

To investigate the current situation of islet autoantibodies detection in China, and to evaluate assay proficiency to improve the diagnosis and classification of autoimmune diabetes.

Islet autoantibodies questionnaire was sent to 20 members of National Clinical Research Center for Metabolic Diseases in April 2015. In accordance with international standardization of islet autoantibodies program, sera of 50 patients with newly diagnosed type 1 diabetes, 100 healthy controls were blindly numbered and assayed in three core units using radioligand assay. The area under the receiver operating characteristic curve (ROC) (AUC) was applied to evaluate the sensitivity and specificity, as well as the consistency of the results. Mann-Whitney U test was used to compare the WHO values of type 1 diabetes mellitus and healthy volunteers autoantibodies. Linear correlation analysis was applied to evaluate the correlation of 3-lab results after converting into WHO standard unit.

(1) All of 20 hospitals carried out the detection of glutamic acid decarboxyase antibody (GADA), and 7 hospitals detect GADA+ protein tyrosinephosphate antibody(IA-2A) paralelly (35%); The detection methods included immunoblotting (30%), chemiluminescence (20%), enzyme-linked immunosorbent assay (20%), radioimmunoassay (15%) and radioligand assay (15%). (2) Among three core units, sensitivity for GADA detection ranged from 72% to 80%, while specificity ranged from 95% to 100%; sensitivity for IA-2A detection ranged from 38% to 58% with the specificity from 98% to 100%. The ROC analysis showed that the AUC of GADA was 0.897-0.935, of IA-2A was 0.716-0.749. The consistency of GADA detection among three units was 92.7%, of IA-2A was 92%.

Islet autoantibodies detection in Chinese hospitals need to be standardized. Radioligand assay is recommended for centralized detection of islet autoantibodies in China.

To evaluate the impact of fasting plasma glucose(FPG) and lipid on distant metastasis of postoperative colorectal neoplasms.

A total of 412 patients with colorectal neoplasms confirmed pathologically in the First Affiliated Hospital of Fujian Medical University from June 2008 to December 2011 were included in this study. There were 231 men and 181 women (aged 21 to 88 years) in this study. The patients were divided into two groups according to follow-up results: patients with distant metastasis and patients without distant metastasis. The glucose and lipid metabolism were compared between the two groups. The univariate analysis and multivariate Cox regression analysis were applied to investigate the relationship between distant metastasis and glucose and lipid metabolism.

The mean follow-up period was (54 ± 22) months till October 2015, and 97 cases were found with distant metastasis. Compared with patient without metastasis, the patients with metastatic colorectal neoplasms had higher degrees of FPG, triglyceride(TG) [5.41(4.90-6.44) vs 5.18(4.70-5.71) mmol/L;1.11(0.81-1.61) vs 1.01 (0.77-1.33) mmol/L, z=-3.024, -2.213, both P<0.05], and was younger[(58±14) vs (61±12)years,t=2.076, P<0.05]. Compared with those in patients without distant metastasis, the rate of FPG≥6.1 mmol/L and TG≥1.1 mmol/L in patients with distants metastasis were both significantly higher(33.0% vs 15.6% and 53.6% vs 40.3%, χ²=14.271, 5.332, both P<0.05). The distant metastasis rate of 30 and 50 months was 29.6% and 39.5% in patients with a FPG≥6.1 mmol/L, and 16.1% and 19.1% in patients with a FPG<6.1 mmol/L(χ²=15.898, P<0.05). The distant metastasis rate of 30 and 50 months was 24.1% and 28.6% in patients with a TG≥1.1 mmol/L, and 15.5% and 18.9% in patients with a TG<1.1 mmol/L(χ²=4.117, P< 0.05).The Cox multivariate regression analysis showed that FPG, TG, TNM stages, perineural invasion were positively correlated with distant metastases (odds ratio=2.898, 1.574, 10.918(TNM Ⅲ stage vs Ⅰ stage), 1.991, allP<0.05), and age was negatively correlated with distant metastases(odds ratio=- 0.619, P<0.05).

The levels of FPG and TG are positively correlated with distant metastases in patients with colorectal neoplasms.

To discuss the relationship between serum total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) of pregnancy and gestational diabetes mellitus (GDM) and/or macrosomia.

