Glucose Control Research Articles

Novel mitochondria-targeted therapy AP39 limits mitochondrial dysregulation and diastolic dysfunction in 2D & 3D human models of diabetic cardiomyopathy

Abstract Introduction Mitochondrial dysregulation has been implicated in many complications of diabetes. Mitochondrial-targeted therapies AP39 and SS31 are renoprotective, but their cardioprotective potential in diabetes has not been fully resolved. Purpose We investigated AP39 and SS31 in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-hCM) and endothelial cells (iPSC-hEC) independently in 2D culture, as well as collectively in a 3D cardiac organoid (iPSC-hCO) model also comprising fibroblasts (iPSC-hFB), under type 2 diabetes (T2D)-like conditions. Methods Cells (iPSC-hCM, iPSC-hEC, iPSC-hFB; foreskin-2 cell line) were exposed to either 5.55mM glucose (control) or T2D conditions (20mM glucose plus fatty acids, endothelin-1 and cortisol) ± AP39 (50nM) or SS31 (1µM) for 48h. Cardiac organoids were subjected to 5.55mM glucose (control) or T2D for 4 days, with AP39 (50nM) or SS31 (1µM) added on day 2. Data are expressed as mean±SEM (fold) with n=4-6 from 2-3 independent experiments. One-way ANOVA with Dunnett`s post hoc analysis was performed with P<0.05 considered significant. Results 2D human cells: After 48h, T2D increased mitochondrial superoxide in iPSC-hCM (2.4±0.1 fold vs control) and iPSC-hEC (3.2±0.29 fold vs control), both P<0.05 (measured by MitoSOX). This was blunted by both AP39 (to 1.1±0.17) and SS31 (to 1.5±0.17) in T2D iPSC-hCM (P<0.05), with similar impact in iPSC-hEC, to 2.9±0.26 and 1.3±0.16 fold, both P<0.05. T2D increased cell death in both iPSC-hCM (1.6±0.09 fold vs control) and iPSC-hEC (1.6±0.12 fold, both P<0.05 measured by propidium iodide staining. Interestingly, AP39 selectively blunted cell death in T2D iPSC-hCM (to 1.1±0.06, P<0.05), mimicked by SS31 in T2D iPSC-hEC only (to 1.0±0.10, P<0.05). Further, T2D-induced mitochondrial hyperpolarisation in iPSC-hCM (1.5±0.09 fold vs control, assessed using TMRM), was only protected by AP39 (1.2±0.06 fold, P<0.05), but not SS31. 3D human cardiac organoids: After 4 days, T2D increased total contraction duration (1.6±0.10 fold control), time to peak (1.7±0.11) and relaxation duration (1.5±0.13, indicative of diastolic dysfunction), assessed by Olympus IX71 with a DP72 camera. All 3 contractile parameters were attenuated with AP39 (to 1.5±0.06, 1.3±0.09 and 1.0±0.04 fold, respectively) or SS31 (to 1.1±0.05, 1.2±0.15 and 1.2±0.12 fold, respectively), all P<0.05. T2D increased mitochondrial superoxide (2.7±0.16 fold control), blunted by AP39 (to 1.8±0.16) and SS31 (to 1.9±0.17), both P<0.05. Cellular injury measured by LDH was evident in T2D iPSC-hCO (2.1±0.23 fold control) was limited by AP39 (to 1.2±0.09) and SS31 (to 1.1±0.07), both P<0.05. Conclusion Our results highlight the cardioprotective potential of AP39 and SS31 to limit mitochondrial dysregulation, cell death and contractile dysfunction in human in vitro models of T2D. These findings may facilitate their clinical progression as therapeutic options for diabetic cardiomyopathy.

Factors associated with type 2 diabetes control in hard-to-reach communities in Esmeraldas, Ecuador

Abstract Background The rising prevalence of type 2 diabetes mellitus (T2DM) and its detrimental effects on population health make it an urgent public health concern. Maintaining blood glucose control is crucial for avoiding complications; however, there are notable socioeconomic disparities in disease management, especially in low- and middle-income settings. We aimed to examine the factors associated with controlled fasting capillary glucose in a difficult-to-access rural setting of Esmeraldas, Ecuador, and to examine the role of social support in this context. Methods Between October 2020 and May 2022, we conducted a cross-sectional study of T2DM adult patients in Esmeraldas’ Eloy Alfaro health district. We collected data on socio-demographic and clinical patient characteristics using a questionnaire and measured Fasting Capillary Blood Glucose levels. We estimated the prevalence of controlled glycaemia and used logistic regression to calculate odds ratios (OR) with 95% confidence intervals. Results Only 18.1% (95%CI: 14.9-21.8) of the 476 study participants had controlled glucose levels, with a significantly higher percentage in men (28.2%) compared to women (13.8%). Participants reported moderate perceived social support (median=2.33, on a scale of 1 to 4), without significant impact on glycaemic control. Women in urbanised areas were more likely to have controlled glucose levels compared to those in rural areas (aOR=2.34, 95%CI: 1.23-4.44) after adjusting for family support. In contrast, unemployed and older men had non-significant trends towards better odds of achieving controlled fasting glycaemia. Conclusions The complex interplay of factors affecting diabetes management and glycaemic control highlights the need for targeted, context and gender-specific public health strategies to address diabetes disparities in vulnerable populations. Key messages • The majority of individuals with T2DM residing in the remote communities of Eloy Alfaro district in Esmeraldas (Ecuador) have uncontrolled glycaemia, showing notable gender-specific disparities. • Participants reported a moderate level of social support, with family as the most important source. Yet, this perceived support may not effectively overcome contextual barriers in T2DM management.

