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Diabetes mellitus is one of the top ten causes of death worldwide, accounting for 6.7 million deaths in 2021, and is one of the most rapidly growing global health emergencies of this century. Although several classes of therapeutic drugs have been invented and applied in clinical practice, diabetes continues to pose a serious and growing threat to public health and places a tremendous burden on those affected and their families. The strategy of reducing carbohydrate digestibility by inhibiting the activities of α-glucosidase and α-amylase is regarded as a promising preventative treatment for type 2 diabetes. In this study, we investigated the dual inhibitory effect against two polysaccharide hydrolytic enzymes of flavonoid derivatives from an in-house chemical database. By combining molecular docking and structure–activity relationship analysis, twelve compounds with docking energies less than or equal to − 8.0 kcal mol−1 and containing required structural features for dual inhibition of the two enzymes were identified and subjected to chemical synthesis and in vitro evaluation. The obtained results showed that five compounds exhibited dual inhibitory effects on the target enzymes with better IC50 values than the approved positive control acarbose. Molecular dynamics simulations were performed to elucidate the binding of these flavonoids to the enzymes. The predicted pharmacokinetic and toxicological properties suggest that these compounds are viable for further development as type 2 diabetes drugs. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is regarded as one of the most critical public health challenges of the 21st century. It has evolved into a burgeoning epidemic since the last century, and today ranks among the major causes of mortality worldwide. Diabetes specialist nurses (DSNs) are central to good patient care and outcomes including confident self-care management. Evidence shows that DSNs are cost-effective, improve clinical outcomes, and reduce length of stay in hospital. In this brief narrative review, we aim to describe the roles of DSNs and their contribution in the treatment and management of patients with DM. This narrative review describes the importance of DSNs in healthcare practice, in the inpatient and outpatient departments, in the pediatrics department, in managing diabetic foot ulcers, in the treatment and management of gestational diabetes, in prescribing medications for DM and in diabetes self-management education on glycosylated hemoglobin, and cardiovascular risk factors. To conclude, DSNs have a crucial role in the treatment and management of patients with DM and its complications. DSNs have a great impact on diabetes therapy, and hence implementation of DSNs and nurse-led diabetic clinics might be beneficial for the health care system. Finally, having DSNs might significantly contribute to good healthcare practice and support. Even though DSNs are not available in several regions around the globe, and even though this post is still new to several health care institutions, the presence of DSNs recognized and certified by the various healthcare systems would be very useful. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes prevalence is steadily increasing worldwide, and South Africa is one of the countries in Africa with the highest prevalence of this disease, along with other non-communicable diseases. The adherence to treatment in male patients with type 2 diabetes is influenced by their attitudes towards medication and how they perceive their condition. To some extent, these factors impact the treatment outcomes for patients undergoing type 2 diabetes treatment. The purpose of this study was to investigate the perceptions of male patients with type 2 diabetes on their adherence to diabetic therapy. The study was conducted in the clinics of the City of Tshwane Metropolitan municipality in Gauteng. Methods: This study followed a qualitative, exploratory design. Data were gathered from 15 male patients who were purposefully sampled through in-person, one-on-one interviews with the principal investigator. The eight steps outlined by Tesch were used to analyse the participant data. Results: Emergent themes indicated that there were barriers to adherence to diabetic treatment and also factors that promoted adherence to diabetic treatment among the participants. Several factors were found to affect treatment uptake among the participants. Conclusion: Patients demonstrated various reactions to diabetic treatment, highlighting the need for reinforcing education at the time of diagnosis and treatment initiation. Additionally, regular patient follow-up may be essential to improve adherence among patients. Contribution: The study highlights the importance of health promotion and the need to develop materials for medication-specific counselling for patients receiving diabetic treatment, in order to promote adherence.

Aim: The comparative effectiveness of basal insulins has been examined in several studies. However, current treatment algorithms provide a list of options with no clear differentiation between different basal insulins as the optimal choice for initiation. Methods: A comprehensive search of MEDLINE, Embase, Cochrane Library, ISI, and Scopus, and a reference list of retrieved studies and reviews were performed up to November 2023. We identified phase III randomized controlled trials (RCTs) comparing the efficacy and safety of basal insulin regimens. The primary outcomes evaluated were HbA1c reduction, weight change, and hypoglycemic events. The revised Cochrane ROB-2 tool was used to assess the methodological quality of the included studies. A random-effects frequentist network metaanalysis was used to estimate the pooled weighted mean difference (WMD) and odds ratio (OR) with 95% confidence intervals considering the critical assumptions in the networks. The certainty of the evidence and confidence in the rankings was assessed using the GRADE minimally contextualized approach. Results: Of 20,817 retrieved studies, 44 RCTs (23,699 participants) were eligible for inclusion in our network meta-analysis. We found no significant difference among various basal insulins (including Neutral Protamine Hagedorn (NPH), ILPS, insulin glargine, detemir, and degludec) in reducing HbA1c. Insulin glargine, 300 U/mL (IGlar-300) was significantly associated with less weight gain (mean difference ranged from 2.9 kg to 4.1 kg) compared to other basal insulins, namely thrice-weekly insulin degludec (IDeg-3TW), insulin degludec, 100 U/ mL (IDeg-100), insulin degludec, 200 U/mL (IDeg-200), NPH, and insulin detemir (IDet), but with low to very low certainty regarding most comparisons. IDeg-100, IDeg-200, IDet, and IGlar-300 were associated with significantly lower odds of overall, nocturnal, and severe hypoglycemic events than NPH and insulin lispro protamine (ILPS) (moderate to high certainty evidence). NPH was associated with the highest odds of overall and nocturnal hypoglycemia compared to others. Network meta-analysis models were robust, and findings were consistent in sensitivity analyses. Conclusion: The efficacy of various basal insulin regimens is comparable. However, they have different safety profiles. IGlar-300 may be the best choice when weight gain is a concern. In contrast, IDeg-100, IDeg-200, IDet, and IGlar-300 may be preferred when hypoglycemia is the primary concern. [ABSTRACT FROM AUTHOR]

