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Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) is involved in lipid and glucose metabolism via mRNA processing. However, whether and how HNRNPA1 alters adipocyte function in obesity remain obscure. Here, we found that the obese state downregulated HNRNPA1 expression in white adipose tissue (WAT). The depletion of adipocyte HNRNPA1 promoted markedly increased macrophage infiltration and expression of proinflammatory and fibrosis genes in WAT of obese mice, eventually leading to exacerbated insulin sensitivity, glucose tolerance, and hepatic steatosis. Mechanistically, HNRNPA1 interacted with Ccl2 and regulated its mRNA stability. Intraperitoneal injection of CCL2-CCR2 signaling antagonist improved adipose tissue inflammation and systemic glucose homeostasis. Furthermore, HNRNPA1 expression in human WAT was negatively correlated with BMI, fat percentage, and subcutaneous fat area. Among individuals with 1-year metabolic surgery follow-up, HNRNPA1 expression was positively related to percentage of total weight loss. These findings identify adipocyte HNRNPA1 as a link between adipose tissue inflammation and systemic metabolic homeostasis, which might be a promising therapeutic target for obesity-related disorders. Article Highlights: Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) is decreased during obesity, but the specific role in adipose tissue remains unclear. Adipocyte-specific depletion of Hnrnpa1 accelerates adipose tissue inflammation and systemic metabolic disorders via enhancing mRNA stability of chemokine CCL2. CCL2 receptor antagonist rescues metabolic dysfunction elicited by Hnrnpa1 depletion. HNRNPA1 expression in human adipose tissue is closely related to BMI, fat percentage, and subcutaneous fat area and is positively associated with percentage of total weight loss 1 year after bariatric surgery. [ABSTRACT FROM AUTHOR]

Objective: We aimed to examine the relationship between osteocalcin (OC) and the risk of incident diabetes and the risk of incident diabetic kidney disease (DKD).Research Design and Methods: We followed 5,396 participants without diabetes (nondiabetes subcohort) and 1,174 participants with diabetes and normal kidney function (diabetes subcohort) at baseline. Logistic regression and modified Poisson regression models were used to estimate the relative risk (RR) of baseline OC levels with incident diabetes and DKD.Results: During a mean 4.6-year follow-up period, 296 cases of incident diabetes and 184 cases of incident DKD were identified. In the nondiabetes subcohort, higher OC levels were linearly associated with a decreased risk of diabetes (RR for 1-unit increase of loge-transformed OC 0.51 [95% CI 0.35-0.76]; RR for highest vs. lowest quartile 0.65 [95% CI 0.44-0.95]; P for trend < 0.05). In the diabetes subcohort, OC levels were linearly inversely associated with incident DKD (RR for 1-unit increase of loge-transformed OC 0.49 [95% CI 0.33-0.74]; RR for highest vs. lowest quartile 0.56 [95% CI 0.38-0.83]; P for trend < 0.05), even independent of baseline estimated glomerular filtration rate and urinary albumin-to-creatinine ratio. No significant interactions between OC and various subgroups on incident diabetes or DKD were observed.Conclusions: Lower OC levels were associated with an increased risk of incident diabetes and DKD. [ABSTRACT FROM AUTHOR]

Objective: To explore the potential relevance of muscle mass as a variable contributor to BMI in limitations on BMI-based predictions of diabetes remission (DR) after Roux-en-Y gastric bypass (RYGB).Research Design and Methods: We evaluated the relationship between muscle mass and BMI in 501 patients with type 2 diabetes mellitus and overweight or obesity, of whom 186 patients who underwent RYGB were studied for determination of the role of baseline muscle mass and BMI in predicting DR. Muscle mass was assessed by estimated fat-free mass index (eFFMI) and psoas cross-sectional area (CSA).Results: A nonlinear relationship existed between psoas CSA and BMI, whereas psoas CSA showed a highly positive correlation with eFFMI. Baseline psoas CSA and eFFMI were better than BMI for predicting 1- and 5-year DR.Conclusions: The nonlinear relationship between muscle mass and BMI may partially contribute to BMI limitations in predicting DR after RYGB. [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]

