Volume 10 · Issue 10 · 2018

Gonadal function and diabetes are closely related and influence each other. Hypogonadism is a risk factor for the onset of diabetes, and conversely, hyperglycemia also has an effect on the hypothalamic-pituitary-gonadal axis. With the deepening of research, the relationship between the two has attracted increasing attention of scholars.

Blood glucose monitoring plays an important role in diabetes management. Self-glucose monitoring (SMBG) is the basic form of blood glucose monitoring, but SMBG compliance is poor, and it is difficult to obtain dynamic and continuous data of patients, so it cannot accurately guide clinical decision-making^[1,2]。 Continuous glucose monitoring (CGM) has become an extremely important part of diabetes management. It can continuously monitor the changes of blood glucose in patients, especially patients with occult hyperglycemia, hypoglycemia and large blood glucose fluctuations, and has become an effective supplement to traditional blood glucose monitoring methods. However, CGM still needs fingertip calibration and cannot completely replace SMBG. In 2016, the flash glucose monitoring system (FGM) approved by the China Food and Drug Administration is different from the previous CGM. It can provide a dynamic glucose map for up to two weeks, and after the improvement of the algorithm, the CGM data can be corrected without the values obtained by fingertip blood glucose detection. This paper will explain the accuracy and clinical application direction of instantaneous FGM from the perspective of evidence-based evidence.

To investigate the glucose metabolism disorder status and clinical features in patients with Turner syndrome (TS).

A total of 61 patients with TS was included in this study. Oral glucose tolerance test (OGTT), glycated hemoglobin A_1c (HbA_1c) and autoimmune antibodies, including glutamic acid decarboxylase antibody (GADA), islet cell antibodies (ICA) and islet cell antigen 2 antibody (IA-2A) were measured in these patients. The t test and Logistic regression were used for statistical analysis.

(1) The mean age of all the patients was (15.2±4.9) years, and mean body mass index (BMI) was (20.5±3.5) kg/m². (2) HbA_1c was 5.4%±1.4%. About 31.5% (17/54) of the patients had abnormal glucose metabolism: 4 patients were diagnosed as diabetes, 4 cases were isolated impaired fasting glucose (IFG), 6 cases were impaired glucose tolerance (IGT), and 3 cases were combined IFG and IGT. Compared to healthy female adolescents (n=40), patients with TS had higher homeostasis model assessment of insulin resistance (HOMA-IR) (3.4±2.7 vs 2.0±0.7, t=3.321, P=0.001), larger areas under glucose curve [(22.3±8.8) vs (17.7±2.4) mmol·h/L, t=2.339, P=0.022] and insulin curve [(284±178) vs (175±86) mU·h/L, t=3.533, P=0.001] during OGTT. Only one patient had one test positive for IA-2A while her glucose tolerance test was normal. (3) Patients were classified into three subgroups according to their karyotypes: 45, XO group (n=23); isoXq group (n=17), including patients with 46X, i(X)(q) and 45, XO/46X, i(X)(q); and other karyotype type group (n=14). The percentage of abnormal glucose metabolism was 47.8% (11/23), 23.5% (4/17), and 14.3% (2/14) in three groups, respectively. There was no statistical significance among the three groups (χ²=3.764, P>0.05).

Compared to healthy female adolescents, young patients with TS have more severe insulin resistance and higher risks for abnormal glucose metabolism. Patients with 45, XO karyotype have higher inclination for abnormal glucose metabolism than patients with other karyotypes.

To compare the clinical efficacy between dapagliflozin and acarbose in type 2 diabetes mellitus (T2DM) by systematic review and Meta-analysis.

Eligible randomized controlled trials were searched to compare dapagliflozin or acarbose monotherapy with placebo from PubMed, the Cochrane Library, Web of Science, CNKI Database, Wan Fang Database and VIP Database until 30 April 2016. Meta-analysis were conducted to evaluate the levels of HbA_1c, body weight and systolic blood pressure (SBP) after treatment of dapagliflozin, acarbose and placebo. Bucher method was applied to convert the summary estimates from Meta-analysis into weighted-mean-difference (WMD).