Diabetes mellitus type 1 (T1D) and type 2 (T2D) develop due to dysfunction of the Langerhans islet β-cells in the pancreas, and this dysfunction is mediated by oxidative, endoplasmic reticulum (ER), and mitochondrial stresses. Although the two types of diabetes are significantly different, β-cell failure and death play a key role in the pathogenesis of both diseases, resulting in hyperglycemia due to a reduced ability to produce insulin. In T1D, β-cell apoptosis is the main event leading to hyperglycemia, while in T2D, insulin resistance results in an inability to meet insulin requirements. It has been suggested that autophagy promotes β-cell survival by delaying apoptosis and providing adaptive responses to mitigate the detrimental effects of ER stress and DNA damage, which is directly related to oxidative stress. As people with diabetes are now living longer, they are more susceptible to a different set of complications. There has been a diversification in causes of death, whereby a larger proportion of deaths among individuals with diabetes is attributable to nonvascular conditions; on the other hand, the proportion of cancer-related deaths has remained stable or even increased in some countries. Due to the increasing cases of both T1D and T2D, these diseases become even more socially significant. Hence, we believe that search for any opportunities for control of this disease is an overwhelmingly important target for the modern science. We focus on two differences that are characteristic of the development of diabetes’s last periods. One of them shows that all-cause death rates have declined in several diabetes populations, driven in part by large declines in vascular disease mortality but large increases in oncological diseases. Another hypothesis is that some T2D medications could be repurposed to control glycemia in patients with T1D. [ABSTRACT FROM AUTHOR]

Insulin treatment is fundamental to diabetes management. Basal insulin therapy reduces intraday glycemic fluctuations upon reaching a steady state. Besides better blood glucose regulation and achieving target HbA1c values in patients, it also offers protection from diabetes complications. In this review, we aimed to compare basal-acting insulins in light of the literature. We reviewed current evidence related to diabetes treatment with basal insulins. This includes discussions on clinical trials and meta-analyses concerning first and second-generation ultra-long-acting basal insulins. Treatment indications for long-acting basal insulins, which have shown benefits and are considered superior or comparable to others in the literature, are derived from current clinical studies and meta-analyses, which form the basis of the recommendations in this review. First and second-generation basal insulins do not show much superiority over each other in terms of blood glucose regulation and reaching the target HbA1c. However, second-generation basal insulins cause fewer hypoglycemic events. We recommend using the appropriate basal insulin in patient-based, individualized treatments. Basal insulin Icodec may become more widely used over time, owing to its association with less hypoglycemia and a reduction in the number of injections. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2DM) is a major cause of morbidity and mortality globally. Carnosine, a naturally occurring dipeptide, has anti-inflammatory, antioxidant, and anti-glycating effects, with preliminary evidence suggesting it may improve important chronic disease risk factors in adults with cardiometabolic conditions. In this randomised controlled trial, 43 adults (30%F) living with prediabetes or T2DM consumed carnosine (2 g) or a matching placebo daily for 14 weeks to evaluate its effect on glucose metabolism assessed via a 2-h 75 g oral glucose tolerance test. Secondary outcomes included body composition analysis by dual energy x-ray absorptiometry (DEXA), calf muscle density by pQCT, and anthropometry. Carnosine supplementation decreased blood glucose at 90 min (−1.31 mmol/L; p = 0.02) and 120 min (−1.60 mmol/L, p = 0.02) and total glucose area under the curve (−3.30 mmol/L; p = 0.04) following an oral glucose tolerance test. There were no additional changes in secondary outcomes. The carnosine group results remained significant before and after adjustment for age, sex, and change in weight (all>0.05), and in further sensitivity analyses accounting for missing data. There were no significant changes in insulin levels. This study provides preliminary support for larger trials evaluating carnosine as a potential treatment for prediabetes and the initial stages of T2DM. Likely mechanisms may include changes to hepatic glucose output explaining the observed reduction in blood glucose without changes in insulin secretion following carnosine supplementation. [ABSTRACT FROM AUTHOR]

Treatment for diabetes includes anti-diabetic medication in addition to lifestyle improvements through diet and exercise. In Japan, protocol-based pharmacotherapy management allows drug treatment to be provided through cooperation between physicians and pharmacists, based on a protocol that is prepared and agreed upon in advance. However, there are no studies to clarify the relationship between patient characteristics and therapeutic effects after pharmacist intervention in protocol-based pharmacotherapy management for patients with diabetes. Therefore, this study aimed to use protocol-based reports from pharmacies to understand the status of outpatient diabetes medication compliance. We classified patients with diabetes on the basis of patient characteristics that can be collected in pharmacies and investigated the characteristics that impacted diabetes treatment. Patients were prescribed oral anti-diabetic drugs at outpatient clinics of Hitachinaka General Hospital, Hitachi, Ltd., from April 2016 to March 2021. Survey items included patient characteristics (sex, age, number of drugs used, observed number of years of anti-diabetic drug prescription, number of anti-diabetic drug prescription days, and presence or absence of leftover anti-diabetic drugs) and HbA1c levels. Graphical analyses indicated the relationship between each categorised patient characteristic using multiple correspondence analyses. Subsequently, the patients were clustered using K-means cluster analysis based on the coordinates obtained for each patient. Patient characteristics and HbA1c values were compared between the groups for each cluster. A total of 1,910 patients were included and classified into three clusters, with clusters 1, 2, and 3 containing 625, 703, and 582 patients, respectively. Patient characteristics strongly associated with Cluster 1 were ages between 65 and 74 years, use of three or more anti-diabetic drugs, use of 3 years or more of anti-diabetic drugs, and leftover anti-diabetic drugs. Furthermore, Cluster 1 had the highest number of patients with worsening HbA1c levels compared with other clusters. Using the leftover drug adjustment protocol, we clarified the patient characteristics that affected the treatment course. We anticipate that through targeted interventions in patients exhibiting these characteristics, we can identify those who are irresponsibly continuing with drug treatment, are not responding well to therapy, or both. This could substantially improve the efficacy of their anti-diabetic care.

