Care, control and complications of hospitalised patients with type 1 diabetes in China: A nationwide-based registry study.

AIMS: To evaluate the status quo of type 1 diabetes (T1D) management and characteristics of hospitalised patients with T1D in China through a nationwide multicentre registry study, the China Diabetes Type 1 Study (CD1S). MATERIALS AND METHODS: Clinical data from the electronic hospital records of all people with T1D were retrospectively collected in 13 tertiary hospitals across 7 regions of China from January 2016 to December 2021. Patients were defined as newly diagnosed who received a diagnosis of diabetes for less than 3 months. RESULTS: Among the 4993 people with T1D, the median age (range) at diagnosis was 23.0 (1.0-87.0) years and the median disease duration was 2.0 years. The median haemoglobin A1c (HbA1c) level was 10.7%. The prevalence of obesity, overweight, dyslipidemia, and hypertension were 2.5%, 10.8%, 62.5% and 25.9%, respectively. The incidence rate of diabetic ketoacidosis at disease onset was 41.1%, with the highest in children <10 years of age (50.6%). In patients not newly diagnosed, 60.7% were diagnosed with at least one chronic diabetic complication, with the highest proportion (45.3%) of diabetic peripheral neuropathy. Chronic complications were detected in 79.2% of people with T1D duration ≥10 years. CONCLUSIONS: In the most recent years, there were still unsatisfactory metabolic control and high incidence of diabetic ketoacidosis as well as chronic diabetic complications among inpatients with T1D in China. The ongoing CD1S prospective study aims to improve the quality of T1D management nationally.

The effect of metformin combined with liraglutide on gut microbiota of Chinese patients with type 2 diabetes.

BACKGROUND: Metformin (MET) is a first-line therapy for type-2 diabetes mellitus (T2DM). Liraglutide (LRG) is a glucagon-like peptide-1 receptor agonist used as a second-line therapy in combination with MET. METHODS: We performed a longitudinal analysis comparing the gut microbiota of overweight and/or pre-diabetic participants (NCP group) with that of each following their progression to T2DM diagnosis (UNT group) using 16S ribosomal RNA gene sequencing of fecal bacteria samples. We also examined the effects of MET (MET group) and MET plus LRG (MET+LRG group) on the gut microbiota of these participants following 60 days of anti-diabetic drug therapy in two parallel treatment arms. RESULTS: In the UNT group, the relative abundances of Paraprevotella (P = 0.002) and Megamonas (P = 0.029) were greater, and that of Lachnospira (P = 0.003) was lower, compared with the NCP group. In the MET group, the relative abundance of Bacteroides (P = 0.039) was greater, and those of Paraprevotella (P = 0.018), Blautia (P = 0.001), and Faecalibacterium (P = 0.005) were lower, compared with the UNT group. In the MET+LRG group, the relative abundances of Blautia (P = 0.005) and Dialister (P = 0.045) were significantly lower than in the UNT group. The relative abundance of Megasphaera in the MET group was significantly greater than in the MET+LRG group (P = 0.041). CONCLUSIONS: Treatment with MET and MET+LRG results in significant alterations in gut microbiota, compared with the profiles of patients at the time of T2DM diagnosis. These alterations differed significantly between the MET and MET+LRG groups, which suggests that LRG exerted an additive effect on the composition of gut microbiota.

Carvacrol improves blood lipid and glucose in rats with type 2 diabetes mellitus by regulating short-chain fatty acids and the GPR41/43 pathway.