A total of 21 studies were included in the Meta-analysis. HbA_1c, body weight and SBP decreased 0.59% [95%CI:(-0.67, -0.51)%, P<0.001], 1.62(-1.80, -1.43) kg, P<0.001] and 2.60(-3.01, -2.19) mmHg (1 mmHg=0.133 kPa), P<0.001] respectively in Dapagliflozin monotherapy than those in placebo therapy; HbA_1c, body weight and SBP decreased 0.52% (-0.64%, -0.40%), P<0.001], 0.7 kg [(-1.10, -0.29) kg, P<0.001] and 0.13 mmHg [(-2.54, 2.28) mmHg, P>0.05] respectively in acarbose monotherapy than those in placebo therapy. By indirect comparison using placebo as a common comparator, HbA_1c decreased 0.07% in dapagliflozin monotherapy than that in acarbose monotherapy, but the difference wasn′t significant [(-0.21, 0.07)%, P=0.341]; Additionally, body weight and SBP decreased 0.92[(-1.37, -0.47) kg, P<0.001] and 2.47[(-4.91, -0.03) mmHg, P<0.05] respectively in dapagliflozin monotherapy than those in acarbose monotherapy.

The monotherapy efficacy of dapagliflozin in HbA_1c reduction is similar to that of acarbose, but the monotherapy effects of dapagliflozin in weight loss and SBP reduction are better than those of acarbose.

To explore the clinical characteristics of drug-induced hypoglycemia in non-diabetic patients.

A case of hypoglycemia caused by sexual enhancement medication containing oral antidiabetic agents was presented. Data of drug-induced hypoglycemia in non-diabetic patients admitted in Peking Union Medical College Hospital from January 2008 to December 2017 were collected and analyzed.

Glibenclamide, phenformin and sildenafil were confirmed by high performance liquid chromatography and liquid chromatography-quadrupole-time of flight mass spectrometry in the sexual enhancement medication, and no recurrent hypoglycemia occurred after discontinuation of the agent. In the past 10 years, a total of 12 cases were admitted in Peking Union Medical College Hospital with the diagnose of drug-induced hypoglycemia in non-diabetic patients. The onset age was 13-76 years old with the median of 64 years old, and the ratio of male to female was 11∶1. The drug components test was performed in 8 cases and demonstrated that glyburide was the most common agent (100%), followed by gliquidone, metformin and phenformin. The common features of drug-induced hypoglycemia in non-diabetic patients were as the follows: no history of sever hepatic and renal diseases, irregular seizures onset pattern, plasma glucose level often less than 2.0 mmol/L at episodes, no significant imaging abnormalities, suspected medication history.

Drug-induced hypoglycemia should be considered in the clinical setting of hypoglycemia in non-diabetic patients. Detailed medication history and drug components test are crucial for the diagnosis and management.

To investigate the status of blood glucose control in children with type 1 diabetes mellitus (T1DM) in Henan Province, and the safety of flash glucose monitoring system (FGMS) in children with T1DM.

Between August 2017 and February 2018, 116 children with TIDM from the Department of Endocrinology in 15 hospitals were selected, including the First Affiliated Hospital of Henan University of Science and Technology and other tertiary hospitals in Henan province. All patients were younger than 14 years old and treated with either continuous subcutaneous insulin infusion (CSII) or multiple daily insulin injection (MDI). All patients wore FGMS for 2 weeks after the selection. Various glucose monitoring indicators and adverse events were recorded during the application of FGMS, and the effects of diabetes duration, insulin injection model and other factors on blood glucose control were also analyzed. The t test, analysis of variance and rank sum test were used to compare the differences between groups, the correlation was analyzed by partial correlation.

