Different Forms Of Diabetes Research Articles

Identification of small molecule glucokinase activators for the treatment of diabetes based on plants from the traditional Chinese medicine: In silico analysis

Mutations in glucokinase (GCK) can either enhance or inhibit insulin secretion, leading to different forms of diabetes, including gestational diabetes. While many glucokinase activators (GKAs) have been explored as treatments, their long-term effectiveness has often been unsatisfactory. However, recent interest has surged with the introduction of dorzagliatin and TTP399. This study investigates the efficacy of four previously studied compounds (Swertiamarin, Apigenin, Mangiferin, and Tatanan A) in activating GCK using computational methods.Initial molecular docking revealed binding affinities ranging from −6.7 to −8.6 kcal/mol. The compounds were then evaluated for drug-likeness and pharmacokinetic properties. Re-docking studies were performed for validation. Based on their favorable binding affinities and compliance with Lipinski's rule and ADMET criteria, three compounds (Swertiamarin, Apigenin, and Tatanan A) were selected for molecular dynamics (MD) simulations.MD simulations demonstrated that Swertiamarin showed excellent stability, as indicated by analyses of RMSD, RMSF, radius of gyration (Rg), hydrogen bonding, and principal component analysis (PCA). These results suggest that Swertiamarin holds promise for further investigation in in vivo and clinical settings to evaluate its potential in enhancing GCK activity and treating diabetes.This study assessed the potential of four compounds as GCK activators using molecular docking, pharmacokinetic profiling, and MD simulations. Swertiamarin, in particular, showed significant stability and adherence to drug-likeness criteria, making it a promising candidate for further research in combating diabetes.

Risk of cardiovascular events after gestational diabetes: a retrospective population study.

To investigate whether the risk for post-partum cardiovascular diseases (CVD) is driven by gestational diabetes (GDM), by GDM-related risk factors and/or by pre-gestational (Pre-GD) or post-gestational diabetes (Post-GD). Women delivering in Tuscany, Italy in years 2010-2012 (n = 74,720), were identified from certificates of care at delivery and further identified as affected with GDM, Pre-GD or Post-GD through regional administrative databases. Women with GDM, Pre-GD or Post-GD were retrospectively evaluated for risk of post-partum hospitalizations for CVD (myocardial infarction or stroke; n = 728) across years 2013-2021, comparing women with different forms of diabetes to those without diabetes. Risk of CVD was assessed as odds ratio (OR 95% CI), after logistic multivariate models, considering all recorded pre-gestational characteristics as covariates. The adjusted OR (aOR) for post-partum CVD hospitalizations was not significantly related to GDM itself (aOR: 0.85; 0.64-1.12; p = ns), but increased in women with Pre-GD (aOR: 2.02; 1.09-3.71; p = 0.024) and Post-GD, associated or not to prior GDM (aOR; 4.21; 2.45-7.23 and respectively aOR: 3.80; 2.38-6.05; p < 0.0001 for both). In presence of pre-pregnancy maternal obesity (BMI ≥ 30kg/m2) the aOR of CVD approximatively doubled (aOR: 1.90; 1.51-2.40); p < 0.0001, independently of GDM and of Post-GD. The adjusted risk of CVD was lower among employed women (aOR: 0.83; 0.70-0.99); p = 0.04 and significantly higher in presence of poorer education levels (aOR: 1.32; 1.11-1.57); p < 0.0001. In this population the risk of post-partum CVD was driven by Pre- and Post-GD, not by GDM alone. Pre-gestational obesity represented a major independent risk factor for post-partum CVD.

