Circular RNAs in stem cells: from basic research to clinical implications.

Circular RNAs (circRNAs) are a special class of endogenous RNAs with a wide variety of pathophysiological functions via diverse mechanisms, including transcription, microRNA (miRNA) sponge, protein sponge/decoy, and translation. Stem cells are pluripotent cells with unique properties of self-renewal and differentiation. Dysregulated circRNAs identified in various stem cell types can affect stem cell self-renewal and differentiation potential by manipulating stemness. However, the emerging roles of circRNAs in stem cells remain largely unknown. This review summarizes the major functions and mechanisms of action of circRNAs in stem cell biology and disease progression. We also highlight circRNA-mediated common pathways in diverse stem cell types and discuss their diagnostic significance with respect to stem cell-based therapy.

The Relationship Between Food Consumption and Bowel Symptoms Among Patients With Rectal Cancer After Sphincter-Saving Surgery.

Dietary self-management is an important strategy for controlling bowel symptoms after sphincter-saving surgery; however, the dietary factors influencing bowel symptoms are not completely clear. This study aimed to explore the relationship between the specific consumption of food components and bowel symptoms. This study applied a cross-sectional study design. Using convenience sampling, a total of 169 patients with rectal cancer after sphincter-saving surgery were selected from a tertiary hospital. Data were collected through three questionnaires, including general and treatment-related questionnaires, the Memorial Sloan Kettering Cancer Center (MSKCC) bowel function scale-Chinese version, and the Food Frequency Questionnaire. Multiple linear regression analysis was used to analyze the collected data. It was found that the consumption of fruit, cholesterol, and protein and the interaction of cereals and milk products were the main dietary factors affecting bowel symptoms in patients after sphincter-saving surgery. The consumption of protein and fruit was negatively correlated with the symptoms of frequent and urgent defecation, and the consumption of fruit and protein was negatively correlated with general bowel function. The consumption of fruit was negatively correlated with the abnormal feeling of defecation, and the interaction between cereals and milk products was positively correlated with the abnormal feeling of defecation. The results of this study provide evidence for medical staff to further develop scientific dietary education programs to relieve bowel symptoms and promote the quality of life of patients in the future. More research is also needed to explore the mechanisms of the effects of different food components on bowel symptoms in patients after sphincter-saving surgery in the future.

The experience of dealing with defecation dysfunction by changing the eating behaviours of people with rectal cancer following sphincter-saving surgery: A qualitative study.

AIM: To explore the experience of dealing with defecation dysfunction by changing the eating behaviours of people with rectal cancer following sphincter-saving surgery. DESIGN: The descriptive qualitative design was applied. METHODS: Individual semi-structured interviews were conducted with 36 purposively selected rectal cancer survivors who had experienced sphincter-saving surgery. All interviews were recorded and transcribed verbatim. The thematic analysis was used to structure the data analysis. RESULTS: Three major themes, namely "have motivations to change diet"; "need strategies to change diet" and "face barriers to change diet" were generated along with 12 subthemes. Overall, needing to change one's dietary behaviour is the most important theme in addressing defecation dysfunction in patients following sphincter-saving surgery. Future studies need to focus more on the specific relationship between different food types and the degree of defecation dysfunction. Systematic, scientific and continuous instructions on eating behaviour are in great need for patients after sphincter-saving surgery.

Immunoreactivity and neutralization study of Chinese Bungarus multicinctus antivenin and lab-prepared anti-bungarotoxin antisera towards purified bungarotoxins and snake venoms.