The general goals of diabetes treatment are to maintain optimal individualized glycemic targets and to prevent complications. Today, there are significant barriers to successful diabetes therapy, such as parenteral drug administration, decreased therapeutic efficacy after an initial improvement in glycemia, inaccessibility of new medicines in lower-income countries, and high drug prices. Accordingly, significant research attention has been devoted to the development of a cheap and comfortable antidiabetic agent, which demonstrates success in lowering blood glucose levels as well as fewer toxicity properties. In recent years, the effects of inorganic and organic vanadium compounds have been investigated in diabetes treatment. These studies have found the low bioavailability of orally administered inorganic vanadium salts; thus, effective doses to reduce blood glucose levels to normal may cause serious adverse events. In addition, the only study with an organo-vanadium compound (bis(maltolato)oxovanadium(IV)), which has reached Phase IIa clinical trial, was terminated after three months due to renal complications. Moreover, despite a growing interest in polyoxovanadates for treating diabetes in the last few years, the toxic potentials of these compounds are still unknown. However, the precise mechanism of their antidiabetic actions remains unclear. A broad spectrum of possible mechanisms and hypotheses, such as enhancement of insulin secretion and enhanced sensitivity to insulin, as well as suppression of hepatic glucose production and decrease of intestinal glucose absorption, have been presented. In conclusion, besides the promising results obtained in animal and human studies, no vanadium compound has successfully reduced blood glucose with acceptable safety and tolerability. More studies of vanadium benefit-risk could lead to a new era in vanadium biomedicine.

Glucose is essential to the physiological processes of vertebrates. Mammalian physiological stability requires a relatively stable blood glucose level (~5 mM), whereas other vertebrates have greater flexibility in regulating blood glucose (0.5–25 mM). GCGR family receptors play an important role in vertebrate glucose regulation. Here, we examine the evolution of the GCGR family ligand-receptor systems in different species. Comparatively, we discover that the conserved sequences among GCG family ligands lead to the non-specific activation of ligands across species. In particular, we observe that glucagon-like peptide 1 receptor (GLP1R), glucagon-like peptide 2 receptor (GLP2R), and glucagon-like receptor (GCGLR, also called GCRPR) are arbitrarily activated by other members of the ligand family in birds. Moreover, we reveal that Gallus gallus GLP2 (gGLP2) effectively activates mammalian GLP1R and improves glucose tolerance in diabetic mice. Our study has important implications for understanding blood glucose stabilization in vertebrates and demonstrates that gGLP2 may be a potential drug for treating type 2 diabetes.

Diabetes: This term includes a number of disorders that are characterized by problems with the hormone insulin, which the pancreas naturally produces to help the body absorb the sugar in the blood, as issues in the production of this hormone raise the level of sugar in the blood and may lead to many other diseases and problems. That may lead to death. We use technology in the field of artificial intelligence to help medical specialists to classify diseases of humans by taking some measurements such as blood pressure, diabetes, heart rate, and other readings according to the diagnosis of the disease within periods of time and working on analyzing these readings to visualize the patient's health state. And may analysis to determine the patient's ability to respond to the system. In this paper, we used a Wireless sensor network technology to transmit patient data to the training server, then used artificial intelligence (AI) in the training and classification phase to find out if a patient has diabetes or not. [ABSTRACT FROM AUTHOR]

Diabetes is one of the leading chronic diseases globally with a significant impact on mortality. This condition is associated with chronic microvascular and macrovascular complications caused by vascular damage. Recently, endothelial progenitor cells (EPCs) raised interest due to their regenerative properties. EPCs are mononuclear cells that are derived from different tissues. Circulating EPCs contribute to regenerating the vessel's intima and restoring vascular function. The ability of EPCs to repair vascular damage depends on their number and functionality. Diabetic patients have a decreased circulating EPC count and impaired EPC function. This may at least partially explain the increased risk of diabetic complications, including the increased cardiovascular risk in these patients. Recent studies have confirmed that many currently available drugs with proven cardiovascular benefits have beneficial effects on EPC count and function. Among these drugs are also medications used to treat different types of diabetes. This manuscript aims to critically review currently available evidence about the ways anti-diabetic treatment affects EPC biology and to provide a broader context considering cardiovascular complications. The therapies that will be discussed include lifestyle adjustments, metformin, sulphonylureas, gut glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor analogs, sodium-glucose transporter 2 inhibitors, and insulin. [ABSTRACT FROM AUTHOR]

