Volume 04 · Issue 07 · 2012

Numerous studies (especially meta-analyses) have shown that diabetes increases the risk of cancer. Since most of the massive data on the diagnosis and treatment of diabetic patients worldwide can be stored through electronic registries, researchers can use these managerial databases to analyze the risk of insulin, oral hypoglycemic drugs and cancer^[1]。 Scholars have published some results that have caused heated debate. For example, the 1999 Journal of the European Diabetes AssociationDiabetologiaPublished 4 reports on the use of insulin, especially insulin glargine, and cancer^[2,3,4,5]and 1 editor's note^[6], causing heated debate in academic circles; 2011 Journal of the American Diabetes SocietyDiabetes CarePublished a large Kaiser Permanente Northern California Diabetes Registry study from the United States, reporting that using pioglitazone for more than 2 years may increase the risk of bladder cancer^[7]。 The U.S. Food and Drug Administration (FDA) therefore requires pioglitazone manufacturers to indicate on drug labels that "long-term use of pioglitazone may cause bladder cancer"^[8]。 On the other hand, studies have also reported that the use of metformin can reduce the risk of cancer^[9]。 Although these studies have the limitations of observational studies and lack of validation by large clinical trials, they inevitably have a significant impact on the clinical use of drugs for diabetic patients-such as avoiding drugs that may cause cancer and using drugs that may have anticancer effects. hypoglycemic drugs. Therefore, some scholars question whether observational research is providing answers or creating problems^[10]?

At present, the diagnosis and treatment concept of diabetes has undergone a fundamental change from focusing on the possible hyperglycemia in the past to focusing on the possible diabetic complications now. The biggest harm of diabetes is complication, which is the main cause of diabetes disability and premature death. The effective means to fundamentally improve the quality of life of diabetic patients is the early diagnosis and reasonable control of diabetes. The occurrence and development of complications are directly related to the control of blood glucose level. Correct assessment of blood glucose level is the key to solve the problem. However, glucose measurement can only reflect the immediate blood glucose level, which can't meet the needs of modern clinical application. Therefore, exploring the detection index that can truly reflect blood glucose level has become the focus of academic attention.

On the morning of June 10, 2012, at the 72nd Annual Meeting of the American Diabetes Society (ADA), the Banting Award for Achievement in Medical Sciences was awarded to Bruce, Professor of Cell Biology and Medicine at Harvard Medical School, at the Pennsylvania International Convention and Exhibition Center in Philadelphia, USA. M. Spiegelman. In his acceptance speech, Professor Spiegelman focused on the hot spot "brown fat" in recent years, from explaining the characteristics of fat classification to how to research, discover and identify the new hormone Irisin and discuss its significance. The content is rich, the evidence is sufficient, the thinking is broad and the vision is beautiful. Wonderful academic reports are like a marching horn, leading scholars from all over the world into a new era of metabolic disease treatment!

To assess the status of glycemic control and treatment of type 2 diabetes mellitus (T2DM) in China.

This was a cross-sectional study carried out all over the China. A total of 400 and 435 hospitals were involved in 2009 and 2010 investigation respectively. Type 2 diabetic outpatients on oral antidiabetic drugs (OADs) only or OADs combined with insulin treatment were included. Data on general characteristics, treatment regimen, complications and blood glucose levels were collected using a questionnaire interview. A glycated hemoglobin A1c(HbA1c) of less than 6.5% was set as treatment target. Data were analyzed using descriptive statistics.

In 2009 and 2010, 143 123 (aged (59±12) years) and 172 199 patients (aged (59±11) years) were enrolled, with 63.8% and 54.7% of the patients with at least one concomitant disease respectively. In 2009, the overall glycated hemoglobin A1c(HbA1c) level was 8.0%±2.0%, and 79.7% of the patients failed to reach the target of HbA1c(<6.5%). Patients treated with OADs only had a HbA1c of 7.7%±1.9%, and 76.6% of them failed to reach the target. Overall HbA1c level in 2010 was 7.9%±1.8%, 83.2% of the patients failed to reach the target of HbA1c(<6.5%). Among all patients treated with OADs-only in both years, the mean values of HbA1c, fasting blood glucose and postprandial glucose did not reach the target under all treatment regimens.

The overall glycemic control in Chinese type 2 diabetic patients is poor. More complex diabetic management are needed to improve blood glucose management.