Optimization of the (pharmacotherapeutic) treatment and care of the diabetes type 2 patient in Belgium through multidisciplinary collaboration between general practitioner and community pharmacist

Introduction: Diabetes type 2 is a chronic condition that can lead to devastating micro-and/or macrovascular complications in the long term when not treated properly. This causes decreased health-related quality of life and an increased risk for morbidity and mortality. Despite safe and effective drugs, there are major challenges in the treatment of diabetes type 2: (1) medication adherence, (2) optimizing pharmacotherapy, (3) non-pharmacotherapy related care (e.g.;eyecare, cardiovascular risk, footcare…). It is clear that the care for these patients can no longer be treated monodisciplinary and that it requires a level of care from the community pharmacists (CP) that goes beyond usual dispensing. The added value of a multidisciplinary collaboration between the CP and general practitioners (GP) lies in a combination of knowledge and competences and joint responsibility.&#x0D; Policy Context And Objective: In 2018, the Royal Association of Pharmacists in Antwerpen (KAVA) and Domus Medica have developed a quality improving program (QIP) in the context of Medical-Pharmaceutical Concertation (MPC). MPC is an initiative from the Belgian Government for Health Insurance (RIZIV) to promote the rational prescribing and dispensing of medication and the safe use of medication in general and provides financial incentives to GP and CP to organize local MPC-projects, based on a QIP. A local MPC-project starts with a ‘kick-off meeting’, to make agreements of the rational use of medication. Most of the time, different cases are discussed in small interprofessional groups. After this meeting, the agreements are subsequently implemented into practice and can be evaluated with quality indicators. &#x0D; This specific QIP focusses on five modules: (1) the pathogenesis of different forms of diabetes, diagnosis, complications and non-pharmacological treatment, (2) Guidelines / medication groups - Treatment of comorbidities and reimbursement criteria, (3) case studies of different patient with heart failure, renal insufficiency, overweight, (4) Care pathways and adherence to therapy, and (5) the safe use of antidiabetics during Ramadan for a specific population.&#x0D; Target Population: MPC targets the GP and CP with mutual diabetes type 2 patients. &#x0D; Highlights: KAVA and Domus Medica strongly believe in this initiative. Currently 17 local MPC-projects have been organized in which 102 CP and 122 GP participated. The 4 most important topics of these MPC-projects are:&#x0D; •lifestyle intervention, comorbidities and pharmacotherapy&#x0D; •Overview and objective of care pathways and organizing good use medication (GGG) interview by CP &amp; feedback to GP&#x0D; •Adherence &#x0D; Conclusion: A MPC is a promising service to support evidence-based practice for optimizing treatment of diabetes patients through constructive collaboration between GP and CP. There was a particular need for good information about the treatment options for diabetes, comorbidities and lifestyle. A second point of attention was the care pathways, which are clearly insufficiently known, let alone implemented. There is certainly a strong will in the local MFO projects to work on compliance, as evidenced by the many indicators around the GGG. Unfortunately, we have no insight into whether these have been effectively worked out in practice and further research is necessary to analyze the impact.&#x0D;

Toll-like Receptor 9 Gene in the Development of Type 2 Diabetes Mellitus in the Saudi Arabian Population.

Diabetes mellitus is a complex disease with a wide range of manifestations. Diabetes, notably type 2 diabetes mellitus (T2DM), is becoming more common in Saudi Arabia as a result of obesity and an aging population. T2DM is classified as a noncommunicable disease, and its incidence in the Saudi population continues to grow as a consequence of socioeconomic changes. Toll-like receptors (TLRs) are innate immune receptors that mediate the inflammatory response in diabetes mellitus. Previous studies have documented the relationship between different SNPs in the TLR9 gene in different forms of diabetes. As a result, the purpose of this study was to investigate the relationship between rs187084, rs352140, and rs5743836 SNPs in the TLR9 gene among T2DM patients in the Saudi population. This was a case-control study that included 100 T2DM cases and 100 control subjects. The three SNPs were identified in the study population (n = 200) using polymerase chain reaction (PCR), restriction enzymes for rs352140, and Sanger sequencing for rs187084 and rs5783836. Next, statistical analyses were performed using various software to determine the association between the SNPs and T2DM. rs187084 and rs5743836 were associated with an increased risk of T2DM development. rs187084 and rs5743836 allelic frequencies were associated with a 3.2 times increased risk of T2DM development (p < 0.05). DBP was associated with T2DM (p = 0.02). rs187084 was associated with TC and HDLc; rs352140 was associated with DBP, HbA1c, and HDLc; rs5743836 was associated with waist (p < 0.05). The CGT haplotype was strongly associated with T2DM (p < 0.003). Gene-gene interaction, graphical presentation, and dendrogram showed the strong association with T2DM patients (p < 0.05). This study concluded that rs187084 and rs5743836 were strongly associated with T2DM in Saudi Arabian patients. This study provides further evidence that SNPs in the TLR9 gene play a significant role in T2DM development in a Saudi community.