The baseline glycated hemoglobin A₁c (HbA_1c) was (8.3±1.7)%. During the application of FCMS, the estimated HbA_1c was (7.8±1.3)%, the mean blood glucose was (9.8±2.1) mmol/L, and the percentage of time of blood glucose reaching the target (3.9-7.8 mmol/L) was (37±14)%. The percentage of time of hypoglycemia (<3.9 mmol/L) was 4% (3, 8)%. The standard deviation of blood glucose (SDBG) was (4.1±1.2) mmol/L and the mean amplitude of glycemic excursion (MAGE) was (8.4±2.5) mmol/L. The SDBG and MAGE in CSII group were decreased compared with MDI group (t=2.65, 2.51, both P<0.05). The partial correlation analysis showed that the SDBG as well as the MAGE was positively correlated with the baseline HbA_1c (r=0.401, 0.357, both P<0.05). No adverse events related to FGMS was recorded during the study period. The drop rate of FGMS sensors was decreased significantly in winter.

T1DM patients under 14 years old in Henan province have a high HbA_1c level, a high risk of hypoglycemia and a large fluctuation of blood glucose. The application of FGMS in children is safe. It may be helpful to reduce the drop of the sensor by avoiding the exposure of FGMS sensors.

To systematically review the effectiveness of general practitioner contract service on blood glucose management and treatment compliance in diabetes patients in the community, and provide a basis and reference for general practitioner to manage diabetes patients.

We searched electronic databases including CNKI, VIP,CBM and WanFang Data for published articles from inception to Jan. 31 2018. Collected all literature on the study of general practitioner contract service and conventional community intervention in diabetic patients. According to the inclusion and exclusion criteria, two reviewers screened literature and extracted data of included studiesindependently. Then, meta-analysis was performed using Stata 12.0 software.

Totally, 38 experiment studies were collected involving 8 809 diabetic patients, including 4 551 patients who received the contract service of general practitioner and 4 258 patients who received conventional community intervention. Compared with conventional community intervention group, the biochemical indexes in the contract service of general practitioner group were significantly lowerthan that of the control groups, except for high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol level. The level of HbA_1c among intervention group was decreased with 1.07% compared with that of control group (SMD=-1.070, 95%CI=-1.309,-0.831). Diastolic blood pressure (DBP) was not significantly different between the intervention and control group (SMD=-0.171, 95%CI=-0.366, 0.025, P>0.05). The patient compliance indexes, such as taking drugs in a timely manner, dietary control, blood glucose monitoring and physical exercise, were significantly improvedamong intervention group:23.9% (RR=1.239,95%CI=1.147,1.338), 28.7% (RR=1.287, 95%CI=1.021,1.622), 39.4% (RR=1.394,95%CI=1.226,1.584) and 38.0% (RR=1.380, 95%CI=1.209,1.576) respectively.

The contract service of general practitioner has much more effectiveness and compliance than the traditional management of diabetes in communities.

To investigate the association of lipid profiles and triglyceride-glucose (TyG) index at the first visit with the risk of gestational diabetes mellitus (GDM).

Between June 2014 and February 2018, a total of 545 pregnant women were divided into normal glucose tolerance (NGT, n=157) and GDM (n=388) according to 75 g oral glucose tolerance test. The characteristic and metabolic indexes, such as TyGindex, triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), were comparedusing Student'st-test or Mann-Whitney U test. Logistic regression was used to analyze the risk factors of GDM during pregnancy. Receiver operating characteristic curve predicted the threshold of each indicator affecting the occurrence of GDM.

The results showed that the level of TG [2.09 (1.44, 2.94) vs 1.47 (1.02, 2.64) mmol/L, Z=-2.169, P=0.030], TyG index [1.75 (1.38, 2.13) vs 1.16 (0.84, 1.70), Z=-3.910, P<0.001], and TG/HDL-C [1.30 (0.86, 1.74) vs 0.96(0.71, 1.44), Z=-2.283, P=0.022] in GDM were significantly higher than NGT. Maternal age, pre-gestational weight, pre-gestational maximum weight, pre-gestational body mass index, proportion of overweight and obesity, prenatal weight, first-degree relatives family history of diabetes, acanthosis, and the incidence of previous adverse pregnancy outcomes were also higher in GDM (P<0.05). Adjusted confounding factors, TyG index [odds ratio (OR)=24.138, 95% confidence interval (CI) 4.167-139.862, P<0.001] was a risk factor for GDM. With the increase of TyG index, the risk of GDM increased significantly (P<0.05). ROC curves showed that the cut-off values of TyG index and TG were 1.38 [sensitivity 75.5% and specificity 65.6%; area under the curve (AUC) 0.730, 95% CI: 0.632-0.827, P<0.001], and 51.59 mmol/L (sensitivity 72.6% and specificity 54.3%; AUC 0.623, 95%CI: 0.513- 0.732, P=0.056), respectively.

