Diabetes is a disease characterized by a relative or absolute lack of insulin, leading to hyperglycaemia. There are two main types of diabetes: type 1 diabetes and type 2 diabetes. Type 1 diabetes is ...due to an autoimmune destruction of the insulin‐producing pancreatic beta cells, and type 2 diabetes is caused by insulin resistance coupled by a failure of the beta cell to compensate. Animal models for type 1 diabetes range from animals with spontaneously developing autoimmune diabetes to chemical ablation of the pancreatic beta cells. Type 2 diabetes is modelled in both obese and non‐obese animal models with varying degrees of insulin resistance and beta cell failure. This review outlines some of the models currently used in diabetes research. In addition, the use of transgenic and knock‐out mouse models is discussed. Ideally, more than one animal model should be used to represent the diversity seen in human diabetic patients.
LINKED ARTICLES
Animal Models
This paper is the latest in a series of publications on the use of animal models in pharmacology research. Readers might be interested in the previous papers.
Robinson V (2009). Less is more: reducing the reliance on animal models for nausea and vomiting research.
Holmes AM, Rudd JA, Tattersall FD, Aziz Q, Andrews PLR (2009). Opportunities for the replacement of animals in the study of nausea and vomiting.
Giacomotto J and Ségalat L (2010). High‐throughput screening and small animal models, where are we?
McGrath JC, Drummond GB, McLachlan EM, Kilkenny C, Wainwright CL (2010). Guidelines for reporting experiments involving animals: the ARRIVE guidelines.
Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG (2010). The ARRIVE guidelines.
Emerson M (2010). Refinement, reduction and replacement approaches to in vivo cardiovascular research.
Berge O‐G (2011). Predictive validity of behavioural animal models for chronic pain.
Vickers SP, Jackson HC and Cheetham SC (2011). The utility of animal models to evaluate novel anti‐obesity agents.
Percie du Sert N, Holmes AM, Wallis R, Andrews PLR (2012). Predicting the emetic liability of novel chemical entities: a comparative study.
The complete series including future publications, as they occur, can be found at http://onlinelibrary.wiley.com/journal/10.1111/(ISSN)1476‐5381/homepage/animal_models.htm.
Abstract Arterial stiffness is an age-related process that is a shared consequence of numerous diseases including diabetes mellitus (DM), and is an independent predictor of mortality both in this ...population and in the general population. While much has been published about arterial stiffness in patients with DM, a thorough review of the current literature is lacking. Using a systematic literature search strategy, we aimed to summarize our current understanding related to arterial stiffness in DM. We review key studies demonstrating that, among patients with established DM, arterial stiffness is closely related to the progression of complications of DM, including nephropathy, retinopathy, and neuropathy. It is also becoming clear that arterial stiffness can be increased even in pre-diabetic populations with impaired glucose tolerance, and in those with the metabolic syndrome (METS), well before the onset of overt DM. Some data suggests that arterial stiffness can predict the onset of DM. However, future work is needed to further clarify whether large artery stiffness and the pulsatile hemodynamic changes that accompany it are involved in the pathogenesis of DM, and whether interventions targeting arterial stiffness are associated with improved clinical outcomes in DM. We also review of the potential mechanisms of arterial stiffness in DM, with particular emphasis on the role of advanced glycation endproducts (AGEs) and nitric oxide dysregulation, and address potential future directions for research.
Type 1 diabetes is an autoimmune disorder afflicting millions of people worldwide. Once diagnosed, patients require lifelong insulin treatment and can experience numerous disease-associated ...complications. The last decade has seen tremendous advances in elucidating the causes and treatment of the disease based on extensive research both in rodent models of spontaneous diabetes and in humans. Integrating these advances has led to the recognition that the balance between regulatory and effector T cells determines disease risk, timing of disease activation, and disease tempo. Here we describe current progress, the challenges ahead and the new interventions that are being tested to address the unmet need for preventative or curative therapies.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Maternal health associated with Gestational Diabetes Mellitus (GDM) has been gaining significant research attention due to its severe risk and adverse health effects. GDM is the leading health ...disease in pregnant women. It is the most common metabolic disease and it can affect up to 25% of women during pregnancy. Pregnancy is a sensitive period that impacts both pregnant women and their unborn children's long-term health. It is a well-known fact that the leading causes of disease and mortality worldwide are diabetes mellitus and cancer, and specifically, women with diabetes mellitus are at a higher risk of developing breast cancer (BC). Women who have diabetes are equally vulnerable to reproductive diseases. Reproductive dysfunctions with diabetes are mainly attributed to coexisting polycystic ovarian syndrome (PCOS), obesity, and hyperinsulinemia, etc. Moreover, India has long been recognized as the world's diabetic capital, and it is widely acknowledged that particularly pregnant and lactating women are among the most affected by diabetes. In India, one-third (33%) of women with GDM had a history of maternal diabetes. Nevertheless, the latest research suggests that gestational diabetes is also a risk factor for cardiometabolic diseases of the mother and offspring. Therefore, in the 21st century, GDM imposes a major challenge for healthcare professionals. We intend to explore the role of diabetes on female reproductive function throughout various stages of life in the perspective of the changing prognosis, prevalence, and prevention of GDM.