The Effect of Vitamin D Supplementation on Incidence of Type 2 Diabetes: A Systematic Review.

With the clinical increase in Type 2 Diabetes worldwide, several interventions to decrease its incidence have been investigated. One such intervention is Vitamin D supplementation, as it affects Insulin secretion from the pancreas and Insulin receptors in the cells of the body. This systematic review addresses whether or not Vitamin D supplementation has a role in reducing the risk of developing Type 2 Diabetes. Systematic searches were conducted on PubMed, and Cochrane Library mainly but also checked Google Scholar. Randomized controlled trials, systematic trials and cohort studies were retrieved that included keywords pertaining to Vitamin D supplementation and the incidence of Type 2 Diabetes. Exclusion criteria included studies that looked at different forms of Diabetes, studies including patients aged less than 18 or more than 85 years of age and studies that were not English language. For all the trials identified, the incidence of Type 2 Diabetes among the cohort receiving vitamin D supplementation was compared to the cohort receiving placebo medication. Additionally, the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was analyzed to observe if there was a difference between Insulin resistance among these two cohorts between the start of the trials and the end. Thirteen randomized controlled trials were identified. Seven of these identified incidences of Type 2 Diabetes as a research outcome, out of which six showed no statistically significant impact of vitamin D on the incidence of Type 2 Diabetes. Out of the 13 trials, 10 analyzed the impact of vitamin D supplementation on patients' HOMA-IR. In six of these trials, patients receiving vitamin D supplementation had a decrease in their HOMA-IR, while it increased in 4 trials. In seven of the ten trials that analyzed for HOMA-IR, the HOMA-IR was less in the vitamin D cohort than the placebo cohort. There is insufficient evidence to suggest that vitamin D supplementation significantly reduces the incidence of Type 2 Diabetes despite its effects on insulin resistance. Further research in this area would be helpful in order to influence clinical guidelines on vitamin D supplementation among patients at risk of Type 2 Diabetes.

Multiple influences of the COVID-19 pandemic on children with diabetes: Changes in epidemiology, metabolic control and medical care.

The coronavirus disease 2019 (COVID-19) pandemic has heavily affected health worldwide, with the various forms of diabetes in children experiencing changes at various levels, including epidemiology, diabetic ketoacidosis rates and medical care. Type 1 diabetes showed an apparent increase in incidence, possibly owing to a direct damage of the virus to the β-cell. Diabetic ketoacidosis also increased in association with the general fear of referring patients to the hospital. Most children with diabetes (both type 1 and type 2) did not show a worsening in metabolic control during the first lockdown, possibly owing to a more controlled diet by their parents. Glucose sensor and hybrid closed loop pump technology proved to be effective in all patients with type 1 diabetes during the pandemic, especially because the downloading of data allowed for the practice of tele-medicine. Telemedicine has in fact grown around the world and National Health Systems have started to consider it as a routine activity in clinical practice. The present review encompasses all the aspects related to the effects of the pandemic on the different forms of diabetes in children.

Monogenic diabetes.