Objective: Hepatocyte nuclear factor 1beta (HNF1beta) is a transcription factor that is critical for pancreatic cell formation and glucose homeostasis. Previous studies have reported that common variants of HNF1beta were associated with type 2 diabetes in Caucasians and West Africans. However, analysis in the subjects from the Botnia study and Malmö Preventive Project produced conflicting results, and the role for HNF1beta in type 2 diabetes susceptibility remains unclear. We therefore investigated common variants across the HNF1beta gene in a Chinese population.Research Design and Methods: Fifteen tagging single nucleotide polymorphisms (SNPs) were analyzed for association with type 2 diabetes in subjects with type 2 diabetes (n = 1,859) and normal glucose regulation (n = 1,785).Results: Consistent with the initial study, we observed evidence that the risk G allele of rs4430796 in intron 2 was significantly associated with type 2 diabetes (odds ratio 1.16 [95% CI 1.05-1.29], P = 0.0035, empirical P = 0.0475). Furthermore, the at-risk G allele was associated with earlier age at diagnosis in the type 2 diabetic subjects (P = 0.0228).Conclusions: The result of this study provides evidence that variants in the HNF1beta region contribute to susceptibility to type 2 diabetes in the Chinese population. [ABSTRACT FROM AUTHOR]

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

Aims: Sex hormones are strongly linked to the occurrence and development of diabetes, and influence glycated hemoglobin (HbA1c) levels in diabetic population; but, the relationship between sex hormones and HbA1c in nondiabetic population remains unknown. This study aimed to explore the extent of influence of sex hormones on HbA1c levels in nondiabetic population. Methods: A total of 1409 nondiabetic subjects, including 601 men and 808 postmenopausal women were recruited from Shanghai community. HbA1c was detected using high performance liquid chromatography, and hemoglobin level was determined by sodium lauryl sulfate colorimetry. Serum estradiol (E2), total testosterone (TT), and sex hormone binding globulin (SHBG) were measured by chemiluminescent microparticle immunoassays. Results: The level of HbA1c was 5.6 (5.4-5.9) % in all subjects, with 5.6 (5.4-5.8) % in men and 5.7 (5.5-5.9) % in postmenopausal women. After adjusting for age, body mass index (BMI), and hemoglobin, E2 was positively correlated with HbA1c in men (r = 0.122, P = 0.003), and SHBG was inversely correlated with HbA1c (r = -0.125, P < 0.001) in women. Other hormones were not correlated with HbA1c (all P > 0.05). Multivariate linear regression analysis showed that, except for traditional factors, such as age, hemoglobin, and BMI, E2 was another determinant of HbA1c (standardized β = 0.137, P = 0.003) in men and the regression equation was HbA1c (%) = 0.001×E2 (pmol/ L) +5.465. In women, SHBG was another determinant of HbA1c (standardized β = -0.178, P < 0.001), except for age and systolic blood pressure (SBP), and the regression equation was HbA1c (%) = -0.002×SHBG (nmol)/L) +5.772. Conclusion: After controlling for confounding factors, E2 is positively correlated with HbA1c in men, and SHBG is inversely correlated with HbA1c in postmenopausal women. Sex hormones influence HbA1c levels in nondiabetic population, but it is very limited to affect the level of HbA1c in the diagnose of diabetes. Disclosure: Y. Bao: None. Y. Xu: None. W. Cao: None. Y. Shen: None. J. Tang: None. Y. Wang: None. X. Ma: None. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the agreement of different measurement methods of saliva 1,5-anhydroglucitol (1,5-AG) in different glucose metabolism populations. Methods: A total of 175 healthy volunteers (21–65 years, 58 males and 117 females) with normal glucose tolerance (NGT) and 80 diabetic patients (18–70 years, 44 males and 36 females) were enrolled from January 2018 to June 2019 and saliva was collected by saliva collection tube. Saliva 1,5-AG was measured using both enzymatic and mass spectrometry methods and serum 1,5-AG was determined by enzymatic method. Results: In subjects with NGT, the serum and saliva 1,5-AG levels detected by enzymatic method were both significantly positively correlated with the saliva 1,5-AG levels detected by liquid chromatography-mass spectrometry (LC-MS) (r = 0.247 and 0.523, respectively, both P < 0.05). However, there was no significant correlation between saliva and serum 1,5-AG levels detected by enzymatic method (r =-0.074, P = 0.333). In diabetic patients, the serum and saliva 1,5-AG levels detected by enzymatic method were both significantly positively correlated with the saliva 1,5-AG levels detected by gas chromatography-mass spectrometry (GC-MS) (r = 0.284 and 0.423, respectively, both P < 0.05). There was no significant correlation between saliva and serum 1,5-AG levels detected by enzymatic method (r ='0.079, P = 0.487). Conclusion: Both the serum and saliva 1,5-AG levels detected by enzymatic method have good agreement with saliva 1,5-AG levels detected by mass spectrometry method. The saliva and serum 1,5-AG levels detected by enzymatic method are not well correlated, so the enzymatic detection of saliva 1,5-AG needs further improvement for clinical practice. Disclosure: Y. Bao: None. C. Jian: None. A. Zhao: None. X. Ma: None. W. Lu: None. W. Zhu: None. Y. Wang: None. J. Zhou: None. [ABSTRACT FROM AUTHOR]