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and dyslipidemia. Carvacrol (CAR) has demonstrated the potential to mitigate dyslipidemia. This study aims to investigate whether CAR can modulate blood glucose and lipid levels in a T2DM rat model by regulating short-chain fatty acids (SCFAs) and the GPR41/43 pathway. The T2DM rat model was induced by a high-fat diet combined with low-dose streptozocin injection and treated with oral CAR and/or mixed antibiotics. Fasting blood glucose, oral glucose tolerance, and insulin tolerance tests were assessed. Serum lipid parameters, hepatic and renal function indicators, tissue morphology, and SCFAs were measured. In vitro, high glucose (HG)-induced IEC-6 cells were treated with CAR, and optimal CAR concentration was determined. HG-induced IEC-6 cells were treated with SCFAs or/and GPR41/43 agonists. CAR significantly reduced blood lipid and glucose levels, improved tissue damage, and increased SCFA levels in feces and GPR41/43 expression in colonic tissues of T2DM rats. CAR also attenuated HG-induced apoptosis of IEC-6 cells and enhanced GPR41/43 expression. Overall, these findings suggest that CAR alleviates blood lipid and glucose abnormalities in T2DM rats by modulating SCFAs and the GPR41/43 pathway.

Distribution of autoantibodies to insulinoma-associated antigen-2 and zinc transporter 8 in type 1 diabetes and latent autoimmune diabetes: A nationwide, multicentre, cross-sectional study.

AIMS: This study investigated insulinoma-associated-2 autoantibody (IA-2A) and zinc transporter 8 autoantibody (ZnT8A) distribution in patients with type 1 diabetes (T1D) and latent autoimmune diabetes (LAD) and the autoantibodies' association with clinical characteristics and HLA-DR-DQ genes. MATERIALS AND METHODS: This cross-sectional study recruited 17,536 patients with diabetes from 46 hospitals across China. A total of 189 patients with T1D and 58 patients with LAD with IA-2A positivity, 126 patients with T1D and 86 patients with LAD with ZnT8A positivity, and 231 patients with type 2 diabetes (T2D) were selected to evaluate islet autoantibodies, clinical phenotypes, and HLA-DR-DQ gene frequency. RESULTS: IA-2A was bimodally distributed in patients with T1D and LAD. Patients with low IA-2A titre LAD had lower fasting C-peptide (FCP) (p < 0.01), lower postprandial C-peptide (PCP) (p < 0.001), and higher haemoglobin A1c (HbA1c) levels (p < 0.05) than patients with T2D. Patients with high IA-2A titre LAD were younger than patients with low IA-2A titre LAD (p < 0.05). Patients with low IA-2A titre T1D had lower FCP (p < 0.01), lower PCP (p < 0.01), and higher HbA1c levels (p < 0.05) than patients with high IA-2A titre LAD. HLA-DR-DQ genetic analysis demonstrated that the frequency of susceptible HLA haplotypes was higher in IA-2A-positive patients (p < 0.001) than in patients with T2D. Patients with high ZnT8A titre LAD had lower FCP (p = 0.045), lower PCP (p = 0.023), and higher HbA1c levels (p = 0.009) and a higher frequency of total susceptible haplotypes (p < 0.001) than patients with low ZnT8A titre LAD. CONCLUSIONS: IA-2A in patients with T1D and LAD was bimodally distributed, and the presence of IA-2A could demonstrate partial LAD clinical characteristics. ZnT8A titre had a certain predictive value for islet functions in patients with LAD.

The continuous spectrum of glycaemic variability changes with pancreatic islet function: A multicentre cross-sectional study in China.