Bungarus multicinctus is the most venomous snake distributed in China and neighboring countries of Myanmar, Laos, north Vietnam and Thailand. The high mortality rate of B. multicinctus envenomation is attributed to the lethal components of α-, ß-, γ- and κ- bungarotoxins contained in the venom. Although anti-B. multicinctus sera were produced in Shanghai, Taiwan and Vietnam, the most widely clinic used product was term as B. multicinctus antivenin and manufactured by Shanghai Serum Bio-technology Co. Ltd. In the present investigation, high purity α-, ß- and γ-bungarotoxins were separately isolated from B. multicinctus crude venom. Rabbit anti- α-, ß- and γ-bungarotoxin antisera were prepared by common methods, respectively. LD50 values of α-, ß- and γ-bungarotoxins were systematically determined via three administration pathways (intraperitoneal, intramuscular and intravenous injections) in Kunming mice. LD50 values of ß-bungarotoxin were closely related with injection routines but those of both α- and γ-bungarotoxins were not dependent on the injection routines. Commercial B. multicinctus antivenin showed strong immunoreaction with high molecular weight fractions of the B. multicinctus but weakly recognized low molecular weight fractions like α- and γ-bungarotoxins. Although B. multicinctus antivenin showed immunoreaction with high molecular weight fractions of Bungarus fasciatus, Naja atra, Ophiophagus hannah venoms but the antivenin only demonstrated animal protection efficacy against O. hannah venom. These results indicated that the high molecular weight fractions of the O. hannah played an important role in venom lethality but those of B. fasciatus and N. atra did not have such a role.

Frozen section of uterine curetting in excluding the possibility of ectopic pregnancy--a clinicopathologic study of 715 cases.

INTRODUCTION: To investigate the utility of frozen section of uterine curetting in excluding the possibility of ectopic pregnancy (EP). MATERIALS AND METHODS: A retrospective analysis of 715 curetting records in the present hospital from July 1999 to May 2009 was obtained. All specimens were processed routinely with frozen section and paraffin section. RESULTS: Of 715 cases, frozen section analyses were discordant in 33 cases (4.6%), including 32 cases under-diagnosed, and one case over-diagnosed, compared with the final diagnoses. Frozen section had a sensitivity of 92.6%, specificity of 99.6%, and frozen section accuracy rate of 95.4%. CONCLUSIONS: Frozen section is a useful and rapid method to differentiate EP from intrauterine pregnancy.

[Epidemiological characteristics of major abnormal electrocardiogram in adults from Shanghai].

OBJECTIVE: To understand the prevalence, characteristics and risk factors of major abnormal electrocardiogram (MA-ECG) in adults living in Shanghai. METHODS: The cross-sectional dataset of prevalence survey on diabetes and metabolic syndrome in adults, aged 20-74 years, from Shanghai, in 2007-2008, was analyzed. Demographic information, personal and, family histories of diseases were collected. Physical examination and laboratory tests were done. Subjects underwent examination on resting 12-leads electrocardiogram (ECG), ECG records were coded according to the Minnesota criteria and classified as MA-ECG or non-MA-ECG. RESULTS: A total number of 5364 subjects (2003 men, 3361 women) were finally included in this analysis. (1) The standardized prevalence of MA-ECG was 7.3% (7.0% in men, 7.7% in women). In both genders, the age-specific prevalence of MA-ECG significantly increased with age (Ptrend < 0.01). The age-specific prevalence of MA-ECG in youths, middle aged and the elderly were 2.3%, 7.7%, and 17.3% in men, and 3.3%, 8.8% and 16.4% in women, respectively (both Ptrend < 0.01). (2) The three most common MA-ECG forms were arrhythmia (28.8%), bundle branch block (26.5%) and ST segment depression (20.0%) in men, while there appeared ST segment depression (44.6%), arrhythmia (23.0%) and combined MA-ECG (11.8%) in women. (3) Data from multivariate logistic regression analysis showed that other than age, coronary heart disease (CHD) was the only independent risk factor of MA-ECG in men, with its corresponding OR being 2.33 - 2.39; while in women, menopause (OR value: 1.72 - 1.85) and hypertension (OR value: 1.33 - 1.34) were main factors related to MA-ECG. CONCLUSION: MA-ECG was prevalent in the middle aged and the elderly, with, arrhythmia and ST segment depression the most frequent forms of MA-ECG. Age, CHD and hypertension were the main risk factors of MA-ECG in the adults from Shanghai.