To investigate glycemic control, treatment regimen and other relevant characteristics in patients with type 2 diabetes mellitus(T2DM) treated with oral antidiabetic drugs (OADs) only in urban areas of China.

A total of 414 hospitals from 81 cities across China participated in the survey. Outpatients with T2DM on OADs treatment only were eligible for this study. General information of patients, medical history for T2DM, laboratory investigations and treatment regimen were collected from July to September in 2010. Logistic regression analysis was applied in the correlation analysis of glycemic control.

A total of 97 315 eligible patients with T2DM were included in this study, with a mean age of (59±11) years and a mean diabetes duration of (5±4) years. The mean glycated hemoglobin A1c(HbA1c) level of all patients was 7.7%±1.6%. Total of 35.1%(34 154 cases) and 17.9%(17 380 cases) of the patients had a HbA1c<7.0% and <6.5%, respectively. Among all the patients, 13.1% (12 748 cases) complicated with at least one macrovascular disease, and 15.1%(14 694 cases) with at least one microvascular disease. Of the patients with macrovascular complication(s), 27.3% achieved optimal glycemic target (HbA1c<7.0%), it was lower than that in patients without macrovascular complication(s) (36.3%). Similarly, 25.2% of the patients with microvascular complication(s) achieved optimal glycemic target and it was lower than that in patients without microvascular complication(s) (36.9%). Among all the OAD treatment regimens, two kinds of OADs (51.3%) and one OAD (34.5%) were most frequently used. It's found that 40.6%, 33.7%, 27.0% and 24.5% of the patients receiving one OAD, two OADs, three OADs and four or more OADs achieved glycemic control target, respectively. The most frequently used OADs were biguanides(30.8%), sulphonylureas(24.6%) and glinides(21.1%). Among the combined treatment regimens, 23.7% were biguanides plus sulphonylureas, 13.6% were biguanides plus glinides. Regression analysis showed that male, duration of diabetes, kinds of OADs, body mass index, combined with macro or micro vascular diseases were inversely associated with rate of achieving HbA1c target (OR=1.025, 0.855, 0.868, 0.852, 0.789, 0.698, all P<0.01).

The status of glycemic control of patients with T2DM treated with OADs only is undesirable in China. Efforts in providing professional education on management of T2DM and adjusting treatment regimen in time are needed to improve glycemic control.

Analysis of the detection rate and distribution of various malignant tumors in patients with type 2 diabetes mellitus, to improve the early detection of tumors in those patients.

A total of 8772 hospitalized patients with type 2 diabetes in Affiliated Jiangmen Hospital of Sun Yat-sen University were recruited from 2004 to 2010. From which, 542 patients with malignant cancer which was preexisting diabetes mellitus or coexisting diabetes. The cancers distribution was analyzed.

The detection rate of cancer in hospitalized patients with type 2 diabetes was about 6.2%(542/8772), Age≥50 years was the risk factor to happen malignancy in type 2 diabetes(OR=1.666, 95%CI: 1.269-2.186), and there was a statistical difference of the prevalence of malignancy between different gender with type 2 diabetes(OR=1.231, 95%CI: 1.034-1.467). The top three cancers in the 542 diabetic patients with malignancy were colorectal cancer(16.1%, 87/542), lung cancer(15.5%, 84/542), and liver cancer(13.8%, 75/542). With male to female ratio 1.18∶1. The top three cancer in male were liver cancer(20.1%, 59/293), lung cancer(19.8%, 58/293), and colorectal cancer(14.7%, 43/293), whereas in female, which were colorectal cancer (17.7%, 44/249), endometrial cancer (11.2%, 28/249), and breast caner(10.8%, 27/249). In the 542 patients, aged≤40 years, 41-50 years, 51-60 years, 61-70 years, >70 years accounted for 2.0%(11/542), 11.1%(60/542), 33.8%(183/542), 30.8%(167/542) and 22.3%(121/542), respectively. For the diabetic history <2 years, 2-5 years, 5-10 years and>10 years after the diabetes onset accounted for 44.6%(242/542), 31.4%(170/542), 17.2%(93/542)and 6.8%(37/542) respectively. The distribution of all malignant tumors were not identical in different age and different time windows.

In type 2 diabetic patient, the detection of malignancy is particularly elevated with aged, and at the time of early diabetic time window. The detection rate of colorectal cancer, lung cancer, liver cancer in diabetic patients is higher.

To observe the efficacy and safety of α-lipoic acid(ALA) on diabetic peripheral neuropathy(DPN).

