Diabetic Conditions Research Articles

Ayurveda’s Role in Managing Diabetes: A Case Study

Diabetes is also known as Diabetes mellitus (DM) which is characterised by high blood sugar levels over a long period. The raised level of Blood Glucose leads to frequent urination. This may occur when the pancreas is unable to produce the proper level of insulin or the inability of body cells to absorb the glucose properly. Insulin regulates the level of glucose in the bloodstream, so its deficiency leads to a rise in the glucose levels in the bloodstream. The condition of Diabetes may lead to various complications if it is not managed properly. A 50-year-old male patient presented with complaints of frequent urination, increased thirst and hunger. The clinical findings and symptoms of the patient are related to Type 2 Diabetes. Diabetes is correlated to Madhumeha in Ayurveda. The patient was given Dia-Beta Plus capsules, Karela capsules, Madhumehantak churna, Fenugreek capsules and Diaplan tea. After 2 months, the patient feels some relief in his symptoms. The random sugar levels of the patient decreased from 240 mg/dL to 130 mg/dL. After the complete course of Ayurveda medication, the blood sugar level of the patient was managed effectively.

Use of physiologically based kinetic modeling to predict neurotoxicity and genotoxicity of methylglyoxal in humans

This study aimed to evaluate human neurotoxicity and genotoxicity risks from dietary and endogenous methylglyoxal (MGO), utilizing physiologically based kinetic (PBK) modeling-facilitated reverse dosimetry as a new approach methodology (NAM) to extrapolate in vitro toxicity data to in vivo dose-response predictions. A human PBK model was defined based on a newly developed and evaluated mouse model enabling the translation of in vitro toxicity data for MGO from human stem cell-derived neurons and WM-266-4 melanoma cells into quantitative human in vivo toxicity data and subsequent risk assessment by the margin of exposure (MOE) approach. The results show that the MOEs resulting from daily dietary intake did not raise a concern for endpoints for neurotoxicity including mitochondrial function, cytotoxicity, and apoptosis, while those for DNA adduct formation could not exclude a concern over genotoxicity. Endogenous MGO formation, especially under diabetic conditions, resulted in MOEs that raised concern not only for genotoxicity but also for some of the neurotoxicity endpoints evaluated. Thus, the results also point to the importance of taking the endogenous levels into account in the risk assessment of MGO.

Metabolic regulation of mitochondrial morphologies in pancreatic beta cells: coupling of bioenergetics and mitochondrial dynamics

Cellular bioenergetics and mitochondrial dynamics are crucial for the secretion of insulin by pancreatic beta cells in response to elevated levels of blood glucose. To elucidate the interactions between energy production and mitochondrial fission/fusion dynamics, we combine live-cell mitochondria imaging with biophysical-based modeling and graph-based network analysis. The aim is to determine the mechanism that regulates mitochondrial morphology and balances metabolic demands in pancreatic beta cells. A minimalistic differential equation-based model for beta cells is constructed that includes glycolysis, oxidative phosphorylation, calcium dynamics, and fission/fusion dynamics, with ATP synthase flux and proton leak flux as main regulators of mitochondrial dynamics. The model shows that mitochondrial fission occurs in response to hyperglycemia, starvation, ATP synthase inhibition, uncoupling, and diabetic conditions, in which the rate of proton leakage exceeds the rate of mitochondrial ATP synthesis. Under these metabolic challenges, the propensities of tip-to-tip fusion events simulated from the microscopy images of the mitochondrial networks are lower than those in the control group and prevent the formation of mitochondrial networks. The study provides a quantitative framework that couples bioenergetic regulation with mitochondrial dynamics, offering insights into how mitochondria adapt to metabolic challenges.