AimThe comparative effectiveness of basal insulins has been examined in several studies. However, current treatment algorithms provide a list of options with no clear differentiation between different basal insulins as the optimal choice for initiation.MethodsA comprehensive search of MEDLINE, Embase, Cochrane Library, ISI, and Scopus, and a reference list of retrieved studies and reviews were performed up to November 2023. We identified phase III randomized controlled trials (RCTs) comparing the efficacy and safety of basal insulin regimens. The primary outcomes evaluated were HbA1c reduction, weight change, and hypoglycemic events. The revised Cochrane ROB-2 tool was used to assess the methodological quality of the included studies. A random-effects frequentist network meta-analysis was used to estimate the pooled weighted mean difference (WMD) and odds ratio (OR) with 95% confidence intervals considering the critical assumptions in the networks. The certainty of the evidence and confidence in the rankings was assessed using the GRADE minimally contextualized approach.ResultsOf 20,817 retrieved studies, 44 RCTs (23,699 participants) were eligible for inclusion in our network meta-analysis. We found no significant difference among various basal insulins (including Neutral Protamine Hagedorn (NPH), ILPS, insulin glargine, detemir, and degludec) in reducing HbA1c. Insulin glargine, 300 U/mL (IGlar-300) was significantly associated with less weight gain (mean difference ranged from 2.9 kg to 4.1 kg) compared to other basal insulins, namely thrice-weekly insulin degludec (IDeg-3TW), insulin degludec, 100 U/mL (IDeg-100), insulin degludec, 200 U/mL (IDeg-200), NPH, and insulin detemir (IDet), but with low to very low certainty regarding most comparisons. IDeg-100, IDeg-200, IDet, and IGlar-300 were associated with significantly lower odds of overall, nocturnal, and severe hypoglycemic events than NPH and insulin lispro protamine (ILPS) (moderate to high certainty evidence). NPH was associated with the highest odds of overall and nocturnal hypoglycemia compared to others. Network meta-analysis models were robust, and findings were consistent in sensitivity analyses.ConclusionThe efficacy of various basal insulin regimens is comparable. However, they have different safety profiles. IGlar-300 may be the best choice when weight gain is a concern. In contrast, IDeg-100, IDeg-200, IDet, and IGlar-300 may be preferred when hypoglycemia is the primary concern.

Background and aimsStomach cells can be converted to insulin-producing cells by Neurog3, MafA, and Pdxl over-expression. Enteroendocrine cells can be similarly made to produce insulin by the deletion of FOXO1. Characteristics and functional properties of FOXO1-expressing stomach cells are not known.MethodsUsing mice bearing a FOXO1-GFP knock-in allele and primary cell cultures, we examined the identity of FOXO1-expressing stomach cells and analyzed their features through loss-of-function studies with red-to-green fluorescent reporters.ResultsFOXO1 localizes to a subset of Neurog3 and parietal cells. FOXO1 deletion ex vivo or in vivo using Neurog3-cre or Atp4b-cre increased numbers of parietal cells, generated insulin- and C-peptide-immunoreactive cells, and raised Neurog3 messenger RNA. Gene expression and ChIP- seq experiments identified the cell cycle regulator cyclin E1 (CCNE1) as a FOXO1 target.ConclusionFOXO1 is expressed in a subset of stomach cells. Its ablation increases parietal cells and yields insulin-immunoreactive cells, consistent with a role in lineage determination.

Abstract Background The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. Methods The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. Results and conclusions All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

A transdermal patch that delivers insulin at high glucose concentrations can offer tremendous advantages to ease the concern of safety and improve the quality of life for people with diabetes. Herein, a novel self‐crosslinkable and glucose‐responsive polymer‐based microneedle patch (MN) is designed to deliver insulin at hyperglycemia. The microneedle patch is made of hyaluronic acid polymers functionalized with dopamine and 4‐amino‐3‐fluorophenylboronic acid (AFBA) that can be quickly crosslinked upon mixing of the polymer solutions in the absence of any chemicalcrosslinking agents or organic solvents. The catechol groups in the dopamine (DA) units form covalent crosslinkages among themselves by auto‐oxidation and dynamic crosslink with phenylboronic acid (PBA) via complexation. The reversible crosslinkages between catechol and boronate decrease with increasing glucose concentration leading to higher swelling and faster insulin release at hyperglycemia as compared to euglycemia. Such superior glucose‐responsive properties are demonstrated by in vitro analyses and in vivo efficacy studies. The hydrogel polymers also preserve native structure and bioactivity of insulin, attributable to the interaction of hyaluronic acid (HA) with insulin molecules, as revealed by experiments and molecular dynamics simulations. The simplicity in the design and fabrication process, and glucose‐responsiveness in insulin delivery impart the matrix microneedle (mMN) patch great potential for clinical translation. [ABSTRACT FROM AUTHOR]

Abstract A transdermal patch that delivers insulin at high glucose concentrations can offer tremendous advantages to ease the concern of safety and improve the quality of life for people with diabetes. Herein, a novel self‐crosslinkable and glucose‐responsive polymer‐based microneedle patch (MN) is designed to deliver insulin at hyperglycemia. The microneedle patch is made of hyaluronic acid polymers functionalized with dopamine and 4‐amino‐3‐fluorophenylboronic acid (AFBA) that can be quickly crosslinked upon mixing of the polymer solutions in the absence of any chemicalcrosslinking agents or organic solvents. The catechol groups in the dopamine (DA) units form covalent crosslinkages among themselves by auto‐oxidation and dynamic crosslink with phenylboronic acid (PBA) via complexation. The reversible crosslinkages between catechol and boronate decrease with increasing glucose concentration leading to higher swelling and faster insulin release at hyperglycemia as compared to euglycemia. Such superior glucose‐responsive properties are demonstrated by in vitro analyses and in vivo efficacy studies. The hydrogel polymers also preserve native structure and bioactivity of insulin, attributable to the interaction of hyaluronic acid (HA) with insulin molecules, as revealed by experiments and molecular dynamics simulations. The simplicity in the design and fabrication process, and glucose‐responsiveness in insulin delivery impart the matrix microneedle (mMN) patch great potential for clinical translation.

