Sodium butyrate improves cognitive dysfunction in high-fat diet/ streptozotocin-induced type 2 diabetic mice by ameliorating hippocampal mitochondrial damage through regulating AMPK/PGC-1α pathway.

Cognitive dysfunction is an important comorbidity of type 2 diabetes mellitus (T2DM). Sodium butyrate (NaB) is a short-chain fatty acid and has an effect improving T2DM-associated cognitive dysfunction. Using a high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM mouse model, the present study investigated the mechanism involved in the beneficial effect of butyrate on diabetic cognitive dysfunction, with a focus on ameliorating mitochondrial damage through regulating the adenosine monophosphate-activated protein kinase/peroxisome proliferator-activated receptor gamma coactivator 1α (AMPK/PGC-1α) pathway considering the important role of mitochondrial impairments in the occurrence of T2DM-associated cognitive dysfunction. We found, based on reconfirmation of the improvement of NaB on cognitive impairment, that NaB treatment improved damaged synaptic structural plasticity including the decrease in dendritic spine density and downregulation in the expression of postsynaptic density protein 95 and synaptophysin in the hippocampus in the model mice. NaB treatment also ameliorated mitochondrial ultrastructural damage, increased mitochondrial membrane potential and adenosine 5'-triphosphate content, and improved mitochondrial biogenesis and dynamics in the model mice. Furthermore, the expression of phosphorylated AMPK and PGC-1α was upregulated after NaB treatment in the model mice. In particular, the above beneficial effects of NaB were blocked by the inhibition of either AMPK or PGC-1α. In conclusion, NaB treatment improved cognitive impairment and damaged synaptic structural plasticity in the hippocampus by ameliorating damage to mitochondrial morphology and function through regulating the AMPK/PGC-1α pathway in HFD/STZ-induced T2DM mice.

Relation between serum sclerostin and CTRP3 levels and bone mineral density in diabetic postmenopausal women.

BACKGROUND: Osteoporosis (OP) is a common finding in diabetic patients especially high-risk populations such as postmenopausal women. Sclerostin is a glycoprotein chiefly secreted by mature osteocytes and is considered a main regulator of bone formation. The C1q/TNF-Related Protein 3 (CTRP3) was found to be significantly associated with OP in postmenopausal women. The effect of type 2 diabetes mellitus (T2DM) on sclerostin and CTRP3 levels in postmenopausal women is rarely investigated. The present study aimed to assess the impact of T2DM on sclerostin and CTRP3 levels and their relation to OP in postmenopausal women. METHODS: The study included 60 postmenopausal women with T2DM and 60 age-matched postmenopausal non-diabetic women. Bone mineral density (BMD) was assessed using dual energy X-ray absorptiometry (DEXA). Serum levels of sclerostin and CTRP3 were assessed using enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: Diabetic group expressed significantly higher serum levels of sclerostin when compared with non-diabetic group (110.0 ± 29.0 versus 51.5 ± 23.2 ng; p < 0.001). Oppositely, CTRP3 were significantly lower in the diabetic group (3.5 ± 3.5 versus 9.9 ± 3.7 ng/ml, p < 0.001). Multivariate logistic regression analysis identified HbA1c levels [OR (95% CI): 0.49 (0.26-0.93), p = 0.028], sclerotin levels [OR (95% CI): 1.06 (1.0-1.012), p = 0.041] and CTRP3 levels [OR (95%) CI: 1.64 (1.0-2.68), p = 0.047] as significant predictors of OP in diabetic patients. CONCLUSIONS: Sclerostin and CTRP3 levels are involved in OP in postmenopausal diabetic patients.

Simultaneous detection of multiple urinary biomarkers in patients with early-stage diabetic kidney disease using Luminex liquid suspension chip technology.

