Volume 04 · Issue 05 · 2012

The advent of insulin in 1921 brought good news to diabetic patients. Since then, a variety of insulin dosage forms and administration methods have emerged, making type 1 diabetes completely possible to control. However, nearly a century later, the International Diabetes Federation (IDF) and the International Juvenile Diabetes Association (ISPAD) issued joint guidelines in 2011^[1]It is pointed out that the most common cause of death in childhood diabetes worldwide (most of which are type 1 diabetes) is still the lack of access to insulin treatment, and many children die before diabetes is diagnosed. This indicates that the standardized treatment of type 1 diabetes needs to be improved urgently.

Polycystic ovary syndrome (PCOS) is the most common endocrine disease in adolescent girls and women of childbearing age, and it is a common cause of female infertility. Its prevalence is 4% ~8%, and even as high as 25% in some areas^[1]。 The disease is mainly characterized by amenorrhea or thin menstruation, ovulatory disturbances, hyperandrogenicity and polycystic changes of the ovaries. PCOS patients are often accompanied by central obesity, insulin resistance, abnormal glucose tolerance (IGT), abnormal lipid metabolism, and their risk of developing type 2 diabetes mellitus (T2DM) and cardiovascular complications is significantly increased. Since 1980 Burghen et al.^[2]Since insulin resistance was first proposed in patients with PCOS, more and more studies have shown that insulin resistance may be the initiating factor and the central link in the occurrence and development of PCOS. Therefore, for PCOS patients, early detection and treatment of insulin resistance is of great significance.

post transplantation diabetes mellitus (PTDM) refers to the newly occurring diabetes after organ transplantation. It is a common chronic complication after transplantation, which will lead to loss of graft function, easy to combine infection and cardiovascular disease, increase mortality, and seriously affect the prognosis of patients. High age, family history of diabetes, obesity, immunosuppressive regimen, hepatitis C virus (HCV) infection are all high risk factors of PTDM. With the prolongation of transplantation survival, PTDM has become an important factor affecting postoperative survival rate of transplantation patients and has been paid more and more attention.

Diabetes is a chronic wasting disease that seriously endangers human health and affects the quality of life. In China, with the improvement of quality of life, the prolongation of average life span and the change of lifestyle, the prevalence of diabetes is increasing at an alarming rate. The latest research shows that the total number of adult diabetic patients in China has reached 92.4 million, making it the country with the largest number of diabetic patients in the world^[1]。 The treatment of diabetes mainly depends on self-management. In diabetes management, self-blood glucose monitoring (SMBG) is crucial and an important part of comprehensive diabetes treatment.

To investigate KCNJ11 gene mutation in three children with diazoxide-unresponsive congenital hyperinsulinism (CHI) so as to identify genetic mechanism of ATP-sensitive K⁺ channel-hyperinsulinism (KATP-HI) in Chinese children.

Three children with diazoxide-unresponsive CHI and their parents were selected as subjects from January 2008 to December 2009. Polymerase chain reaction (PCR)-DNA direct sequencing was used to analyze the exon of the KCNJ11 gene.

In case 1, a Q235E heterozygous inactivation mutation was found in KCNJ11 gene, although the genotype of the mother was normal (C/C). No mutations were detected in case 2 and 3.

KCNJ11 Q235E mutation could lead to the onset of KATP-HI. Minority of patients with autosomal dominant KCNJ11 mutation may be unresponsive to diazoxide treatment.

To investigate the change of glucose variability and the relationship between glucose variability and the severity of coronary artery stenosis in patients with type 2 diabetes mellitus(T2DM) with acute coronary syndrome(ACS).

A total of 64 hospitalized patients with T2DM and ACS were recruited from November 2010 to October 2011. Thirty cases(19 males and 11 females, aged (60±11) yrs) underwent emergency coronary angiography (group A), and 34 cases(15 males and 19 females, aged (59±10) yrs) in stable condition underwent selective coronary angiography after one week(group B). Twenty T2DM cases without ACS in the same period were set as control group(12 males and 8 females, aged (54±13)yrs). All the participants underwent continuous glucose monitoring(CGM) for 72 hours to evaluate CGMS parameters such as largest amplitude of blood glucose excursion(LAGE), mean amplitude of glycemic excursions(MAGE), standard deviation of blood glucose(SDBG), absolute means of daily differences(MODD), postprandial glucose excursion(MPPGE), the mean postprandial maximum glucose(MPMG). The correlation was analyzed between the parameters and clinical biochemical and the severity of coronary artery stenosis (Gensini score)in T2DM patients with ACS. The measurement data of multiple groups were compared with single factor analysis of variance, and the comparison between two groups was performed with LSD test, correlation analysis with Pearson correlation and multiple stepwise regression analysis.