Objectives: The need for a unified definition of weight loss (WL) after bariatric surgery has recently been highlighted. We aimed to evaluate the reliability of two clinically common WL indications including percentage of total WL (%TWL) and percentage of excess WL (%EWL) through comparing their performances in predicting metabolic syndrome (MetS) remission 1 year after bariatric surgery. Methods: A total of 430 individuals with obesity who underwent bariatric surgery were enrolled. Participants were evaluated for changes in anthropometric parameters, metabolic indexes, MetS components and medications before and 1 year after surgery. MetS was defined using the criteria of the National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. Results: The prevalence of MetS is 92.3% (397) at baseline. One year after bariatric surgery, 337 individuals (84.9%) were in MetS remission. The multivariate adjusted odds ratios (ORs) were 1.16 (95% confidence interval [CI] 1.10-1.22) for each 1% increase in %TWL for MetS remission and 1.18 (95% CI 1.11-1.25) for each 5% increase in %EWL. This association with MetS remission remained statistically significant for %TWL after additional adjustment for %EWL (P for trend 0.029), and disappeared for %EWL. Receiver operating curve (ROC) analyses showed that the %TWL was more predictive than the %EWL (AUC%TWL vs. AUC %EWL, 0.749 vs. 0.700, p=0.023). The Youden index indicated that the optimal %TWL cut-off point to identify MetS remission was 25%. Conclusions: We recommend that good responders to bariatric surgery should be defined as those exhibiting % TWL ≥25%. Clinical Trial Registration: Evaluation of the effectiveness and safety of metabolic surgery for obesity: a clinical cohort study; Chinese Clinical Trial Registration:ChiCTR1900028513. Disclosure: Y. Tu: None. Y. Pan: None. J. Han: None. J. Pan: None. Y. Bao: None. H. Yu: None. Funding: National Key Research and Development Project of China (2016YFA0502003); National Natural Science Foundation of China (81670791); Municipal Natural Science Foundation of Shanghai (17ZR1421200); Shanghai Key Clinical Center for Metabolic Disease (2017ZZ01013) [ABSTRACT FROM AUTHOR]

Background: The association between long-term glycemic variability and diabetic retinopathy (DR) among patients with type 2 diabetes has not been clarified yet. Objective: The aim of this study was to investigate the association of visit-to-visit variability of hemoglobin A1c (HbA1c) and glycated albumin (GA) with the risk of DR in patients with type 2 diabetes. Design: A prospective cohort study of 315 patients (191 males and 124 females) with at least 3 measurements of HbA1c and GA prior to baseline was performed. Different GA and HbA1c variability markers were calculated, including coefficient of variation (CV), variability independent of the mean (VIM), and the average real variability (ARV). Cox proportional hazard regression models were used to explore the association between visit-to-visit HbA1c and GA variability and the risk of DR. Results: During a mean follow-up period of 3.42 years, 81 participants developed incident DR. Multivariate-adjusted hazard ratios (HRs) of DR across tertiles of GA-CV values were 1.00, 1.42, and 2.12 (P for trend=0.027), respectively. When we used GA-VIM and GA-ARV values as exposures, similar positive associations with the risk of DR were found. Multivariable-adjusted HRs of DR associated with each unit increase in GA-CV, GA-VIM, and GA-ARV were 1.05 (95% CI 1.02-1.09), 1.69 (95% CI 1.24-2.32), and 1.13 (95%CI 1.04-1.23), respectively. However, there was no significant association between visit-to-visit variability of HbA1c and the risk of DR after multivariate adjustment. Conclusion: The visit-to-visit variability of GA can predict the risk of incident DR in patients with type 2 diabetes, and the prediction ability is independent of the average HbA1c levels. Disclosure: J. Zhou: None. D. Dai: None. Y. Shen: None. J. Lu: None. Y. Wang: None. W. Zhu: None. Y. Bao: None. G. Hu: None. Funding: National Key Research and Development Project of China (2018YFC2000802); Shanghai Municipal Education Commission (20161430); Shanghai Municipal Key Clinical Specialty [ABSTRACT FROM AUTHOR]

