analogs/agonists
Legend: HSP70 = heat shock protein 70; NLRP3 = nucleotide-binding oligomerization domain-like receptor protein 3; SGLTs = sodium-glucose co-transporters; GLUTs, glucose transporters; SIRT6=Sirtuin 6; FGFs = fibroblast growth factors; GPGRs = G protein–coupled receptors; GLP-1= glycogen-like peptide 1; ADPN = adiponectin; CTB APSL = cholera toxin B subunit and active peptide from shark liver; TGF-a = transforming growth factor-alpha; DKD = diabetic kidney disease [ 51 ].
The conventional approaches in the management of DM do not resolve the causes of the ailment and are laden with adverse effects. Hence, there is a quest for a desirable different therapeutic regimen. The cellular-based therapeutic technique currently in use in DM management is based on the pancreas or islet-cell transplantation to revive the beta cells for insulin secretion. This approach is restricted due to a lack of donor organs. These problems lead to the exploration of the possibility of constructing beta cells using stem cells. The peculiar rebuilding potential of stem cells might be an important tool that could be used in the management of DM. Development of replenishable islets source using stem cells might avert the recent supply/demand problems in the transplantation of islet and furnish DM subjects with a prolonged source of beta cells for insulin secretion. Hence, in the management of DM, stem cell investigation has become a promising approach [ 52 ].
The stem cell DM therapy is aimed at the replacement of malfunctioning or damaged pancreatic cells by employing pluripotent or multipotent stem cells. This technique has exploited the ability of various kinds of stem cells including induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), and adult stem cells using diverse methods to produce surrogate beta cells or to bring back the physiologic role of the beta cell [ 53 ].
Advancement in technology has facilitated the development of stem cells using different kinds of tissue sources such as adipose tissue, skin, bone marrow, umbilical cord blood, periosteum, and dental pulp. In searching for promising stem cells, the first organ of choice is usually the pancreas. Studies with animal models have indicated that a small number of pancreatic tissue when made available could bring back the optimum pancreatic beta-cell mass [ 54 ]. This is sequel to the differentiated beta cells from the pancreatic duct undergoing replication and dedifferentiation culminating in the formation of pluripotent cells which in turn synthesize more beta cells. Additional study suggested that these ductal cells populations could be produced in vitro and directed to produce insulin synthesizing clusters [ 55 , 56 ].
Moreover, the haemopoietic adult stem cells such as HSCs and mesenchymal stem cells (MSCs) have the potential to transdifferentiate into so many cell lineages such as the brain, liver, and lung as well as gastrointestinal tract cells [ 57 , 58 , 59 ]. A different group of researchers experimented on the multipotent differentiation of haemapoietic progenitors to replenish the beta cell number in T1DM. It was reported that the bone marrow of mouse was differentiated ex vivo into functional beta cells [ 60 ]. Relatedly, studies using the mice model indicated that cells of the bone marrow could be amenable to the pancreas as a target and that elevated blood glucose could be normalized [ 61 ]. An experiment with autologous HSCs demonstrated an improvement in T1DM and T2DM [ 62 , 63 ]. These studies furnish potential outcomes for the usage of autologous HSCs in the management of DM.
In addition to the aforementioned innovations in the management of diabetes, several drugs are still at different stages of clinical trial for eventual use. Others are ready and have been recently introduced into the market.
Tirzepatide: The drug was recently approved by the FDA under the trade name mounjaro for the treatment of T2DM [ 64 ]. Tirzepatide is an injectable given under the skin once in a week which targets the receptors of hormones which play central role in the metabolism of glucose. These hormones are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). While the GLP-1 reduces blood glucose by several mechanisms, including stimulating insulin secretion and suppressing glucagon release during hyperglycemia, GIP stimulates insulin release during hyperglycemia, but it also stimulates glucagon release during hypoglycemia.
Tirzepatide acts as agonist to their receptors [ 65 ], hence elongating their functions which results in blood glucose control. The efficacy of tirzepatide was established against a placebo, a GLP-1 receptor agonist (semaglutide) and two long-acting insulin analogs either as monotherapy or in combination with other antidiabetic agents [ 64 ]. In comparison to the placebo, it lowered the HbA1c by 11.6% and 1.5% as monotherapy and combination therapy, respectively. In comparison to other antidiabetic drugs, at the highest dose of 15 mg, it lowered the HbA1c 0.5% more than semaglutide, 0.9% more than insulin degludec and 1.0% more than insulin glargine [ 64 ]. Because of the efficacy therein and the once in a week dosing, tirzepatide provides a desirable paradigm shift in the management of T2DM.
Several drug candidates are at different phases of development for the management of DM. These are listed below.
LY3502970: LY3502970 is a partial agonist, biased toward G-protein activation over β-arrestin recruitment at the (GLP-1 receptor (GLP-1R). The molecule is highly potent and selective against other class B G-protein-coupled receptors (GPCRs) with a pharmacokinetic profile favorable for oral administration [ 66 ]. It is a product that is currently being developed by Eli lilly.
