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To evaluate the potential association of anemia with micro- and macrovascular complications in Chinese patient with type 2 diabetes mellitus (T2DM).A total of 1997 patients with T2DM were included in this cross-sectional study. Patients were defined as anemic, if hemoglobin (Hb) levels were13 g/dL in males and12 g/dL in females. Data on demographics, anthropometric parameters, and co-morbidities were extracted for each patient.Twenty two percent of T2DM patients (439/1997) had anemia, and those patients with higher rates of micro- and macrovascular complications had higher rates of anemia. Univariate logistic regression analysis showed that anemia was a risk factor of microvascular complications (OR = 1.83, 95% CI: 1.45 - 2.31; P0.001) and macrovascular complications (OR = 2.10, 95% CI: 1.63 - 2.71; P0.001). After adjusting for conventional risk factors, anemia remained positively associated with microvascular complications (OR = 1.52, 95% CI: 1.17 - 1.99), but lost its association with macrovascular complications (OR = 1.01, 95% CI: 0.73 - 1.41). Anemia was also independently associated with diabetic retinopathy, nephropathy, and peripheral neuropathy.These findings suggest that anemia was related to both micro- and macrovascular complications in Chinese patients with T2DM, but was only an independent risk factor of microvascular complications. Assessment of Hb levels in T2DM patients may help to prevent subsequent diabetic micro- and macrovascular complications.

To compare the detection rates of atherosclerosis by carotid versus lower limb ultrasound in newly diagnosed type 2 diabetics and analyze the relationship between atherosclerosis and cardio-cerebrovascular events.A total of 148 newly diagnosed type 2 diabetics were recruited. Both carotid and lower extremity atherosclerosis were assessed by Doppler ultrasound. Diabetic atherosclerosis was defined as the presence of either carotid or lower extremity plaques in any of the above-mentioned arterial segments. A kappa value was computed to document the agreement between isolated carotid (or lower limb) atherosclerosis and diabetic atherosclerosis. The prevalence of cardio-cerebrovascular events was compared among different distribution types of atherosclerosis.According to the diagnostic criteria, the prevalence of diabetic atherosclerosis was 66.2% in the newly diagnosed type 2 diabetes. Based on carotid or lower extremity ultrasound, the prevalence of diabetic atherosclerosis was 27.0% and 62.2% respectively in newly diagnosed type 2 diabetes. The kappa values for the agreement between carotid/lower limb atherosclerosis and diabetic atherosclerosis were 0.32/0.91 (95% confidence interval 0.22-0.42 for carotid vs 0.84-0.98 for lower extremity). The combination of carotid and lower extremity arterial atherosclerosis was associated with a significantly increased detection rate of cardio-cerebrovascular events (26.5%) versus those with either carotid or lower extremity arterial atherosclerosis (0% and 10.3% respectively).The combination of carotid and lower extremity ultrasonography can more accurately reflect the atherosclerotic lesions in type 2 diabetes. Due to a higher prevalence of cardio-cerebrovascular events, type 2 diabetics with both carotid and lower extremity atherosclerosis should be managed more aggressively to reduce the risk of cardio-cerebrovascular events.

To observe the effects of leptin on activity of GSK-3β and explore its mechanism.C2C12 myoblasts differentiated for 3 days into myotubes in differentiation medium. Myotubes were stimulated by leptin (100 nmol/L) for 0, 5, 15 or 30 min respectively. Western blot was used to detect the expression levels of GSK-3β and phospho-GSK-3β (ser-9). Co-immunoprecipitation (CO-IP) was performed to determine the relationship among APPL1, leptin receptor and GSK-3β in the presence or absence of leptin. The expression level of GSK-3β at phospho-GSK-3β (ser-9) was detected in APPL1-suppressed C2C12 myotube while that of APPL1 at phospho-APPL1 (ser-401) determined in GSK-3β overexpressed/inhibited C2C12 cell.Leptin time-dependently increased the phosphorylation level of GSK-3β at ser-9 in C2C12 cell, and the pGSK-3β level in cells incubated by leptin for 30 min was as 4.08 times as which in control cells (P0.01). The triple complex of APPL1, leptin receptor and GSK-3β, in the presence of leptin, the binding capacity between APPL1 and GSK-3β was stronger. The level of phospho-GSK-3β was significantly lower in APPL1-suppressed C2C12 cell compared with that in control cells. And the phosphorylation of APPL1 at ser-401 could be induced by GSK-3β.Leptin promotes muscle glycogen synthesis by inducing phosphorylation of GSK-3β in C2C12 cell. Such a function may be mediated by the triple complex of APPL1, leptin receptor and GSK-3β. Meanwhile, GSK-3β can also increase the phosphorylation of APPL1 at ser-401.

Waist circumference, as a brief indicator of visceral obesity, is associated with multi-metabolic disorders and cardiovascular diseases. The present study was aimed to find out the relationship between waist circumference and carotid intima media thickness (C-IMT), as well as the best waist circumference cutoff for identifying C-IMT elevation in Chinese male patients with newly-diagnosed diabetes.Five hundred and seventy-eight patients from Department of Endocrinology and Metabolism in Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University were enrolled. Both physical examination (for measurement of waist circumference) and carotid ultrasonography (for measurement of C-IMT) were performed.After grouping according to the quartiles of C-IMT, the waist circumference increased across all its quartiles. The waist circumference in 3rd and 4th quartiles (90.7±9.8 cm and 90.8±9.6 cm) was significant higher than in 1st and 2nd quartiles (P0.05). When subjects were divided into 4 groups according to waist circumference, the C-IMT of subjects with waist circumference 90-95 cm was significant higher than that of subjects with waist circumference 85-90 cm and less than 85 cm respectively (P0.05). Both spearman and partial correlation analysis showed that C-IMT was positively correlated with waist circumference (P0.01). C-IMT was found significantly elevated with the increase of waist circumference. Multiple stepwise regression analysis showed that waist circumference was one of the independent risk factors of C-IMT. After an average of 2.23±0.85 years follow up, there was a significant elevation of C-IMT in the group with baseline waist circumference over 90 cm P0.05), while no significant difference was detected in the group with baseline waist circumference less than 90 cm (P=0.27). Logistic regression showed that baseline waist circumference over 90 cm was associated with a relative risk to C-IMT elevation of 1.132 (95% CI 1.043-1.431, P0.05).Among newly-diagnosed diabetic male patients, waist circumference over 90 cm not only reflects sub-clinical atherosclerosis in early stage, but also predicts the progression of atherosclerosis.

To evaluate whether waist circumference (WC) ≥85 cm is related to asymptomatic preclinical atherosclerosis in women from Shanghai, China.A total of 2365 females aged ≥20 years recruited from 4 communities underwent physical examination and carotid artery scanning. Their carotid intima-media thickness (C-IMT) was measured.The C-IMT was significantly higher in overweight or obese women with their BMI ≥25.0 kg/m2(P0.01) and in those with their WC ≥85 cm than in those with their WC85 cm (P0.01). Spearman and partial correlation analysis showed that the C-IMT was significantly correlated with WC which was independent of menopausal status. The C-IMT significantly increased with the increasing WC and reached to a platform in about 85 cm. An increment tendency was found in the subgroup with its WC85 cm (P0.01) while no significant tendency was found in the subgroup with its WC≥85 cm (P=0.07).Multiple stepwise regression analysis showed that the WC was an independent risk factor for C-IMT. In logistic regression model, the odd ratio of WC ≥80 cm, ≥80 cm and85 cm and ≥85 cm for evaluating the risk of C-IMT elevation was 1.632, 1.501, and 1.878, respectively.WC is significantly correlated with C-IMT in women from Shanghai, China, and WC≥85 cm may be used in identifying the risk of subclinical carotid atherosclerosis.

To explore the associations of the level of glycated albumin (GA) with coronary artery disease (CAD).A total of 306 patients undergoing coronary angiography (CA) were collected. There were 201 males and 105 females with an age range of 38-86 years. CA was the major diagnostic criteria of CAD. Metabolic syndrome was diagnosed according to the Guideline on PreventionTreatment of Blood Lipid Abnormality in Chinese Adults.(1) CAD was found in 227 patients (74.2%). The levels of 2 h postprandial glucose, GA and hemoglobin A1c in the CAD patients were higher than those in the non-CAD counterparts (all P0.05). (2) In the subgroup of normal glucose tolerance (NGR), the CAD patients had a higher level of GA than the non-CAD patients ((15.0 ± 2.1)% vs (13.3 ± 1.7)%, P0.01). And the level of GA was higher in the patients with 1-vessel ((14.8 ± 2.1)% vs (13.3 ± 1.7)%, P0.05) and multi-vessel lesions ((15.1 ± 2.1)% vs (13.3 ± 1.7)%, P0.05) than that in the non-CAD counterparts (all P0.05). Similar results were obtained in the hyperglycemia subgroup. (3) Logistic regression demonstrated that the level of GA was independently correlated with CAD after adjusting other traditional factors among all subjects, NGR and hyperglycemia subgroup.The serum level of GA becomes significantly elevated the CAD patients. And it is an independent risk factor of CAD in both hyperglycemic and NGR patients.

