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The purpose of the present study was to investigate the effect of high-sensitivity C-reactive protein (hs-CRP) on the risk of cardiovascular disease (CVD) in a Chinese population. A total of 2,656 participants (aged 30 to 95 years) with baseline hs-CRP levels available were monitored for the incidence of a composite of CVD events (stroke and coronary heart disease) during a 5.5-year period. With increasing quartiles of hs-CRP (<0.47, 0.47 to 0.97, 0.97 to 2.09, and ≥2.09 mg/L), the incidence of CVD increased progressively (11.7, 16.4, 24.7, and 36.5 per 1,000 person-years, respectively). In a Cox model adjusted for other traditional risk factors (e.g., age, blood pressure, diabetes mellitus, lipids, body mass index, smoking status), elevated hs-CRP (≥2.0 mg/L) independently predicted the risk of CVD (hazard ratio 1.39; 95% confidence interval 1.04 to 1.87). The effect was especially significant for stroke (hazard ratio 1.58; confidence interval 1.08 to 2.31). In conclusion, the results of our study suggest that elevated hs-CRP (≥2.0 mg/L) is an effective predictor of CVD in a Chinese population. [Copyright &y& Elsevier]

Abstract: Objective: To determine the appropriate cutoffs for visceral fat area (VFA) measured by magnetic resonance imaging linking to risk of the metabolic syndrome (MetS) and the corresponding waist circumference in Chinese. Methods and results: Totally 1140 individuals (men 525, women 615) aged from 35 to 75 years were included. The components of the MetS were defined by International Diabetes Federation (IDF) and Chinese Diabetes Society (CDS) definition, respectively. Receive operating characteristic curve analyses were used to determine the appropriate cutoffs of VFA and corresponding waist circumference in the prediction of the MetS. The optimal VFA cutoff was near 80cm2 in identifying the MetS with two or more components but not including overweight/obesity by either of the two definitions in all subjects. There was no difference in men by ages while women aged <50 years tended to have lower VFA cutoff than those aged ≥50 years by the two definitions. The appropriate waist circumference cutoffs were 90cm in men and 85cm in women for the MetS. Conclusion: The optimal cutoff of waist circumference for abdominal obesity is 90cm for men and 85cm for women in Chinese. [Copyright &y& Elsevier]

Background: Low muscle mass likely results in reduced capacity for glucose disposal, leading to a significant but under-appreciated contribution to increasing the risk of diabetes. But few prospective studies have investigated the association between the loss of muscle mass and the occurrence of diabetes. We aimed to investigate whether short-term changes in muscle mass affect the incidence of diabetes in a Chinese population. Methods: This study included 1275 individuals without evident diabetes at baseline. In the baseline and re-examination, individuals completed the risk factors survey and underwent body composition measurement. Muscle mass index was defined as the percentage skeletal muscle mass, which was measured by an automatic bioelectric analyzer. Results: After a median follow-up of 2.1 years, 142 individuals developed diabetes (11.1%). There was an inverse association between basal skeletal muscle mass index and the risk of diabetes in participants with impaired glucose regulation but not in those with normal glucose tolerance. Multivariate-adjusted hazard ratios for the risk of developing diabetes were 0.85 (95% CI: 0.74–0.98) and 1.15 (95% CI: 0.98–1.34), respectively. Furthermore, Cox regression analysis revealed that a two-year change in skeletal muscle mass was also inversely associated with the incidence of diabetes in both participants with normal glucose tolerance and with impaired glucose regulation (HR: 0.76, 95% CI: 0.65–0.89; HR: 0.81, 95% CI: 0.71–0.91). Conclusions: These findings emphasized the importance of early detection and control of muscle mass loss for the prevention of diabetes. [ABSTRACT FROM AUTHOR]

Aims/Introduction: To define the target value for the percentage coefficient of variation for glucose (%CV) as a measure of glycemic variability (GV) in Chinese diabetes patients. Materials and Methods: This retrospective study included 3,007 diabetes patients who underwent continuous glucose monitoring for 3 days. Type 2 diabetes was divided into groups according to the received treatment: group 1, non‐insulinotropic agent (n = 138); group 2, insulinotropic agent (n = 761); group 3, basal insulin therapy (n = 100); group 4, premixed insulin (n = 784); and group 5, intensive insulin therapy (n = 612). Type 1 diabetes patients were included as group 6 (n = 612). %CV and percentage of time per day within, below (3.9mmol/L; TBR3.9) and above (10.0 mmol/L) the target glucose range (3.9–10.0 mmol/L) were computed. TBR3.9 ≥4% was defined as excessive hypoglycemia. Results: Type 2 diabetes with a premixed or intensive insulin regimen had an increased %CV compared with those receiving oral therapy or basal insulin. The upper limit of %CV in group 1 was 33%, which was adopted as the threshold to define excessive GV. For each treatment group, the percentage of people with TBR3.9 ≥4% was significantly greater in the subgroup with %CV >33% than ≤33% (P < 0.001). In participants who achieved TBR3.9 <4%, the time per day spent within the target glucose range of 3.9–10.0 mmol/L > 70% and time per day above 10.0 mmol/L <25%, the 95th percentile of %CV was 32.70%. Further receiver operating characteristic curve analysis showed that the cut‐off values of %CV for predicting TBR3.9 ≥4% varied by the type of diabetes and glycated hemoglobin categories. Conclusions: A %CV of 33% was set as the threshold for excess glucose variability in Chinese diabetes patients. Meanwhile, glycated hemoglobin and the type of diabetes should be considered for the goal‐setting of %CV. [ABSTRACT FROM AUTHOR]

