Volume 08 · Issue 05 · 2016

Human understanding of diabetes has been over 3 500 years, but understanding of gestational diabetes mellitus (GDM) is less than 200 years old. In recent decades, GDM has been paid more and more attention, but there are still some questions that affect clinical diagnosis and treatment, especially the diagnosis and differential diagnosis of pregnancy complicated by various hyperglycemia states, exercise during pregnancy, hypoglycemia judgment during pregnancy, etc. This article expounds these problems.

In recent years, the incidence of diabetes in China has increased year by year^[1,2,3], 2010 Yang et al.^[4]The study found that among Chinese women over the age of 20, 8.8% have diabetes, and 14.9% of women are in the pre-diabetic stage, and the risk of diabetes gradually increases with age. Xu et al.^[5]The study shows that among Chinese women, the incidence of diabetes is 11.0%, and only 3.4% of them have a clear diagnosis, and the incidence of undiagnosed diabetes is 7.6%.

In the 2015 Guidelines for Diagnosis and Treatment of Gestational Diabetes, the International Federation of Gynecology and Obstetrics (FIGO) used insulin and metformin as the first-line drugs for lowering glucose in late pregnancy in patients with gestational diabetes mellitus (GDM)^[1]。 In recent years, the efficacy and safety of metformin in the treatment of GDM have been continuously demonstrated, especially in obese and overweight patients^[2]。 Because there are many risk factors for insulin resistance in some patients with GDM, metformin alone may not be satisfactory for glycemic control, and insulin should be added to help reduce glycemic^[3]。 At present, there are three treatment options for GDM: metformin alone, metformin plus insulin, and insulin alone. This article will evaluate the efficacy and safety of each hypoglycemic regimen in the treatment of GDM, analyze the proportion and prediction methods of insulin needed for metformin, and recommend how to choose a treatment regimen for GDM.

To assess the prevalence and association of hypertensive disorders and diabetes mellitus in pregnancy.

Fifteen hospitals in Beijing were randomly sampled from June 2013 to November 2013 and 15 194 deliveries were evaluated. Overall prevalence of maternal hypertensive disorders and diabetes mellitus in pregnancy were assessed. Prevalence of hypertensive disorders of pregnancy, preeclampsia and severe preeclampsia were compared among non-diabetes, gestational diabetes, and pre-gestational diabetes groups, as well as the prevalence of gestational diabetes between chronic hypertension and non-chronic hypertension groups. Logistic regression analysis was used to explore the association between risk factors and hypertensive disorders and diabetes mellitus. Risk factors included in the model were chronic hypertension, diabetes, age, parity, education status, family income, pre-gestational body mass index and gestational weight gain.

The prevalence of hypertensive disorders, preeclampsia, severe preeclampsia and chronic hypertension was 4.4% (672/15 194), 2.7% (417/15 194), 1.8% (279/15 194) and 2.3% (350/15 194), respectively.The prevalence of gestational diabetes and pre-gestational diabetes was 19.7%(2 986/15 194)and 1.4%(208/15 194). When dividing the population into non-diabetic group, gestational diabetic group and pre-gestational diabetic group, the incidence of hypertensive disorders of pregnancy increased accordingly (3.8%(454/12 000), 6.2%(185/2 986), 15.9%(33/208), χ ²=96.8, P<0.05), as well as the incidence of preeclampsia (2.4%(291/12 000), 3.7%(111/2 986), 7.2% (15/208), χ²=34.3, P<0.05) and severe preeclampsia (1.5%(184/12 000), 2.5%(75/2 986), 2.9%(6/208), χ²= 14.9, P<0.05). The incidence of gestational diabetes (31.4%(110/350) vs 19.4%(2 876/14 844), χ²=42.1, P< 0.05) and pre-gestational diabetes (7.1% (25/350) vs 1.2% (183/14 844), χ²=113.2, P<0.05) in the chronic hypertensive group were higher than those in the non-hypertensive group. Maternal body mass index before pregnancy (OR:1.22, 95% CI 1.15-1.29), gestational weight gain (1.08, 1.05-1.12), maternal complications of gestational diabetes (1.90, 1.20-3.01) and pre-gestational diabetes (4.44, 1.50-13.21) were identified as risk factors for hypertensive disorders. Significant risk factors for gestational diabetes were maternal body mass index (BMI) before pregnancy (1.09, 1.08-1.10), age (1.03, 1.02-1.04) and maternal complication of chronic hypertension (1.57, 1.23-2.00).

