scholarly journals Brakes on the accelerator: the journey of accelerator hypothesis from “the missing link” to “an evolving concept”

Author(s):  
Devi Dayal ◽  
Balasubramaniyan Muthuvel

<p>The incidence of Type 1 diabetes (T1D) has increased significantly over the past few decades but the causes for this increase are poorly understood and hence the strategies for preventing T1D are difficult to design. T1D is characterised by autoimmune destruction of pancreatic β-cells resulting in insulin deficiency as opposed to Type 2 diabetes (T2D) characterised by weight driven insulin resistance (IR). The accelerator hypothesis (AH), proposed by the late Prof Terence Wilkin in 2001 offers an alternative mechanism for T1D and a different approach to prevention of T1D. This hypothesis considers both T1D and T2D as one and proposes that obesity driven IR is the key factor that may lead to either type of diabetes. It thus offers an easy explanation for the increasing worldwide incidence of childhood diabetes which is paralleled by the increase in childhood obesity rates. However, one of the key predictions of AH that the obesity related IR accelerates the onset of diabetes and hence heavier children should develop diabetes at a younger age, has remained a matter of debate since the hypothesis was first proposed. Since the inception of AH, the results of a number of studies which aimed at testing the hypothesis in diverse patient populations have shown support or opposed this key prediction. This article discusses the relevance of AH in the context of data from these studies.</p>

2014 ◽  
Vol 222 (3) ◽  
pp. G13-G25 ◽  
Author(s):  
James E Bowe ◽  
Zara J Franklin ◽  
Astrid C Hauge-Evans ◽  
Aileen J King ◽  
Shanta J Persaud ◽  
...  

The pathophysiology of diabetes as a disease is characterised by an inability to maintain normal glucose homeostasis. In type 1 diabetes, this is due to autoimmune destruction of the pancreatic β-cells and subsequent lack of insulin production, and in type 2 diabetes it is due to a combination of both insulin resistance and an inability of the β-cells to compensate adequately with increased insulin release. Animal models, in particular genetically modified mice, are increasingly being used to elucidate the mechanisms underlying both type 1 and type 2 diabetes, and as such the ability to study glucose homeostasisin vivohas become an essential tool. Several techniques exist for measuring different aspects of glucose tolerance and each of these methods has distinct advantages and disadvantages. Thus the appropriate methodology may vary from study to study depending on the desired end-points, the animal model, and other practical considerations. This review outlines the most commonly used techniques for assessing glucose tolerance in rodents and details the factors that should be taken into account in their use. Representative scenarios illustrating some of the practical considerations of designingin vivoexperiments for the measurement of glucose homeostasis are also discussed.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jomana Khawandanah

Abstract Diabetes mellitus is a worldwide epidemic affecting the health of millions of people. While type 1 diabetes (T1D) is caused by autoimmune destruction of the insulin-producing beta cells of the pancreas, type 2 diabetes (T2D) results from a combination of insulin resistance and beta cell insulin secretory defect. Clear definition and diagnosis of these two types of diabetes has been increasing more and more difficult, leading to the inclusion of a new category, namely double or hybrid diabetes (DD) that demonstrates symptoms of both T1D and T2D via the accelerator hypothesis. In this review, we discuss the worldwide prevalence of DD, its main physiological characteristics, including beta-cell autoimmunity, insulin resistance, and cardiovascular disease, the main risk factors of developing DD, mainly genetics, obesity and lifestyle choices, as well as potential treatments, such as insulin titration, metformin and behavioural modifications. Increasing awareness of DD among the general population and primary care practitioners is necessary for successfully treating this complex, hybrid disease in the future.


2020 ◽  
Vol 57 (10) ◽  
pp. 1245-1253
Author(s):  
S. R. Tittel ◽  
◽  
K. M. Sondern ◽  
M. Weyer ◽  
T. Poeplau ◽  
...  