Effects of SGLT-2i and GLP-1RA in vascular function parameters: the impact of the weight loss

Abstract Background Arterial stiffness and endothelial function markers flag increased cardiovascular disease risk in patients with type 2 Diabetes Mellitus (T2DM), while weight management plays a crucial role for the management of glycemic control and prevention of complications in these patients. Purpose To investigate the effects of novel antidiabetic agents on arterial stiffness and endothelial function as well as the metabolic parameters of HbA1c and Weight in T2DM patients. Patients and Methods: We enrolled 99 consecutive patients under stable antidiabetic therapy who did not reach therapeutic targets. Subjects were assessed to receive an additional antidiabetic agent to optimize glucose control; glucagon like peptide-1 receptor agonist (GLP-1RA, n=50) or sodium/glucose cotransporter-2 inhibitor (SGLT-2i, n=49). Glycosylated hemoglobin (Hba1c) and weight expressed through Body Mass Index (BMI) along with carotid-femoral pulse wave velocity (PWV) and flow-mediated dilatation (FMD), as biomarkers of arterial stiffness and endothelial function accordingly, were measured at baseline and 3 months after treatment intensification. Results There were no differences between the study groups in traditional risk factors of age and sex or baseline HbA1c, BMI, PWV, and FMD levels (ps=NS for all). In both groups PWV values displayed a statistically significant improvement from 11.2±2.5 to 9.3±2.2 m/sec (p<0.001) in the GLP-1RA group and from 10.7±2.4 to 8.9±2.0 m/sec (p=0.001) in the SGLT-2i group, as presented in Figure 1 through the differences in the values of PWV. FMD values were also significantly improve in both groups from baseline to follow-up; from 6.04±1.22 to 6.50±1.26% (p<0,001) for the GLP-1RA group and from 6.38±1.21 to 6.81±1.29% (p<0.001) for the SGLT-2i group. Moreover, both groups achieved better weight management goals in terms of BMI values between baseline and follow-up; from 33.6±4.9 to 31.5±4.6 kg/m2 for the GLP-1RA group (p<0.001) and from 31.8±5.5 to 30.5±5.6 kg/m2 for the SGLT-2i group (p<0.001), in addition to achieving better glycemic control in terms of HbA1c values, as seen in their paired differences: for GLP-1RA: 1.3±0.7% and for SGLT-2i: 0.8±0.5%. Interestingly, in the SGLT-2i group the magnitude of the PWV improvement was correlated with the weight loss (r=0.368, p=0.007). Conclusion These data provide evidence that the newer antidiabetic drugs, both GLP1-RA and SGLT-2i, have actions that benefit both vascular function, endothelium as well as metabolic parameters. Interestingly, in the patients receiving SGLT-2i the magnitude of the PWV improvement was correlated with the weight loss.delta PWV for SGLT-2i & GLP-1RA groupsCorrelation of deltaWeight & deltaPWV

Association of HbA1C with mortality and cardiovascular outcome in patients with type 2 diabetes using drugs with different hypoglycemic risk

Abstract Background Previous clinical trials showed that intensive glucose control did not reduce macrovascular events and mortality. It was speculated that severe hypoglycaemia contributed to these adverse outcomes. More contemporary clinical trials using newer anti-diabetic agents with less hypoglycaemic potential showed a linear relationship between major adverse cardiovascular events (MACE) and HbA1c reduction according to a meta-regression analysis. Purpose The aim of this study was to examine the association between clinical outcomes and HbA1c under different treatment backgrounds in the real-world setting. We hypothesised that when using drugs with minimal hypoglycaemic risk, lower HbA1c would be associated with better outcomes. Methods This was a retrospective population-based cohort study using a multi-centre electronic medical record database. Eligible patients were those diagnosed with type 2 diabetes between 2009 and 2020 who received non-insulin antidiabetic drugs. Patients were stratified into two groups based on the drugs received: drugs with high hypoglycaemic risk (sulphonylurea, meglitinide) and drugs with low hypoglycaemic risk (thiazolidinediones, acarbose, DPP4 inhibitors, GLP1 agonists, SGLT-2 inhibitors). Patients were excluded if they had received these drugs for less than 180 days or had received both high and low hypoglycaemic risk oral drugs simultaneously. HbA1c levels were assessed from the index date to the date of the interested outcome or the end of the study period (31 December 2021), whichever came first. The relationship between HbA1c and clinical outcomes was examined using a Cox proportional hazards model. The outcomes of interest included all-cause mortality and MACE. Results The study population consisted of 6,923 patients, including 3,639 high hypoglycaemic risk drug users and 3,284 low hypoglycaemic risk drug users. Patients with lower HbA1c levels during the follow-up period were older and frailer. After adjusting for baseline covariates, the association between the risk of death and HbA1c presented a U-shaped pattern, and this U-shaped association was similar in the two treatment cohorts (Table 1). On the other hand, the association between the risk of MACE and HbA1c presented a J-shaped pattern. In the high hypoglycaemic risk drug cohort, patients with the highest HbA1c levels (mean HbA1c 9.6%) were associated with a higher risk of MACE compared to the group with a mean HbA1c of 7.2% (hazard ratio [HR] 4.16, 95% confidence interval [CI] 2.07-8.37); lower HbA1c levels were not associated with a lower risk of MACE (Table 2). In contrast, in the low hypoglycaemic risk drug cohort, lower HbA1c levels were associated with a higher risk of MACE (HR 3.82, 95% CI 1.29-11.28). Conclusion Lower HbA1c levels were not associated with a lower risk of all-cause mortality and MACE. Furthermore, this phenomenon was independent of the hypoglycaemic risk of anti-diabetic drugs.

