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Objective. The aim of this study was to explore the association of 1,5-anhydroglucitol with acute C peptide response (ACPR) to arginine among patients with type 2 diabetes. Methods. Patients with type 2 diabetes were enrolled from the Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital. ACPR was assessed using arginine stimulation test. Decreased β-cell function was defined as ACPR < 2.1. Multivariable logistic regression models were used to demonstrate the association between 1,5-anhydroglucitol and decreased β-cell function. Results. Finally, 623 patients with type 2 diabetes were enrolled into the analysis. Multivariable-adjusted odds ratios for decreased β-cell function across quartiles of 1,5-anhydroglucitol were 1.00, 0.47 (95% confidence interval (CI) 0.23-0.99), 0.41 (95% CI 0.20-0.84), and 0.27 (95% CI 0.13-0.57) ( P trend = 0.042), respectively. When 1,5-anhydroglucitol was considered as a continuous variable after logarithm, the corresponding odds ratio was 0.40 (95% CI 0.23-0.71). Conclusions. We demonstrated a dose-response linear association between 1,5-anhydroglucitol and ACPR. 1,5-Anhydroglucitol was likely to be associated with β-cell function. Further analysis with large sample size and prospective study design is warranted to validate our findings. [ABSTRACT FROM AUTHOR]

Background. Accumulating evidence has shown that neck circumference (NC) is associated with obesity-related metabolic abnormalities. Nonalcoholic fatty liver disease (NAFLD) is regarded as a liver manifestation of metabolic syndrome. This study aimed to investigate the relationship between NC and liver fat content (LFC) and NAFLD. Methods. A total of 1698 subjects (577 men and 1121 women) from the Shanghai community were enrolled. All the subjects underwent NC measurement and biochemical measurements. LFC was calculated using the parameters from abdominal ultrasound images. Elevated NC was defined as NC ≥38.5 cm in men and NC ≥34.5 cm in women. Results. Subjects with NAFLD based on the LFC measurement had higher values of NC, liver enzyme profiles, homoeostasis model assessment-insulin resistance index, and LFC than those without NAFLD (all P < 0.05), irrespective of sex. NC showed an upward trend with the increase of LFC in both men and women (both P < 0.05). An elevated NC could identify 55.22% of men and 50.29% of women with NAFLD based on quantitative ultrasonography. The positive correlation between NC and LFC remained significant even after adjustment for central obesity (both P < 0.05). After adjusting for confounding factors, the risk of NAFLD in subjects with an elevated NC was 1.52-fold higher in men (P = 0.036) and 2.31-fold higher in women (P < 0.001). Conclusions. There was a significant and positive correlation between NC and LFC. The risk of NAFLD increased significantly in subjects with an elevated NC. [ABSTRACT FROM AUTHOR]

Previous studies have reported that glycated albumin (GA) is affected by body fat distribution. Sex hormones are reported to play an important role in fat metabolism. This study aimed to explore the influence of sex hormones on the relationship between body fat and GA in a community population. We recruited 763 middle-aged and elderly subjects with normal glucose tolerance from communities. GA was determined using the enzyme method, and serum estradiol (E 2), total testosterone, and sex hormone–binding globulin (SHBG) were detected using chemiluminescent microparticle immunoassays. There was a statistically significant association between SHBG and GA remained after adjusting for body fat in both men and women. The average serum GA levels were 13.40 ± 1.10% in the 298 men and 465 postmenopausal women included in this study. GA presented a significant downward trend with increasing quartiles of total fat mass (FM), limb FM, and trunk FM in both men and women (all P for trend <.01). In men, total testosterone, free testosterone, and SHBG were positively correlated with GA (both P <.01), and the correlation between SHBG and GA remained after adjusting for body fat (P <.01). In women, E2, free testosterone, bioactive testosterone, and SHBG were correlated with GA (all P <.01); furthermore, the positive correlation between SHBG and GA and the inverse correlation between E2 and GA remained after adjusting for body fat (both P <.05). Multivariate linear regression analyses showed that in addition to trunk FM, SHBG was positively correlated with GA in both men and women (standardized β = 0.136, P =.035; standardized β = 0.101, P =.033); however, E2 was not independently correlated with GA in women. SHBG may contribute to the influence of body fat, especially trunk fat on GA levels. This study used an automated bioelectrical impedance analyzer to measure segmental body composition including limb FM and trunk FM and further investigated the role of segmental body fat in the correlation between SHBG and GA. Sex hormones may explain in part why body fat content and distribution can alter GA levels. SHBG is positively correlated with serum GA levels, and this correlation is independent of total or segmental body fat. Xu Y, Ma X, Shen Y, et al. Influence of Sex Hormones on the Relationship Between Body Fat and Glycated Albumin Levels. J Sex Med 2020;17:903–910. [ABSTRACT FROM AUTHOR]

Aims: This study aimed to explore the level of and changes in the 1,5-anhydroglucitol × glycated hemoglobin A1c/100 (AH index, AHI) associated with different glucose metabolism statuses and to evaluate the islet function and insulin sensitivity of patients with type 2 diabetes (T2DM) with different AHI levels. Methods: Of the 3562 subjects enrolled in this study, 1697 had T2DM. The disposition index (DI) was the product of islet secretion function and insulin sensitivity-related indexes. Results: The mean AHI level was 1.0 (0.7–1.3) in the general population, while the mean AHI level in the T2DM group was 0.8 (0.5–1.2), which was significantly lower than that in the impaired glucose regulation and normal glucose tolerance group (both 1.2 (0.9–1.5), both P < 0.01). We further divided patients with T2DM into four subgroups according to the quartile of AHI. The results showed that with the increase in AHI level, the homeostasis model assessment of insulin resistance (HOMA-IR) decreased, while HOMA-β, insulin generation index, insulin sensitivity index, and DI increased (all Pfor trend < 0.01). Multivariate logistic regression showed that the odds ratios for a low DI for increasing levels of AHI were 1.00, 0.22 (0.16–0.29), 0.16 (0.11–0.22), and 0.09 (0.06–0.13), showing a decreasing trend (Pfor trend < 0.05). Conclusion: The AHI could reflect the variation in glycemic disorder and the function of islet β cells. The lower the AHI, the worse the glycemic disorder, as well as the islet β-cell function. [ABSTRACT FROM AUTHOR]

Background: Acarbose (ACA) can effectively reduce the postprandial blood glucose and has similar antidiabetic effects as metformin (MET). To our knowledge, few studies have compared the effect of ACA or MET on glucose fluctuations. In the present study, we explored the effect of ACA or MET combined with premixed insulin (INS) on glycemic control and glycemic variability (GV). Methods: This was an open-label randomized trial that was conducted in type 2 diabetic patients taking premixed insulin. The patients were assigned to 12 weeks of MET (n = 62) or ACA (n = 62) treatment combined with INS. The main outcomes were changes in GV and glycosylated hemoglobin A1c (HbA1c) compared with baseline. Results: Compared with baseline, several GV indices (standard deviation [SD], mean amplitude of glycemic excursions [MAGE]) and blood glucose control indices (mean glucose [MG], time in range [TIR] and HbA1c) were both significantly improved in INS+ACA and INS+MET after 12-week therapy. However, coefficient of variation (CV) was significantly reduced in INS+ACA but not in INS+MET. Moreover, compared with INS+MET, INS+ACA led to a more pronounced percentage change from baseline in CV (26.3% [1.7%-44.6%] vs. 11.9% [-7.0% to 29.9%], P = 0.022), MAGE (40.5% [20.1%-60.5%] vs. 25.2% [-2.1% to 43.4%], P = 0.007) and SD (38.6% [25.2%-57.9%] vs. 30.1% [10.8%-46.5%], P = 0.041). Conclusion: Both MET and ACE combined with INS effectively reduced blood glucose. Compared with MET, ACA combined with INS reduced GV. [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]