Pregnant women with TyG index>1.38 is prone to occur GDM during pregnancy.

To study the mechanism of telmisartan on peroxisome proliferator-activated receptors (PPAR) γ phosphorylation mediated by cyclin-dependent kinase (CDK) 5 and regulation of adiponectin expression in 3T3-L1 adipocytes.

3T3-L1 with differentiation rate above 80% adipocytes were stimulated with different concentrations of tumor necrosis factor (TNF)-α (10, 50, 100 ng/ml for T₁₀, T₅₀, and T₁₀₀ groups respectively) for 1 h. Different doses of telmisartan (0.1, 5, 10 μmol/L) treated T ₁₀₀ group for 24 h. The expression of CDK5 and p35 protein and the PPARγ phosphorylation levels were detected with Western blotting; Quantitative real-time polymerase chain reaction (qPCR) assessed CDK5, p35, PPARγ gene expression changes. Enzyme-linked immunosorbent assay (ELISA) was used to measure adiponectin concentration. 3T3-L1 cells were constructed and packaged with retroviruses carrying the p35 gene. The empty vector virus was used as a control and a CDK5 inhibitor group was set up to detect the CDK5, p35/p25, phosphorylation levels of PPARγ and the adiponectin level. Data were expressed in±s, data among multiple groups were compared using One-Way ANOVA.

Compared with untreated group, the relative expression levels of CDK5 mRNA and protein in the T₁₀, T₅₀, and T₁₀₀ groups were not statistically different (all P>0.05). The relative expression of p35 mRNA (2.11±0.66, 2.71±0.59 vs 1.22±0.35, q=3.77, 4.91) and protein (0.32±0.02, 0.45±0.04 vs 0.09±0.01, q=2.19, 4.55) in the T₅₀ and T₁₀₀ groups were up-regulated, the differences were statistically significant (all P<0.05). There was no significant difference in the relative expression of PPARγ mRNA and protein among each group (allP>0.05). pPPARγ/PPARγ was increased in the T₅₀ and T₁₀₀ groups (0.21±0.03, 0.47±0.04 vs 0.11±0.02, q=3.89, 6.91) while adiponectin concentration was decreased (1.56±0.34, 1.07±0.12 vs 2.36±0.55, q=6.32, 6.99, all P>0.05). After telmisartan intervention there was no significant difference in the relative mRNA and protein expression levels of CDK5 and p35 compared with the T₁₀₀ group (all P>0.05). Tel₅ and Tel₁₀ groups had significant decreases in pPPARγ/PPARγ (0.11±0.03, 0.05±0.01vs 0.38±0.02, q=4.91, 5.22) and increase in adiponectin release (1.71±0.06, 1.92±0.27 vs 1.11±0.05, q=5.77, 6.43) (all P<0.05). Over-expression of p35 led to p25 expression, elevation of pPPARγ/PPARγ (0.87±0.12vs 0.07±0.02, q=9.13) and down-regulation of adiponectin (1.39±0.12 vs 2.21±0.33, q=5.67). In the inhibitor group, pPPARγ/PPARγ significantly decreased (0.15±0.01vs 0.87±0.12, q=3.14) and adiponectin increased (1.95±0.24 vs 1.39±0.12, q=4.99) (all P<0.05).

Telmisartan regulates 3T3-L1 adipocyte adiponectin expression by inhibiting PPARγ phosphorylation induced by CDK5 overactivation.