Context: Unlike other commonly used invasive blood glucose monitoring methods, saliva detection prevents patients from suffering the physical uneasiness. Serum 1,5-anhydroglucitol (1,5-AG) is a new indicator for assessing short-term glycemic control. However, there are currently few studies on saliva 1,5-AG in diabetes mellitus (DM). Objective: This study aimed to evaluate the effectiveness of saliva 1,5-AG in diabetes screening in a Chinese population. Design and Participants: A total of 641 subjects without a valid diabetic history (251 men and 390 women) were recruited from September 2018 to June 2019 and underwent an oral glucose tolerance test (OGTT). Fasting saliva 1,5-AG (1,5-AG0) and postload 2-hour saliva 1,5-AG (1,5-AG120) were measured with liquid chromatography-mass spectrometry. Serum 1,5-AG0 and 1,5-AG120 were measured with enzymatic method. Results: Saliva 1,5-AG levels in DM subjects were lower than those in nondiabetes mellitus subjects (both P < 0.05). Saliva 1,5-AG was positively correlated with serum 1,5-AG and negatively correlated with blood glucose and glycated hemoglobin (HbA1c) (all P < 0.05). The optimal cutoff points of saliva 1,5-AG0 and 1,5-AG120 for diabetes screening were 0.436 μg/mL and 0.438 μg/mL, respectively. Fasting plasma glucose (FPG) combined with saliva 1,5-AG0 and HbA1c combined with saliva 1,5-AG120 reduced the proportion of people who required an OGTT by 47.22% and 51.41% compared with FPG alone and HbA1c combined with FPG, respectively. Conclusion: The optimal cutoff point of saliva 1,5-AG for diabetes screening was 0.44 μg/mL. Saliva 1,5-AG combined with FPG or HbA1c improved the efficiency of diabetes screening. Saliva 1,5-AG is robust in nonfasting measurements and a noninvasive and convenient tool for diabetes screening. Disclosure: Y. Bao: None. C. Jian: None. A. Zhao: None. X. Ma: None. K. Ge: None. W. Lu: None. W. Zhu: None. Y. Wang: None. J. Zhou: None. W. Jia: None. [ABSTRACT FROM AUTHOR]

Background: Lifestyle interventions, including dietary adjustment and exercise, are important for weight loss in the context of obesity. Objective: This study aimed to compare the short-term effects of a low-carbohydrate diet (LCD) and exercise nondiabetic overweight and obese adults. Design: A total of 45 eligible subjects were randomized into a low-carbohydrate diet group (LC, n=22) and an exercise group (EX, n=23); the participants adopted a LCD (carbohydrate intake < 30 mins/day) for 3 weeks. Weekly follow-ups were conducted and flash glucose monitoring sensors were used.≥50 g/day) or performed moderate-to-vigorous exercise (Results: After the 3-week intervention, body mass index, total fat% and total fat mass (FM), waist circumference, visceral fat area and subcutaneous fat area decreased significantly in both the LC and EX, but the LC lost 2.32 kg more weight than the EX. Total fat-free mass (FFM) and total body water (TBW) in the LC were significantly reduced but remained unchanged in the EX. Triglycerides (TGs), total cholesterol and low-density lipoprotein cholesterol (LDL-c) decreased in the EX, while TGs decreased and LDL-c increased in the LC. Glycemic variability and insulin resistance were improved in both groups, but the effect in the LC was faster and greater. Mean sensor glucose declined significantly in the LC. Three days after stopping the intervention, body weight, FM and FFM increased significantly in the LC, and most of the FFM regained was TBW, which remained stable in the EX. Conclusion: A short-term LCD was more effective for weight loss and glycemic stability than exercise, and it mainly reduced body fat and body water. However, body weight was regained to a greater extent after stopping the LCD, which was due to body water retention. Exercise was less effective for fat loss than LCD and had no significant influence on body water. Disclosure: J. Zhou: None. L. Cai: None. J. Yin: None. X. Ma: None. Y. Mo: None. L. Cheng: None. W. Lu: None. Y. Bao: None. W. Jia: None. [ABSTRACT FROM AUTHOR]