Hypertensive disorders of pregnancy and diabetes mellitus in pregnancy are closely correlated to each other. Pre-gestational diabetes and gestational diabetes are risk factors for hypertensive disorders of pregnancy. Chronic hypertension is a risk factor for gestational diabetes.Pre-gestational body mass index is the common risk factor for both diseases.

To investigate the correlation between gestational diabetes mellitus(GDM) and the hepatic metabolism in the first trimester of pregnancy.

This prospective cohort study was conducted in Peking University Third Hospital from January 2012 to December 2014. Pregnant women who visited our hospital during the first trimester were enrolled. Total of 3 126 participants were found with a positive 75 g oral glucose tolerance test (OGTT); then of them, 766 women without any other complications were selected into the GDM group, while 352 cases of healthy pregnant women were set as the control group. The prevalence of GDM and its association with age, height, weight, body mass index (BMI), hypertension, family history of diabetes, alanine aminotransferase (ALT), asparate aminotransferase(AST), total bilirubin (TB), direct bilirubin(DB), gamma-glutamyltransferase(γ-GT), total bile acid(TBA), alkaline phosphatase (ALP), total protein(TP), albumin(ALB), fasting plasma glucose(FPG), prothrombin time(PT), fibrinogen(FIB), activated partial thromboplastin time(APTT), thrombin time(TT), hemoglobin(Hgb), uric acid(UA) were studied in the first trimester. Data analyses were conducted by using single factor analysis and Logistic regression analysis.

The age of pregnant women in group GDM was significantly higher than that in control group ((32±3) vs (30±7) years, t=-6.089, P<0.01), and the BMI was significantly higher in group GDM ((22.1±3.2) vs (20.6±2.5) kg/m², t=-8.346, P<0.01). And the γ-GT (z=10.366), FIB (t=-3.758) were significantly higher in group GDM than those in control group (both P<0.01), besides ALP, FPG, UA were also markedly higher than those in control group (t= -2.215,-9.793,-6.878, all P<0.05). While the DB(z=-3.813), TB (z=-3.241) and HGB (t=2.069) were remarkably lower than those in control group (all P< 0.05). It indicated in multivariable logistic regression analysis that age, BMI, AST, γ-GT, TB, FIB were the independent risk factors of GDM(OR=0.951-1.358, all P<0.05).

It suggests that γ-GT, AST, ALP, T-Bil, FIB in the first trimester of pregnancy are useful predictors of impending GDM.

To identify the features and its pathogenic mechanism in a boy with type 1 diabetes mellitus combined with common variant immunodeficiency syndrome (CVID).

A 9 year old boy with type 1 diabetes was identified with CVID during hospitalization. The clinical features was analyzed. Genomic DNA was extracted, followed by amplification with polymerase chain reaction, whole-exome sequencing (WES) and then Sanger sequencing in his family members.

A novel heterozygous missense mutation c.1073T>C, P.Leu358Ser of signal transducer and activator of transcription 3 (STAT3) gene was confirmed by genetic testing, this mutation was located in the "DNA binding domain", which might affect the functional domains of STAT3 protein predicted by SIFT, PloyPhen and other software.

The patient may be the first case of Chinese children with type 1 diabetes mellitus combined with CVID and carrying the STAT3 gene novel mutation after retrieving the existing database, which expands the phenotypic spectrum of STAT3 gene mutations.

To explore the applicability of body adiposity index (BAI) among Chinese people in the Shanghai area.

487 subjects aged from 20 to 81 years in the Shanghai area were included in the study and analysis was made in the whole group as well as in the subgroups divided by gender (male/female), age (60 years old) and BMI (24 kg/m²) from 2013 to 2014 .Magnetic resonance image(MRI) technology was used to measure subcutaneous adipose area (SA), visceral adipose area (VA), femoral adipose area (FA) and subcutaneous and visceral adipose area (SAVA). Height, weight, waist circumference (WC), hip circumference (Hip) and blood pressure (BP) were measured and waist hip ratio (WHR), body mass index (BMI) and body adiposity index (BAI) was calculated using the following formula: BAI=[Hip circumference (cm)/height (m)^1.5]-18. Blood glucose, blood lipid and other biochemical parameters were tested. We assessed the difference between the two groups with Student’s t test for independent samples and we analyzed the correlation relationships between BAI and BMI with regional fat content using multiple linear regression analysis.