Emphysematous pyelonephritis caused by Raoultella ornithinolytica: a case report

BackgroundEmphysematous pyelonephritis is a rare and severe urinary tract infection that is potentially life-threatening and easily progresses to septic shock. In this report, we present a unique case of emphysematous pyelonephritis caused by Raoultella ornithinolytica.Case presentationAn 86-year-old man presented with severe back pain of 3 days’ duration. He had a history of hypertension and diabetes for more than 20 years, and his infection indicators and serum creatinine were elevated. Abdominal computed tomography revealed an abnormal gas shadow around his right kidney and the anterior edge of his right psoas muscle. Consequently, he was initially diagnosed with emphysematous pyelonephritis. There was no evidence of nephrolithiasis or other anatomical or structural abnormalities that could have precipitated this focal renal infection. Both blood and drainage fluid cultures revealed R. ornithinolytica. After early anti-infection treatment, percutaneous drainage and moderate control of blood glucose, the patient gradually recovered.ConclusionsEmphysematous pyelonephritis caused by R. ornithinolytica is rare but has a high drug resistance rate potentially and may cause severe infections. Early diagnosis, prompt use of antibiotics that are sensitive to the organism, and decompression drainage could be the key to treatment.

Switching from Premixed Insulin to Insulin Degludec/Insulin Aspart for the Management of Type 2 Diabetes Mellitus: Implications of a Real-World Study on Insulin Degludec Dosing.

When switching from premixed insulin to insulin degludec/aspart (IDegAsp), IDegAsp usually starts at the same dose as the premixed insulin according to limited clinical experience or at a dose according to clinician discretion. The dose of insulin degludec used in the real world after switching has been poorly investigated. A retrospective analysis was conducted on patients with type 2 diabetes who switched from premixed insulin to IDegAsp from October 2016 to December 2023. Repeated measures analysis of variance was used to compare changes in insulin dose, glycated hemoglobin (HbA1c), fasting blood glucose (FBG), and postprandial blood glucose (PBG) before and after switching. Sixty-six patients with prior low-ratio premixed insulin and 22 with prior mid-ratio premixed insulin were included. Among the low-ratio insulin users, the total daily dose of insulin degludec (IDeg) decreased by 21.43% and 19.05% at 3 and 6months, respectively, after switching, compared with prior basal insulin dose (both p < 0.001). Conversely, among mid-ratio insulin users, the IDeg daily dose increased by 10.71% and 32.14% at 3 and 6months, respectively, after switching, compared with prior basal insulin dose (both p < 0.001). In all patients, HbA1c levels decreased by 0.70%, FBG decreased by 1.00mmol/l, and PBG decreased by 1.61mmol/l after 6months of switching (all p < 0.05); the total daily insulin dose and injection frequency significantly decreased after switching (both p < 0.05); age and disease duration did not affect IDegAsp effects on HbA1c reduction. In the setting of transition to IDegAsp from premixed insulin, the dose of basal insulin in the premixed formulation can be a valuable reference for adjusting insulin degludec dose. IDegAsp is superior to premixed insulin in blood glucose control with reduced total daily dose and injection frequency. IDegAsp could be the best choice for the management of diabetes in elderly patients.

A mathematical model of glomerular fibrosis in diabetic kidney disease to predict therapeutic efficacy

