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.
Diabetes mellitus (DM) increases the risk of infections, but the effect of better control has not been thoroughly investigated.
With the use of English primary care data, average glycated hemoglobin ...(HbA
) during 2008-2009 was estimated for 85,312 patients with DM ages 40-89 years. Infection rates during 2010-2015 compiled from primary care, linked hospital, and mortality records were estimated across 18 infection categories and further summarized as any requiring a prescription or hospitalization or as cause of death. Poisson regression was used to estimate adjusted incidence rate ratios (IRRs) by HbA
categories across all DM, and type 1 and type 2 DM separately. IRRs also were compared with 153,341 age-sex-practice-matched controls without DM. Attributable fractions (AF%) among patients with DM were estimated for an optimal control scenario (HbA
6-7% 42-53 mmol/mol).
Long-term infection risk rose with increasing HbA
for most outcomes. Compared with patients without DM, those with DM and optimal control (HbA
6-7% 42-53 mmol/mol, IRR 1.41 95% CI 1.36-1.47) and poor control (≥11% 97 mmol/mol, 4.70 4.24-5.21) had elevated hospitalization risks for infection. In patients with type 1 DM and poor control, this risk was even greater (IRR 8.47 5.86-12.24). Comparisons within patients with DM confirmed the risk of hospitalization with poor control (2.70 2.43-3.00) after adjustment for duration and other confounders. AF% of poor control were high for serious infections, particularly bone and joint (46%), endocarditis (26%), tuberculosis (24%), sepsis (21%), infection-related hospitalization (17%), and mortality (16%).
Poor glycemic control is powerfully associated with serious infections and should be a high priority.
Background
Diabetes and periodontitis are chronic non‐communicable diseases independently associated with mortality and have a bidirectional relationship.
Aims
To update the evidence for their ...epidemiological and mechanistic associations and re‐examine the impact of effective periodontal therapy upon metabolic control (glycated haemoglobin, HbA1C).
Epidemiology
There is strong evidence that people with periodontitis have elevated risk for dysglycaemia and insulin resistance. Cohort studies among people with diabetes demonstrate significantly higher HbA1C levels in patients with periodontitis (versus periodontally healthy patients), but there are insufficient data among people with type 1 diabetes. Periodontitis is also associated with an increased risk of incident type 2 diabetes.
Mechanisms
Mechanistic links between periodontitis and diabetes involve elevations in interleukin (IL)‐1‐β, tumour necrosis factor‐α, IL‐6, receptor activator of nuclear factor‐kappa B ligand/osteoprotegerin ratio, oxidative stress and Toll‐like receptor (TLR) 2/4 expression.
Interventions
Periodontal therapy is safe and effective in people with diabetes, and it is associated with reductions in HbA1C of 0.27–0.48% after 3 months, although studies involving longer‐term follow‐up are inconclusive.
Conclusions
The European Federation of Periodontology (EFP) and the International Diabetes Federation (IDF) report consensus guidelines for physicians, oral healthcare professionals and patients to improve early diagnosis, prevention and comanagement of diabetes and periodontitis.
The severity of the metabolic abnormality can progress, regress, or stay the same. ... the degree of hyperglycemia reflects the severity of the underlying metabolic process and its treatment more ...than the nature of the process itself.
Aim
To describe diabetes nurses' perspectives on the impact of the COVID‐19 pandemic on people with diabetes and diabetes services across Europe.
Methods
An online survey developed using a rapid ...Delphi method. The survey was translated into 17 different languages and disseminated electronically in 27 countries via national diabetes nurse networks.
Results
Survey responses from 1829 diabetes nurses were included in the analysis. The responses indicated that 28% (n = 504) and 48% (n = 873) of diabetes nurses felt the COVID‐19 pandemic had impacted ‘a lot’ on the physical and psychological risks of people with diabetes, respectively. The following clinical problems were identified as having increased ‘a lot’: anxiety 82% (n = 1486); diabetes distress 65% (n = 1189); depression 49% (n = 893); acute hyperglycaemia 39% (n = 710) and foot complications 18% (n = 323). Forty‐seven percent (n = 771) of respondents identified that the level of care provided to people with diabetes had declined either extremely or quite severely. Self‐management support, diabetes education and psychological support were rated by diabetes nurse respondents as having declined extremely or quite severely during the COVID‐19 pandemic by 31% (n = 499), 63% (n = 1,027) and 34% (n = 551), respectively.
Conclusion
The findings show that diabetes nurses across Europe have seen significant increases in both physical and psychological problems in their patient populations during COVID‐19. The data also show that clinical diabetes services have been significantly disrupted. As the COVID‐19 situation continues, we need to adapt care systems with some urgency to minimise the impact of the pandemic on the diabetes population.
Type 1 and type 2 diabetes, along with their accompanying hyperglycemia, are associated with a multitude of comorbidities including the development of diabetic kidney disease. Although the hallmarks ...of these metabolic disorders have been well characterized in population and animal studies, it is becoming increasingly apparent that diabetes manifests itself differently in men and women. This review summarizes the recent diabetic literature with a focus on known sex differences in clinical and preclinical studies. It explores the physiological differences of glucose handling and the development of diabetes between men and women. This review also uncovers potential mechanisms for these differences, honing in on the vital role that sex hormone signaling plays in the progression of diabetes and renal complications.
The use of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems has gained wide acceptance in diabetes care. These devices have been demonstrated to be ...clinically valuable, improving glycemic control and reducing risks of hypoglycemia in ambulatory patients with type 1 diabetes and type 2 diabetes. Approximately 30-40% of patients with type 1 diabetes and an increasing number of insulin-requiring patients with type 2 diabetes are using pump and sensor technology. As the popularity of these devices increases, it becomes very likely that hospital health care providers will face the need to manage the inpatient care of patients under insulin pump therapy and CGM. The American Diabetes Association advocates allowing patients who are physically and mentally able to continue to use their pumps when hospitalized. Health care institutions must have clear policies and procedures to allow the patient to continue to receive CSII treatment to maximize safety and to comply with existing regulations related to self-management of medication. Randomized controlled trials are needed to determine whether CSII therapy and CGM systems in the hospital are associated with improved clinical outcomes compared with intermittent monitoring and conventional insulin treatment or with a favorable cost-benefit ratio.
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.
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