Overall the correlation coefficients between WC and WHR were higher with BMI (r=0.68, P<0.01;r=0.73, P<0.01) than with BAI (r=0.59, P<0.01;r=0.69, P<0.01). BAI and BMI correlated significantly with SA (r=0.78 for BAI, r=0.58 for BMI, P<0.01), VA(r=0.44 for BAI, r=0.55 for BMI,P<0.01), FA(r=0.63 for BAI, r=0.40 for BMI, P<0.01) and SAVA (r=0.78 for BAI, r=0.68 for BMI, P< 0.01). In age, gender and BMI stratified analysis, BAI showed a weaker correlation with SA and SAVA than BMI only in the male group(BAI:r=0.62, 0.67, BMI: r=0.65, 0.73; all P<0.001), but BAI was more correlated with VA than BMI in the female group (BAI:r=0.60, BMI: r=0.52, all P<0.001). In the multiple linear regression model with BAI and BMI as the dependent variables, adjusted by gender and age, the contribution rates of BAI and BMI, were respectively 70%, 51% for SAVA and they differed significantly (P<0.01).

In the whole group except the male subgroup, BAI is better than BMI in estimating body fat content in the Shanghai area. This indicates that BAI could be cautiously adopted to predict the body fat in such situations without accurate weighing apparatus or without knowing the exact body weight.

To investigate the relationship between ambulatory blood pressure rhythm and islet α-cells function in patients with type 2 diabetes suffered from sleep disorder.

Four hundred and six patients with type 2 diabetes treated from January 2012 to July 2014 in Metabolic Disease Hospital of Tianjin Medical University were divided into two groups according to Pittsburgh Sleep Quality Index(PSQI): patients without sleep disorder (242 cases) and patients with sleep disorder (164 cases). Oral glucose tolerance test (OGTT), insulin releasing test, glucagon releasing test and 24 h ambulatory blood pressure monitoring were performed in those patients. The differences of α-cells function after fasting and glucose-load, as well as the circadian rhythm of blood pressure and blood pressure variation were compared between the two groups. The correlation analysis was performed between PSQI score and other indicators, and Logistic regression analysis was performed between blood pressure circadian rhythm and influence indicators.

The level of glucagon and glucagon/insulin ratio at each time point as well as area under curve of glucagon and 0, 30, 60, 180 min glucagon/glucose ratio were significantly higher in patients with sleep disorder than those in patients without sleep disorder(t=2.109-14.188, all P<0.05). The levels of 24 h systolic and diastolic blood pressure, nocturnal systolic and diastolic blood pressure and systolic blood pressure of daytime were all significantly higher in diabetic patients with sleep disorder than those in patients without sleep disorder((135±8) vs (130±7) mmHg(1 mmHg=0.133 kPa), (74±6) vs (72±6) mmHg, (131±7) vs (126±6) mmHg, (72±5) vs (68±5) mmHg, (138±8) vs (133±8) mmHg, respectively,t=6.162, 2.254, 8.432, 5.940, 5.585, all P<0.05). The percentage of decreased systolic blood pressure at night and percentage of decreased diastolic blood pressure at night were lower, whereas 24 h systolic and diastolic blood pressure standard deviation as well as variation coefficient were higher in patients with sleep disorder those in patients without sleep disorder(t=2.232-10.065, all P<0.05). Logistic regression analysis showed that blood pressure circadian rhythm was positively related to the percentage of decreased systolic blood pressure at night(OR:2.014-3.006), and negatively related to area under curve of glucagon (OR:0.652-0.975) and PSQI score (OR:0.623-0.818) (all P<0.05).

Circadian rhythm of blood pressure may be related to islet α-cells dysfunction in patients with type 2 diabetes suffered from sleep disorder.

To analyze retrospectively the trend of fasting plasma glucose (FPG) levels and related factors in Tianjin urban residents.

The data were based on the urban screening program conducted in the Cancer Prevention Center, the Tianjin Cancer Institute and Hospital from 2004 to 2012. The demographic information, FPG, serum triglyceride (TG) and total cholesterol (TC) in 294 177 subjects were measured. Chi square trend test, one way analysis of variance, Pearson analysis and Logistic regression analysis were used for statistical analysis.