Compared with control group((5.6±1.5), (2.5±1.0) mmol/L), the levels of MAGE and MPPGE in group A((7.2±2.2), (3.3±1.1) mmol/L) and group B ((6.2±4.4), (3.2±1.4) mmol/L) were higher (F=8.543, 3.465, all P<0.05). LAGE, MAGE, MODD, MPPGE, homeostatic model assessment-insulin resistance(HOMA-IR), C-reactive protein (CRP)were positively related to Gensini score(r=0.463, 0.439, 0.633, 0.595, 0.282, 0.224, all P<0.05), while left ventricular ejection fraction(LVEF)were negatively related to Gensini score(r=-0.579, P<0.01). Multiple stepwise regression analysis indicated that MODD, LVEF and MPPGE were dependent risk to Gensini score(Y=388.629+ 33.794MODD-93.824 LVEF+ 8.531MPPGE).

Glucose variability of the patients with type 2 diabetes increases obviously in the acute phase of ACS. MODD and MPPGE were dependent positively correlated to the severity of coronary artery stenosis in patients with T2DM and ACS.

To investigate the glucose metabolism in 2020 patients of non-endocrinology department.

All adult inpatients of non-endocrinology department were recruited from November 1 to December 30 in 2010. A total of 2020 patients' records were included in this study. Fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PBG) and glycated hemoglobin A1c (HbA1c) of the patients during hospitalization were collected to judge the glucose metabolism. Average data between two groups were compared by independent-samplest test, the frequency in different groups was evaluated by χ ² test.

The detection rate of diabetes in non-endocrinology department was 14.2%, and the detection rate of diabetes and impaired fasting plasma glucose, FBG, 2 h PBG, HbA1c was 40.8%, 87.7%, 1.4%, 10.0%, respectively, in inpatients of non-endocrinology department. The detection rate of HbA1c in diabetic patients was 25.8%. Of the 2020 inpatients, 1.5% were diagnosed with diabetes after being admitted to the hospital. Patients with a FBG ≥5.6 mmol/L but received no further diagnosis amounted to 26.6%. When the patients were grouped according to the age(≤30, >30-45, >45-65, ≥65 years), the detection rate of diabetes increased with the age and there were statistical differences between the groups(χ ²=92.08, P<0.01). The detection rate of diabetes was 22.9% in patients complicated with cardiovascular, the rate was 10.4% in patients without (χ²=54.55, P<0.01).

The detection rate of diabetes and abnormal glucose metabolism in non-endocrinologic inpatients is high, but most of the patients don't receive glucose tolerance test, so the diabetes and abnormal glucose metabolism may be missed diagnosed.

To investigate the effects of metformin and pioglitazone on plasma ghrelin in patients with newly diagnosed abnormal glucose metabolism and abdominal obesity.

From April to September 2010, 39 patients with abnormal glucose metabolism (including impaired glucose tolerance and newly diagnosed type diabetes mellitus, glycated hemoglobin A1c(HbA1c)<7%) and obesity were enrolled in the study. They were randomly assigned to metformin group(500 mg tid,n=20, 15 females and 5 males, aged (51±9) years, MET group) or pioglitazone group (30 mg/d, n=19, 11 females and 8 males, aged (53±7) years, PIO group) on the basis of diet and exercise therapy for 3 months.Three males in PIO group with drawed because of itching and edema. At baseline and after 3 months, plasma glucose, serum insulin and ghrelin levels during oral glucose tolerance test(OGTT, 0 min, 0.5, 1.0, 2.0, 3.0 h), body weight, body mass index(BMI), HbA1c, etc were measured.The t test or Wilcoxon rank-sum test was used for statistical analysis. Partial correlation and multiple regression analysis were performed to examine the association between serum ghrelin levels and influencing factors.