Background. Fulminant type 1 diabetes mellitus (FT1DM) onsets abruptly and usually occurs within 1 week after the onset of hyperglycemic symptoms. Glycated albumin (GA) and 1,5-anhydroglucitol (1,5-AG) are indicators that reflect short-term glucose levels. This study was aimed at investigating whether the 1,5-AG/GA index (AGI) is a suitable indicator for early FT1DM identification. Methods. A total of 226 subjects were enrolled, all with glycated hemoglobin A 1 c Hb A 1 c < 8.7 %. FT1DM was diagnosed based on the 2012 Japan Diabetes Society criteria. Results. The AGI level was 0.54 (0.17–1.36) in the whole group. It was lower in FT1DM patients (0.16 [0.10–0.25]). Among the participants whose HbA1c did not exceed 7.0%, the AGI of FT1DM decreased significantly compared to type 1A diabetes (T1ADM) and latent autoimmune diabetes in adults (LADA) patients (0.16 [0.12–0.26] vs. 0.46 [0.24–0.72] vs. 0.31 [0.19–0.43], both P < 0.05). The receiver operating characteristic (ROC) curve showed that AGI can be used to distinguish FT1DM and T1ADM patients with Hb A 1 c < 8.7 %. Diagnosing FT1DM based on AGI ≤ 0.3 only can help narrow down suspected FT1DM by up to 26.87%. If we diagnosed FT1DM when AGI was ≤0.3 and HbA1c was ≤7.0%, the success rate further increased to 86.57%, among which 85.00% of FT1DM and 87.23% of T1ADM patients were successfully identified. Therefore, using the combination criteria of AGI and HbA1c would improve the differential diagnosis efficacy by 61.11% compared with the AGI criterion only. Conclusion. AGI can help facilitate the early differential diagnosis of FT1DM and T1ADM when Hb A 1 c < 8.7 % , with an optimal cut-off point of 0.3. [ABSTRACT FROM AUTHOR]

Background: The aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio is suggested to be related to the increased risks of many metabolic diseases, whereas its association with neurological function in type 2 diabetes mellitus (T2DM) has not been understood. In this study, we aim to investigate the relationships between serum liver enzymes (ALT, AST, the AST/ALT ratio, gamma-glutamyl transferase (GGT)) and peripheral nerve function in patients with T2DM. Methods: In Group 1, we analyzed the associations between parameters of nerve function and liver enzymes in 460 T2DM patients from rural area of Shanghai. Besides, the same methods were applied to another group of 828 T2DM subjects from urban area of Shanghai. Results: In Group 1, the AST/ALT ratio was significantly higher in patients with abnormal nerve conduction (P = 0. 0 0 5). The peripheral nerve function significantly declined with increasing tertiles of AST/ALT ratio (P s < 0. 0 5). After adjustment for all potential confounders, the ratio of AST/ALT was still negatively correlated with the composite Z-scores of conduction velocity (CV). In Group 2, similar significant associations were found between the AST/ALT ratio and peripheral nerve function after adjustment for covariates. Conclusions: In two independent T2DM populations, the AST/ALT ratio was independently and consistently related to peripheral nerve function. The AST/ALT ratio might be helpful to highlight T2DM patients at high risk for diabetic peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Background: Time in range (TIR) is an emerging metric of glycemic control and is reported to be associated with microvascular complications of diabetes. We sought to investigate the association of TIR obtained from continuous glucose monitoring (CGM) with carotid intima-media thickness (CIMT) as a surrogate marker of cardiovascular disease (CVD). Methods: Data from 2215 patients with type 2 diabetes were cross-sectionally analyzed. TIR of 3.9-10.0 mmol/L was evaluated with CGM. CIMT was measured using high-resolution B-mode ultrasonography and abnormal CIMT was defined as a mean CIMT ≥1.0 mm. Logistic regression models were used to examine the independent association of TIR with CIMT. Results: Compared with patients with normal CIMT, those with abnormal CIMT had significantly lower TIR (P < 0.001). The prevalence of abnormal CIMT progressively decreased across the categories of increasing TIR (P for trend <0.001). In a fully adjusted model controlling for traditional risk factor of CVD, each 10% increase in TIR was associated with 6.4% lower risk of abnormal CIMT. Stratifying the data by sex revealed that TIR was significantly associated with CIMT in males but not in females. In a subset of patients (n = 612) with complete data on diabetic retinopathy and albuminuria, we found that the relationship between TIR and CIMT remained to be significant, regardless of the status of microvascular complications. Conclusions: TIR is associated with CIMT in a large sample of patients with type 2 diabetes, suggesting a link between TIR and macrovascular disease. [ABSTRACT FROM AUTHOR]

Introduction: Diabetic foot ulcers develop with deviations in the distribution of plantar pressure. It is difficult to interpret any alteration in plantar pressure under different conditions of type 2 diabetes mellitus (T2DM). The aim of this study was to gain a better insight into the variations in plantar pressure with increased duration of diabetes. Methods: Plantar pressure was examined in 1196 participants with or without T2DM. Subjects with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) were assigned to control groups, and those with T2DM were divided into five groups according to diabetes duration (< 2 years, 2–5 years, 5–10 years, 10–15 years, and > 15 years). The clinical characteristics, plantar peak pressure, and pressure–time integral (PTI) were compared among the seven study groups, and factors associated with peak pressure and the PTI were analyzed. Results: At the hallux, peak pressure exhibited an upward trend in patients with T2DM within 5 years of diabetes duration, followed by a distinct downward slope with further progression of the disease (trend analysis, p < 0.05). An uneven distribution of peak pressure was found at other locations, but this unevenness was ultimately lower than that in the two control groups (p < 0.05). No obvious trend was noted for PTI among patients with different diabetes duration; however, those with diabetes for > 10 years manifested a significantly sharper increase in the PTI at the metatarsus (11.63 Ns/cm2, p < 0.05) and heel (14.12 Ns/cm2, p < 0.05) than at the hallux (8.76 Ns/cm2). A fluctuation in the PTI was also detected at the hallux and midfoot of diabetes patients, which was broadly flat when compared with that of the two control groups. The stepwise multiple regression analysis revealed that the variation in plantar pressure was independently associated with age, body mass index, and vibration perception threshold (VPT) (p < 0.05). Conclusions: There would appear to be an association between longer diabetes duration and decreased peak pressure for the hallux, suggesting that individuals with diabetes for > 10 years will have an increased PTI for the metatarsus and heel. The reduced pressure on the hallux is believed to be transferred to the metatarsus. Age, BMI, and VPT are distinct risk factors of abnormal plantar pressure. [ABSTRACT FROM AUTHOR]

The purpose of the current study was to investigate the clinical characteristics of fulminant type 1 diabetes mellitus (FT1DM) in Chinese patients and to further determine their glycaemic profiles through continuous glucose monitoring (CGM). Thirty subjects who were diagnosed with FT1DM according to the 2012 JDS criteria were enrolled. Clinical characteristics were compared to those reported in Japanese FT1DM. All subjects received retrospective CGM for 3 days after being converted to subcutaneous insulin injection therapy. Chinese FT1DM patients presented with a shorter duration of symptoms (2.84 ± 2.42 days vs 4.4 ± 3.1 days, P < 0.01), worse islet function (fasting C‐peptide, 0.09 ± 0.11 ng/mL vs 0.30 ± 0.21 ng/mL; 2‐hour C‐peptide, 0.13 ± 0.14 ng/mL vs 0.30 ± 0.30 ng/mL, both P < 0.01), lower prevalence of flu‐like symptoms (46.7% vs 71.4%, P < 0.05), and a significantly higher GADA positive rate (23.3% vs 5.1%, P < 0.01) when compared with Japanese patients. The CGM results showed that the mean time in range (TIR) of FT1DM patients was 49.8 ± 22.1%, while mean amplitude of glycaemic excursion (MAGE) and standard deviations of sensor glucose (SDSG) were 7.58 ± 3.59 mmol/L and 3.19 ± 1.22 mmol/L, respectively, with nearly 1/3 participants coefficient of variation (CV) > 36% (all are male), suggesting a large glucose fluctuation. The female patients were further divided into pregnancy‐related FT1DM (PF) and non‐PF (NPF) subgroups (both n = 5), and we found that PF patients had a significantly higher TIR than NPF patients (77.0 ± 16.1% vs 41.0 ± 22.4%, P < 0.05). There were heterogeneities in the clinical characteristics of FT1DM patients, and the CGM results indicated a very low TIR and large glucose fluctuation which needs careful attention. [ABSTRACT FROM AUTHOR]