[Relationship between glycated albumin level and pancreatic ß cell function in newly diagnosed type 2 diabetics].

OBJECTIVE: To explore the relationship between glycated albumin (GA) level and pancreatic ß cell function in newly diagnosed type 2 diabetics. METHODS: The subjects sought the confirmation of diabetes diagnosis or underwent diabetes screening tests in high-risk patients from January 2008 to October 2010. All of them underwent 75 g oral glucose tolerance test (OGTT) and insulin releasing test. The levels of GA and hemoglobin A1c (HbA1c) were analyzed by liquid enzymatic method and high performance liquid chromatography respectively. Homeostasis model assessment (HOMA) was used to evaluate the basal insulin resistance (HOMA-IR) and pancreatic ß cell function (HOMA-ß). ΔI30/ΔG30 was used to evaluate early-phase insulin secretion after a glucose load. RESULTS: (1) Among 500 type 2 diabetics according to the diagnostic criteria of WHO (1999), 279 were males and 221 were females. Average age was 56.3 ± 12.3, GA (21.1 ± 5.4)% and HbA1c (7.0 ± 1.3)%. (2) A significantly positive relationship was shown between HbA1c and GA (r = 0.691, P < 0.01). GA was also positively correlated with fasting plasma glucose (FPG), 0.5 hPG, 1 hPG, 2 hPG and 3 hPG after a glucose load of OGTT test (r = 0.511 - 0.627, P < 0.01). (3) GA was negatively correlated with body mass index (BMI) (r = -0.112, P < 0.01), HOMA-ß (r = -0.350, P < 0.01) and ΔI30/ΔG30 (r = -0.263, P < 0.01). (4) Multivariant stepwise regression analysis showed that HbA1c, FPG, 3 hPG and ΔI30/ΔG30 were independent factors of GA level. CONCLUSION: Glycated albumin level is closely correlated with the function of early-phase insulin secretion in newly diagnosed type 2 diabetics.

Liver enzymes concentrations are closely related to prediabetes: findings of the Shanghai Diabetes Study II (SHDS II).

OBJECTIVE: To investigate the relationship of liver enzymes with hyperglycemia in a large population in Shanghai and identify the association between liver enzymes and insulin resistance. METHODS: A total of 3 756 participants were enrolled. Each participant underwent an oral glucose tolerance test and completed a questionnaire. Anthropometric indices were recorded and serum samples were collected for measurement. RESULTS: Liver enzymes concentrations were independently associated with i-IGT, IFG+IGT, and diabetes. With the increase of ALT and GGT concentrations, ORs for i-IGT, IFG+IGT, and diabetes increased gradually. By comparing patients in the highest quartile of GGT concentrations or ALT concentrations with those in the lowest quartile (Q1), ORs for i-IGT, IFG+IGT, or diabetes was significant after adjustment. Both ALT and GGT concentrations were linearly correlated with HOMA-IR and independently associated with HOMA-IR [ALT OR (95% CI): 2.56 (1.51-4.34) P=0.00; GGT OR (95% CI): 2.66 (1.53-4.65) P=0.00]. CONCLUSION: Serum ALT and GGT concentrations were closely related to pre-diabetes and diabetes in the Shanghai population and positively associated with insulin resistance.

[Combined utility of hemoglobin A1c and glycated albumin in diabetic screening].

