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Type 2 diabetes (T2D) is characterized by β-cell dedifferentiation, but underlying mechanisms remain unclear. The purpose of the current study was to explore the mechanisms of β-cell dedifferentiation with and without long-term control of calorie intake. We used a diabetes mouse model (db/db) to analyze the changes in the expression levels of β-cell-specific transcription factors (TFs) and functional factors with long-term caloric restriction (CR). Our results showed that chronic euglycemia was maintained in the db/db mice with long-term CR intervention, and β-cell dedifferentiation was significantly reduced. The expression of Glut2, Pdx1, and Nkx6.1 was reversed, while MafA expression was significantly increased with long-term CR. GLP-1 pathway was reactivated with long-term CR. Our work showed that the course of β-cell dedifferentiation can intervene by long-term control of calorie intake. Key β-cell-specific TFs and functional factors play important roles in maintaining β-cell differentiation. Targeting these factors could optimize T2D therapies. [ABSTRACT FROM AUTHOR]

Characteristic bone metabolism was observed in obesity and diabetes with controversial conclusions. Type 2 diabetes (T2DM) and obesity may manifest increased bone mineral density. Also, obesity is more easily to occur in T2DM. Therefore, we infer that some factors may be linked to bone and obesity as well as glucose metabolism, which regulate all of them. Bone morphogenetic proteins (BMPs), belonging to the transforming growth factor- (TGF-) beta superfamily, regulate a diverse array of cellular functions during development and in the adult. More and more studies revealed that there exists a relationship between bone metabolism and obesity as well as glucose metabolism. BMP2, BMP4, BMP6, BMP7, and BMP9 have been shown to affect the pathophysiological process of obesity and glucose metabolism beyond bone metabolism. They may exert functions in adipogenesis and differentiation as well as insulin resistance. In the review, we summarize the literature on these BMPs and their association with metabolic diseases including obesity and diabetes. [ABSTRACT FROM AUTHOR]

Objective. Glucagon-like peptide-1 (GLP-1) receptor agonist is effective in decreasing blood glucose and body weight. It could improve fatty liver with unclear mechanisms. Hence, we aimed to explore whether GLP-1 could improve fatty liver by regulating the BMP4-related signaling pathway. Methods. Fifteen C57BL/6 mice were randomly assigned to 3 groups. Group A and Group B were fed with a high-fat diet (HFD) to induce fatty liver while Group C was fed with a regular diet (RD) for 24 weeks. Group A and Group B received a subcutaneous injection of exenatide and vehicle (0.9% NaCl), respectively, once daily at doses of 10 nmol/kg during the last 8 weeks. Bodyweight, liver weight, and lipid levels were measured. Histological analyses of liver tissue were performed. The expression of protein and gene measured by western blotting and real-time polymerase chain reaction (RT-PCR) was compared. Results. Eight-week exenatide treatment significantly decreased body weight in Group A (from 44.08 ± 2.89 g to 39.22 ± 1.88 g, P = 0.045). Group A had lower body weight and liver weight than Group B at 24 weeks (39.22 ± 1.88 g vs. 47.34 ± 2.43 g, P = 0.001 and 1.70 ± 0.20 g vs. 2.48 ± 0.19 g, P = 0.001, respectively). Moreover, Group A showed significantly less liver steatosis than Group B. Additionally, Group A led to slightly decreased serum triglyceride (TG) and cholesterol (TC) levels compared to Group B. Western blotting showed that exenatide could prevent HFD-induced upregulation of BMP4 levels and downstream activation of Smad1/5/8 and the P38 MAPK signaling pathway in the liver. Furthermore, exenatide treatment could reduce BMP4 and enhance UCP-1 (an important thermogenin) in brown adipose tissue (BAT). Conclusion. Exenatide could improve HFD-induced hepatic steatosis and enhance thermogenesis in BAT, which may be partly attributed to the inhibition of the BMP4-related signaling pathway. [ABSTRACT FROM AUTHOR]

