Shanghai Clinical Center for Diabetes

Shanghai, China

Shanghai Clinical Center for Diabetes

Shanghai, China

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Bao Y.-Q.,Shanghai Clinical Center for Diabetes | Bao Y.-Q.,Mellitus | Bao Y.-Q.,Shanghai Diabetes Institute | Zhou M.,Shanghai Clinical Center for Diabetes | And 21 more authors.
Clinical and Experimental Pharmacology and Physiology | Year: 2011

Summary: 1. Recent reports have described the role of osteocalcin in glucose metabolism and glycaemic variability has been proven to be associated with an increased risk of diabetes complications. However, the relationship between osteocalcin and glycaemic variability remains unclear. The aim of the present study was to examine the relationship between serum osteocalcin and glycaemic variability, as determined by a continuous glucose monitoring (CGM) system in patients with Type 2 diabetes mellitus (T2DM).2. Fifty-nine T2DM patients with glycosylated haemoglobin (HbA1c) levels between 7.0% and 10.9% were recruited to the present study. Biochemical information and CGM parameters were collected at baseline and after 8 weeks of antihyperglycaemic therapy (either sulphonylurea, sulphonylurea + an α-glucosidase inhibitor or insulin + metformin combination therapy).3. Compared with baseline, serum osteocalcin increased significantly (P = 0.014), whereas parameters related to glucose variability, including the mean amplitude of glycaemic excursions (MAGE) and the standard deviation of blood glucose values, decreased significantly (P < 0.001) after the 8 week treatment period. At baseline, there was a positive correlation between serum osteocalcin levels and fasting C-peptide levels (P = 0.004) and homeostatic model assessment of 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 (P < 0.001). 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. © 2010 The Authors. Clinical and Experimental Pharmacology and Physiology © 2010 Blackwell Publishing Asia Pty Ltd.


Hu C.,Shanghai JiaoTong University | Hu C.,Shanghai Diabetes Institute | Hu C.,Shanghai Clinical Center for Diabetes | Zhang R.,Shanghai Diabetes Institute | And 23 more authors.
PLoS ONE | Year: 2010

Background: Single nucleotide polymorphisms (SNPs) from GCK, GCKR, G6PC2 and MTNR1B were found to modulate the fasting glucose levels. The current study aimed to replicate this association in the Chinese population and further analyze their effects on biphasic insulin secretion. Methods/Principal Findings: SNPs from GCK, GCKR, G6PC2 and MTNR1B were genotyped in the Shanghai Chinese, including 3,410 type 2 diabetes patients and 3,412 controls. The controls were extensively phenotyped for the traits related to glucose metabolism and insulin secretion. We replicated the association between GCK rs1799884, G6PC2 rs16856187 and MTNR1B rs10830963 and fasting glucose in our samples (p = 0.0003,2.061028). GCK rs1799884 and G6PC2 rs16856187 showed association to HOMA-b, insulinogenic index and both first- and second-phases insulin secretion (p = 0.0030,0.0396). MTNR1B rs10830963 was associated to HOMA-b, insulinogenic index and first-phase insulin secretion (p = 0.0102,0.0426), but not second-phase insulin secretion (p = 0.9933). Combined effect analyses showed individuals carrying more risk allele for high fasting glucose tended to have a higher glucose levels at both fasting and 2 h during OGTTs (p = 1.7610213 and0.0009, respectively), as well as lower HOMA-b, insulinogenic index and both first- and second-phases insulin secretion (p = 0.0321,1.161027). Conclusions/Significance: We showed that SNPs from GCK, G6PC2 and MTNR1B modulated the fasting glucose levels in the normoglycaemic population while SNPs from G6PC2 and GCKR was associated with type 2 diabetes. Moreover, we found GCK and G6PC2 genetic variants were associated to both first- and second-phases insulin secretion while MTNR1B genetic variant was associated with first-phase insulin secretion, but not second-phase insulin secretion. © 2010 Hu et al.