Background: A diabetes diagnosis has significant implications and affects the individual’s health and social opportunities; it may also carry ethical and cultural consequences, especially when self-injectable treatment is involved. Therefore, it is important to understand lived experiences of patients on self-injectable diabetes treatment to establish initiatives and develop coping mechanisms that may reduce disease morbidity. Aim: This study explored and described patients’ lived experiences of self-injectable treatment for diabetes mellitus type 1 and 2. Setting: The study was conducted in the Rundu health district, Kavango east region, Namibia. Method: A phenomenological qualitative design was used. The sample consisted of 10 purposively selected patients on self-injectable treatment and data were collected through unstructured individual interviews. Data analysis followed an interpretative phenomenological approach. Ethical principles were adhered to, including respect for autonomy, non-maleficence, beneficence, and justice and ethical clearance was obtained. Results: Self-injectable treatment is cost-effective, promotes self-care, and relieves the burden on nurses and doctors. But it is a lonely journey, causing uncertainty about the future and self-stigmatisation. Moreover, unfamiliarity with injection techniques, challenges in storing medication, and disposing of used needles and other waste were revealed. Conclusion: Patients on self-injectable diabetes treatment have positive and negative lived experiences. It is recommended that family members provide adequate support and that healthcare workers reinforce education on diabetes for these individuals. Contribution: The findings can be used to develop patients’ education and training packages, guide the development and implementation of diabetes coping mechanisms, and initiate intersectoral collaboration to assist patients undergoing injectable treatment.

Background: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. Methods: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. Results and conclusions: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease. [ABSTRACT FROM AUTHOR]

While type 2 diabetes mellitus (T2DM) increases the risk of cardiac complications, diabetes treatment choices may increase or decrease the rates of cardiac events. In the present review, we comprehensively discussed the treatment options of diabetic subjects with cardiac conditions. Current evidence related to diabetes treatment in cardiac situations has been reviewed. Clinical trials and meta-analyses on cardiac safety of anti-diabetic medicines are discussed. Treatment choices with proven benefits and those at least without associated increased cardiac risk were drawn from clinical trials; meta-analyses and cardiac safety studies in the recent medical literature were the basis of the suggestions in the present review. We can suggest that hypoglycemia and extreme hyperglycemia should be avoided in acute ischemic heart conditions. Certain diabetic treatment options, especially sodium-glucose cotransporter-2 (SGLT2) inhibitors, can reduce overall cardiovascular mortality and hospitalization due to heart failure. Therefore, we suggest that physicians should choose SGLT2 inhibitors as the first-line treatment option in diabetic patients with heart failure or those who have a high risk of heart failure development. T2DM increases the risk of atrial fibrillation (AF), and metformin and pioglitazone seem to reduce the risk of AF in diabetic population. [ABSTRACT FROM AUTHOR]

IntroductionEvidence on the association between diabetes and risk of bladder cancer has been controversial. In addition, findings on the associations between duration of diabetes, diabetes treatment, and risk of bladder cancer have been inconsistent.MethodsA total of 148,208 participants in Women's Health Initiative study were included. Information on diabetes status, diabetes duration, and treatment was collected both at baseline and during follow-up. Information on potential confounders including age, race/ethnicity, education, occupation, family history of cancer, smoking status, alcohol consumption, total physical activity, body mass index, and daily dietary intake were collected at baseline. Bladder cancer cases were collected and confirmed by a centralized review of pathology reports. Cox proportional hazard models with time-varying covariates were used to examine associations of diabetes status, duration of diabetes, and diabetes treatment with bladder cancer risk.ResultsDuring a median follow-up of 18.5 years, 865 bladder cancer cases were identified. There were no significant associations of diabetes, duration of diabetes, or diabetes treatment with risk of bladder cancer. Participants with prevalent diabetes did not have significantly higher risk of bladder cancer compared with those without diabetes.ConclusionDiabetes was not significantly associated with risk of bladder cancer among postmenopausal women.

Abstract Aims/Introduction Hypertriglyceridemia is common in patients with diabetes. Although the fatty acid (FA) composition of triglycerides (TGs) is suggested to be related to the pathology of diabetes and its complications, changes in the fatty acid composition caused by diabetes treatment remain unclear. This study aimed to identify short‐term changes in the fatty acid composition of plasma triglycerides after diabetes treatment. Materials and Methods This study was a sub‐analysis of a prospective observational study of patients with type 2 diabetes aged between 20 and 75 years who were hospitalized to improve glycemic control (n = 31). A lipidomic analysis of plasma samples on the 2nd and 16th hospital days was conducted by supercritical fluid chromatography coupled with mass spectrometry. Results In total, 104 types of triglycerides with different compositions were identified. Most of them tended to decrease after treatment. In particular, triglycerides with a lower carbon number and fewer double bonds showed a relatively larger reduction. The inclusion of FA 14:0 (myristic acid), as a constituent of triglyceride, was significantly associated with a more than 50%, and statistically significant, reduction (odds ratio 39.0; P

The increase in blood glucose causes a myriad of pathways and molecular components to malfunction, leading to diabetes. Diabetes affects each organ differently by activating distinct pathways. It has an impact on the liver, pancreas, kidney (nephropathy), eyes (retinopathy), and nervous system (neuropathy). Understanding the effects of diabetes on each organ is the first step in developing a sustained treatment for the disease. Among the many cellular molecules impacted by diabetes is Ca2+/calmodulin-dependent protein kinase II (CaMKII), a complex Ca2+/calmodulin-activated serine/threonine-protein kinase. When intracellular [Ca2+] rises, it binds to calmodulin (CaM) to produce Ca2+/CaM, which activates CaMKIIs. This factor is involved in the pancreas, liver, heart, muscles, and various organs. Thus, Understanding CaMKII action in each organ is critical for gaining a complete picture of diabetic complications. Therefore, this review covers CaMKII's functions in many organs and how it affects and has been affected by diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Type 1 diabetes is a common and debilitating disease that requires regular glycemic control to prevent potentially fatal hypoglycemia. Objective: The aim of this study is to demonstrate the purpose, process, and consequences of pancreatic islet transplantation in patients with type 1 diabetes. Additionally, the results of the procedure after several years are described based on the available publications. Materials and Methods: The authors created a summary of available publications on pancreatic islet transplantation, based on databases such as PubMed and Google Scholar. Using the terms listed in the "key words" section, the authors searched for relevant information in other scientific papers to create the following review. Conclusions: Reducing the number of donors and developing alternative sources of pancreatic islet cells for transplantation is an active area of research, that promises to expand access and indications for pancreatic islet transplantation in future diabetes treatment.