Aim. To investigate the effects of alcohol on serum glycated albumin (GA) levels in Chinese men. Methods. A total of 2314 male subjects from the Jinuo ethnic group in China were enrolled. Of these, 986 subjects drank alcohol frequently and 404 subjects did not. Lifestyle information was gathered by using a questionnaire, and measurements of blood pressure, body mass index, blood glucose level, liver function, and kidney function were collected. GA was measured by using an enzymatic method. Frequent drinking was defined as a history of drinking ethanol > 80 g/d within the past two weeks. Nondrinking was defined as no alcohol consumption in the past three months. Subjects with an alcohol intake between 0 and 80 g/d in the past two weeks were included in the drinking-occasionally group. Analysis of variance (ANOVA), correlation analysis, and linear regression were used to evaluate the effects of drinking on serum GA levels. Decision tree regression (DTR) algorithm was used to evaluate the effect of features (variables) on GA levels. Results. We found that male subjects who drank frequently had significantly lower serum GA levels than subjects who did not drink (13.0 ± 1.7 vs. 14.1 ± 3.7, p < 0.05). Spearman's correlation analysis calculated a coefficient of −0.152 between drinking and GA (p < 0.005). Linear regression established that drinking was an independent predictor for GA levels with a standardized regression coefficient of −0.144 (p < 0.05). Decision tree regression showed that the effect of drinking on GA levels (0.0283) is five times higher than that of smoking (0.0057). Conclusions. Frequent alcohol consumption could result in decreased GA levels in men of the Jinuo ethnic group in China. [ABSTRACT FROM AUTHOR]

Aim: To assess the efficacy and safety of polyethylene glycol loxenatide (PEX168), a new glucagon‐like peptide‐1 receptor agonist, as an add‐on to metformin therapy in Chinese patients with type 2 diabetes (T2D). Materials and methods: This was a multicentre, randomized, double‐blind, placebo‐controlled phase 3b trial. After metformin monotherapy (≥1500 mg/day) for 8 weeks or more, patients with uncontrolled T2D (HbA1c of 7.0%‐10.5%) from 44 sites were randomized (1:1:1) to metformin + placebo, metformin + PEX168 100 μg, and metformin + PEX168 200 μg. The core treatment period lasted for 24 weeks, followed by a 28‐week extension period. The primary endpoint was the change in HbA1c levels at week 24. The main secondary endpoint was the proportion of patients with an HbA1c of less than 7.0% at week 24. Results: The least‐square mean (standard error) change in HbA1c levels was significantly greater (P <.001 for superiority) in the PEX168 groups (−1.16% [0.08%] and −1.14% [0.08%] with 100 and 200 μg, respectively) than in the placebo group (0.35% [0.08%]). The proportion of patients with an HbA1c of less than 7.0% at week 24 was significantly higher in the PEX168 100 μg (37.4%) and PEX168 200 μg (40.6%) groups than in the placebo group (16.8%; both P <.001). The gastrointestinal reactions were mild; the risks of hypoglycaemia and weight gain did not increase. Anti‐PEX168 antibodies were noted in less than 2% of patients. No treatment‐emergent serious adverse events occurred. Conclusion: The subcutaneous injection of PEX168 once a week can effectively, continuously and safely improve HbA1c levels in patients with T2D when combined with metformin. [ABSTRACT FROM AUTHOR]

Background: Clinical and basic investigations have indicated a significant association between circulating growth differentiation factor 15 (GDF15) and cardiovascular disease; however, the relationship between GDF15 and lower extremity atherosclerotic disease (LEAD) has been less studied. The present study aimed to explore the association between GDF15 and LEAD in Chinese patients with type 2 diabetes mellitus (T2DM). Considering that obesity is an important factor associated with circulating GDF15 levels, whether the relationship between serum GDF15 levels and LEAD is affected by body mass index (BMI) was also analysed. Methods: A total of 376 hospitalized T2DM patients were enrolled (161 with LEAD and 215 without LEAD). A sandwich enzyme-linked immunosorbent assay was used to detect the serum GDF15 levels. The femoral intima-media thickness (F-IMT) and LEAD were assessed by ultrasonography. Results: Patients with LEAD had significantly higher serum GDF15 levels than those without LEAD, regardless of whether their BMI was < 25 kg/m2 or ≥ 25 kg/m2 (both P < 0.05). Serum GDF15 levels were independently positively related to the F-IMT (standardized β = 0.162, P = 0.002). After adjusting for confounding factors, per 1-standard deviation (SD) increase in the serum GDF15 levels was significantly related to an approximately 1.4-fold increased risk of LEAD in the total population (P < 0.05). Regardless of whether the BMI was < 25 kg/m2 or ≥ 25 kg/m2, this association remained significant, with approximately 1.6- and 1.4-fold increased risks of LEAD, respectively (both P < 0.05). Conclusions: High serum GDF15 levels were significantly correlated with an increased risk of LEAD in T2DM patients, and this relationship was independent of BMI. [ABSTRACT FROM AUTHOR]