Background: Several urinary biomarkers have good diagnostic value for diabetic kidney disease (DKD); however, the predictive value is limited with the use of single biomarkers. We investigated the clinical value of Luminex liquid suspension chip detection of several urinary biomarkers simultaneously. Methods: The study included 737 patients: 585 with diabetes mellitus (DM) and 152 with DKD. Propensity score matching (PSM) of demographic and medical characteristics identified a subset of 78 patients (DM = 39, DKD = 39). Two Luminex liquid suspension chips were used to detect 11 urinary biomarkers according to their molecular weight and concentration. The biomarkers, including cystatin C (CysC), nephrin, epidermal growth factor (EGF), kidney injury molecule-1 (KIM-1), retinol-binding protein4 (RBP4), α1-microglobulin (α1-MG), ß2-microglobulin (ß2-MG), vitamin D binding protein (VDBP), tissue inhibitor of metalloproteinases-1 (TIMP-1), tumor necrosis factor receptor-1 (TNFR-1), and tumor necrosis factor receptor-2 (TNFR-2) were compared in the DM and DKD groups. The diagnostic values of single biomarkers and various biomarker combinations for early diagnosis of DKD were assessed using receiver operating characteristic (ROC) curve analysis. Results: Urinary levels of VDBP, RBP4, and KIM-1 were markedly higher in the DKD group than in the DM group (p < 0.05), whereas the TIMP-1, TNFR-1, TNFR-2, α1-MG, ß2-MG, CysC, nephrin, and EGF levels were not significantly different between the groups. RBP4, KIM-1, TNFR-2, and VDBP reached p < 0.01 in univariate analysis and were entered into the final analysis. VDBP had the highest AUC (0.780, p < 0.01), followed by RBP4 (0.711, p < 0.01), KIM-1 (0.640, p = 0.044), and TNFR-2 (0.615, p = 0.081). However, a combination of these four urinary biomarkers had the highest AUC (0.812), with a sensitivity of 0.742 and a specificity of 0.760. Conclusions: The urinary levels of VDBP, RBP4, KIM-1, and TNFR-2 can be detected simultaneously using Luminex liquid suspension chip technology. The combination of these biomarkers, which reflect different mechanisms of kidney damage, had the highest diagnostic value for DKD. However, this finding should be explored further to understand the synergistic effects of these biomarkers.

Glycated albumin may have a complementary role to glycated hemoglobin in glucose monitoring in childhood acute leukemia.

PURPOSE: Glycated hemoglobin (HbA1c) as a glycemic index may have limited value in pediatric patients with acute leukemia as they often present with anemia and/or pancytopenia. To address this issue, we evaluated the usefulness of glycated albumin (GA) as a glycemic monitoring index in pediatric patients with acute leukemia. METHODS: Medical records of 25 patients with type 2 diabetes mellitus (T2DM), 63 patients with acute leukemia, and 115 healthy children from Seoul St. Mary's Hospital, The Catholic University of Korea, were retrospectively investigated for serum GA, HbA1c, and fasting blood glucose (FBG) levels, along with demographic data. RESULTS: GA, HbA1c, and FBG levels did not differ between the control and acute leukemia groups. In the T2DM group, positive correlations were observed among GA, HbA1c, and FBG (P<0.01). Although GA level was not associated with the HbA1c level in the control group, GA and HbA1c levels showed a positive correlation in the acute leukemia group (P=0.045). Regression analysis revealed GA and HbA1c levels to be positively correlated in the acute leukemia and T2DM groups even after adjusting for age, sex, and body mass index z-score (P=0.007, P<0.01). CONCLUSION: GA may be a useful complementary parameter to HbA1c for glycemic monitoring in pediatric patients with acute leukemia, similar to its use in patients with T2DM.

Correlation between retinal vascular geometric parameters and pathologically diagnosed type 2 diabetic nephropathy.

Background: Diabetic nephropathy (DN) and diabetic retinopathy (DR) are common microvascular complications of diabetes. The purpose of this study was to investigate the correlation between retinal vascular geometric parameters and pathologically diagnosed type 2 DN and to determine the capacity of retinal vascular geometric parameters in differentiating DN from non-diabetic renal disease (NDRD). Methods: The study participants were adult patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease who underwent a renal biopsy. Univariate and multivariable regression analyses were performed to evaluate associations between retinal vessel geometry parameters and pathologically diagnosed DN. Multivariate binary logistic regression analyses were performed to establish a differential diagnostic model for DN. Results: In total, 403 patients were examined in this cross-sectional study, including 152 (37.7%) with DN, 157 (39.0%) with NDRD and 94 (23.3%) with DN combined with NDRD. After univariate logistic regression, total vessel fractal dimension, arteriolar fractal dimension and venular fractal dimension were all found to be associated with DN. In multivariate analyses adjusting for age, sex, blood pressure, diabetes, DR and other factors, smaller retinal vascular fractal dimensions were significantly associated with DN (P < .05). We developed a differential diagnostic model for DN combining traditional clinical indicators and retinal vascular geometric parameters. The area under the curve of the model established by multivariate logistic regression was 0.930. Conclusions: Retinal vessel fractal dimension is of great significance for the rapid and non-invasive differentiation of DN. Incorporating retinal vessel fractal dimension into the diagnostic model for DN and NDRD can improve the diagnostic efficiency.

Serum tumor markers: Can they clinically implicate in type 2 diabetes mellitus?