BackgroundGlomerular fibrosis is a tissue damage that occurs within the kidneys of chronic and diabetic kidney disease patients. Effective treatments are lacking, and the mechanism of glomerular damage reversal is poorly understood.MethodsA mathematical model suitable for hypothesis-driven systems pharmacology of glomerular fibrosis in diabetes was developed from a previous model of interstitial fibrosis. The adapted model consists of a system of ordinary differential equations that models the complex disease etiology and progression of glomerular fibrosis in diabetes.ResultsWithin the scope of the mechanism incorporated, advanced glycation end products (AGE)—matrix proteins that are modified due to high blood glucose—were identified as major contributors to the delay in the recovery from glomerular fibrosis after glucose control. The model predicted that inhibition of AGE production is not an effective approach for accelerating the recovery from glomerular fibrosis. Further, the model predicted that treatment breaking down accumulated AGE is the most productive at reversing glomerular fibrosis. The use of the model led to the identification that glucose control and aminoguanidine are ineffective treatments for reversing advanced glomerular fibrosis because they do not remove accumulated AGE. Additionally, using the model, a potential explanation was generated for the lack of efficacy of alagebrium in treating advanced glomerular fibrosis, which is due to the inability of alagebrium to reduce TGF-β.ImpactUsing the mathematical model, a mechanistic understanding of disease etiology and complexity of glomerular fibrosis in diabetes was illuminated, and then hypothesis-driven explanations for the lack of efficacy of different pharmacological agents for treating glomerular fibrosis were provided. This understanding can enable the development of more efficacious therapeutics for treating kidney damage in diabetes.

The prevention and improvement effects of vitamin D on type 2 diabetes mellitus: evidence from an umbrella review on Meta-analyses of cohort studies and randomized controlled trials

BackgroundTo clarify whether Vitamin D prevent the occurrence of type 2 diabetes mellitus (T2DM) and improve glucose control in T2DM patients, we conducted this umbrella review, taking into account the inconsistent results of existing Meta-analyses. We aim to reveal the causal relationship between Vitamin D and T2DM through summarizing Meta-analyses of observational studies, and clarify the improvement on glucose control in T2DM patients through summarizing Meta-analyses of RCT studies between Vitamin D supplementation and T2DM patients, especially in T2DM patients with Vitamin D deficiency.MethodsWe collected the Meta-analyses of observational studies and RCTs in PubMed, Scopus, Embase, Web of Science, and Cochrane.Results16 Meta-analyses (6 effect sizes for cohort studies and 10 effect sizes for RCTs) were included in the umbrella Meta-analyses. Random-effects model was carried out to calculate the pooled point estimates and their respective 95% confidence intervals (CI). The results revealed that lower 25(OH)D levels increased the risk of T2DM (Pooled ESRR = 1.34; 95%CI: 1.16, 1.53), Vitamin D supplementation ameliorated FBG (ES = −0.56; 95%CI: −1.00, −0.11), HbA1c (ES = −0.11; 95%CI: −0.20, −0.02), insulin (ES = −0.38; 95%CI: −0.59, −0.18) and HOMA-IR (ES = −0.37; 95%CI: −0.57, −0.16) in T2DM patients, especially in those with Vitamin D deficiency (FBG = −0.98; HbA1c = −0.27; HOMA-IR = −0.52).ConclusionThe present umbrella Meta-analyses demonstrates the potential benefits of higher serum Vitamin D levels and Vitamin D supplementation in reducing the development and symptoms of T2DM.

Novel Protocol for the Use of Advanced Hybrid Closed-Loop System in Adolescents Engaged in Contact Sports.

Managing exercise remains challenging for adolescent athletes with type 1 diabetes (T1D), especially in contact sports. Even the use of hybrid closed loops can cause problems due to the need to disconnect the pump during some training or competitions. This study evaluated the efficacy of a novel protocol for the use of an Advanced Hybrid Closed-Loop System in adolescent football players with T1D during a sports camp. Eleven boys aged 14.9 years (25-75th percentile: 14-15.5), with a diabetes duration of 5.7 years (5.2-7) and regular training schedules in junior football leagues, participated in the study. They started AHCL (MiniMed780G, Medtronic) therapy a month before a week-long sports camp and were observed during the sports camp and the preceding week. Daily camp activities included two 1.5-hour training sessions. Protocol included a 90-minute temporary target of 150 mg/dL before and insulin pump disconnection during training. Physical activity was tracked using wGT3X-BT Actigraph monitors. The camp provided conditions of demanding physical activity (6.6[6-6.9] hours/day of moderate-to-vigorous intensity). After starting AHCL, the average participant time spent in the target glucose range (70-180mg/dL) was 79.34±8.46%, and no significant change was observed during the camp (mean difference +0.79±8.24%, p=0.7581). Median glucose levels dropped by 10.91±12.08mg/dL (p=0.0134), and time in the tight target range increased by 11.41±11.60% (p=0.0008) without increasing the time below range (&lt;70mg/dL) or glycemic variability. During the camp, daily insulin dose and basal/bolus ratio remained comparable with baseline, but the relative amount of automated bolus insulin decreased by 14.24±4.65% (p&lt;0.0001). The predefined regimen, including a temporary target before and disconnection of AHCL during football training, was safe and may provide satisfactory glucose control in active adolescents with T1D. This protocol could be adapted for use in other intensive contact sports.