Purpose:This observational study investigated the association between serum osteocalcin level and blood pressure in a Chinese population. Materials and methods:A total of 2241 subjects (909 men and 1,332 women; age, 24–78 years) from Shanghai communities were recruited. Subjects were divided into non-hypertensive and hypertensive groups according to diagnosis of hypertension based on the 1999 World Health Organization-International Society of Hypertension Guidelines. Serum osteocalcin levels were measured using an electrochemiluminescence immunoassay. Results:Men in the hypertensive group showed lower serum osteocalcin level compared with those in the non-hypertensive group, [16.37 (13.34–20.11) ng/mL versus 17.01 (14.23–20.79) ng/mL,p = .039]. No difference in serum osteocalcin level was found between the two groups of women (p = .675). An inverse association was observed between serum osteocalcin level and systolic blood pressure (SBP) in men (p = .004), but serum osteocalcin level was not associated with diastolic blood pressure (DBP) in men (p = .472). No associations were detected between serum osteocalcin level and SBP or DBP in women (SBP:p = .108; DBP:p = .575). A multiple stepwise regression analysis showed an inverse association between serum osteocalcin level and SBP in men after adjusting for age, smoking status, family history of hypertension, and lipid and C-reactive protein levels (standardized β = –0.074,p = .023), but the association disappeared after adjustment for body mass index, waist circumference, blood glucose, and homeostasis model assessment of insulin resistance (p = .327). Conclusions:Serum osteocalcin level was not independently associated with blood pressure in a Chinese population. [ABSTRACT FROM PUBLISHER]

Background In subjects who present a first fasting plasma glucose (FPG 1 ) ≥ 7.0 mmol/l without classic symptoms of diabetes, diagnosis of diabetes will likely be missed without an additional oral glucose tolerance test (OGTT) in the Chinese population. Recent studies have shown that glycated albumin (GA) has advantages in reflecting postprandial hyperglycemia. Therefore, the present study evaluated whether additional measurement of GA could reduce the rate of missed diagnosis of diabetes. Methods A total of 1287 participants (711 men, 576 women) with a FPG 1 ≥ 7.0 mmol/l without classic symptoms of diabetes were enrolled and underwent a 75-g OGTT. Serum GA was measured by a liquid enzyme method. Diabetes was diagnosed based on the 2010 American Diabetes Association (ADA) criteria. Results A total of 992 (77.08%) participants were diagnosed diabetes by OGTT and glycated hemoglobin A 1c (HbA 1c ). The diagnostic validity of 2-h postload plasma glucose (2hPG) was superior to other glycemic index (the diagnostic sensitivity of 2hPG, HbA 1c , the second FPG (FPG 2 ) was 87.50%, 73.99%, 63.21%, respectively). Without 2hPG after OGTT, repeat testing of FPG 2 alone would result in missed diagnosis of 36.79% of diabetic participants, whereas testing FPG 2 with HbA 1c was associated with a missed diagnosis rate of 14.31%. While using the combined criteria of FPG 2 ≥ 7.0 mmol/l and/or HbA 1c ≥ 6.5% and/or GA ≥ 17.1%, the rate of missed diagnosis was merely 9.48%. That is, the rate of missed diagnosis was reduced by 33.75% with the addition of GA measurement. The k value reflecting the consistency of diagnosis between the FPG 2 and/or HbA 1c and/or GA criteria and the 2010 ADA criteria was 0.788. Conclusions For subjects with FPG 1 ≥ 7.0 mmol/l without classic symptoms of diabetes, additional measurement of GA can help prevent missed diagnosis of diabetes in Chinese population. [ABSTRACT FROM AUTHOR]