Aims: The goals of the current study were to explore the level of and changes in the AH index (AHI, defined as 1,5-anhydroglucitol × glycated hemoglobin A1c/100) associated with different glucose metabolism statuses, and to evaluate the islet function and insulin sensitivity of type 2 diabetes mellitus (T2DM) patients with different AHI levels. Methods: A total of 3562 individuals were enrolled in the study. According to the 2010 American Diabetes Association (ADA) diagnostic criteria, 1697 subjects were diagnosed as T2DM. The disposition index (DI) was defined as the product of insulin sensitivity-related indexes and islet secretion function. Results:The overall AHI level was 1.0 (0.7-1.3), while the AHI level of the T2DM group was 0.8 (0.5-1.2), which was significantly lower than that of the normal glucose tolerance group and the impaired glucose regulation group [both AHI 1.2 (0.9-1.5), and P < 0.01]. The T2DM group was further divided into four subgroups according to the quartile of AHI level. The results demonstrated that the homeostasis model assessment of insulin resistance (HOMA-IR) decreased with the increase of AHI level (P for trend < 0.01). However, other parameters [i.e., HOMA of β-cell function (HOMA-β), insulin generation index, insulin sensitivity index, and DI] increased while AHI level increased (all P for trend < 0.01). Multivariate logistic regression illustrated 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), respectively, showing a decreasing trend (P for trend < 0.01). Conclusion: AHI could reflect the changes in the trend of glucose metabolism disorder and the function of islet β cells to some extent. The lower AHI was associated with worsening of the glucose metabolism disorder in recent years, and the islet β-cell function was correspondingly poor. Disclosure: X. Ma: None. H. Su: None. Y. Shen: None. X. He: None. L. Ying: None. W. Zhu: None. Y. Wang: None. Y. Bao: None. J. Zhou: None. [ABSTRACT FROM AUTHOR]

Introduction: Metabolic surgery, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), is the only proven means of sustained weight loss and type diabetes mellitus (T2DM) remission/control but data are limited in China. Method: Patients underwent laparoscopic RYGB or SG at 6 Chinese sites from Aug 2014 to Jan 2016 and returned for follow-up regularly after surgery. We evaluated the impact on a composite measure of glycemic control, which was defined as Complete Remission: HbA1c < 6% and FPG < 5.6 mmol/L for 1 year absent antidiabetic medications; Partial Remission: HbA1c 6 - 6.4% and FPG 5.6 - 6.9 mmol/L for 1 year absent antidiabetic medications; Improvement: Reduction in HbA1c (> 1%) or FPG (>1.4 mmol/L) or reduction accompanied by a decrease in antidiabetic medication for at least 1 year; Unchanged: Absence of remission or improvement; Recurrence: HbA1c or FPG in the diabetic range or need for antidiabetic medication after initial remission. Results: There were 101 procedures completed. The mean (±SD) age of the patients was 37.1±9.7 years, and 52% were women. The mean BMI was 35.0±5.0 and mean HbA1c was 8.1±1.7% at baseline. Outcomes at 2-year follow-up were available for 80 patients (63 RYGB and 17 SG) and showed substantial improvements. Complete or partial remission at 2 years was achieved in at least 83% of patients in two groups (33 [53.2%] and19 [30.6%] in RYGB; 12 [70.6%] and 3 [17.6%] in SG), less than 5% were unchanged and recurrence was not seen in either group. There was a significant reduction in HbA1c from baseline in both RYGB and SG (-2.4 ± 1.8% [P>0.001] and -2.1 ± 1.8% [P>0.001]). Concurrent significant improvements in cardiometabolic parameters such as triglycerides and blood pressure, and reductions in antidiabetic medication usage were also observed. Conclusion: The 2 years data demonstrate a clinically meaningful impact on a composite measure of glycemic control with a majority of patients demonstrating complete remission of T2DM in both groups. Disclosure: Y. Bao: None. H. Liang: None. P. Zhang: None. C. Wang: None. T. Jiang: None. N. Zhang: None. J. Zhu: None. H. Yu: None. J. Han: None. S. Lin: None. J. Yang: None. W. Yang: None. S. Chen: None. D. Du: None. Y. Ma: None. E.J. Fegelman: Employee; Self; Ethicon US, LLC. M. Schwiers: Employee; Self; Ethicon, Inc. J. Waggoner: Employee; Self; Ethicon, Inc. T. Yang: Employee; Self; Johnson & Johnson Medical Devices Companies. R. Zhang: None. W. Jia: None. Funding: Ethicon Inc. [ABSTRACT FROM AUTHOR]