"Serum tumor markers expression (CA19-9, CA242, and CEA) and its clinical implications in type 2 diabetes mellitus" authored by Meng and Shi presents an observational case-control study investigating the correlation between tumor markers and type 2 diabetes mellitus (T2DM). The study explores the diagnostic accuracy of tumor markers, particularly cancer antigen 19-9 (CA19-9), CA242, and carcinoembryonic antigen, in poorly controlled T2DM patients with hemoglobin A1c levels exceeding 9%, employing receiver operating characteristic curve analysis. Though study offers valuable insights into the potential utility of tumor markers in clinical practice, caution is advised regarding routine tumor marker testing due to challenges such as limited availability and cost. Additionally, the study overlooks potential confounding factors like smoking and alcohol consumption. Variations in CA19-9 and CA242 expression underscore the complex interplay between tumor markers and systemic diseases, warranting further investigation into their diagnostic and prognostic implications. While Meng and Shi represent a significant contribution to the field, more extensive research is needed to fully elucidate the role of tumor markers in diabetes management and beyond.

Remission of type 2 diabetes mellitus.

The surge in type 2 diabetes mellitus (T2DM) is tightly linked to obesity, leading to ectopic fat accumulation in internal organs. Weight management has become a cornerstone of T2DM treatment, with evidence suggesting that significant weight loss can induce remission. Remission, defined as sustained hemoglobin (HbA1c) below 6.5% for at least 3 months without medication, can be achieved through various approaches, including lifestyle, medical, and surgical interventions. Metabolic bariatric surgery offers significant remission rates, particularly for patients with severe obesity. Intensive lifestyle modifications, including low-calorie diets and exercise, have also demonstrated significant potential. Medications like incretin-based agents show robust results in improving beta-cell function, achieving glycemic control, and promoting weight loss. While complete remission without medication may not be attainable for everyone, especially those with severe insulin resistance or deficiency, early and aggressive glycemic control remains a crucial strategy. Maintaining HbA1c below 6.5% from the time of diagnosis reduces the risk of long-term complications and mortality. Moreover, considering a broader definition of remission, encompassing individuals with sustained control on medication, could offer a more comprehensive and inclusive approach to managing this chronic disease.

Charting Wellness in India: Piloting the iTHRIVE's Functional Nutrition Approach to Improve Glycaemic and Inflammatory Parameters in Prediabetes and Type 2 Diabetes Mellitus.

Introduction Type 2 diabetes mellitus (T2DM) is characterized by elevation of blood glucose levels due to underlying insulin resistance and inflammation. Multiple modifiable risk factors such as unhealthy dietary habits, physical inactivity, obesity, smoking and psychological stress contribute to T2DM. We investigated the efficacy of a comprehensive functional nutrition approach aimed at mitigating T2DM using the iTHRIVE approach which encompassed anti-inflammatory and elimination diets, micronutrient supplements, physical activity, stress management and environmental modifications through a pre-post study design. The research assessed changes in blood glucose and inflammatory markers following the implementation of the functional nutrition program. Methods A prospective pre-post intervention pilot study was conducted at ThriveTribe Wellness Solutions Pvt Ltd. (iTHRIVE), where 50 study participants from urban areas of Pune city, India (n=25 each group) were recruited voluntarily in the age group of 20-60 years. The participants were subjected to 90 days of the iTHRIVE functional nutrition approach which consisted of eliminating certain inflammatory foods and adding a combination of nutritious organic foods, adding dietary supplements like magnesium, vitamin D, alpha lipoic acid, chromium picolinate, berberine and biogymnema, physical activities like resistance training, stress reduction techniques like meditation and deep breathing exercises along with environmental changes. The blood parameters like fasting blood glucose, postprandial blood glucose, glycated haemoglobin (HbA1C), fasting serum insulin, post-prandial serum insulin, high sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), vitamin D, body weight and waist circumference were measured before and after the intervention. The changes were statistically analyzed using a paired t-test. Results The mean age of the participants was found to be 43.76±10.58 years. Around 68% of the participants were prediabetic (HbA1c: 5.7-6.4%) and 32% had T2DM (HbA1c ≥6.5%). A significant reduction was observed in the average HbA1c (13.75% reduction, p<0.0001), average post-prandial blood glucose levels (14.51% reduction, p<0.048), average post-prandial serum insulin (34.31% reduction, p<0.017) and average ESR levels (34.51% reduction, p<0.006). The hs-CRP levels were reduced by 6.6%, but not statistically significant. The average body weight of the participants dropped from 78.59±15.18 kg to 75.20±14.20 kg with a mean loss of 2.91 kg (p<0.05) whereas the waist circumference decreased from 37.54±5.09 to 35.97±4.74 inches with an average loss of 1.19 inches (p<0.0004). Conclusions Following the intervention, several health indicators indicated significant improvements. Particularly, there was a significant drop in HbA1c levels, suggesting better long-term blood glucose control. Blood glucose and serum insulin levels after a meal dropped significantly, indicating enhanced insulin sensitivity. There was a decrease in systemic inflammation as evidenced by the decrease in ESR levels. These results imply that the iTHRIVE functional nutrition approach used in this investigation might be beneficial for enhancing glycemic control and insulin sensitivity, along with reducing inflammatory markers in people with prediabetes and T2DM. Larger sample sizes and longer periods of monitoring would be useful in subsequent research to validate and build on these encouraging findings.