Aims/Introduction It has not been reported whether chronic hepatitis B virus infection ( CHB) is associated with a specific type of diabetes. We sought to investigate the prevalence of CHB status in different diabetes subtypes among a Chinese population. Materials and Methods This was a cross-sectional study. A total of 381 patients with adult-onset autoimmune diabetes, 1,365 patients with type 2 diabetes and 1,365 non-diabetic controls were recruited from June 2005 to February 2014. The exclusion criteria included: (i) hepatitis C virus antibody positive; (ii) hepatic cirrhosis; and (iii) malignant neoplasm and severe renal dysfunction (serum creatinine >450 μmol/L). Patients were grouped as hepatitis B virus-negative and CHB status. Results Patients with type 2 diabetes had a higher prevalence of CHB than the controls in the overall population (13.5 vs 10.0%, P = 0.004) and among patients with normal hepatic function (13.3 vs 8.8%, P = 0.002). There was no difference in the prevalence of CHB status between patients with adult-onset autoimmune diabetes and the controls. Multiple logistic regression analysis showed that the odds ratio of CHB increased by ~1.5-fold in patients with type 2 diabetes than in the control group after adjustment for age, sex and body mass index, regardless of hepatic function status. Conclusions CHB status was more prevalent in patients with type 2 diabetes than in individuals with adult-onset autoimmune diabetes and the controls among the Chinese population. Further research is required to ascertain whether CHB status increases the risk of developing type 2 diabetes, or whether type 2 diabetes, but not adult-onset autoimmune diabetes, increases the risk of CHB. [ABSTRACT FROM AUTHOR]

Aims/Introduction Individuals with type 2 diabetes mellitus are vulnerable to micro- and macrovascular complications in the presence of microalbuminuria. Adipocyte fatty acid-binding protein (A-FABP) was proposed as an indicator for albuminuria in patients with diabetes. The present study aimed to explore the associations between serum A-FABP levels and microalbuminuria in the hyperglycemic population. Materials and Methods Serum A-FABP levels were detected using sandwich enzyme-linked immunosorbent assay. Microalbuminuria was identified by urinary albumin-to-creatinine ratio (UACR), when the value was between 30-300 mg/g. The participants were divided into the subgroups based on sex and the status of impaired glucose regulation or newly diagnosed type 2 diabetes mellitus. Results A total of 939 participants, consisting of 436 men and 503 women, were enrolled. Serum levels of A-FABP were much higher in participants with microalbuminuria than those without microalbuminuria. This result held true for all subgroups (all P < 0.05). For Spearman's correlation analyses, serum A-FABP levels showed a positive relationship with the UACR in men and women (both P < 0.01). Multiple stepwise regression analysis showed that serum A-FABP levels were independently and positively correlated with UACR in both sexes (men: standardized β = 0.256, P < 0.001; women: standardized β = 0.155, P = 0.001). This relationship remained significant in every subgroup (all P < 0.01). Conclusions For hyperglycemic individuals, serum A-FABP levels increased in the presence of microalbuminuria. Serum A-FABP levels were identified as an independent factor positively associated with the UACR. [ABSTRACT FROM AUTHOR]

Background: Diabetes is associated with genetic susceptibility, and family history is a risk factor. The study investigated the association between different family history risk levels and the prevalence of diabetes in a multi high-risk cohort and evaluated the impact of family history of diabetes on insulin secretion and insulin sensitivity.Materials and Methods: We analyzed data from 9754 adults who participated in the Shanghai High-Risk Diabetic Screen Project between 2002 and 2012. The association among three family history risk levels (mild, moderate, and high) with the prevalence of diabetes, insulin secretion, and insulin sensitivity was evaluated in the multi high-risk cohort.Results: Overall, 69.6%, 24.8%, and 5.6% of participants were categorized as having mild, moderate, and high familial risk, respectively. The standardized prevalence was higher in the high family history risk group (43.1%) than in the moderate group (37.3%) and in the mild group (23.5%) (P < 0.001). The odds ratios (ORs) were significantly increased in the moderate group (OR 1.27, 95% confidence interval [CI] 1.15-1.40, P < 0.05) and in the high group (OR 1.69, 95% CI 1.41-2.02, P < 0.05). Among the 3245 normal glucose tolerance participants, insulin secretion significantly declined with increasing levels of family history risk, but there were no significant differences in insulin sensitivity among the three groups.Conclusion: The prevalence of diabetes was independently associated with an increasing family history risk level among multi high-risk Chinese populations. Subjects with moderate and high familial history of diabetes displayed a significant decrease in insulin secretion. [ABSTRACT FROM AUTHOR]