Aims: This study was designed to investigate the interrelationships between three bone-derived factors [serum osteocalcin (OCN), fibroblast growth factor (FGF) 23, and neutrophil gelatinase-associated lipocalin (NGAL) levels] and body fat content and distribution, in order to reveal the potential endocrine function of bone in the development of obesity. Methods: We recruited 1179 people (aged 59.5 ± 6.2 years) from communities in Shanghai. Serum OCN levels were determined using an electrochemiluminescence immunoassay, and thus serum FGF-23 and NGAL levels were determined using a sandwich enzyme-linked immunosorbent assay. The abdominal fat distribution, including visceral fat area (VFA), was assessed by magnetic resonance imaging. Visceral obesity was defined as a VFA ≥ 80 cm2. Results: Serum OCN levels were inversely correlated with body fat parameters, while FGF-23 and NGAL were positively correlated (P < 0.05). After adjusting for confounders, waist circumference (W) and VFA had a closer relationship with serum OCN, FGF-23, and NGAL levels than body mass index (BMI) and body fat percentage (fat%, all P < 0.05). The risk of visceral obesity significantly increased with higher FGF-23 and/or NGAL levels, as well as with reduced OCN levels (all P < 0.05). In addition, serum OCN, FGF-23, and NGAL levels were independently associated with visceral obesity (all P < 0.01). The relationships persisted among subjects with normal glucose tolerance or subjects with hyperglycaemia (both P < 0.05). Conclusions: Compared to overall adiposity, visceral adiposity was more closely related to serum OCN, FGF-23 and NGAL levels. There was no interaction among the relationship of three bone-derived factors with visceral obesity, which suggested the independent relationship of endocrine function of skeleton with body fat. Disclosure: Y. Bao: None. Y. Xu: None. X. Ma: None. X. Pan: None. X. He: None. Y. Xiao: None. [ABSTRACT FROM AUTHOR]

Aims: Osteocalcin is involved in energy metabolism and is sufficient to prevent age-related muscle loss. The aim of the present study was to investigate the association of serum osteocalcin levels with muscle mass and the role of metabolic factors in this association. Methods: A total of 1742 middle-aged and elderly subjects (median age: 61.2 years; interquartile range: 56.9-65.3 years) were enrolled from Shanghai communities, including 775 men and 967 postmenopausal women. Serum osteocalcin levels were measured by an electrochemical immunoluminescence assay. An automatic bioelectric impedance analyser (BIA) was used to measure body compositions. Relative skeletal muscle index (SMI) was calculated using the BIA equation from Janssen et al. Results: SMI was significantly higher in men than in postmenopausal women (37.30% [35.14%-39.63%] versus 27.72% [25.99%-29.66%], P < 0.001). Increasing SMI was associated with decreases in the frequency of overweight/obesity, central obesity, dyslipidaemia, elevated blood pressure, and hyperglycaemia (all P < 0.001). Serum osteocalcin levels were positively correlated with SMI in both men and women, regardless of treatment as a categorical or continuous variable (all P < 0.001). However, after accounting for confounding variables, the relationship remained only in men with hyperglycaemia (standardized β = 0.068, P = 0.024). Among men with isolated impaired glucose tolerance, the odds ratio of increased SMI was 2.861 in the fourth osteocalcin quartile compared with the lowest (P = 0.046). Multiple stepwise regression revealed that each standard deviation (SD) increase of serum osteocalcin levels resulted in an increase of 0.131 SD in SMI (P = 0.024). Conclusion: In men with hyperglycaemia, especially in those with isolated impaired glucose tolerance, serum osteocalcin levels were positively correlated to SMI. However, no association was detected in postmenopausal women. Disclosure: Y. Xu: None. X. Ma: None. Y. Shen: None. C. Gu: None. J. Tang: None. Y. Bao: None. [ABSTRACT FROM AUTHOR]