AIMS: To investigate glycaemic variability (GV) patterns in patients with type 1 diabetes (T1D), type 2 diabetes (T2D), and latent autoimmune diabetes in adults (LADA). MATERIALS AND METHODS: A total of 842 subjects (510 T1D, 105 LADA, 227 T2D) were enrolled and underwent 1 week of continuous glucose monitoring (CGM). Clinical characteristics and CGM parameters were compared among T1D, LADA, and T2D. LADA patients were divided into two subgroups based on glutamic acid decarboxylase autoantibody titres (≥180 U/mL [LADA-1], <180 U/mL [LADA-2]) and compared. The C-peptide cut-offs for predicting a coefficient of variation (CV) of glucose ≥36% and a time in range (TIR) > 70% were determined using receiver operating characteristic analysis. RESULTS: Twenty-seven patients (9 T1D, 18 T2D) were excluded due to insufficient CGM data. Sex, diabetes duration and HbA1c were comparable among the three groups. Fasting and 2-h postprandial C-peptide (FCP, 2hCP) increased sequentially across T1D, LADA, and T2D. T1D and LADA patients had comparable TIR and GV, whereas those with T2D had much higher TIR and lower GV (p < 0.001). The GV of LADA-1 was close to that of T1D, while the GV of LADA-2 was close to that of T2D. CP exhibited the strongest negative correlation with GV. The cut-offs of FCP/2hCP for predicting a CV ≥ 36% and TIR >70% were 121.6/243.1 and 128.9/252.8 pmol/L, respectively. CONCLUSIONS: GV presented a continuous spectrum across T1D, LADA-1, LADA-2, and T2D. More frequent glucose monitoring is suggested for patients with impaired insulin secretion. CLINICAL TRAIL REGISTRATION: Chinese Clinical Trial Registration (ChiCTR) website approved by WHO; http://www.chictr.org.cn/ - ChiCTR2200065036.

High-glucose induced toxicity in HK-2 cells can be alleviated by inhibition of miRNA-320c.

Diabetic nephropathy (DN) is a major healthcare challenge worldwide. MiRNAs exert a regulatory effect on the progress of DN. Our study proposed to investigate the miR-320c expression and its function on the pathogenesis of DN in vitro. The level of miR-320c in HK-2 cells was quantified by RT-qPCR. Cell morphology, invasion, and migration were observed by optical microscope, Transwell invasion assay, and scratch wound assay. Then, the levels of PTEN, α-SMA, vimentin, E-cadherin, p-PI3K, PI3K, AKT, and p-AKT were analyzed through western blotting. A Dual-luciferase reporter assay was conducted to explore the target relationship between miR-320c and PTEN. It was discovered that miR-320c was over-expressed in high glucose (HG)-treated HK-2 cells. Furthermore, inhibition of miR-320c could alleviate the epithelial-mesenchymal transition (EMT) of HG-induced HK-2 cells and retain the normal morphology of HK-2 cells. Additionally, the miR-320c inhibitor decreased the invasiveness and migration of HG-treated HK-2 cells. Next, the target gene of miR-320c, PTEN, was identified, and the function of miR-320c was reversed by down-regulation of PTEN. Finally, we found inhibition of miR-320c restrained the PI3K/AKT pathway. Therefore, inhibition of miR-320c could alleviate toxicity of HK-2 cells induced by HG via targeting PTEN and restraining the PI3K/AKT pathway, illustrating that miR-320c may act as a new biomarker in the diagnosis of DN.

Plasma periostin as a biomarker of osteoporosis in postmenopausal women with type 2 diabetes.

INTRODUCTION: Periostin, as an emerging biomarker, is involved in multiple steps in bone metabolism. This study aimed to investigate the correlation between periostin levels and bone mineral density as well as bone turnover markers in postmenopausal women with type 2 diabetes (T2DM). MATERIALS AND METHODS: This study was a cross-sectional study that included 164 postmenopausal women with T2DM as study subjects and 32 age-matched nondiabetic postmenopausal women with normal bone mineral density (BMD) as healthy control subjects. A total of 164 subjects with T2DM were then divided into three groups according to BMD: the normal BMD group (n = 29), the osteopenia group (n = 70), and the osteoporosis group (n = 65). The clinical data of all subjects along with the relevant biochemical parameter data were collected. Plasma periostin was detected using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma periostin levels were significantly increased in T2DM patients with normal BMD compared with healthy controls (p < 0.05). In the diabetic group, plasma periostin levels were significantly elevated with decreased BMD, were positively correlated with osteocalcin levels (r = 0.162, p = 0.039) and were inversely associated with femoral neck BMD (r = - 0.308, p < 0.001) and total femur BMD (r = - 0.295, p < 0.001). In the case of chronic complications, periostin levels were slightly increased in individuals with complications of diabetic retinopathy, diabetic nephropathy and fracture (p > 0.05). CONCLUSIONS: The current study demonstrated that plasma periostin levels were significantly associated with BMD in patients with T2DM, and periostin might act as a novel biochemical marker of osteoporosis in postmenopausal women with type 2 diabetes.