Association Between Visceral Obesity and Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Retrospective Study.

Purpose: To investigate the association between visceral obesity and glycemic control in patients with type 2 diabetes mellitus. Patients and Methods: A retrospective analysis involved 714 patients diagnosed with type 2 diabetes mellitus from the National Metabolic Management Center from November 2021 to February 2024. Medical data included sociodemographic data, lifestyle behaviors, and anthropometric and biochemical measurements. Multivariate logistic regression analysis was used to analyze their associations. Results: Among the patients, 251 (35.2%) achieved good glycemic control (HbA1c < 7.0%). On univariate analysis, higher diastolic blood pressure, longer duration of type 2 diabetes mellitus, tobacco smoking, alcohol drinking, insulin treatment, higher levels of fasting plasma glucose, homeostasis model assessment of insulin resistance, triglyceride, total cholesterol, and low-density lipoprotein cholesterol, visceral obesity (visceral fat area ≥ 100cm2) and diabetic peripheral neuropathy were all positively correlated with poor glycemic control; female, older age, higher levels of C peptide and serum uric acid were inversely associated with poor glycemic control (all P < 0.05). On multivariate logistic regression analysis, the results suggested that higher diastolic blood pressure [OR: 1.021, 95% CI (1.002, 1.040), P = 0.030], insulin treatment [currently used: OR = 2.156, 95% CI (1.249, 3.724), P = 0.006], higher level of fasting plasma glucose [OR: 1.819, 95% CI (1.598, 2.069), P < 0.001], and visceral obesity [OR: 1.876, 95% CI (1.158, 3.038), P = 0.011] were risk factors for poor glycemic control. Conclusion: This study indicated that visceral obesity (visceral fat area ≥ 100cm2) is positively associated with poor glycemic control, and serves as an independent risk factor for poor glycemic control (HbA1c ≥ 7.0%) in patients with type 2 diabetes mellitus. Screening for visceral obesity should be emphasized, and targeted interventions should be taken to improve glycemic control in patients with type 2 diabetes mellitus.

The effect of Andaliman (Zanthoxylum acanthopodium DC.) fruit extracted with ethanol on TNF-α and TRPA-1 levels in type II diabetes-induced mice.

Objective: The present study investigated the effects of Andaliman fruit extract on tumor necrosis factor-alpha (TNF-α) and transient receptor potential ankyrin-1 (TRPA-1) levels in type 2 diabetes mellitus (T2DM) mouse models induced with streptozocin (STZ) and a high-fat diet (HFD). Materials and Methods: In this research, mice were allocated into six distinct groups: normal, negative control (HFD and STZ), positive control (metformin, HFD, and STZ), and three treatment groups (HFD, STZ, and Andaliman extract at varying dosages of 100, 300, and 500 mg/kg, respectively). Body weight and blood glucose levels (BGLs) were recorded at weeks 1 (baseline), 8, 12, and 16. The levels of TNF-α and TRPA-1 were measured during the 16th week. Results: Phytochemical screening of the Andaliman extract revealed the presence of flavonoids, alkaloids, tannins, saponins, and glycosides. The one-way ANOVA revealed significantly elevated BGL at week 16 in the negative control group in comparison to the other groups (p < 0.05). The Kruskal-Wallis test followed by Bonferroni-corrected pairwise comparisons showed that the negative control had significantly higher TNF-α levels than the Andaliman-groups (z = 22.11, p < 0.01). TRPA-1 was significantly higher in the negative control group compared to the treatment groups (p < 0.05). Furthermore, Spearman's rho analysis revealed a statistically significant positive association between BGL and both TNF-α and TRPA-1, as well as between TNF-α and TRPA. Conclusion: Andaliman extract potentially serves as a therapy for diabetic neuropathy in T2DM by lowering BGL and inhibiting the expression of TNF-α and TRPA-1.