Monogenic diabetes includes several clinical conditions generally characterized by early-onset diabetes, such as neonatal diabetes, maturity-onset diabetes of the young (MODY) and various diabetes-associated syndromes. However, patients with apparent type 2 diabetes mellitus may actually have monogenic diabetes. Indeed, the same monogenic diabetes gene can contribute to different forms of diabetes with early or late onset, depending on the functional impact of the variant, and the same pathogenic variant can produce variable diabetes phenotypes, even in the same family. Monogenic diabetes is mostly caused by impaired function or development of pancreatic islets, with defective insulin secretion in the absence of obesity. Themost prevalent form of monogenic diabetes is MODY, which may account for 0.5-5% of patients diagnosed with non-autoimmune diabetes but is probably underdiagnosed owing to insufficient genetic testing. Most patients with neonatal diabetes or MODY have autosomal dominant diabetes. More than 40 subtypes of monogenic diabetes have been identified to date, the most prevalent being deficiencies of GCK and HNF1A. Precision medicine approaches (including specific treatments for hyperglycaemia, monitoring associated extra-pancreatic phenotypes and/or following up clinical trajectories, especially during pregnancy) are available for some forms of monogenic diabetes (including GCK- and HNF1A-diabetes) and increase patients' quality of life. Next-generation sequencing has made genetic diagnosis affordable, enabling effective genomic medicine in monogenic diabetes.

COVID-19 and diabetes mellitus: a review of the incidence, pathophysiology and management of diabetes during the pandemic

ABSTRACT Introduction The COVID-19 pandemic has changed the landscape of modern medicine on a global scale. An emerging concern is the recognition of a bidirectional relationship between COVID-19 and diabetes. Diabetes is a risk factor for severe COVID-19 illness. Intriguingly, recent epidemiological and in vitro studies suggest that infection with SARS-CoV-2, the causative viral agent of COVID-19, is associated with new-onset diabetes and worsening diabetes control. These factors have affected the management of diabetes. Areas covered This review provides an overview of our current understanding of the incidence and prevalence of diabetes in relation to the COVID-19 pandemic, highlights studies evaluating SARS-CoV-2’s beta cell tropism and its effects on insulin secretion and sensitivity and evaluates the impact of the pandemic on diabetes management and metabolic control. Expert opinion Epidemiological studies have noted an increase in the incidence of new-onset diabetes associated with COVID-19 in patients with phenotypes of type 1 diabetes, type 2 diabetes and Ketosis-Prone Diabetes. Prospective studies are needed to fully elucidate the association between COVID-19 and diabetes and to characterize persons at risk of developing diabetes after SARS-CoV-2 infection, identify those who should be screened for diabetes, and determine the natural histories of different forms of diabetes associated with COVID-19.

Emphasizing the Main Factors Involved between the Green Zones Created Near the Natural Salted Lakes or Springs and the Treatment of Some Nervous System Disorders

In recent years, more and more data has become available about the benefits of green in and around towns and cities. Vegetation helps people to recover faster from illness; this reduces costs of healthcare and improves the patients’ quality of life. This aspect of introducing vegetation in and around hospitals is increasingly becoming a topic of focus in connection with the concept of a ‘healthy environment’. Since the creation of the first people’s parks, urban planners have been aware of the fact that vegetation enhances the quality of life for townspeople. Green areas are places where people can go for recreation and physical exercise or simply to find some peace and quiet. This benefits their health and reduces the stress levels of the average city dweller. A positive correlation exists between the amount of green in a person’s living environment and that person’s sense of safety. In highly urbanized locations, the design of green elements requires special attention. Our paper presents a multidisciplinary study of areas located near the old salt mines and their recovery by entering in the spa and leisure circuit. Specific components were monitored, like the salted waters quality in lakes and/or springs and in the selection of different plant species adapted to high salinity of the soil. According to studies conducted in Europe, the environment plays a crucial role in physical, mental and social development of the population. In recent years, the continuous degradation of environmental quality due to factors such as air pollution, noise, chemical compounds and disappearance of natural areas, in combination with lifestyle changes led to the emergence of a growing number of diseases such as different forms of diabetes, cardiovascular and nervous system disorders and cancer.

SGLT2 inhibitors therapy protects glucotoxicity-induced β-cell failure in a mouse model of human KATP-induced diabetes through mitigation of oxidative and ER stress.