SCO-094: SCO-094 is a drug candidate identified by SCOHIA company which has a dual target of the receptors of GIP and GLP-1 [ 67 ]
Ladarixin (LDX): Ladarixin is an inhibitor of the interleukin-8 receptors CXCR1 and CXCR2, in new-onset T1DM [ 68 ]. It is a drug candidate developed by Dompe Farmaceutici. Short term LDX treatment of newly diagnosed patients with T1DM had no appreciable effect on preserving residual beta cell function [ 68 ].
DM is a complex, progressive, and multifactorial metabolic disorder needing more complex treatments over time. Globally, researchers have worked assiduously in the discovery and development of novel drugs for the treatment of diabetes. There is significant progress in research into the cause and management of T1DM [ 69 ]. Mounting evidence indicates that modern insulin therapy in combination with glucose self-monitoring including blood pressure and lipid monitoring has profoundly improved the long-term prognosis of T1DM [ 70 ]. The literature indicates that regular exercise and improved diet may enhance the quality of life for diabetic subjects but in the absence of adequate exercise and diet, medications may help diabetic persons regulate their blood glucose level. Moreover, implantation of insulin producing cells could furnish the basal glucose level essential for maintaining glucose homeostasis in vivo and thus hinder long-term injury from occurring in different tissues regardless of hormone administration [ 71 ].
The attainment of the full potential of gene therapy technique could be obtained via the design of gene delivery vectors that are safe, efficient, and specific and/ or the development of a technique for engineering of cell, in which the stem cell seems to be of great importance. Thus, the establishment of a reliable, sensitive, and acutely monitored feedback system is needed for the generation of a safe and efficient vector to facilitate diabetes gene therapy for clinical trial. Probably, the curtailment of islet transplantation rejection is the first clinical technique to DM gene therapy approach. On the other hand, insulin gene therapy is carried out in concert with conventional insulin treatment culminating in tight glycemic regulation in the absence of fasting hypoglycemia in T1DM subjects, as reported in T1DM rats [ 72 ].
Physical activity and nutrition therapy could help individuals with DM achieve metabolic goals. Employing diverse lifestyle approaches might help. Regulation of metabolic parameters such blood pressure, glucose, glycated hemoglobin, lipids, and body weight including the assessment of life quality are critical in determining the level of treatment goals by lifestyle changes [ 73 ]. However, different countries have focused on DM management and its complications on the normalization of glycemic control as assessed by hemoglobin A1 or fasting blood glucose which only addresses the need of subjects who were already diabetic. Thus, it is imperative to design programs for the early detection of altered glucose metabolism and to carry out robust approaches for the normalization of this changed state. Furthermore, through robust prevention strategies, better diagnostic tests, early risk detection, and management of the risks will help mitigate the incidence of DM and reduce or prevent events associated with end-organ failure [ 73 ].
Besides glycemic control, multifactorial interventions using different treatment regimen, including nanotechnology, gene therapy, stem cell, medical nutrition therapy, and lifestyle modification have yielded significant results in ameliorating the impact of DM but not without some challenges. Regardless of the promising nature of nanotechnology and its projected ability to turn around the fortunes in diabetes management, it is still faced with some challenges. One of the major limitations is the cost. Most of the gadgets required for CGM, and insulin delivery are very expensive. This limits their use to the rich class even when diabetes cuts across different economic classes. More so, there is an increased risk of infection via the implantation of sensors and cannulas which increases inflammation and could be frightening sometimes [ 24 ].
Notwithstanding the merits linked with the gene therapy approach, there could equally be problems. For example, genes introduced employing a viral vector might provoke an immune response and aggravate the disease condition [ 74 ]. Additionally, gene therapy studies are still mostly carried out using animal models and their safety is yet to be validated in humans [ 46 ].
Currently, it is established that gene delivery technology is the primary hurdle for successful gene therapy. The prime factors for an effective gene delivery technique include efficiency, stability, specificity, safety, and convenience. Thus, the greatest obstacle in gene therapy is the method of delivery of the corrective gene to the target site safely and efficiently. There is, therefore, a requirement of desirable gene delivery technology or vector to furnish the therapeutic potential where required. The two main vectors currently employed are viral and non-viral vectors. The merit of the non-viral vector is that it has low immunity, a low financial burden, and its preparation is convenient but the major obstacles for its extensive use emanate from the inefficiency of delivery method and expression of gene transiently [ 75 ]. Contrastingly, reports show that viral vectors are more efficient in gene delivery as several of them use a distinct mechanism for DNA delivery to the cells. Viral vectors are arranged as viral particles having precisely the important modulated sequences of the virus and from which all the genes of the virus have been excised. These viruses, when prepared very well, are defective that after target cell infection, there is no probable replication or infection theoretically [ 76 ]. Viral DNA is integrated with the genome of the host cell, thereby bestowing the capability for sturdy therapeutic gene expression.