(1)In PIO group, serum ghrelin levels after treatment were OGTT 0 min (1069±467)ng/L, 0.5 h (898±407)ng/L, 1.0 h (812±371)ng/L, 2.0 h (705±328)ng/L and 3.0 h (1059±606)ng/L, respectively. All increased than those before treatment ((905±449), (688±378), (614±358), (572±334)and(720±403)ng/L, Z value was from -2.354 to -3.351, respectively, all P<0.05). (2) In MET group, serum ghrelin levels at OGTT 0 min, 1.0, 2.0, 3.0 h after treatment were (731±241) , (642±208), (525±195), (462±146) and (611± 267)ng/L, respectively. Compared with the ghrelin levels before treatment((731±241) , (642±208), (525±195) , (462±146) and (611±267)ng/L), only the difference at 0 min, 2.0, 3.0 h was statistically significant(allP<0.05). Serum ghrelin levels of MET group at OGTT 0.5, 1.0 and 3.0 h were lower than that of PIO group (Z value was-2.012, -2.006, -2.226, respectively, all P<0.05).

Compared with those in PIO group, patients treated with metformin lose more weight, but their serum ghrelin levels only partially increase at different point OGTT. This may be one of the reasons why metformin controls weight better.

To evaluate the level of urinary mindin in patients with type 2 diabetes mellitus (T2DM), and analyze the association between the renal injury and the lvels of urinary mindin.

Type 2 diabetic patients (n=124) with normoalbuminuria(urinary albumin<30 mg/24 h,n=60), microalbuminuria (30≤urinary albumin<300 mg/24 h,n=32), macroalbuminuria (urinary albumin≥300 mg/24 h, n= 32), and normal control group (n=30) were enrolled.The levels of urinary mindin were measured by using ELISA kits, the serum/urine creatinine, serum urea nitrogen, cystatin C, blood glucose, glycated hemoglobin, C-peptide and other clinical indicators were measured by conventional methods.The estimated eGFR level was calculated using the formula proposed by Macisaac, and statistical analysis were made with the SPSS 13.0 software.

The levels of urinary mindin in the T2DM group were significantly higher than those of the normal control group which were increased gradually with the increases of albuminuric levels.The urinary mindin levels in patients with normoalbuminuria, microalbuminuria, macroalbuminuria and normal controls were 161(119~255), 332(181~445), 426(230~937) and 93(51~121) ng·ml^-1·μmol^-1·L^-1, respectively(F=30.196, P<0.05). Urinary mindin was correlated with urinary albumin(r=0.453, P<0.05); The level of urinary mindin was positively correlated with serum urea nitrogen(r=0.426, P<0.05), creatinine(r=0.236, P<0.05), cystatin C(r=0.383, P<0.05), blood glucose(r=0.344, P<0.05), 24 h-urinary albumin(r=0.453, P<0.05) and the course of diabetic disease(r=0.511, P<0.05), which was negatively correlated with eGFR(r=-0.383, P<0.05); Logistic regression analysis showed that the urinary mindin might be one of the high-risk factors to identify renal injury in patients with T2DM.

This study indicates that urinary mindin might be closely related to diabetic nephropathy and in participates in the progress of diabetic nephropathy; urinary mindin can reflect the early course of renal injury and be associated with renal function. Urinary mindin needs to be investigated as a potential marker for diabetic nephropathy early diagnosis and indicator of curative effect.

To investigate the association of the ghrelin gene Arg51Gln and Leu72Met polymorphisms with type 2 diabetes mellitus and lipid metabolism in Dongxiang, Hui, Han population in Gansu province.

From October 2008 to February 2010, 744 patients(386 males and 358 females) with type 2 diabetes mellitus(T2DM group) from Gansu Provincial People's Hospital, People's Hospital of Linxia and Dongxiang County Hospital were recruited, including 242 cases of Dongxiang nationality, 242 cases of Hui nationality, 260 cases of Han nationality. Total of 673 healthy volunteers from above 3 hospitals at the same time were regarded as the control group, including 223 Dongxiang nationality, 203 Hui nationality and 247 Han nationality.Ghrelin gene Arg51Gln and Leu72Met polymorphisms were analyzed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Plasma glucose, lipids and other clinical indicators were detected. The genotype and allele frequency distribution were compared with the χ ² test, while the correlation of genotype and plasma lipid levels were compared using correlation analysis and logistic regression analysis.

(1)The carriers of A (GA+ AA) had a higher risk tendency in T2DM group than the non-carriers in Arg51Gln, and the carriers of A (CA+ AA) had a higher risk tendency than the non-carriers in Leu72Met, but the differences were no statistical significance(all OR>1, allP>0.05). No correlations were found in Arg51Gln, Leu72Met polymorphisms with T2DM after adjusted the gender, age, body mass index(BMI) and blood pressure, etc(allP>0.05). (2)In the T2DM group, Arg51Gln genotype(GA+ AA) in Dongxiang and Hui population was positively correlated with low-density lipoprotein cholesterol (LDL-C) level after adjusted for gender, age, BMI and total cholesterol(r=0.406, 0.377, all P<0.05). Leu72Met genotype(GA+ AA) in Dongxiang and Hui population was positively correlated with total cholesterol level after adjusted for gender, age, BMI and LDL-C(r=0.189, 0.208, all P<0.05).