6494 GLP-1/GIP/Glucagon Triagonist Improves Glycemic Control via Gαq Signaling Pathway and TRPM5 Activation

Abstract Disclosure: N. Khajavi: None. P.C. Schreier: None. P. Beyerle: None. P.S. Reinach: None. A. Breit: None. I. Boekhoff: None. T.D. Müller: Grant Recipient; Self; Novo Nordisk. Speaker; Self; Novo Nordisk. Stock Owner; Self; Novo Nordisk. T. Gudermann: None. Cutting-edge research on obesity and diabetes strives to pioneer innovative drug combinations targeting various dysfunctional metabolic regulatory pathways. The single-molecule triagonist has been developed to directly interact with the glucagon-like peptide-1 receptor (GLP-1R), glucose-dependent insulinotropic polypeptide receptor (GIPR), and the glucagon receptor (GcgR). It provides a breakthrough in the treatment of obesity and type 2 diabetes because of greater efficacy compared to conventional single-agonist therapy. While the triagonist is already undergoing phase two clinical trials, the downstream mechanism requires further study. Previously, we showed that triagonist elicits transient rises in intracellular Ca2+ concentration that augment glucose-induced rises in insulin secretion in murine (MIN6) and human (1.1B4) pancreatic β cell lines. Although Gαs signaling is known as the main mediator of both GLP-1 and GIP signaling, our research indicates that the superior effect of the triagonist on insulin secretion is not solely dependent on the activation of the classical Gαs pathway and the exchange factor activated by cAMP (EPAC) signaling. Instead, we report that the triagonist enhances glucose-induced rises in insulin secretion via Gαq signaling and its downstream effector, the TRPM5 channel. This involvement is evident, as blocking Gαq signaling with a specific blocker, YM254890, reduced triagonist-induced rises in insulin secretion in mouse pancreatic islets. Similarly, blocking TRPM5 with the TPPO blocker attenuated triagonist-induced increases in insulin secretion and Ca2+ signaling in mouse pancreatic islets. Strikingly, both blockers had no remarkable impact on GLP-1- and GIP-induced rises in insulin secretion. Our in vivo analysis demonstrates that the triagonist improves glucose tolerance in diet-induced obese wild-type mice, but this effect was absent in TRPM5 knockout mice. Notably, the triagonist augments glucose-induced insulin secretion in isolated islets of wild-type mice more than treatment with GLP1 and GIP mono-agonists. Furthermore, this enhanced response is absent in TRPM5 knockout islets. Recent studies propose that persistent membrane depolarization of β cells leads to a switch from Gαs to Gαq signaling, which is a major amplifying pathway of insulin secretion under diabetic conditions. Our study shows that the enhancing effect of the triagonist, acting as a biased agonist, on insulin secretion is dependent on TRPM5 activation through the Gαq signaling pathway. Presentation: 6/2/2024

7513 Presence Of Hispanic/Latino Physicians In Academic Research. Are We There Yet?

Abstract Disclosure: C.E. Guillen Lopez: None. A. Patel: None. A. Rocha: None. C. Arima: None. A. Molkina: None. L. Robles: None. A. Arce Gastelum: None. Hispanic/Latino endocrinologists' presence and active involvement in diabetes research play a pivotal role in shaping the trajectory of healthcare initiatives in the United States. Diabetes, a prevalent and complex health condition, disproportionately affects diverse communities, with Hispanics/Latinos being among the groups facing higher incidence rates. In this context, the significance of Hispanic/Latino endocrinologists cannot be overstated, as their unique perspectives and cultural insights contribute to a more nuanced understanding of the multifaceted factors influencing diabetes prevalence, management, and outcomes in the U.S. By actively involving Hispanic/Latino endocrinologists in diabetes research, we not only enhance the representation of diverse patient populations but also foster a more comprehensive approach to addressing the intricate intersections of genetics, lifestyle, and socio-cultural factors contributing to diabetes disparities in the nation. In the 2021 Physician Specialty Data Report, the Association of American Medical Colleges (AAMC) incorporated physician race and ethnicity information for the first time. Within the 7,354 actively practicing endocrinologists surveyed, only 636 individuals identified as Hispanic/Latino. The majority of these endocrinologists were predominantly dedicated to clinical practice. A descriptive analysis of 1011 abstracts on diabetes and glucose metabolism presented at the Endo Society from 2021 to 2023 revealed that 549 were authored by women and 458 by men. The majority (705 posters, 69.7%) originated from the U.S., and 306 (30.26%) were classified as international posters. Among these, 152 posters (15%) were associated with the Hispanic or Latino authors, but only 91 (9%) were published in the U.S. In conclusion, the engagement of Hispanic/Latino physicians in endocrinology is indispensable for advancing healthcare. Their participation brings diverse perspectives, facilitates a better understanding of health disparities, and promotes innovative research and patient care strategies. By actively involving Hispanic/Latino physicians, we contribute to a more comprehensive understanding of endocrine disorders and work towards a healthcare system that prioritizes inclusivity, cultural sensitivity, and collaboration, ultimately benefiting the well-being of individuals across diverse communities. Presentation: 6/2/2024

Potential pathogenic roles of ferroptosis and cuproptosis in cadmium-induced or exacerbated cardiovascular complications in individuals with diabetes.