Exercise as a therapeutic approach to alleviate diabetic kidney disease: mechanisms, clinical evidence and potential exercise prescriptions

Diabetic kidney disease (DKD) is a global and severe complication that imposes a significant burden on individual health, families, and society. Currently, the main treatment approaches for DKD include medication, blood glucose control, protein-restricted diet, and blood pressure management, all of which have certain limitations. Exercise, as a non-pharmacological intervention, has attracted increasing attention. This review introduces the mechanisms and clinical evidence of exercise on DKD, and proposes potential exercise prescriptions. Exercise can improve blood glucose stability related to DKD and the renin-angiotensin-aldosterone system (RAAS), reduce renal oxidative stress and inflammation, enhance the crosstalk between muscle and kidneys, and improve endothelial cell function. These mechanisms contribute to the comprehensive improvement of DKD. Compared to traditional treatment methods, exercise has several advantages, including safety, effectiveness, and no significant side effects. It can be used as an adjunct therapy to medication, blood glucose control, protein-restricted diet, and blood pressure management. Despite the evident benefits of exercise in DKD management, there is still a lack of large-scale, long-term randomized controlled trials to provide more evidence and develop exercise guidelines for DKD. Healthcare professionals should actively encourage exercise in DKD patients and develop personalized exercise plans based on individual circumstances.

Clinical efficacy observation of electroacupuncture based on the "ascending lucidity and descending turbidity" theory： a study of gut microbiota in patients with diabetic gastrointestinal dysfunction

To explore the efficacy of electroacupuncture (EA) based on the "ascending lucidity and descending turbidity" theory in patients with diabetic gastrointestinal dysfunction and its regulatory effect on gut microbiota. A total of 48 patients with diabetic gastrointestinal dysfunction were randomly divided into the EA group (24 cases, 3 cases dropped-off) and the control group (24 cases, no dropped off). Both groups received blood glucose control and basic symptomatic treatment. EA (15 Hz/100 Hz) was applied to Zhongwan (CV12), Tianshu (ST25), Zhongfu (LU1), bilateral Zhangmen (LR13), bilateral Taibai (SP3), bilateral Taiyuan (LU9), bilateral Zusanli (ST36), and bilateral Shangjuxu (ST37) in the EA group. Sham EA was applied to corresponding non-acupoints without electric stimulation in the control group. Both groups received treatment for 30 min per time, once daily, for a total of 5 treatments followed by a 2-day break, over a consecutive period of 2 weeks. Symptoms were evaluated by gastrointestinal symptom rating scale (GSRS) and gastroparesis cardinal symptom index (GCSI) before and after treatment, and 4 weeks after treatment. During the treatment period, fasting blood glucose levels were monitored daily. Stool samples were collected before and after treatment for 16S rDNA sequencing analysis to examine changes in gut microbiota. Compared with the control group, GSRS and GCSI scores in the EA group were significantly decreased (P<0.001) after treatment and at follow-up at the same time point, and compared with those before treatment, GSRS and GCSI scores in the EA group were significantly decreased after treatment and at follow-up (P<0.001). After treatment, the 16S rDNA sequencing showed that at the phylum level, the ratio of Proteobacteria in the EA group was higher than that in the control group (FDR<0.05). At the genus level, a total of 18 different gut microbiota were identified between the two groups. Compared to the control group, patients in the EA group showed a significant decrease in the abundance of Pseudomonas and Alkalibacter (FDR<0.05), while the abundance of the remaining 16 gut microbiota was significantly increased (FDR<0.05). Compared to the baseline, the EA group showed a significant up-regulation of Olsenella (FDR<0.05) and a significant down-regulation of Pseudomonas (FDR<0.05) after treatment. EA based on the "ascending lucidity and descending turbidity" theory can effectively improve the symptoms of patients with diabetic gastrointestinal dysfunction. EA can also affect the distribution of gut microbiota by up-regulating the levels of certain beneficial bacteria and suppressing pathogenic bacteria .

Analysis of self-monitoring of blood glucose metrics in gestational diabetes mellitus and their association with infants born large for gestational age: A historical observational cohort study of 879 pregnancies.

Self-monitoring of blood glucose (SMBG) is the standard of care for women with gestational diabetes mellitus (GDM). This study aimed to review SMBG profiles in women with GDM and to examine how glucose metrics derived from SMBG relate to fetal overgrowth and infants born large for gestational age (LGA, >90th percentile). This was a single-center, historical, observational cohort study of 879 GDM pregnancies in Sweden. The diagnosis of GDM was based on a universal 75 g oral glucose tolerance test at gestational week 28 or 12 in high-risk women. The glucose metrics derived from the SMBG profiles were calculated. Treatment targets for glucose were <5.3 mmol/L fasting, and ≤7.8 mmol/L 1-h postprandial. The median (interquartile range) number of glucose measurements in the analysis for each woman was 318 (216-471), including 53 (38-79) fasting glucose measurements. Associations between glucose metrics and LGA were analyzed using binary logistic regression analysis adjusted for maternal age, body mass index, smoking, nulliparity, and European/non-European origin. Receiver operating characteristic (ROC) curves were used to evaluate glucose levels for LGA prediction. Differences in means were tested using analysis of variance. The proportion of LGA infants was 14.6%. Higher mean glucose levels and smaller proportion of readings in target (glucose 3.5-7.8 mmol/L) were significantly associated with LGA (odds ratio [95% confidence interval]: 3.06 [2.05-4.57] and 0.94 [0.92-0.96], respectively). The strongest association was found with mean fasting glucose (3.84 [2.55-5.77]). The ability of mean fasting glucose and overall mean glucose to predict LGA infants in the ROC curves was fair, with areas under the curve of 0.738 and 0.697, respectively (p < 0.001). The corresponding discriminating thresholds were 5.3 and 6.1 mmol/L, respectively. Mean glucose levels increased and readings in target decreased with increasing body mass index category and at each step of adding pharmacological treatment, from diet alone to metformin and insulin (p < 0.001). Higher mean glucose levels and a smaller proportion of readings within the target range were associated with an increased risk of LGA. Suboptimal glucose control is associated with obesity and the need for pharmacological treatment.