Adding vitamin D3 to the dipeptidyl peptidase-4 inhibitor saxagliptin has the potential to protect ß-cell function in LADA patients: A 1-year pilot study.

AIMS: This trial was conducted to explore the protective effect on ß-cell function of adding vitamin D3 to DPP-4 inhibitors to treat patients with latent autoimmune diabetes in adults (LADA). METHODS: 60 LADA patients were randomized to group A (n = 21) - conventional therapy with metformin (1-1.7 g/day) and/or insulin treatment; group B (n = 20) - saxagliptin (5 mg/day) plus conventional therapy; and group C (n = 19) - vitamin D3 (2000 IU/day) plus saxagliptin and conventional therapy for 12 months. Fasting and 2-hour postprandial blood samples were collected to measure blood glucose, glycosylated hemoglobin and C-peptide levels at baseline and after 3, 6 and 12 months of treatment. RESULTS: During the 12 months of follow-up, the levels of fasting C-peptide (FCP), 2-hour postprandial C-peptide (PCP) and the C-peptide index (CPI, serum C-peptide-to-plasma glucose level ratio) were maintained in group C. In contrast to those in group A and group B, FCP levels decreased significantly in group B, and CPI levels declined significantly in group A during the 1-year treatment (P < .05). Additionally, the levels of GADA titers in group C significantly decreased compared with those at baseline (P < .05), but no significant differences in GADA titers levels were detected in group A and group B. No significant differences were found among the three groups in the levels of FCP, PCP, the CPI or GADA titers. CONCLUSIONS: The data suggested that adding 2000 IU/day vitamin D3 to saxagliptin might preserve ß-cell function in patients with LADA.

Identification of a distinct phenotype of elderly latent autoimmune diabetes in adults: LADA China Study 8.

BACKGROUND: Latent autoimmune diabetes in adults (LADA) exhibits significant clinical heterogeneity, but the underlying causes remain unclear. The aim of this study was to investigate whether age of onset of LADA contributes to the observed clinical heterogeneity by comparing the clinical, metabolic, and immunogenetic characteristics between elderly and young LADA patients. METHODS: The cross-sectional study included a total of 579 patients with LADA which was further divided into elderly LADA (E-LADA) group (n = 135, age of onset ≥60 years) and young LADA (Y-LADA) group (n = 444, age of onset <60 years). Age-matched subjects with type 2 diabetes were served as control (E-T2D group, n = 622). Clinical characteristics, serum autoantibodies, and HLA-DQ haplotypes were compared among these groups. RESULTS: Compared with patients with Y-LADA, patients with E-LADA have better residual beta-cell function and higher level of insulin resistance (both P < .01), more metabolic syndrome characteristics, similar proportion of islet autoantibody positivity, and strikingly different HLA-DQ genetic background. In comparison with E-T2D patients, E-LADA patients tend to have similar metabolic syndrome prevalence, comparable C-peptide levels, and insulin resistance levels and share similar HLA-DQ genetic characteristics. CONCLUSIONS: Elderly LADA differs phenotypically and genetically from Y-LADA but has a clinical and genetic profile more similar to that of E-T2D. These distinct phenotypes could potentially help physicians better manage patients with E-LADA.

What sleep behaviors are associated with bruxism in children? A systematic review and meta-analysis.