Diabetes and its complications are major diseases that affect human health. Diabetic cardiovascular complications such as cardiovascular diseases (CVDs) are the major complications of diabetes, which are associated with the loss of cardiovascular cells. Pathogenically the role of ferroptosis, an iron-dependent cell death, and cuproptosis, a copper-dependent cell death has recently been receiving attention for the pathogenesis of diabetes and its cardiovascular complications. How exposure to environmental metals affects these two metal-dependent cell deaths in cardiovascular pathogenesis under diabetic and nondiabetic conditions remains largely unknown. As an omnipresent environmental metal, cadmium exposure can cause oxidative stress in the diabetic cardiomyocytes, leading to iron accumulation, glutathione depletion, lipid peroxidation, and finally exacerbate ferroptosis and disrupt the cardiac. Moreover, cadmium-induced hyperglycemia can enhance the circulation of advanced glycation end products (AGEs). Excessive AGEs in diabetes promote the upregulation of copper importer solute carrier family 31 member 1 through activating transcription factor 3/transcription factor PU.1, thereby increasing intracellular Cu+ accumulation in cardiomyocytes and disturbing Cu+ homeostasis, leading to a decline of Fe-S cluster protein and reactive oxygen species accumulation in cardiomyocytes mitochondria. In this review, we summarize the available evidence and the most recent advances exploring the underlying mechanisms of ferroptosis and cuproptosis in CVDs and diabetic cardiovascular complications, to provide critical perspectives on the potential pathogenic roles of ferroptosis and cuproptosis in cadmium-induced or exacerbated cardiovascular complications in diabetic individuals.

Swimming exercise regulates indices of skeletal muscle glucose metabolism and attenuates cardiac inflammatory cytokines activity via IL-6/TNF-α pathway in streptozotocin-induced diabetic rats

Diabetes mellitus (DM) manifests with impaired glucose metabolism that affects the musculoskeletal and cardiovascular systems. This study investigated the effects of swimming exercise on some indices of muscle glucose metabolism and cardiac inflammatory markers in diabetic rats induced with streptozotocin. Wistar rats of both sexes (150–200 g) were assigned into five groups of seven (7) rats. Group 1: Control (CON), Group 2: Diabetes only (DM), Group 3: Exercise only (EX), Group 4: Diabetes + Exercise (DM + EX), Group 5: Diabetes + Insulin (DM + IN). Type 1 DM was induced via intraperitoneal injection of streptozotocin (60 mg/kg). Insulin (6 IU/g) was administered (IP) to animals in group 5. Swimming exercise test was done for 27 days after which animals were euthanized. Blood samples were collected while hamstring muscles and heart were harvested and homogenized to assess biochemical parameters. The body weight, serum insulin level, muscle glucose metabolic indices (glycogen, Glut-4, CK-MB), and cardiac troponin-T were significantly (P < 0.05) decreased. In contrast, the random blood glucose, cardiac TNF-α, and IL-6 levels were increased (P < 0.05) in diabetic rats when compared with the control group. Swimming exercise regimen significantly (P < 0.05) reversed these anomalies by reducing blood glucose and cardiac inflammatory cytokines (TNF-α and IL-6) levels, improving serum insulin, muscle glycogen, and GLUT-4 expression in diabetic rats when compared to the DM group. The cardiac inflammatory cytokine levels in DM + EX were comparable to the DM + IN group. In conclusion, swimming exercise improves muscle glucose metabolism and protects the heart against cardiac inflammation in diabetic conditions.