In the period of 2004 to 2012, the blood glucose levels in Tianjin urban residents was increased about 18% with age from (4.4±0.5) mmol/L(in 15-19 yrs group) to (5.2±1.4) mmol/L(in 70 yrs or elder group). During the nine years, the FPG abnormal (higher than upper limit of normal value) detective rates increased from 5.8%(419/7 189) and 3.7%(301/8 240) to 11.9% (3 342/28 122) and 6.2% (1 706/27 401) in male and female respectively(P<0.01). The mean FPG level for male in 2004 increased from (4.6±1.2) mmol/L to (5.1±1.6) mmol/L in 2012, and from (4.5±1.0) mmol/L to (4.8±1.2) mmol/L for female. Pearson correlation analysis showed that FPG was correlated with gender, age, year, TG and TC (r= -0.078, 0.199, 0.062, 0.167 and 9.138, respectively, all P<0.001). The related independent factors for abnormal blood glucose were gender, age, TG and TC (theOR and 95% CI was 0.628(0.608, 0.649), 1.051(1.050, 1.053), 1.237(1.227, 1.247), 1.164(1.146, 1.182),respectively, all P< 0.01).

The FPG levels and abnormal detection rates in Tianjin urban residents continues to rise, especially with higher trend for male than female, which is associated with age, TG and TC levels.

To investigate the association between physiological serum bilirubin concentration and duration of type 2 diabetes.

A total of 1 272 patients with type 2 diabetes admitted to the Department of Endocrinology of Ningbo First Hospital from January 2013 to June 2015 were included for the study. Clinic parameters were collected from electronic medical records. All subjects were classified into four groups by diabetes duration quartiles (<5 years, 5-9 years, 10-14 years and ≥15 years). The adjusted concentration of three types of bilirubin were calculated and compared using covariance analysis. Pearson correlation analysis and multiple linear regression analysis were adopted to examine the relationship between duration of diabetes and serum bilirubin.

With increase of diabetes duration from the lowest quartiles to the highest quartiles, serum total bilirubin, direct bilirubin and indirect bilirubin concentration tended to decrease. This trend persisted after adjustment for age, gender, hemoglobin, smoking, drinking, blood pressure, lipid profile, weight, ALT, AST, HbA_1c and statin use. The adjusted mean concentration of total bilirubin from the lowest quartiles to the highest quartiles for diabetes duration was 13.26, 12.36, 12.07 and 11.71 μmol/L ( F=4.36, P=0.005). The direct bilirubin was 5.01, 4.67, 4.47 and 4.35 μmol/L ( F=4.63, P=0.003).The indirect bilirubin was 8.25, 7.69, 7.60 and 7.37 μmol/L ( F=2.96, P=0.033). Pearson correlation analysis showed that total bilirubin concentration (r=-0.241, P<0.01), direct bilirubin concentration (r=-0.23, P<0.01), and indirect bilirubin concentration (r=-0.21, P<0.01) were inversely correlated with duration of diabetes. Multiple linear regression analysis showed that an increment of one year in diabetes duration was associated with 0.087 mmol/L decrease in total bilirubin, 0.037 mmol/L in direct bilirubin and 0.051 mmol/L in indirect bilirubin separately.

Serum bilirubin concentration is negatively correlated with duration of type 2 diabetes mellitus in Chinese patients.

To investigate the effect and mechanism of miR-92a in glucose-induced endothelial cells dysfunction.

Primary human umbilical vein endothelial cells were stimulated by different concentration (5 mmol/L and 30 mmol/L)of glucose. The effect of the miR-92a inhibitor was observed by using lipofection transfection. The cells were divided into 4 groups: blank control group (Con), high glucose group (HG), transfecting negative control group (NC) and transfecting miR-92a inhibitor group(IN). The level of miR-92a was detected by qRT-PCR and florescence observation. Hoechst staining was used to investigate the change of nucleus. MTS was applied to observe cell activity. The level of caspase-3 and cleaved caspase-3 protein level were analyzed by Western blotting.