"The effects of non-surgical periodontal treatment plus zinc and magnesium supplementation on oxidative stress and antioxidants enzymes in type 2 diabetes patients: a quasi-experimental study".

BACKGROUND: Periodontal Disease (PD) associated with Type 2 Diabetes Mellitus (T2DM) is a chronic condition that affects the oral cavity of people living with T2DM. The mechanisms of the interaction between type 2 Diabetes Mellitus and Periodontal diseases are complex and involve multiple pathophysiological pathways related to the systemic inflammatory process and oxidative stress. Non-surgical periodontal treatment (NSTP) is considered the standard for the management of this disease; however, patients with systemic conditions such as type 2 Diabetes Mellitus do not seem to respond adequately. For this reason, the use of complementary treatments has been suggested to support non-surgical periodontal treatment to reduce the clinical consequences of the disease and improve the systemic conditions of the patient. The use of zinc gluconate and magnesium oxide as an adjunct to non-surgical periodontal treatment and its effects on periodontal clinical features and oxidative stress in patients with Periodontal diseases -type 2 Diabetes Mellitus is poorly understood. METHODS: A quasi-experimental study was performed in patients with periodontal diseases associated with T2DM. Initially, 45 subjects who met the selection criteria were included. 19 were assigned to a control group [non-surgical periodontal treatment] and 20 to the experimental group (non-surgical periodontal treatment + 500 mg of magnesium oxide and 50 mg of zinc gluconate for oral supplementation for 30 days) and the data of 6 patients were eliminated. Sociodemographic characteristics, physiological factors, biochemical parameters, and clinical features of periodontal diseases were assessed. RESULTS: In this research a change in periodontal clinical characteristics was observed, which has been associated with disease remission. Additionally, a shift in MDA levels was presented for both groups. Furthermore, the supplementation group showed an increase in antioxidant enzymes when compared to the group that only received NSPT. CONCLUSION: The use of Zinc gluconate and magnesium oxide can serve as a complementary treatment to non-surgical periodontal treatment, that supports the remission of PD as a result of regulation-reduction of oxidative biomarkers and increase in antioxidant enzymes activity. TRIAL REGISTRATION: https://www.isrctn.com ISRCTN 14,092,381. September 13º 2023. Retrospective Registration.

Pharmacokinetic/Pharmacodynamic modelling of Saxagliptin and its active metabolite, 5-hydroxy Saxagliptin in rats with Type 2 Diabetes Mellitus.

BACKGROUND AND PURPOSES: It is unclear whether the parent Saxagliptin (SAX) in vivo is the same as that in vitro, which is twice that of 5-hydroxy Saxagliptin (5-OH SAX). This study is to construct a Pharmacokinetic-Pharmacodynamic (PK-PD) link model to evaluate the genuine relationship between the concentration of parent SAX in vivo and the effect. METHODS: First, we established a reliable Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS/MS) method and DPP-4 inhibition ratio determination method. Then, the T2DM rats were randomly divided into four groups, intravenous injection of 5-OH SAX (0.5 mg/kg) and saline group, intragastric administration of SAX (10 mg/kg) and Sodium carboxymethyl cellulose (CMC-Na) group. Plasma samples were collected at different time points for subsequent testing. Finally, we used the measured concentrations and inhibition ratios to construct a PK-PD link model for 5-OH SAX and parent SAX. RESULTS: A two-compartment with additive model showed the pharmacokinetic process of SAX and 5-OH SAX, the concentration-effect relationship was represented by a sigmoidal Emax model and sigmoidal Emax with E0 model for SAX and 5-OH SAX, respectively. Fitting parameters showed SAX was rapidly absorbed after administration (Tmax=0.11 h, t1/2, ka=0.07 h), widely distributed in the body (V ≈ 20 L/kg), plasma exposure reached 3282.06 ng*h/mL, and the elimination half-life was 6.13 h. The maximum plasma dipeptidyl peptidase IV (DPP-4) inhibition ratio of parent SAX was 71.47%. According to the final fitting parameter EC50, EC50, 5-OH SAX=0.46EC50, SAX(parent), it was believed that the inhibitory effect of 5-OH SAX was about half of the parent SAX, which is consistent with the literature. CONCLUSIONS: The PK-PD link model of the parent SAX established in this study can predict its pharmacokinetic process in T2DM rats and the strength of the inhibitory effect of DPP-4 based on non-clinical data.

Remnant cholesterol and the risk of diabetic nephropathy progression to end-stage kidney disease in patients with type 2 diabetes mellitus: a longitudinal cohort study.