Hu C.,Shanghai JiaoTong University | Hu C.,Shanghai Diabetes Institute | Hu C.,Shanghai Clinical Center for Diabetes | Zhang R.,Shanghai Diabetes Institute | And 23 more authors.
PLoS ONE | Year: 2010

Background: Recent meta-analysis of genome-wide association studies in European descent samples identified novel loci influencing glucose and insulin related traits. In the current study, we aimed to evaluate the association between these loci and traits related to glucose metabolism in the Chinese. Methods/Principal Findings: We genotyped seventeen single nucleotide polymorphisms (SNPs) from fifteen loci including GIPR, ADCY5, TCF7L2, VPS13C, DGKB, MADD, ADRA2A, FADS1, CRY2, SLC2A2, GLIS3, PROX1, C2CD4B, SLC30A8 and IGF1 in 6,822 Shanghai Chinese Hans comprising 3,410 type 2 diabetic patients and 3,412 normal glucose regulation subjects. MADD rs7944584 showed strong association to type 2 diabetes (p = 3.5×10-6, empirical p = 0.0002) which was not observed in the European descent populations. SNPs from GIPR, TCF7L2, CRY2, GLIS3 and SLC30A8 were also associated with type 2 diabetes (p = 0.0487~2.×10-8). Further adjusting age, gender and BMI as confounders found PROX1 rs340874 was associated with type 2 diabetes (p = 0.0391). SNPs from DGKB, MADD and SLC30A8 were associated with fasting glucose while PROX1 rs340874 was significantly associated with OGTT 2-h glucose (p = 0.0392~0.0014, adjusted for age, gender and BMI), the glucose-raising allele also showed association to lower insulin secretion. IGF1 rs35767 showed significant association to both fasting and 2-h insulin levels as well as insulin secretion and sensitivity indices (p = 0.0160~0.0035, adjusted for age, gender and BMI). Conclusions/Significance: Our results indicated that SNPs from GIPR, TCF7L2, DGKB, MADD, CRY2, GLIS3, PROX1, SLC30A8 and IGF1 were associated with traits related to glucose metabolism in the Chinese population. © 2010 Hu et al.


Dou J.,Shanghai JiaoTong University | Dou J.,Shanghai Clinical Center for Diabetes | Dou J.,Shanghai Diabetes Institute | Dou J.,Mellitus | And 29 more authors.
Clinical and Experimental Pharmacology and Physiology | Year: 2013

The present study was designed to investigate the relationship between serum osteocalcin levels and non-alcoholic fatty liver disease (NAFLD) in Chinese men. In all, 1558 men (21-78 years old) were recruited to the study. Serum osteocalcin, glucose and lipid profiles were determined. Demographic and clinical characteristics were recorded. All participants underwent hepatic ultrasonographic examination. Serum osteocalcin levels were significantly lower in subjects with NAFLD than those without (P < 0.01). All study subjects were divided into four subgroups according to quartiles of serum osteocalcin levels. The frequency of NAFLD increased progressively with declining serum osteocalcin levels (Ptrend < 0.01). Serum osteocalcin levels were inversely correlated with NAFLD (P < 0.01). However, the significant association between serum osteocalcin levels and NAFLD disappeared in logistic regression analyses. Furthermore, multiple stepwise regression analysis showed that serum osteocalcin levels were independently associated with serum alanine aminotransferase levels in Chinese men (P < 0.01). The findings of the present study suggest that serum osteocalcin levels are not directly correlated with NAFLD. © 2013 The Authors Clinical and Experimental Pharmacology and Physiology © 2013 Wiley Publishing Asia Pty Ltd.