Arg51Gln, Leu72Met polymorphisms in ghrelin gene are probably unrelated to T2DM in Dongxiang, Hui and Han population, but might related to lipid metabolism in Dongxiang and Hui population.

To investigate the effects of lipopolysaccharide (LPS) on autophagy and apoptosis of rat insulinoma INS-1 cells and the underlying mechanisms.

INS-1 cells at log growth phase were treated with 0.1, 1.0 or 10.0 mg/L LPS for 24 h, then sulforhodamine B(SRB) assay was carried out to evaluate the effect of LPS on cell viability, and reactive oxygen species (ROS) were detected by dichlorofluorescein-diacetate (DCFH-DA) fluoro-probe. The autophagy marker microtubule-associated protein 1 light chain 3 (Map1LC3-Ⅱ) on the membrane of autophagosomes and the apoptosis marker cleaved poly ADP ribose polymerase (PARP) were detected by Western blotting analysis. The autophagy essential gene Atg7 was silenced via siRNA-mediated RNAi method, then cells were treated with 1.0 mg/L LPS for another 24 h. Atg7, Map1LC3-Ⅱ and cleaved PARP were detected by Western blotting analysis. INS-1 cells were treated with 400 μmol/L N-acetylcysteine (NAC). And 1 h later the cells were treated with 10.0 mg/L LPS for another 24 h. Map1LC3-Ⅱ and cleaved PARP were detected with Western blotting methods. Differences between groups were calculated with analysis of variance and t test.

Compared with the control group(0.755±0.030), the cell viabilities significantly decreased in 0.1, 1.0 and 10.0 mg/L LPS groups (0.658±0.042, 0.658±0.015, 0.634±0.029, respectively, F=30.98, P<0.01). Compared with the control group(0.447±0.012), the protein levels of Map1LC3-Ⅱ significantly increased in 0.1, 1.0 and 10.0 mg/L LPS groups (0.992±0.030, 0.949±0.020, 0.982±0.013, respectively,F=525.79, P<0.01). Compared with the control group (0.055±0.001), the levels of cleaved PARP significantly increased in 0.1, 1.0 and 10.0 mg/L LPS groups (0.313±0.007, 0.390±0.011, 0.500±0.033, respectively,F=327.093, P<0.01). A remarkable increase of ROS was detected in INS-1 cells treated with 10.0 mg/L LPS for 24 h. Compared with the control, the protein levels of Atg7, Map1LC3-Ⅱ and cleaved PARP significantly decreased inAtg7 siRNA transfection group (t=156.069, 123.154, 103.246, all P<0.01). Compared with LPS 10.0 mg/L group, the protein level of Map1LC3-Ⅱ and cleaved PARP significantly decreased in 10.0 mg/L LPS + NAC group(t=66.37, 26.84, P<0.01).

LPS induces autophagy and apoptosis in INS-1 cells, and autophagy promotes apoptosis herein. Reactive oxygen species are involved in autophagy and apoptosis in INS-1 cells induced by LPS.

The incidence of two chronic diseases, diabetes and osteoporosis, is increasing year by year. Epidemiological studies have found that elderly patients with diabetes have an increased risk of fracture^[1]More scholars have begun to pay attention to this phenomenon. Due to the complex pathogenesis of diabetes combined with osteoporosis, the research results are inconsistent. Risk factors for an increased risk of fractures due to diabetes include both skeletal and non-skeletal factors. The latter mainly include the number and type of falls, chronic complications of diabetes (such as loss of vision, kidney damage, nerve damage, and loss of skeletal muscle strength), and side effects of drugs. But the most important risk factor is the bone itself, mainly a decrease in bone density or bone quality^[2]。 It has been established that patients with type 1 diabetes, whether adults or children, have reduced bone density and increased fracture risk; However, in type 2 diabetic patients, although the risk of fracture increases, the bone mineral density does not decrease significantly^[3,4]。 Despite inconsistencies in bone density, bone mass varies in different types of diabetes, leading to an increased risk of fragile fracture and inadequate bone regeneration after fracture^[5]。 Therefore, in diabetes, impaired bone mass is a key point of increased fracture risk, but the mechanism is not clear^[6]。