Glycated albumin (GA) levels are affected by body fat and its distribution. We explored the association of waist circumference (WC) with GA and to assess the extent to which WC influences GA. We recruited 1799 subjects (age 26–82 y) from communities. GA was determined using the enzyme method, and glycated hemoglobin A 1c (HbA 1c) was detected using high-performance liquid chromatography. Subjects with central obesity had lower GA and GA/HbA 1c than those without (both P <.01). GA and GA/HbA 1c were negatively correlated with central obesity (both P <.01), whereas HbA 1c was not correlated (P =.833). In the euglycemic and hyperglycemic subpopulations, GA and GA/HbA 1c showed decreasing trends as WC levels increased (both P for trends <0.01). WC was a significant negative determinant of GA (P <.05). In the hyperglycemic subpopulation, the GA value decreased by approximately 0.15% for each 5 cm increment in WC regardless of the presence of central obesity. The GA value was reduced by approximately 0.15% for each 5 cm increment in WC, suggesting that more attention should be paid to actual blood glucose underestimated by GA in obese people. • Glycated albumin (GA) levels are affected by body fat and its distribution. • Waist circumference (W), a simple indicator of central obesity, was significantly and inversely associated with GA. • The GA value was reduced by approximately 0.15% for each 5 cm increment in W. [ABSTRACT FROM AUTHOR]

• The high FGF21 level and NAFLD were potential risk factor for MACE, respectively. • The association between FGF21 and MACE may be interacted by NAFLD. • Early screening and intervention for NAFLD are of great importance. We aimed to investigate whether there was a joint effect of fibroblast growth factor 21 (FGF21) and non-alcoholic fatty liver disease (NAFLD) or interaction on the incidence of cardiovascular diseases based on a community-dwelling population. Serum FGF21 levels were determined using an enzyme-linked immunosorbent method. NAFLD was diagnosed via ultrasonography. Multivariable-adjusted cox proportional hazards models were used to assess the joint effects of FGF21 and NAFLD on the major adverse cardiovascular events (MACE). A total of 1194 participants were enrolled in the final analysis. The multivariable-adjusted hazard ratio (HR) of MACE was 1.84 (95% confidence interval (CI) 1.18–2.86) in participants with diagnosed NAFLD at baseline, compared with those without NAFLD at baseline. The multivariable-adjusted HRs of MACE across quintiles of serum FGF21 levels at baseline were 1.00, 1.48 (95%CI 0.68–3.21), 2.01 (95%CI 0.98–4.13), 1.94 (95%CI 0.94–4.02) and 2.14 (95%CI 1.03–4.44) respectively. Participants with high FGF21 levels and NAFLD at baseline showed the highest risk of MACE with a significant interaction between the presence of NAFLD and serum FGF21 levels. Both FGF21 and NAFLD were associated with MACE, while the association between FGF21 and MACE may be interacted by the presence of NAFLD at baseline. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The relationship between glycemic variability (GV) and diabetic complications has gained much interest and remains under debate. Furthermore, the association of GV with diabetic complications has not been examined in latent autoimmune diabetes of the adult (LADA). Therefore, we evaluated the relationships among several metrics of GV with diabetic retinopathy (DR) in patients with LADA and type 2 diabetes mellitus. Materials and Methods: A total of 192 patients with LADA and 2,927 patients with type 2 diabetes mellitus were enrolled. After continuous glucose monitoring for 72 h, three metrics of GV including standard deviation, coefficient of variation and mean amplitude of glycemic excursions were calculated. DR was assessed by fundus photography performed with a digital non‐mydriatic camera. Results: The prevalence of DR was 20.3 and 26.4% in LADA and type 2 diabetes mellitus patients (P < 0.001), respectively. Generally, LADA patients had fewer cardiometabolic risk factors than type 2 diabetes mellitus patients, and all GV metrics were significantly higher in LADA than in type 2 diabetes mellitus. In the multivariate logistic regression analysis, no metrics for GV were identified as independent risk factors of DR (standard deviation: P = 0.175; coefficient of variation: P = 0.769; mean amplitude of glycemic excursions: P = 0.388) in LADA. However, the standard deviation was significantly associated with DR (OR 1.15, P = 0.017) in patients with type 2 diabetes mellitus after adjusting for confounders. The independent relationships of coefficient of variation and mean amplitude of glycemic excursions with DR (P = 0.194 and P = 0.251, respectively) did not reach statistical significance in type 2 diabetes mellitus. Conclusions: GV is more strongly associated with DR in type 2 diabetes than in LADA, suggesting that different glucose‐lowering strategies should be used for these two types of diabetes. [ABSTRACT FROM AUTHOR]

Objective: The presence of low-grade albuminuria (LGA) suggested that the pathophysiology of vascular dysfunction has been initiated. Clear evidence supports a role for osteocalcin in energy metabolism and a great incidence of pathological cardiovascular changes. The observational community-based study aims to examine the association of osteocalcin with LGA, which may provide new insight into potential involvement of osteocalcin in cardiovascular diseases.Methods: A total of 1951 adults [58.37 (53.34-63.13) years, 41.3% men] from Shanghai were enrolled. LGA was defined as a urinary albumin-to-creatinine ratio (UACR) < 30 mg/g. Serum osteocalcin was measured using an electrochemiluminescence immunoassay.Results: Serum osteocalcin level in men decreased with increasing UACR after adjusting for potential covariates (p = 0.045); however, the adjusted association disappeared in women (p = 0.258). Linear regression analysis showed that osteocalcin was a negative variable of UACR in men (standardized β = -0.074, p = 0.030), particularly prominent in non-hyperglycemic, non-hypertensive men, even regardless of estimated glomerular filtration rate (eGFR) (60 ≤ eGFR <90 mL/min/1.73 m2, standardized β =-0.422, p = 0.004; ≥ 90 mL/min/1.73 m2, standardized β = -0.167, p = 0.037).Conclusion: After controlling for confounders, serum osteocalcin level was independently associated with LGA in men, which suggested that osteocalcin was closely related with atherosclerosis and vascular dysfunction. [ABSTRACT FROM AUTHOR]

Background & Aims: Serum adipocyte fatty acid‐binding protein (A‐FABP) is closely correlated to metabolic disorders such as obesity and insulin resistance (IR). Non‐alcoholic fatty liver disease (NAFLD) is a typical feature of IR in the liver. The aim of this study was to explore the relationship between serum A‐FABP levels and NAFLD. Methods: The study enrolled 728 subjects with normal glucose tolerance from communities. Serum A‐FABP levels were measured using a sandwich enzyme‐linked immunosorbent assay. The liver fat content was assessed by ultrasonography. The fatty liver index (FLI) was calculated to quantify the degree of liver steatosis. The upper quartile of homoeostasis model assessment‐insulin resistance (HOMA‐IR) in the total population was defined as IR. Adipose tissue insulin resistance (Adipo‐IR) was calculated to evaluate the impaired suppression of lipolysis in IR. Results: Serum A‐FABP levels were significantly higher in subjects with NAFLD than in those without (P < 0.01). Moreover, subjects with IR had higher levels of A‐FABP than those without (P < 0.01). The proportion of IR or NAFLD and the levels of fasting free fatty acid (FFA) or Adipo‐IR displayed an upward trend as A‐FABP increased (P for trend < 0.05). After adjusting for gender, age, body fat, metabolic factors and liver enzymes, A‐FABP was independently correlated with NAFLD (P < 0.01). A‐FABP was a positive determinant of FLI (P = 0.006). Conclusions: Serum A‐FABP levels were significantly elevated in NAFLD patients among a population with normal glucose tolerance. Serum A‐FABP levels were independently correlated with NAFLD after adjusting for confounding factors. [ABSTRACT FROM AUTHOR]

To develop a non-invasive assessment tool and compare it to other assessment tools among middle-aged and elderly Shanghainese, 15,309 individuals, who were 45-70 years old, not previously diagnosed with diabetes, and from a cross-sectional survey conducted between April 2013 and August 2014 in Shanghai, were selected into this study. The participants were randomly assigned to either the exploratory group or the validation group. Undiagnosed diabetes was defined according to the American Diabetes Association diagnostic criteria, and score points were generated according to the logistic regression coefficients. Age, family history of diabetes, hypertension, overweight/obesity, and central obesity all contributed to the constructed model, the Shanghai Nicheng diabetes screening score, with the area under the receiver-operating characteristic curve (AUC) being 0.654 (95% CI 0.637-0.670) in the exploratory group and 0.669 (95% CI 0.653-0.686) in the validation group. The score value of 6 was the optimal cut-point with the largest Youden's index. When applied to the validation group, our model had a similar discriminative ability to the New Chinese Diabetes Risk Score (AUC: 0.669 vs. 0.662, p = 0.187), and performed better than other screening scores for Chinese. However, our model was inferior to fasting plasma glucose, 2-hour plasma glucose, and glycosylated hemoglobin in detecting prevalent undiagnosed diabetes (AUC: 0.669 (0.653-0.686) vs. 0.881 (0.868-0.894), 0.934 (0.923-0.944), and 0.834 (0.819-0.848), all p < 0.001). Although non-invasive models, based on demographic and clinical information, are advisable in resource-scarce developing areas, regular blood glucose screening is still necessary among those aged 45 or older. [ABSTRACT FROM AUTHOR]