OBJECTIVE: To assess the validity of combined detection of hemoglobin A1c (HbA1c) and glycated albumin (GA) in diabetic screening. METHODS: A total of 1480 subjects at our out-patient department from March 2007 to December 2009. Those suspected of diabetes or at a high risk of diabetes were enrolled. The study population included 677 males and 803 females with a mean age of 52.7 years. All subjects received an oral glucose tolerance test (OGTT) after a 10-hour fasting. Glycated albumin (GA) and hemoglobin A1c (HbA1c) were measured with liquid enzyme method and high pressure liquid chromatography respectively. RESULTS: (1) According to World Health Organization diabetes diagnosis criteria, there were 562 subjects with normal glucose tolerance (NGT), 411 subjects with impaired glucose regulation (IGR) and 507 subjects with newly diagnosed diabetes mellitus (DM). The level of HbA1c and GA had a rising tendency among NGT, IGR and DM groups (P < 0.01). (2) Pearson correlation analysis demonstrated that HbA1c had a positive association with GA (r = 0.75, P < 0.01). (3) Using OGTT as golden standard of diabetic diagnosis, receiver operator characteristic (ROC) curve indicated that HbA1c and GA were strong predictors of diabetes. The area under curve (AUC) was 0.882 and 0.881 respectively with no significant difference (P > 0.05). (4) The sensitivity of combined use of HbA1c and GA at optimal cut-off points of 6.1% and 17.1% was significantly higher than that of single use of HbA1c or GA in diabetic screening (94.7% vs 81.1%, 88.4%, P < 0.01). CONCLUSION: A combined detection of HbA1c and GA may improve the efficacy of diabetic screening. The subject with HbA1c ≥ 6.1% or GA ≥ 17.1% is recommended to undergo OGTT for confirming a diagnosis of diabetes.

Non-alcoholic fatty liver disease's prevalence and impact on alanine aminotransferase associated with metabolic syndrome in the Chinese.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is becoming a major public health hazard in China. The present study aimed to estimate the prevalence of NAFLD, NAFLD with abnormal serum alanine aminotransferase (ALT) levels, and determine the potential associations of ALT levels with the components of metabolic syndrome (MetS) in the absence or presence of NAFLD in Chinese adults. METHODS: A population-based cross-sectional survey was conducted with 2226 participants. Physical examinations, laboratory tests and hepatic ultrasounds were performed. Individuals were further stratified into higher or lower ALT subgroups with the upper quartiles of ALT in this population. The MetS was identified according to the criteria of the Chinese Joint Committee for Developing Chinese Guidelines (JCDCG). RESULTS: The standardized prevalence of NAFLD was 23.3% (NAFLD with abnormal ALT levels, 3.1%), 26.5% (NAFLD with abnormal ALT levels, 5.1%) in males, and 19.7% (NAFLD with abnormal ALT levels, 0.9%) in females. Multivariate logistic analysis revealed that higher ALT was significantly associated with elevated triglyceride (TG) in the non-NAFLD participants, independent of age, smoking status, drinking status, and other MetS-related measures with odds ratios (95% confidence intervals) of 3.4 (1.6-7.1) and 2.3 (1.4-3.7) in males and females, respectively. On the other hand, the higher ALT was statistically associated with elevated TG and hyperglycemia in the NAFLD cases with odds ratios of 2.2 to 2.5 (P<0.05). CONCLUSIONS: The prevalence of NAFLD has become epidemic in Shanghai adults. NAFLD combined with ALT levels may be used to identify the individuals at the different risk levels of metabolic disorders.

Patients' experience of living with glaucoma: a phenomenological study.

AIM: To explore the life experiences of those living with glaucoma and describe their strategies to deal with the consequences of this disorder. BACKGROUND: Glaucoma, the second most common cause of worldwide blindness, often imposes limitations on the daily functions of its victims, thus resulting in a decline in their quality of life and high costs in healthcare. METHODS: A hermeneutical phenomenological research approach was adopted. Fourteen people with glaucoma were selected for in-depth interviews, and another ten were interviewed in two focus groups. Participants were recruited from a specialized eye hospital in Shanghai. The data were collected from July to September 2009. An interpretive analysis of the data was performed. FINDINGS: The core theme was identified while interpreting the data on the patients' life experiences as 'learning to living with glaucoma' by one of our participants. The meaning of this is demonstrated in four interwoven themes: (1) seeking support; (2) coping with everyday tasks; (3) living with future uncertainties; and (4) adapting to the declined quality of life. CONCLUSION: This paper provides an insight into the living experiences of the patients with glaucoma using 1-on-1 and focus-group interviews, suggesting that the latter can also offer a means of phenomenological inquiry. We found that those with glaucoma can experience uncertainty surrounding treatment, illness prognosis and family members' risk status. In addition, the Chinese culture can influence the patients' strategies of maintaining a healthy lifestyle. In helping those with glaucoma considerations should be taken towards the feelings of future uncertainty that may develop.

