Indices Of Glucose Metabolism Research Articles

Exploring the active components and potential mechanisms of Alpiniae oxyphyllae Fructus in treating diabetes mellitus with depression by UPLC-Q-Exactive Orbitrap/MS, network pharmacology and molecular docking.

The growing incidence of diabetes mellitus (DM) and depression is a global public health issue. Alpiniae oxyphyllae Fructus (AOF) is a kind of medicinal and edible plant which be found with anti-diabetic property, and could improve depression-like symptoms. This study aimed to screen active targets and potential mechanisms of AOF in treating DM with depression. Injection of streptozotocin (STZ) and exposure to chronic unpredictable mild stress (CUMS) for 4 weeks were used to conduct the DM with depression mice model. Behavioral tests, indexes of glucose metabolism, monoamine neurotransmitters, inflammatory cytokine and oxidative stress were measured. Histopathological change of hippocampus tissue was observing by HE and Nissl staining. UPLC-Q-Exactive Orbitrap/MS, network pharmacology and molecular docking were used to explore the chemical components and mechanisms of AOF on the DM with depression. AOF showed a reversed effect on body weight in DM with depression mice. Glucose metabolism and insulin resistance could be improved by treatment of AOF. In addition, AOF could alleviate depression-like behaviors based on the results of behavior tests and monoamine neurotransmitters. AOF also attenuated STZ-CUMS induced neuron injury in hippocampus. Next, a total of 61 chemical components were identified in the UPLC-Q-Exactive Orbitrap/MS analysis of the extract of AOF. Network pharmacology analysis suggested that 12 active components and 227 targets were screened from AOF, and 1802 target genes were screened from DM with depression, finally 126 intersection target genes were obtained. Drug-disease targets network was constructed and implied that the top five components with a higher degree value includes quercetin, nootkatone, baicalein, (-)-epicatechin and nootkatol. Protein-protein interaction (PPI) network showed that MAPK1, FOS, AKT1, IL6 and TP53 may be the core intersection targets. The mechanism of the effect of AOF on DM with depression was analyzed through gene ontology (GO), and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis, mainly involved in AGE/RAGE, PI3K/AKT, and MAPK signaling pathways. The results of molecular docking indicated that quercetin, nootkatone, baicalein, (-)-epicatechin and nootkatol all had good binding to the core intersection targets. Overall, our experimental researches have demonstrated that AOF could exert the dual effects of anti-diabetic and anti-depression on DM with depression mice, through multi-targets and multi-pathways.

#715 Adiponectin / leptin ratio as an index to determine the risk of metabolic and rejection complications in patients after kidney transplantation

Abstract Background and Aims Adipose tissue, as an endocrine and paracrine organ, produces several hormones that are involved in the regulation of metabolic and inflammatory processes or immune system activity. While leptin is the main pro-inflammatory marker of adipose tissue, adiponectin is characterized by its anti-inflammatory effects. The adiponectin / leptin (A/L) ratio had been shown to correlate better with the occurrence of cardiometabolic risk factors than hormone concentrations alone. Results in the general population suggest that an A/L ratio > 1 can be considered normal, an A/L ratio of 0.5-1 indicates a moderate increase, and an A/L ration < 0.5 a high increase in cardiometabolic risk. The first aim of our study was to determine the risk of developing post-transplant diabetes mellitus (PTDM), prediabetes and other metabolic risk factors in relation to the A/L ratio in patients after kidney transplantation (KT). The second aim was to determine the risk of developing acute graft rejection in relation to the A/L ratio in patients after KT. Method A total of 104 patients were included in our prospective analysis after applying inclusion and exclusion criteria. Pre-transplantation and subsequently at 3, 6 and 12 months after KT, we recorded baseline characteristics of donors and recipients, including parameters characterizing graft function, metabolic (lipid profile, indices of glucose metabolism) and anthropometric parameters. At the same time, we examined serum adipocytokine concentrations (adiponectin, leptin) and calculated the A/L ratio. In the third month after KT, all patients underwent protocol graft biopsy and donor specific antibody (DSA) testing by Luminex method. Results We found that during the follow-up period, there was a significant increase in the A/L ratio in the control group (p = 0.0013) and, on the other hand, a significant decrease in the group who developed PTDM (p = 0.0003). Comparing the different subgroups divided on the A/L ratio one year after KT, we found that patients with an A/L < 0.5 were significantly longer in the dialysis program, had higher body mass index (BMI), waist circumference, worse graft function, and a higher prevalence of prediabetes and PTDM compared with those whose A/L ratio was > 1. Using logistic regression in multivariate analysis, we identified age at the time of KT [OR 1.0709, (p = 0.0337)], triglycerides level at 1 year after KT [OR 2.7735, (p = 0.446)] and A/L ratio < 0.5 [OR 3.1724, (p = 0.014)] as independent risk factors for the development of prediabetes and PTDM 1 year after KT. At the same time, after adjusting for differences in baseline donor and recipient characteristics, we identified the subgroup with an A/L ratio < 0.5 pre-transplant [HR 1.6126, (p = 0.0133)] and 3 months after KT [HR 1.3150, (p = 0.0172)] as an independent risk factor for the development of acute graft rejection. In the subsequent specification of the rejection episode, we found that A/L ratio < 0.5 pre-transplant [HR 2.2353, (p = 0.0357)] and 3 months after KT [HR 3.0954, (p = 0.0237)] is and independent risk factor for the occurrence of acute humoral rejection with DSA positivity. Conclusion In our study, we found that an A/L ratio < 0.5 is an independent risk factor for the development of prediabetes, PTDM 1 year after KT and acute humoral graft rejection with de novo DSA production in the third month after KT. This is the first study to investigate the correlation of the A/L ratio with the risk of developing metabolic and immunological complications in patients after KT.