Yu W.,Shanghai JiaoTong University | Yu W.,Shanghai Diabetes Institute | Yu W.,Shanghai Clinical Center for Diabetes | Hu C.,Shanghai JiaoTong University | And 22 more authors.
Clinical Pharmacology and Therapeutics | Year: 2011

The aim of this study was to explore the impact of KCNQ1 variants on the responses to oral antidiabetic drugs in a Chinese study population. A 48-week randomized pharmacogenetics study compared the effects of repaglinide and rosiglitazone in 209 newly diagnosed patients with type 2 diabetes. In the repaglinide cohort, individuals who were rs2237892 TT homozygotes exhibited lower 2-h glucose levels and significantly higher cumulative attainment rates of target 2-h glucose levels (Plog-rank = 0.0383) than the C allele carriers; patients with a greater number of rs2237892 C alleles showed larger augmentations in both fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.0166 and 0.0026, respectively); moreover, the rs2237895 C allele was also associated with greater increments in both fasting insulin and HOMA-IR (P = 0.0274 and 0.0259, respectively). In contrast, only an association between rs2237897 and decrease in 2-h glucose levels was detected in the rosiglitazone cohort (P = 0.0321). Our results indicated that KCNQ1 polymorphisms are associated with repaglinide efficacy, and might also be associated with rosiglitazone response, in Chinese patients with type 2 diabetes.


Zhu Y.,Shanghai JiaoTong University | Zhu Y.,Mellitus | Zhang M.,Shanghai JiaoTong University | Zhang M.,Mellitus | And 11 more authors.
Biomedical and Environmental Sciences | Year: 2011

To determine whether smoking increases the risk for developing metabolic syndrome (MetS) in Chinese men. A total of 693 men with no MetS at baseline were followed for 2.9-5.5 years. Subjects were divided into nonsmokers, ex-smokers, and current smokers according to baseline smoking status. After adjusting for age, education level, alcohol intake, fasting plasma insulin, HOMA-IR index, and BMI at baseline and weight change, current smokers were dose-dependently associated with increased risk for developing new MetS compared with nonsmokers. The odds ratio (OR) was 2.131 (95 CI, 1.264, 3.592; P<0.01) for the NCEPIII definition or 3.083 (95 CI, 1.807, 5.295; P<0.01) for the JCDCG definition of MetS. Ex-smokers who had quit for ≥13 years significantly decreased the risk for developing new MetS defined by the JCDCG definition. Compared with nonsmokers, current smokers were significantly associated with increased incidence of hypertriglyceridemia and low HDL-C. Smoking is a risk factor for developing MetS in Chinese men after adjusting for age, education level, alcohol intake, fasting plasma insulin, HOMA-IR, BMI, and weight change. This could be due to an increased incidence of dyslipidemia. Smoking cessation for >13 years decreased the risk for developing MetS defined by the JCDCG definition. © 2011 The Editorial Board of Biomedical and Environmental Sciences.


Li L.,Shanghai JiaoTong University | Li L.,Mellitus | Wang C.,Shanghai JiaoTong University | Wang C.,Mellitus | And 7 more authors.
Clinical and Experimental Pharmacology and Physiology | Year: 2012

Obesity results in an increased risk of metabolic syndrome (MetS) and Type 2 diabetes (T2DM). Body fat percentage (BF%) is a common index of body composition. The aim of the present study was to determine the optimal BF% cut-offs for obesity to predict MetS and T2DM in Chinese adults. The baseline study group comprised 3916 Chinese adults (age 30-70 years of age); 2033 subjects without MetS or T2DM were followed up for a maximum of 5.5 years. The BF% was estimated using bioelectrical impedance analysis. Optimal BF% cut-offs were analysed by receiver operating characteristic (ROC) curves. Binary logistic regression analysis was performed to measure the association between obesity at baseline defined by BF% and newly developed MetS and T2DM. Mean BF% levels were lower in men than in women (23.9 ± 6.1% vs 33.5 ± 7.1%, respectively; P < 0.01). For men, the optimal BF% cut-offs for the prediction of MetS and T2DM were 25.45% and 26.65%, respectively; for women, the corresponding values were 34.95% and 36.55%. Subjects with high BF% (≥ 25% in men; ≥ 35% in women) had higher risks of incident MetS or T2DM than those with low BF% (< 25% in men; < 35% in women). The relative risks were 3.43 (95% confidence intervals (CI) 2.59-4.54) and 2.92 (95% CI 1.85-4.60), respectively. The optimal BF% cut-offs for obesity for the prediction of MetS and T2DM in Chinese men and women were around 25% and 35%, respectively. © 2012 Blackwell Publishing Asia Pty Ltd.