To examine the prevalence of metabolic syndrome (MS) and microalbuminuria (MAU) in subjects with different levels of glucose tolerance and probe the risk factors for the development of MAU.A total of 951 subjects were divided into 3 groups according to the results of oral glucose tolerance test (OGTT). Among them, there were 674 subjects with normal glucose tolerance (NGT), 195 with impaired glucose regulation (IGR) and 82 newly-diagnosed cases of type 2 diabetes mellitus (T2DM). MAU was diagnosed if urine albumin-to-creatinine ratio (UACR) was 30 - 300 mg/g.(1) Compared to the NGT subjects, both the IGR and newly-diagnosed T2DM subjects had the significantly higher levels of age, body mass index (BMI), waist circumference, fasting plasma glucose, 2-hour post OGTT glucose (2 hPG), glycated hemoglobin, glycated albumin, fasting insulin, homeostasis model of assessment-insulin resistance (HOMA-IR), triglyceride, systolic blood pressure (SBP) and UACR but a lower level of high density lipoprotein-cholesterol (HDL-C); (2) The incident rate of MS and MAU in the IGR and newly-diagnosed T2DM subjects was 54.4% (106/195), 12.3% (24/195) and 61.0% (50/82), 12.2% (10/82) respectively versus 9.1% (61/674) and 4.9% (33/674) in the NGT subjects. The incident rate of abdominal obesity, hypertension, hypertriglyceridemia, low HDL-C, MS and MAU in the IGR and newly-diagnosed T2DM subjects was significantly higher than that of the NGT subjects (all P0.05); (3) Multiple regression analysis showed that BMI, SBP and 2 hPG were independently associated with UACR. Logistic regression analysis indicated that BMI, SBP and 2 hPG were independent risk factors of MAU.The prevalence of MS and MAU is significantly higher in the IGR and newly-diagnosed T2DM subjects. BMI, SBP and 2 hPG are independent risk factors of MAU.

To explore the relationship between glycated albumin (GA) level and pancreatic β cell function in newly diagnosed type 2 diabetics.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 β cell function (HOMA-β). ΔI30/ΔG30 was used to evaluate early-phase insulin secretion after a glucose load.(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, P0.01). 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, P0.01). (3) GA was negatively correlated with body mass index (BMI) (r = -0.112, P0.01), HOMA-β (r = -0.350, P0.01) and ΔI30/ΔG30 (r = -0.263, P0.01). (4) Multivariant stepwise regression analysis showed that HbA1c, FPG, 3 hPG and ΔI30/ΔG30 were independent factors of GA level.Glycated albumin level is closely correlated with the function of early-phase insulin secretion in newly diagnosed type 2 diabetics.

To assess the validity of combined detection of hemoglobin A1c (HbA1c) and glycated albumin (GA) in diabetic screening.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.(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 (P0.01). (2) Pearson correlation analysis demonstrated that HbA1c had a positive association with GA (r = 0.75, P0.01). (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 (P0.05). (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%, P0.01).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.

A patient with insulinoma diagnosed by clinical features and localized preoperatively using a combination of contrast-enhanced ultrasonography (CEUS), dual phase contrast enhanced spiral computed tomography (DPSCT) and arterial stimulation and venous sampling (ASVS) was reported. A 37-year-old man was admitted to our hospital because of hypoglycemic attacks, palpitations, and muscular weakness. Fajans' ratio reported to be an index for insulinoma was positive. Transabdominal computed tomography and ultrasonography failed to detect any abnormalities. CEUS showed a small low echoic lesion in the pancreatic body with blood flow and the early arterial phase of DPSCT revealed a small strengthening focus, which mimicked a pancreatic tumor in the pancreatic body. ASVS showed that the insulin levels in the hepatic vein were extremely increased by calcium injection to the gastroduodenal artery. An open intra-abdominal operation was performed and an insulinoma was confirmed in the pancreatic body. Enucleation of tumor was undertaken and histopathological examination showed an adenoma, insulin expression was positive in immunofluorescence staining. Symptomatic hypoglycemia never happened even without glucose infusion since the operation. His blood glucose level improved to within the normal range.

To investigate a potential relationship between Solute carrier family 30 (zinc transporter) member 8 (SLC30A8) rs13266634 variant and efficacy of rosiglitazone or repaglinide in treating newly diagnosed Chinese type 2 diabetes patients.A total of 209 diabetic patients without any antihyperglycemic history were recruited and treated with repaglinide or rosiglitazone randomly for 48 weeks (104 and 105 patients, respectively). Anthropometric measurements and clinical laboratory tests were carried out before and after the treatment. An non-synonymous variant rs13266634 was genotyped by matrix-assisted laser desorption ionization-time of flight mass spectroscopy.Ninety-one patients in repaglinide group and ninety-three patients in rosiglitazone group completed the study. Δ value of homeostasis model assessment of beta cell function (HOMA-B) and Δ value of fasting proinsulin levels were statistically significant between three genotype groups (P=0.0149 and 0.0246, respectively) after rosiglitazone treatment. However, no genotype association was observed in the repaglinide or rosiglitazone group with other parameters.The SLC30A8 variant was associated with the efficacy of insulin sensitizer monotherapy on insulin secretion in patients with newly diagnosed type 2 diabetes mellitus in Shanghai, China.

To find out the features of glycemic excursion via continuous glucose monitoring system (CGMS) during continuous subcutaneous insulin infusion (CSII) treatment in type 2 diabetics and discuss the possibility of predicting nocturnal hypoglycaemia with bedtime glucose level.A total of 257 diabetes patients (156 males and 101 females, aged from 27 - 88 years old) with 0.1 - 40 years diabetic history were recruited. Their HbA1c level was (10.97 ± 2.11)%. Glycated albumin level was (31.88 ± 7.51)%. All patients were switched to CSII therapy while a 72-hour period of CGMS was performed. Participants were divided into hypoglycemia group and non-hypoglycemia group according to the reading of hypoglycemic events from CGMS data.(1) From CGMS profiles, the investigators found that MBG was (9.66 ± 2.00) mmol/L and SDBG (2.98 ± 1.03) mmol/L. (2) A total of 243 hypoglycemia events occurred in 118 participants at early stage of CSII treatment. (3) When bedtime blood glucose was below 5.9 mmol/L, the youden index was maximal on a receiver operating characteristic curve. The sensitive was 54.8% and specificity 77.8%. Positive predictive value was 44.3% and negative predictive value 84.2%. So the cut-off point of bedtime blood glucose to predict nocturnal hypoglycemia might be 5.9 mmol/L.(1) Hypoglycemia as detected by CGMS occurs in almost 1/2 type 2 diabetics during CSII therapy. (2) There is a higher risk of nocturnal hypoglycemia if the bedtime blood glucose concentration falls below 5.9 mmol/L.

To study the effect of FAM172A protein related to diabetic macroangiopathy on apoptosis and proliferation in HEK293 cells.The pDrive-FAM172A plasmid constructed in our previous study was used as a template to amplify human FAM172A open reading frame by a polymerase chain reaction. The resulting PCR products were subcloned into the eukaryotic expression vector PDC315 to construct recombinant PDC315-FAM172A plasmid. PDC315-FAM172A plasmid was identified by enzyme cleavage and sequencing analysis. HEK293 cells were transiently transfected respectively with appropriate PDC315 or PDC315-FAM172A plasmid by Lipofectamine 2000 according to the manufacturer's instruction. XTT assay and growth curve were used to observe the effect of over-expression of FAM172A gene on HEK293 cell proliferation. PI and Annexin V/PI staining method were used to assess the effect of FAM172A gene on apoptosis and cell cycle of HEK293 cell.Eukaryotic expression vector PDC315-FAM172A was successfully constructed and identified by enzyme cleavage and sequencing analysis. Compared with PDC315 plasmid transfection, the XTT assay showed that optical density (A) value increased by 52% when transfected with PDC315-FAM172A plasmid (0.21±0.07 vs 0.32±0.06, P0.01). Growth curve revealed that HEK293 cells transfected with PDC315-FAM172A plasmid proliferated faster than those transfected with PDC315 plasmid. PI staining showed that, as compared with PDC315 plasmid transfection, the apoptotic rate of HEK293 cells transfected with PDC315-FAM172A plasmid decreased by 38.5% (23.79±1.36 vs 14.64±0.95, P0.01), cell percentage of G0-G1 phases significantly decreased (66.79±1.73 vs 58.16±0.75, P0.01) and cell percentage of S phases significantly increased (22.62±1.16 vs 33.56±0.94, P0.01). Annexin V/PI staining revealed that, as compared with PDC315 plasmid transfection, the percentage of early and advanced apoptotic cells decreased by 28% (13.63±0.56 vs 9.79±0.39, P0.01) and 29% (7.70±0.29 vs 5.43±0.29, P0.01) respectively.FAM172A protein promotes cell proliferation, inhibits cell apoptosis and facilitates S-phases entry. It indicates that FAM172A protein is involved in cell growth regulation. Our findings provide a clue for further study on its physiological functions and roles in diabetic macroangiopathy.