Objective: Continuous glucose monitoring (CGM) has provided new measures of glycemic control that link to diabetes complications. This study investigated the association between the time in range (TIR) assessed by CGM and diabetic retinopathy (DR).Research Design and Methods: A total of 3,262 patients with type 2 diabetes were recruited. TIR was defined as the percentage of time spent within the glucose range of 3.9-10.0 mmol/L during a 24-h period. Measures of glycemic variability (GV) were assessed as well. DR was determined by using fundus photography and graded as 1) non-DR; 2) mild nonproliferative DR (NPDR); 3) moderate NPDR; or 4) vision-threatening DR (VTDR).Results: The overall prevalence of DR was 23.9% (mild NPDR 10.9%, moderate NPDR 6.1%, VTDR 6.9%). Patients with more advanced DR had significantly less TIR and higher measures of GV (all P for trend <0.01). The prevalence of DR on the basis of severity decreased with ascending TIR quartiles (all P for trend <0.001), and the severity of DR was inversely correlated with TIR quartiles (r = -0.147; P < 0.001). Multinomial logistic regression revealed significant associations between TIR and all stages of DR (mild NPDR, P = 0.018; moderate NPDR, P = 0.014; VTDR, P = 0.019) after controlling for age, sex, BMI, diabetes duration, blood pressure, lipid profile, and HbA1c. Further adjustment of GV metrics partially attenuated these associations, although the link between TIR and the presence of any DR remained significant.Conclusions: TIR assessed by CGM is associated with DR in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Our study examined whether osteocalcin contributed to identifying carotid intima-media thickness (C-IMT) over the atherosclerotic cardiovascular disease (ASCVD) risk score. Methods: We recruited 618 middle-aged and elderly men from communities in Shanghai. Serum osteocalcin levels were determined using an electrochemiluminescence immunoassay. C-IMT was measured by ultrasonography. Results: The study included 245 men with low ASCVD risk and 373 men with moderate-to-high ASCVD risk. Serum osteocalcin levels were lower in the moderate-to-high risk vs. low risk men (p=0.042). Multivariate stepwise regression analysis showed that body mass index (BMI) and glycated hemoglobin were predictors for reduced osteocalcin levels (both p<0.001). Among all subjects, the proportion with an elevated C-IMT was higher in the low-osteocalcin group than in the high-osteocalcin group (p=0.042), and the significance of this result was greater when considering only subjects with a moderate-to-high ASCVD risk (p=0.011). The recognition rate of elevated C-IMT was superior with both low osteocalcin and moderate-to-high ASCVD risk vs. either parameter alone (p<0.001 and p=0.015, respectively). Osteocalcin was independently and inversely associated with elevated C-IMT after adjusting for the 10-year ASCVD risk score (p=0.004). The negative relationship remained statistically significant in subjects with a moderate-to-high ASCVD risk in particular (standardized β=−0.104, p=0.044). Conclusions: In middle-aged and elderly men, serum osteocalcin levels strengthen identifying subclinical atherosclerosis over ASCVD risk score, especially among subjects with a moderate-to-high ASCVD risk. [ABSTRACT FROM AUTHOR]

Background Recent studies have discussed the relationship between body mass index (BMI) and glycated albumin (GA) level. However, the extent of the influence of BMI on GA remains uncertain. We investigated the associations between BMI and GA, glycated hemoglobin A 1c (HbA 1c ) and GA/HbA 1c , and to analyze the influence of obesity on GA, HbA 1c , and GA/HbA 1c in both Chinese diabetic and non-diabetic populations. Methods A total of 2562 participants, including 1177 men and 1385 women (age 20–80 y), were enrolled. Each subject underwent a 75-g oral glucose tolerance test. Serum GA was detected using a liquid enzyme method, and HbA 1c was assayed using high-performance liquid chromatography. Results In the diabetic patients ( n  = 1223), the GA, HbA 1c, and GA/HbA 1c levels were 16.7 ± 3.0%, 6.6 ± .9% (49 ± 9 mmol/mol), and 2.51 ± .33, respectively. In the non-diabetic subjects ( n  = 1339), the GA, HbA 1c, and GA/HbA 1c concentrations were 13.8 ± 1.7%, 5.6 ± .4% (38 ± 4 mmol/mol), and 2.47 ± .31, respectively. Decreasing trends in the GA and GA/HbA 1c concentrations and an increasing trend in the HbA 1c concentration (all P for trend <.05) were found to accompany with the increase in BMI, regardless of diabetes status. Multiple regression analysis revealed that BMI was independently related to HbA 1c in the non-diabetic population (standardized β  = .158, P <  .001); however, the relationship disappeared in the diabetic population ( P >  .05). Moreover, in the diabetic and non-diabetic populations, BMI was negatively correlated with GA (standardized β  = −.167 and − .231, both P <  .001) and GA/HbA 1c (standardized β  = −.273 and − .310, both P <  .001). Further analysis showed that a 1 kg/m 2 increment in BMI was associated with a .13% decrease in the absolute value of GA. Conclusions In both diabetic and non-diabetic populations, GA and GA/HbA 1c levels are independently and negatively associated with BMI. For every 1 kg/m 2 increment in BMI, the absolute value of GA decreases approximately .13%. [ABSTRACT FROM AUTHOR]

Glucose monitoring has evolved from self-monitoring of blood glucose to glycated hemoglobin, and the latest continuous glucose monitoring (CGM). A key challenge to adoption of CGM for management of diabetes in Asia is the lack of regional CGM recommendations. Hence, thirteen diabetes-specialists from eight Asia-Pacific (APAC) countries/regions convened to formulate evidence-based, APAC-specific CGM recommendations for individuals with diabetes. We defined CGM metrics/targets and developed 13 guiding-statements on use of CGM in: (1) people with diabetes on intensive insulin therapy, and (2) people with type 2 diabetes on basal insulin with/without glucose lowering drugs. Continual use of CGM is recommended in individuals with diabetes on intensive insulin therapy and suboptimal glycemic control, or at high risk of problematic hypoglycemia. Continual/intermittent CGM may also be considered in individuals with type 2 diabetes on basal insulin regimen and with suboptimal glycemic control. In this paper, we provided guidance for optimizing CGM in special populations/situations, including elderly, pregnancy, Ramadan-fasting, newly diagnosed type 1 diabetes, and comorbid renal disease. Statements on remote CGM, and stepwise interpretation of CGM data were also developed. Two Delphi surveys were conducted to rate the agreement on statements. The current APAC-specific CGM recommendations provide useful guidance for optimizing use of CGM in the region. [ABSTRACT FROM AUTHOR]

Summary: Recent studies have shown that circulating fibroblast growth factor (FGF) 23 and vitamin D levels are closely correlated with insulin resistance. The aim of this study was to investigate the relationship among serum FGF 23 levels, serum 25‐hydroxyvitamin D [25(OH)D] levels, and non‐alcoholic fatty liver disease (NAFLD) in Chinese patients with type 2 diabetes mellitus (T2DM). This study enrolled 331 hospitalized T2DM patients (209 patients with NAFLD and 122 patients without NAFLD). Serum FGF23 levels were measured using a sandwich enzyme‐linked immunosorbent assay. Serum 25(OH)D levels were determined by an electrochemiluminescence immunoassay. NAFLD was diagnosed by hepatic ultrasound, and the fatty liver index (FLI) was calculated to quantify hepatic steatosis. Results showed that T2DM patients with NAFLD had significantly higher serum FGF23 levels (44.17 [37.92‐51.30] pg/mL vs 40.21 [34.07‐48.33] pg/mL, P = .002), but lower serum 25(OH)D levels (16.43 [12.70‐21.37] ng/mL vs 19.59 [13.78‐26.26] ng/mL, P = .002) than those without NAFLD. Moreover, the incidence rate of NAFLD increased with increasing serum FGF23 levels and decreased with increasing 25(OH)D levels (both P < .05). Logistic regression analysis showed that both serum FGF23 and 25(OH)D levels were independent factors for NAFLD (both P < .05). Furthermore, a multiple stepwise regression analysis also revealed that both serum FGF23 and 25(OH)D levels were independently correlated with FLI (both P < .01). In conclusion, both high FGF23 and low vitamin D levels showed an independent relationship with NAFLD in Chinese T2DM patients, indicating that FGF23 and vitamin D function via different regulatory pathways in the liver. [ABSTRACT FROM AUTHOR]