PURPOSE: The aim of this article was to assess the sleep behaviors that serve as risk factors related to bruxism in children ages 0 to 12 years by performing a systematic review and meta-analysis of published studies. METHODS: Seven databases were searched to identify all peer-reviewed articles potentially relevant to the review. Data were pooled for random-effects modeling. Sleep risk factors related to bruxism in this age group are summarized using pooled odds ratios (ORs), 95% confidence intervals (CIs), and P values. RESULTS: Of 5637 initially identified articles, 14 met inclusion criteria. Study qualities of all case-control studies were high. Quality of cross-sectional studies was more variable. The pooled ORs, 95% CIs, and P values were as follows: snoring (2.86, 1.85-4.42, <0.0001), mouth breathing (1.51, 1.04-2.18, 0.029), restless sleep (2.31, 1.89-2.83, <0.0001), drooling (1.79, 1.07-2.97, 0.026), stomach position during sleep (1.70, 1.0-2.39, 0.003), and inadequate sleep time (2.56, 1.48-4.43, 0.001). CONCLUSIONS: Snoring, mouth breathing, restless sleep, drooling, stomach position during sleep, and lack of sleep were the risk factors related to bruxism in children.

Pim2 is required for maintaining multiple myeloma cell growth through modulating TSC2 phosphorylation.

Multiple myeloma (MM) is the second most common hematologic malignancy. Despite recent treatment advances, it remains incurable. Here, we report that Pim2 kinase expression is highly elevated in MM cells and demonstrate that it is required for MM cell proliferation. Functional interference of Pim2 activity either by short hairpin RNAs or by a potent and selective small-molecule inhibitor leads to significant inhibition of MM cell proliferation. Pim inhibition results in a significant decrease of mammalian target of rapamycin C1 (mTOR-C1) activity, which is critical for cell proliferation. We identify TSC2, a negative regulator of mTOR-C1, as a novel Pim2 substrate and show that Pim2 directly phosphorylates TSC2 on Ser-1798 and relieves the suppression of TSC2 on mTOR-C1. These findings support Pim2 as a promising therapeutic target for MM and define a novel Pim2-TSC2-mTOR-C1 pathway that drives MM proliferation.

Wnt-inhibitory factor 1 dysregulation of the bone marrow niche exhausts hematopoietic stem cells.

The role of Wnt signaling in hematopoietic stem cell fate decisions remains controversial. We elected to dysregulate Wnt signaling from the perspective of the stem cell niche by expressing the pan Wnt inhibitor, Wnt inhibitory factor 1 (Wif1), specifically in osteoblasts. Here we report that osteoblastic Wif1 overexpression disrupts stem cell quiescence, leading to a loss of self-renewal potential. Primitive stem and progenitor populations were more proliferative and elevated in bone marrow and spleen, manifesting an impaired ability to maintain a self-renewing stem cell pool. Exhaustion of the stem cell pool was apparent only in the context of systemic stress by chemotherapy or transplantation of wild-type stem cells into irradiated Wif1 hosts. Paradoxically this is mediated, at least in part, by an autocrine induction of canonical Wnt signaling in stem cells on sequestration of Wnts in the environment. Additional signaling pathways are dysregulated in this model, primarily activated Sonic Hedgehog signaling in stem cells as a result of Wif1-induced osteoblastic expression of Sonic Hedgehog. We find that dysregulation of the stem cell niche by overexpression of an individual component impacts other unanticipated regulatory pathways in a combinatorial manner, ultimately disrupting niche mediated stem cell fate decisions.

Simultaneous quantitation of seven alkaloids in processed Fuzi decoction by rapid resolution liquid chromatography coupled with tandem mass spectrometry.

A rapid analytical method based on rapid resolution LC coupled with MS/MS was first established to quantify seven alkaloids in processed Fuzi decoction. The chromatographic method was optimized to allow simultaneous analysis of all analytes in 5 min and demonstrated good linearity (r > 0.9995), repeatability (RSD < 4.36%), intra- and interday precisions (RSD < 5.07%) with good accuracies (97.76-105.08%) and good recovery (95.0-107.5%) of seven alkaloids, namely higenamine, benzoylhypaconine, benzoylmesaconine, benzoylaconine, aconitine, hypaconitine, and mesaconitine. The LODs for these markers were in the range of 2.30-17.00 pg/mL. Quantitative analysis of the seven alkaloids in Baifupian decoction and Heishunpian decoction showed that the content of the seven marker chemicals varied significantly and concluded that the quality of Fuzi was greatly affected by different processed methods. The developed method could be used as a rapid, sensitive, and reliable approach for assessment of the quality of processed Fuzi and related decoction.

