Junling Tang

Serum osteocalcin concentrations in relation to glucose and lipid metabolism in Chinese individuals.

OBJECTIVES Osteocalcin, a bone-derived protein, has recently been reported to affect energy metabolism. We investigated the relationship between serum osteocalcin and parameters of adiposity, glucose tolerance, and lipid profile in Chinese subjects. METHODS Serum osteocalcin was measured by electrochemiluminescence immunoassay in 254 men (128 with newly diagnosed type 2 diabetes mellitus (T2DM) and 126 with normal glucose tolerance (NGT)), 66 premenopausal women (33 with T2DM and 33 with NGT) as well as 180 postmenopausal women (92 with T2DM and 88 with NGT). Their associations with parameters of adiposity, glucose tolerance, and lipid profile were examined. RESULTS Serum osteocalcin concentrations in diabetic patients were significantly lower than those in NGT subjects after adjusted for age, gender, and body mass index (P=0.003). Postmenopausal women had higher osteocalcin concentrations than premenopausal women and men (both P<0.001). Multiple stepwise regression analysis showed that age, %fat, high-density lipoprotein cholesterol, fasting plasma glucose, and fasting serum insulin were independently associated with osteocalcin in men (P<0.05). Age and HbA1c were independently correlated with osteocalcin in postmenopausal women. Besides age and HbA1c, serum triglyceride was also an independent factor influencing osteocalcin in premenopausal women. In addition, osteocalcin was also positively associated with homeostasis model assessment of beta-cell function. Furthermore, multiple logistic regression analysis demonstrated that osteocalcin was independently associated with T2DM. CONCLUSIONS Serum osteocalcin was closely associated with not only fat and glucose metabolism but also with lipid metabolism.

Glycated haemoglobin A1c for diagnosing diabetes in Chinese population: cross sectional epidemiological survey

Objectives To evaluate haemoglobin A1c (HbA1c) in diagnosing diabetes and identify the optimal HbA1c threshold to be used in Chinese adults. Design Multistage stratified cross sectional epidemiological survey. Setting Shanghai, China, 2007-8. Participants 4886 Chinese adults over 20 years of age with no history of diabetes. Main outcome measures Performance of HbA1c at increasing thresholds for diagnosing diabetes. Results The area under the receiver operating characteristics curve for detecting undiagnosed diabetes was 0.856 (95% confidence interval 0.828 to 0.883) for HbA1c alone and 0.920 (0.900 to 0.941) for fasting plasma glucose alone. Very high specificity (96.1%, 95% confidence interval 95.5% to 96.7%) was achieved at an HbA1c threshold of 6.3% (2 SD above the normal mean). Moreover, the corresponding sensitivity was 62.8% (57.1% to 68.3%), which was equivalent to that of a fasting plasma glucose threshold of 7.0 mmol/l (57.5%, 51.7% to 63.1%) in detecting undiagnosed diabetes. In participants at high risk of diabetes, the HbA1c threshold of 6.3% showed significantly higher sensitivity (66.9%, 61.0% to 72.5%) than both fasting plasma glucose ≥7.0 mmol/l (54.4%, 48.3% to 60.4%) and HbA1c ≥6.5% (53.7%, 47.6% to 59.7%) (P<0.01). Conclusions An HbA1c threshold of 6.3% was highly specific for detecting undiagnosed diabetes in Chinese adults and had sensitivity similar to that of using a fasting plasma glucose threshold of 7.0 mmol/l. This optimal HbA1c threshold may be suitable as a diagnostic criterion for diabetes in Chinese adults when fasting plasma glucose and oral glucose tolerance tests are not available.

Relationship between serum osteocalcin and glycaemic variability in Type 2 diabetes

1. Recent reports have described the role of osteocalcin in glucose metabolism and glycaemic variability has been proven to be associated with an increased risk of diabetes complications. However, the relationship between osteocalcin and glycaemic variability remains unclear. The aim of the present study was to examine the relationship between serum osteocalcin and glycaemic variability, as determined by a continuous glucose monitoring (CGM) system in patients with Type 2 diabetes mellitus (T2DM).

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

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

Combined assessment of glycated albumin and fasting plasma glucose improves the detection of diabetes in Chinese subjects

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.

Serum glycated albumin is inversely influenced by fat mass and visceral adipose tissue in Chinese with normal glucose tolerance.