Association of exposure to multiple perfluoroalkyl and polyfluoroalkyl substances and glucose metabolism in National Health and Nutrition Examination Survey 2017-2018.

To investigate the relationships between perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposure and glucose metabolism indices. Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 waves were used. A total of 611 participants with information on serum PFASs (perfluorononanoic acid (PFNA); perfluorooctanoic acid (PFOA); perfluoroundecanoic acid (PFUA); perfluorohexane sulfonic acid (PFHxS); perfluorooctane sulfonates acid (PFOS); perfluorodecanoic acid (PFDeA)), glucose metabolism indices (fasting plasma glucose (FPG), homeostasis model assessment for insulin resistance (HOMA-IR) and insulin) as well as selected covariates were included. We used cluster analysis to categorize the participants into three exposure subgroups and compared glucose metabolism index levels between the subgroups. Least absolute shrinkage and selection operator (LASSO), multiple linear regression analysis and Bayesian kernel machine regression (BKMR) were used to assess the effects of single and mixed PFASs exposures and glucose metabolism. The cluster analysis results revealed overlapping exposure types among people with higher PFASs exposure. As the level of PFAS exposure increased, FPG level showed an upward linear trend (p < 0.001), whereas insulin levels demonstrated a downward linear trend (p = 0.012). LASSO and multiple linear regression analysis showed that PFNA and FPG had a positive relationship (>50 years-old group: β = 0.059, p < 0.001). PFOA, PFUA, and PFHxS (≤50 years-old group: insulin β = -0.194, p < 0.001, HOMA-IR β = -0.132, p = 0.020) showed negative correlation with HOMA-IR/insulin. PFNA (>50 years-old group: insulin β = 0.191, p = 0.018, HOMA-IR β = 0.220, p = 0.013) showed positive correlation with HOMA-IR/insulin, which was essentially the same as results that obtained for the univariate exposure-response map in the BKMR model. Association of exposure to PFASs on glucose metabolism indices showed positive interactions between PFOS and PFHxS and negative interactions between PFOA and PFNA/PFOS/PFHxS. Our study provides evidence that positive and negative correlations between PFASs and FPG and HOMA-IR/insulin levels are observed, respectively. Combined effects and interactions between PFASs. Given the higher risk of glucose metabolism associated with elevated levels of PFAS, future studies are needed to explore the potential underlying mechanisms.

Dietary Betaine Improves Glucose Metabolism in Obese Mice

BackgroundObesity caused by the overconsumption of energy-dense foods high in fat and sugar has contributed to the growing prevalence of type 2 diabetes. Betaine, found in food or supplements, has been found to lower blood glucose concentrations, but its exact mechanism of action is not well understood. ObjectivesA comprehensive evaluation of the potential mechanisms by which betaine supplementation improves glucose metabolism. MethodsHyperglycemic mice were fed betaine to measure the indexes of glucose metabolism in the liver and muscle. To explore the mechanism behind the regulation of betaine on glucose metabolism, Ribonucleic Acid-Seq was used to analyze the livers of the mice. In vitro, HepG2 and C2C12 cells were treated with betaine to more comprehensively evaluate the effect of betaine on glucose metabolism. ResultsBetaine was added to the drinking water of high-fat diet-induced mice, and it was found to reduce blood glucose concentrations and liver triglyceride concentrations without affecting body weight, confirming its hypoglycemic effect. To investigate the specific mechanism underlying its hypoglycemic effect, protein-protein interaction enrichment analysis of the liver revealed key nodes associated with glucose metabolism, including cytochrome P450 family activity, insulin sensitivity, glucose homeostasis, and triglyceride concentrations. The Kyoto Encyclopedia of Genes and Genomes and gene ontogeny enrichment analyses showed significant enrichment of the Notch signaling pathway. These results provided bioinformatic evidence for specific pathways through which betaine regulates glucose metabolism. Key enzyme activities involved in glucose uptake, glycogen synthesis, and glycogenolysis pathways of the liver and muscle were measured, and improvements were observed in these pathways. ConclusionsThis study provides new insight into the mechanisms by which betaine improves glucose metabolism in the liver and muscle and supports its potential as a drug for the treatment of metabolic disorders related to glucose.