Background: Glycemic variability (GV) has been demonstrated to contribute to the development of diabetic complications. The current study sought to investigate the effect of partial meal replacement (PMR) on GV in type 2 diabetes. Methods: 123 individuals with newly diagnosed and untreated type 2 diabetes were randomized to receive either lifestyle intervention (LI) together with breakfast replacement with a liquid formula (LI+PMR, n=62) or LI alone (n=61) for 4 weeks. All participants underwent continuous glucose monitoring (CGM) for 72 hours both before and after intervention. GV metrics obtained from CGM included the incremental area under the curve of postprandial blood glucose (AUCpp), standard deviation of blood glucose (SDBG), glucose coefficient of variation (CV), and mean amplitude of glycaemic excursions (MAGE). Results: At the end of the study, patients in LI+PMR exhibited more pronounced improvements in systolic blood pressure (P=0.046) and time in range (P=0.033) than those in LI. More importantly, LI+PMR led to significantly greater improvements in all GV metrics including SDBG (P=0.005), CV (P=0.002), MAGE (P=0.016) and AUCpp (P<0.001) than did LI. In addition, multiple regression analysis revealed that LI+PMR (vs. LI) was independently associated with the improvements in GV after adjusting for covariates (all P<0.05). Conclusion: Our study showed that LI+PMR resulted in significantly greater improvements in GV than did LI, suggesting that LI+PMR could be an effective treatment to alleviate glucose excursions. Disclosure: J. Zhou: None. J. Lu: None. X. Ma: None. J. Peng: None. L. Ying: None. W. Lu: None. W. Zhu: None. Y. Bao: None. Funding: Shanghai Municipal Education Commission; Gaofeng Clinical Medicine Grant (20161430) [ABSTRACT FROM AUTHOR]

Background: The relationship between subcutaneous fat area (SFA) and diabetes mellitus (DM) is still not well described due to the fact that SFA has two aspects; it can buffer energy surplus and also reflect obesity severity. Methods: 3967 subjects, from baseline survey data of the Shanghai Nicheng Cohort Study, were analyzed. Thigh subcutaneous fat area (TSFA), abdominal subcutaneous fat area (ASFA), and visceral fat area (VFA) were measured by magnetic resonance imaging. TSFA% and ASFA% were calculated as the ratio of TSFA and ASFA to the sum of VFA, ASFA, and TSFA, respectively and reflects the propensity to store energy in a given location. Diagnosis of newly diagnosed diabetes mellitus (NDM) as well as assessments of insulin sensitivity (Homeostatic Model Assessment of insulin resistance and ISI0,120 [GUTT]), and β-cell function (early-, first- and second-phase disposition indices) were made based on an oral glucose tolerance test. Results: Compared to those without DM, TSFA%, ASFA%, and VFA% in men and women with NDM were 0.25 versus 0.21, 0.39 versus 0.38, and 0.36 versus 0.41; and 0.37 versus 0.32, 0.38 versus 0.37, and 0.26 versus 0.31, respectively. Before and after adjustment for potential confounding factors, each 1-SD increase in TSFA% was associated with a 37-47% and a 34-39% decreased likelihood of NDM in Chinese men and women, respectively (both P <0.05). Multivariable linear regression showed that TSFA% was mildly positively associated with all indicators of β-cell function and/or insulin sensitivity in women and mildly positively associated with DI1st in men. The favorable associations of NDM, insulin sensitivity, and β-cell function with TSFA% were stronger than with ASFA%. Conclusion: TSFA% reflects the propensity to store energy in subcutaneous fat which is associated with a lower risk of NDM and better β-cell function in both genders. Disclosure: X. Hou: None. P. Chen: None. L. Wei: None. Y. Bao: None. W. Jia: None. [ABSTRACT FROM AUTHOR]

To assess the role of body fat and serum C-reactive protein (CRP) level in the prediction of cardiovascular events among individuals from Shanghai communities. A total of 5502 individuals aged over 20 years from 1998 to 2001 in two communities of Shanghai were included. In this cohort 2790 individuals aged over 30 years underwent a five year follow-up. Logistic regression model was used to estimate the relationship between CRP level and the risk of metabolic syndrome (MS). Receiver operating characteristic curve was used to find out the best cut-point for body mass index (BMI) and waist circumference (W) to assess MS defined as Chinese Diabetes Society (2004) working definition. Our data showed: 1.Compared with those subjects in the lowest quartile, individuals in the highest quartile of CRP level (men 2.11 mg/L, women 2.22mg/L) had increased risk of MS(10 times in men, 8.5 times in women) at baseline. 2.The best cut-point for BMI in assessing MS was 25kg/m² in both men and women, and for W was 85cm in men and 80cm in women at baseline. 3.Compared with the subgroup of BMI<25 kg/m² with CRP<2 mg/L, the relative risk of cardiovascular events was as following: 1.98 in the subgroup of BMI≥25kg/m² with CRP<2mg/L,1.55 in the subgroup of BMI<25kg/m² with CRP≥2mg/L and 2.26 in the subgroup of BMI≥25kg/m² with CRP≥2mg/L. 4.Compared with the subgroup of W<85cm with CRP<2 mg/L in men and W<80cm with CRP<2 mg/L in women, the relative risk of cardiovascular events was as following: in men 1.83 in the subgroup of W≥85cm with CRP<2mg/L, 1.15 in the subgroup of W<85cm with CRP≥2mg/L and 2.34 in the subgroup of W≥85cm with CRP≥2mg/L; and in women 1.61 in the subgroup of W≥80cm with CRP<2mg/L, 1.25 in the subgroup of W<80cm with CRP≥2mg/L and 2.21 in the subgroup of W≥80cm with CRP≥2mg/L. In conclusion, 1.The risk of MS was dramatically increased in subjects with CRP level above 2mg/L. 2.To determine MS the optimal cut-point for BMI was 25kg/m² and for W was 85cm in men and 80cm in women. 3. In a five year follow-up study, the risk of cardiovascular events was significantly elevated not only in individuals with BMI over 25kg/m² but also in men with W over 85cm and in women with W over 80cm independent of CRP level. The risk of cardio vascular events was further increased in subjects with elevated CRP level combined with either higher BMI or W. [ABSTRACT FROM AUTHOR]