Relationship between serum osteocalcin and glycaemic variability in Type 2 diabetes.

1. Recent reports have described the role of osteocalcin in glucose metabolism and glycaemic variability has been proven to be associated with an increased risk of diabetes complications. However, the relationship between osteocalcin and glycaemic variability remains unclear. The aim of the present study was to examine the relationship between serum osteocalcin and glycaemic variability, as determined by a continuous glucose monitoring (CGM) system in patients with Type 2 diabetes mellitus (T2DM). 2. Fifty-nine T2DM patients with glycosylated haemoglobin (HbA1c) levels between 7.0% and 10.9% were recruited to the present study. Biochemical information and CGM parameters were collected at baseline and after 8 weeks of antihyperglycaemic therapy (either sulphonylurea, sulphonylurea + an α-glucosidase inhibitor or insulin + metformin combination therapy). 3. Compared with baseline, serum osteocalcin increased significantly (P = 0.014), whereas parameters related to glucose variability, including the mean amplitude of glycaemic excursions (MAGE) and the standard deviation of blood glucose values, decreased significantly (P < 0.001) after the 8 week treatment period. At baseline, there was a positive correlation between serum osteocalcin levels and fasting C-peptide levels (P = 0.004) and homeostatic model assessment of ß-cell function (P = 0.048), but a negative correlation between serum osteocalcin levels and fasting plasma glucose (P = 0.023), HbA1c (P = 0.020), glycated albumin (P = 0.019) and 24 h mean blood glucose (P < 0.001). Multiple stepwise regression analysis indicated that baseline osteocalcin was the single parameter that best predicted the change in MAGE (ß = -0.122; P = 0.039). 4. In conclusion, serum osteocalcin concentrations increased with improved glucose control. High initial osteocalcin levels were associated with subsequent improvements in glucose variability during glucose-lowering treatment.

SLC22A2 gene 808 G/T variant is related to plasma lactate concentration in Chinese type 2 diabetics treated with metformin.

AIM: To investigate the potential relationship between the SLC22A2 gene polymorphism and blood lactate concentration in Shanghai Hans suffering from type 2 diabetes mellitus (T2DM). METHODS: The SLC22A2 single nucleotide polymorphism (SNP) 808G/T was genotyped in 400 T2DM patients, including a metformin-treated group (n=200) and a non-metformin-treated group (n=200). Fasting plasma lactic acid levels were measured with an enzyme-electrode assay. Biochemical indexes, including plasma alanine aminotransferase (ALT), creatinine (Cr), and glycolated hemoglobin (HbA1c), were also measured. RESULTS: The fasting plasma lactate concentration in the metformin-treated group was significantly higher than that in the non-metformin-treated group (1.29+/-0.45 mmol/L vs 1.18+/-0.44 mmol/L, P=0.015). Additionally, the ratio of patients with hyperlactacidemia was 8% (16/200) for the metformin-treated group and 5.5% (11/200) for the non-metformin-treated group, with no lactic acidosis found in either group. The frequency of the SLC22A2 808G/T T allele was 12.9%. Patients with the mutant genotype (TT) had a higher blood lactate concentration in the metformin-treated group than those in the non-metformin-treated group (t=2.492, P=0.013). This trend was not observed in the GG and GT genotypes when compared with metformin-treated and non-metformin-treated groups. Patients with the mutant genotype (TT) in the metformin-treated group also had a higher incidence of hyperlactacidemia compared with the GG genotype (40.0% vs 6.9%, P=0.050) in the metformin-treated group and the GG (6.0%, P=0.042) or GT (4.3%, P=0.043) genotypes in the non-metformin-treated group. In the metformin-treated group, there were significant gender differences in lactate concentrations in the TT (2.18+/-0.15 vs 1.04+/-0.27 mmol/L, P=0.008) and GG genotypes (1.40+/-0.51 vs 1.19+/-0.35 mmol/L, P=0.004). The lactate levels of women with the TT genotype were the highest in the metformin-treated group, but differences in lactate levels among the genotypes were not observed in the non-metformin-treated group. CONCLUSION: There is an 808G/T polymorphism in the SLC22A2 gene in Chinese Hans with T2DM. The 808G>T variance in the SLC22A2 gene can affect the plasma lactate level and the incidence of hyperlactacidemia in T2DM patients undergoing metformin therapy. Additionally, the female patients carrying the TT genotype are prone to lactatemia.

