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Objective. Neck circumference (NC) is a simple anthropometric index for the assessment of upper body obesity. Thyroid hormones are closely related to obesity, body fat distribution indicators, and metabolic parameters. However, there are currently no reports on the association between NC and thyroid hormones in the Chinese population. This study aimed to explore the relationship between NC and thyroid hormones in men with normal thyroid function. Methods. A total of 737 euthyroid men from Shanghai communities were enrolled. Anthropometric parameters, including NC and waist circumference (WC), were measured. Serum thyroid hormones were measured by electrochemical luminescence immunoassay. Results. NC, WC, and body mass index (BMI) were significantly positively correlated with serum free triiodothyronine (FT3) (all P < 0.05). FT3 levels all presented significant upward trends with the increase in NC, WC, or BMI quartiles (all P for trend < 0.05), whereas there were no significant correlations between the three obesity indices and free thyroxine or thyroid-stimulating hormone (both P > 0.05). After adjustment for metabolic confounding factors such as age, blood pressure, blood glucose, lipid profiles, and CRP in multiple linear regression analysis, the correlation between FT3 and NC disappeared (standardized β = −0.015, P = 0.705), and FT3 remained significantly associated with WC (standardized β = 0.103, P = 0.012) and BMI (standardized β = 0.082, P = 0.047). Conclusions. In euthyroid men from Shanghai communities, there was no independent correlation between serum FT3 levels and NC. The trial was registered with ChiCTR1900024011. [ABSTRACT FROM AUTHOR]

Previous studies found that thyroid hormones stimulate osteoblast-like cells to secrete osteocalcin. We aimed to investigate the association between serum thyroid hormone and serum osteocalcin in euthyroid population. The study recruited 1152 community-based euthyroid subjects (average age 59 ± 8 years), among whom 677 were women. Serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and osteocalcin were measured by electrochemiluminescence immunoassays. After adjusting for age and gender, partial correlation analysis showed that FT3 and FT3/FT4 were both positively correlated with body mass index (BMI) and serum osteocalcin levels (all P < 0.05) and BMI was negatively correlated with serum osteocalcin levels P < 0.01 , while FT4 and TSH were not correlated with serum osteocalcin levels (all P > 0.05). Age, gender, blood pressure, thyroid hormones, and multiple metabolic risk factors were included in the ridge regression model. FT3 and FT3/FT4 were independently and positively associated with serum osteocalcin levels (all P < 0.05), while BMI was independently and negatively associated with serum osteocalcin levels P < 0.01 . The mediating effect model showed that FT3 and FT3/FT4 suppressed the negative association between BMI and serum osteocalcin levels, with suppressing effects of 6.41% and 10.39%, respectively. In euthyroid subjects, both FT3 and FT3/FT4 were positively associated with serum osteocalcin levels, and they further suppressed the negative association between BMI and serum osteocalcin levels. [ABSTRACT FROM AUTHOR]

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

Osteocalcin is a bone-derived hormone that plays an important role in the crosstalk between bone and energy metabolism. Previous studies have found that treatment with uncarboxylated osteocalcin can protect mice from high-fat diet-induced nonalcoholic fatty liver disease (NAFLD). However, the potential mechanisms remain unclear. Although the G protein-coupled receptor family C group 6 subtype A (GPRC6A) is the putative receptor of osteocalcin, there is no direct evidence showing that GPRC6A mediates the effects of uncarboxylated osteocalcin in alleviating NAFLD in mice. We aimed to figure out this using liver-specific GPRC6A knockout (GPRC6ALKO) mice. Consistent with previous studies, uncarboxylated osteocalcin significantly protected high-fat diet-fed wild-type mice from obesity and NAFLD, while it did not protect high-fat diet-fed GPRC6ALKO mice from NAFLD. Differential mRNA expression of lipogenesis and lipolysis between GPRC6ALKO mice and control mice revealed that GPRC6A mediated the effects of osteocalcin in alleviating NAFLD through inhibiting lipid synthesis and promoting lipolysis. In conclusion, this study found that uncarboxylated osteocalcin alleviates NAFLD in mice through the GPRC6A signaling pathway. Our study suggests that liver GPRC6A may be a potential target for treating NAFLD. [ABSTRACT FROM AUTHOR]

Nocturnal hypoglycemia is a serious complication of insulin-treated diabetes, and it is often asymptomatic. A novel CGM metric-gradient was proposed in this paper, and a method of combining mean sensor glucose (MSG) and gradient was presented for the prediction of nocturnal hypoglycemia. For this purpose, the data from continuous glucose monitoring (CGM) encompassing 1,921 patients with diabetes were analyzed, and a total of 302 nocturnal hypoglycemic events were recorded. The MSG and gradient values were calculated, respectively, and then combined as a new metric (i.e., MSG+gradient). In addition, the prediction was conducted by four algorithms, namely, logistic regression, support vector machine, random forest, and long short-term memory. The results revealed that the gradient of CGM showed a downward trend before hypoglycemic events happened. Additionally, the results indicated that the specificity and sensitivity based on the proposed method were better than the conventional metrics of low blood glucose index (LBGI), coefficient of variation (CV), mean absolute glucose (MAG), lability index (LI), etc., and the complex metrics of MSG+LBGI, MSG+CV, MSG+MAG, and MSG+LI, etc. Specifically, the specificity and sensitivity were greater than 96.07% and 96.03% at the prediction horizon of 15 minutes and greater than 87.79% and 90.07% at the prediction horizon of 30 minutes when the proposed method was adopted to predict nocturnal hypoglycemic events in the aforementioned four algorithms. Therefore, the proposed method of combining MSG and gradient may enable to improve the prediction of nocturnal hypoglycemic events. Future studies are warranted to confirm the validity of this metric. [ABSTRACT FROM AUTHOR]

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]

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]

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]

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]

Type 2 diabetes and its chronic complications have become a worldwide epidemic nowadays. However, its molecular mechanism is still unknown. We have previously identified a novel variant rs12742393 of NOS1AP for type 2 diabetes susceptibility in the Chinese population. In this study, we analyzed the total serum profiling among three genotypes of rs12742393 to discover potential crosstalk under the variant and the disease through proteomic analyses for the first time. We used OFFGEL peptide fractionation, LC-MS/MS analysis, and label-free quantification to profile the fasting human serum samples of the genotypes in rs12742393 (n = 4, for CC, AC, and AA, resp.). Four proteins were identified, including apoA4, alpha1-ACT, HABP2, and keratin 10, with blood levels changed significantly between CC and AA homozygotes of rs12742393. Compared with AA group, the levels of apoA4 increased (P = 0.000265), whereas the concentration of alpha1-ACT, HABP2, and keratin 10 decreased in CC group (P = 0.011116, 0.021175, and 0.015661, resp.). Then we selected additional fasting serum samples for ELISA and western blot validation. However, no significant differences were identified by neither ELISA nor western blot (P > 0.05). The protein profiling changes between the genotypes of rs12742393 indicated that this SNP might play a role in the development of type 2 diabetes.