Diabetes is one of the leading chronic diseases globally with a significant impact on mortality. This condition is associated with chronic microvascular and macrovascular complications caused by vascular damage. Recently, endothelial progenitor cells (EPCs) raised interest due to their regenerative properties. EPCs are mononuclear cells that are derived from different tissues. Circulating EPCs contribute to regenerating the vessel’s intima and restoring vascular function. The ability of EPCs to repair vascular damage depends on their number and functionality. Diabetic patients have a decreased circulating EPC count and impaired EPC function. This may at least partially explain the increased risk of diabetic complications, including the increased cardiovascular risk in these patients. Recent studies have confirmed that many currently available drugs with proven cardiovascular benefits have beneficial effects on EPC count and function. Among these drugs are also medications used to treat different types of diabetes. This manuscript aims to critically review currently available evidence about the ways anti-diabetic treatment affects EPC biology and to provide a broader context considering cardiovascular complications. The therapies that will be discussed include lifestyle adjustments, metformin, sulphonylureas, gut glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor analogs, sodium-glucose transporter 2 inhibitors, and insulin.

Background: Neonatal diabetes mellitus (NDM) is a rare form of diabetes. We analyzed a novel insulin gene (INS) mutation of a Chinese permanent neonatal diabetes mellitus (PNDM) patient to explore the clinical and genetic characteristics and put forward some opinions on treatment and its longterm management. Case description: A proband was recruited who was diagnosed with permanent neonatal diabetes on his first day after birth. His clinical and follow-up data were collected for 10 years. All of the family members were given an oral glucose tolerance test. Whole exome sequencing was performed on the proband, and the genomic DNA of family members was used for verification by first-generation Sanger sequencing technology. The pathogenic variant was screened according to the American College of Medical Genetics and Genomics classification guidelines and the clinical phenotype of the patient. Diagnostic assessment: The proband was diagnosed on the first day after birth, presenting with low birth weight, progressive hyperglycemia, and insulin deficiency. His parents and grandfathers were confirmed to have normal blood sugar levels. A novel homozygous mutation of c.1T>C in the INS gene was detected in the proband, located in the initiation codon. The heterozygous mutations were found in four family members, including his mother, father, and grandfathers. With regular insulin injections, long-term regular follow-up, close monitoring of blood glucose, balanced exercise and diet, and psychological and mutual family support, the blood glucose level was well controlled; there were no acute or chronic complications during this decade. The patient's growth and nervous system development are now no different to those of the same age. Conclusion: A favorable prognosis is presented for a permanent neonatal diabetes mellitus (PNDM) patient with a novel mutation in the INS gene in China. The present findings indicate that the genetic diagnosis, early use of insulin, close monitoring of blood glucose, and psychological and mutual family support for patients with INS mutation are necessary for their favorable long-term prognosis. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Hypertriglyceridemia is common in patients with diabetes. Although the fatty acid (FA) composition of triglycerides (TGs) is suggested to be related to the pathology of diabetes and its complications, changes in the fatty acid composition caused by diabetes treatment remain unclear. This study aimed to identify short‐term changes in the fatty acid composition of plasma triglycerides after diabetes treatment. Materials and Methods: This study was a sub‐analysis of a prospective observational study of patients with type 2 diabetes aged between 20 and 75 years who were hospitalized to improve glycemic control (n = 31). A lipidomic analysis of plasma samples on the 2nd and 16th hospital days was conducted by supercritical fluid chromatography coupled with mass spectrometry. Results: In total, 104 types of triglycerides with different compositions were identified. Most of them tended to decrease after treatment. In particular, triglycerides with a lower carbon number and fewer double bonds showed a relatively larger reduction. The inclusion of FA 14:0 (myristic acid), as a constituent of triglyceride, was significantly associated with a more than 50%, and statistically significant, reduction (odds ratio 39.0; P < 0.001). The total amount of FA 14:0 as a constituent of triglycerides also decreased significantly, and its rate of decrease was the greatest of all the fatty acid constituents. Conclusions: A 2 week comprehensive risk management for diabetes resulted in decreased levels of plasma triglycerides and a change in the fatty acid composition of triglycerides, characterized by a relatively large reduction in FA 14:0 as a constituent of triglycerides. [ABSTRACT FROM AUTHOR]