Insulin at the intersection of thermoregulation and glucose homeostasis

Mammals are protected from changes in environmental temperature by altering energetic processes that modify heat production. Insulin is the dominant stimulus of glucose uptake and metabolism, which are fundamental for thermogenic processes. The purpose of this work was to determine the interaction of ambient temperature induced changes in energy expenditure (EE) on the insulin sensitivity of glucose fluxes. Short-term and adaptive responses to thermoneutral temperature (TN, ∼28 °C) and room (laboratory) temperature (RT, ∼22 °C) were studied in mice. This range of temperature does not cause detectable changes in circulating catecholamines or shivering and postabsorptive glucose homeostasis is maintained. We tested the hypothesis that a decrease in EE that occurs with TN causes insulin resistance and that this reduction in insulin action and EE is reversed upon short term (<12h) transition to RT. Insulin-stimulated glucose disposal (Rd) and tissue-specific glucose metabolic index were assessed combining isotopic tracers with hyperinsulinemic-euglycemic clamps. EE and insulin-stimulated Rd are both decreased (∼50%) in TN-adapted vs RT-adapted mice. When RT-adapted mice are switched to TN, EE rapidly decreases and Rd is reduced by ∼50%. TN-adapted mice switched to RT exhibit a rapid increase in EE, but whole-body insulin-stimulated Rd remains at the low rates of TN-adapted mice. In contrast, whole body glycolytic flux rose with EE. This higher EE occurs without increasing glucose uptake from the blood, but rather by diverting glucose from glucose storage to glycolysis. In addition to adaptations in insulin action, ‘insulin-independent’ glucose uptake in brown fat is exquisitely sensitive to thermoregulation. These results show that insulin action adjusts to non-stressful changes in ambient temperature to contribute to the support of body temperature homeostasis without compromising glucose homeostasis.

The Evolution of the Bone Turnover Marker in Patients Following Recovery from Diabetic Ketoacidosis.

The aim of the study was to investigate whether the biomarkers for bone turnover could rapidly recover during the period of diabetic ketoacidosis (DKA). Bone turnover biomarkers, including 25-hydroxyvitamin D3, N-terminal middle molecular fragment of osteocalcin (NMID), and β-C terminal cross-linking telopeptide of type 1 collagen were evaluated using in-patient data (n=627) from Shanghai Pudong Hospital from 2018-2022. The comparison was performed between type 2 diabetes (T2D only) (n=602) and DKA (n=25), in which we checked the bone turnover markers at pre-treatment and recovery. After matching by body mass index (BMI), we found that except for 25-OH-VitD3, the age difference, indices of glucose metabolism, and bone turnover were significant between the 2 groups (p<0.05). We found only a significant restoration of NMID (p<0.001). NMID and β-CTX, when compared with T2D, showed overt distinction between recovery and T2D (p<0.05). In addition, the investigations demonstrated a substantial difference between 25-OH-VitD3 in males and NMID in females, regardless of age (p<0.05). Multilinear regression analysis revealed that 2 hours postprandial plasma C-peptide was an independent predictor of the NMID in both pre-treatment (β=0.58, p=0.003) and recovery (β=0.447, p=0.025), although sex was significant in pre-treatment (β=-0.444, p=0.020). Finally, we found that only age variation affected DKA's fasting plasma glucose level (p<0.05). The study revealed that the bone turnover of DKA is significantly different in pre-treatment and recovery; however, NMID might recover quickly if the patients received appropriate treatment. Importantly, pancreatic function plays a critical role in changing bone turnover biomarkers.