Effects and Dynamics of D-alanine under Diabetic Conditions

Effects and Dynamics of D-alanine under Diabetic Conditions

Antidiabetic Potential and Chemical Profiling of Chloroform Fraction from Euclea racemosa subsp. schimperi In Vitro

Background: The chloroform fraction (CHCl3 Fr.) of Euclea racemosa subsp. schimperi has enormous interest for its potential therapeutic properties in managing diabetes and oxidative stress-related conditions. This study aimed to evaluate the chemical composition and biological activities of CHCl3 Fr. through LC-ESI-MS/MS and GC-MS analyses. Methods: The CHCl3 Fr. was analyzed using LC-ESI-MS/MS for identification of bioactive compounds, and its inhibitory effects on α-amylase and α-glucosidase were assessed in vitro. Additionally, the impact on insulin secretion, C-peptide levels, and oxidative stress markers (MDA and NO) were measured. Results: Nineteen bioactive compounds, including flavonoids, pentacyclic triterpenes, and monounsaturated fatty acids, were identified in the chloroform fraction (CHCl3 Fr.). It significantly inhibited α-amylase and α-glucosidase, with IC50 values of 21.16 ± 2.13 and 13.49 ± 0.83 µg/ml, respectively. In insulin-resistant Huh7 cells, CHCl3 Fr. reduced glucose levels and increased insulin and C-peptide levels (p &lt; 0.05). While it decreased malondialdehyde and nitric oxide, it did not significantly enhance catalase or total antioxidant capacity (p &gt; 0.05). Compared to metformin, CHCl3 Fr. showed less efficacy but may improve insulin resistance and reduce oxidative stress, likely due to its bioactive compounds. Conclusion: The presence of diverse bioactive compounds contributes to the antidiabetic effects of CHCl3 Fr. from E. r. ssp. shimperi, showed its potential as a natural therapeutic agent for diabetes management and oxidative stress reduction. Further investigations are warranted to explore its clinical applications and underlying mechanisms.

A novel trident shaped microstrip antenna sensor for glucose detection in human blood

A novel trident-shaped microstrip patch antenna sensor with great sensitivity is developed to estimate the amounts of glucose in blood samples of human. The suggested sensor is built on a 30 × 24 × 1.6 mm3 FR-4 substrate layer with a quality factor of 64 and a dielectric constant value of 4.3 resonating at 4.5 GHz. A finger phantom is the replica of the human finger and it is originated in the electromagnetic simulator in order to forecast the glucose content. By positioning the phantom replica at various localities on the constructed antenna sensor, the frequency shifts are observed for various levels of glucose concentration in different degrees, ranging from 0 to 1000 mg/dL are detected. The proposed sensor can identify diabetic conditions in patients as it has a finger phantom positioned parallel to the feed at the top of the antenna giving a 156 MHz paramount shift in frequency, sensitivity of 156 kHz/(mg/dL), and a minimum frequency shift of 24 MHz and sensitivity of 24 kHz/(mg/dL). To confirm the suggested sensor's functionality in a real-time environment, its performance is examined for various actual human finger postures, and the resulting resonance frequencies are observed. In order to detect the levels of glucose concentration, the suggested sensor's error performance is calculated and are found to be near to 1%.

Fam3a-mediated prohormone convertase switch in α-cells regulates pancreatic GLP-1 production in an Nr4a2-Foxa2-dependent manner