Progressive loss of pancreatic β-cell functional mass and anti-diabetic drug responsivity are classic findings in diabetes, frequently attributed to compensatory insulin hypersecretion and β-cell exhaustion. However, loss of β-cell mass and identity still occurs in mouse models of human KATP-gain-of-function induced Neonatal Diabetes Mellitus (NDM), in the absence of insulin secretion. Here we studied the temporal progression and mechanisms underlying glucotoxicity-induced loss of functional β-cell mass in NDM mice, and the effects of sodium-glucose transporter 2 inhibitors (SGLT2i) therapy. Upon tamoxifen induction of transgene expression, NDM mice rapidly developed severe diabetes followed by an unexpected loss of insulin content, decreased proinsulin processing and increased proinsulin at 2-weeks of diabetes. These early events were accompanied by a marked increase in β-cell oxidative and ER stress, without changes in islet cell identity. Strikingly, treatment with the SGLT2 inhibitor dapagliflozin restored insulin content, decreased proinsulin:insulin ratio and reduced oxidative and ER stress. However, despite reduction of blood glucose, dapagliflozin therapy was ineffective in restoring β-cell function in NDM mice when it was initiated at >40 days of diabetes, when loss of β-cell mass and identity had already occurred. Our data from mouse models demonstrate that: i) hyperglycemia per se, and not insulin hypersecretion, drives β-cell failure in diabetes, ii) recovery of β-cell function by SGLT2 inhibitors is potentially through reduction of oxidative and ER stress, iii) SGLT2 inhibitors revert/prevent β-cell failure when used in early stages of diabetes, but not when loss of β-cell mass/identity already occurred, iv) common execution pathways may underlie loss and recovery of β-cell function in different forms of diabetes. These results may have important clinical implications for optimal therapeutic interventions in individuals with diabetes, particularly for those with long-standing diabetes.

Diagnostic Test Accuracy of Urine C-peptide Creatinine Ratio for the Correct Identification of the Type of Diabetes: A Systematic Review

Objective: To examine the accuracy of urine c-peptide creatinine ratio (UCPCR) for identifying the type of diabetes in appropriate clinical settings. Design: Systematic review of test accuracy studies on patients with different forms of diabetes. Data sources: Medline, Embase and Cochrane library databases from 1 January 2000 to 15 November 2020. Eligibility criteria: Studies reporting the use of UCPCR for diagnosing patients with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) and monogenic forms of diabetes (categorized as maturity-onset diabetes of the young [MODY]). Study selection and data synthesis: Two reviewers independently assessed articles for inclusion and assessed the methodological quality of the studies using the Quality Assessment of Diagnostic Accuracy Studies-2 tool, with input from a third reviewer to reach consensus when there was a dispute. Meta-analysis was performed with the studies reporting complete data to derive the pooled sensitivity, specificity and diagnostic odds ratio (DOR), and narrative synthesis only for those with incomplete data. Results: Nine studies with 4,488 patients were included in the qualitative synthesis, while only four of these (915 patients) had complete data and were included in the quantitative synthesis. All the studies had moderate risk of bias and applicability concerns. Meta-analysis of three studies (n=130) revealed sensitivity, specificity and DOR of 84.4% (95% confidence interval [CI] 68.1–93.2%), 91.6% (82.8–96.1%) and 59.9 (32.8–106.0), respectively, for diagnosing T1DM using a UCPCR cut-off of <0.2 nmol/mmol. For participants with T2DM (three studies; n=739), UCPCR >0.2 nmol/mmol was associated with sensitivity, specificity and DOR of 92.8% (84.2–96.9%), 81.6% (61.3–92.5%) and 56.9 (31.3–103.5), respectively. For patients with MODY in the appropriate clinical setting, a UCPCR cut-off of >0.2 nmol/mmol showed sensitivity, specificity and DOR of 85.2% (73.1–92.4%), 98.0% (92.4–99.5%) and 281.8 (57.5–1,379.7), respectively. Conclusions: Based on studies with moderate risk of bias and applicability concerns, UCPCR confers moderate to high sensitivity, specificity, and DOR for correctly identifying T1DM, T2DM and monogenic diabetes in appropriate clinical settings. Large multinational studies with multi-ethnic participation among different age groups are necessary before this test can be routinely used in clinical practice. Study registration: Protocol was registered as PROSPERO CRD42017060633.