Hu C.,Shanghai JiaoTong University | Hu C.,Mellitus | Hu C.,Shanghai Clinical Center for Diabetes | Zhang R.,Shanghai JiaoTong University | And 26 more authors.
Diabetes | Year: 2011

OBJECTIVE - Diabetic nephropathy and retinopathy are two important microvascular diabetes complications with a high concordance rate in diabetic patients. A recent genome-wide association study in type 1 diabetic patients of European descent identified four loci to be associated with diabetic nephropathy. The aim of this study was to test the effects of single nucleotide polymorphisms (SNPs) from these four loci on diabetic nephropathy and retinopathy in Chinese type 2 diabetic patients. RESEARCH DESIGN AND METHODS - In stage 1, we recruited 1,276 type 2 diabetic patients, including 378 patients with diabetic nephropathy but no retinopathy, 374 patients with diabetic retinopathy but no nephropathy, 244 patients with both diabetic retinopathy and nephropathy, and 280 control subjects with diabetes for >10 years and no diabetic retinopathy or nephropathy. Fifty-five SNPs from four loci (CPVL/CHN2, FRMD3, CARS, and IRS2) were genotyped. The SNPs that showed associations to diabetic retinopathy or nephropathy were genotyped in stage 2 samples for replication. RESULTS - SNPs from CPVL/CHN2 and FRMD3 were associated with diabetic retinopathy with rs39059 and rs10868025 as the top SNPs (odds ratio [OR] 1.292, 95% CI 1.097-1.523, P = 0.0022, for rs39059; 1.201, 1.014-1.422, P = 0.0343, for rs10868025) in stage 1 samples. In stage 2 analysis, only rs39059 showed similar effect to diabetic retinopathy (OR 1.269, 0.989-1.628, P = 0.0689), and meta-analysis showed a significant association between rs39059 and diabetic retinopathy, with an OR of 1.285 (1.120-1.474, P = 0.0003). CPVL/CHN2 rs39059 was also associated with levels of diabetic retinopathy (P = 0.0007 for trend). However, no association was detected between these SNPs and diabetic nephropathy. CONCLUSIONS - In this study, we found CPVL/CHN2 rs39059 was associated with diabetic retinopathy in the Chinese type 2 diabetic patients. © 2011 by the American Diabetes Association.


Hu C.,Shanghai JiaoTong University | Hu C.,Shanghai Diabetes Institute | Hu C.,Shanghai Clinical Center for Diabetes | Wang C.,Shanghai Diabetes Institute | And 17 more authors.
Diabetologia | Year: 2010

Aims/hypothesis: Chromosome 1q21-q24 has been shown to be linked to type 2 diabetes. The International Type 2 Diabetes 1q Consortium showed that one of the nominal associations was located in the NOS1AP gene. Although this association was not replicated in additional samples of European descent, it remains unknown whether NOS1AP plays a role in Chinese individuals. Methods: In stage 1 analyses, 79 single nucleotide polymorphisms (SNPs) of the NOS1AP gene were successfully genotyped in a group of Shanghai Chinese individuals, comprising 1,691 type 2 diabetes patients and 1,720 control participants. In stage 2 analyses, the SNP showing the strongest association was genotyped in additional Chinese individuals, including 1,663 type 2 diabetes patients and 1,408 control participants. Results: In stage 1 analyses, 20 SNPs were nominally associated with type 2 diabetes (p<0.05), with SNP rs12742393 showing the strongest association (OR 1.24 [95% CI 1.11-1.38]; p=0.0002, empirical p=0.019). Haplotype analysis also confirmed the association between rs12742393 and type 2 diabetes. In stage 2 analyses, the difference in allele frequency distribution of rs12742393 did not reach statistical significance (p=0.254). However, the meta-analysis showed a significant association between rs12742393 and type 2 diabetes with an OR of 1.17 (95% CI 1.07-1.26; p=0.0005). Conclusions/ interpretation: Our data suggest that NOS1AP variants may not play a dominant role in susceptibility to type 2 diabetes, but a minor effect cannot be excluded.

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