A total of 27 152 women who delivered from June, 2013 to November, 2014 in 15 hospitals in Beijing were enrolled and assigned in GDM group (n=5 582) and normal group (n= 21 113) after excluding the exclusion criteria. These women were also grouped as macrosomia group (birth weight ≥4 000 g) (n=2 343) and normal weight (<4 000 g,n=24 352). The correlations between blood lipids of the first trimester and GDM, the difference of blood lipids between GDM and normal pregnancy women were analyzed. The relationship of blood lipids in each trimester and macrosomia and/or GDM was also concerned. Correlation analyses and logistic regression was used to analyze the correlation between GDM and macrosomia.

A positive correlation was found between GDM and serum TG or TC in the first trimester(OR=1.169, 1.291, 95% CI: 1.036-1.319, 1.201-1.388, all P<0.01), while HDL-C levels appeared reverse correlation with GDM (OR= 0.669, 95%CI: 0.567-0.789, P<0.01). Serum TG concentrationsin GDM group were significantly higher (F=4.220-11.707, P<0.01), while serum HDL-C was significantly lower than that in the normal group (F=-9.22--2.47, P<0.05) throughout pregnancy. The incidence of macrosomia in GDM mothers was higher than normal healthy mothers (10.0% vs 7.8%, χ²=23.418, P<0.01). In the first, second and third trimester, macrosomia mothers had higher TG (t=4.845, 3.707, 5.366, P<0.01), and lower HDL-C (t=- 2.917, - 2.622, - 5.38, P<0.01) than mothers who delivered normal birth weight babies.

Serum TG and TC in the first trimester have a positive correlation with GDM, while HDL-C levels appear reverse correlation with GDM. Both macrosomia and GDM mothers have higher serum TG and lower HDL-C.

To observe the variation of serum fibroblast growth factor 21 (FGF-21) in people with different fasting plasma glucose (FPG) and to investigate the correlation between FGF-21 and glucose and lipid metabolism.

A total of 54 type 2 diabetes mellitus (T2DM) patients from January to December 2014 were enrolled as study subjects (group A). Two control groups were selected as impaired fasting plasma glucose (IFG) (group B, n=50) and normal fasting plasma glucose (group C, n=50) from those who were conducting regular health check during the same time period. All of the subjects in each group were matched based on age and gender. Body mass index (BMI), waist/hip ratio (WHR), islet function and FGF-21, and plasma bio-chemical measurements were collected. Pearson correlation analysis and multiple linear stepwise regression analysis were introduced to explore the correlation between FGF-21 and glucose and lipid metabolic indexes.

The serum FGF-21 concentrations in group A, B and C were (3.0±0.6), (2.9±0.5), (1.9±0.4) μg/L, respectively, and the differences were statistically significant ( F= 3.352, P<0.05). Pearson correlation analysis showed that FGF-21 was positively correlated with FPG, glycated hemoglobin (HbA_lc), fasting plasma insulin, homeostasis model of assessment (HOMA) for insulin resistence index (HOMA-IR) and low-density lipoprotein cholesterol (LDL-C) (r=0.193-0.676, all P<0.05), and negatively correlated with HOMA-β (r=-0.548, P<0.05). Multivariate linear stepwise regression model suggested that FGF-21 closely correlated with FPG, HOMA-IR, HOMA-β, total cholesterol (with standard regression equation as: Y_FGF-21=0.204 × FPG + 0.285 × HOMA-IR- 0.231 × HOMA-β + 0.098 × TC, allP<0.05).

Serum FGF-21 is closely correlated with glucose and lipid metabolic parameters, which increases with the escalation of blood glucose, insulin resistance and lipid metabolism disorder.

To explore the effect of different doses of vitamin D (VitD) and calcium supplementation on blood glucose and insulin sensitivity in middle-aged and elderly patients with impaired glucose tolerance (IGT).

A total of 150 individuals with IGT [aged (57±4) years] were chosen during physical examination from January 2013 to May 2015, of which 80 cases were male and 70 were female. They were randomly divided into three groups: regular dose group (group A, n=49, VitD 125 U/d + calcium 600 mg/d), double dose group (group B, n=51, VitD 250 U/d + calcium 1 200 mg/d), and control group (group C, n=50, no medication). Oral glucose tolerance test (OGTT) was performed before and after VitD and calcium supplementation. Blood biochemical parameters were measured. Homeostasis model assessment (HOMA) insulin resistance index (HOMA-IR) and HOMA islet β-cell function index (HOMA-β) were calculated. Comparison of means was done by one-way analysis of variance (ANOVA). LSD- t test was used when P<0.05 as the limit for statistical significance.appropriate. Correlation analysis was performed using Pearson correlation analysis and multiple stepwise regression analysis.