Microneedles (MN) technology is an emerging technology for the transdermal delivery of therapeutics. When combined with photoresponsive (PR) materials, MNs can deliver therapeutics precisely and effectively with enhanced efficacy or synergistic effects. This review systematically summarizes the therapeutic applications of PRMNs in cancer therapy, wound healing, diabetes treatment, and diagnostics. Different PR approaches to activate and control the release of therapeutic agents from MNs are also discussed. Overall, PRMNs are a powerful tool for stimuli-responsive controlled-release therapeutic delivery to treat various diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: A diabetes diagnosis has significant implications and affects the individual's health and social opportunities; it may also carry ethical and cultural consequences, especially when self-injectable treatment is involved. Therefore, it is important to understand lived experiences of patients on self-injectable diabetes treatment to establish initiatives and develop coping mechanisms that may reduce disease morbidity. Aim: This study explored and described patients' lived experiences of self-injectable treatment for diabetes mellitus type 1 and 2. Setting: The study was conducted in the Rundu health district, Kavango east region, Namibia. Method: A phenomenological qualitative design was used. The sample consisted of 10 purposively selected patients on self-injectable treatment and data were collected through unstructured individual interviews. Data analysis followed an interpretative phenomenological approach. Ethical principles were adhered to, including respect for autonomy, non-maleficence, beneficence, and justice and ethical clearance was obtained. Results: Self-injectable treatment is cost-effective, promotes self-care, and relieves the burden on nurses and doctors. But it is a lonely journey, causing uncertainty about the future and self- stigmatisation. Moreover, unfamiliarity with injection techniques, challenges in storing medication, and disposing of used needles and other waste were revealed. Conclusion: Patients on self-injectable diabetes treatment have positive and negative lived experiences. It is recommended that family members provide adequate support and that healthcare workers reinforce education on diabetes for these individuals. Contribution: The findings can be used to develop patients' education and training packages, guide the development and implementation of diabetes coping mechanisms, and initiate intersectoral collaboration to assist patients undergoing injectable treatment. [ABSTRACT FROM AUTHOR]

Automated insulin delivery (AID) systems, known as artificial pancreas or closed-loop glucose control systems, have been developed to improve the glycemic outcomes of people with type 1 diabetes. These systems use a control algorithm that automatically modifies the amount of insulin infused into a patient based on real-time blood glucose measurements. This study presents a summary of key clinical and technical issues related to the development of the first commercial AID systems and their evolution into commercial biomedical devices. Highlights of each AID system are summarized through timelines, ranging from the definition of the core strategy of the control algorithm to the practical application and subsequent commercial approval. Tabulated information regarding the conducted main clinical studies is also presented. Insulin therapy has evolved up to the current commercial AID systems available, which have provided patients access to a safer and more effective therapy owing to automatic adjustments to insulin. However, this technology is relatively new and can be significantly improved. Limitations include the resistance of healthcare providers, high costs, and the availability of this treatment. The future of this technology is directed toward obtaining fully automatic control systems. [ABSTRACT FROM AUTHOR]

Background and Aims: Stomach cells can be converted to insulin-producing cells by Neurog3, MafA, and Pdx1 overexpression. Enteroendocrine cells can be similarly made to produce insulin by the deletion of FOXO1. Characteristics and functional properties of FOXO1-expressing stomach cells are not known. Methods: Using mice bearing a FOXO1-GFP knock-in allele and primary cell cultures, we examined the identity of FOXO1-expressing stomach cells and analyzed their features through loss-of-function studies with red-to-green fluorescent reporters. Results: FOXO1 localizes to a subset of Neurog3 and parietal cells. FOXO1 deletion ex vivo or in vivo using Neurog3-cre or Atp4b-cre increased numbers of parietal cells, generated insulin- and C-peptide-immunoreactive cells, and raised Neurog3 messenger RNA. Gene expression and ChIP-seq experiments identified the cell cycle regulator cyclin E1 (CCNE1) as a FOXO1 target. Conclusion: FOXO1 is expressed in a subset of stomach cells. Its ablation increases parietal cells and yields insulin-immunoreactive cells, consistent with a role in lineage determination.

Abstract Aims/Introduction Diabetes patients develop a variety of metabolic abnormalities in addition to hyperglycemia. However, details regarding change in various metabolites after comprehensive diabetes treatment remain unknown. This study aimed to identify the short‐term change in metabolome in inpatients who were subject to comprehensive diabetes treatment, using gas chromatography/mass spectrometry‐based non‐target metabolomics techniques. Materials and Methods Participants of the present study were randomly recruited from the patients with type 2 diabetes hospitalized due to problems with glycemic control (n = 31) and volunteers without diabetes (n = 30), both of whom were aged between 20 and 75 years. A metabolomic analysis of fasting plasma samples on the 2nd (pre‐treatment) and 16th hospital (post‐treatment) day with gas chromatography/mass spectrometry using a multiple reaction monitoring mode was carried out. Results A principal component analysis showed that metabolome of fasting plasma was different between individuals with and without diabetes. The metabolome of fasting plasma in diabetes patients after treatment was different from that of pre‐treatment, as well as individuals without diabetes. Many amino acids (proline, glycine, serine, threonine, methionine, pyroglutamic acid, glutamine and lysine) were significantly increased by >10% after administering the inpatient diabetes treatment. A hierarchical clustering analysis showed that in the case of patients with markedly decreased monosaccharide levels and increased 1,5‐anhydroglucitol, the levels of amino acids increased more significantly. Conclusions After a 2‐week comprehensive treatment, the plasma levels of various amino acids increased in conjunction with the reduction in monosaccharide levels in poorly controlled type 2 diabetes patients.

Background: The prevalence of diabetes mellitus is growing worldwide, showing almost a 10-fold increase in the last five decades. Despite advances in the understanding of the disease mechanisms, preventive measures, and treatment options, morbidity and mortality remain high. Moreover, the burden of uncontrolled glycemia and associated complications have a significant impact on healthcare costs. To be ready for the future and emerging issues in the management of diabetes and related disorders, a holistic approach is essential for the prevention of the next generations. So many challenges in the management of diabetes exist globally, which differ according to the health infrastructure, and cultural, economic, and sociodemographic status of the nations. Conclusions: In this minireview and commentary on previously unaddressed needs relating to the management of diabetes, we discuss the ubiquitous and most compelling challenges and suggest potential solutions in the care of patients with diabetes.