Pitavastatin calcium significantly improves glucose and lipid metabolism of patients with coronary atherosclerosis and reduces the occurrence of adverse cardiovascular events

Purpose: To determine the efficacy of pitavastatin calcium and atorvastatin calcium on coronary atherosclerosis (CA) and compare the influence of the two schemes on adverse cardiovascular events.&#x0D; Methods: The medical records of 198 patients with CA admitted at Affiliated Hospital of Jiangsu University, China from August 2019 to May 2011 were analyzed retrospectively. The patients were grouped into pitavastatin calcium group (n = 102) and atorvastatin calcium group (n = 96). The efficacy, incidence of adverse cardiovascular events, as well as changes in blood lipid metabolism and blood glucose metabolism indices before and after therapy were recorded and compared.&#x0D; Results: Compared with atorvastatin calcium group, pitavastatin calcium group yielded a significantly higher overall response rate (ORR, p &lt; 0.05) and presented a significantly lower total incidence of cardiovascular adverse events (p &lt; 0.05). After therapy, pitavastatin calcium group displayed significantly lower triglyceride, total cholesterol and low-density lipoprotein-cholesterol levels (p &lt; 0.05), and also presented significantly higher high-density lipoprotein-cholesterol levels (p &lt; 0.05) in contrast to atorvastatin calcium group. Furthermore, pitavastatin calcium group presented significantly lower fasting blood glucose and glycosylated hemoglobin levels than atorvastatin calcium group (p &lt; 0.05).&#x0D; Conclusion: Compared with atorvastatin calcium, pitavastatin calcium displays a better therapeutic effect in patients with CA, lowers the incidence of adverse cardiovascular events and improves glucose and lipid metabolism of patients. Future studies will focus on longer follow-up sessions to better understand the impact of the drugs on patient’s prognosis.

Joint associations among non-essential heavy metal mixtures and nutritional factors on glucose metabolism indexes in US adults: evidence from the NHANES 2011-2016.

Dietary intake can modify the impact of metals on human health, and is also closely related to glucose metabolism in human bodies. However, research on their interaction is limited. We used data based on 1738 adults aged ≥20 years from the National Health and Nutrition Examination Survey 2011-2016. We combined linear regression and restricted cubic splines with Bayesian kernel machine regression (BKMR) to identify metals associated with each glucose metabolism index (P < 0.05 and the posterior inclusion probabilities of BKMR >0.5) in eight non-essential heavy metals (barium, cadmium, antimony, tungsten, uranium, arsenic, lead, and thallium) and glucose metabolism indexes [fasting plasma glucose (FPG), blood hemoglobin A1c (HbA1c) and homeostatic model assessment of insulin resistance (HOMA-IR)]. We identified two pairs of metals associated with glucose metabolism indexes: cadmium and tungsten to HbA1c and barium and thallium to HOMA-IR. Then, the cross-validated kernel ensemble (CVEK) approach was applied to identify the specific nutrient group (nutrients) that interacted with the association. By using the CVEK model, we identified significant interactions between the energy-adjusted diet inflammatory index (E-DII) and cadmium, tungsten and barium (all P < 0.05); macro-nutrients and cadmium, tungsten and barium (all P < 0.05); minerals and cadmium, tungsten, barium and thallium (all P < 0.05); and A vitamins and thallium (P = 0.043). Furthermore, a lower E-DII, a lower intake of carbohydrates and phosphorus, and a higher consumption of magnesium seem to attenuate the positive association between metals and glucose metabolism indexes. Our finding identifying the nutrients that interact with non-essential heavy metals could provide a feasible nutritional guideline for the general population to protect against the adverse effects of non-essential heavy metals on glucose metabolism.

Application value of serum S100B combined with glucose metabolism indexes in predicting adverse pregnancy outcomes of patients with severe preeclampsia.

S100 calcium-binding protein B (S100B) and glucose control are reflective of maternal-fetal risks. We investigated the value of serum S100B combined with fasting blood glucose (FBG)/hemoglobin A1c (HbA1c) in evaluating the pregnancy outcomes of patients with severe preeclampsia (SPE). The clinical characteristics of SPE patients/controls were collected. FBG/HbA1c and serum S100B levels were measured, with their correlations analyzed. SPE patients were subdivided into adverse/non-adverse outcome groups based on follow-up results. The value of different indexes in predicting pregnancy outcomes was analyzed. SPE patients showed higher systolic blood pressure, diastolic blood pressure, urine protein, and body mass index and lower platelets, gestational age at delivery, and infant birth weight than healthy controls. FBG and HbA1c were positively correlated with serum S100B. SPE patients with adverse outcomes exhibited increased serum S100B and FBG/HbA1c levels. The area under the curve of serum S100B + FBG/HbA1c in evaluating adverse pregnancy outcomes of SPE patients was 0.8412 (77.05% sensitivity/84.21% specificity), higher than either alone. Serum S100B and FBG/HbA1c were independent risk factors for adverse outcomes of SPE patients. Overall, serum S100B positively-correlates with FBG/HbA1c in SPE patients. Serum S100B and FBG/HbA1c are independent risk factors, and their combination has high value on predicting adverse pregnancy outcomes of SPE patients.