Background Recent studies have revealed that body mass index (BMI) inversely influenced serum glycated albumin (GA), which may cause an underestimation of GA-monitored short-term hyperglycemic control. Objective This study was to investigate the association between anthropometric variables (BMI and waist circumference (W)) and accurate adiposity variables (percentage of body fat (%fat), fat mass, free fat mass (FFM), subcutaneous fat area (SFA), and visceral fat area (VFA)) with serum GA. Design A total of 2563 subjects (1037 men, 593 premenopausal women, and 933 postmenopausal women) with normal glucose tolerance underwent bioelectrical impedance body fat content measurement and magnetic resonance imaging. Serum GA and absolute value of GA (aGA) were measured by enzymatic assay. Results Compared to the BMI <25.0 kg/m2 group, the BMI ≥25.0 kg/m2 group had significantly higher fasting plasma glucose, glycated hemoglobin A1c, and body fat parameters including W, %fat, fat mass, FFM, SFA, and VFA, but significantly lower aGA, and GA in all the three sex- and menopause-stratified groups (all P<0.05). GA decreased with the increment of fat mass for all three groups (all P for trend <0.001). In the same BMI category, men and postmenopausal women with elevated %fat (men, ≥25%; women, ≥35%) still had significantly lower GA than those with normal %fat (men, <25%; women, <35%) (all P<0.05). Multiple stepwise regression showed that %fat, fat mass, and VFA were independently associated with GA. Conclusions Serum GA was inversely influenced by fat mass and visceral adipose tissue in Chinese with normal glucose tolerance.

Serum Levels of Fibroblast Growth Factor 19 Are Inversely Associated with Coronary Artery Disease in Chinese Individuals

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.

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

1. The aim of the present study was to compare the effects of glipizide controlled‐release (CR) tablets monotherapy with that of glipizide CR tablets plus acarbose on glycaemic variability in newly diagnosed Type 2 diabetes (T2DM) patients using a continuous glucose‐monitoring system (CGMS).

Serum lipocalin-2 levels positively correlate with coronary artery disease and metabolic syndrome

BackgroundThe lipocalin-2 (LCN2) cytokine, primarily known as a protein of the granules of human neutrophils, has been recently reported to be implicated in metabolic and inflammatory disorders. This study was designed to evaluate the relationship between serum LCN2 levels and coronary artery disease (CAD).MethodsSerum LCN2 levels of 261 in-patients who underwent coronary angiography were measured by sandwich enzyme immunoassay. Demographic (169 men and 92 postmenopausal women) and clinical (metabolic syndrome (MS), triglyceride (TG) and C-reactive protein (CRP) levels) characteristics were collected to assess independent factors of CAD (CAD: 188 and non-CAD: 73) and serum LCN2 levels by multiple logistic regression and multivariate stepwise regression analyses, respectively.ResultsSerum LCN2 levels were significantly higher in men (37.5 (27.4-55.4) vs. women: 28.2 (18.7-45.9) ng/mL, p < 0.01) and men with CAD (39.2 (29.3-56.5) vs. non-CAD men: 32.7 (20.5-49.7) ng/mL, p < 0.05), and showed significant positive correlation with CAD in men (odds ratio = 2.218, 95% confidence interval: 1.017-4.839). Similarly, serum LCN2 levels were significantly higher in men with MS (40.2 (31.9-59.4) vs. non-MS: 32.0 (21.7-47.6) ng/mL, p < 0.01) and showed a significant positive correlation with the number of MS components (p for trend < 0.05). No significant differences or correlations were seen in women. TG and neutrophils (standard β = 0.238 and 0.173) were independent factors of serum LCN2 levels in men, and only neutrophils (standard β = 0.286) affected levels in women (all p < 0.05).ConclusionsIncreased serum LCN2 levels are positively correlated with the presence of CAD and MS in a Chinese cohort.