Abstract Aims To compare diabetes patients with hyperglycaemic hyperosmolar state (HHS), diabetic ketoacidosis (DKA), and patients without decompensation (ND). Methods In total, 500,973 patients with type 1 or type 2 diabetes of all ages registered in the diabetes patient follow-up (DPV) were included. Analysis was stratified by age (≤ / > 20 years) and by manifestation/follow-up. Patients were categorized into three groups: HHS or DKA—during follow-up according to the most recent episode—or ND. Results At onset of diabetes, HHS criteria were met by 345 (68.4% T1D) and DKA by 9824 (97.6% T1D) patients. DKA patients had a lower BMI(-SDS) in both diabetes types compared to ND. HbA1c was higher in HHS/DKA. During follow-up, HHS occurred in 1451 (42.2% T1D) and DKA in 8389 patients (76.7% T1D). In paediatric T1D, HHS/DKA was associated with younger age, depression, and dyslipidemia. Pump usage was less frequent in DKA patients. In adult T1D/T2D subjects, metabolic control was worse in patients with HHS/DKA. HHS and DKA were also associated with excessive alcohol intake, dementia, stroke, chronic kidney disease, and depression. Conclusions HHS/DKA occurred mostly in T1D and younger patients. However, both also occurred in T2D, which is of great importance in the treatment of diabetes. Better education programmes are necessary to prevent decompensation and comorbidities.


2018 ◽  
Vol 7 (1) ◽  
pp. R38-R46 ◽  
Author(s):  
Stavroula A Paschou ◽  
Nektaria Papadopoulou-Marketou ◽  
George P Chrousos ◽  
Christina Kanaka-Gantenbein

Type 1 diabetes mellitus (T1DM) results from the autoimmune destruction of β cells of the endocrine pancreas. Pathogenesis of T1DM is different from that of type 2 diabetes mellitus, where both insulin resistance and reduced secretion of insulin by the β cells play a synergistic role. We will present genetic, environmental and immunologic factors that destroy β cells of the endocrine pancreas and lead to insulin deficiency. The process of autoimmune destruction takes place in genetically susceptible individuals under the triggering effect of one or more environmental factors and usually progresses over a period of many months to years, during which period patients are asymptomatic and euglycemic, but positive for relevant autoantibodies. Symptomatic hyperglycemia and frank diabetes occur after a long latency period, which reflects the large percentage of β cells that need to be destroyed before overt diabetes become evident.


2021 ◽  
Vol 19 (1) ◽  
pp. 614-634
Author(s):  
Ayodele T. Odularu ◽  
Peter A. Ajibade

Abstract The aim of this review study was to assess the past significant events on diabetes mellitus, transformations that took place over the years in the medical records of treatment, countries involved, and the researchers who brought about the revolutions. This study used the content analysis to report the existence of diabetes mellitus and the treatments provided by researchers to control it. The focus was mainly on three main types of diabetes (type 1, type 2, and type 3 diabetes). Ethical consideration has also helped to boost diabetic studies globally. The research has a history path from pharmaceuticals of organic-based drugs to metal-based drugs with their nanoparticles in addition to the impacts of nanomedicine, biosensors, and telemedicine. Ongoing and future studies in alternative medicine such as vanadium nanoparticles (metal nanoparticles) are promising.


2021 ◽  
Vol 73 (1) ◽  
Author(s):  
Awadhesh Kumar Singh ◽  
Kamlesh Khunti

The prevalence of diabetes in people with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has varied worldwide. Most of the available evidence suggests a significant increase in severity and mortality of COVID-19 in people with either type 1 (T1DM) or type 2 diabetes mellitus (T2DM), especially in association with poor glycemic control. While new-onset hyperglycemia and new-onset diabetes (both T1DM and T2DM) have been increasingly recognized in the context of COVID-19 and have been associated with worse outcome, no conclusive evidence yet suggests direct tropism of SARS-CoV-2 on the β cells of pancreatic islets. While all approved oral antidiabetic agents appear to be safe in people with T2DM having COVID-19, no conclusive data are yet available to indicate a mortality benefit with any class of these drugs, in the absence of large randomized controlled trials. Expected final online publication date for the Annual Review of Medicine, Volume 73 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.