Risikofaktoren für die Entstehung und Progression der diabetischen Retinopathie

Purpose. Diabetes mellitus is a global disease in which a reduced insulin production or effect affects the blood sugar metabolism. The incidence of the illness is rising steadily. An elevated blood sugar level implies changes in the vascular walls and, in the long term, a reduced blood flow to some ar- eas of the retina As a result, growth factors such as VEGF are overexpressed, which can lead to vitreous haemorrhage and traction-related retinal detachment via the formation of new blood vessels. The aim of this work is to review the literature to discuss the risk factors relevant for the development and progression of diabetic retinopathy. Material and Methods. We carried out a differentiated liter- ature review regarding the risk factors relevant to the devel- opment and/or progression of diabetic retinopathy based on a detailed description of the different forms of diabetes. The different risk factors were discussed and evaluated in the context of the different stages of diabetic retinopathy. Results. The risk of retinal conditions increases with the du- ration of the underlying diabetic disease and a significantly higher blood pressure. In insulin-dependent type 1 diabetics, optimising the time in range can reduce the risk. In type 2 diabetics, whose disease is often associated with obesity and increased blood lipid levels, an increase in physical activity can be useful in addition to optimal blood sugar control. All factors that reduce blood circulation, such as nicotine consumption or an increase in intraocular pressure, are to be regarded as risk factors. The first visible ocular signs of diabetic retinopathy are outpouching of the vascular walls (microaneurysms), the number of which correlates with the risk of progression of the retinal disease. Conclusion. It is crucial to understand the systemic and ocular risk factors to reduce the risk of developing or progressing diabetic retinopathy. A clear risk factor that can be reduced is nicotine. Interrupting an anti-VEGF therapy may lead to the progression of diabetic retinopathy. Keywords Risk factors, diabetic retinopathy, proliferative diabetic retinopathy, development and progression

The β Cell in Diabetes: Integrating Biomarkers With Functional Measures.

The pathogenesis of hyperglycemia observed in most forms of diabetes is intimately tied to the islet β cell. Impairments in propeptide processing and secretory function, along with the loss of these vital cells, is demonstrable not only in those in whom the diagnosis is established but typically also in individuals who are at increased risk of developing the disease. Biomarkers are used to inform on the state of a biological process, pathological condition, or response to an intervention and are increasingly being used for predicting, diagnosing, and prognosticating disease. They are also proving to be of use in the different forms of diabetes in both research and clinical settings. This review focuses on the β cell, addressing the potential utility of genetic markers, circulating molecules, immune cell phenotyping, and imaging approaches as biomarkers of cellular function and loss of this critical cell. Further, we consider how these biomarkers complement the more long-established, dynamic, and often complex measurements of β-cell secretory function that themselves could be considered biomarkers.

Type-3c Diabetes Mellitus, Diabetes of Exocrine Pancreas - An Update.

The incidence of diabetes is increasing steeply; the number of diabetics has doubled over the past three decades. Surprisingly, the knowledge of type 3c diabetes mellitus (T3cDM) is still unclear to the researchers, scientist and medical practitioners, leading towards erroneous diagnosis, which is sometimes misdiagnosed as type 1 diabetes mellitus (T1DM), or more frequently type 2 diabetes mellitus (T2DM). This review is aimed to outline recent information on the etiology, pathophysiology, diagnostic procedures, and therapeutic management of T3cDM patients. The literature related to T3cDM was thoroughly searched from the public domains and reviewed extensively to construct this article. Further, existing literature related to the other forms of diabetes is reviewed for projecting the differences among the different forms of diabetes. Detailed and updated information related to epidemiological evidence, risk factors, symptoms, diagnosis, pathogenesis and management is structured in this review. T3cDM is often misdiagnosed as T2DM due to the insufficient knowledge differentiating between T2DM and T3cDM. The pathogenesis of T3cDM is explained which is often linked to the history of chronic pancreatitis, pancreatic cancer. Inflammation, and fibrosis in pancreatic tissue lead to damage both endocrine and exocrine functions, thus leading to insulin/glucagon insufficiency and pancreatic enzyme deficiency. Future advancements should be accompanied by the establishment of a quick diagnostic tool through the understanding of potential biomarkers of the disease and newer treatments for better control of the diseased condition.