AIM: Diabetic nephropathy (DN) is the most common cause of end-stage kidney disease (ESKD). Remnant cholesterol has been investigated as a predictor for the progression of DN in type 1 diabetes mellitus patients, as well as the incidence of DN in type 2 diabetes mellitus (T2DM) patients. This study aimed to evaluate the longitudinal relationship between baseline remnant cholesterol and kidney outcomes using a Chinese T2DM with biopsy-confirmed DN cohort. METHODS: We included 334 patients with T2DM and biopsy-confirmed DN during 2010-2019 West China Hospital T2DM-DN cohort. Remnant cholesterol was defined by Martin-Hopkins equation. Patients were divided into four groups based on the median (IQR) remnant cholesterol concentration at the time of renal biopsy. The kidney outcome was defined as ESKD, which was defined as the need for chronic kidney replacement therapy or estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2. The relationship between remnant cholesterol and kidney outcome was analyzed using the Kaplan‒Meier method and Cox regression analysis. RESULTS: The mean age was 51.1 years, and 235 (70%) were men. During follow-up, a total of 121 (36.2%) patients reached ESKD. The Kaplan‒Meier analysis showed that patients in the highest quartile (quartile 4) group had lower cumulative renal survival (log-rank test, p = 0.033) and shorter median renal survival time [34.0 (26.4-41.6) vs. 55.0 (29.8-80.2) months] than patients in the lowest quartile (quartile 1) group. By univariate analysis, the high remnant cholesterol group was associated with a higher risk of progression to ESKD. Moreover, the risk of progression to ESKD in the highest quartile was still 2.857-fold (95% CI 1.305-6.257, p = 0.009) higher than that in the lowest quartile, and one-SD increase of remnant cholesterol was associated with a higher risk (HR = 1.424; 95% CI 1.075-1.886, p = 0.014) of progression to ESKD, after adjusted for confounding factors. CONCLUSIONS: High remnant cholesterol is independently associated with a higher risk of ESKD in patients with T2DM-DN, and it may be a new noninvasive marker of ESKD. CLINICAL RELEVANCE: Calculated remnant cholesterol has the advantages of being economical and clinically accessible. Moreover, to our knowledge, there are no longitudinal cohort studies for investigating the risk of progression of T2DM-DN to ESKD. In our study, higher remnant cholesterol was associated with a higher risk of ESKD in patients with T2DM-DN, and it may be a new noninvasive predictor of ESKD.

Effect of Gegen Qinlian Decoction combined with dietary management on patients with damp-heat Type-2 diabetes mellitus and metabolic syndrome.

Objective: To explore the effect of Gegen Qinlian Decoction (GQD) combined with dietary management in the treatment of patients with Type-2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) (T2DM MetS). Methods: This is a retrospective analysis of 102 cases of T2DM in the Brain Hospital of Hunan Province, China from April 2020 to February 2023. Of them, 49 patients received conventional drug treatment (control group), and 53 patients received GQD combined with dietary management on the basis of conventional drugs (observation group). Treatment efficacy was calculated, and blood glucose levels before and after the treatment, blood lipid-related indicators, tumor necrosis factor-α (TNF-α) and adiponectin (ADP) levels, and incidence of adverse reactions were compared between the two groups. Results: The total efficacy of the observation group (92.45%) was significantly higher than that of the control group (75.51%) (P<0.05). After the treatment, blood glucose and lipid indicators in both groups were significantly improved compared to pretreatment levels, and were significantly better in the observation group than in the control group (P<0.05). After the treatment, TNF-α levels in both groups decreased compared to before the treatment, and were significantly lower in the observation group compared to the control group. Levels of ADP after the treatment increased, and were significantly higher in the observation group compared to the control group (P<0.05). Conclusions: When taken as an adjunct to the conventional drug regimen, GQD combined with dietary management can effectively regulate blood glucose and lipid metabolism in patients with T2DM and MetS (T2DM MetS), improve TNF-α and ADP levels, and enhance disease treatment effectiveness.

Development and validation of a nomogram for screening patients with type 2 diabetic ketoacidosis.