Incretins are a group of gastrointestinal hormones consisting primarily of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Compared with intravenous glucose, oral administration of equal amounts of glucose can promote more insulin secretion, so the effects of GLP-1 and GIP as effectors of intestinal hypoglycemic effect are evident. Patients with type 2 diabetes have reduced GLP-1 levels to varying degrees. Artificially increasing GLP-1 levels in the body, including injection of GLP-1 receptor agonists and oral administration of GLP-1 degrading enzyme dipeptidyl peptidase IV (DPP-4) inhibitors, can well promote insulin secretion and maintain blood glucose homeostasis^[1,2]。

Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia caused by a variety of genetic factors and environmental factors. Recent studies have found that β-cell-specific zinc transporter 8 (ZnT8) is both a major self-target antigen in type 1 diabetes^[1]Which encodes a geneSLC30A8It is also a genetic marker of type 2 diabetes^[2], indicating that ZnT8 has a dual role in diabetes. In recent years, the research related to ZnT8 has made great progress. This paper reviews the latest research on the clinical significance and mechanism of ZnT8 in type 1 diabetes and type 2 diabetes.

In recent years, the number of diabetic patients in the world has increased rapidly, and the prevalence of diabetes in China is also high. The control and management of diabetes are facing severe challenges^[1,2]。 Compared with the Caucasian population, the Chinese diabetic population is mainly type 2 diabetes, and it has the characteristics of severe islet β cell function damage in the early stage of disease, obvious insulin secretion loss in the first phase, and high proportion of patients with fasting and postprandial blood glucose not meeting the standard at the same time^[3,4]。 Type 2 diabetes is a progressive disease. With the progression of the disease, when patients cannot achieve satisfactory hypoglycemic efficacy through lifestyle intervention and oral hypoglycemic drugs, insulin therapy needs to be initiated.

As one of the most common complications of diabetes, the incidence of diabetic neuropathy is increasing year by year. Diabetic mononeuropathy is a special type of peripheral neuropathy, which is rare in clinic. It can involve somatic nerves and cranial nerves, accounting for 17.9% of diabetic peripheral neuropathy^[1,2,3], easily misdiagnosed. A case of diabetes complicated with unilateral recurrent laryngeal neuropathy admitted to our department in January 2012 is reported as follows.

Women with polycystic ovary syndrome have a higher incidence of diabetes and dyslipidemia. This study aimed to investigate the role of different metabolic pathways in the development of diabetes mellitus in rats with polycystic ovary syndrome induced by high androgen and high fat diet.

In order to improve the risk of cardiovascular disease in patients, overweight and obese individuals are currently encouraged to lose 5% to 10% of their body weight. However, there is limited evidence to support this recommendation, especially for patients with type 2 diabetes.

To elucidate the combined effects of forkhead transcription factor 1 in the hypothalamus and pancreas, the researchers created a forkhead transcription factor 1 gene knock-in (KI) mouse model.

Metreptine can effectively improve metabolic control in patients with lipid metabolism disorders, but its efficacy has not been demonstrated in obese patients with concomitant type 2 diabetes.

In this study, 16 patients with morbid obesity were divided into insulin-sensitive group and insulin-resistant group based on the insulin resistance index of steady-state model. The contents of subcutaneous fat, mesenteric fat and omental fat in abdomen were compared between the two groups. The results confirmed that the activity of adenosine monophosphate-activated protein kinase was decreased in the insulin resistant group. In the omental fat of the insulin resistant group, the expression of various inflammation-related genes was increased, while the peroxisome proliferator-activated receptor gamma coactivator 1 α andNamptGene expression decreased. In contrast, the expression of protein tyrosine phosphatase 1b, vascular endothelial growth factor alpha, gamma interferon, plasma plasminogen activator inhibitor-1 and nitric oxide synthase-2 increased in abdominal subcutaneous adipose tissue in these patients, but these indicators did not change in omental fat. Only angiotensinogen and CD₄⁺mRNA levels were increased in both omental fat and subcutaneous fat in the insulin resistant group. Expression of tumor necrosis factor alpha is increased only in mesenteric fat.

piceatannol is a natural stilbene that is structurally similar to resveratrol. Although resveratrol has been used to treat obesity, the mechanism of action of piceatannol in adipose tissue formation and related diseases remains unclear.