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 (P0.001) 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 β-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 (P0.001). Multiple stepwise regression analysis indicated that baseline osteocalcin was the single parameter that best predicted the change in MAGE (β = -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.

To analyze the diagnostic value of employing the parameters of glucose metabolism as screening tests for insulinoma.Blood glucose profiles within 72 h were recorded by continuous glucose monitoring system (CGMS). Blood samples were collected to detect the HbA1c and GA levels. All subjects received a delayed 75 g oral glucose tolerance test (OGTT) and a simultaneous insulin and C peptide releasing test.Levels of HbA1c [(4.49 +/- 0.63)% vs (5.60 +/- 0.25)%, (5.28 +/- 0.48)%], fasting blood glucose [(3.44 +/- 0.78) mmol/L vs (4.82 +/- 0.35) mmol/L, (4.70 +/- 0.49) mmol/L] and the lowest blood glucose with CGMS [(2.31 +/- 0.24) mmol/L vs (3.28 +/- 0.45) mmol/L, (3.28 +/- 0.99) mmol/L] in insulinoma group were significantly lower than that in impaired glucose tolerance or diabetic patient group and functional hypoglycemia group (P value0.05). On the contrary, the levels of IRI (insulin release index) (0.38 +/- 0.07 vs 0.11 +/- 0.06, 0.16 +/- 0.03), CPI (C-peptide index) (0.03 +/- 0.01 vs 0.02 +/- 0.01, 0.02 +/- 0.01) in insulinoma group were higher than those of two other groups (P value0.05). Areas of ROC curve were 0.875, 0.955, 0.974, 0.848, 0.916 respectively as screening tests for insulinoma.The measurements of HbA1c, fasting blood glucose, IRI, CPI and the lowest blood glucose with CGMS might be useful screening tools to identify insulinoma.

To study the RBP4 mRNA expression between subcutaneous and visceral adipose tissue in obese and type 2 diabetic patients and to investigate the factors that influence RBP4 mRNA expression in Human visceral adipose tissue.9 individuals with normal weight normal glucose regulation subjects, 9 obesity subjects and 9 type 2 diabetes subjects were enrolled. All of the subjects were prepared to undergone an operation because of nondiabetes disease. Subcutaneous and visceral adipose tissue were taken out as soon as cultured. RT-PCR and Real-time PCR were used to assay the relative expression of RBP4 mRNA.RBP4 mRNA level in visceral adipose tissue of obesity group was (2.10 +/- 1.84), and that of type 2 diabetes group was (1.54 +/- 0.46), both were significantly higher than that in normal weight normal glucose group (0.75 +/- 0.28, P0.01, P0.05). RBP4 mRNA level in subcutaneous adipose tissue of the three groups were (1.05 +/- 0.15 vs 0.99 +/- 0.14 vs 1.13 +/- 0.07), no difference among them(P0.05). Insulin, dexamethasone, pioglitazone, free fatty acids can significantly increase RBP4 mRNA expression, compared with the control group, respectively, have an increase of 2.13 times, 0.84 times, 2.04 times, 4.88 times; however, tumor necrosis factor-alpha can significantly lower RBP4 mRNA level, compared with the control group decreased by 38%.RBP4 mRNA expression in visceral adipose tissue were significantly higher in obesity and type 2 diabetes subjects. In vitro system, RBP4 gene expression in visceral adipose tissue of normal weight normal glucose subjects was regulated by insulin, dexamethasone, pioglitazone, palmitic acid and TNF-alpha, such factors were also participated in the pathophysiological process of insulin resistance and type 2 diabetes.

1. The aim of the present study was to assess the validity of glycated albumin (GA) and fasting plasma glucose (FPG) as a screening tool for the early detection of diabetes in Chinese subjects. 2. A total of 1971 outpatient subjects underwent a 75 g oral glucose tolerance test (OGTT) and GA measurement. The receiver operating characteristic curve (ROC) was plotted to examine the sensitivity, specificity, and positive and negative predictive values of GA and FPG in detecting undiagnosed diabetes at the different cut-off levels. 3. The prevalence of impaired glucose regulation and diabetes was 27.40% and 38.30%. For these diabetic individuals, 4.64% had isolated fasting hyperglycemia, 50.86% had isolated postprandial hyperglycemia and 44.50% had both. Using ROC analysis, a GA of 17.1% gave an optimal sensitivity of 76.82% (95% confidence interval: 73.64-79.79%) and specificity of 76.89% (74.42-79.23%) for the diagnosis of diabetes. Likewise, a FPG of 6.1 mmol/L gave an optimal sensitivity of 80.93% (77.94-83.67%) and specificity of 85.94% (83.86-87.84%). If subjects met both criteria, they were regarded as having diabetes; the positive predictive value of the combined criteria, FPG ≥ 6.1 mmol/L and GA ≥ 17.1%, was relatively high (84.79% (81.62-87.60%)), and this would have avoided 76% of the OGTT in our survey. 4. In conclusion, a GA value of 17.1%, an optimal cut-off in Chinese subjects, identified a high proportion of potential diabetic individuals. Simultaneous measurement of FPG and GA would enhance the sensitivity of diabetes screening in our population and avoid 76% of OGTT.

To investigate the relationship between serum uric acid (UA) level and lower extremity arterial disease (LEAD) in type 2 diabetes mellitus (T2DM) subjects.A total of 2174 T2DM individuals (1228 males, 946 females) were investigated. The case history, physical examination and biochemical tests were conducted. And LEAD was diagnosed by high-resolution ultrasound.In women, the serum UA levels with LEAD was significantly higher than that without LEAD [(304 +/- 76) micromol/L vs (287 +/- 71) micromol/L, P0.01], but not in men [(332 +/- 76) micromol/L vs (328 +/- 77) micromol/L, P = 0.45]. The subjects were divided into 4 groups (groups A, B, C, D) according to sex-specific quartiles of serum UA levels (240 micromol/L, 240 - 284 micromol/L, 285 - 340 micromol/L andor= 341 micromol/L in women and275 micromol/L, 275 - 322 micromol/L, 323 - 377 micromol/L andor= 378 micromol/L in men). In women, the prevalence of LEAD of 4 groups were 38.56%, 44.02%, 47.54% and 50.00% respectively (P0.01). And the prevalence of LEAD in groups C and D was significantly higher than that in group A (P0.05). But in men there was no significant difference between 4 groups. After adjusting for age, duration of diabetes mellitus, smoking status, systolic blood pressure, body mass index, total cholesterol, triglyceride and C reactive protein, the serum UA levels in women was an independent risk factor associated with the prevalence of LEAD. And the odds ratios (95%CI) of sex-specific quartiles of serum UA were 1.0, 1.25 (0.87 to 1.81), 1.44 (1.01 to 2.08) and 1.59 (1.10 to 2.30) respectively.The increase of serum UA levels is associated with LEAD in women, in addition to age, duration of diabetes mellitus, smoking status, systolic blood pressure, body mass index, total cholesterol, triglyceride and C reactive protein. Serum UA levels is an independent risk factor of LEAD in women diabetics.

To investigate the effect of hemoglobin A1c (HbA1c) and glycated albumin (GA) on serum CA199 in diabetic patients.29 NGT matched control subjects and 371 hospitalized diabetic patients were enrolled. Diabetic patients were divided into satisfactory group (6.5%), general group (6.5%-7.5%) and dissatisfactory group (7.5%) by the level of HbA1c. The levels of serum CA199 among three groups were compared. The relationship between HbA1c and CA199, GA and CA199 was analysed. Multiple stepwise regression analysis was performed to compare the effect of different variables on CA199 as the independent variables were sex, age, duration, TC, TG, HDL, LDL, FBG, PBG, HbA1c and GA.(1) CA199 level of the group of HbA1c above 7.5% was significantly higher than the group of HbA1c between 6.5% and 7.5% and the group of HbA1c less than 6.5%. (2) The coefficient of correlation between HbA1c and CA199 was 0.394 (P = 0.000), and that was 0.381 between GA and CA199 (P = 0.000). (3) Multiple stepwise regression analysis show standard regression coefficient of HbA1c is 0.364 (P = 0.000).(1) CA199 level of diabetic patient in poor glucose control was significantly higher than the patient in good control. (2) CA199 was positively correlated with FBG, PBG, HbA1c and GA. (3) HbA1c is the independent risk factor of CA199. The elevated CA199 in diabetic patient has close relationship with poor glucose control in a long period.