In previous epidemiological screening in China, glycated albumin (GA) was mostly detected during the fasting state. This strict restriction causes some problems with diabetes screening. It is unclear if GA could help improve the efficiency of screening for diabetes for subjects who are not in the fasting state. The present study analyzed the differences between fasting and postload (30, 60, 120, and 180 min) GA levels. A total of 691 participants were enrolled in the present study. The Bland-Altman difference plots revealed that 95.4, 94.8, 93.6, and 93.9% of data points were within the limits of agreement for each time point. The receiver operating characteristic curve showed that the areas under the curve (AUC) for baseline GA and postload GA for every time point were 0.822 (95% CI 0.791–0.849), 0.821 (95% CI 0.790–0.848), 0.833 (95% CI 0.803–0.860), 0.840 (95% CI 0.811–0.867), and 0.840 (95% CI 0.810–0.867), with sensitivities of 67.5, 68.1, 69.3, 71.6, and 69.3%, respectively. There was no difference between the baseline and postload GA levels in either AUC or sensitivity (all p>0.05). In conclusion, postload serum GA levels were in good agreement with those at baseline, and thus, it may be reasonable to employ nonfasting measurements of GA levels for diabetes screening. [ABSTRACT FROM AUTHOR]

Serum uric acid (SUA) levels are highly heritable and an increased SUA level is one of important risk factors for gout, diabetes, metabolic syndrome, and cardiovascular diseases. The genetic variants underlying SUA remains largely unexplored. The aim was to explore new genetic variants underlying SUA in Chinese Han. We performed a genome-wide association study of SUA levels in Han Chinese. The discovery set contained 1634 samples and subsequent replication was comprised of 1649 females and 1169 males. 2620 subjects were recruited in the detailed analysis of rs671, alcohol drinking and SUA. We found a genome-wide significant association between SUA level and the SNP rs671 at ALDH2 ( P  = 1.2 × 10 −10 ) in the merged data. In addition, we also replicated the signal from rs3733590 at SLC2A9 ( P  = 1.0 × 10 −10 ). In males, about 0.21% to 1.95% of the total variance for SUA can be explained by rs671 using linear regression models in four independent cohorts. Of those, 56.75% to 93.51% might be explained by altering alcohol consumption due to rs671. No statistical association of rs671 and SUA was observed in females ( P  = 0.409). Furthermore, we observed a causal relationship between alcohol consumption and SUA in males using rs671 as an instrumental variable ( P  = 5.1 × 10 −4 ). We replicated the previous findings in SLC2A9 . Our evidence supported that rs671 was associated with SUA by affecting alcohol consumption in males. This finding strongly suggests a role for alcohol consumption in the development of hyperuricaemia and uric acid related traits. [ABSTRACT FROM AUTHOR]

Objectives: To investigate whether serum fibroblast growth factor 21 (FGF21) levels can be used to predict the future development of major adverse cardiovascular events (MACEs). Methods: This study included 253 patients who received subsequent follow-up, and complete data were collected for 234 patients. Independent predictors of MACEs were identified by using the Cox proportional-hazards regression analysis. The prognostic value of FGF21 levels for MACEs was evaluated by Kaplan-Meier survival analysis. Results: Of 229 patients finally enrolled in the analysis, 27/60 without coronary artery disease (CAD) at baseline experienced a MACE, and 132/169 patients with CAD at baseline experienced a MACE. Among patients with CAD at baseline, serum FGF21 levels were significantly higher in patients with MACEs (p < 0.05) than in patients without MACEs. Kaplan-Meier survival analysis showed patients with a higher serum FGF21 had a significantly lower event-free survival (p = 0.001) than those with a lower level. Further Cox proportional-hazards regression analysis, including the traditional risk factors for cardiovascular disease, showed that serum FGF21 was an independent predictor of MACE occurrence. Conclusions: In patients with CAD at baseline, an elevated serum FGF21 level was associated with the development of a MACE in the future. [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]

Abstract: Aims/Introduction: The present study aimed to investigate the performance of a new real‐time continuous glucose monitoring system. Materials and Methods: Interstitial glucose levels were monitored for 7 days in 63 patients with type 1 or type 2 diabetes using the Medtrum A6 TouchCare® CGM System. Venous blood was collected on a randomized day of the wear period. Plasma glucose levels were measured as reference values. Results: Among 1,678 paired sensor–reference values, 90.5% (95% confidence interval 89.1–91.9%) were within ±20%/20 mg/dL of the reference values, with a mean absolute relative difference of 9.1 ± 8.7% (95% CI: 8.9–9.2%). The percentages of paired sensor–reference values falling within zone A and B of the Clarke error grid analysis (EGA) and the type 1 diabetes consensus EGA were 99.1 and 99.8%. Continuous EGA showed that the percentages of accurate readings, benign errors, and erroneous readings were 89.9, 6.3 and 3.8%, respectively. Surveillance EGA showed that 90.6, 9.2, and 0.2% of sensor–reference values with no, slight and lower moderate risk, respectively. The mean absolute relative difference was 16.6, and 96.0% of the sensor values fell within zones A and B of the consensus EGA for hypoglycemia. More than 85% of sensor values were within ±20%/20 mg/dL of reference values, the mean absolute relative difference was <11, and >99.5% of the sensor values fell in zones A and B of the consensus EGA. Conclusions: The Medtrum real‐time continuous glucose monitoring system was numerically and clinically accurate over a large glucose range across 7 days of wear. [ABSTRACT FROM AUTHOR]

We investigated whether the serum osteocalcin levels at baseline were associated with the incidence of major adverse cardiovascular events (MACE) in a population-based retrospective cohort study of Chinese subjects. Coronary angiography was used to diagnose coronary artery disease (CAD). Survival curves were analyzed by performing log-rank tests with Kaplan-Meier figures. Multivariable Cox proportional hazards regression was performed to identify the association of serum osteocalcin levels with the incidence of MACE. A total of 247 subjects with a mean age of 65.50 ± 10.38 years were enrolled in the analysis. After a mean follow-up time of 4.4 ± 2.6 years, MACE occurred in 175 cases. For men patients, those with serum osteocalcin levels higher than 17.22 ng/mL had significantly lower fasting plasma glucose (FPG) than those with serum osteocalcin levels lower than 17.22 ng/mL ( P < .05). According to the multivariate Cox proportional hazards regression, the lower serum osteocalcin levels and the higher risk of future MACE occurred in men with CAD at baseline (hazard ratio = 0.970; 95% confidence interval 0.943-0.999, P = .04). However, this difference was not significant either in men without CAD or in women. In conclusion, relatively lower serum osteocalcin levels were associated with a higher risk of MACE in Chinese men with CAD. [ABSTRACT FROM AUTHOR]

Background: The rate of glycemic control among diabetes patients in China is currently low. The current study aims at determining the effect of structured self-monitoring of blood glucose (SMBG) on blood glucose control as well as quality of life (QoL) in Chinese diabetes patients.Methods: In a 24-week, single-center, randomized, open-label, prospective trial, patients with glycated hemoglobin A1c (HbA1c) >8.0% were randomized to an intervention group for structured SMBG (n = 121) or a control group (n = 129). Patient data were analyzed separately according to treatment with or without insulin. At 0, 3rd, and 6th months, life satisfaction was assessed using the Chinese Normal Audit of Diabetes-Dependent Quality of Life (CN-ADDQoL) questionnaire.Results: The mean HbA1c decrease from baseline to the study end was significant for both groups with insulin treatment (intervention group: -1.79% ± 1.97%, P < 0.001; control group: -1.05% ± 1.87%, P < 0.001) or without insulin treatment (intervention group: -1.91% ± 1.90%, P < 0.001; control group: -1.35% ± 1.82%, P < 0.001). Moreover, the insulin-treated patients in the intervention group showed a significantly more robust HbA1c decrease than those in the control group (P = 0.007). Both therapeutic subgroups in the intervention group had a significantly higher frequency of SMBG than those in the control group (P < 0.001), but no strict deterioration of the QoL was detected. In addition, a significant HbA1c reduction after 6 months of SMBG was seen for both insulin-treated patients (P = 0.027) and noninsulin-treated patients (P = 0.006) younger than 66 years.Conclusions: Featured with no strict deterioration of QoL, structured SMBG was proven to be effective on the glycemic control in patients with insulin treatment, as well as in young and middle-aged patients without insulin treatment. [ABSTRACT FROM AUTHOR]