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•Gestational diabetes mellitus (GDM) is the most prevalent disease among pregnant women, affecting up to 15–25% of pregnancies worldwide.•GDM is associated with both short and long-term complications, including type 2 diabetes, hyperglycemia, pre-eclampsia, and macrosomia, etc.•Moreover, GDM women are also prone to breast cancer and various reproductive disorders.•We have explored the role of GDM on female metabolic and reproductive function throughout various stages of life.
Closed-loop systems that automate insulin delivery may improve glycemic outcomes in patients with type 1 diabetes. In this 6-month randomized, multicenter trial involving such patients, a closed-loop ...system led to a greater percentage of time with the glucose level in a target range than did a sensor-augmented insulin pump.
Initial studies found increased severity of coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in patients with diabetes ...mellitus. Furthermore, COVID-19 might also predispose infected individuals to hyperglycaemia. Interacting with other risk factors, hyperglycaemia might modulate immune and inflammatory responses, thus predisposing patients to severe COVID-19 and possible lethal outcomes. Angiotensin-converting enzyme 2 (ACE2), which is part of the renin-angiotensin-aldosterone system (RAAS), is the main entry receptor for SARS-CoV-2; although dipeptidyl peptidase 4 (DPP4) might also act as a binding target. Preliminary data, however, do not suggest a notable effect of glucose-lowering DPP4 inhibitors on SARS-CoV-2 susceptibility. Owing to their pharmacological characteristics, sodium-glucose cotransporter 2 (SGLT2) inhibitors might cause adverse effects in patients with COVID-19 and so cannot be recommended. Currently, insulin should be the main approach to the control of acute glycaemia. Most available evidence does not distinguish between the major types of diabetes mellitus and is related to type 2 diabetes mellitus owing to its high prevalence. However, some limited evidence is now available on type 1 diabetes mellitus and COVID-19. Most of these conclusions are preliminary, and further investigation of the optimal management in patients with diabetes mellitus is warranted.
Adult-onset autoimmune diabetes is a heterogeneous disease that is characterized by a reduced genetic load, a less intensive autoimmune process and a mild metabolic decompensation at onset compared ...with young-onset type 1 diabetes mellitus (T1DM). The majority of patients with adult-onset autoimmune diabetes do not require insulin treatment for at least 6 months after diagnosis. Such patients are defined as having latent autoimmune diabetes in adults (LADA), which is distinct from classic adult-onset T1DM. The extensive heterogeneity of adult-onset autoimmune diabetes is apparent beyond the distinction between classic adult-onset T1DM and LADA. LADA is characterized by genetic, phenotypic and humoral heterogeneity, encompassing different degrees of insulin resistance and autoimmunity; this heterogeneity is probably a result of different pathological mechanisms, which have implications for treatment. The existence of heterogeneous phenotypes in LADA makes it difficult to establish an a priori treatment algorithm, and therefore, a personalized medicine approach is required. In this Review, we discuss the current understanding and gaps in knowledge regarding the pathophysiology and clinical features of adult-onset autoimmune diabetes and highlight the similarities and differences with classic T1DM and type 2 diabetes mellitus.
Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in ...preventing SHEs in 50-80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment.
This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA1c <7.0% (53 mmol/mol) at day 365 and freedom from SHEs from day 28 to day 365 after the first transplant.
The primary end point was successfully met by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA1c level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients.
Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.
In this trial, high-risk nondiabetic relatives of patients with type 1 diabetes were randomly assigned to receive teplizumab (an anti-CD3 monoclonal antibody) or placebo and were followed for type 1 ...diabetes. Teplizumab delayed progression to clinical type 1 diabetes in high-risk participants.
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