During evaluation of new investigational medical devices, the FDA recommends that investigators design a crossover clinical trial, in which the patients are arranged to cross over from one treatment arm to another. The FDA annually receives the premarket applications of investigational medical devices, in which sponsors design and conduct crossover trials as their confirmatory clinical trials for evaluating safety and effectiveness of the devices. This article reviews the use of crossover clinical trial in pivotal clinical trials for high-risk medical devices regulated and approved by the United States Food and Drug Administration (FDA) from 2005 to 2018. As an example, in which a crossover trial was implemented during the regulatory approval process of a new device, the article additionally presents the FDA-approved premarket approval (PMA) submission of the Medtronic MiniMed 530G system, an artificial pancreas device system that mimic a normally functioning pancreas by monitoring glucose levels and administering insulin at a certain threshold maintained by sensing blood glucose levels. The article also reiterates the critical regulatory considerations that the FDA made regarding the design and analysis of crossover trials in its guidance for industry.

Background:  Type 2 diabetes prevalence is steadily increasing worldwide, and South Africa is one of the countries in Africa with the highest prevalence of this disease, along with other non-communicable diseases. The adherence to treatment in male patients with type 2 diabetes is influenced by their attitudes towards medication and how they perceive their condition. To some extent, these factors impact the treatment outcomes for patients undergoing type 2 diabetes treatment. The purpose of this study was to investigate the perceptions of male patients with type 2 diabetes on their adherence to diabetic therapy. The study was conducted in the clinics of the City of Tshwane Metropolitan municipality in Gauteng., Methods:  This study followed a qualitative, exploratory design. Data were gathered from 15 male patients who were purposefully sampled through in-person, one-on-one interviews with the principal investigator. The eight steps outlined by Tesch were used to analyse the participant data., Results:  Emergent themes indicated that there were barriers to adherence to diabetic treatment and also factors that promoted adherence to diabetic treatment among the participants. Several factors were found to affect treatment uptake among the participants., Conclusion:  Patients demonstrated various reactions to diabetic treatment, highlighting the need for reinforcing education at the time of diagnosis and treatment initiation. Additionally, regular patient follow-up may be essential to improve adherence among patients.Contribution: The study highlights the importance of health promotion and the need to develop materials for medication-specific counselling for patients receiving diabetic treatment, in order to promote adherence.

Despite the potential benefits of close-looped insulin delivery systems in regulating glycemic homeostasis and effectively alleviating diabetes, they still encounter challenges such as limited effectiveness in preventing low glycemic episodes due to sluggish glucose response, and issues with the instability of enzymes and carriers. In this study, dually-crosslinked and glucose oxidase (GOx)-immobilized insulin nanogels (DC-NGs@Ins) are developed for rapid-responsive and sustained hypoglycemic therapy. The DC-NGs@Ins with the phenylborate ester linker enabled the insulin release in a close-looped fashion, and moreover, immobilized GOx-generated hydrogen peroxide (H 2 O 2 ) by consuming the glucose, which can further bind to phenylborate ester for enhancing glucose response and accelerating the insulin release. The dually-crosslinked structure (phenylboronic ester and UV-crosslinking) effectively minimized the initial burst release of insulin, thus preventing the potential risk of hypoglycemia. More interestingly, GOx immobilized in the nanogels mitigated GOx leakage and enhanced its multiple utilization compared to free GOx. In vivo study demonstrated that DC-NGs@Ins effectively maintained glycemic levels (BGLs) below 200 mg dL -1 for at least 8 h compared to singly-crosslinked nanogels (SC-NGs@Ins). Therefore, this intelligent insulin delivery system shows potential applications in diabetes treatment., (© 2024 Wiley‐VCH GmbH.)

The Goto-Kakizaki (GK) rat is a non-obese experimental model of type 2 diabetes mellitus (T2DM) that allows researchers to monitor diabetes-induced changes without jeopardizing the effects of obesity. This rat strain exhibits notable gastrointestinal features associated with T2DM, such as marked alterations in intestinal morphology, reduced intestinal motility, slow transit, and modified microbiota compared to Wistar rats. The primary treatments for diabetic patients include administration of hypoglycemic agents and insulin, and lifestyle changes. Emerging procedures, including alternative therapies, metabolic surgeries, and modulation of the intestinal microbiota composition, have been shown to improve the diabetic state of GK rats. This review describes the morpho-physiological diabetic-associated features of the gastrointestinal tract (GIT) of GK rats. We also describe promising strategies, e.g., metabolic surgery and modulation of gut microbiota composition, used to target the GIT of this animal model to improve the diabetic state.

Diabetes mellitus is one of the most serious public health problems in the world. Repeated daily injections of subcutaneous insulin is the standard treatment for patients with type 1 diabetes mellitus; however, subcutaneous insulin injections can potentially cause local discomfort, patient noncompliance, hypoglycemia, failure to regulate glucose homeostasis, infections, and fat deposits at the injection sites. In recent years, numerous attempts have been made to produce safe and efficient nanoparticles for oral insulin delivery. Oral administration is considered the most effective alternative route to insulin injection, but it is accompanied by several challenges related to enzymatic proteolysis, digestive breakdown, and absorption barriers. A number of natural and synthetic polymeric, lipid‐based, and inorganic nanoparticles have been investigated for use. Although improvements have recently been made in potential oral insulin delivery systems, these require further investigation before clinical trials are conducted. In this review, new approaches to oral insulin delivery for diabetes treatment are discussed, including polymeric, lipid‐based, and inorganic nanoparticles, as well as the clinical trials performed for this purpose. [ABSTRACT FROM AUTHOR]