Glipizide controlled-release tablets, with or without acarbose, improve glycaemic variability in newly diagnosed Type 2 diabetes.

1. The aim of the present study was to compare the effects of glipizide controlled-release (CR) tablets monotherapy with that of glipizide CR tablets plus acarbose on glycaemic variability in newly diagnosed Type 2 diabetes (T2DM) patients using a continuous glucose-monitoring system (CGMS). 2. Forty newly diagnosed T2DM patients whose glycated haemoglobin A1c (HbA1c) levels ranged from 7.0% to 9.8% were randomized to either monotherapy or combination therapy. Overall glycaemic control and blood glucose variability were evaluated by CGMS parameters. 3. After 8 weeks treatment, fasting and postprandial blood glucose, HbA1c, glycated albumin (GA), mean blood glucose (MBG), mean amplitude of glycaemic excursions (MAGE), postprandial incremental area under the curve (AUC(pp)) and homeostasis model assessment of insulin resistance decreased significantly in both groups (P < 0.01). There was also a significant decrease in the mean of daily differences (MODD) in the combination therapy group. Mean changes in MBG, MAGE, MODD and AUC(pp) were significantly greater in the combination therapy group than in the monotherapy group (all P < 0.01), whereas no significant differences were found in the mean changes of HbA1c and GA. Multivariate regression analysis showed that the decrement in AUC(pp) was significantly associated with decreases in MAGE. 4. In conclusion, glipizide CR tablets alone or in combination with acarbose can improve overall blood glucose levels and glycaemic variability. Combination therapy using glipizide CR tablets and acarbose was more effective in reducing intraday and day-to-day glycaemic variability than glipizide CR tablet monotherapy.

[Comparison of the application of three diagnostic criteria of metabolic syndrome in familial type 2 diabetic pedigrees].

OBJECTIVE: To compare the significance of the application of three diagnostic criteria of metabolic syndrome (MS), issued by the National Cholesterol Education Program Adult Treatment Panel II (ATPIII) in 2005, International Diabetes Federation (IDF) in 2005 and Chinese Diabetes Society (CDS) in 2004, in type 2 diabetes mellitus pedigrees. METHODS: Totally,4468 subjects (including spouses) from 715 type 2 diabetic pedigrees were selected in this study. Complete laboratory data, including blood pressure, lipid profile and plasma glucose, were collected. The prevalence rates of MS and the unity of three criteria were analyzed. RESULTS: The prevalence rates of MS were 44.94% (2008/4468), 37.87% (1692/4468) and 23.86% (1066/4468) according to the ATPIII, IDF and CDS criteria respectively. It subsequently increased in second-degree relatives, spouses, first-degree relatives and probands (ATP III: 23.78% (117/492), 35.77% (318/889), 45.40% (1077/2372) and 69.37% (496/715); IDF: 20.53% (101/492), 31.61% (281/889), 38.74% (919/2372) and 54.69% (391/715); CDS: 8.94% (44/492), 16.99% (151/889), 25.08% (595/2372) and 38.60% (276/715); ATPIII: chi2 = 266.359, IDF: chi2 = 155.950, CDS: chi2 = 165.087, respectively, P < 0.01). The prevalence rates of MS, as defined by the ATP III and IDF criteria, were higher in females than in males (ATP III: 47.47% (1156/2435) and 41.91% (852/2033); IDF: 43.00% (1047/2435) and 31.73% (645/2033); chi2 = 13.871 and 60.169, respectively, P < 0.01), and was lower in females than in males as defined by the CDS criterion (22.38% and 25.63%, respectively, chi2 = 6.423, P = 0.011). The agreement in the diagnosis of MS using ATPIII and IDF, ATPIII and CDS, IDF and CDS was 92.93%, 75.56% and 77.21% respectively. Kappa index were 0.855, 0.484 and 0.478 respectively (P < 0.01). CONCLUSION: ATP III criterion showed the highest prevalence of MS and the percent of risk factor aggregation which best reflected the characteristics of MS in familial type 2 diabetic pedigrees.