Background As the association between uric acid and macrovascular disease has been heavily debated, we aimed to confirm whether there is a causal relationship between uric acid and diabetic macrovascular disease through Mendelian randomization analysis. Methods In 3207 type 2 diabetes patients, seventeen SNPs (single nucleotide polymorphisms) related to uric acid were genotyped. A weighted GRS (genetic risk score) was calculated using selected SNPs and the strength of their effects on uric acid levels. Diabetic macrovascular disease was diagnosed through vascular ultrasound, magnetic resonance imaging or other clinical evidence. Associations of diabetic macrovascular disease with uric acid and weighted GRS were evaluated separately. Results In total participants and among females, the prevalence of diabetic macrovascular disease was significantly higher in hyperuricemic group than in normouricemic group, and uric acid was associated with diabetic macrovascular disease (OR = 1.068, p = 0.0349; OR = 1.122, p = 0.0158). The prevalence of diabetic macrovascular disease increased with the weighted GRS in a J-shaped manner for the females. The weighted GRS was positively correlated with uric acid in total population, male patients and female patients (β = 0.203, p < 0.0001; β = 0.255, p < 0.0001; β = 0.142, p < 0.0001, respectively). The weighted GRS was significantly associated with diabetic macrovascular disease in female patients (OR = 1.184, p = 0.0039). Among females, the observed association between weighted GRS and diabetic macrovascular disease was greater than predicted. Conclusions Using the uric acid-related weighted GRS as an instrumental variable for Mendelian randomization analysis, our study provided an evidence for causal relationship between uric acid and diabetic macrovascular disease in Chinese females with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Aims: To explore the factors mediating the relationship between body mass index (BMI) and diabetic retinopathy (DR) in Chinese type 2 diabetes patients. Methods: This is a cross-sectional study. Data of 2,533 patients with type 2 diabetes were studied from the Shanghai Diabetes Registry Database. DR was assessed using non-mydriatic fundus photography and graded as non-DR, mild-moderate (DR I-II), and sight-threatening (DR III-IV). BMI (kg/m) was classified as normal weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30), and obese (BMI ≥ 30). β cell function was evaluated by fasting C-peptide (FCP). Results: DR was present in 701 (27.7 %) patients. Patients with DR had lower BMI (24.3 vs. 24.9 kg/m, P = 0.001) and fasting C-peptide (1.46 vs. 1.86 ng/ml, P < 0.001) than those without DR. The association between BMI (2 kg/m interval) and DR was U-shaped; patients with BMI 28-29.9 kg/m had the lowest DR rate. Compared with normal weight, overweight was associated with reduced risk of any DR [odds ratio (OR) 0.73], DR I-II (OR 0.76), and DR III-IV (OR 0.64) after adjustment for sex, age at diabetes diagnosis, and duration of diabetes. This negative association attenuated after adjustment for other confounders and became nonsignificant after further adjustment for FCP. Patients with different BMI categories had similar DR risk when stratified by FCP tertiles. Conclusion: Overweight patients have lower DR prevalence than normal weight individuals, which may be attributable to better β cell function in overweight patients. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the relationship between serum vitamin D level and carotid intima-media thickness (C-IMT) in Chinese postmenopausal women. Methods: Nine hundred and twenty six Chinese postmenopausal women without carotid artery plaque or history of cardiovascular disease were selected for analysis. Measurements of serum 25 hydroxyvitamin D3 (25(OH)D3) concentration and C-IMT were made by electrochemiluminescence immunoassay and B-mode ultrasound, respectively. Trend analysis was conducted according to tertiles of C-IMT. Results: The median serum 25(OH)D3 level was 11.03 ng/mL, with an interquartile range of 8.22–14.70. A decreasing trend of serum 25(OH)D3 level was accompanied by increased C-IMT tertiles (P for trend = 0.001). Correlation analysis found an inverse relationship between serum 25(OH)D3 level and C-IMT (r = –0.113, P = 0.001). After adjustment for confounding factors, multiple regression analysis showed that serum 25(OH)D3 level independently and negatively associated with C-IMT (Standard β = –0.112, P < 0.001). Moreover, the inverse correlation of serum 25(OH)D3 with C-IMT was also found in a subgroup of women with normal glucose tolerance, blood pressure and body mass index, and without undergoing lipid-lowering therapy (standard β = –0.140, P = 0.018). Conclusions: Serum 25(OH)D3 level was inversely correlated with C-IMT in Chinese postmenopausal women. [ABSTRACT FROM AUTHOR]

Background: This study was designed to clarify the influence of metformin on serum carbohydrate antigen 199 (CA199) levels and its associated factors in Chinese type 2 diabetes mellitus (T2DM) patients. Subjects and Methods: In total, 1,253 T2DM patients were enrolled, including a non-metformin group ( n=616), a short-term metformin group (at least 1 week to 2 years; n=325), and a long-term metformin group (≥2 years; n=312). Their clinical and biochemical characteristics were collected and compared. After 1 year, the biochemical parameters were re-examined in 296 patients. Sex hormones were determined, and associations between CA199 and other variables were assessed. Results: At baseline, the incidence of abnormal CA199 levels was 14.7%, 8.9%, and 4.7% in the non-metformin, short-term metformin, and long-term metformin groups, respectively. CA199 levels in females were significantly higher than in males ( P<0.01) and decreased significantly with the time of taking metformin (25.60±13.68 U/mL in non-metformin controls vs. 17.62±10.87 U/mL in the short-term group vs. 10.54±8.14 U/mL in the long-term group; P=0.000). The correlation and multiple stepwise regression analysis revealed that glycosylated hemoglobin, metformin, gender, total cholesterol, and follicle-stimulating hormone were independent impact factors on CA199 concentrations (all P<0.05). Binary logistic regression revealed that the risk of abnormal CA199 concentrations of the total population with short-term metformin or long-term metformin treatment decreased 11% (odds ratio=0.89; P=0.001) and 30% (odds ratio=0.70; P=0.000), respectively, at baseline. After a 1-year follow-up, the incidence of high CA199 level decreased in both the short-term and the long-term metformin group compared with that of controls ( P<0.05). The extent of CA199 decrease in the long-term metformin group was the greatest (−17% vs. −4.9% in the short-term group vs. 3% in controls, P=0.000), and the group's risk of high blood CA199 level was reduced 67% (odds ratio=0.33; P=0.023). The reduction in women was more apparent than that in men (−18% vs. −5%, P=0.000). Conclusions: Metformin therapy reduced the CA199 level in Chinese T2DM patients, and its greatest decrease occurred in women with longer therapeutic time. [ABSTRACT FROM AUTHOR]