Glycated haemoglobin, HOMA2-B, C-peptide to glucose ratio and type 2 diabetes clusters as predictors for therapy failure in individuals with type 2 diabetes without insulin therapy: A registry analysis.

Some people with type 2 diabetes mellitus (T2D) and declining β-cell function do require insulin over time. Various laboratory parameters, indices of glucose metabolism or phenotypes of T2D (clusters) have been suggested, which might predict future therapy failure (TF), indicating the need for insulin therapy initiation. This analysis evaluated glycated haemoglobin (HbA1c), homeostatic model assessment (HOMA)2-B, C-peptide to glucose ratio (CGR) and diabetes clusters as predictive parameters for the occurrence of glycaemic TF in individuals diagnosed with T2D without previous insulin therapy. In total, 159 individuals with T2D [41% female, median age 50 (IQR: 53-69) years, diabetes duration 9 (5-15) years], without insulin therapy were prospectively evaluated for the occurrence of a composite primary endpoint, including HbA1c increasing or remaining >8.0% (64 mmol/mol) 3 months after baseline on non-insulin glucose-lowering agents, insulin initiation or hospital admissions because of acute hyperglycaemic events. Diabetes clusters were formed according to previously described characteristics. Only severe autoimmune diabetes clusters were excluded because of a small amount of glutamate decarboxylase antibody-positive participants. The other clusters were distributed as mild age-related diabetes 33%; severe insulin-deficient diabetes 31%; mild obesity-related diabetes 20%; and severe insulin-resistant diabetes 15%. During a median observation of 57 months, higher tertiles of HbA1c at baseline, HOMA2-B, as well as a lower CGR were significantly predictive for the occurrence of the primary endpoint. The probability of meeting the primary endpoint was the highest for mild obesity-related diabetes [hazard ratio 3.28 (95% confidence interval 1.75-6.2)], followed by severe insulin-deficient diabetes [hazard ratio 2.03 (95% confidence interval 1.1-3.7)], mild age-related diabetes and the lowest for severe insulin-resistant diabetes. The best performance to predict TF with an area under the curve (AUC) of 0.77 was HbA1c at baseline, followed by HOMA2-B (AUC 0.69) and CGR (AUC 0.64). HbA1c, indices of insulin secretion capacity (HOMA2-B and CGR) and T2D clusters might be applicable tools to guide practitioners in the decision of whether insulin is required in people already diagnosed with T2D. These findings need to be validated in prospective studies.

Dietary carbohydrate quality index and cardio-metabolic risk factors.

Introduction: Improving the quality of diet is known as one of the practical ways to reduce cardio-metabolic risk factors (CMRFs). The carbohydrate quality index (CQI) is a relatively new index to evaluate diet quality. It is calculated based on the ratio of solid carbohydrates to total carbohydrates, dietary fibre intake, glycemic index and the ratio of whole grains to total grains. This systematic review and meta-analysis was designed to investigate the association between dietary CQI and CMRFs. Methods: In this systematic review, some international databases, including Scopus, PubMed, EMBASE, Web of Science, and Google Scholar up to July 2022, were searched according to appropriate keywords. All observational studies with an English full text assessing the association between the dietary CQI and CMRFs were included. Two researchers independently extracted the data and assessed the quality of the articles with the Newcastle-Ottawa Scale. Random/fixed-effect meta-analysis was used to pool standardized mean difference (SMD) as an effect size. Results: 11 studies with a total of 63962 subjects were found to be eligible and included in the qualitative synthesis; only BMI, WC and metabolic syndrome reached the threshold of 3 reports with the same effect size and thus only 5 were included in the meta-analysis. The main finding of the included studies was that there were inverse associations between CQI and CMRFs, mainly obesity, glucose metabolism indices, and blood pressure. In the five studies included in the random effect meta-analysis, the association between CQI and body mass index (SMD: 0.45, 95%CI: -0.12, 1.01), waist circumference (SMD: -0.09, 95%CI: -0.34, 0.15) and metabolic syndrome (SMD: 0.63, 95%CI: -0.01, 1.28) was not statistically significant. Conclusion: Although the qualitative findings support the positive association of CQI with CMRFs, the evidence is insufficient to conclude robust findings. Further observational and interventional studies are needed to clearly elucidate this association.

Efficacy of metformin combined with liraglutide on the glucose and lipid metabolism, vascular endothelial function, and oxidative stress of patients with T2DM and metabolic syndrome.