[Analgesic effect of sinomenine on SSNI model rats and monoamine neurotransmitters in striatal extracellular fluid].

OBJECTIVE: To observe the analgesic effect of sinomenine on the neuropathic pain rat model induced by SSNI, and discuss its impact on monoamine neurotransmitters in striatal extracellular fluid. METHOD: Male SD rats were randomly divided into the sham operation group, the SSNI model group, the gabapentin group (100 mg x kg(-1)), the sinomenine high dose group (40 mg x kg(-1)) and the sinomenine low dose group (20 mg x kg(-1)). Mechanical hyperalgesia and cold pain sensitivity were evaluated by Von Frey hairs and cold spray. Striatum was sampled by microdialysis. High performance liquid chromatography-electrochemical detector (HPLC-ECD) were used to detect the content of such neurotransmitters as monoamine neurotransmitters noradrenaline (NE), dopamine (DA), 5-hydroxy tryptamine (5-HT) and their metabolites dihydroxyphenylacetic phenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA). RESULT: SSNI model rats showed significant improvement in mechanical withdrawal threshold and cold pain sensitivity, significant decrease in intracerebral NE and notable increase in DA, 5-HT and their metabolites. Compared with the model group, the sinomenine high dose group showed significant increase in mechanical withdrawal threshold at 60, 90, 180 and 240 min after abdominal administration (P < 0.01), significant decrease in cold pain sensitivity score during 30-240 min (P < 0.05). Sinomenine can significantly up-regulated NE content in striatal extracellular fluid during 45-135 min (P < 0.05), remarkably reduce DA content and DOPAC at 45, 75 and 135 min (P < 0.05), 5-HT content during 45-135 min, DOPAC during 75-165 min (P < 0.05), and 5-HIAA during 45-135 min (P < 0.05). CONCLUSION: Sinomenine has the intervention effect on neuropathic pain in SSNI model rats. Its mechanism may be related to disorder of monoamine neurotransmitters in striatal extracellular fluid.

The correlation between circulating growth differentiation factor 11 and the risk of osteopenia/osteoporosis in men.

Our results suggest that the serum GDF11 concentration is significantly associated with the risk of bone metabolism dysfunction in men and may be a useful target for prediction of osteopenia/osteoporosis to enable prompt intervention for this common but invariably under- or misdiagnosed condition in men. PURPOSE: Male osteopenia/osteoporosis remains a neglected subject or is under- or misdiagnosed. Many studies have confirmed the role of growth differentiation factor 11 (GDF11) in bone metabolism, although its role in bone metabolism remains controversial. In this study, we aimed to investigate the association between serum GDF11 levels and the prevalence of osteopenia/osteoporosis (OP) in a male cohort and explore the possibility of GDF11 to be a useful target for prediction of osteopenia/osteoporosis to enable prompt intervention for this disease. METHODS: This cross-sectional study included 121 native Chinese men randomly aged 20-87 years, excluded the subjects who had the conditions of bone metabolism-related disease and administration of hormonal drugs, and grouped the subjects to OP and non-OP, based on the WHO definition and latest guidelines of OP. The serum GDF11 concentration was determined using a GDF11-specific immunoassay. Bone mineral density (BMD) was measured using dual-energy X-ray absorptiometry. Tartrate-resistant acid phosphatase 5b (TRAP-5b) were measured in serum samples with ELISA method. RESULTS: We observed a negative correlation between serum GDF11 levels and age, a positive correlation between serum GDF11 levels and the femoral neck BMD, and a negative correlation between serum GDF11 levels and TRAP-5b in men. The prevalence and risk of OP were significantly higher in men with low serum GDF11 levels. CONCLUSIONS: The serum GDF11 concentration is significantly associated with the risk of bone metabolism dysfunction and may be a useful target for prediction of OP in male cohort.