Despite the fact that viral vectors are more efficient in comparison to non-viral vectors as gene delivery systems, there are still challenges associated with them, including inflammation, cytotoxicity, and immunogenicity which are needed to be looked into during the construction of viral vector system [ 46 ].
Notwithstanding the huge and novel impacts recorded in the applicable areas of stem cell biology in the management of DM, it is still in its primitive stage. A lot of hurdles still hinder the progression of stem cell research technologically and ethically, including:
The use of ESCs is confronted with the formation of teratomas and the danger of malignancy [ 77 ], thus raising safety concerns. This makes it imperative for a thorough investigation and screening of the probable adverse effects prior to its deployment in clinical trials and human treatment.
The primary hurdle associated with transplantation is autoimmune rejection. This makes it necessary for a stable and appropriate regimen for immunosuppression. There is a need for the stabilization of current transplantation protocols with the standard testing module. The transplantation of stem cells needs a few experimental works to appraise the problems linked with the stability, durability, and the survival of the transplanted cell with appropriate vascular and neural support in the new microenvironment.
The challenges of scale-up problems arise after the optimization of the appropriate developmental procedures. The number of cells must be enough to cope with the requisite request for future research including clinical investigations. Hence, an efficient method is required for the maximization of the yield via an adjustment in the culture requirements. The stem cells’ scale-up ability is needed for future exploration for the provision of surplus transplanted cellular reserves in order to strike equilibrium between demand and usage.
As a result of where it is obtained from, the ESCs are the potential targets for the ethicists. Normally, ESCs are obtained from embryos not fertilized or used during ex vivo fertilization in hospitals. Informed consent is usually required in the procurement of these ESCs from the donor prior to the usage in clinical research. Sadly, though, in the majority of instances, there is the destruction of the embryo during the process of obtaining the cells from the embryo, and this questions the source of life and the ethical license to terminate the fetus. Adult stem cells are preferable to embryonic ones as the controversy about their usage is limited. The current advancement in technology in induced pluripotent stem cell research is to allow the use of ones’ stem cells for diverse uses [ 78 ]. The adult cells are reprogrammed in such cases to pluripotent conditions and thereafter transformed into working beta cells. This approach might eventually resolve the impasse linked with ESCs and contribute to further safety issues likely to be tackled later in the future.
DM has become a public clinical challenge that requires urgent attention and the increasing trend in its cases is suggested to continue for more decades. Currently, there is no permanent cure for DM. Many treatment regimens have shown promising results in DM management. Yet, notwithstanding the potential of these giant treatment plans, DM remains a serious challenge that may continue to threaten public health. Thus, the problems encountered in each of these approaches need to be addressed to achieve a robust, efficient, and safe clinical management plan. There is a need for optimal metabolic regulation of glucose, blood pressure, and body weight which requires proper education and support for the improvement of diet, physical activity, and reduction in body weight. To effectively and successfully manage the control of this disease, an emphasis on public policies to reinforce health care access and resources, the promotion of a patient-centred care approach, and health-promoting infrastructures at environmental level are required.
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conception and Design: C.A., C.O.E. and I.A.; Data Collection: C.A., C.O.E., P.N.O. and N.A.O.; Data Analysis and Table Creation: C.A., P.M.A., J.C. and B.O.A. Writing the Manuscript: C.A., C.O.E., P.M.A., N.A.O., J.C., B.O.A., P.N.O. and I.A.; Vetting the manuscript for intellectual content: I.A.; Approval of the manuscript for submission: All the authors. All authors have read and agreed to the published version of the manuscript.
Informed consent statement, data availability statement, conflicts of interest.
The authors declare that they have no conflict of interest.
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Intended for healthcare professionals
Type 1 diabetes is an autoimmune condition resulting in insulin deficiency and eventual loss of pancreatic β cell function requiring lifelong insulin therapy. Since the discovery of insulin more than 100 years ago, vast advances in treatments have improved care for many people with type 1 diabetes. Ongoing research on the genetics and immunology of type 1 diabetes and on interventions to modify disease course and preserve β cell function have expanded our broad understanding of this condition. Biomarkers of type 1 diabetes are detectable months to years before development of overt disease, and three stages of diabetes are now recognized. The advent of continuous glucose monitoring and the newer automated insulin delivery systems have changed the landscape of type 1 diabetes management and are associated with improved glycated hemoglobin and decreased hypoglycemia. Adjunctive therapies such as sodium glucose cotransporter-1 inhibitors and glucagon-like peptide 1 receptor agonists may find use in management in the future. Despite these rapid advances in the field, people living in under-resourced parts of the world struggle to obtain necessities such as insulin, syringes, and blood glucose monitoring essential for managing this condition. This review covers recent developments in diagnosis and treatment and future directions in the broad field of type 1 diabetes.