To clone a novel diabetic angiopathy related protein gene-C5orf21 and study its roles in diabetic macroangiopathy.The open reading frame (ORF) of C5orf21 gene was cloned into vector from human aortic tissues by a RT-PCR-based approach and identified by enzyme-cutting and sequencing. The structure and function of C5orf21 gene and protein were further analyzed by bioinformatics technology. The mRNA expression of C5orf21 gene in human tissues and in vascular cells was analyzed by RT-PCR. RT-PCR was used to observe the effect of high glucose, low-density lipoprotein (LDL) and free fatty acid (FFA) upon the expression of C5orf21 gene in macrophages.C5orf21 gene was successfully inserted into pDrive vector and identified for the first time at the level of mRNA. There are five C5orf21 gene splice variants in human aortic tissue and their length of ORF are 1251, 1113, 894, 810 and 810 bp respectively. Two kinds of splice variants have yet to be included in GenBank database. Two kinds of splice variants have the same ORF and their differences are mainly in the bases in the 5' untranslated region. Bioinformatics analysis found that C5orf21 gene was located in chromosome 5q15 and C5orf21 protein contained Arb2 domain associated with histone H3 lysine 9 methylation. C5orf21 gene was normally expressed in many tissues. Fat and aortic tissues had the highest expression. The expression of C5orf21 gene could be detected in human aortic endothelial cell, aortic smooth muscle cell and macrophages. High glucose, LDL and FFA (esp.high glucose) up-regulated the expression of C5orf21 gene in macrophage.C5orf21 gene contains five splice variants and it is identified for the first time at the level of mRNA. The changes of C5orf21 gene expression are correlated with diabetic macroangiopathy.

To investigate the characteristics of glycemic stability in the first-degree relatives of type 2 diabetes mellitus (T2DM) patients by continuous glucose monitoring system (CGMS).Twenty-two first-degree relatives (FDRs) of T2DM patients and 28 age and gender-matched controls underwent CGMS to obtain the mean blood glucose (MBG), standard deviation of MBG (SDBG), mean of daily differences (MODD), and mean amplitude of glycemic excursions (MAGE). Oral glucose tolerance test (OGTT) was conducted. Blood glucose, serum lipids, and serum insulin were assayed. The insulin sensitivity and resistance was assessed by HOMA-beta, HOMA-IR, DeltaI(30)/DeltaG(30) and modified beta cell function index (MBCI).There were no significant differences between the FDR and control groups in the levels of plasma glucose in OGTT, MBG, SDBG, and MOOD. However, the MAGE level of the FDR group was (2.3 +/- 0.5) mmol/L, significantly higher than that of the control group [(2.0 +/- 0.6) mmol/L, P0.05]. The MBCI level of the FDR group was 17.6 (16.9 - 50.0), significantly lower than that of the control group [36.0 (15.7 - 59.6), P0.05]. There were no significant differences in the serum lipids profile, body fat distribution, HOMA-beta, HOMA-IR, and DeltaI(30)/DeltaG(30) between these two groups.The excursion of blood glucose is greater in the FDRs of T2DM patients. CGMS is more sensitive to discover such change than OGTT.

To investigate the prevalence, clinical features of latent autoimmune diabetes in adults (LADA) from phenotypic type 2 diabetic patients and the relationship between LADA and metabolic syndrome (MS).Sera from 1711 phenotypic type 2 diabetic patients were screened for glutamic acid decarboxylase antibody (GAD-Ab) and protein tyrosine phosphatase antibody (IA2-Ab) through radioligand assay. The prevalence of LADA and its relation with clinical features were analyzed.(1) The prevalence of LADA in phenotypic type 2 diabetic patients was 6.7% (115/1711), the positive frequency of GAD-Ab and IA2-Ab was 6.0% and 2.4% respectively. (2) The prevalence of LADA from phenotypic type 2 diabetic patients with a duration of diabetes less than 1 year which was much higher than that of patients with a duration over 1 year (10.4% vs 5.9%, P0.01). (3) The prevalence of LADA was higher in patients with younger age at onset, lower body mass index and lower level of postprandial C peptide and without diabetes family history. (4) 51.3% of LADA patients were suffered from at least one kind of metabolic disorders besides hyperglycemia, 21.7% of them were with MS. The prevalence from high to low of those metabolic disorders were as follows: hypertension, dyslipidemia, overweight/obesity.(1) 6.7% of phenotypic type 2 diabetic patients were LADA, of whom early diagnosis of diabetic type should be made to guide clinical therapies. (2) More than 1/5 patients with MS were found in LADA patients, indicating an overall screening and intervention of metabolic disorder factors is important in LADA patients.

To analyze the mRNA expression of omentin mRNA level in subcutaneous and omental adipose tissues of normal, obese, and type 2 diabetic individuals and to investigate the relationship between omentin mRNA expression and serum omentin level, body fat parameters, glucose and lipid metabolism, and insulin resistance indexes.36 patients with benign diseases undergoing selective abdominal operation, 19 males and 17 females, aged 20 - 65, included 12 with normal glucose regulation and normal weight (NGR-NW group), 12 with normal glucose regulation and overweight/obesity (NGR-OW/OB group), and 12 with type 2 diabetes and overweight/obesity (T2DM-OW/OB group). Abdominal subcutaneous and omental adipose tissues were obtained during operation. Real-time quantitative PCR was used to measure the omentin mRNA level. The level of fasting serum omentin was measured by ELISA. Meanwhile blood glucose, HbA(1C), lipids and insulin levels were measured. Body weight, BMI and waist hip ratio (WHR) were evaluated and insulin sensitivity was assessed by homeostasis model assessment insulin resistance index (HOMA-IR).The omentin mRNA level in omental adipose tissue of the NGR-NW group was (1.52 +/- 0.32), significantly higher than that in subcutaneous adipose tissue [(0.019 +/- 0.006), P0.01]. The omentin mRNA level of the males was (1.46 +/- 0.31), not statistically different from that of the female [(1.58 +/- 0.29), P = 0.416]. The omentin mRNA level of the NGR-OW/OB group was (1.18 +/- 0.29), significantly lower than that of the NGR-NW group [(1.52 +/- 0.32), P0.05], and the omentin mRNA level of the T2DM-OW/OB group was (0.98 +/- 0.37), both significantly lower than those of the other 2 groups (both P0.05). Partial correlation analysis showed that the omentin mRNA was negatively correlated with HOMA-IR, body weight, WHR, triglyceride, BMI, and fasting insulin, and positively correlated to serum omentin level and HDL-C. Multiple linear regression analysis showed that serum omentin level, HOMA-IR, and body weight were independent variables of omentin.Omentin mRNA is highly expressed in omental adipose tissue. The omentin mRNA expression level decreases in the overweight/obese individuals and decreases further when overweight/obesity is combined with type 2 diabetes. Omentin mRNA is positively correlated to serum omentin level, obese indexes, insulin resistance, and lipid metabolism parameters. Decreased omentin gene expression may contribute to the underlying pathophysiology of insulin resistance syndrome.

Apelin is an adipokine that contributes to the pathogenesis of type 2 diabetes. The plasma levels of apelin increased in obese patients and diabetic subjects. This study aimed to investigate the effects of apelin genetic variants on type 2 diabetes and related quantitative traits.We selected three single nucleotide polymorphisms (SNPs) that could capture all common variants in APLN gene region and genotyped them in 1892 type 2 diabetic patients and 1808 normal glucose regulation controls. The clinical features related to glucose metabolism were measured in the controls. The comparison of allele and genotype distribution in the cases and controls were performed by using chi(2) tests. The association between SNPs and quantitative traits were analyzed using Wilcoxon's rank-sum test.None of the SNPs or haplotypes showed evidence of association to type 2 diabetes. However, rs2235306 was nominally associated with fasting plasma glucose levels in the male subjects with normal glucose regulation ((4.93 +/- 0.03) vs (5.01 +/- 0.03) mmol/L, P = 0.04). No significant difference was observed between all three SNPs and other variables.APLN SNP rs2235306 was associated with fasting plasma glucose levels in males. It suggests that APLN genetic variants may contribute to clinical features related to glucose metabolism in Chinese population.