Relationship of plasma creatinine and lactic acid in type 2 diabetic patients without renal dysfunction.

BACKGROUND: As one of most widely-used biguanides, metformin can induce the lactic acidosis in patients with renal failure though its incidence is very low. However, lactic acidemia induced by metformin was reported in patients without renal dysfunction. It is unclear that whether lactatemia exists in diabetic patients with normal renal function in Chinese or not and its influencing factors. This study aimed to clarify the influencing factors of lactic acid, and identify a practiced clinical marker to predict the hyperlactacidemia in diabetics with normal renal function. METHODS: The clinical data and venous blood samples of 1024 type 2 diabetic patients treated with (n = 426) or without metformin (n = 599) were collected. The lactic acid was assayed by enzyme-electrode method. The biochemical indexes included creatinine (Cr) and hepatase were measured with enzymatic procedures. The lactic acid concentrations of different Cr subgroups were compared, and the correlation and receiver operating characteristic curve analysis were used. RESULTS: The mean lactic acid level and the proportion of hyperlactatemia of metformin group were significantly higher than that of non-metformin group (P < 0.01), but no lactic acidosis was found in all patients. The correlation and multiple stepwise regression analysis indicated that the correlative factors of lactic acid in turn were Cr, metformin, alanine transferase (ALT), body mass index (BMI), Urine albumin (Ualb), and blood urea nitrogen (BUN) in total patients; and Cr, ALT, BMI and BUN in non-metformin treated patients; Cr and ALT in metformin-group. The lactate concentration increased with the increment of Cr levels, and reached its peak at Cr 111-130 micromol/L, and the optimal cutoff of Cr in predicting hyperlactacidemia was 96.5 micromol/L. CONCLUSIONS: Metformin can increase the incidence of lactatemia in type 2 diabetic patients without renal dysfunction. Cr, ALT, and BMI are independent associated factors of blood lactic acid levels. There is low proportion of lactatemia in type 2 diabetics without metformin therapy, the optimal cutoff of Cr to predict lactatemia in these patients is 96.5 micromol/L.

[Prevalence of and risk factors associated with diabetic retinopathy in pre-diabetic and diabetic population in Shanghai community].

OBJECTIVE: To determine the prevalence and risk factors of diabetic retinopathy (DR) in the Diabetes Mellitus (DM) and impaired glucose regulation (IGR) population in Shanghai Community. METHODS: DR screening after the epidemiologic study of metabolic syndrome in Huayang and Caoyang Community, Shanghai was conducted among 1300 patients with DM or IGR during June 2005 and March 2006, Digital non-mydriatic fundus photography was performed for each eye in all subjects. Other factors, including diabetes related history, BMI, WHR, fasting plasma glucose, HbA1c, serum lipid and blood pressure were also assessed. 642 patients, 312 males and 330 females, aged 65 +/- 13, with complete data were enrolled into the analysis. RESULTS: The prevalence of DR was 19.9% in the diabetic population, and the prevalence of mild, moderate, severe non-proliferative retinopathy and proliferative retinopathy was 12.0%, 5.1%, 2.3% and 0.5%, respectively; the prevalence of DR in IGR reached 8.0%. Logistic regression analysis revealed that HbA1c level and diabetes duration were both independently associated with diabetic retinopathy. CONCLUSION: The prevalence of DR was high in both DM and IGR population. Bad blood glucose control and long diabetes duration both increased occurrence of DR.