BackgroundFam3a has been demonstrated to regulate pancreatic β-cell function and glucose homeostasis. However, the role and mechanism of Fam3a in regulating α-cell function remain unexplored. MethodsGlucagon and glucagon-like peptide-1 (GLP-1) levels in pancreas and plasma were measured in global Fam3a knockout (Fam3a−/−) mice. Human islet single-cell RNA sequencing (scRNA-seq) datasets were utilized to analyze gene expression correlations between FAM3A and PCSK1 (encoding PC1/3, which processes proglucagon into GLP-1). Mouse pancreatic α-cell line αTC1.9 cells were transfected with Fam3a siRNA or plasmid for Fam3a knockdown or overexpression to explore the effects of Fam3a on PC1/3 expression and GLP-1 production. The downstream mediator (including Nr4a2) was identified by transcriptomic analysis, and its role was confirmed by Fam3a knockdown or overexpression in αTC1.9 cells. Based on the interacted protein of Nr4a2 and the direct binding to Pcsk1 promoter, the transcription factor Foxa2 was selected for further verification. Nuclear translocation assay and dual-luciferase reporter assay were used to clarify the involvement of Fam3a-Nr4a2-Foxa2 pathway in PC1/3 expression and GLP-1 production. Moreover, α-cell-specific Fam3a knockout (Fam3aα−/−) mice were constructed to evaluate the metabolic variables and hormone levels under normoglycemic, high-fat diet (HFD)-fed and streptozotocin (STZ)-induced diabetic conditions. Exendin 9–39 (Ex9), a GLP-1 receptor antagonist, was used to investigate GLP-1 paracrine effects in Fam3aα−/− mice and in their primary islets. ResultsCompared with wild-type mice, pancreatic and plasma active GLP-1 levels were increased in Fam3a−/− mice. Analysis of human islet scRNA-seq datasets showed a significant negative correction between FAM3A and PCSK1 in α-cells. Fam3a knockdown upregulated PC1/3 expression and GLP-1 production in αTC1.9 cells, while Fam3a overexpression displayed inverse effects. Transcriptomic analysis identified Nr4a2 as a key downstream mediator of Fam3a, and Nr4a2 expression in αTC1.9 cells was downregulated and upregulated by Fam3a knockdown and overexpression, respectively. Nr4a2 silencing increased PC1/3 expression, albeit Nr4a2 did not directly bind to Pcsk1 promoter. Instead, Nr4a2 formed a complex with Foxa2 to facilitate Fam3a-mediated Foxa2 nuclear translocation. Foxa2 negatively regulated PC1/3 expression and GLP-1 production. Besides, Foxa2 inhibited the transcriptional activity of Pcsk1 promoter at specific binding sites 10 and 6, and this inhibition was intensified by Nr4a2 in αTC1.9 cells. Compared with Flox/cre littermates, improved glucose tolerance, increased active GLP-1 level in pancreas and plasma, upregulated plasma insulin level in response to glucose, and decreased plasma glucagon level were observed in Fam3aα−/− mice. Primary islets isolated from Fam3aα−/− mice also showed an increase in active GLP-1 and insulin release. In addition, the insulinotropic effect of intra-islet GLP-1 was blocked by Ex9 in Fam3aα−/− mice and in their primary islets. Similarly, HFD-fed Fam3aα−/− mice also exhibited an improved glucose tolerance. Both HFD-fed and STZ-induced diabetic Fam3aα−/− mice showed an increased pancreatic active GLP-1 level, an elevated plasma insulin level and a reduced plasma glucagon level. ConclusionsFam3a deficiency in α-cells enhances pancreatic GLP-1 production to improve β-cell function via paracrine signaling in an Nr4a2-Foxa2-PC1/3-dependent manner. Our study unveils a novel strategy for reprogramming α-cell proglucagon processing output from glucagon to GLP-1 and deepen the understanding of crosstalk between α-cells and β-cells.

Alpha(α)-mangostin (Xanthone of Garcinia mangostana L.): Augmenting Macrophages Activity for an Effective Diabetic Wound Healing

Diabetic wounds are particularly difficult to treat medically because they heal at a slower pace than regular wounds. Macrophages are essential in all stages of normal wound healing, including inflammation, proliferation and rem odelling. When wound healing is affected, macrophages can reduce the level of growth factor and increase the level of interleukin-6 (IL-6), disrupt the balance between tissue inhibitors of metalloproteinase (TIMPs) and matrix metalloproteinase (MMPs), which can slow down healing. Alpha(α)-mangostin, a natural xanthone derived from the pericarp of the mangosteen, has gained considerable attention due to its anti-inflammatory properties, suggesting its potential to promote wound healing. However, its exact role in healing diabetic foot ulcers, common in diabetes, remains unclear. Hence, this study aims to explore how α-mangostin might affect diabetic wound healing by evaluating its impact on PDGF, CTGF, BFGF, VEGF, TGF-β, MMP-9, TIMP-2 and IL-6 secretion in macrophage cells. Human monocytic macrophages (THP-1) were incubated with a 35 mM glucose solution for 72 h to create a glucose-enriched medium. The cells were then incubated with α-mangostin (0.15, 2.5 and 5 µg/mL) together with 35 mM glucose. Carboxymethyl cellulose (CMC) served as positive controls; glucose-enriched media and media-alone served as negative controls. Protein expression was measured using ELISA. α-mangostin (2.5 µg/mL) increased the levels of PDGF and VEGF and decreased the level of MMP-9 compared to glucose controls. There was no significant difference in other growth factors, TIMP-2 and IL-6 protein levels across any of the treatment groups compared to glucose controls. In conclusion, α-mangostin particularly at 2.5 µg/mL demonstrated a significant increase in PDGF and VEGF levels while simultaneously reducing MMP-9 in macrophage cells under glucose-induced conditions. These findings suggest that α-mangostin holds the potential for enhancing the healing of chronic wounds in diabetic conditions. HIGHLIGHTS Treatment of macrophages (THP-1 cells) with 2.5 µg/mL Alpha (α)-mangostin in a high glucose medium led to a significant increase in PDGF and VEGF secretion compared to glucose control. Treatment of the cells with 2.5 µg/mL Alpha (α)-mangostin in a high glucose medium led to a significant reduction of MMP-9 secretion compared to glucose control. There is no significant effects of Alpha (α)-mangostin on IL-6 and TIMP secretion compared to controls This study suggests that Alpha (α)-mangostin may be beneficial in promoting diabetic wound healing via stimulation of PDGF and VEGF secretion and reducing MMP-9 levels. GRAPHICAL ABSTRACT