This study evaluates the impact of metformin combined with liraglutide on the glucose and lipid metabolism, oxidative stress, and vascular endothelium of patients with type-2 diabetes mellitus (T2DM) and metabolic syndrome. Medical records of 78 patients with T2DM and metabolic syndrome, admitted to Caoxian People's Hospital from July 2021 to July 2022, were retrospectively analysed. Thirty five patients were treated with metformin (control group), and 43 patients were treated with metformin combined with liraglutide (observation group). Indexes of glucose and lipid metabolism, function of vascular endothelium and the oxidative stress of both groups were compared before and after the treatment. There was a significant decrease in the levels of fasting plasma glucose (FPG), Glycosylated Hemoglobin A1c (HbA1c), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP), diastolic blood pressure (DBP) and waist circumference in both groups three months after the treatment, These indexes were significantly lower in the observation group compared to the control group (P<0.05). High-density lipoprotein cholesterol (HDL-C) levels were higher in the observation group (P<0.05). There was a significant improvement in the levels of nitric oxide (NO), endothelin-1 (ET-1), superoxide dismutase (SOD), and malondialdehyde (MDA) after the treatment, and these indexes were markedly better in the observation group compared to the control group (P<0.05). Metformin combined with liraglutide treatment is associated with better outcomes than metformin alone in patients with T2DM and metabolic syndrome. Combined treatment results in improved glucose and lipid metabolism, vascular endothelial function, and oxidative stress index values.

Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance.

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease featured by insulin resistance (IR) and decreased insulin secretion. Currently, vitamin D deficiency is found in most patients with T2DM, but the relationship between vitamin D and IR in T2DM patients requires further investigation. To explore the risk factors of IR and the effects of vitamin D supplementation on glucose and lipid metabolism in patients with T2DM. Clinical data of 162 T2DM patients treated in First Affiliated Hospital of Harbin Medical University between January 2019 and February 2022 were retrospectively analyzed. Based on the diagnostic criteria of IR, the patients were divided into a resistance group (n = 100) and a non-resistance group (n = 62). Subsequently, patients in the resistance group were subdivided to a conventional group (n = 44) or a joint group (n = 56) according to the treatment regimens. Logistic regression was carried out to analyze the risk factors of IR in T2DM patients. The changes in glucose and lipid metabolism indexes in T2DM patients with vitamin D deficiency were evaluated after the treatment. Notable differences were observed in age and body mass index (BMI) between the resistance group and the non-resistance group (both P < 0.05). The resistance group exhibited a lower 25-hydroxyvitamin D3 (25(OH)D3) level, as well as notably higher levels of 2-h postprandial blood glucose (2hPG), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c) than the non-resistance group (all P < 0.0001). Additionally, the resistance group demonstrated a higher triglyceride (TG) level but a lower high-density lipoprotein-cholesterol (HDL-C) level than the non-resistance group (all P < 0.0001). The BMI, TG, HDL-C, 25(OH)D3, 2hPG, and HbA1c were found to be risk factors of IR. Moreover, the post-treatment changes in levels of 25(OH)D3, 2hPG, FBG and HbA1c, as well as TG, total cholesterol, and HDL-C in the joint group were more significant than those in the conventional group (all P < 0.05). Patients with IR exhibit significant abnormalities in glucose and lipid metabolism parameters compared to the non-insulin resistant group. Logistic regression analysis revealed that 25(OH)D3 is an independent risk factor influencing IR. Supplementation of vitamin D has been shown to improve glucose and lipid metabolism in patients with IR and T2DM.

Salsalate and/or metformin therapy confer beneficial metabolic effects in olanzapine treated female mice

Antipsychotic medications are used in the management of schizophrenia and a growing number of off-label conditions. While effective at reducing psychoses, these drugs possess noted metabolic side effects including weight gain, liver lipid accumulation and disturbances in glucose and lipid metabolism. To counter the side effects of antipsychotics standard of care has typically included metformin. Unfortunately, metformin does not protect against antipsychotic induced metabolic disturbances in all patients and thus additional treatment approaches are needed. One potential candidate could be salsalate, the prodrug of salicylate, which acts synergistically with metformin to improve indices of glucose and lipid metabolism in obese mice. The purpose of the current investigation was to compare the effects of salsalate, metformin and a combination of both drugs, on weight gain and indices of metabolic health in female mice treated with the antipsychotic, olanzapine. Herein we demonstrate that salsalate was equally as effective as metformin in protecting against olanzapine induced weight gain and liver lipid accumulation with no additional benefit of combining both drugs. Conversely, metformin treatment, either alone or in combination with salsalate, improved indices of glucose metabolism and increased energy expenditure in olanzapine treated mice. Collectively, our findings provide evidence that dual therapy with both metformin and salsalate could be an efficacious approach with which to dampen the metabolic consequences of antipsychotic medications.

Differential effects on renal function and glucose metabolism of renal dependent bezafibrate and non-renal dependent pemafibrate in patients with hypertriglyceridemia.