Development and validation of a predictive scoring system for hypoglycaemic agents for optimal control of blood glucose during glucocorticoid therapy.

Glucocorticoid (GC) treatments are often used. There is limited information on the prediction of hyperglycaemia after GC administration. This study aimed to identify the risk factors for hyperglycaemia after glucocorticoid (GC) administration and the need for hypoglycaemic agents to correct it and to develop and validate a novel scoring system for predicting GC-induced hyperglycaemia. In a development set, 508 adults receiving prednisolone (PSL) for the first time were divided into two groups based on treatment with or without hypoglycaemic agents. Clinical and laboratory parameters were compared, and risk factors were identified using logistic regression analysis after performing univariate analyses between the two groups. A point-addition scoring system with several categories and coefficients for each risk factor was constructed to predict the need for hypoglycaemic agents. The scoring system was then applied and validated on two validation sets: A and B. Older age, higher glycated haemoglobin percentage, body mass index and initial PSL dosage were identified as risk factors. The sensitivity, specificity and accuracy of the scoring system were 70.6%, 81.9% and 77.1% in the development set; 75.8%, 78.4% and 77.4% in validation set A; and 79.4%, 73.9% and 75.3% in validation set B respectively. By fitting the total score in the development set and the probability of hyperglycaemia to a logistic curve, a figure was created to show the probability of GC-induced hyperglycaemia in patients scheduled to receive GC. This scoring system is a novel, valid and reliable tool for predicting GC-induced hyperglycaemia and the need for hypoglycaemic agents to correct it.

Yeast β-glucan supplementation lowers insulin resistance without altering microbiota composition compared to placebo in subjects with Type II diabetes: a phase I exploratory study.

The increased global prevalence of type II diabetes mellitus (T2DM) is associated with consumption of low fibre "Western diets". Characteristic metabolic parameters of these individuals include insulin resistance, high fasting and postprandial glucose, as well as low-grade systemic inflammation. Gut microbiota composition is altered significantly in these cohorts suggesting a causative link between diet, microbiota and disease. Dietary fibre consumption has been shown to alleviate these changes and improve glucose parameters in individuals with metabolic disease. We previously reported that yeast β-glucan (yeast beta-1,3/1,6-D-glucan; Wellmune) supplementation ameliorated hyperinsulinemia and insulin resistance in a murine model. Here we conducted a randomised, placebo-controlled, two-armed dietary fibre phase I exploratory intervention study in patients with T2DM. The primary outcome measure was alteration to microbiota composition while the secondary outcome measures included markers of glycaemic control, inflammation as well as metabolomics. Patients were supplemented with 2.5g/day of maltodextrin (placebo) or yeast β-1,3/1,6-D-glucan (treatment). Yeast β-glucan (Wellmune) lowered insulin resistance (HOMA-IR) compared to the placebo maltodextrin after 8 weeks of consumption. TNFα was significantly lower after 4 weeks of β-glucan supplementation. Significantly higher faecal concentrations of several bile acids were detected in the treatment group when compared to the placebo after 8 weeks. These included tauroursodeoxycholic acid (TUDCA) which was previously shown to improve glucose control and lower insulin resistance. Interestingly, the hypoglycaemic and anti-inflammatory effect of yeast β-glucan was independent of any changes in faecal microbiota composition or short-chain fatty acid (SCFA) levels. Our findings highlight the potential of yeast β-glucan to lower insulin resistance in patients with T2DM.

Transcutaneous stimulation as a niche theme in gastroparesis therapy

Introduction Gastroparesis, a global condition causing bile salt accumulation, is prevalent globally. Diagnosis techniques like bile salt titration and nitric oxide sulfate can improve patient care. However, simptomatic control is needed to reduce inflammation and control potential diseases. Neurological techniques like gyroscope stimulation and endoscopy can diagnose refractive gastroparesis. Interdisciplinary collaboration and bibliometric research are crucial for finding effective treatments. Gastroparesis, a motility issue affecting 0.9-1.3% of diabetics, can be improved by new diagnostic methods like osmotic pressure and gastric emptying, enhancing patient treatment. Methods This study uses a literature review methodology to gather data from the Scopus database on neuroaid, analyzing it using Biblioshiny and VOSviewer software. The focus is on dietary adjustments, glucose regulation, and transcutaneous stimulation’s role in gastroparesis treatment, using quantitative and qualitative analysis. Results The research trend found are documents by year, most relevant sources, factorial map of the most cited documents, factorial map of The documents with the highest contributes, documents by author, documents by country or territory, documents by subject area, documents by affiliation, network visualization, overlay visualization of scopus database using vosviewer, density visualization, thematic map, thematic evolution, cluster analysis, topic dendogram, and country collaboration map. According to our analysis, transcutaneous stimulation holds great promise for treating gastroparesis. We also found the necessity of multidisciplinary collaboration in the management of this illness. Conclusions The study on gastroparesis highlights key themes like diet modification, glucose control, medication therapy, Cajal’s role in smooth muscle concentration, common causes, transcutaneous stimulation, motorcycle themes, vagus nerve, and emerging devices and electronics. Basic themes include gastrointestinal disorders, neuromodulation, patients, diabetes, and gastric electrical stimulation. The management of gastroparesis involves multidisciplinary approaches, lifestyle changes, medication therapy, and bedtime interventions, with further investigation into transcutaneous stimulation being warranted.