Background: Elevated serum uric acid concentration is an independent risk factor and predictor of type 2 diabetes (T2D). Whether the uric acid-associated genes have an impact on T2D remains unclear. We aimed to investigate the effects of the uric acid-associated genes on the risk of T2D as well as glucose metabolism and insulin secretion. Method: We recruited 2,199 normal glucose tolerance subjects from the Shanghai Diabetes Study I and II and 2,999 T2D patients from the inpatient database of Shanghai Diabetes Institute. Fifteen single nucleotide polymorphisms (SNPs) mapped in or near 11 loci (PDZK1, GCKR, LRP2, SLC2A9, ABCG2, LRRC16A, SLC17A1, SLC17A3, SLC22A11, SLC22A12 and SF1) were genotyped and serum biochemical parameters related to uric acid and T2D were determined. Results: SF1 rs606458 showed strong association to T2D in both males and females (p = 0.034 and 0.0008). In the males, LRRC16A was associated with 2-h insulin and insulin secretion (p = 0.009 and 0.009). SLC22A11 was correlated with HOMA-B and insulin secretion (p = 0.048 and 0.029). SLC2A9 rs3775948 was associated with 2-h glucose (p = 0.043). In the females, LRP2 rs2544390 and rs1333049 showed correlations with fasting insulin, HOMA-IR and insulin secretion (p = 0.028, 0.033 and 0.052 and p = 0.034, 0.047 and 0.038, respectively). SLC2A9 rs11722228 was correlated with 2-h glucose, 2-h insulin and insulin secretion (p = 0.024, 0.049 and 0.049, respectively). Conclusions: Our results indicated that the uric acid-associated genes have an impact on the risk of T2D, glucose metabolism and insulin secretion in a Chinese population. [ABSTRACT FROM AUTHOR]

Background: To investigate the impact of common variants of FNDC5 on type 2 diabetes and clinical traits related to glucose metabolism in a large Chinese population sample. Methods: Three tagging single nucleotide polymorphisms within the region of the FNDC5 gene were selected and genotyped in 6822 participants. Detailed clinical investigations and biochemistry measurements were carried out in all of the participants. Subjects without diabetes were classified into normal weight and overweight/obese subgroups according to body mass index (BMI). Results: None of the SNPs were associated with either the risk of type 2 diabetes in all of the participants or with any of the clinical quantitative traits in the controls with normal glucose regulation. Subgroup analysis showed that in controls with normal weight (BMI <25 kg/m2), the rs16835198 major allele G was significantly associated with fasting insulin levels, and that each additional copy of the allele resulted in a 0.0178 mU/L increment of the values (p = 0.046). Moreover, after adjusting for confounding variables, there were trends towards correlation of rs16835198 with HOMA-insulin resistance (HOMA-IR) (p = 0.057) and low-density lipoprotein cholesterol (LDL-C) levels (p = 0.083). In overweight/obese subjects (BMI ≥25 Kg/m2), we noted rs16835198 showed trends towards association with fasting insulin (p = 0.057) and HOMA-IR levels (p = 0.091), both of which declined with additional copies of the major allele G. Moreover, rs16835198 was significantly associated with high-density lipoprotein cholesterol (HDL-C) levels (p = 0.013), and HOMA-β cell function (p = 0.028) in the overweight/obese subjects. Finally, we observed a significant interaction between BMI-rs16835198 and fasting insulin levels in the control group (p = 0.003). Conclusions: Our data indicate that the effect of the common FNDC5 SNP rs16835198 on fasting insulin was significantly modified by BMI in the Chinese Han population. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the effect of the E23K variant of the potassium inwardly rectifying channel, subfamily J, member 11 ( KCNJ11) gene on gliclazide modified release ( MR) treatment in newly diagnosed patients with type 2 diabetes mellitus (T2 DM). A total of 108 diabetic patients with no history of antidiabetic medication was treated with gliclazide MR for 16 weeks and underwent follow up at Weeks 2, 4, 8, 12 and 16. All patients were genotyped for KCNJ11 E23K (rs5219). At baseline, patients with the KK genotype had higher blood glucose and lower serum insulin levels after oral glucose administration than patients with the EE and EK genotypes ( P < 0.05 for all). During treatment, individuals with the KK genotype had lower fasting glucose levels and were more likely to attain the target fasting glucose level ( Plog rank = 0.028) than E allele carriers. Patients with the KK genotype had larger augmentations in changes (Δ) in acute insulin response ( P = 0.049) and Δ body mass index ( P = 0.003). Moreover, patients with the EK genotype had a lower variance in changes in fasting insulin levels ( P = 0.049) and homeostasis model assessment of β-cell function (P = 0.021) than those with the KK genotype. The findings of the present study suggest that the KCNJ11 E23K variant is associated with a greater effect of sulphonylurea treatment in newly diagnosed Chinese patients with T2 DM. [ABSTRACT FROM AUTHOR]