To investigate the relationship between the blood glucose variability and microalbuminuria (MAU) in type 2 diabetic patients with well-controlled glycosylated hemoglobin (HbA1c) and the influencing factors of blood glucose variability.One hundred and seventy-six type 2 diabetic patients with HbA1c under 6.5% and 48 subjects with normal glucose regulation were monitored using the continuous glucose monitoring system (CGMS). The mean blood glucose (MBG) and mean amplitude of glucose excursions (MAGE) were analyzed.(1) The MBG and MAGE levels of type 2 diabetic patients were (7.0+/-0.9) and (3.8+/-2.5) mmol/L respectively, both higher than those of the subjects with normal glucose regulation [(5.4+/-0.6) and (2.0+/-0.7) mmol/L respectively, both P0.01]. (2) The incidence ratio of MAU of the patients with ascended MAGE level was 18.7%, significantly higher of those with normal MAGE (7.1%, P0.05). (3) The MAGE level was positively correlated with age, duration of diabetes, and systolic blood pressure, and negatively correlated with glomerular filtration rate and the levels of fasting and postprandial C-peptide. Multivariant regression analyses indicated that duration of diabetes and the level of postprandial C-peptide 30 min after meal were the independent influential factors of MAGE. (4) In the type 2 diabetic patients, the MAGE of the MAU group was higher than that of the non-MAU group (P0.05). Logistic regression analyses indicated that diastolic blood pressure and MAGE were the risk factors of MAU (OR=1.201 and 1.357, both P0.05).In well-controlled patients with type 2 diabetes, blood glucose variability is one of the risk factors for MAU, duration of diabetes and early stage of insulin secretion function are the main factors influencing glycemic variability.

Type 2 diabetes is a chronic disease characterized by a progressive loss of beta cell functions. However, the evaluation of beta cell functions is either expensive or inconvenient for clinical practice. We aimed to elucidate the association between the changes of insulin responsiveness and the fasting plasma glucose (FPG) during the development of diabetes.A total of 1192 Chinese individuals with normal blood glucose or hyperglycemia were enrolled for the analysis. The early insulinogenic index (DeltaI30/DeltaG30), the area under the curve of insulin (AUC-I), and homeostasis model assessment were applied to evaluate the early phase secretion, total insulin secretion, and insulin resistance respectively. Polynomial regression analysis was performed to estimate the fluctuation of beta cell functions.The DeltaI30/DeltaG30 decreased much more rapidly than the AUC-I accompanying with the elevation of FPG. At the FPG of 110 mg/dl (a pre-diabetic stage), the DeltaI30/DeltaG30 lost 50% of its maximum while the AUC-I was still at a compensated normal level. The AUC-I exhibited abnormal and decreased gradually at the FPG of from 130 mg/dl to higher (overt diabetes), while the DeltaI30/DeltaG30 almost remained at 25% of its maximum value. When hyperglycemia continuously existed at180 mg/dl, both the DeltaI30/DeltaG30 and AUC-I were totally lost.The increased fasting plasma glucose reflects progressive decompensation of beta cell functions, and could be used to guide the strategy of clinical treatments.

To elucidate the principal of orthogonal factor analysis, using an example of factor analysis of metabolic syndrome. The basic structures and the fundamental concepts of orthogonal factor analysis were introduced and data involving 1877 women aged of 35-65 years, selected from a cross-sectional study, which was conducted in 1998 - 2001 in Shanghai, were included in this study. Factor analysis was carried out using principle components analysis with Varimax orthogonal rotation of the components of the metabolic syndrome. The different components of the metabolic syndrome were not linked closely with the other components and loaded on the six different factors,which mainly reflected by the variables of obesity, blood pressure, plasma glucose, plasma insulin, triglycerides and HDL-cholesterol respectively. Six major factors of the metabolic syndrome were uncorrelated with each other and explained 86% of the variance in the original data. The factor score and total factor score for the individual could be obtained according to the component score coefficient matrix. Although the components of the metabolic syndrome were related statistically, the finding of six factors suggested that the components of the metabolic syndrome did not show high degrees of intercorrelation. As a linear method of data reduction, the mode reduced a large set of measured intercorrelation variables into a smaller set of uncorrelated factors, which explained the majority of the variance in the original variables. Factor analysis was well suited for revealing underlying patterns or structure among variables showing high degrees of intercorrelation.

The aim of this study was to investigate the association of KCNJ11 E23K and ABCC8 exon16-3T/C with the therapeutic effect of repaglinide in patients with type 2 diabetes.A total of 100 Chinese patients with newly diagnosed type 2 diabetes were treated with repaglinide for 24 weeks. Arginine stimulation tests were performed to evaluate beta cell function. Gene variations were detected with PCR-restriction fragment length polymorphism. Responders were defined by a greater than 25% decrease in fasting plasma glucose or a greater than 20% decrease in hemoglobin A1c (HbA1c) values (or both) after the 24 week repaglinide treatment.Both baseline HbA1c and the decrease of HbA1c were significantly higher in patients with E/K and K/K genotypes of the KCNJ11 E23K variant when compared with E/E homozygotes (P=0.0103 and 0.0221, respectively). The decrease in 2 h postprandial plasma glucose (2hPG) was significantly greater in E/K heterozygotes than E/E homozygotes (P=0.0367). There was a significant difference in the response rate to repaglinide treatment between the E and K alleles (68% vs 82%, P=0.0324). The changes in fasting insulin and the homeostasis model assessment of insulin resistance were significantly greater in patients with ABCC8 exon16-3 C/C versus the T/C and T/T genotypes (P=0.0372 and 0.0274, respectively).The KCNJ11 E23K variant was associated with the therapeutic effect of repaglinide. In addition, The C/C homozygotes of the ABCC8 exon16-3T/C variant responded better to repaglinide in insulin sensitivity than the T/C and T/T genotypes.

To evaluate the applicability of the Cockcroft-Gault equation and the abbreviated Modification of diet in Renal Disease (MDRD) study equation to estimate the renal function of diabetic patients.Glomerular filtration rates measured by these two equations were compared with the value of GFR measured by 99Tc(m)-DTPA dynamic renal Imaging (considered as gold standard), to determine which equation is more appropriate in the subjects with diabetes.Both of the results of the two equations deviated from the GFR measured by 99Tc(m)-DTPA dynamic renal Imaging: the GFRCG result was lower and the GFR(MDRD) result was higher than the real GFR value. However, the correlation analysis, coherence testing, and accuracy by receiver operating characteristic curve analysis showed that the coefficient of correlation, coherence rate, and accuracy of the GFR(MDRD) formula with the gold standard were all higher than those of the GFR(CG) formula.The abbreviated style of MDRD equation is more appropriate than Cockcroft-Gault equation for the estimating of renal function in diabetic patients.

To provide evidence for assessing glycated albumin (GA) appropriately cliniccally through determining the GA level of type 2 diabetes mellitus (DM) patients and analyzing its influential factors.Continuous glucose monitor system was used to monitor the levels of fasting plasmic glucose (FPG), 2-hour post-prandial plasmic glucose (2hPG), GA, and glycated hemoglobin (HbA1c) in 445 type 2 DM in-patients.(1) The mean GA value was 24.9% +/- 7.0% and the mean HbA1c was 8.9% +/- 2.2%. (2) GA value was associated with HbA1c (P0.001). GA was positively correlated with FPG, 2hPG, and mean blood glucose (MBG) (all P0.01). (3) GA value was negatively correlated with BMI (P0.01). (4) Multiple stepwise regression analysis showed that HbA1c, BMI, and FPG were the main influential factors of GA.(1) GA value has good relationship with HbA1c, a golden standard to reflect the glycemic control in a long period. (2) BMI should be concerned when assessing GA value of DM patients, especially of the obese and thin subjects.

To investigate the effect of single nucleotide polymorphism (SNP) + 45 of the adiponectin (ADIPOQ) gene on the response to therapy with rosiglitazone maleate in patients with type 2 diabetes.A total of 103 newly diagnosed type 2 diabetes patients without taking any drug were enrolled and treated with rosiglitazone maleate (4 or 8 mg/d) for 24 weeks. On scheduled time phenotype measured were height, weight, waist, hip; blood pressure; HbA1c; plasma glucose level, serum insulin level, serum proinsulin level of blood obtained at 0, 2, 4 and 6 minute during arginine stimulation test; serum lipid level including total cholesterol, triglyceride, high-density and low-density lipoprotein cholesterol. Response to the rosiglitazone maleate therapy was defined by both aor = 20% decrease in fasting plasma glucose and aor = 15% decrease in HbA1c values after 24 weeks of rosiglitazone maleate treatment. All patients were genotyped for the ADIPOQ SNP + 45 by PCR-RFLP.(1) Of the 103 patients, the frequencies of TT, TG and GG genotypes of ADIPOQ SNP + 45 were 0.55, 0.36 and 0.09 respectively. The T allele frequency and G allele frequency were 0.73 and 0.27 respectively. (2) There was a significant difference in the response rate to rosiglitazone maleate treatment between the TT genotype and the TG + GG genotype (P = 0.0295). Response rate of the TG + GG genotype (56.41%) was higher than that of the TT genotype (33.93%). Furthermore, multivariate Logistic regression analysis revealed that SNP + 45 of ADIPOQ gene and HbA1c were the independent risk factors for rosiglitazone maleate treatment response. (3) After 24 weeks of treatment period, the FPG, 2hPG, HbA1c and HOMA-IR were significantly decreased in comparison with pre-treatment in both genotype groups. (4) The change in the clinical parameters after 24 weeks of treatment period showed no significant difference between the SNP + 45 of ADIPOQ gene.SNP + 45 of ADIPOQ gene is associated with the response rate to rosiglitazone maleate treatment in patients with type 2 diabetes and may be the major determinant of response rate. The response rate of the TG + GG genotype is higher than that of the TT genotype.