Among fibrates as triglyceride-lowering agents, bezafibrate and fenofibrate are predominantly renally excreted, while pemafibrate is mainly hepatically metabolized and biliary excreted. To elucidate possible different properties among fibrates, this retrospective observational study examined the changes in clinical laboratory parameters, including indices of renal function and glucose metabolism, in cases of switching from bezafibrate to pemafibrate. In 93 patients with hypertriglyceridemia, the average values of laboratory parameters including serum creatinine, estimated glomerular filtration rate (eGFR), plasma glucose, and hemoglobin A1c on respective two occasions before and after switching from bezafibrate to pemafibrate were evaluated. Triglycerides, low-density and high-density lipoprotein cholesterol, creatine kinase, and uric acid did not change before and after switching from bezafibrate to pemafibrate. Serum creatinine significantly decreased and eGFR significantly increased after switching from bezafibrate to pemafibrate (p<0.001, respectively). Plasma glucose tended to increase (p=0.070) and hemoglobin A1c significantly increased (p<0.001) after switching to pemafibrate. The degrees of changes in creatinine, eGFR, glucose, and hemoglobin A1c before and after drug switching were not affected by the presence or absence of coexisting disease, and with or without drug treatment including statin and renin-angiotensin system inhibitor. Our findings indicate that switching from bezafibrate to pemafibrate produces a significant decrease in serum creatinine and increases in eGFR and hemoglobin A1c in patients with hypertriglyceridemia, suggesting that the effects on renal function and glucose metabolism differ among fibrates.

Effects of Salinity Stress on Histological Changes, Glucose Metabolism Index and Transcriptomic Profile in Freshwater Shrimp, Macrobrachium nipponense.

Salinity is an important factor in the aquatic environment and affects the ion homeostasis and physiological activities of crustaceans. Macrobrachium nipponense is a shrimp that mainly lives in fresh and low-salt waters and plays a huge economic role in China's shrimp market. Currently, there are only a few studies on the effects of salinity on M. nipponense. Therefore, it is of particular importance to study the molecular responses of M. nipponense to salinity fluctuations. In this study, M. nipponense was set at salinities of 0, 8, 14 and 22‱ for 6 weeks. The gills from the control (0‱) and isotonic groups (14‱) were used for RNA extraction and transcriptome analysis. In total, 593 differentially expressed genes (DEGs) were identified, of which 282 were up-regulated and 311 were down-regulated. The most abundant gill transcripts responding to different salinity levels based on GO classification were organelle membrane (cellular component), creatine transmembrane transporter activity (molecular function) and creatine transmembrane transport (biological function). KEGG analysis showed that the most enriched and significantly affected pathways included AMPK signaling, lysosome and cytochrome P450. In addition, 15 DEGs were selected for qRT-PCR verification, which were mainly related to ion homeostasis, glucose metabolism and lipid metabolism. The results showed that the expression patterns of these genes were similar to the high-throughput data. Compared with the control group, high salinity caused obvious injury to gill tissue, mainly manifested as contraction and relaxation of gill filament, cavity vacuolation and severe epithelial disintegration. Glucose-metabolism-related enzyme activities (e.g., pyruvate kinase, hexokinase, 6-phosphate fructose kinase) and related-gene expression (e.g., hexokinase, pyruvate kinase, 6-phosphate fructose kinase) in the gills were significantly higher at a salinity of 14‱. This study showed that salinity stress activated ion transport channels and promoted an up-regulated level of glucose metabolism. High salinity levels caused damage to the gill tissue of M. nipponense. Overall, these results improved our understanding of the salt tolerance mechanism of M. nipponense.

Clinical correlates and thyroid hormones of metabolic syndrome in first-episode and drug-naïve major depressive disorder outpatients with and without hyperglycemia: a comprehensive cross-sectional study

Hyperglycemia and metabolic syndrome (MetS) are common in patients with major depressive disorder (MDD). This study aimed to explore the prevalence and clinical factors of MetS in first-episode and drug-naïve MDD (FEDND) patients with and without hyperglycemia. A total of 1,718 FEDND patients’ symptoms were assessed using the Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and positive subscale of the Positive and Negative Syndrome Scale (PANSS). Blood glucose levels, metabolic index, and thyroid hormones were measured during fasting. The prevalence of MetS in FEDND patients with hyperglycemia was 35.67 times higher than in FEDND patients without hyperglycemia. FEDND patients with MetS were older, had later age of onset, and were predominantly married than those without MetS (p < 0.05). Among FEDND patients without hyperglycemia, suicide attempts, severe anxiety, HAMD, HAMA, PANSS subscale scores, thyroid stimulating hormone, antithyroglobulin, and total cholesterol levels were all higher in patients with MetS than those without MetS (all p < 0.05). In FEDND patients without hyperglycemia, the combination of age and TgAb distinguished those patients with and without MetS. Our results suggest a high prevalence of MetS in FEDND patients with hyperglycemia. Several clinical variables and thyroid function-related hormones impact MetS in patients with FEDND.