Insulin autoimmune syndrome is a rare disease that causes insulin resistance and repeated spontaneous hypoglycemia, often induced by sulfhydryl-containing drugs. This paper reports a case of insulin autoimmune syndrome caused by insulin analogues, which was finally diagnosed as type 1 diabetes and obtained good therapeutic effect. Through analyzing the clinical characteristics of this patient and analyzing the problems existing in the process of diagnosis and treatment, we hope to have some enlightenment for clinical work.

polycystic ovary syndrome (PCOS) is a common endocrine and reproductive system disease in women of childbearing age, with an incidence rate of 5% ~10%^[1]。 PCOS is a disease that accompanies women throughout their lives. Obesity and abnormal glucose tolerance may occur in adolescence, and the risk of hypertension, diabetes, infertility, miscarriage, etc. may increase in childbearing age. With the increase of age, the risk of endometrial cancer and cardiovascular diseases increases. With the deepening of understanding of PCOS, insulin resistance is considered to play an important role in the pathogenesis of PCOS. Therefore, metformin, a drug that enhances insulin sensitivity, is widely used in the treatment of PCOS. However, there are still uncertainties about the role of metformin in the metabolic regulation of PCOS at present. This paper summarizes the metabolic regulation and mechanism of metformin in PCOS patients.

The traditional idea is that absolute or relative lack of insulin secretion is the most important pathophysiological defect of diabetes, which is "insulin-centric theory". In recent years, the role of islet alpha cells in the regulation of blood glucose homeostasis and the pathogenesis of diabetes mellitus has received increasing attention. glucagon is a hormone secreted by alpha cells, which plays an important role in antagonizing insulin. It mainly acts through glucagon receptor (GcgR). The most important physiological function of glucagon is to stimulate the production of liver glucose under fasting state, and provide glucose for vital organs of the body. Its blood concentration is tightly negatively regulated by blood glucose level. There is an absolute or relative deficiency of insulin levels in diabetic individuals with elevated fasting and post-load glucagon levels. At the same time, the responsiveness of α cells to glucose is impaired, and the increase of blood sugar cannot inhibit the secretion of glucagon, which can further aggravate hyperglucagonemia. In addition, histological studies showed that the number of α cells in diabetic animals and patients was unchanged or compensated, and the ratio of α/β cells was significantly higher than that in non-diabetic individuals^[1]。 Therefore, diabetes is currently considered as a class of diseases with double hormone imbalance, and α cell function and phenotypic changes are involved in the occurrence and development of diabetes. Both inhibiting glucagon secretion and blocking glucagon receptor signaling pathway can reduce blood glucose. On the other hand, promoting the conversion of α cells into β cells can reestablish the total number of functional β cells and restore blood glucose homeostasis.

In recent decades, the number of diabetic patients worldwide has increased at an alarming rate. It is expected that by 2030, the number of diabetic patients will grow to 380 million, and most of them will be concentrated in developing countries. In 2013, it was reported that the prevalence of diabetes among adults in China has reached 11.6%, and diabetes has become a major public health problem that seriously affects the physical and mental health of Chinese people^[1]。 Dietary therapy is the basis of diabetes treatment, and it is an essential measure for prevention and control at any stage of the natural course of diabetes. Dietary problems are twice as frequent in diabetics as in non-diabetic peers^[2]。 Among them, the most common are eating disorders (eating disorders)^[3]。 Eating disorders are common in type 1 diabetes mellitus (T1DM), with an incidence of up to 40%^[2]。

After the concept of evidence-based medicine was introduced, a large amount of clinical research evidence was applied to guide clinical practice, including guidelines and consensus building. However, in the past decade, a large amount of real-world evidence (RWE) has gradually emerged in a series of high-level clinical research journals such as New England Journal of Medicine and The Lancet. At the end of 2016, the 21st Century Cure Act published by the U.S. Congress also proposed to use evidence generated by real-world study (RWS) for the approval of medical devices^[1]。 real-world data (RWD) is data related to the patient's own health status and/or provision of health care obtained through a range of means, such as electronic health records, billing data, disease registration information, and patient's own reports. RWE is the clinical evidence related to the utilization of clinical resources and medical products and their potential benefits and risks obtained by processing and analyzing these RWDs^[1]。 So what is the difference between RWE and randomized controlled trial (RCT)? This review will introduce the characteristics of RWE based on these questions.