Best Evidence Summary for Management of Older People With Type 2 Diabetes Mellitus Using 'Internet Plus Nursing Services'.

To evaluate and summarise the evidence for the management of older people with Type 2 diabetes mellitus (T2DM) using 'Internet Plus nursing services (IPNS)'. This study was conducted as an evidence summary, adhering strictly to the evidence summary reporting standards established by Fudan University Center for Evidence-based Nursing. We systematically searched for the best available evidence pertaining to the management of older people with T2DM using the IPNS. The literature types encompassed clinical guidelines, expert consensuses, systematic reviews, evidence summaries and original research studies. In order to gather pertinent information, we conducted a comprehensive search across various databases, including UpToDate, BMJ Best Practice, Joanna Briggs Institute, Guidelines International Network, National Institute for Health and Care Excellence, Registered Nurses Association of Ontario, Scottish Intercollegiate Guidelines Network, the Cochrane Library, PubMed, Web of Science, Yi Maitong Guidelines Network, SinoMed, CNKI, WanFang database, Chinese Biomedical Literature Database and China Science and Technology Journal Database. The search spanned from the inception of each database up to July 2023, ensuring an extensive coverage of relevant resources. After rigorous screening and evaluation, our study ultimately identified 19 articles with high-quality research outcomes. These articles consisted of three guidelines, two expert consensus documents, three systematic reviews and eleven original research studies. Through collaborative and in-depth discussions, we extracted and synthesised 27 pieces of evidence related to the application of the IPNS to enhance the T2DM management for older people. We categorised the evidence into five primary themes: mobile terminal design, team building, health education design, interaction and social support, and information feedback. In designing the IPNS for older people with T2DM, utmost attention should be paid to the intricacies of Internet module development preceded by comprehensive guidance. It is imperative to establish multidisciplinary teams to oversee the curation of patient educational content, ensuring its relevance and effectiveness. Leveraging Internet-based information feedback mechanisms is crucial for fostering peer support, assisting in blood glucose control, enhancing self-management capabilities and ultimately improving overall quality of life. Healthcare professionals are supposed to customise the IPNS for this vulnerable population, taking into account institutional resources and local contextual realities. It is highly recommended that clinical medical personnel worldwide adhere to the evidence-based recommendations for better care of older people with T2DM using the IPNS. No patient or public contribution was incorporated in this study. Our study provides structured ideas for the application of IPNS in T2DM management, provides practicable new ways for IPNS to improve self-management of older people with T2DM, and encourages the provision of Internet-based nursing services based on the needs and characteristics of older people, and jointly solves the challenges of T2DM management in order to enhance the effectiveness of nursing services.

A model predictive control algorithm for double-hormone artificial pancreas based on optimal three-branch decision switching rules

At present, double-hormone artificial pancreas is a hotspot in the research of regulating blood glucose level; however, there are few studies on switching mechanism of the subsystems for double-hormone artificial pancreas, and most of the existing studies rely on the prior knowledge of application fields. A model predictive control algorithm for double-hormone artificial pancreas based on optimal three-branch decision switching rules is proposed to solve this problem. The blood glucose controllers of insulin subsystems, zero infusion subsystems, and glucagon subsystems are constructed using model predictive control algorithms. Then, using the three-branch decision theory, switching rules between the three subsystems are designed, and the optimal switching threshold value can be solved by the mixed fruit fly algorithm. The algorithm can realize automatic acquisition of the threshold in the three-branch decision switching rules and gets rid of the dependence on the prior knowledge in the field of diabetes research. By the end, the UVa simulation platform is used to conduct experiments on 33 virtual patients and the simulation results verify that the proposed algorithm can control blood glucose effectively within the normal range and can achieve satisfactory performabce in error of tracking set point, safety, operation efficiency, group control quality, and system stability.

Inhibition of viability of human retinal microvascular endothelial cells by vialinin A under high glucose condition.