Diabetes mellitus types: Key genetic determinants and risk assessment

The characteristic symptom of diabetes is consistently elevated levels of blood sugar. This is instigated either by complete lack of insulin production (type 1 diabetes), reduced level of insulin production (type 2 diabetes) or insulin resistance (inability of body cells to take up glucose). Other types of diabetes include maturity onset of diabetes of the young (MODY), a form of type 2 diabetes and gestational diabetes which affects pregnant women mostly in second or third trimester. The term type-3-diabetes is now being used for insulin resistance in brain. Apart from environmental and dietary causes which pose the risk of diabetes, genetic constitution and gene mutations execute the manifestation of diabetes. So far, several hundreds of genes having genomic, metabolic and immunological functions have been associated with different forms of diabetes. Due to complexity in diabetes etiology, involvement of multiple genetic factors and overlap between phenotypes, the treatment for diabetes remains a major challenge. Single gene mutations can be potentially targeted therapeutically; however, the prevalence of single gene mutations in diabetic condition is rare. Comprehensive analysis of genes and genetic variants relevant to diabetes enables development of effective treatment or interventional strategies. The current literature survey was conducted and reviewed to identify studies that proposed the genetic basis for specific subtypes of diabetes and related complications. In addition, this review emphasizes the role of genome wide association studies and epigenetic factors. In the present review, we have identified some of the most significant protein encoding genes whose mutations have great impact in the development of diabetic condition. The characteristic features of these genes such as the risk level associated with the genes and inter-genic associations both in terms of position and functional proximity have been discussed. Additionally, genomic studies and epigenetic aspects have also been highlighted for wider comprehension of the diabetic condition from a genetic perspective. The present review would be of significance in prevention, screening, diagnosis, treatment and management of different forms of diabetes.

An overview of insulin therapy in pharmacotherapy of diabetes mellitus type I

Type 1 diabetes mellitus is a chronic disease, which characterizes itself with body’s inability to produce insulin from pancreas. This condition can happen from different autoimmune processes, which subsequently leads into destruction of beta cells in pancreas, the cells responsible for production of insulin. This condition account for about 5-10% of all different forms of diabetes, which should be taken very seriously since its incidence seems to be increasing worldwide and it can result in different devastating short and long-term complications. Management and approaches in patients with type 1 DM is of major concern worldwide since in the lack of proper management these patients cannot survive. Therefore, it is very important to have a multidisciplinary health management team that can have full focus on every aspect of this condition from continuous glucose monitoring, meal planning, screening for different complications to insulin therapy, which is the mainstay in treatment of patients in this group. American Diabetes Association (ADA) suggests using patient’s age in establishment of glycaemic goals, with targets for pre-prandial, bedtime and haemoglobin A1c levels. It is very important to educate patients on how to adjust the level of their insulin injection according to the amount of carbohydrate intake, premeal blood glucose, and anticipated activity. Insulin is and will remain the most important treatment approach in patients suffering from type 1 DM. According to recommendations of ADA, it is best when patients with type 1 DM are treated with multiple daily doses of insulin injections, such as three to four daily basal and prandial injections, or continuous subcutaneous insulin infusion devices should be used.

Recapitulating and Deciphering Human Pancreas Development From Human Pluripotent Stem Cells in a Dish.