(1) Compared with group C, fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG) and insulin (2hINS), glycated hemoglobin A_1c (HbA_1c), HOMA-IR in group A and B declined significantly (P<0.05) after 6 and 12 months of VitD and calcium treatment, while the level of serum 25(OH)D and HOMA-β were dramatically increased (allP<0.05). (2) After 6 and 12 months treatment, HbA_1c, HOMA-IR significantly declined from baseline [HbA_1c: (5.9±0.5)%,(5.9±0.6)%; HOMA-IR:(3.8±0.9, 3.7±0.7)] in group A [HbA_1c:(5.7±0.2)%, (5.6± 0.6)%; HOMA-IR: 3.6±1.1, 3.4±1.5] and group B [HbA_1c:(5.7±0.6)%,(5.5±0.4)%; HOMA-IR: 2.8±1.5 vs 2.0±1.2] (all P<0.05). And the levels of FPG and 2hPG were also reduced. The differences were significantly (allP<0.05). (3) In addition, FINS, 2hINS, HbA_1c and HOMA-IR in 12 months after treatment were declined in group B compared with group A, while the level of serum 25(OH)D in group B was increased [(40±5) vs (32±6) μg/L] (all P<0.05).(4) Pearson correlation coefficient analysis showed that serum 25(OH)D in 12 months post-treatment was positively correlated with HOMA-β(r=0.210), serum calcium (r=0.444) (both P< 0.05); while was negatively correlated with HbA_1c(r=- 0.241), FPG (r=- 0.215) and HOMA-IR (r=- 0.225) (P<0.05). Multiple regression analysis indicated that serum 25(OH)D in patients with IGT was markedly positively correlated with HbA_1c(r=2.138) VitD doses (r=7.160 for regular-dose, 7.330 for double dose) and total cholesterol (r=2.319) (P<0.05).

Vitamin D and calcium supplementation can improve blood glucose and insulin sensitivity in middle-aged and elderly patients with IGT, in a dose and time dependent manner.

To investigate the effects of adenosine monophosphate activated protein kinase(AMPK) regulated autophagy on restoring the sensitivity of diabetic myocardium to ischemic postconditioning(IPO).

Healthy male Sprague-Dawley rats(weighed 220-280 g) were used in this study. Thirty healthy rats were randomly divided into: sham group (N+S group), ischemia reperfusion group (N+IR group) and ischemia postconditionig group(N+IPO group); type 1 diabetic rat models were induced by a single intraperitoneal injection of streptozotocin at the dose of 60 mg/kg and confirmed by blood glucose concentration≥16.7 mmol/L; all rats were raised for 8 weeks. Fifty-four diabetic rats were randomly assigned into diabetic sham group (D + S group), diabetic ischemia group(D + IR group), diabetic ischemia postconditionig group(D+IPO group), diabetic ischemia+AMPK activtor A-769662 group(D+IR+A group), diabetic ischemia postconditionig+A-769662 group(D+IPO+A group). There were 6 rats in N+S and D+S group and 12 rats each in the other groups. Myocardial ischemia reperfusion model was completed by occlusion of the anterior descending branch of left coronary artery for 30 min followed by 120 min of reperfusion. IPO was induced by 3 cycles of 10 second of reperfusion and ischemia at the onset of reperfusion. AMPK agonist A-769662(6 mg/kg) was given as intraperitoneal injection 30 min before ischemia. Myocardium infarct size (IS) was detected by triphenyltetrazolium chloride staining. Transmission electron microscopeserum was used to observe autophagosomes. Arterial blood was collected to detect creatine kinase-MB(CK-MB) and lactate dehydrogenase(LDH) release. The phosphorylation of AMPK (p-AMPK) and mammalian target of rapamycin (p-mTOR), the ratio of microtubule-associated protein 1 light chain 3B/A(LC3B/A) and ubiquitin binding protein p62 in heart tissues were examined by Western blotting. The t test was adopted to detect the differences between two groups, one-way analysis of variance was used to analyze the differences between groups.