OBJECTIVE AND BACKGROUND: The early detection of diabetic ketoacidosis (DKA) in patients with type 2 diabetes (T2D) plays a crucial role in enhancing outcomes. We developed a nomogram prediction model for screening DKA in T2D patients. At the same time, the input variables were adjusted to reduce misdiagnosis. METHODS: We obtained data on T2D patients from Mimic-IV V0.4 and Mimic-III V1.4 databases. A nomogram model was developed using the training data set, internally validated, subjected to sensitivity analysis, and further externally validated with data from T2D patients in Aviation General Hospital. RESULTS: Based on the established model, we analyzed 1885 type 2 diabetes patients, among whom 614 with DKA. We further additionally identified risk factors for DKA based on literature reports and multivariate analysis. We identified age, glucose, chloride, calcium, and urea nitrogen as predictors in our model. The logistic regression model demonstrated an area under the curve (AUC) of 0.86 (95%CI: 0.85-0.90]. To validate the model, we collected data from 91 T2D patients, including 15 with DKA, at our hospital. The external validation of the model yielded an AUC of 0.68 (95%CI: 0.67-0.70). The calibration plot confirmed that our model was adequate for predicting patients with DKA. The decision-curve analysis revealed that our model offered net benefits for clinical use. CONCLUSIONS: Our model offers a convenient and accurate tool for predicting whether DKA is present. Excluding input variables that may potentially hinder patient compliance increases the practical application significance of our model.

A sensitive fluorescence assay of serum dipeptidyl peptidase IV activity to predict the suitability of its inhibitors in patients with type 2 diabetes mellitus.

DPP-IV inhibitors, which are close to the natural hypoglycemic pathway of human physiology and have few side effects, have been extensively employed in the management of type 2 diabetes mellitus (T2DM). However, there are currently no specific blood indicators that can indicate or predict a patient's suitability for DPP-IV inhibitors. In this study, based on the self-developed high-specificity fluorescent substrate glycyl-prolyl-N-butyl-4-amino-1, 8-naphthimide (GP-BAN), a detection method of human serum DPP-IV activity was established and optimized. The method demonstrates a favorable lower limit of detection (LOD) at 0.32 ng/mL and a satisfactory lower limit of quantification (LOQ) of 1.12 ng/mL, and can be used for the detection of DPP-IV activity in trace serum (2 µL). In addition, Vitalliptin and Sitagliptin showed similar IC50 values when human recombinant DPP-IV and human serum were used as enzyme sources, and the intra-day and inter-day precision obtained by the microplate analyzer were less than 15 %. These results indicate that the microplate reader based detection technique has good accuracy, repeatability and reproducibility. A total of 700 volunteers were recruited, and 646 serum samples were tested for DPP-IV activity. The results showed that serum DPP-IV activity was higher in patients with T2DM than in controls (P < 0.01). However, the statistical data of family history of diabetes, gender and age of diabetic patients showed no statistical significance, and there was no contrast difference. The DPP-IV activity of serum in T2DM patients ranged from 2.4 µmol/min/L to 78.6 µmol/min/L, with a huge difference of up to 32-fold. These results suggest that it is necessary to test DPP-IV activity in patients with T2DM when taking DPP-IV inhibitors to determine the applicability of DPP-IV inhibitors in T2DM patients. These results suggest that it is necessary to detect the activity of DPP-IV in blood before taking DPP-IV inhibitors in patients with T2DM to judge the applicability of DPP-IV inhibitors in patients with T2DM.

One-step non-invasive diagnosis of metabolic dysfunction-associated steatohepatitis and fibrosis in high-risk population.

BACKGROUND AND AIM: Type 2 Diabetes mellitus (T2DM), age, and obesity are risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to assess the performance of non-invasive tests (NITs) for the diagnosis of metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis in high-risk subjects. METHODS: Multicentre cross-sectional study that included 124 biopsy-proven MASLD in more than 50 years-old patients with overweight/obesity and T2DM. Vibration-controlled transient elastography, Fibrosis-4 index (FIB-4), Non-alcoholic fatty liver disease fibrosis score (NFS), OWLiver Panel (OWLiver DM2 + Metabolomics-Advanced Steatohepatitis Fibrosis Score -MASEF) and FibroScan-AST were performed. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and area under the receiver operating characteristic curve (AUC) were calculated. NITs were assessed individually and in sequential/parallel combinations. RESULTS: 35 (28.2%) patients had early MASH and 66 (53.2%) had MASH with significant fibrosis (at-risk MASH). The OWLiver Panel correctly classified 86.1% as MASH, showing an accuracy, sensitivity, specificity, PPV, and NPV of 0.77, 0.86, 0.35, 0.85, and 0.36, respectively. Class III obesity, diabetes control, or gender did not impact on the performance of the OWLiver Panel (p > 0.1). NITs for at-risk MASH showed an AUC > 0.70 except for NFS. MASEF showed the highest accuracy and NPV for at-risk MASH (AUC 0.77 [0.68-0.85], NPV 72%) and advanced fibrosis (AUC 0.80 [0.71-0.88], NPV 92%). Combinations of NITs for the identification of at-risk MASH did not provide any additional benefit over using MASEF alone. CONCLUSION: One-step screening strategy with the OWLiver Panel has high accuracy to detect MASH and at-risk MASH in high-risk subjects for MASLD.