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]

Background. Our previous study indicated that serum 1,5-anhydroglucitol (1,5-AG) levels slightly increased after a glucose load; therefore, this study was conducted to explore short-term changes in 1,5-AG levels after a steamed bread meal test (SBMT) and compare the agreement of 1,5-AG, glycated albumin (GA), and glycated hemoglobin A1c (HbA1c) levels between fasting and postprandial states after an SBMT. Methods. 104 participants were recruited and underwent a 100 g SBMT. Fasting, 30 min, and 120 min of 1,5-AG, GA, and HbA1c were measured. Results. Levels of 1,5-AG slightly increased from 30 to 120 min after an SBMT (P<0.01), and HbA1c and GA levels showed stability at 30 and 120 min. The Passing-Bablok regression linear equation showed that postprandial 1,5-AG, GA, and HbA1c levels were well fitted (all P>0.05), and Bland-Altman difference plot showed that 100% of data points for HbA1c30 and HbA1c120 fell within the limits of agreement; 94.2%, 96.2%, 95.2%, and 95.2% of data points for 1,5-AG30, 1,5-AG120, GA30, and GA120 fell within the limits of agreement, respectively. Conclusion. Agreement analyses indicated good stability of 1,5-AG, GA, and HbA1c levels after the SBMT. HbA1c had an optimal stability, which was superior to that of GA or 1,5-AG. [ABSTRACT FROM AUTHOR]

Aim: The relationship between fibroblast growth factor 21 (FGF21) and cardiovascular disease has been well established in recent studies. This study aimed to investigate the relationship between FGF21 and left ventricular systolic dysfunction and cardiac death. Methods: Two-dimensional echocardiography was used to measure the left ventricular ejection fraction (LVEF) to estimate left ventricular systolic function. The optimal cutoff of FGF21 for identifying left ventricular systolic dysfunction at baseline was analyzed via receiver operating characteristic (ROC) curves. The identification of different serum levels of FGF21 and their association with cardiac death was analyzed via Kaplan-Meier survival curves. Serum FGF21 level was measured by an enzyme-linked immunosorbent assay kit, and serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP) level was determined by a chemiluminescent immunoassay. Results: A total of 253 patients were recruited for this study at baseline. Patients were excluded if they lacked echocardiography or laboratory measurement data, and there were 218 patients enrolled in the final analysis. The average age was 66.32 ± 10.10 years. The optimal cutoff values of FGF21 and NT-pro-BNP for identifying left ventricular systolic dysfunction at baseline were 321.5 pg/mL and 131.3 ng/L, respectively, determined separately via ROC analysis. The areas under the curves were non-significant among FGF21, NT-pro-BNP and FGF21 + NT-pro-BNP as determined by pairwise comparisons. Both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP were independent risk factors for left ventricular systolic dysfunction at baseline (odd ratio (OR) 3.138 [1.037-9.500], P = 0.043, OR 9.207 [2.036-41.643], P = 0.004, separately). Further Kaplan-Meier survival analysis indicated an association between both a higher serum level of FGF21 and a higher serum level of NT-pro-BNP with cardiac death in 5 years [RR 5.000 (1.326-18.861), P = 0.026; RR 9.643 (2.596-35.825), P = 0.009, respectively]. Conclusions: Serum FGF21 level was significantly correlated with left ventricular systolic dysfunction at baseline. Patients with higher serum levels of FGF21 tended to suffer greater risks of cardiac death than patients with lower serum levels of FGF21. The identification of FGF21 and its relationship with left ventricular systolic function and cardiac death were non-inferior to NT-pro-BNP. [ABSTRACT FROM AUTHOR]

Aims: We assessed the impact of changes in body mass index (BMI), body fat percentage (BF%), and waist circumference (WC) on prediabetes among Chinese middle-aged and elderly adults.Subjects, Materials and Methods: 2.5-year changes in BMI, BF%, and WC were calculated by subtracting baseline levels from follow-up, based on a cohort of 3,632 participants with prediabetes, and outcomes were defined as remission to normal glucose regulation (NGR), persistence in prediabetes, and progression to newly diagnosed diabetes mellitus (NDM).Results: Among participants with prediabetes, 16.9% returned to NGR and 24.6% progressed to NDM. Changes in BMI, BF%, but not WC were associated with remission and progression of prediabetes (risk ratio per standard deviation increase of BMI: 0.86 [0.79-0.93] and 1.15 [1.08-1.23]; BF%: 0.91 [0.84-0.98] and 1.11 [1.03-1.19]). Among participants with combined impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), only BF% change was significantly associated with remission of prediabetes.Conclusion: Short-term management of BMI and BF% should be stressed to promote the remission and prevent the progression of prediabetes, regardless of whether someone is obese. Moreover, it is of particular clinical importance to monitor BF% among people with combined IFG and IGT. [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]

Aims: Previous studies showed that serum 1,5-anhydroglucitol (1,5-AG) levels are significantly reduced in patients with diabetes mellitus (DM). However, it remains unclear how 1,5-AG levels acutely change in response to a glucose load. This study explored acute changes in 1,5-AG levels after a glucose load and the related influencing factors in individuals with differing degrees of glucose tolerance. Methods: A total of 681 participants (353 without DM and 328 with DM) without a prior history of DM were enrolled. All participants underwent an oral glucose tolerance test. Fasting and postload (30, 60, 120, and 180 min) levels of plasma glucose, serum 1,5-AG, and insulin were measured. Results: In all participant groups, serum 1,5-AG levels were slightly elevated after a glucose load and reached peak values at 120 min after loading (all P < 0.05). Regression analysis showed that body weight was negatively associated with the difference between peak and baseline 1,5-AG levels (Δ1,5-AG, standardized β = −0.119, P < 0.01). A strong and positive association between 1,5-AG and Δ1,5-AG was also found independent of other confounding factors (standardized β = 0.376, P < 0.01). The ratio of the Δ1,5-AG to the 1,5-AG was higher in DM patients (7.3% [3.4-11.5%]) than in those without DM (6.2% [3.6-9.2%]). Conclusions: In contrast to the established decline in 1,5-AG levels with long-term hyperglycemia, the present study showed that serum 1,5-AG levels slightly increased by 6-7% after a glucose load. Further studies in different 1,5-AG transport models are needed to investigate the relevant metabolic pathways. [ABSTRACT FROM AUTHOR]

Aims: To investigate the association between non-alcoholic fatty liver disease (NAFLD) and carotid and lower limb atherosclerotic lesions in a large group of hospitalized-based type 2 diabetic population and to assess the prevalence and characteristics of NAFLD in Chinese subjects with type 2 diabetes (T2DM).Methods: A total of 8571 patients (4804 men) with T2DM were included in this cross-sectional study. The main outcome measures were detection of NAFLD, carotid intima-media thickness (C-IMT), carotid and lower limb atherosclerotic plaque formation, and classical risk factors.Results: The prevalence of carotid (56.5% vs. 44.5%; p<0.001) and lower limb plaque (56.2% vs. 48.7%; p<0.001), and carotid (11.2% vs. 6.8%; p<0.001) and lower limb stenosis (15.1% vs. 10.3%; p<0.001) was markedly higher in the diabetic patients with NAFLD than in those without, after controlling for age. However, there was no significant difference in C-IMT between diabetic patients with and without NAFLD (0.82±0.30mm vs. 0.85±0.39mm) after controlling for age. Fully adjusted multiple linear regression and logistic regression analyses revealed that NAFLD was significantly associated with increased prevalence of carotid and lower limb atherosclerotic plaque but not with C-IMT. NAFLD, age, sex, longer duration of diabetes and the presence of hypertension were independently associated with carotid and lower limb atherosclerotic plaque (p<0.05).Conclusion: NAFLD was not associated with elevated C-IMT but was associated with carotid and lower limb atherosclerotic plaque independent of conventional cardiovascular disease risk factors and metabolic syndrome in Chinese inpatients with T2DM. [ABSTRACT FROM AUTHOR]