All of 284 type 2 diabetic inpatients with DPN in sixteen hospitals were selected from August 2009 to March 2010. The patients received ALA 600 mg/d in 250 ml normal saline by intravenous drip infusion once a day for 10-14 days. Before and after the management, total symptom score(TSS) was used to evaluate the nervous symptoms, including numbness, sting sensation, burning sensation and hypoesthesia.The clinical data before and after treatment was compared using paired t test.

Total of 269 patients completed the trial. After at least 10-day treatment, the TSS decreased significantly compared with that at the baseline(3.4±2.2 vs 6.7±2.6, P<0.01). The symptom scores of numbness, sting sensation, hypoesthesia and burning sensation reduced significantly after ALA treatment(t=20.82, 16.29, 16.82, 22.49, respectively, all P<0.01). About 99.2%(267/269) doctors and 97.8%(263/269) patients were satisfied with the treatment effect.One patient complained of dizziness and one presented cutaneous eruption, the symptoms were mild and recovered spontaneously. The efficacy of ALA was positively correlated with course of treatment, the severity of nervous symptoms, decline of blood glucose and blood glucose level before treatment (r=0.125, 0.602, 0.150, 0.172, all P<0.05), and negatively correlated with the urine microalbuminuria (r=-0.200, P<0.01).

α-lipoic acid can improve the symptoms of DPN in type 2 diabetic patients effectively and safely, especially for numbness, sting sensation.

To investigate the alterations of expression and imprinting status of insulin growth factor 2 (IGF2) and H19 gene in diabetes mellitus patients' placenta.

66 pregnant women delivered between February to September 2009 were inrolled, 33 cases with diabetes mellitus (Patient group, GDM 23 cases (NDDG (National Diabetes Data Group) criteria), DM 10 cases) and 31 cases with normal glucose tolerance(Control group). RNA and DNA were extracted from the placenta of all objects. Real-Time PCR was performed to compare the expression of IGF2 and H19 gene in different groups, and RELP was used to identify the alternations of imprinting status . Statistical analyses were done by SPSS software (V10.0, SPSS Inc, USA). P values <0.05 were considered statistically significant.

(1) Compared with the control group, the expression of IGF2 gene was significantly higher (2.4±1.2 vs 1.9±0.8, t=-2.2, P<0.05)in the patients groups. The expression ofH19 gene was higher (7.2±3.6 vs 6.1±2.7, t=-1.5, P>0.05) in the patient group compared with that of control group, whereas there were no significant difference between them. (2) The genetic heterogeneity ofIGF2 gene Apa1 locus was 60.9% (39/64), and the geneticheterogeneity of H19 gene Rsa1 locus was 34.4%(22/64). (3) The expression of IGF2 gene Apa1 locus and H19 gene Rsa1 locus was no loss of imprinting in the patient group and the control group.

(1) The expression of IGF2 gene is increased in the placenta of diabetes mellitus patients. (2) The expression of IGF2 and H19 gene in the placenta of gestational hyperglycemia patients has no loss of imprinting.

To explore the role of umbilical cord blood leptin in intrauterine growth so as to provide evidence for early intervention for metabolic diseases.

Two hundred and sixty-six healthy newborns (140 males, 126 females, gestational age>37 weeks) and their healthy mothers were enrolled in this study. Birth weight, birth length, head circumference, and ponderal index were measured before the neonates were assigned to low birth weight (LBW), normal birth weight (NBW) and high birth weight (HBW) groups. The level of leptin in the umbilical cord plasma was assayed by radioimmunoassay (RIA). Student'st test, Pearson correlation analysis and multi factor line regression were used for data analysis.

Leptin was significantly decreased in the LBW group ((7±5) μg/L) and increased in the HBW group ((15±7) μg/L) when compared with the NBW group ((9±5) μg/L) ( t values were 3.216 and -4.026, respectively; both P<0.05). Leptin in female neonates ((11±6) μg/L) was significantly higher than that in male neonates ((8±5) μg/L) (t=-3.800, P<0.01). In Pearson correlation analysis, leptin was positively correlated with birth weight, height, body mass index (BMI) and placental weight (r values were 0.391, 0.280, 0.361 and 0.323, respectively; all P<0.01). After adjustment for maternal age, pre-pregnancy BMI, newborn gender and gestational age, leptin showed a liner relationship with birth weight.