Diabetic rats characterized with lower body weight, p-AMPK expression, autophagosomes number and LC3B/A ratio and higher CK-MB, LDH, p-mTOR, p62 and blood glucose when compared with nondiabetic rats(t=4.15- 34.65, all P<0.05). Compared with N+ IR group, the level of IS, CK-MB, LDH in D+IR group increased significantly(t=3.55, 4.70, 7.20, all P<0.05). Compared with N + S group, p-AMPK level, autophagosomes number and LC3B/A ratio significantly increased, p-mTOR and p62 expressions remarkably deceased in N+IR group(t=6.56, 5.51, 3.76, 3.59, 2.98, all P<0.05); while those changes were not found between D+S and D+IR group (allP>0.05). Compared with D+IR group, the IS(28%±5% vs 45%±6%), CK-MB((1 047±178) vs (2 050±325) U/L), LDH((1 303±365) vs (2 558±189) U/L), p-mTOR(0.48±0.24 vs 1.29±0.25), p62(0.74±0.12 vs 1.04±0.24) decreased significantly, and the p-AMPK level(1.81±0.19 vs 0.61±0.15), autophagosomes number(9.3±1.4 vs 3.8±0.9) and LC3B/A ratio (1.43±0.23 vs 0.65±0.13) increased significantly in D+ IPO+ A group (t=5.26- 11.82, all P<0.05).

AMPK/mTOR activation by A-769662 can restore the sensitivity of diabetic hearts to IPO-induced cardioprotection through autophagy promotion.

To preliminarily investigate application value of polyethylene glycol precipitation (PEG) and gel chromatography in the differential diagnosis of hypoglycemia induced by exogenous insulin in patients with diabetes mellitus. PEG precipitation and gel chromatography were used to detect the serum in two diabetic patients with recurrent unexplained hypoglycemia during injection of insulin. The results showed that case 1 was diagnosed as hypoglycemia induced by excess exogenous insulin, because there was no significant difference in the level of serum insulin before and after PEG precipitation, gel chromatography showed normal insulin peak. Case 2 was diagnosed as exogenous insulin antibody syndrome, because the level of serum insulin after PEG precipitation was significantly lower than before PEG precipitation, gel chromatography showed high molecular weight of insulin peak. The study shows PEG precipitation and gel chromatography can be used to determine whether there is insulin antibody for diabetic patients with unexplained hypoglycemia during injection of insulin.

Adipose tissue can secrete many tissue factors and hormones involved in regulating the metabolic balance of the body. Obesity and diabetes are chronic low-grade inflammatory diseases, and their adipose tissues secrete anti-inflammatory and pro-inflammatory adipokines. The imbalance of the two functions is the key factor leading to obesity and diabetes^[1]。 Therefore, there have been a lot of studies on adipokines in recent years, among which adiponectin (APN) has been studied more. APN is an insulin-sensitizing adipokines, which can play a role in regulating glycolipid metabolism in many aspects^[2,3]。 The complement C1q/tumor necrosis factor-related proteins (CTRPS), which are homologous to adiponectin, is a superfamily of adipokines, and 15 family members (CTRP1~15) have been found^[4]。 CTRP12 is a member of the CTRP superprotein family. It was developed in 2011 and 2012 by Enomoto et al.^[5]And Wei et al.^[6]Two independent laboratory teams led by the group identified a new adipokine, mainly expressed in adipose tissue and kidney^[6]Has the effects of improving blood glucose metabolism, inhibiting liver gluconeogenesis, improving insulin sensitivity, reducing inflammatory reaction in adipose tissue, and may also have the function of stimulating pancreatic islet β cells to promote insulin secretion^[5,6]。 However, the relationship between serum CTRP12 levels and obesity and its associated diseases such as type 2 diabetes is unknown. This study was the first to compare serum CTRP12 levels between healthy controls and obese and newly diagnosed type 2 diabetic patients, and analyze its relationship with parameters related to glucose and lipid metabolism, inflammatory indexes, insulin resistance, etc., aiming to further elucidate the pathophysiological significance of CTRP12.

Nutrients such as protein, carbohydrate, fat, vitamin, mineral and trace elements are all involved in the repair and healing of diabetic foot ulcer^[1]。 The deficiency of these nutrients easily leads to the occurrence and aggravation of foot ulcers, prolonged wound healing time, weak wound healing, increased risk of infection and post-surgical complications.