The Role of social care in health organizations for managing chronic Medical Conditions: A Comprehensive Review

This review examines the role of social care in managing chronic medical conditions within health organizations. Chronic diseases such as diabetes, hypertension, and cardiovascular conditions require comprehensive management strategies that extend beyond medical treatment to address the broader social determinants of health, including socioeconomic factors, social support systems, and community resources. The integration of social care into healthcare settings has emerged as a critical approach to improving patient outcomes and reducing healthcare costs. This review highlights the impact of social care models, such as Accountable Care Organizations (ACOs) and Health Homes, on chronic disease management. By analyzing current literature and case studies, the review explores how health organizations have successfully integrated social services to support patients with chronic conditions. Challenges such as funding, workforce development, and institutional barriers are also discussed. The findings suggest that a multidisciplinary approach combining medical care with social support can enhance care continuity, patient engagement, and long-term disease management. This review emphasizes the need for policy changes and innovative models to facilitate the effective integration of social care into chronic disease management frameworks.

EXPLORING THE STREPTOZOTOCIN-NICOTINAMIDE MOUSE MODEL IN BALB/C MICE: GAINING INSIGHTS INTO DIABETIC PNEUMOPATHY

Background: Diabetic pneumopathy has been a topic of interest in the present era, and it caught the eye during the COVID-19 pandemic. Extensive research provides compelling data supporting the association between diabetes and lung injury, establishing the lung as a principal organ affected by diabetes. However, the understanding of diabetic lung has always remained under shadow. For this purpose, we aimed to search for diabetic lung conditions by using a type 2 diabetic model in BALB/c mice. Methods: The study spanned from May to June 2023 at Ziauddin University. Nicotinamide, followed by streptozotocin, was injected into the mice. Mice were confirmed diabetic on the 7th day and housed for the onset of diabetic lung complications. After 28 days, mice underwent an oral glucose tolerance test and were then sacrificed, followed by the collection of bronchoalveolar lavage fluid and the extraction of the lungs. Lungs were fixed for histological analysis. Results: The presence of increased glycaemic levels, further verified by abnormal glucose tolerance, confirmed the establishment of the type 2 diabetic model. Additionally, the diabetic group showed lung fibrotic changes. Conclusion: The foundation of a type 2 diabetic model with the target of generating pneumopathy was accomplished successfully. Pak J Physiol 2024;20(3):31?6, DOI: https://doi.org/10.69656/pjp.v20i3.1673

Redefining C-peptide: Therapeutic Potential in Mitigating Diabetic Microvascular Complications

This review examines the changing insights into C-peptide and its potential for therapeutic actions against the backdrop of diabetic microvascular complications. C-peptide, formerly regarded as just a byproduct of insulin production, has recently surfaced as a bioactive peptide with important physiological effects. Findings indicate that C-peptide has anti-inflammatory and antioxidant capabilities, strengthens glucose utilization, and raises insulin sensitivity. Trial results for C-peptide replacement therapy show hope for treating diabetic neuropathy and nephropathy conditions. The article reviews the influence of C-peptide on cells, focusing on interactions with cell surface receptors and the stimulation of signaling molecules inside cells. C-peptide's role in generating nitric oxide, activating Na+K+ATPase, and improving the flow of blood in microvessels is emphasized. The review explores how C-peptide affects red blood cell deformability and its potential capabilities in reducing multiple diabetic complications. Besides, the article examines current research into C-peptide analogs that have a long-lasting effect and clinical trials that assess C-peptide replacement therapy. ErsattaTM, a new generation of weekly dosage disease-modifying replacement peptides, is seen as a promising advance in the treatment of chronic diabetes complications. Overall, this review stresses the increased acceptance of C-peptide as a powerful agent for the management of microvascular complications in diabetes, giving hope for superior results in patients with both type 1 and potentially type 2 diabetes.