Latent Autoimmune Diabetes in Adults and Metabolic Syndrome-A Mini Review.

Latent autoimmune diabetes in adults (LADA) is a heterogeneous subtype of diabetes characterized by islet cell destruction mediated by islet autoimmunity and insulin resistance. Metabolic syndrome (MetS) is a state in which many risk factors for metabolic and cardiovascular diseases accumulate in an individual. Based on clinical data, this review covers the prevalence of MetS in LADA, focusing on the risk associated with and the role of insulin resistance in the development of LADA from the perspective of inflammatory factors, environmental factors, and the gut microbiota, aiming to improve our understanding of this condition.

Liraglutide inhibits receptor for advanced glycation end products (RAGE)/reduced form of nicotinamide-adenine dinucleotide phosphate (NAPDH) signaling to ameliorate non-alcoholic fatty liver disease (NAFLD) in vivo and vitro.

The study was designed to investigate the effects of liraglutide and reveal its action mechanism associated with RAGE/NAPDH in NAFLD. The liver tissue was collected for HE, Masson, and ROS staining. Apoptosis levels were detected through TUNEL staining and ROS levels were evaluated through ROS staining. The expression levels of c-Jun N-terminal kinase (JNK) and transforming growth factor-ß (TGF-ß) were detected through Western blot. JNK and the expression of Collagenα1, Collagenα2 and connective tissue growth factor (CTGF) were detected through RT-qPCR and Western blot and the expression in mouse liver stellate cells (JS-1) cells were evaluated through immunofluorescence staining. We detected the effects of liraglutide on NAFLD in high-fat diet (HFD)-fed mice. Liraglutide treatment improved bridging fibrosis and liver function, as well as lessening ROS levels and the protein levels of RAGE, NOX1, NOX2 and NOX4. In PA and H2O2-induced AML12 cells, liraglutide treatment was able to decrease cell apoptosis, ROS levels and the levels of inflammatory factors including tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6, while it effects were reversed by the induction of RAGE overexpression or NOX2 overexpression. In JS-1 cells treated with medium culturing AML12 cells, liraglutide markedly suppressed cell proliferation and activation, while RAGE overexpression or NOX2 overexpression blunted these effects of liraglutide. Taken together, liraglutide exerts a protective role in improving liver injury caused by HFD, which could be related to decreased apoptosis and oxidative stress of liver cells, as well as decreased proliferation and activation of hepatic stellate cells through RAGE/NOX2.

Associations of insulin resistance and beta-cell function with abnormal lipid profile in newly diagnosed diabetes.

BACKGROUND: Abnormal lipids are strong predictors of cardiovascular disease in type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). However, the potential associations of insulin resistance (IR) and beta-cell function (BCF) with abnormal lipids in newly diagnosed T1DM or T2DM patients are not fully understood. METHODS: A cross-sectional survey of 15,928 participants was conducted. Homeostasis model assessment and postprandial C-peptide levels were used to estimate IR and BCF. A restricted cubic spline (RCS) nested in binary logistic regression was used to examine the associations of IR and BCF with abnormal lipids. RESULTS: High triglyceride (TG), low high-density lipoprotein cholesterol, and high low-density lipoprotein cholesterol (LDL-C) accounted for 49.7%, 47.8%, and 59.2% of the participants, respectively. In multivariable analysis, high IR was associated with an increased risk of high TGs ( P for trend <0.001) in T1DM and is associated with an elevated risk of high TG and low HDL-C (all P for trend <0.01) in T2DM. Low BCF was not associated with risks of dyslipidemia in patients with T1DM or T2DM after adjustment for potential confounders. CONCLUSION: High IR had different associations with the risk of dyslipidemia in newly diagnosed T1DM and T2DM patients, suggesting that early treatment that improves IR may benefit abnormal lipid metabolism.

Metabolic syndrome associated with higher glycemic variability in type 1 diabetes: A multicenter cross-sectional study in china.