To study the prevalence and risk factors of nonalcoholic fatty liver (NAFL) of patients with type 2 diabetes.A total of 1335 patients with type 2 diabetes were divided into NAFL group and control group according to type B ultrasonic tomography results.(1) The prevalence of NAFL in type 2 diabetic patients was 42.1%. Among the patients younger than 50 years old, the prevalence of NAFL in males was higher than that in females. However, among the patients older than 50 years old, the case was just the opposite, higher in females. (2) The prevalences of overweight/obesity, dyslipidemia, hypertension, and metabolic syndrome (MS) of NAFL group were 59.4%, 66.4%, 57.7% and 71.7% respectively, all significantly higher than those of control group (P0.01). The risk for NAFL paralled with the increment of number of components of MS. Those patients with four components of MS had higher risk of NAFL than those patients with isolated type 2 diabetes (OR = 11.1 and 10.6, both P0.001). (3) The body mass index, diastolic blood pressure, fasting plasma glucose, hemoglobin A(1)c, total cholesterol, triglyceride, C-reactive protein (CRP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase, the level of serum uric acid and C-peptide of NAFL group were all higher than those of control group (P0.05 - 0.01). The level of serum high density lipoprotein-cholesterol and the AST/ALT rate were lower than those of control group (P0.05 - 0.01). Triglyceride, body mass index, CRP, the level of postprandial C-peptide at 30 min and fasting plasma glucose were the risk factors of NAFL. (4) The incidence of type 2 diabetic patients with increased CRP levels were 29.1% in male and 33.8% in female. patients with increased CRP levels had higher incidence of NAFL (54.4% vs 35.3% in male, 62.0% vs 38.4% in female, both P0.01).(1) About 2/5 of in-patients with type 2 diabetes had NAFL, and NAFL was closely associated with MS. (2) The increased level of CRP, as well as obesity, hyperglycemia, dyslipidemia and the increased level of postprandial C-peptide might increase the risk of NAFL in the patients with type 2 diabetes.

To explore the adult lipid profile of Huayang community from 1998 to 2000 and Caoyang communities in 2001.Representative serum samples of 5628 adults (aged 20 - 95 years) were obtained in Huayang and Caoyang communities during 1998.9 and 2001.11. Standard epidemiology questionnaire, physical check-ups and serum lipids data were analyzed.After standardization to Chinese census statistics of 2000, the age-and sex-standardized means of total cholesterol, HDL-C, LDL-C and triglycerides of the two communities (Huayang vs. Caoyang) were 5.01 mmol/L vs. 4.43 mmol/L, 1.28 mmol/L vs. 1.32 mmol/L, 3.37 mmol/L vs. 2.99 mmol/L, 1.97 mmol/L vs. 1.60 mmol/L respectively, and the age- and sex- standardized prevalence of dyslipidemia was 52.9% vs. 25.1%, and the prevalence for borderline dyslipidemia was 76.0% vs. 56.2%, respectively. The decreasing order of dyslipidemia prevalence of the two communities was: elevated TG, decreased HDL-C, elevated LDL-C and TC. The standardized proportions of optimal HDL-C level were only 15.7% and 16.1% in Huayang and Caoyang respectively which was much lower than these of TG, LDL and TC.The standardized prevalence of adult dyslipidemia and borderline dyslipidemia in the two communities were high. Dyslipidemia of the two communities was TG and decreased.

To investigate the change of pigment epithelium-derived factor (PEDF) in type 2 diabetic nephropathy, and to explore the significance of PEDF in the development of diabetic nephropathy.ELISA was used to detect the serum PEDF and immunoturbidimetry was used to measure the urinary albumin excretion (UAE) in 49 healthy controls and 132 type 2 diabetic patients, including 48 with normal urinary albumin excretion rate (NA group), 50 with microalbuminuria (MA group), and 34 with overt diabetic nephropathy (PR group). HbA1c, triglyceride (TG), total cholesterol, high density lipoprotein cholesterol (HDL-c), and highly sensitive C-reactive protein (hs-CRP) were simultaneously determined.The serum PEDF levels of the NA, MA, and PR groups were (3.7 +/- 2.2) mg/L, (4.7 +/- 2.9) mg/L, and (5.7 +/- 2.8) mg/L respectively, all significantly higher than that of the control group (2.7 +/- 1.3) mg/L. P0.05, 0.01, and 0.01 respectively). The serum PEDF levels of the MA and PR groups were significantly higher than that of the NA group (both P0.01), and that of the PR group was significantly higher than that of the MA group (P0.05). Correlation analysis demonstrated that serum PEDF level was positively correlated with HbA1c (r = 0.198, P0.01), FPG (r = 0.231, P0.01), TG (r = 0.302, P0.01), hs-CRP (r = 0.214, P0.01), and urinary albumin excretion rate (UAER) (r = 0.169, P0.05), significantly, but negatively correlated with HDL-c (r = -0.237, P0.01). Stepwise multiple linear regression analysis showed that TG (beta = 0.314, P0.01), hs-CRP (beta = 0.260, P0.01), and UAER (beta = 0.148, P0.05) were significant independent determinants for serum PEDF.Serum PEDF level significantly increases in type 2 diabetic patients, and the magnitude of PEDF is related to the severity of diabetic nephropathy. TG, hs-CR and UAER are significant independent determinant for serum PEDF. The increase of PEDF may involve in the development of diabetic nephropathy.

To establish reference values of glycemic parameters for continuous glucose monitoring in Chinese.Forty-eight individuals with normal glucose regulation were observed with continuous glucose monitoring system (CGMS) for 3 days. Indexes in CGMS were analyzed, including mean level of 24 h blood glucose (BG) values (24 h MBG) and its standard deviation (SDBG), percentage of time above 7.8 mmol/L or below 3.9 mmol/L, area under the curve (AUC) of BG above 5.6 mmol/L, the largest amplitude of glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE) and absolute means of daily differences (MODD).(1) The upper limits of indexes for continuous glucose monitoring were as follows: 6.5 mmol/L for 24 h MBG, 6.0 mmol/L, 6.3 mmol/L and 6.0 mmol/L for mean BG levels 1 h before breakfast, lunch and dinner respectively, 7.0 mmol/L, 6.7 mmol/L and 7.0 mmol/L for mean BG levels 3 h after breakfast, lunch and dinner respectively, 1.4 mmol/L for SDBG, 5.7 mmol/L for LAGE, 3.4 mmol/L for MAGE and 1.4 mmol/L for MODD. The percentage of time over 7.8 mmol/L was less than 9%, while the percentage of time below 3.9 mmol/L was less than 20%. The AUC of BG above 5.6 mmol/L was less than 0.9 d x mmol x L(-1). There was no statistical difference among sex subgroups (P0.05). (2) The correlations of 24h MBG with MAGE, MODD and SDBG were not significant (P0.05). MAGE was positively correlated with SDBG (r = 0.93, P0.01).The reference values of glycemic parameters for continuous glucose monitoring are initially established and can be used as a temporary reference for clinical practice in Chinese. The CGMS profile can reflect the overall BG control and the feature of glycemic excursions in detail.

To investigate the association between the polymorphisms of melanocortin-4 receptor (MC4R) gene and obesity.The genotypes of three polymorphisms, nt-216C/T, nt-178A/C, and Val103Ile, were determined through DNA sequencing in 563 Chinese from Shanghai, including 258 individuals with body mass index (BMI) over 30 kg/m(2) and 305 individuals with BMI less than 23 kg/m(2). Height and body weight were measured to calculate BMI. Blood pressure was measured. Waistline, hipline, and femoral waist to calculate the waist-to-hip ratio and waist-to-femoral ratio were measured. Oral glucose tolerance test was conducted to detect the plasma glucose level during fasting condition and 120 minute after glucose loading. The levels of serum lipids, including total cholesterol, triglyceride, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol.(1) The frequencies of nt-216C/T, nt-178A/C, and Val103Ile were all less than 5%. (2) Logistic regression showed that the Val103Ile variant was an independent risk factor for obesity (OR = 0.414, P = 0.040). The frequency of Ile was less in the obese individuals compared with the controls. (3) In the controls and obese individuals, no association was detected between the genotypes and phenotypes.Val103Ile variant of MC4R gene is associated with obesity in Chinese.