Modelling the Non-linear Associations between Age and Health: Implications for Care

Abstract Background Ageing is a complex biological process that weakens the body's defences against various health problems and diseases. This decline is not uniform or linear; rather, it varies significantly among individuals. Understanding the non-linear progression of ageing is crucial for identifying critical periods where intervention might be most beneficial. This study aimed to explore nonlinearities in the association between age and health outcomes. Methods Using generalised additive models, we analysed data from the 2020 wave of the United States Health and Retirement Study. This modelling approach allows for the detailed examination of nonlinearities in health outcomes across different ages. Our sample consisted of adults aged over 50 (n = 1338; mean = 68; range = 50 – 95). We assessed seven health outcomes (heart conditions, diabetes, cholesterol, blood pressure, fatigue, back pain, and headaches) and seven protective behaviours (prostate exams, mammograms, cholesterol screenings, pap smears, flu vaccinations, dental check-ups, and smoking patterns) reflecting various aspects of health status and behaviour. Results The analysis indicated a significant and pronounced non-linear relationship between age and certain health outcomes, namely headaches, blood pressure, diabetes, and heart conditions. Additionally, ageing was non-linearly associated with specific health behaviours, including the uptake of prostate exams, mammograms, flu vaccinations, and smoking prevalence. Notably, distinct patterns emerged concerning health behaviours in relation to age-specific screening policies. Conclusion The findings of this study reveal that the probability of developing health problems or engaging in health protective behaviours do not increase/decrease linearly in direct proportion to age. Rather, the probability curve exhibits fluctuations, presenting periods of heightened odds interspersed with phases of relative stability. Such non-linearity may be partially attributed to policy decisions but could also reflect a complex interplay of factors such as weakened immune systems, access to healthcare, personal health beliefs, and the evolving perception of risk as one grows older.

A Performance Analysis of RNN Algorithms for Accurate Hypoglycemia Prediction in Type-1 Diabetes

Diabetes is a chronic disease originating from preeminent blood glucose levels where there is an impairment in the ability of the human body to produce or effectively use insulin, therefore resulting in possible complications to various organ systems. Hypoglycemia can be defined as a critical condition in diabetes that is characterized by very low levels of blood sugar and can emanate from any imbalance between insulin, glucose, and external factors such as medication or physical activity. The prediction of hypoglycemia is a very important task in diabetes management, which encompasses sophisticated technologies and deep-learning systems, such as RNNs, in performing analyses on patient-specific data. These must provide timely warnings to avoid hazardous blood sugar dips. This paper takes a close look at the performance of RNN in the case of accurate hypoglycemia prediction among patients with Type-1 Diabetes, considering a dataset from Shanghai T1DM. In this work, three different RNN architectures are considered for performance evaluation: Long-Short-Term Memory (LSTM), Gated Recurrent Unit (GRU), and Simple RNN. The main goal was to compare their predictive performances in forecasting hypoglycemic events, which is an issue of utmost relevance when it comes to proactive diabetes management. The results show generally variable performances by the RNN models. Overall, GRU performed with striking accuracy in hypoglycemia predictions, while LSTM had high specificity. These findings underline that various metrics should be considered for the comprehensive evaluation of predictive models in the management of diabetes. It will give an idea about various RNN algorithms, strengths, and weaknesses to develop more effective and personalized strategies related to hypoglycemia prediction in Type-1 Diabetes.

The association of systemic condition and medications on alveolar bone loss and tooth attrition.