[Prevalence and clinical characteristics of the mitochondrial tRNA(Leu(UUR)) gene 3243 A to G mutation in familial diabetes mellitus in Chinese population].

OBJECTIVE: To study the prevalence and clinical characteristics of the A to G mutation at nucleotide 3243 of the mitochondrial tRNA(Leu(UUR)) gene in familial diabetes in Shanghai, Jiangsu and Zhejiang Province of China. METHODS: The mt3243 A to G mutation in 770 randomly selected, unrelated probands of diabetic pedigrees were screened by PCR-RFLP technique and PCR-direct sequencing. Genetic and clinical analyses were further performed in the probands and their family members. RESULTS: Thirteen diabetic patients (13/770, 1.69%) with mt3243 A to G mutation were detected. Eleven diabetic patients and 8 normal glucose tolerance (NGT) first-degree relatives of these 13 probands were also found bearing the mutation. Seventeen patients were associated with sensory hearing loss. In the 24 patients harboring the mutation, the majority had lower body mass index (BMI), 18 showed typical maternal inheritance, 15 had sensory hearing loss, 13 had insulin resistance and 14 required insulin therapy due to secondary failure to oral hypoglycemic agents. CONCLUSION: The mutation of mt3243 A to G in the mitochondrial tRNA(Leu(UUR)) gene is an important cause of diabetes in Shanghai, Jiangsu and Zhejiang Province of China. Mitochondrial gene mutation diabetes (MDM) is clinically characterized by early onset, emaciation, maternal inheritance, sensorineural hearing loss, and lower islet beta cell function, and some have insulin resistance.

[Study on the mitochondrial DNA mutations in familial diabetes mellitus in Chinese population].

OBJECTIVE: To assess the prevalence of mutations or variants of the mitochondrial DNA (mtDNA) in familial diabetes mellitus in Chinese population, and to explore the relationship between mtDNA mutations or variants and diabetes. METHODS: Seven hundred and seventy randomly selected, unrelated probands of diabetes pedigrees and 309 controls over 60 years of age with normal glucose tolerance were recruited. PCR-RFLP and PCR-direct sequencing were applied to the screening of mtDNA mutations or variants, including the mutations at nucleotides 3243, 3256 in tRNALeu region, 12258 in tRNASer region, 14709 in tRNAGlu region, 8296, 8344, 8363 in tRNALys region, 3316, 3394, 3426 in ND1 region and 12026 in ND4 region. RESULTS: In the diabetic group, 13 (1.69%) had mt3243 A>G mutation, 9(1.17%) had tRNAGlu 14709 T>C variant, 17 (2.21%) carried mt3316 G>A variant, 18 (2.34%) had mt3394 T>C variant, and 28 (3.63%) harbored the 12026 A>G variant. In the control group, the 14709, 3316, 3394, 12026 variants were detected in 5(1.62%), 5(1.62%), 6(1.94%), and 9(2.91%) subjects respectively. The 3256, 8296, 8344, 8363, 3426 and 12258 point mutations were not detected both in the diabetic patients and the controls. In the diabetic group, we found two double mutations, one was A3243G and T3394C, the other was A3243G and A12026G. Except that the A3243G mutation was only observed in the diabetic group, the frequencies of the other variants mentioned above were not statistically different between the diabetic and control groups. Moreover, clinical characteristics such as age of onset, BMI, and insulin resistance index were not different between diabetic patients with and without the variants. CONCLUSION: The tRNA (LeuUUR) 3243 A>G mutation may be the major cause of diabetes, representing 1.69% of the familial diabetes mellitus in Chinese. The other variants may be polymorphisms in this population, and the mutations not detected in our studied population may not be common contributors to diabetes mellitus in Chinese.