Objectives: The study aims to compare the prevalence of hypogonadism in male patients with latent autoimmune diabetes (LADA) and classic type 1 diabetes (T1DM) and type 2 diabetes (T2DM), and explore risk factors for hypogonadism in those patients. Methods: Form 1 January 2016 and 9 October 2019, a total of 399 male patients with LADA(n=71), T1DM (n=72) and T2DM (n=256) respectively were recruited from the endocrinology department in Shanghai Tenth People's Hospital for this cross-sectional study. Serum FSH, LH, testosterone, lipid profile, uric acid, HbA1c, and beta-cell function were determined in blood samples. The diagnosis of hypogonadism was based on the levels of LH, FSH, and total testosterone. Results: The mean age of male patients with LADA, T1DM and T2DM was 54.44 ± 1.54, 47.50±1.83 and 56.55±0.74 years old, respectively. The serum total testosterone concentration in the LADA group was similar to the T1DM group, but higher than those in the T2DM group. The rate of hypogonadism in the LADA group, T1DM group, T2DM group were 1.6%, 2.4% and 20.8%, respectively (p <0.05). Total testosterone was positively correlated with SHBG and HDL-c, and negatively correlated with uric acid, HbA1c, BMI, SBP, DBP and TG in all, LADA, T1DM and T2DM groups. Logistic regression indicate that after adjusting for age, duration of diabetes, smoking, drinking and family history of diabetes, the independent risk factors for developing hypogonadism in male with diabetes were BMI (OR=1.31, P<0.05), C-peptide (OR=1.88, P<0.05), HDL-c (OR=0.41,P<0.05) and SBP (OR=1.01,P<0.05). Conclusion: Our results indicate that in a population of admission to a large urban hospital in China, the rate of hypogonadism was lower in LADA patients and T1DM patients than T2DM patients. High levels of BMI, C-peptide, SBP and low level of HDL-c are risk factors for developing hypogonadism in male with diabetes. Disclosure: M. Cai: None. J. Gao: None. C. Sheng: None. H. Li: None. S. Qu: None. M. Zhang: None. Funding: National Key Research and Development Program of China (2018YFC1314100); National Natural Science Foundation of China (81970677) [ABSTRACT FROM AUTHOR]

Accumulating evidence has demonstrated that serum uric acid (UA), a natural powerful antioxidant, plays a beneficial role in bone health in the general population. However, few reports are available on the association between serum UA and bone in patients with type 2 diabetes mellitus (T2DM). We therefore investigated whether the benefit of serum UA for bone health was still present in those patients. 626 males and 609 postmenopausal females with T2DM were enrolled in this cross-sectional study. Serum UA concentrations and bone mineral density (BMD) measured at lumbar spine, femoral neck and total hip by dual-energy X-ray absorptiometry were obtained from all subjects. Meanwhile, data on osteoporosis prevalence, glucose metabolism, bone turnover markers and other serum biochemical indexes were collected. After adjustment for potential confounders, the results suggested that serum UA was positively associated with BMD in patients with normal weight, but this positive association varied by gender and skeletal sites in overweight T2DM patients [body mass index (BMI) ≥ 25 kg/m2]. Moreover, significantly lower odds ratios (ORs) for osteoporosis were found in postmenopausal patients with the highest UA tertile and male patients with medium UA tertile [adjusted OR 0.315, 95% confidence interval (CI) 0.170-0.581 for postmenopausal patients; adjusted OR 0.464, 95% CI 0.225-0.955 for male patients]. The positive association between serum UA and BMD found in Chinese T2DM patients may imply that relatively high UA is a protective factor for bone in these patients. Large intervention studies are needed to further confirm the outcomes and provide possible explanations. [ABSTRACT FROM AUTHOR]

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]

Objective: This study presents nine patients with mitochondrial tRNA Leu (UUR) m.3243A>G mutation and compares the clinical characteristics and diabetes complications with type 1 diabetes (T1DM) or early onset type 2 diabetes (T2DM).Methods: The study covers 9 patients with MIDD, 33 patients with T1DM and 86 patients (age of onset ≤35years) with early onset T2DM, matched for sex, age at onset of diabetes, duration of diabetes. All patients with MIDD were confirmed as carrying the m.3243A>G mitochondrial DNA mutation. Serum HbA1c, beta-cell function, retinal and renal complications of diabetes, bone metabolic markers, lumbar spine and femoral neck BMD bone mineral density were compared to characterize the clinical features of all patients.Results: Nine patients were from five unrelated families, and the mean (SD) onset age of those patients was 31.2±7.2year. Two patients required insulin at presentation, and six patients progressed to insulin requirement after a mean of 7.2years. β-Cell function in the MIDD group was intermediate between T1DM and early-onset T2DM. In MIDD, four patients were diagnosed as diabetic retinopathy (4/9) and five patients (5/9) had macroalbuminuria. The number of patients with diabetic retinopathy and macroalbuminuria in the MIDD group was comparable to T1DM or early-onset T2DM. The rate of osteoporosis (BMD T-score<-2.5 SD) in the patient with MIDD was higher than the T1DM or early-onset T2DM group.Conclusion: Our study indicates that of the nine subjects with MIDD, three patients (1-II-1, 1-II-3, 1-II-4) who came from the same family had a history of acute pancreatitis. Compared with T1DM or early-onset T2DM matched for sex, age, duration of diabetes, MIDD patients had the highest rate of osteoporosis. [ABSTRACT FROM AUTHOR]