Recently, 5 amino acids were identified and verified as important metabolites highly associated with type 2 diabetes (T2D) development. This report aims to assess the association of tryptophan with the development of T2D and to evaluate its performance with existing amino acid markers. A total of 213 participants selected from a ten-year longitudinal Shanghai Diabetes Study (SHDS) were examined in two ways: 1) 51 subjects who developed diabetes and 162 individuals who remained metabolically healthy in 10 years; 2) the same 51 future diabetes and 23 strictly matched ones selected from the 162 healthy individuals. Baseline fasting serum tryptophan concentrations were quantitatively measured using ultra-performance liquid chromatography triple quadruple mass spectrometry. First, serum tryptophan level was found significantly higher in future T2D and was positively and independently associated with diabetes onset risk. Patients with higher tryptophan level tended to present higher degree of insulin resistance and secretion, triglyceride and blood pressure. Second, the prediction potential of tryptophan is non-inferior to the 5 existing amino acids. The predictive performance of the combined score improved after taking tryptophan into account. Our findings unveiled the potential of tryptophan as a new marker associated with diabetes risk in Chinese populations. The addition of tryptophan provided complementary value to the existing amino acid predictors. [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]

• A method has been developed to quantify the levels of salivary amino acids which may indicate dysfunction of the body. • Salivary amino acid profile is quantified by a single quadrupole mass detector (QDa), which is very simple and easy to operate in routine laboratory. • The developed method is rapid which only takes 6min to complete a single run after 10min derivatization. • The method has potential value in the clinical translational application. Abnormal salivary amino acid (AA) levels may indicate dysfunction of the body. Being noninvasive, sampling easily and cost-effective of saliva, a rapid, precise and simple analysis method has become very important for quantitative salivary AA profiles. After one-step to precipitate protein, the resultant extraction was derived with 6-aminoquinolyl- N -hydroxysuccinimidyl carbamate (AQC) within 10 min. Quantitation of AA profile was achieved within 6 min in a single run by ultra-high performance liquid chromatography coupled with a single quadrupole mass spectrometry (UHPLC-QDA detector). The method was validated with acceptable accuracy ranging from 80.33 % to 122.31 %, appropriate linearity with the coefficient (R2) more than 0.991, good intra- and inter-day precision, repeatability and stability (RSD < 15 %). The recoveries at three different spiked concentrations ranged over 79.18 %–125.36 % while the matrix effect was from −19.86 % to 11.95 %. This simple, rapid and robust method was successfully applied to quantify human salivary 30 amino acids, in which the levels of taurine, γ-aminobutyric acid, methionine and tryptophan in healthy people were close to the LOQs. Besides, the levels of histidine and cystine were not able to be measured due to their relatively high LOQs, which were considered as the limitations of this developed method. [ABSTRACT FROM AUTHOR]

Aim: We aimed to investigate the association between uric acid related genetic loci and DKD susceptibility in type 2 diabetes patients.Methods: Seventeen single nucleotide polymorphisms (SNPs) from thirteen loci related to serum uric acid were genotyped in 2,892 type 2 diabetes patients. Associations between SNPs and uric acid, SNPs and quantitative traits related to DKD or its susceptibility were evaluated.Results: In this study, uric acid showed a strong association with DKD (OR=1.006, p<0.0001). GCKR rs780094, SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142, SLC22A12 rs505802 and NRXN2 rs506338 were positively associated with serum uric acid (p=3.79E-05, 0.0002, 2.04E-10, 2.23E-09, 0.0018 and 0.0015, respectively). SLC2A9 rs11722228 and SF1 rs606458 were significantly associated with DKD (OR=0.864, p=0.0440; OR=1.223, p=0.0038). SLC2A9 rs3775948 and ABCG2 rs2231142 were associated with DKD marginally (OR=0.878, p=0.0506; OR=0.879, p=0.0698). SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142 and SF1 rs606458 were significantly associated with the estimated glomerular filtration rate (p=0.0005, 0.0006, 0.0003, and 0.0424, respectively).Conclusions: Our study indicated that the uric acid related alleles of SLC2A9 rs11722228, SLC2A9 rs3775948, ABCG2 rs2231142 might affect DKD susceptibility and possibly through non-uric acid pathway in the Chinese people with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: This cross-sectional study aimed to determine the prevalence and associated risk factors of chronic kidney disease (CKD) in Chinese type 2 diabetic patients.Methods: A total of 3301 patients with type 2 diabetes were included in this study. Anthropometric parameters and biochemical indices were measured. The main outcome measures were detection of CKD, albuminuria and estimated glomerular filtration rate (eGFR).Results: The prevalence of CKD and albuminuria in Shanghai Chinese type 2 diabetic patients was 27.1% and 25.2%. The prevalence of mildly decreased renal function or worse (eGFR<60/mL/min/1.73m(2)) was 6%. The prevalence of glomerular hyperfiltration was 12.2%. The prevalence of diabetic kidney disease (DKD) according to the newest NKF's KDOQI classification was 12.03%. Risk factors associated with DKD were SBP, retinopathy, neuropathy, TG, LDL, anemia and HbA1c. Clinical factors associated with both albuminuria and low eGFR (≥60/<60) were SBP, retinopathy, TC, TG and anemia.Conclusion: In conclusion, CKD and DKD were common in the Shanghai Chinese patients with T2DM and were similar to that in Western patients. Prevention and control of diabetes should be a high priority in reducing the CKD burden in China. [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]

We investigated the relationship between serum cystatin C levels and the prognosis of diabetic foot ulcerations (DFU). A population-based cohort study involving 1018 patients with type 2 diabetes was conducted. These patients recruited and divided into two groups: nondiabetic foot ulcer group (NDF, n = 865, 85.5%) and diabetic foot ulcer group (DFU, n = 147, 14.5%).After a 1-year-follow-up, DFUs were grouped into healing ( n = 110, 74.8%) and nonhealing ( n = 37, 25.2%) group based on the clinical prognosis. Compared with the healing group, the nonhealing group were older, had long diabetic duration and had significantly increased serum cystatin C concentrations in DFU ( p < 0.01). After adjustments for age, diabetes duration, renal function and infection control, multiple logistical regression analysis revealed that cystatin C remained associated increased risk of undesirable DFU outcome (OR = 7.279, 95% CI: 1.299-40.784, p < 0.05). When divided into quartiles according to cystatin C levels, the healing rate of Quartile 4 was significantly lower (57.9%) compared with other groups ( p < 0.01). The odd is ratio (OR) analysis showed that the risk of undesirable DFU outcome in Quartile 4 was significantly higher (OR = 4.554, 95% CI: 3.14-5.12, p < 0.05) compared with that in Quartile 1. We concluded that there was a strong and independent association between serum cystatin C and diabetic foot ulceration prognosis, cystatin C > 1.35 mg/L predicts more than sixfold increased risk of incurable foot ulceration. [ABSTRACT FROM AUTHOR]

Aim: This study explored the possibility of developing an alternative, simple and rapid test for the screening of distal symmetrical polyneuropathy (DSPN), for use in local primary care facilities.Methods: 4023 patients with type 2 diabetes mellitus (T2DM), aged 18-80 years, from 21 hospitals in China were screened for inclusion in a prospective diagnostic assessment of DSPN, between April 2011 and March 2012. Patients underwent nerve conduction study (NCS; as the gold standard) and clinical assessments of ankle reflexes (AR) and thermal (T), vibration (V), pressure (P), and pinprick (PP) sensations.Results: Results from various combinations of these clinical assessments were compared to determine the optimal screening regimens. The Toronto Consensus Panel definition was used to confirm clinical DSPN (symptoms or signs plus abnormal NCS). 3883 of the 4023 patients (M:F, 2162:1721; mean age, 56.79±13.16 years) were included. No significant differences were found between the two most efficient clinical assessment combinations, AR+PP+T+V and AR+T+V (P=0.9612). Compared to the diagnosis made using AR+T+V, the same diagnosis was reached using AR+PP+P+V+T in 100% of patients with probable clinical DSPN, 84.05% with possible clinical DSPN, and 96.84% with no DSPN. The AR+T+V assessment was also ∼40% faster than the AR+PP+P+V+T assessment.Conclusions: Combined AR+T+V assessment is a valuable tool for screening diabetic patients for DSPN, potentially decreasing costs to local primary care facilities and making care more available to underserved populations. [ABSTRACT FROM AUTHOR]