The level of leptin in umbilical cord blood may be associated with birth weight and could be used as an indicator of intrauterine growth.

To study the effects and potential mechanisms of Forkhead transcription factor O1 (FoxO1) on free fatty acid (FFA) induced insulin resistance (IR) and steatosis.

HepG-2 cells were induced to a status of insulin resistance by being exposed to 5.0×10^-4 mmol/L palmitic acid (PA) for 24 hours. HepG-2 cells were devided into 4 groups, the HepG-2 cell group cultured with normal medium, the palmitic acid group, the blank plasmid group, and the siFoxO1 group. PA was added to normal medium to a final concentration of 5.0×10^-4 mol/L. The expression levels of FoxO1 in different groups were detected by RT-PCR. The glucose consumption was detected by using glucose oxidase method. MTT method was used to detect the proliferation of HepG-2 cells. Steatosis of HepG-2 cells was observed by Oil Red O staining. The mRNA and protein expression of SREBP-1c were determined by RT-PCR and Western blot.

Compared with control, the glucose consumption of cells cultured with FFA was significantly reduced(1.17±0.56 vs 4.31±0.21, t=10.587, P<0.01). Cellular lipid accumulation, the expressions of FoxO1 mRNA(0.78±0.10 vs 0.51±0.12,t=3.629, P<0.05), SREBP-1c mRNA (0.71±0.17 vs 0.25±0.08,t=6.290, P<0.05), and the protein of SREBP-1c (0.69±0.10 vs 0.41±0.07,t=4.797, P<0.01)was increased .After transfected by siFoxO1 plasmids using Lipofectamine 2000, the mRNA expression of FoxO1 (0.38±0.06 vs 0.78±0.10,t=7.164, P<0.01), SREB9-1c (0.45±0.13 vs 0.71±0.17,t=2.479, P<0.05) and the SREBP-1c protein expression (0.41±0.06 vs 0.69±0.10,t=4.797, P<0.01) were significantly decreased after tranfected by siFoxO1 plasminds, whereas the glucose consumption obviously the glucose consumption obviously increased(2.26±0.41 vs 1.17±0.56,t=3.144, P<0.05). The cellular lipod accumulation was decrease after transfected by siFoxO1. There was no remarkable difference between the palmitic acid group, and the blank plasmid group.

Inhibiting the expression of FoxO1 could improve FFA-induced IR and steatosis by down-regulating SREBP-1c expression.

To investigate the effect of rituximab on cell cycle, proliferation and apoptosis of Ramos B lymphocytes in the presence of high levels of glucose.

Ramos B lymphocytes were treated with or without rituximab in the presence of different concentrations of glucose (5.5, 10.0, 15.0 and 25.0 mmol/L)(Glucose group and Rituximab group). The cells were cultured for 3-7 days. Cell cycle and apoptosis were studied by flow cytometry. Cell proliferation was measured by counting the cells using a hemocytometer after trypan blue staining. Paired t test was applied when data were compared between the two groups.

The numbers of B cells in 5.5, 10.0, 15.0 and 25.0 mmol/L glucose groups were (1.96±0.41)×10^6, (3.49±0.51) ×10^6, (3.44±0.67) ×10⁶ and (3.04±0.52) ×10^6, respectively; the percentages of apoptotic cells were 5.0%±0.9%, 4.0%±0.8%, 6.2%±1.8% and 7.6%±1.3%, respectively; the percentages of cells in S phase were 32%±6%, 41%±8%, 40%±7% and 36%±6%, respectively. The numbers of B cells in rituximab groups with increasing concentrations of glucose were (1.23±0.23)×10^6, (1.52±0.29)×10^6, (1.38±0.23)×10⁶ and (1.06±0.23)×10^6, respectively; the percentages of apoptotic cells were 23.1%±3.2%, 21.2%±4.2%, 24.4%±4.8% and 26.9%±6.0%, respectively; the percentages of cells in S phase were 22%±4%, 28%±5%, 26%±4% and 20%±5%, respectively. Compared with those in glucose group, the B cell proliferation was significantly inhibited (t=9.19, 5.52, 9.75, 14.22, all P<0.01), the apoptosis rates were significantly raised (t=16.62, 12.51, 11.53, 9.12, all P<0.01), and the percentage of cells in S phase increased significantly (t=5.87, 5.19, 9.91, 7.73, all P<0.01) in Rituximab group. Highest cellular proliferation and percentage of cells in S phase were observed in the presence of 10.0 mmol/L glucose. Highest rate of apoptosis occurred in the presence of 25.0 mmol/L glucose.