Previous studies have shown that adipose-derived serum retinol binding protein 4 (RBP4) is up-regulated in insulin-resistant mouse models and in subjects with insulin resistance or type 2 diabetes. However, the association of visceral fat and serum RBP4 has not been studied. The purpose of this study was to investigate the relationship between serum RBP4 levels and regional fat distribution in Chinese non-diabetes and diabetes subjects. We measured serum RBP4 concentrations from 1033 Chinese subjects (age 52±3,477 men/556 women) enrolled in the Shanghai Diabetes Studies (SHDS) and tested the association of serum RBP4 and visceral fat accumulation. In a subgroup (25 men/26 women) of this study, we also performed euglycemic hyperinsulinemic clamp to measure insulin sensitivity. In addition, the association of fat distribution and serum RBP4 levels was also determined in a subgroup (14 men/8 women) in response to treatment of rosiglitazone, an insulin sensitizer, in patients with diabetes. We found serum RBP4 concentrations were not closely correlated with body-mass-index, but with visceral adipose accumulation in subjects with or without insulin resistance. Subjects with visceral obesity (VO) had higher serum RBP4 concentrations than those without visceral obesity (NVO) irrespective to insulin sensitivity status (mean±SEM: 27.0±0.5 vs. 24.2±0.6 µg,/ml, VO vs. NVO with insulin resistance, p<0.01; 24.8±0.8 vs. 22.9±0.5 µg/ml, VO vs. NVO without insulin resistance, p<0.05). Rosiglitazone treatment in diabetes subjects resulted in an improvement in insulin sensitivity and reduction in serum RBP4 concentration. These changes are accompanied by a reduction of visceral fat area in the subjects. The change of visceral adipose area is highly correlated with that of serum RBP4 concentration (r=0.471, p=0.027). In conclusion, visceral fat accumulation is closely associated with an elevated serum RBP4 level irrespective of insulin resistance status. Visceral fat plays an important role in the regulation of RBP4 production. [ABSTRACT FROM AUTHOR]

Objective: We aimed to examine the relationship between osteocalcin (OC) and the risk of incident diabetes and the risk of incident diabetic kidney disease (DKD)., Research Design and Methods: We followed 5,396 participants without diabetes (nondiabetes subcohort) and 1,174 participants with diabetes and normal kidney function (diabetes subcohort) at baseline. Logistic regression and modified Poisson regression models were used to estimate the relative risk (RR) of baseline OC levels with incident diabetes and DKD., Results: During a mean 4.6-year follow-up period, 296 cases of incident diabetes and 184 cases of incident DKD were identified. In the nondiabetes subcohort, higher OC levels were linearly associated with a decreased risk of diabetes (RR for 1-unit increase of loge-transformed OC 0.51 [95% CI 0.35-0.76]; RR for highest vs. lowest quartile 0.65 [95% CI 0.44-0.95]; P for trend < 0.05). In the diabetes subcohort, OC levels were linearly inversely associated with incident DKD (RR for 1-unit increase of loge-transformed OC 0.49 [95% CI 0.33-0.74]; RR for highest vs. lowest quartile 0.56 [95% CI 0.38-0.83]; P for trend < 0.05), even independent of baseline estimated glomerular filtration rate and urinary albumin-to-creatinine ratio. No significant interactions between OC and various subgroups on incident diabetes or DKD were observed., Conclusions: Lower OC levels were associated with an increased risk of incident diabetes and DKD., (© 2022 by the American Diabetes Association.)

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 HbA 1c . 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., (© 2018 by the American Diabetes Association.)