Low serum levels of the innate immune component ficolin-3 is associated with insulin resistance and predicts the development of type 2 diabetes

Dear Editor, Impaired insulin secretion and insulin resistance are the two main mechanisms that lead to type 2 diabetes mellitus (T2DM). Insulin resistance associated with innate immune system is known to be triggered by the activation of patternrecognition receptors (PRRs) (Olefsky and Glass, 2010). Recently, our research group showed that serum ficolin-3, a kind of soluble PRR within the lectin pathway varied significantly between individuals with normal glucose tolerance (NGT) and those with T2DM (Li et al., 2008). Here we performed a human crosssectional study and a prospective study to investigate whether serum ficolin-3 levels associate with insulin resistance and predict the incidence of T2DM. In the cross-sectional study, in which 170 had NGT and 95 had T2DM without any diabetic complications, we found that serum ficolin-3 in the T2DM group was significantly lower than that in the NGT group and multiple linear stepwise regression analyses revealed that serum ficolin-3 was independently correlated with high-density lipoprotein-cholesterol (HDL-c), homeostasis model assessment index of insulin resistance (HOMA-IR), hemoglobin A1c (HbA1c), and age (Supplementary Tables S1 and S2). The glucose disposal rate (GDR) used as a measurement of insulin sensitivity by euglycemic–hyperinsulinemic clamp technique was positively correlated with serum ficolin-3 in 51 NGT subjects (Figure 1A). Further logistic regression analyses showed that there was a significant correlation between serum ficolin-3 and T2DM, after adjustment for age and sex (model I), age, sex, HDL-c, HOMA-IR and HbA1c (model II), age, sex, HDL-c, HOMA-IR, HbA1c, triglycerides (TG), systolic blood pressure (SBP), C-reactive protein, creatinine and uric acid (model III) (Supplementary Table S3). To explore the role of serum ficolin-3 in the prediction of future risk of T2DM, we performed a prospective study in which 1951 subjects recruited from China communities for the Shanghai Diabetes Study (conducted in 1998–2001) and had returned for the follow-up assessment (an average of 3 years). Among them, 1742 had NGT and 209 had impaired glucose regulation at baseline. Serum ficolin-3 was significantly lower in subjects with impaired glucose regulation than in those with NGT (Supplementary Table S4). After the followup, 130 subjects had developed T2DM. The baseline level of serum ficolin-3 was significantly lower in subjects who developed T2DM than those who did not (Supplementary Table S5). Participants in the highest quartile of serum ficolin-3 had a significantly decreased risk of diabetes compared with those belonging to the lowest quartile even after the adjustment of age, sex, body mass index, and waist circumference (Figure 1B). The relative risk (RR) of T2DM for serum ficolin-3 was affected by further adjustment for HDL-c, TG, fasting plasma glucose, SBP, diastolic blood pressure (DBP), and HOMA-IR separately (Figure 1C). In subgroup analysis, a significant association was found between serum ficolin-3 and risk of diabetes among participants who were females, and those who had hyperglycemia, non-abdominal obesity, dyslipidemia, and hypertension (Figure 1D). Ficolin-3, a secreted PRR, was first identified as a serum glycoprotein that reacted with autoantibodies from patients with systemic lupus erythematosus (Epstein and Tan, 1973) and considered to have a primary role in the activation of the lectin pathway in the complement system and in the clearance of late apoptotic cells (Honore et al., 2007). Besides these specific effects on the immune response, a new phenomenon of ficolin-3 was detected in this study. Serum ficolin-3 was significantly lower in T2DM patients and was independently related to insulin resistance which was further confirmed by euglycemic– hyperinsulinemic clamp technique. The mechanism linking ficolin-3 with insulin resistance is not yet fully understood. Ficolin-3, containing the C-type carbohydrate recognition domain and the fibrinogen h/g (homology) domain, has evolved to recognize the surface sugar codes of microbes. Toll-like receptors, which are membrane-bound PRRs, have a similar function, in that they can bind to cell surface carbohydrate molecules in the same way as ficolin-3 does (Smith et al., 2011). Toll-like receptors have been shown to be associated with insulin resistance in T2DM (Raetzsch et al., 2009) through the activation of the innate immune response and subsequent inflammatory pathways in combination with free fatty acids. In addition, mannan-binding lectin, which shares many structural and functional similarities with ficolin-3, has previously been reported to be associated with the development of insulin resistance by increasing fatty acid oxidation in the rat soleus muscle (Fernandez-Real et al., 2006). However, it is unclear whether ficolin-3 affects the development of insulin resistance by similar mechanisms. The most important finding in the prospective study was that low serum ficolin-3 levels at baseline predicted the incidence of T2DM. Interestingly, an inverse association was observed among participants with elevated levels (within the non-diabetic range) of plasma glucose, 256 | Journal of Molecular Cell Biology (2012), 4, 256–257 doi:10.1093/jmcb/mjs032 Published online June 7, 2012