Type 1 diabetes is an autoimmune condition that occurs as a result of destruction of the insulin producing β cells of the pancreatic islets, usually leading to severe endogenous insulin deficiency. 1 Without treatment, diabetic ketoacidosis will develop and eventually death will follow; thus, lifelong insulin therapy is needed for survival. Type 1 diabetes represents 5-10% of all diabetes, and diagnosis classically occurs in children but can also occur in adulthood. The burden of type 1 diabetes is expansive; it can result in long term complications, decreased life expectancy, and reduced quality of life and can add significant financial burden. Despite vast improvements in insulin, insulin delivery, and glucose monitoring technology, a large proportion of people with type 1 diabetes do not achieve glycemic goals. The massive burden of type 1 diabetes for patients and their families needs to be appreciated. The calculation and timing of prandial insulin dosing, often from food with unknown carbohydrate content, appropriate food and insulin dosing when exercising, and cost of therapy are all major challenges. The psychological realities of both acute management and the prospect of chronic complications add to the burden. Education programs and consistent surveillance for “diabetes burnout” are ideally available to everyone with type 1 diabetes.
In this review, we discuss recent developments in the rapidly changing landscape of type 1 diabetes and highlight aspects of current epidemiology and advances in diagnosis, technology, and management. We do not cover the breadth of complications of diabetes or certain unique scenarios including psychosocial aspects of type 1 diabetes management, management aspects specific to older adults, and β cell replacement therapies. Our review is intended for the clinical reader, including general internists, family practitioners, and endocrinologists, but we acknowledge the critical role that people living with type 1 diabetes and their families play in the ongoing efforts to understand this lifelong condition.
We did individual searches for studies on PubMed by using terms relevant to the specific topics covered in this review pertaining to type 1 diabetes. Search terms used included “type 1 diabetes” and each individual topic—diagnosis, autoantibodies, adjuvant therapies, continuous glucose monitoring, automated insulin delivery, immunotherapies, diabetic ketoacidosis, hypoglycemia, and under-resourced settings. We considered all studies published in the English language between 1 January 2001 and 31 January 2023. We selected publications outside of this timeline on the basis of relevance to each topic. We also supplemented our search strategy by a hand search of the references of key articles. We prioritized studies on each highlighted topic according to the level of evidence (randomized controlled trials (RCTs), systematic reviews and meta-analyses, consensus statements, and high quality observational studies), study size (we prioritized studies with at least 50 participants when available), and time of publication (we prioritized studies published since 2003 except for the landmark Diabetes Control and Complications Trial and a historical paper by Tuomi on diabetes autoantibodies, both from 1993). For topics on which evidence from RCTs was unavailable, we included other study types of the highest level of evidence available. To cover all important clinical aspects of the broad array of topics covered in this review, we included additional publications such as clinical reviews as appropriate on the basis of clinical relevance to both patients and clinicians in our opinion.
The incidence of type 1 diabetes is rising worldwide, possibly owing to epigenetic and environmental factors. Globally in 2020 an estimated 8.7 million people were living with type 1 diabetes, of whom approximately 1.5 million were under 20 years of age. 2 This number is expected to rise to more than 17 million by 2040 ( https://www.t1dindex.org/#global ). The International Diabetes Federation estimates the global prevalence of type 1 diabetes at 0.1%, and this is likely an underestimation as diagnoses of type 1 diabetes in adults are often not accounted for. The incidence of adult onset type 1 diabetes is higher in Europe, especially in Nordic countries, and lowest in Asian countries. 3 Adult onset type 1 diabetes is also more prevalent in men than in women. An increase in prevalence in people under 20 years of age has been observed in several western cohorts including the US, 4 5 Netherlands, 6 Canada, 7 Hungary, 8 and Germany. 9
Classically, type 1 diabetes presents over the course of days or weeks in children and adolescents with polyuria, polydipsia, and weight loss due to glycosuria. The diagnosis is usually straightforward, with profound hyperglycemia (often >300 mg/dL) usually with ketonuria with or without ketoacidemia. Usually, more than one autoantibody is present at diagnosis ( table 1 ). 10 The number of islet autoantibodies combined with parameters of glucose tolerance now forms the basis of risk prediction for type 1 diabetes, with stage 3 being clinical disease ( fig 1 ). 11 The originally discovered autoantibody, islet cell antibody, is no longer used clinically owing to variability of the assay despite standardisation. 12
Autoantibody characteristics associated with increased risk of type 1 diabetes 10
Natural history of type 1 diabetes. Adapted with permission from Insel RA, et al. Diabetes Care 2015;38:1964-74 11
Half of all new cases of type 1 diabetes are now recognized as occurring in adults. 13 Misclassification due to misdiagnosis (commonly as type 2 diabetes) occurs in nearly 40% of people. 14 As opposed to typical childhood onset type 1 diabetes, progression to severe insulin deficiency, and therefore its clinical presentation in adults, is variable. The term latent autoimmune diabetes of adults (LADA) was introduced 30 years ago to identify adults who developed immune mediated diabetes. 15 An international consensus defined the diagnostic criteria for LADA as age >30 years, lack of need for insulin use for at least six months, and presence of islet cell autoantibodies. 16 However, debate as to whether the term LADA should even be used as a diagnostic term persists. The American Diabetes Association (ADA) Standards of Care note that for the purpose of classification, all forms of diabetes mediated by autoimmune β cell destruction are included in the classification of type 1 diabetes. 17 Nevertheless, they note that use of the term LADA is acceptable owing to the practical effect of heightening awareness of adults likely to have progressive autoimmune β cell destruction and thereby accelerating insulin initiation by clinicians to prevent diabetic ketoacidosis.