Objective. Recent studies have shown that hyperuricemia (HUA) is associated with hypertension, dyslipidemia, insulin resistance, and metabolic syndrome (MetS). We aimed to examine the relationship of serum UA with Acanthosis nigricans (AN) and related metabolic indices in obese patients. Methods. A cross-sectional study with 411 obese patients recruited from our department was analyzed in this study. Weight, body mass index (BMI), UA, lipid profile, liver function, and renal function were measured in all participants. Oral glucose tolerance tests were performed, and serum glucose, insulin, and C peptide were measured at 0, 30, 60, 120, and 180 min. Results. AN group had higher serum UA levels than OB group. Circulating UA levels were associated with BMI, dyslipidemia, hypertension, IR, and AN. In logistic regression analyses (multivariable‐adjusted), a high serum UA level was associated with high odds ratios (ORs) (95% confidence interval [CI]) for AN in females (ORs = 3.00 and 95% CI [1.02–8.84]) and males (ORs = 6.07 and 95% CI [2.16–17.06]) in the highest quartile (Q4) of serum UA. Conclusions. Serum UA levels were positively associated with multiple metabolic abnormalities including obesity, hypertension, hyperglycemia, hyperlipidemia, and AN and may be an important risk factor in the development of AN; further evidences in vitro and in vivo are needed to investigate the direct or indirect relationship. [ABSTRACT FROM AUTHOR]

Obesity is now recognized as a low-grade, chronic inflammatory disease that is linked to a myriad of disorders including cardiovascular diseases, type 2 diabetes, and liver diseases. Recently it is found that eosinophils accelerate alternative activation macrophage (AAM) polarization by secreting Th2 type cytokines such as interleukin-4 and interleukin-13, thereby reducing metainflammation in adipose tissue. In this review, we focused on the role of eosinophils in regulating metabolic homeostasis and obesity. [ABSTRACT FROM AUTHOR]

Background The aim of the present study was to investigate the contribution of maturity-onset diabetes of the young ( MODY) genes to the etiology of 14 Chinese MODY families and to assess phenotypic differences between patients with MODY but without a known genetic cause of diabetes ( MODYX) and those with early onset type 2 diabetes ( T2D). Methods The study included 14 MODY probands from unrelated families and 59 patients (age of onset ≤35 years) diagnosed as early onset T2D. A standard meal test and metabolic studies were performed to characterize the clinical features of all patients. All probands with MODY were analyzed for nucleotide variations in promoters, exons, and exon-intron boundaries of 13 known MODY genes by direct DNA sequencing. Results Mutations in 13 known MODY genes were not present in the 14 Chinese families and they were classified as MODYX. However, different polymorphisms were identified, with I27L (42.9%; 12/28) and S487N (46.4%; 13/28) of hepatocyte nuclear factor 4 α ( HNF1α/ MODY3) being two most frequent polymorphisms. Two new polymorphisms, namely T412I and D504H, were detected in carboxyl ester lipase ( CEL/ MODY8). Compared with patients with early onset T2D, patients with MODYX were diagnosed with diabetes at a younger age (28.3 ± 6.5 vs 24.3 ± 6.5 years; P < 0.05) and had a lower body mass index ( BMI; 28.3 ± 6.1 vs 24.1 ± 4.3 kg/m2; P < 0.01) and homeostatic model assessment of β-cell function (47.6 [22.2-89.4] vs 18.5 [6.5-33.7]; P < 0.05). Conclusion Herein we report on 14 Chinese families with MODYX and describe its phenotype. Compared with early onset T2D, MODYX is characterized by lower BMI and decreased insulin-secreting capacity. [ABSTRACT FROM AUTHOR]