Electronic Glycemic Management System Improved Glycemic Control and Reduced Complications in Patients With Diabetes Undergoing Coronary Artery Bypass Surgery: A Randomized Controlled Trial.

BACKGROUND: In-hospital hyperglycemia poses significant risks for patients with diabetes mellitus undergoing coronary artery bypass graft (CABG) surgery. Electronic glycemic management systems (eGMSs) like InsulinAPP offer promise in standardizing and improving glycemic control (GC) in these settings. This study evaluated the efficacy of the InsulinAPP protocol in optimizing GC and reducing adverse outcomes post-CABG. METHODS: This prospective, randomized, open-label study was conducted with 100 adult type 2 diabetes mellitus (T2DM) patients post-CABG surgery, who were randomized into two groups: conventional care (gCONV) and eGMS protocol (gAPP). The gAPP used InsulinAPP for insulin therapy management, whereas the gCONV received standard clinical care. The primary outcome was a composite of hospital-acquired infections, renal function deterioration, and symptomatic atrial arrhythmia. Secondary outcomes included GC, hypoglycemia incidence, hospital stay length, and costs. RESULTS: The gAPP achieved lower mean glucose levels (167.2 ± 42.5 mg/dL vs 188.7 ± 54.4 mg/dL; P = .040) and fewer patients-day with BG above 180 mg/dL (51.3% vs 74.8%, P = .011). The gAPP received an insulin regimen that included more prandial bolus and correction insulin (either bolus-correction or basal-bolus regimens) than the gCONV (90.3% vs 16.7%). The primary composite outcome occurred in 16% of gAPP patients compared with 58% in gCONV (P < .010). Hypoglycemia incidence was lower in the gAPP (4% vs 16%, P = .046). The gAPP protocol also resulted in shorter hospital stays and reduced costs. CONCLUSIONS: The InsulinAPP protocol effectively optimizes GC and reduces adverse outcomes in T2DM patients' post-CABG surgery, offering a cost-effective solution for inpatient diabetes management.

Polyphenols in foods: a potential strategy for preventing and managing the postprandial hyperglycemic response.

Type 2 diabetes mellitus (T2DM) is a significant health risk worldwide, and effective management strategies are needed. Polyphenols exhibit diverse biological functions, are abundant in various plants, and influence carbohydrate digestion and absorption. This review provides a comprehensive overview of clinical evidence regarding the relationship between dietary polyphenols and the postprandial hyperglycemic response. Human intervention studies have demonstrated the benefits of polyphenol-rich foods in improving glucose and insulin metabolism, underscoring their role in preventing T2DM. These findings highlight the potential of polyphenol-rich foods for managing hyperglycemia and mitigating T2DM risk and provide insight into effective dietary strategies for glycemic control and overall health.

Resveratrol reversed rosiglitazone administration induced bone loss in rats with type 2 diabetes mellitus.

Rosiglitazone (RSG), as an insulin-sensitizing drug to treat type 2 diabetes mellitus (T2DM) is reported to decrease bone quality and increase bone fracture risk. The multiple off-target effects of Resveratrol (RSV), a natural specific agonist of Sirtuin1 (Sirt1) with pro-osteoblastogenesis and anti-adipogenesis effects, on bone loss in T2DM are still under discussion. In this study, successfully ovariectomized rats were fed with high-fat diet and STZ (HFD/STZ) to induced T2DM mice. RSV alone, RSG alone or co-administration of RSV and RSG were given orally to T2DM rats for 8 weeks to determine whether RSV administration had any prevention effect on T2DM osteoporosis. Bone mesenchymal stem cells (BMSCs) and bone marrow­derived macrophages (BMMs) were cultured under high glucose condition and were induced to osteoblasts or adipocytes and osteoclasts, respectively. µCT and HE staining showed that in T2DM osteoporotic rats, RSV co-administration prevents RSG induced-bone loss. ELISA results confirmed that RSV suppressed osteoclast activity and promoted osteoblast activity in diabetic osteoporosis rats and RSG-administrated diabetic osteoporosis rats. In vitro study showed that RSV significantly reversed RSG induced inhibition on osteogenesis and promotion on adiopogenesis of BMSC under high glucose (HG). Moreover, RSV significantly reverse RSG induced osteoclast formation and mature under HG. Taken together, these findings uncover a previously unappreciated anti-osteoporosis effect of concomitant treatment with RSV in RSG-administrated diabetic rats, suggesting the clinical use of RSV as an adjuvant in the treatment of T2DM for preventing or reversing RSG administration-associated bone loss.