Background: To assess the association of albuminuria and retinopathy with metabolic syndrome (MetS) and the related metabolic components defined by various criteria in Chinese community-based subjects. Methods: A total of 3240 Chinese subjects were recruited from urban communities and classified into subgroups with isolated or concomitant state of the two microvascular diseases. MetS was defined according to the standard of International Diabetes Federation, the National Cholesterol Education Program's Adult Treatment Panel III and Chinese Diabetes Society (CDS), separately. Albuminuria was defined as an elevated morning urine albumin-to-creatinine ratio. Retinopathy were identified with nonmydriatic retinal photographs according to the Diabetic Retinopathy Disease Severity Scale. Logistic regression was performed to analyze the contributive risk factors. Results: The subgroup of isolated retinopathy was the oldest (P<0.05), with higher blood pressure (P<0.001) and larger waist circumference (P<0.05). After adjusting for age, sex and other metabolic components, individuals with blood pressure over 130/85 mmHg were prone to have isolated albuminuria (OR: 1.51, P = 0.0001); while individuals with fasting plasma glucose over 5.6 mmol/L were in high risk of retinopathy concomitant with albuminria (OR: 3.04, P = 0.006). Larger waist circumference was a potential risk factors for isolated albuminuria and isolated retinopathy, though not significant after further adjustment of other metabolic components. The risk for albuminuria and retinopathy increased with the aggregation of three or more metabolic components. However, the MetS per se did not have synergic effect and only the MetS defined by CDS remained as a risk factor. Conclusions: Albuminuria and retinopathy were highly associated with accumulated metabolic abnormalities including sub-clinical elevated blood pressure and elevated fasting plasma glucose. [ABSTRACT FROM AUTHOR]

Background: The fibroblast growth factor 19 (FGF19) has been implicated in recent studies as a potential regulator of glucose and lipid metabolism, which may lead to atherosclerosis. Here, we investigated the association of FGF19 with the presence and severity of coronary artery disease (CAD) in a Chinese population. Methods: A total of 315 patients with suspected or established CAD, including 205 males and 110 postmenopausal females, were enrolled and assessed by coronary angiography. CAD severity was determined by the Gensini score. Serum FGF19 was measured by quantitative sandwich ELISA. Results: FGF19 levels were not significantly different between male and female patients (median [interquartile range], 143.40 [87.96–250.80] vs. 141.60 [87.13–226.32] pg/mL, P = 0.773). CAD patients had lower levels of FGF19 than those without CAD (128.20 [80.62–226.58] vs. 188.00 [105.10–284.70] pg/mL, P = 0.007). FGF19 was negatively correlated with 2hPG (r = –0.150, P = 0.008), FINS (r = –0.169, P = 0.004), HOMA-IR (r = –0.171, P = 0.004), and the Gensini score (r = –0.141, P = 0.012), but positively correlated with HDL-c (r = 0.116, P = 0.041) and adiponectin (r = 0.128, P = 0.024). Moreover, FGF19 was found to be independently correlated with 2hPG (β = –0.146, P = 0.022) and adiponectin (β = 0.154, P = 0.016). After adjusting for other CAD risk factors, FGF19 was demonstrated to be an independent factor for Gensini score (β = –0.140, P = 0.019) and the presence of CAD (β = –1.248, P = 0.036). Conclusions: Serum FGF19 is associated with the presence and severity of CAD in a Chinese population. [ABSTRACT FROM AUTHOR]