Here, we review how human pluripotent stem cell models of pancreas development have emerged and became an important tool to study human development and disease. Initially developed toward the production of β cells for diabetes therapy, the protocols have been refined based on knowledge of pancreas development in model organisms. While the cells produced are closer and closer to the end goal of a functional β cell, these models have also been used to carry out functional experiments addressing gene function and expression as well as regulatory and epigenetic landscape changes during human pancreas development. They thereby complement model organisms and reports from human genetic variants predisposing to different forms of diabetes, as well as observations on human fetal tissue. In this review, we therefore compare these different sources of information and discuss how human stem cell models are evolving to inform us on pancreatic diseases and possible treatments.

Glycogen phosphorylase inhibition improves beta cell function.

Glycogen phosphorylase (GP) is the key enzyme for glycogen degradation. GP inhibitors (GPi-s) are glucose lowering agents that cause the accumulation of glucose in the liver as glycogen. Glycogen metabolism has implications in beta cell function. Glycogen degradation can maintain cellular glucose levels, which feeds into catabolism to maintain insulin secretion, and elevated glycogen degradation levels contribute to glucotoxicity. The purpose of this study was to assess whether influencing glycogen metabolism in beta cells by GPi-s affects the function of these cells. The effects of structurally different GPi-s were investigated on MIN6 insulinoma cells and in a mouse model of diabetes. GPi treatment increased glycogen content and, consequently, the surface area of glycogen in MIN6 cells. Furthermore, GPi treatment induced insulin receptor β (InsRβ), Akt and p70S6K phosphorylation, as well as pancreatic and duodenal homeobox 1(PDX1) and insulin expression. In line with these findings, GPi-s enhanced non-stimulated and glucose-stimulated insulin secretion in MIN6 cells. The InsRβ was shown to co-localize with glycogen particles as confirmed by in silico screening, where components of InsR signalling were identified as glycogen-bound proteins. GPi-s also activated the pathway of insulin secretion, indicated by enhanced glycolysis, mitochondrial oxidation and calcium signalling. Finally, GPi-s increased the size of islets of Langerhans and improved glucose-induced insulin release in mice. These data suggest that GPi-s also target beta cells and can be repurposed as agents to preserve beta cell function or even ameliorate beta cell dysfunction in different forms of diabetes. This article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc.

The course of diabetes in children, adolescents and young adults: does the autoimmunity status matter?

BackgroundInitial classification of diabetes of young may require revision to improve diagnostic accuracy of different forms of diabetes.The aim of our study was to examine markers of beta-cell autoimmunity in a cohort of young (0–25 years) patients with type 1 diabetes and compare the presentation and course of the disease according to the presence of pancreatic antibodies.MethodsCross-sectional population-based study was performed covering 100% of pediatric (n = 860) and 70% of 18–25 years old adult patients (n = 349) with type 1 diabetes in Lithuania.ResultsNo antibodies (GAD65, IA-2, IAA and ICA) were found in 87 (7.5%) cases. Familial history of diabetes was more frequent in those with antibodies-negative diabetes (24.1 vs. 9.4%, p < 0.001). Gestational age, birth weight and age at diagnosis was similar in both groups. Ketosis at presentation was more frequent in patients with autoimmune diabetes (88.1 vs. 73.5%, p < 0.05). HbA1c at the moment of investigation was 8.6 (3) vs. 8.7 (2.2)% in antibodies-negative and antibodies-positive diabetes groups, respectively, p > 0.05. In the whole cohort, neuropathy was found in 8.8% and nephropathy - in 8.1% of cases, not depending on autoimmunity status. Adjusted for age at onset, disease duration and HbA1c, retinopathy was more frequent in antibodies-negative subjects (13.8 vs. 7.8%, p < 0.05).ConclusionAntibodies-negative pediatric and young adult patients with type 1 diabetes in this study had higher incidence of family history of diabetes, higher frequency of retinopathy, less frequent ketosis at presentation, but similar age at onset, HbA1c, incidence of nephropathy and neuropathy compared to antibodies-positive patients.

Exercise and Sport Participation for Individuals with Type 1 Diabetes

Exercise and Sport Participation for Individuals with Type 1 Diabetes