Objective: It has prompted concerns about the risk of thyroid nodules and thyroid tumors with liraglutide treatment. Our study intends to provide clinical observations on thyroid nodules in T2DM patients treated with liraglutide. Methods: We collected T2DM patients treated with or without liraglutide from January 2015 to September 2020 in Shanghai Tenth People's Hospital. Thyroid ultrasonography was available, including the size of thyroid nodule and TI-RADS classification. Results: A total of 268 T2DM patients were included in liraglutide group (L) and 328 T2DM in control group(C). Before liraglutide injection, 97 patients diagnosed of thyroid nodules in L group with an average size of 16.37±7.28mm, including 7 in TI-RADS 1, 15 in TI-RADS 2, and 75 in TI-RADS 3. There were 108 patients diagnosed of thyroid nodules in C group with an average size of 17.65±9.27mm, including 6 in TI-RADS 1, 22 in TI-RADS 2, and 80 in TI-RADS 3. After treating with liraglutide of 1.18±0.26mg/ day for 24.1±2.8 months, the average size of nodules in L group was 17.54±7.89mm, with 5 patients in TI-RADS 1, 13 in TI-RADS 2 and 79 in TI-RADS 3. The average size of nodules in C group was 18.19±8.52mm, with 5 patients in TI-RADS 1, 20 in TI-RADS 2, and 81 in TI-RADS 3. There was one patient with hyperthyroidism and one papillary thyroid carcinoma(PTC)in L group, and 2 PTC in C group. The nodules size was not significantly increased (P < 0.01). Conclusion: There was no significant changes of thyroid nodules size during the continuous administration of liraglutide in T2DM patients, and liraglutide was not considered associated with risk of thyroid tumor. However, the effect of liraglutide on thyroid function still needs further investigation. Disclosure: M. Zhang: None. Y. Wang: None. J. Yin: None. X. Zha: None. C. Sheng: None. P. Yang: None. H. Li: None. S. Qu: None. Funding: National Key Research and Development Project of China (2018YFC1314101); Shanghai Committee of Science and Technology (19DZ1910200, 18411951803, 17DZ1910603) [ABSTRACT FROM AUTHOR]

Background: Hyperuricemia is related to obesity and fat accumulation. This study aimed to observe the effects of laparoscopic sleeve gastrectomy (LSG) on serum uric acid (sUA) level and body fat distribution in obese patients. The relationships between post-LSG improvement in sUA levels and body fat distribution changes, as well as their sex-related differences, were also explored. Methods: In total, 128 obese patients (48 men; 80 women) who underwent LSG were enrolled. Anthropometric indicators, glucose and lipid metabolic indicators, and sUA levels were measured pre-LSG and 6 months post-LSG. The body compositions were measured via dual-energy X-ray absorptiometry. The patients were divided into normal-sUA (NUA) and high-sUA (HUA) groups based on preoperative sUA levels. Results: Compared with the NUA group, the reduction of sUA levels 6 months post-LSG was more significant in the HUA group. In addition, sUA reduction in the female HUA group was more significant than that of the male HUA group (P < 0.01). Changes in serum uric acid levels (ΔsUA) in the male HUA group was positively correlated with changes in body weight, body mass index, neck circumference, and hip circumference (r = 0.618, 0.653, 0.716, and 0.501, respectively; P < 0.05 in all cases). It was also positively correlated with changes in fat mass in the gynoid region, android region, and legs, (r = 0.675, 0.551, and 0.712, respectively; P < 0.05 in all cases), and negatively correlated with changes in total testosterone (ΔTT) (r = − 0.517; P = 0.040). Furthermore, ΔTT in this group was closely associated with the improved sex-related fat distribution. The ΔsUA in the female HUA group was positively correlated with changes in fasting serum C peptide and ΔLNIR (r = 0.449 and 0.449, respectively; P < 0.05 in both cases). In addition, it was also positively correlated with changes in visceral adipose tissue (VAT) fat mass, VAT fat volume, and VAT fat area (r = 0.749, 0.749, and 0.747, respectively; P < 0.01 in all cases). Conclusions: sUA levels of obese patients with hyperuricemia improved 6 months after LSG. Reduction of sUA after LSG was correlated with improved body fat distribution, and the relationships also displayed sex-based differences. Uric acid might be an important metabolic regulator associated with fat distribution and sex hormones. [ABSTRACT FROM AUTHOR]