Abstract: Aims/hypothesis: The aim of this study was to investigate clinical spectrum of hepatocyte nuclear factor-1β (HNF-1β) mutation in Chinese diabetic patients with renal dysfunction and/or structure abnormalities. Materials and methods: A total of 104 diabetic patients with renal structural abnormalities and/or non-diabetic renal dysfunction were recruited and HNF-1β mutation was screened by direct sequencing. Results: Three heterozygous missense mutations including c.494G>A (p.R165H), c.662A>T (p.D221V) and c.780G>C (p.E260D) were identified. Progression of diabetes and mild decline of renal function were observed in the mutation carriers during the follow-up. The p.R165H mutation carrier had severe β-cell dysfunction and different extrapancreatic phenotypes. Compared with type 2 diabetes and normoglycemics, the p.R165H mutation carrier had a lower basal C-peptide (0.30, 0.61±0.07 and 0.50±0.04nmol/L for p.R165H, type 2 diabetes and normoglycemics, respectively) and low values of acute C-peptide response to arginine (0.15, 0.48±0.18 and 0.76±0.08nmol/L for p.R165H, type 2 diabetes and normoglycemics, respectively). Conclusion: Patients with the HNF-1β mutation in our population can have different pancreatic and extrapancreatic phenotypes. The exact contributions of mutations to the phenotypes await functional confirmation. [Copyright &y& Elsevier]

OBJECTIVE--Hepatocyte nuclear factor 1β (HNF1β) is a transcription factor that is critical for pancreatic cell formation and glucose homeostasis. Previous studies have reported that common variants of HNF1β were associated with type 2 diabetes in Caucasians and West Africans. However, analysis in the subjects from the Botnia study and Malmö Preventive Project produced conflicting results, and the role for HNF1β in type 2 diabetes susceptibility remains unclear. We therefore investigated common variants across the HNF1β gene in a Chinese population. RESEARCH DESIGN AND METHODS--Fifteen tagging single nucleotide polymorphisms (SNPs) were analyzed for association with type 2 diabetes in subjects with type 2 diabetes (n = 1,859) and normal glucose regulation (n = 1,785). RESULTS--Consistent with the initial study, we observed evidence that the risk G allele of rs4430796 in intron 2 was significantly associated with type 2 diabetes (odds ratio 1.16 [95% CI 1.05-1.29], P = 0.0035, empirical P = 0.0475). Furthermore, the at-risk G allele was associated with earlier age at diagnosis in the type 2 diabetic subjects (P = 0.0228). CONCLUSIONS--The result of this study provides evidence that variants in the HNF1β region contribute to susceptibility to type 2 diabetes in the Chinese population. Diabetes 58:1023-1027, 2009 [ABSTRACT FROM AUTHOR]

Background: First-degree relatives of patients with diabetes (FDR) tend to have impaired insulin activity, which lead to the alternation of circulating cytokine levels. Liver is a main target tissue of insulin action; therefore, liver fat content (LFC) has a close relationship with insulin resistance. This study aimed to find the alteration in serum osteocalcin levels in FDR and the relationship of serum osteocalcin levels with FDR and non-alcoholic fatty liver disease (NAFLD).Methods: In total, 1206 subjects including 413 men and 793 women from the communities, aged 59.7 (range, 54.8-64.3) years, were enrolled. An electrochemiluminescence immunoassay was performed to measure the levels of serum osteocalcin. LFC was measured using quantitative ultrasonography.Results: A significant decrease was found in serum osteocalcin levels in subjects with NAFLD (P < 0.001) as well as in FDR (19.8 ± 5.7 ng/mL versus 20.7 ± 6.8 ng/mL, P = 0.028). Furthermore, among the subjects with NAFLD, those with FDR had lower levels of osteocalcin than those without FDR (P = 0.011). The presence of FDR remained a predictor for decreased serum osteocalcin levels after adjusting for body mass index, blood glucose, blood lipids, and LFC (standardized β = - 0.057, P = 0.028).Conclusions: FDR had lower serum osteocalcin levels than non-FDR. The inverse association between FDR and serum osteocalcin levels was independent of metabolic factors. [ABSTRACT FROM AUTHOR]

The PSMD6 variant rs831571 has been identified as a susceptibility locus for type 2 diabetes mellitus (T2DM). This study aimed to investigate the association of this variant with therapeutic effects of oral antidiabetic drugs in Chinese T2DM patients. 209 newly diagnosed T2DM patients were randomly assigned to treatment with repaglinide or rosiglitazone for 48 weeks, and the therapeutic effects were compared. In the rosiglitazone cohort, rs831571 showed significant associations with fasting plasma glucose (FPG), 2-h glucose and decrement of glycated haemoglobin (HbA1c) levels after 24 weeks of treatment (P = 0.0368, 0.0468 and 0.0247, respectively). The C allele was significantly associated with a better attainment of FPG at 24 and 32 weeks (P = 0.0172 and 0.0257, respectively). Survival analyses showed CC homozygotes were more likely to attain a standard FPG level (P = 0.0654). In the repaglinide cohort, rs831571 was significantly associated with decreased HbA1c levels after 24 weeks of treatment, the homeostatic model assessment of insulin resistance and fasting insulin level after 48 weeks of treatment with repaglinide (P = 0.0096, 0235 and 0.0212, respectively). In conclusion, we observed that the PSMD6 variant rs831571 might be associated with the therapeutic effects of rosiglitazone and repaglinide in Chinese T2DM patients. However, these findings need to be confirmed in the future. [ABSTRACT FROM AUTHOR]