The investigation of adults with suspected type 1 diabetes is not always straightforward ( fig 2 ). 18 Islet cell autoantibodies such as glutamic acid decarboxylase antibody (GADA), tyrosine phosphatase IA2 antibody, and zinc transporter isoform 8 autoantibody act as markers of immune activity and can be detected in the blood with standardized assays ( table 1 ). The presence of one or more antibodies in adults with diabetes could mark the progression to severe insulin deficiency; these individuals should be considered to have type 1 diabetes. 1 Autoantibodies, especially GADA, should be measured only in people with clinically suspected type 1 diabetes, as low concentrations of GADA can be seen in type 2 diabetes and thus false positive measurements are a concern. 19 That 5-10% of cases of type 1 diabetes may occur without diabetes autoantibodies is also now clear, 20 and that the diabetes autoantibodies disappear over time is also well appreciated. 21
Flowchart for investigation of suspected type 1 diabetes in adults, based on data from white European populations. No single clinical feature in isolation confirms type 1 diabetes. The most discriminative feature is younger age at diagnosis (<35 years), with lower body mass index (<25), unintentional weight loss, ketoacidosis, and glucose >360 mg/dL at presentation. Adapted with permission from Holt RIG, et al. Diabetes Care 2021;44:2589-625 1
Genetic risk scoring (GRS) for type 1 diabetes has received attention to differentiate people whose classification is unclear. 22 23 24 Developed in 2019, the T1D-GRS2 uses 67 single nucleotide polymorphisms from known autoimmune loci and can predict type 1 diabetes in children of European and African ancestry. Although GRS is not available for routine clinical use, it may allow prediction of future cases of type 1 diabetes to allow prevention strategies with immune intervention (see below).
A major change in the type 1 diabetes phenotype has occurred over the past few decades, with an increase in obesity; the reasons for this are complex. In the general population, including people with type 1 diabetes, an epidemic of sedentary lifestyles and the “westernized diet” consisting of increased processed foods, refined sugars, and saturated fat is occurring. In people with type 1 diabetes, the overall improvement in glycemic control since the report of the Diabetes Control and Complications Trial (DCCT) in 1993 (when one or two insulin injections a day was standard therapy) has resulted in less glycosuria so that the typical patient with lower body weight is uncommon in high income countries. In the US T1D Exchange, more than two thirds of the adult population were overweight or obese. 25
Similarly, obesity in young people with type 1 diabetes has also increased over the decades. 26 The combination of autoimmune insulin deficiency with obesity and insulin resistance has received several descriptive names over the years, with this phenotype being described as double diabetes and hybrid diabetes, among others, 26 27 but no formal nomenclature in the diabetes classification exists. Many of these patients have family members with type 2 diabetes, and some patients probably do have both types of diabetes. Clinically, minimal research has been done into how this specific population responds to certain antihyperglycemic oral agents, such as glucagon-like peptide 1 (GLP-1) receptor agonists, given the glycemic, weight loss, and cardiovascular benefits seen with these agents. 28 These patients are common in most adult diabetes practices, and weight management in the presence of insulin resistance and insulin deficiency remains unclear.
The introduction of home blood glucose monitoring (BGM) more than 45 years ago was met with much skepticism until the report of the DCCT. 29 Since then, home BGM has improved in accuracy, precision, and ease of use. 30 Today, in many parts of the world, home BGM, a static measurement of blood glucose, has been replaced by continuous glucose monitoring (CGM), a dynamic view of glycemia. CGM is superior to home BGM for glycemic control, as confirmed in a meta-analysis of 21 studies and 2149 participants with type 1 diabetes in which CGM use significantly decreased glycated hemoglobin (HbA 1c ) concentrations compared with BGM (mean difference −0.23%, 95% confidence interval −3.83 to −1.08; P<0.001), with a greater benefit if baseline HbA 1c was >8% (mean difference −0.43%, −6.04 to −3.30; P<0.001). 31 This newer technology has also evolved into a critical component of automated insulin delivery. 32
CGM is the standard for glucose monitoring for most adults with type 1 diabetes. 1 This technology uses interstitial fluid glucose concentrations to estimate blood glucose. Two types of CGM are available. The first type, called “real time CGM”, provides a continuous stream of glucose data to a receiver, mobile application, smartwatch, or pump. The second type, “intermittently scanned CGM,” needs to be scanned by a reader device or smartphone. Both of these technologies have shown improvements in HbA 1c and amount of time spent in the hypoglycemic range compared with home BGM when used in conjunction with multiple daily injections or “open loop” insulin pump therapy. 33 34 Real time CGM has also been shown to reduce hypoglycemic burden in older adults with type 1 diabetes ( table 2 ). 36 Alerts that predict or alarm with both hypoglycemia and hyperglycemia can be customized for the patient’s situation (for example, a person with unawareness of hypoglycemia would have an alert at a higher glucose concentration). Family members can also remotely monitor glycemia and be alerted when appropriate. The accuracy of these devices has improved since their introduction in 2006, so that currently available sensors can be used without a confirmation glucose concentration to make a treatment decision with insulin. However, some situations require home BGM, especially when concerns exist that the CGM does not match symptoms of hypoglycemia.