Periodontal disease is caused by subgingival bacteria that adversely affect the host immune system and create and maintain unmitigated inflammation in gingival and periodontal tissues. The condition is also linked to systemic conditions including cardiovascular disease, diabetes, and arthritis. Periodontitis elevates the bacterial load and spreads systemic inflammation through infection and inflammation. The main radiographic sign of periodontitis is marginal bone loss. Risk factors, including medications, smoking, age, and sex, are known to influence periodontal health. However, there is little information about the impact of systemic conditions and medications on tooth wear. The aim of the present study was to assess the association between systemic conditions and medications and radiographic signs of tooth wear and marginal bone loss. This retrospective analysis was conducted on a group of 2,223 consecutive patients who came for dental treatment in the clinics of a large Health Maintenance Organization in Israel. Data available for the study included details of concomitant systemic diseases and medication and full-mouth radiographic surveys. Odds ratio and logistic regression analysis were used to detect associations between systemic conditions and medication, and marginal bone loss and tooth wear. The results indicated an elevated odds ratio for tooth wear associated with age, sex, and smoking across all age groups. Among young patients, those using proton pump inhibitors and psychiatric medications had an elevated risk of tooth wear. Age, smoking, and diabetes conditions were associated with an increased odds ratio for marginal bone loss in all age groups. Psychiatric medications and sex elevated the odds ratio for marginal bone loss only among older patients. The results highlight the significant impact of age, sex, and smoking on tooth wear, and extend these risks to alveolar bone loss when combined with diabetes and psychiatric conditions.

Unraveling the complex interplay between abnormal hemorheology and shape asymmetry in flow through stenotic arteries

Background and Objective:Stenosis or narrowing of arteries due to the buildup of plaque is a common occurrence in atherosclerosis and coronary artery disease (CAD), limiting blood flow to the heart and posing substantial cardiovascular risk. While the role of geometric irregularities in arterial stenosis is well-documented, the complex interplay between the abnormal hemorheology and asymmetric shape in flow characteristics remains unexplored. Methods:This study investigates the influence of varying hematocrit (Hct) levels, often caused by conditions such as diabetes and anemia, on flow patterns in an idealized eccentric stenotic artery using computational fluid dynamics simulations. We consider three physiological levels of Hct, 25%, 45%, and 65%, representing anemia, healthy, and diabetic conditions, respectively. The numerical simulations are performed for different combinations of shape eccentricity and blood rheological parameters, and hemodynamic indicators such as wall shear stress (WSS), oscillatory shear index (OSI), are relative residence time (RRT) are calculated to assess the arterial health. Results:Our results reveal the significant influence of Hct level on stenosis progression. CAD patients with anemia are exposed to lower WSS and higher OSI, which may increase the propensity for plaque progression and rupture. However, for CAD patients with high Hct level—as is often the case in diabetes—the WSS at the minimal lumen area increases rapidly, which may also lead to plaque rupture and cause adverse events such as heart attacks. These disturbances promote endothelial dysfunction, inflammation, and thrombus formation, thereby intensifying cardiovascular risk. Conclusions:Our findings underscore the significance of incorporating hemorheological parameters, such as Hct, into computational models for accurate assessment of flow dynamics. We envision that insights gained from this study will inform the development of tailored treatment strategies and interventions in CAD patients with common comorbidities such as diabetes and anemia, thus mitigating the adverse effects of abnormal hemorheology and reducing the ever-growing burden of cardiovascular diseases.

Impact of Diabetic Condition on the Remodeling of In Situ Tissue-Engineered Heart Valves.

Most in situ tissue-engineered heart valve (TEHV) evaluation studies are conducted in a healthy physical environment, which cannot accurately reflect the specific characteristics of patients. In this study, we established a diabetic rabbit model and implanted decellularized extracellular matrix (dECM) into the abdominal aorta of rabbits through interventional surgery with a follow-up period of 8 weeks. The results indicated that dECM implants in diabetic rabbits exhibited poorer endothelialization and more severe fibrosis compared to those in healthy animals. Furthermore, mechanistic studies revealed that high glucose induced endothelial cell (EC) apoptosis and impeded their proliferation and migration, accompanied by an increase in reactive oxygen species (ROS) concentration and a decrease in the nitric oxide (NO) level. High glucose also led to elevated ROS levels and an increased expression of inflammatory factors and transforming growth factor β1 (TGF-β1) in macrophages, contributing to fibrosis. These findings suggest that oxidative-stress-mediated mechanisms are likely the primary pathways affecting heart valve repair and regeneration under diabetic conditions. Therefore, future design and evaluation of TEHVs may concern more patient-specific circumstances.