Rituximab inhibited B cell proliferation by inhibiting cell cycle progression and inducing apoptosis, and the inhibitory effects were most significant in the presence of high levels of glucose.

Sleep, as a necessary process to recover people's physical strength and various physiological functions, plays a vital role. However, with the acceleration of people's life, there are many new problems that threaten sleep, such as Internet addiction and sleep deprivation and sleep disorder caused by work stress. In recent decades, people's sleep time has decreased by 1.5~2.0 h on average, and more than 1/3 of them sleep less than 6 h. Human beings have entered an era of sleep deprivation^[1]。 The survey shows that there are both lack of sleep and excessive sleep problems in China^[2]。 China chronic disease surveillance data in 2007 showed that 35.7% of the survey respondents reported that their sleep quality was poor^[3]。 At the same time that these sleep problems emerged, the prevalence of diabetes gradually increased. Studies have shown that there is a link between sleep and diabetes. The relevant research situation is described as follows.

Polycystic ovary syndrome (PCOS) is a common female endocrine and metabolic disorder, with an incidence of 6% to 10% in women of childbearing age. The current diagnostic criteria were proposed by the European Society for Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM) at the Rotterdam meeting in 2003, that is, it is recommended that the diagnosis of PCOS should meet two of the following three criteria after excluding other diseases: (1) anovulation or thin ovulation; (2) clinical and/or biochemical manifestations of hyperandrogenism; (3) Polycystic ovarian changes. The main manifestations of PCOS are menstrual disorder or amenorrhea, obesity, infertility, polycystic ovarian changes, hyperandrogenemia, elevated ratio of luteinizing hormone (LH) to follicle stimulating hormone (FSH), hyperinsulinemia, etc. There are many causes of PCOS and its pathophysiological changes are extensive. A large number of studies have confirmed the presence of insulin resistance in PCOS patients, and compensatory hyperinsulinemia and hyperandrogenemia caused by insulin resistance play an important role in the pathophysiological changes of PCOS.

Diabetes is currently one of the most common non-communicable diseases in the world. The number of diabetes patients worldwide was 366 million in 2011 and is expected to reach 552 million in 2030^[1]。 The latest epidemiological survey shows that the number of adults with diabetes in China has reached 92.4 million, ranking first in the world^[2]。 Compared with non-diabetic patients, the risk of cardiovascular disease in diabetic patients increases by 2 to 4 times, and up to 50% of diabetic patients have cardiovascular disease. Cardiovascular disease is not only the main cause of death in diabetic patients, but also accounts for more than 85% of the medical expenses of diabetic patients. Although the prevention of cardiovascular diseases is constantly advancing, the incidence and mortality of cardiovascular diseases in the overall population have decreased, but the incidence of cardiovascular events in diabetic patients remains high. The latest research shows that the mortality rate related to cardiovascular events in diabetic patients is still as high as 10 cases/1000 cases per year^[3]。 Therefore, how to more effectively stop the occurrence and development of cardiovascular diseases in diabetic patients is an urgent topic to be solved in diabetology.

Type 2 diabetes is associated with an increased risk of multiple cancers and reduced post-cancer survival. We hypothesized that diabetic patients had a lower survival rate after diagnosis of solid cancer than non-diabetic patients, and that metformin treatment could affect their survival rate.

Insulin resistance is involved in the development of liver cancer, and metformin treatment can reduce insulin resistance. This study aimed to evaluate the effect of metformin treatment on the prognosis of cirrhosis after compensated viral hepatitis C in patients with type 2 diabetes.

Numerous studies have shown that patients with diabetes who take metformin have a reduced risk of cancer. However, the effect scale is difficult to assess because different studies use different between-group controls. To this end, this study aimed to analyze in-depth whether metformin treatment is associated with a decrease in cancer risk and the size of its association.

Type 2 diabetes is associated with an increased risk of cancer. This study aimed to elucidate the relationship between type 2 diabetes mellitus, metformin therapy and malignancy in a Belgian primary healthcare population.

Previous studies have shown that biguanides can reduce the risk of cancer progression. This study aimed to observe the efficacy of phenformin in immunocompromised mice infected with estradiol receptor-positive MCF7 breast cancer cells and receptor triple-negative MDAMB231 breast cancer cells.