Summary of trials for each topic covered
Analysis of CGM reports retrospectively can assist therapeutic decision making both for the provider and the patient. Importantly, assessing the retrospective reports and watching the CGM in real time together offer insight to the patient with regard to insulin dosing, food choices, and exercise. Patients should be encouraged to assess their data on a regular basis to better understand their diabetes self-management. Table 3 shows standard metrics and targets for CGM data. 52 Figure 3 shows an ambulatory glucose profile.
Standardized continuous glucose monitoring metrics for adults with diabetes 52
Example of ambulatory glucose profile of 52 year old woman with type 1 diabetes and fear of hypoglycemia. CGM=continuous glucose monitoring; GMI=glucose management indicator
Improvements in technology and evidence for CGM resulting in international recommendations for its widespread use have resulted in greater uptake by people with type 1 diabetes across the globe where available and accessible. Despite this, not everyone wishes to use it; some people find wearing any device too intrusive, and for many the cost is prohibitive. These people need at the very least before meal and bedtime home BGM.
A next generation implantable CGM device (Sensionics), with an improved calibration algorithm that lasts 180 days after insertion by a healthcare professional, is available in both the EU and US. Although fingerstick glucose calibration is needed, the accuracy is comparable to that of other available devices. 53
The discovery of insulin in 1921, resulting in a Nobel Prize, was considered one of the greatest scientific achievements of the 20th century. The development of purified animal insulins in the late 1970s, followed by human insulin in the early 1980s, resulted in dramatic reductions in allergic reactions and lipoatrophy. Introduction of the first generation of insulin analogs, insulin lispro in the mid-1990s followed by insulin glargine in the early 2000s, was an important advance for the treatment of type 1 diabetes. 54 We review the next generation of insulin analogs here. Table 4 provides details on available insulins.
Pharmacokinetics of commonly used insulin preparations
Insulin degludec was developed with the intention of improving the duration of action and achieving a flatter profile compared with the original long acting insulin analogs, insulin glargine and insulin detemir. Its duration of action of 42 hours at steady state means that the profile is generally flat without significant day-to-day variability, resulting in less hypoglycemia compared with U-100 glargine. 39 55
When U-100 insulin glargine is concentrated threefold, its action is prolonged. 56 U-300 glargine has a different kinetic profile and is delivered in one third of the volume of U-100 glargine, with longer and flatter effects. The smaller volume of U-300 glargine results in slower and more gradual release of insulin monomers owing to reduced surface area in the subcutaneous space. 57 U-300 glargine also results in lesser hypoglycemia compared with U-100 glargine. 58
Rapid acting insulin analogs include insulin lispro, aspart, and glulisine. With availability of insulin lispro, the hope was for a prandial insulin that better matched food absorption. However, these newer insulins are too slow to control the glucose spike seen with ingestion of a high carbohydrate load, leading to the development of insulins with even faster onset of action.
The first available ultra-rapid prandial insulin was fast acting insulin aspart. This insulin has an onset of appearance approximately twice as fast (~5 min earlier) as insulin aspart, whereas dose-concentration and dose-response relations are comparable between the two insulins ( table 4 ). 59 In adults with type 1 diabetes, mealtime and post-meal fast acting aspart led to non-inferior glycemic control compared with mealtime aspart, in combination with basal insulin. 60 Mean HbA 1c was 7.3%, 7.3%, and 7.4% in the mealtime faster aspart, mealtime aspart, and post‐meal faster aspart arms, respectively (P<0.001 for non-inferiority).
Insulin lispro-aabc is the second ultra-rapid prandial insulin. In early kinetic studies, insulin lispro-aabc appeared in the serum five minutes faster with 6.4-fold greater exposure in the first 15 minutes compared with insulin lispro. 61 The duration of exposure of the insulin concentrations in this study was 51 minutes faster with lispro-aabc. Overall insulin exposure was similar between the two groups. Clinically, lispro-aabc is non-inferior to insulin lispro, but postprandial hyperglycemia is lower with the faster acting analog. 62 Lispro-aabc given at mealtime resulted in greater improvement in post-prandial glucose (two hour post-prandial glucose −31.1 mg/dL, 95% confidence interval −41.0 to −21.2; P<0.001).