To investigate the effects of vialinin A on viability of human retinal endothelial cells (HRECs) under high glucose condition and its potential mechanism. The HRECs were divided into four groups: normal glucose control group (NG, 5 mmol/L D-glucose), high glucose group (HG, 30 mmol/L D-glucose), HG+1 µmol/L vialinin A group, and HG+5 µmol/L vialinin A group. The cell viabilities were measured with cell counting kit-8 (CCK-8) assay for proliferation, with scratch assay for migration, and tube formation, for evaluation of the impact of vialinin A on cellular behaviour. Real-time PCR and Western blotting were used to determine the expression level of vascular endothelial growth factor (VEGF). The proliferative capacity and migration of HRECs was reduced by 5 µmol/L vialinin A in high glucose environment (both P<0.05). Vialinin A also inhibited high-glucose-induced tube formation of HRECs. The expression level of VEGF and PI3K in HRECs was also significantly decreased by vialinin A (P<0.05). Vialinin A inhibits the cell viability of HRECs. It may serve as a potential target for anti-angiogenic therapy.

The Association Between Type 2 Diabetes Mellitus and Levels of Total Cholesterol, Low-Density Lipoprotein (LDL) Cholesterol, Very Low-Density Lipoprotein (VLDL) and the Role of Dehydrated Vegetables in Glycemic Control

Objective: This study aimed to assess Total Cholesterol, Low-Density Lipoprotein (LDL) and Very Low-Density Lipoprotein (VLDL) Levels, identify specific lipid markers altered in individuals with type 2 diabetes mellitus (T2DM), and evaluate the correlation between HbA1C and total cholesterol, LDL cholesterol, and VLDL levels. Materials and Methods: Ninety-six volunteers aged 35-72 with confirmed T2DM underwent total cholesterol, LDL, VLDL and HbA1c testing using the COBAS INTEGRA 400 PLUS device. Data on age, gender, diabetes status, and lipid profiles were collected in November 2023 to April 2024 from Layla Qasim Health Center located in Erbil, Iraq and then analyzed. Results: Result: In our study, the prevalence of dyslipidemia among type 2 diabetes mellitus (T2DM) patients was 50.88%. This varied regionally, from 59.3% in China to 83.9% in Saudi Arabia. Dyslipidemia was more common in patients with poor blood glucose control. Weight and waist circumference were positively correlated with HbA1c levels, while age showed no significant effect on glycemic control. Women showed higher LDL and HbA1c levels than men. Although weak correlations were observed between HbA1c and LDL cholesterol, LDL was strongly correlated with total cholesterol and moderately with VLDL. Early detection and management of dyslipidemia is important to reduce the risk of cardiovascular disease in patients with T2DM. Conclusion: Our study highlights the significant prevalence of dyslipidemia among patients with type 2 diabetes mellitus (T2DM), emphasizing the importance of lipid profile management to reduce the risk of cardiovascular disease. We found associations between weight, waist circumference and HbA1c levels, with gender differences in lipid profiles. While the association between HbA1c and LDL cholesterol was weak, early diagnosis and management of dyslipidemia could significantly reduce CVD risk, advocating a comprehensive strategy targeting both glycemic control and lipid management in T2DM patients.

A Pilot Study Using Continuous Glucose Monitoring among Patients with a Low 1-Hour Glucose Challenge Test Result versus Controls to Detect Maternal Hypoglycemia.

A low 1-hour glucose challenge test (GCT) result (<10th percentile for population) has been associated with neonatal morbidity, including small-for-gestational-age birth weight, and it is hypothesized that underlying maternal hypoglycemia may contribute to this neonatal morbidity. We sought to assess whether eligible patients would undergo continuous glucose monitoring to allow comparison of maternal hypoglycemia between those with a low GCT result versus controls. This exploratory study enrolled patients who completed a GCT between 24 and 30 weeks' gestation from June to September 2022. English- or Spanish-speaking participants aged ≥18 years wore a blinded continuous glucose monitor (CGM) for 10 days. There were 10 participants each in the low GCT (<82 mg/dL) and normal GCT group. Proportions were calculated to determine recruitment rates and describe the low versus normal glycemic groups across clinical and sociodemographic characteristics. Maternal hypoglycemia, defined using various proposed thresholds, was analyzed as continuous data (time duration) with Student's t-tests and categorical data (number of episodes) with chi-square tests and bivariate analyses were performed comparing participants with a low versus normal GCT. Primary outcome measures were recruitment, enrollment, and adherence rates, and overall glycemic values for each group. Of 64 eligible patients, 58 (91%) were approached, and of them, 20 (35%) were enrolled. All 20 participants had CGM data to review with 100% adherence. Average glucose values were similar between participants in the low GCT and normal GCT groups (111.7 ± 18.0 vs. 111.6 ± 11.7 mg/dL, p = 0.99), and participants with a low GCT value did not demonstrate more hypoglycemia than those with a normal GCT value across five proposed thresholds on CGM analysis. In this pilot study, participants wore blinded CGMs to collect glycemic data, and those with a low GCT result did not experience more hypoglycemia than those with a normal GCT on CGM analysis. · Study participants wore continuous glucose monitors in blinded mode to gather glycemic data with 100% adherence.. · Participants with a low GCT result (<82 mg/dL) as compared with those with a normal GCT result were not more likely to demonstrate maternal hypoglycemia using several thresholds on CGM analysis.. · In our cohort, there were few participants in either glycemic group who reported food insecurity or lived in a food desert..