Medicina ◽  
2021 ◽  
Vol 57 (9) ◽  
pp. 973
Author(s):  
Adrian Vlad ◽  
Viorel Serban ◽  
Romulus Timar ◽  
Alexandra Sima ◽  
Veronica Botea ◽  
...  

Background and Objective: It is known that several viruses are involved in the pathogenesis of type 1 diabetes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new worldwide spread virus that may act as a trigger for the autoimmune destruction of the β-cells, as well, and thus lead to an increase in the incidence of type 1 diabetes. Material and Methods: The Romanian National Organization for the Protection of Children and Adolescents with Diabetes (ONROCAD) has collected information regarding new cases of type 1 diabetes in children aged 0 to 14 years from all over the country since 1996 and has computed the incidence of type 1 diabetes in this age group. Results: We observed a marked increase in the incidence of type 1 diabetes in the first year of the COVID-19 pandemic, with 16.9%, from 11.4/100,000 in 2019 to 13.3/100,000 in 2020, much higher compared to previous years (mean yearly increase was 5.1% in the period 1996–2015 and 0.8% in the interval 2015–2019). The proportion of newly diagnosed cases was significantly higher in the second half of 2020 compared to the second half of the previous years (57.8 vs. 51%, p < 0.0001). Conclusions: All these aspects suggest the role that SARS-CoV-2 could have in triggering pancreatic autoimmunity. To confirm this, however, collecting information from larger populations from different geographical regions, monitoring the incidence curves over a period of several years, and gathering background information on COVID-19 and/or data on COVID-19 specific antibodies are needed.


2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Paul C Langley ◽  
Taeho Greg Rhee

Over the past 20 years a number of simulations or models have been developed as a basis for tracking and evaluating the impact of pharmacological and other interventions in type 1 and type 2 diabetes mellitus. These models have typically tracked the natural course of these diseases generating long-term composite claims for cost-effectiveness. These claims can extend over the lifetime of the modeled patient cohort. Set against the standards of normal science, however, these claims lack credibility. The claims presented are all too often either immune to failure or are presented in a form that is non-testable. As such they fail to meet the key experimental requirements of falsification and replication. Unfortunately, there is a continuing belief that long-term or lifetime models are essential to decision-making. This is misplaced. The purpose of this review is to argue that there is a pressing need to reconsider the needs of health system decision makers and focus on modeled or simulated claims that are meaningful, testable, reportable and replicable in evaluating interventions in diabetes mellitus.   Type: Commentary


2018 ◽  
Vol 499 (4) ◽  
pp. 960-966 ◽  
Author(s):  
Jihyun Um ◽  
Nunggum Jung ◽  
Dongjin Kim ◽  
Sanghyuk Choi ◽  
Sang-Ho Lee ◽  
...  

Author(s):  
Fazilat Arifovna Bakhritdinova ◽  
◽  
Urmanova Firuza Makhkamovna ◽  
Nabiyeva Iroda Fayzullayevna ◽  
◽  
...  

In this review, the authors performed an overview of the literature on early diagnosis, treatment and methods for predicting the outcomes of the disease. According to regional endocrinological dispensaries, for 2020 registered SD for RUZ 277 926., Of these, type 1 type 18178, SD 2 type 259,748 patients. At the same time, the number of patients with DR was 2020 g of 83,632 persons, of which 73690 persons with di type 2. The real number of patients exceeds a registered 10 times, over the past 18 years, the number of patients with a rope in Uzbekistan increased by 2.4 times (according to the Ministry of Health of RUZ). The prevalence of others among patients of the CD is 10-90%, according to some specialists, up to 97-98.5%. For example, the frequency of development dr in India is lower than among Europeans and Americans, and among the black population more frequent than among the white. According to the WHO research group, it was revealed that the highest frequency of DR was detected in Oklahoma (76.4%), Zagreb (73.1%) and Hong Kong (58.1%). The lowest frequency was observed in Tokyo (29.7%). The prevalence of DR in patients in China amounted to 47.4%, and the frequency of DR in Poland was 31.4%.


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