Both ultra-rapid acting insulins can be used in insulin pumps. Lispro-aabc tends to have more insertion site reactions than insulin lispro. 63 A meta-analysis including nine studies and 1156 participants reported increased infusion set changes on rapid acting insulin analogs (odds ratio 1.60, 95% confidence interval 1.26 to 2.03). 64
The quickest acting insulin is pulmonary inhaled insulin, with an onset of action of 12 minutes and a duration of 1.5-3 hours. 65 When used with postprandial supplemental dosing, glucose control is improved without an increase in hypoglycemia. 66
Approved automated insulin delivery systems.
CGM systems and insulin pumps have shown improvement in glycemic control and decreased risk of severe hypoglycemia compared with use of self-monitoring of blood glucose and multiple daily insulin injections in type 1 diabetes. 67 68 69 Using CGM and insulin pump together (referred to as sensor augmented pump therapy) only modestly improves HbA 1c in patients who have high sensor wear time, 70 71 but the management burden of diabetes does not decrease as frequent user input is necessary. Thus emerged the concept of glucose responsive automated insulin delivery (AID), in which data from CGM can inform and allow adjustment of insulin delivery.
In the past decade, exponential improvements in CGM technologies and refined insulin dosing pump algorithms have led to the development of AID systems that allow for minimization of insulin delivery burden. The early AID systems reduced hypoglycemia risk by automatically suspending insulin delivery when glucose concentrations dropped to below a pre-specified threshold but did not account for high glucose concentrations. More complex algorithms adjusting insulin delivery up and down automatically in response to real time sensor glucose concentrations now allow close replication of normal endocrine pancreatic physiology.
AID systems (also called closed loop or artificial pancreas systems) include three components—an insulin pump that continuously delivers rapid acting insulin, a continuous glucose sensor that measures interstitial fluid glucose at frequent intervals, and a control algorithm that continuously adjusts insulin delivery that resides in the insulin pump or a smartphone application or handheld device ( fig 4 ). All AID systems that are available today are referred to as “hybrid” closed loop (HCL) systems, as users are required to manually enter prandial insulin boluses and signal exercise, but insulin delivery is automated at night time and between meals. AID systems, regardless of the type used, have shown benefit in glycemic control and cost effectiveness, improve quality of life by improving sleep quality, and decrease anxiety and diabetes burden in adults and children. 72 73 74 Limitations to today’s HCL systems are primarily related to pharmacokinetics and pharmacodynamics of available analog insulins and accuracy of CGM in extremes of blood glucose values. The iLet bionic pancreas, cleared by the US Food and Drug Administration (FDA) in May 2023, is an AID system that determines all therapeutic insulin doses for an individual on the basis of body weight, eliminating the need for calculation of basal rates, insulin to carbohydrate ratios, blood glucose corrections, and bolus dose. The control algorithms adapt continuously and autonomously to the individual’s insulin needs. 38 Table 5 lists available AID systems.
Schematic of closed loop insulin pump technology. The continuous glucose monitor senses interstitial glucose concentrations and sends the information via Bluetooth to a control algorithm hosted on an insulin pump (or smartphone). The algorithm calculates the amount of insulin required, and the insulin pump delivers rapid acting insulin subcutaneously
Comparison of commercially available hybrid closed loop systems 75
Do-it-yourself (DIY) closed loop systems—DIY open artificial pancreas systems—have been developed by people with type 1 diabetes with the goal of self-adjusting insulin by modifying their individually owned devices. 76 These systems are built by the individual using an open source code widely available to anyone with compatible medical devices who is willing and able to build their own system. DIY systems are used by several thousand people across the globe but are not approved by regulatory bodies; they are patient-driven and considered “off-label” use of technology with the patient assuming full responsibility for their use. Clinicians caring for these patients should ensure basic diabetes skills, including pump site maintenance, a knowledge of how the chosen system works, and knowing when to switch to “manual mode” for patients using an artificial pancreas system of any kind. 76 The small body of studies on DIY looping suggests improvement in HbA 1c , increased time in range, decreased hypoglycemia and glucose variability, improvement in night time blood glucose concentrations, and reduced mental burden of diabetes management. 77 78 79 Although actively prescribing or initiating these options is not recommended, these patients should be supported by clinical teams; insulin prescription should not be withheld, and, if initiated by the patient, unregulated DIY options should be openly discussed to ensure open and transparent relationships. 78
In January 2023, the US FDA cleared the Tidepool Loop app, a DIY AID system. This software will connect the CGM, insulin pump, and Loop algorithm, but no RCTs using this method are available.
For patients with type 1 diabetes who meet specific clinical criteria, β cell replacement therapy using whole pancreas or pancreatic islet transplantation can be considered. Benefits of transplantation include immediate cessation of insulin therapy, attainment of euglycemia, and avoidance of hypoglycemia. Additional benefits include improved quality of life and stabilization of complications. 80 Chronic immunosuppression is needed to prevent graft rejection after transplantation.