To study the clinical characteristics of hypertensive subjects with metabolic syndrome and its components in communities.Totally 5628 subjects aged over 20 years were included. Measurement indicators included height, weight, waist circumference (W) , hip circumference, systolic pressure (SP) , diastolic pressure (DP) , total cholesterol ( TC) , triglyceride (TG) , high-density lipoprotein cholesterol (HDL-C) , low-density lipoprotein cholesterol (LDL-C) , fasting plasma glucose (FPG) , 2 h postprandial plasma glucose (2hPG) , fasting serum insulin (FIN) , and 2 h postprandial serum insulin (2hIN). Body mass index (BMI) , waist to hip ratio (WHR), and homeostatic model approach-insulin resistance index (HOMA-IR) were calculated. According to 1999 WHO definition of metabolic syndrome, these individuals were divided into 4 groups: non-metabolic disorder group, isolated hypertension group, hypertension with one component of metabolic syndrome group, hypertension with two components of metabolic syndrome group, and hypertension with three components of metabolic syndrome group.Among subjects with hypertension, 15. 37% were patients with isolated hypertension, 32. 40% with one component of metabolic syndrome, 33. 36% with two components of metabolic syndrome, and 18. 87% with three components of metabolic syndrome. BMI, W, WHR, TC, TG, LDL-C, FPG, 2hPG, FIN, 2hIN and HOMA-IR in three groups (hypertension with one component of metabolic syndrome group, hypertension with two components of metabolic syndrome group, and hypertension with three components of metabolic syndrome group) significantly increased than those in isolated hypertension group (P0. 01 ). The hypertensive patients showed a higher insulin resistance, despite other metabolic disorders. Furthermore, the hypertensive patients with more components of metabolic syndrome showed a higher chance to get insulin resistance. Multiple stepwise regression analysis showed FPG, 2hPG, FIN, 2hIN, BMI, SP and TC were risk factors of HOMA-IR.Patients with isolated hypertension are rare in community-based population. About 85% of hypertensive patients have more than one metabolic disorders, more than half of were metabolic syndrome. The percentage of total body fat, levels of plasma glucose, serum insulin, total cholesterol and systolic blood pressure are independent risk factors of insulin resistance.

To study the changes of insulin sensitivity in individuals with impaired glucose tolerance and diabetes and the relationship between insulin sensitivity and over weight/obesity (OW/OB) .Fifty-two individuals were divided into 4 groups according to WHO diagnostic criteria of obesity (1998) and diabetes (1999): normal weight with normal glucose tolerance (NW-NGT) group, OW/OB with normal glucose tolerance (OW/OB-NGT) group, OW/OB with impaired glucose tolerance (OW/OBIGT) group and OW/OB with diabetes mellitus (OW/OB-DM) group. Individuals in OW/OB-NGT group were further classified into 3 subgroups: over weight subgroup, mild obesity subgroup, and mediate obesity subgroup. Abdominal fat area was measured with magnetic resonance imaging. Visceral obesity was defined as intra-abdominal fat area over 100 cm(2). All subjects with NGT were divided into visceral obesity (VA) group and non-visceral obesity ( Non-VA) group. Extended hyperinsulinemic euglycemic clamp was performed to assess the peripheral tissue insulin sensitivity in all subjects.The rates of insulin mediated glucose disappearance (Rd) were (3. 25+/-0. 13) mg x kg (-1) min (-1) in OW/OB-NGT group, (3. 06+/-0. 26) mg x kg(-1) x min(-1) in OW/OB-IGT group, and (3.19+/-0.44) mg x kg(-1) x min (-1) in OW/OB-DM group, which were significantly lower than that in NW-NGT group [ (5. 86+/-0. 65) mg x kg (-1) min (-1) ] (P0. 05, P0.01). The Rd in over weight subgroup [(3.50+/-0. 19) mg kg(-1) x min(-1) ] , mild obesity subgroup [(3. 03+/-0. 13) mg x kg (-1) min(-1)] , and mediate obesity subgroup [(2. 75 +/-0. 24) mg x kg (-1) min(-1)] were significantly lower than that of NW-NGT group (P0. 05, P0. 01). The Rd [ (2. 97+/-0. 12) mg kg(-1) x min(-1) vs (4.55+/-0.43) mg x kg(-1) x min(-1)] and glucose oxidation [(1.47 +/-0. 19) mg x kg(-1) min(-1) vs (2.24 +/-0. 19) mg kg(-1) x min(-1) in VA group were significantly decreased than that in non-VA group (P0. 05, P0. 01). Body mass index, waist and hip ratio, waist circumference, and intra-abdominal fat area were negatively correlated with Rd, respectively (P0. 01). Multiple regression analysis showed that body mass index, intra-abdominal fat area and abdominal subcutaneous fat area were the main risk factors of insulin sensitivity.Insulin sensitivity decreased in OW/OB individuals with or without hyperglycemia. Insulin sensitivity is lower in subjects with visceral obesity. Total body fat and abdominal fat are the main risk factors of insulin sensitivity.

To evaluate the efficacy of neuropathy symptom score/neuropathy disability score (NSS/NDS), Michigan Neuropathy Screening Instrument (MNSI), vibration perception threshold (VPT) and 24010 g monofilament examination in the diagnosis of diabetic peripheral neuropathy (DPN).240 patients with type 2 diabetes underwent the 4 simple tests: NSS/NDS, MNSI, VPT, and 10 g monofilament examination and nerve conduction velocity (NCV) examination. Using the results of NCV as golden criteria, the sensitivity, specificity, positive and negative predictive values, accuracy and kappa values of these tests were analyzed.The sensitivity, specificity, accuracy, and kappa value of MNSI score over 2 were 78.15%, 88.43%, 83.33%, and 0.67 respectively. The validity could be ranked in the following order with respect to the diagnosis of DPN: MNSIVPTNSS/NDS10 g monofilament examination.MNSI is a rapid, simple and reliable test for screening DPN in both diabetes clinics and epidemiological surveys.

To investigate the relationship between serum C-reactive protein (CRP) and metabolic disorders in individuals in Shanghai communities and to assess the value of CRP level on the risk of metabolic disorders.A total of 5502 individuals (males 2379, females 3123) aged over 20 years with complete baseline data on metabolic syndrome (MS) and serum CRP from 1998 to 2001 in two communities of Shanghai were included. Highly sensitive CRP was tested by kinetics nephelometry. Quartiles of concentration of CRP were computed. Hyperglycemia (diabetes or impaired glucose regulation), hypertension, dyslipidemia, central obesity and MS were defined by WHO (1999) working definition of MS. Logistic regression model was used to estimate the relation between CRP level and relative risks of metabolic disorders.(1) In this two communities based population the prevalences of metabolic syndrome and its components were as follow: hyperglycemia 21.63% (diabetes 9.21%, impaired glucose regulation 12.41%), hypertension 32.95%, high triglyceride (TG)/low high-density lipoprotein cholesterol (HDL-C) 46.04%, central obesity 40.68% and metabolic syndrome 13.98%. (2) Serum CRP level was gradually elevated with the increment of ages in both men and women (P0.01). (3) Serum CRP level was increased with the increment of the components of metabolic disorders (P0.01). In individuals with MS, CRP level was higher than in those with 1 or 2 components of metabolic disorders (P0.01). (4) The highest quartile of CRP was 2.11 mg/L in men and 2.22 mg/L in women. (5) Compared with those in the lowest quartile, men in the highest quartile had increased relative risk of hyperglycemia (3.8 times), central obesity (5.5 times), hypertension (2.8 times), hyper triglyceride (1.3 times), low HDL-C (1.5 times) and MS (10 times). Similarly, women in the highest quartile had increased relative risk of hyperglycemia (7.7 times), central obesity (12.2 times), hypertension (6.1 times), hypertriglyceride (5.6 times), low HDL-C (1.1 times) and MS (8.5 times).(1) CRP level was related to the increment of age. (2) Individuals with more components of metabolic syndrome had higher serum CRP level. (3) The incidence of metabolic syndrome was increased with the increment of CRP level. The risk of metabolic disorders including hyperglycemia, hypertension, dyslipidemia, central obesity and metabolic syndrome was significantly elevated in men with CRP level over 2.11 mg/L and women with CRP level over 2.22 mg/L.