Aims: The comorbidity of metabolic syndrome (MetS) and type 1 diabetes mellitus (T1DM) is an obstacle to glucose control in patients with T1DM. We compared glycemic profiles using continuous glucose monitoring (CGM) systems in patients with T1DM with or without MetS. Methods: This was a multicenter cross-sectional study of patients with T1DM (N = 207) with or without MetS. CGM data were collected from study enrollment until discharge during a 1-week study session. We analyzed baseline HbA1c, average glucose, estimated HbA1c, time in range (TIR), time above range (TAR), time below range (TBR), coefficient of variation (CV), postprandial glucose excursions (PPGE) and other glycemic variability (GV) metrics. Logistic regression was developed to investigate the association between MetS and CGM metrics. Results: The results showed higher average baseline HbA1c levels, and a higher percentage of patients with baseline HbA1c levels ≥7.5%, in the T1DM with MetS group. Furthermore, MetS was associated with GV, which indicated a higher CV in patients with T1DM with MetS. However, our results showed that TAR, TIR, TBR and other GV metrics were comparable between the two groups. The T1DM with MetS group also had a higher proportion of patients with high CV (≥ 36%) than the group without MetS. In multivariable logistic regression analysis, the presence of MetS was a risk factor for high CV (≥ 36%) in our study participants. Conclusions: T1DM patients with MetS in our study had better ß-cell function. However, MetS was associated with worse glycemic control characterized by higher GV and HbA1c levels. Efforts should be expanded to improve treatment of MetS in patients with T1DM to achieve better glycemic control.

A self-healing, magnetic and injectable biopolymer hydrogel generated by dual cross-linking for drug delivery and bone repair.

Injectable hydrogels based on various functional biocompatible materials have made rapid progress in the field of bone repair. In this study, a self-healing and injectable polysaccharide-based hydrogel was prepared for bone tissue engineering. The hydrogel was made of carboxymethyl chitosan (CMCS) and calcium pre-cross-linked oxidized gellan gum (OGG) cross-linked by the Schiff-base reaction. Meanwhile, magnetic hydroxyapatite/gelatin microspheres (MHGMs) were prepared by the emulsion cross-linking method. The antibacterial drugs, tetracycline hydrochloride (TH) and silver sulfadiazine (AgSD), were embedded into the MHGMs. To improve the mechanical and biological properties of the hydrogels, composite hydrogels were prepared by compounding hydroxyapatite (HAp) and drug-embedded MHGMs. The physical, chemical, mechanical and rheological properties of the composite hydrogels were characterized, as well as in vitro antibacterial tests and biocompatibility assays, respectively. Our results showed that the composite hydrogel with 6% (w/v) HAp and 10 mg/mL MHGMs exhibited good magnetic responsiveness, self-healing and injectability. Compared with the pure hydrogel, the composite hydrogel showed a 38.8% reduction in gelation time (196 to 120 s), a 65.6% decrease in swelling rate (39.4 to 13.6), a 51.9% increase in mass residual after degradation (79.5 to 120.8%), and a 143.7% increase in maximum compressive stress (53.6 to 130.6 KPa). In addition, this composite hydrogel showed good drug retardation properties and antibacterial effects against both S. aureus and E. coli. CCK-8 assay showed that composite hydrogel maintained high cell viability (> 87%) and rapid cell proliferation after 3 days, indicating that this smart hydrogel is expected to be an alternative scaffold for drug delivery and bone regeneration. STATEMENT OF SIGNIFICANCE: Biopolymer hydrogels have been considered as the promising materials for the treatment of tissue engineering and drug delivery. Injectable hydrogels with and self-healing properties and responsiveness to external stimuli have been extensively investigated as cell scaffolds and bone defects, due to their diversity and prolonged lifetime. Magnetism has also been involved in biomedical applications and played significant roles in targeted drug delivery and anti-cancer therapy. We speculate that development of dual cross-linked hydrogels basing biopolymers with multi-functionalities, such as injectable, self-healing, magnetic and anti-bacterial properties, would greatly broaden the application for bone tissue regeneration and drug delivery.