Aim: The association between thyroid stimulating hormone (TSH) and type 2 diabetes mellitus (T2DM) is well known. However, whether TSH is related to diabetic peripheral neuropathy (DPN) has not been studied. The aim of this study was to explore the relationship between TSH and DPN in Chinese patients with T2DM.Methods: In this cross-sectional study, 605 patients with T2DM were enrolled. Subclinical hypothyroidism (SCH) was defined as an elevated TSH level (>4.0mIU/L) and a normal free thyroxine level. DPN was evaluated by neurological symptoms, neurological signs, and electromyogram.Results: Serum TSH levels were significantly higher in DPN and signs of DPN compared with non-DPN T2DM patients (both P<0.01).The prevalence of DPN and signs of DPN in SCH subjects was higher than that in euthyroid subjects (both P<0.01). Spearman's correlation analysis showed that the serum TSH level was positively associated with DPN (r=0.172, P<0.01). A significant independent association between TSH and DPN was found by multiple logistic regression analysis after adjusting for potential confounding variables [odds ratio (OR)=1.365, P<0.01]. The patients were sequentially assigned to quartiles according to TSH level. Compared with quartile 1, patients in quartile 2 (P<0.01), quartile 3 (P=0.01), and quartile 4 (P<0.01) had a higher risk of DPN. Receiver-operating characteristic curve analysis revealed that the optimal cutoff point of TSH to indicate DPN was 3.045mIU/L in men and 2.94mIU/L in women.Conclusion: TSH level is independently associated with DPN in Chinese population with T2DM. A high serum TSH level may be a potential risk factor for DPN. [ABSTRACT FROM AUTHOR]

Aims: Ficolin-3, a soluble molecule of the innate immune system, has a primary role in the activation of the lectin pathway in the complement system. Considering that inflammatory mechanisms are involved in complement activation and take part in the pathophysiology of diabetic peripheral neuropathy (DPN), we conducted this study to explore the link between serum ficolin-3 and DPN in diabetic patients. Methods: A total of 466 diabetic patients were enrolled in this cross-sectional study. DPN was evaluated by neurological symptoms, neurological signs, neurothesiometer and electromyogram. The concentration of serum ficolin-3 was determined by enzyme-linked immunosorbent assay. Results: The concentration of serum ficolin-3 was lower in DPN patients compared with non-DPN patients (18.73 ± 4.75 vs. 26.69 ± 5.68 ng/mL, P < 0.001). In addition, it was found negatively correlated to the vibration perception threshold ( r = −0.158; P = 0.025). The results of multiple regression analysis of DPN indicated that age, diabetes duration, serum ficolin-3 were all independent impact factors for DPN ( P < 0.05). Patients were then assigned into quartiles according to the serum ficolin-3 levels, and the prevalence of DPN ascended as the concentration of ficolin-3 descended (Trend analysis, P < 0.001). Compared with ficolin-3 Quartile 1 (referent), the risk of DPN was significantly greater in Quartile 2 (OR 2.76; 95 % CI 1.56-4.88; P < 0.001), Quartile 3 (OR 3.02; 95 % CI 1.69-5.40; P < 0.001) and Quartile 4 (OR 6.84; 95 % CI 3.39-13.80; P < 0.001). Conclusions: Lower ficolin-3 level is independently associated with DPN, and it may be a potential biomarker for DPN. [ABSTRACT FROM AUTHOR]

The automatic extraction of blood vessels in non-fluorescein eye fundus images is a tough task in applications such as diabetic retinopathy screening. However, vessel shapes have complex variations, and accurate modeling of retinal vascular structures is challenging. We have therefore developed a new approach to accurately extract blood vessels in non-fluorescein fundus images using an orientation-aware detector (OAD). The detector was designed according to the intrinsic property of vessels being locally oriented and having linearly elongated structures. We employ the OAD to extract vessel shapes with no assumptions on parametric orientations of vessel shapes. The orientations of vessels can be efficiently modeled by the energy distribution of Fourier transformation. Accordingly, both wide and thin vessels can be extracted with two-scale segmentation in which line operators are applied in large scale and the Gabor filter bank is applied in small scale. A post-processing technique, based on the path opening operation, is applied to eliminate false responses to nonvascular areas, such as retinal structures (optic disc and macula) and pathologies (exudates, hemorrhages,and microaneurysms). This makes the detector robust and structure-aware. By achieving a competitive CAL measurement of 80.82% for the DRIVE database and 68.94% for the STARE, the experimental results demonstrated that the OAD approach outperforms existing segmentation methods. Furthermore, the proposed approach effectively works with non-fluorescein fundus images and proves highly accurate and robust in complicated regions such as the central reflex, close vessels, and crossover points, despite a high level of illumination noise in the original data. [ABSTRACT FROM AUTHOR]

Background: Fibroblast growth factor 21 (FGF21) exerts wide-range effects on carbohydrate and lipid metabolism. However, its perturbation in type 2 diabetes mellitus (T2DM) remains elusive. Besides, previous human studies in T2DM simply investigated fasting or stimulated levels of FGF21. The current study sought to evaluate the temporal changes of circulating FGF21 in subjects with and without T2DM. Methods: Ten patients with T2DM and 16 normal controls (NC) were recruited. Participants were categorized as obese (BMI≥25 kg/m2) or lean (BMI<25 kg/m2). Blood samples were drawn every 30 min within 7 hours (8 a.m.-3 p.m.). Serum FGF21, blood glucose, insulin, free fatty acids (FFAs) and adiponectin were measured in all subjects. Results: The peak levels of FGF21 were observed in the fasting state (8 a.m.) both in T2DM and NC groups (267.35 ±158.72 ng/L vs. 178.93±121.37 ng/L, P = 0.096). FGF21 AUC did not differ significantly between the two groups (T2DM: 949.4±471.47 ng/L; NC: 883.13±561.40 ng/L, P = 0.770). Obese subjects had higher FGF21 levels than lean ones in patients either with or without T2DM. The pattern of FFAs closely resembled that of FGF21. Correlation analysis showed that temporal levels of FGF21 were significantly related to FFAs (r = 0.749, P = 0.002),but not blood glucose, insulin or adiponectin (all P> 0.05). Conclusions: These findings suggest that the pattern of circulating FGF21 does not differ significantly between T2DM and NC,although T2DM patients showed a trend toward higher fasting FGF21 than healthy subjects. The pattern of circulating FFAs is significantly associated with that of FGF21. [ABSTRACT FROM AUTHOR]

Fibroblast growth factor 23 (FGF23) has been reported to be involved in cardiovascular disease. The aim of this study was to investigate the association between FGF23 and the presence of coronary artery disease (CAD), as well as the number of stenotic vessels. A total of 254 eligible participants (167 men and 87 postmenopausal women) were enrolled in this study. Coronary angiography was used for diagnosis of CAD. Serum intact FGF23 levels were determined by a twosided sandwich enzyme-linked immunosorbent assay. The median serum FGF23 levels of the entire study population were 39.9 (33.1–47.5) pg/mL. Serum FGF23 levels were higher in subjects with one-vessel disease than those without CAD (P < 0.05), which further increased significantly in the subjects with multi-vessel disease (P < 0.05). Serum FGF23 levels increased with cumulative number of stenotic vessels (P for trend < 0.001). Multiple stepwise regression analysis revealed estimated glomerular filtration rate (standardized β = 0.298; P < 0.001) and body mass index (standardized β = 0.132; P = 0.049) were independent factors correlated with FGF23. Multivariate logistic regression analysis showed that FGF23 was positively and independently associated with the presence of CAD (odds ratio = 1.058, 95% confidence interval = 1.025–1.092; P = 0.001). Additionally, FGF23 was also correlated with multi-vessel disease significantly (odds ratio = 1.034, 95% confidence interval = 1.007–1.062; P = 0.013). In conclusion, serum FGF23 levels exhibit positive and independent association with the presence of CAD and increase with the cumulative number of stenotic vessels. [ABSTRACT FROM AUTHOR]