To investigate the prevalence of peripheral vascular disease (PVD) in patients with diabetes mellitus (DM) and impaired glucose regulation (IGR).Follow-up 5 years after the previous epidemiologic study of metabolic syndrome in Chaoyang community, Shanghai, 2000 - 2001 was conducted among 717 patients with DM or IGR. Questionnaire survey about general status and DM-related history and behaviors, including smoking, was carried out. Physical examination was made. Ankle/brachial index (A/BI) was measured. Intermittent claudication was surveyed by Edinburgh claudication questionnaire (ECQ). Blood sugar and blood lipid were detected. 427 patients, 210 males and 217 females, aged 67.3 +/- 14.0 (21 - 104), with intact data were enrolled into the analysis.The overall prevalence of PVD was 12.2% in the hyperglycemic population. The prevalence of PVD in the diabetics was 15.1%, significantly higher than that of the IGP subjects (7.7%, P = 0.022). The rate of intermittent claudication in those with the A/BIor= 0.9 was 13.5%. Logistic regression revealed that age, sex, diabetic duration, and total cholesterol were independent risk factors of diabetic PVD.The PVD prevalence is rather high in both diabetics and IGR subjects. Most PVD patients are asymptomatic. AB/I measurement helps early diagnosis of PVD.

To study the characteristics of insulin ultradian pulses of individuals with normal glucose tolerance, overweight, and impaired glucose tolerance (IGT).Blood samples were taken every 15 minutes from 10 individuals with normal glucose tolerance, 6 individuals with overweight and 3 individuals with IGT for 24 hours. Blood glucose, insulin, and C-peptide of every time point were measured. Standard diet was used in the study. The 24 h-ISR profile was submitted to time series analysis.(1) As given standard diet, 2 to 4 pulses occurred after each meal, 3 to 4 pulses occurred during the night, and 12 to 15 pulses occurred in the whole 24-hour period. The first insulin pulse always occurs 30 to 60 minutes after meal. The maximum amplitude of pulse occurred 45 to 90 minutes after meal. These characteristics were not significantly different among the 3 groups. (2) The average amplitude of 24-hour insulin secretion rate (ISR) of the normal group was 357 pmol/min +/- 11 pmol/min, significantly lower than those of the overweight and IGT groups (820 pmol/min +/- 37 pmol/min and 666 pmol/min +/- 53 pmol/min respectively, both P0.05). (3) The average periodicity of insulin ultradian pulse were 75 min and 75 - 90 min in the control group and overweight group respectively. The periodicity of insulin ultradian pulse in the IGT group was undefined. (4) The cross-correlation function were 0.72 +/- 0.11, 0.80 +/- 0.11 and 0.51 +/- 0.11 respectively in the normal, overweight, and IGT groups.(1) As given standard diet, the occurring numbers and time of insulin ultradian oscillations are not statistically significantly different among the normal, overweight, and IGT groups. (2) The insulin secretion amplitude is increased in the overweight and IGT groups. (3) The rhythm and concomitance coefficient of the ISR and glucose are low in the individuals with IGT.

To study the features of postprandial glucose state in individuals with normal glucose regulation (NGR) and type 2 diabetes (T2DM) and the relations between hemoglobin A1c (HbA1c) and postprandial glucose in T2DM.41 NGR individuals and 60 newly diagnosed T2DM patients without previous management in Shanghai were measured by continuous glucose monitoring system for 3 days. The postprandial glucose spike (PGS), time to PGS (Deltat), postprandial glucose excursion (PPGE), duration of postprandial glucose (DUR) and incremental area under the curve of postprandial glucose (IAUC) were calculated in each individual.(1) The levels of PGS and Deltat in the T2DM group were significantly higher than those of the NGR group (all P0.01). The levels of PPGE, DUR and IAUC of the T2DM group were 5.87 mmol/L +/- 0.19 mmol/L, 14.1 h +/- 0.3 h and 2.04 mmol.L(-1).d +/- 0.09 mmol.L(-1).d respectively, all significantly higher than those of the NGR group (2.10 mmol/L +/- 0.12 mmol/L, 8.3 h +/- 0.4 h and 0.43 mmol.L(-1).d +/- 0.03 mmol.L(-1).d respectively, all P0.01). The breakfast had higher PGS and lower Deltat than those of lunch and dinner in the T2DM group (both P0.01). The PPGE was arranged from high to low in the order of breakfast, dinner and lunch. The highest IAUC appeared during dinner. (2) There was a significantly correlation between PPGE and IAUC (r = 0.93, P0.01) in the T2DM group. After being adjusted by preprandial glucose, the partial correlation of HbA1c and IAUC disappeared (before r = 0.29, P = 0.03, after P = 0.05). (3) The relative contribution of postprandial glucose to overall glucose levels in the T2DM group was significantly higher than that of the NGR group (18.1% +/- 0.8% vs 8.0% +/- 0.7%, P0.01), but both were significantly lower than those of preprandial glucose. (4) Relative contribution of postprandial hyperglycemia to overall diurnal hyperglycemia decreased progressively from the lowest to the highest quarter of HbA1c. By contrast, the relative contribution of preprandial hyperglycemia showed a significant increase with increasing levels of HbA1c. Postprandial hyperglycemia played a major role when the HbA1c level below 7.5% (P0.05).(1) The features of postprandial glucose state in T2DM is representative in the delay of PGS and excessive glucose excursion for a long time after the ingestion of a meal. (2) HbA1c can't reflect postprandial glucose excursions. PPGE can be used as a simple clinic index to evaluate the amplitude of postprandial glucose excursions. (3) Postprandial glucose excursions play a major role in T2DM suffering from mild or moderate hyperglycemia. The present results suggest that postprandial hyperglycemia is an important target for intervention when T2DM patients are approaching the ideal glycemic control.

To investigate the relationship of the C to T variant at the -55 site of the promoter region of uncoupling protein 3 gene (UCP3) with the resting energy expenditure and the parameters of body fat in Chinese population.Three hundred Chinese (91 normal weight subjects, 209 overweight/obesity subjects) were genotyped for the UCP3 gene -55(CT) by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Resting energy expenditure (REE), fat mass (FM), fat free mass (FFM) and the parameters for regional adipose tissue distribution were measured.Genotype frequencies of UCP3 gene -55(CT) were not associated with obesity and different types of obesity. The REE level in normal weight subjects with TT homozygotes was higher than that in those with CT heterozygotes and CC homozygotes (P=0.0200). Similar tendency was also observed in overweight/obesity subjects. The FM/FFM exhibited significant difference between the overweight/obesity subjects with a TT genotype and those with a CT or CC genotype (P=0.0096).The level of difference in REE caused by the polymorphism of promoter region of UCP3 -55(CT) may play a role in energy metabolism in Chinese.

To study serum adiponectin level in relation to body fat distribution and tissue insulin sensitivity by using the extended hyperinsulinemic euglycemic clamp technique.Extended hyperinsulinemic euglycemic clamp was performed in 44 Chinese individuals with normal glucose tolerance from Shanghai area, including 12 subjects with normal weight [body mass index (BMI)25 kg/m(2)], 19 with overweight (25 kg/m(2)or = BMI30 kg/m(2)), and 13 with obesity (BMIor = 30 kg/m(2)). The rate of insulin-mediated glucose disposal (Rd) during the steady state of glucose clamp was used to assess the peripheral tissue insulin sensitivity. Total body fat depots [BMI, percentage of body fat (FAT%), and body fat mass (FM)], regional body fat depots [waist circumference (W), hip circumference (H), W and H ratio (WHR), abdominal subcutaneous fat area (SA), intra-abdominal fat area (VA), and femoral subcutaneous fat area (FA)] were measured on all subjects. Fasting serum adiponectin level was determined by radioimmunoassay.(1) After the adjustment for age and sex, the serum adiponectin concentrations in the overweight and obesity groups were (8.7 +/- 4.8) mg/L and (6.7 +/- 0.8) mg/L, both significantly lower than that in the normal weight group [(15.7 +/- 1.8) mg/L, both P0.01]. (2) Serum adiponectin concentration was negatively correlated with BMI, W, WHR, FAT%, FM and VA, especially with W and VA (r = -0.46, P0.01, and r = -0.53, P0.01). (3) Serum adiponectin concentration was positively correlated with Rd (r = 0.52, P0.01) and the rate of glycogen synthesis (r = 0.36, P0.05), and was negatively correlated with free fatty acid level (r = -0.41, P0.05). (4) Stepwise regression analysis indicated that in addition to sex, BMI, WHR or VA and SA, serum adiponectin level was also the independent contributing factor for Rd, which explains 3.52% and 4.84% of the variance respectively (P all0.05).(1) The decrease in serum adiponectin level is associated with the increase of total body fat depot, especially the increase of total body fat depot in intra-abdominal fat area. (2) Serum adiponectin level is an independent contributing factor for insulin sensitivity.