Denosumab Improves Glycaemic Parameters in Postmenopausal Osteoporosis Patients with Combined Type 2 Diabetes Mellitus.

This study aimed to determine whether RANKL inhibitors in postmenopausal osteoporosis patients with combined type 2 diabetes mellitus (T2DM) could improve their glucose metabolism index. First of all, 84 patients affected with postmenopausal osteoporosis with combined T2DM attending the Department of Endocrinology at the Third Hospital of Hebei Medical University were selected and randomized into two groups of 42 patients each. One group was given Denosumab 60 mg once every six months (denosumab group, D.G.), and the other group was given 2 mg ibandronate once every three months (ibandronate group, I.G.). Blood glucose parameters were compared before and after treatment in both groups and serum active GLP-1 levels and DPP-4 levels were also assessed. After treatment, there was no significant difference in fasting glucose between the two groups, but there was a significant decrease in fasting glucose in the Denosumab Group (D.G.) compared to before treatment. There was a significant difference in 2-hour postprandial glucose (2hPG) between the two groups after treatment, with the D.G. being lower than the ibandronate group (I.G.). Glycosylated haemoglobin (HbA1c) was lower in the D.G. than in the I.G. after treatment, but the difference between them was insignificant. In the D.G., serum active GLP-1 levels increased after treatment, and serum DPP-4 levels decreased. Serum GLP-1 and DPP-4 levels in the I.G. did not change compared with those before treatment. In conclusion, In the clinical management of postmenopausal osteoporosis patients with combined T2DM, the choice of RANKL inhibitors as anti-osteoporosis therapy may benefit their glycaemic parameters by elevating serum active GLP-1 levels and decreasing serum DPP-4 levels.

Former long-term use of combined hormonal contraception and glucose metabolism disorders in perimenopausal women: A prospective, population-based cohort study.

Current use of combined hormonal contraceptives worsens glucose tolerance and increases the risk of type 2 diabetes mellitus at late fertile age, but the impact of their former use on the risk of glucose metabolism disorders is still controversial. This was a prospective, longitudinal birth cohort study with long-term follow-up consisting of 5889 women. The cohort population has been followed at birth, and at ages of 1, 14, 31 and 46. In total, 3280 (55.7%) women were clinically examined and 2780 also underwent a 2-h oral glucose tolerance test at age 46. Glucose metabolism indices were analyzed in former combined hormonal contraceptive users (n = 1371) and former progestin-only contraceptive users (n = 52) and in women with no history of hormonal contraceptive use (n = 253). Compared with women with no history of hormonal contraceptive use, those who formerly used combined hormonal contraceptives for over 10 years had an increased risk of prediabetes (odds ratio [OR] 3.9, 95% confidence interval [CI]: 1.6-9.2) but not of type 2 diabetes mellitus. Former progestin-only contraceptive use was not associated with any glucose metabolism disorders. The results persisted after adjusting for socioeconomic status, smoking, alcohol consumption, parity, body mass index and use of cholesterol-lowering medication. Former long-term use of combined hormonal contraceptives was associated with a significantly increased risk of prediabetes in perimenopausal women, which potentially indicates a need of screening for glucose metabolism disorders in these women.

Glucose Metabolism Indices and the Development of Chronic Kidney Disease: A Cohort Study of Middle-Aged and Elderly Chinese Persons.

Chronic kidney disease (CKD) has become a major global health issue, and abnormalities of glucose metabolism are a risk factor responsible for development of CKD. We aimed to investigate associations between glucose metabolism indices and CKD in a Chinese population and determine which index is superior for predicting incident CKD. We performed a community-based population on 5232 subjects aged ≥40 years without baseline CKD. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g. We examined the associations of glucose metabolism indices, including fasting plasma glucose (FPG), 2-hour (2 h) oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-β and the development of CKD. With an average follow-up of 3.6 years, 6.4% of the subjects developed CKD. Pearson's correlation analysis revealed that FPG, HbA1c, fasting insulin, and HOMA-IR were all significantly correlated with UACR and eGFR. The association persisted in multivariate linear regression analysis adjusted for age and sex. Compared with other glucose indices, HOMA-IR exhibited the strongest associations with CKD in COX multivariate regression analysis (HR = 1.17, 95% CI: 1.04-1.31). HOMA-IR is superior to other routine indices of glucose metabolism for predicting the development of CKD in middle-aged Chinese persons. Screening with HOMA-IR may help prevent the development of CKD in the general population.