Compared with the Con group, HUVECs treated with high concentration of glucose have induced significant morphologic damage and apoptosis. The miR-92a level of HG group was increased for 31% (1.31±0.37 vs 1, t=1.93, P<0.05) and cell activity was decreased for 19% ((81%±2%) vs 1,t= -29.85 , P<0.01) ,while caspase-3/cleaved caspase-3 protein level was increased for 24% (0.31±0.07 vs 0.25±0.02,t=2.18, P<0.05). In contrast, compared with HG group, there were significant alleviation on morphologic damage and apoptosis in IN group. Cell activity of IN group was increased for 9% than that in HG group ((88%±11%) vs (81%±2%),t=2.18, P<0.05) and cleaved caspase-3/caspase-3 was reduced for 26% (0.23±0.03 vs 0.31±0.07,t= -2.65, P<0.05).

miR-92a inhibitor may release high-glucose-induced endothelial damage and reduce apoptosis pathway activation. miR-92a maybe the potential treatment target of diabetes vascular complications.

gestational diabetes mellitus (GDM) refers to the abnormality of glucose metabolism that occurs for the first time during pregnancy, excluding diabetes or prediabetes that already exists before pregnancy. Physiological insulin resistance occurs during pregnancy, and GDM occurs when maternal islet function is insufficient to compensate for this resistance^[1]。 Applying the latest International Diabetes and Pregnancy Study Group (IADPSG) diagnostic criteria, the global prevalence of GDM is as high as 17.8%^[2]。 The effects of GDM on both maternal and infant generations are not terminated by termination of pregnancy, and the risk of developing various metabolic-related diseases after delivery is significantly increased.

farnesoid X receptor (FXR), also known as bile acid receptor, belongs to a member of the nuclear receptor subfamily 1 group H member 4 (NR1H4) and is a ligand-activated transcription factor. As an endogenous ligand of FXR, bile acids are not only important substances in the digestion and absorption of lipids, but also can be used as signaling molecules to transmit information through FXR-mediated signaling pathways and participate in the regulation of metabolism in vivo. FXR not only plays an important role in regulating bile acid and glucose and lipid metabolism in the body, but also is related to a variety of metabolic diseases, and is expected to become the target of disease treatment. The mechanism of action of FXR regulating body metabolism and the application of FXR agonists are reviewed.

The epidemic of type 2 diabetes (T2DM) and malignant tumors has become a major public issue affecting human health. In 2013, there were 382 million diabetic patients worldwide, and the International Diabetes Federation (IDF) predicts that the number of patients will reach 592 million by 2035^[1]； There were 14 million malignant tumor patients worldwide in 2012, and the WHO predicts that the number of patients will reach 22 million by 2032, with most new cases and deaths coming from developing countries^[2]With the aging of the population and the change of lifestyle brought by economic development, the global incidence of T2DM and malignant tumors is entering a "blowout" stage. The relationship between T2DM and malignant tumors has been studied for decades. With the deepening of research, T2DM has been confirmed to be prone to malignant tumors, and its epidemiological characteristics are as follows.

Autoimmune pancreatitis (AIP) is autoimmune-induced chronic pancreatitis with characteristic laboratory, histological, and morphological changes. The clinical symptoms of AIP are diverse, including symptoms of chronic pancreatitis such as epigastric pain, diarrhea, weight loss and obstructive jaundice, and extrapancreatic symptoms such as sclerosing cholangitis, dacryoadenitis, retroperitoneal fibrosis and diabetes. This article reviews the related studies of AIP complicated with diabetes to help clinicians identify and treat diabetes secondary to AIP in diabetic patients. This article will elaborate from the epidemiology, pathogenesis, clinical symptoms, imaging, histopathology, laboratory tests, diagnosis and differential diagnosis, and treatment of AIP with diabetes mellitus.

Elderly diabetic patients are those with diabetes aged ≥60 years, including those diagnosed before and after the age of 60 years^[1]。 With the acceleration of population aging, the improvement of people's living standard and the change of lifestyle, the prevalence of diabetes in the elderly increases rapidly. Diabetic patients will still suffer from diabetes for 10 to 30 life years after old age. Therefore, it is of great clinical and social significance to actively prevent and treat diabetes and its complications in the elderly.

In recent years, sodium glucose co-transporter 2 inhibitor (SGLT-2i) has received extensive attention as a class of new drugs for the treatment of T2DM. However, SGLT-2i promotes urinary glucose excretion by selectively inhibiting sodium-glucose cotransporter (SGLT), and its unique mechanism of action is to exert hypoglycemic effect independently of insulin.