Whole pancreas transplantation, first performed in 1966, involves complex abdominal surgery and lifelong immunosuppressive therapy and is limited by organ donor availability. Today, pancreas transplants are usually performed simultaneously using two organs from the same donor (simultaneous pancreas-kidney transplant (SPKT)), sequentially if the candidate has a living donor for renal transplantation (pancreas after kidney transplant (PAKT)) or on its own (pancreas transplantation alone). Most whole pancreas transplants are performed with kidney transplantation for end stage diabetic kidney disease. Pancreas graft survival at five years after SPKT is 80% and is superior to that with pancreas transplants alone (62%) or PAKT (67%). 81 Studies from large centers where SPKT is performed show that recipients can expect metabolic improvements including amelioration of problematic hypoglycemia for at least five years. 81 The number of pancreas transplantations has steadily decreased in the past two decades.
Islet transplantation can be pursued in selected patients with type 1 diabetes marked by unawareness of hypoglycemia and severe hypoglycemic episodes, to help restore the α cell response critical for responding to hypoglycemia. 82 83 Islet transplantation involves donor pancreas procurement with subsequent steps to isolate, purify, culture, and infuse the islets. Multiple donors are needed to provide enough islet cells to overcome islet cell loss during transplantation. Survival of the islet grafts, limited donor supply, and lifelong need for immunosuppressant therapy remain some of the biggest challenges. 84 Islet transplantation remains experimental in the US and is offered in a few specialized centers in North America, some parts of Europe, and Australia. 85
Therapies targeting T cells, B cells, and cytokines that find use in a variety of autoimmune diseases have also been applied to type 1 diabetes. The overarching goal of immune therapies in type 1 diabetes is to prevent or delay the loss of functional β cell mass. Studies thus far in early type 1 diabetes have not yet successfully shown reversal of loss of C peptide or maintenance of concentrations after diagnosis, although some have shown preservation or slowing of loss of β cells. This suggests that a critical time window of opportunity exists for starting treatment depending on the stage of type 1 diabetes ( fig 1 ).
Teplizumab is a humanized monoclonal antibody against the CD3 molecule on T cells; it is thought to modify CD8 positive T lymphocytes, key effector cells that mediate β cell death and preserves regulatory T cells. 86 Teplizumab, when administered to patients with new onset of type 1 diabetes, was unable to restore glycemia despite C peptide preservation. 87 However, in its phase II prevention study of early intervention in susceptible individuals (at least two positive autoantibodies and an abnormal oral glucose tolerance test at trial entry), a single course of teplizumab delayed progression to clinical type 1 diabetes by about two years ( table 2 ). 43 On the basis of these results, teplizumab received approval in the US for people at high risk of type 1 diabetes in November 2022. 88 A phase III trial (PROTECT; NCT03875729 ) to evaluate the efficacy and safety of teplizumab versus placebo in children and adolescents with new diagnosis of type 1 diabetes (within six weeks) is ongoing. 89
Thus far, targeting various components of the immune response has been attempted in early type 1 diabetes without any long term beneficial effects on C peptide preservation. Co-stimulation blockade using CTLA4-Ig abatacept, a fusion protein that interferes with co-stimulation needed in the early phases of T cell activation that occurs in type 1 diabetes, is being tested for efficacy in prevention of type 1 diabetes ( NCT01773707 ). 90 Similarly, several cytokine directed anti-inflammatory targets (interleukin 6 receptor, interleukin 1β, tumor necrosis factor ɑ) have not shown any benefit.
Adjunctive therapies for type 1 diabetes have been long entertained owing to problems surrounding insulin delivery, adequacy of glycemic management, and side effects associated with insulin, especially weight gain and hypoglycemia. At least 50% of adults with type 1 diabetes are overweight or obese, presenting an unmet need for weight management in these people. Increased cardiovascular risk in these people despite good glycemic management presents additional challenges. Thus, use of adjuvant therapies may tackle these problems.
Metformin, by decreasing hepatic glucose production, could potentially decrease fasting glucose concentrations. 91 It has shown benefit in reducing insulin doses and possibly improving metabolic control in obese/overweight people with type 1 diabetes. A meta-analysis of 19 RCTs suggests short term improvement in HbA 1c that is not sustained after three months and is associated with higher incidence of gastrointestinal side effects. 92 No evidence shows that metformin decreases cardiovascular morbidity in type 1 diabetes. Therefore, owing to lack of conclusive benefit, addition of metformin to treatment regimens is not recommended in consensus guidelines.
Endogenous GLP-1 is an incretin hormone secreted from intestinal L cells in response to nutrient ingestion and enhances glucose induced insulin secretion, suppresses glucagon secretion, delays gastric emptying, and induces satiety. 93 GLP-1 promotes β cell proliferation and inhibits apoptosis, leading to expansion of β cell mass. GLP-1 secretion in patients with type 1 diabetes is similar to that seen in people without diabetes. Early RCTs of liraglutide in type 1 diabetes resulted in weight loss and modest lowering of HbA 1c ( table 2 ). 49 50 Liraglutide 1.8 mg in people with type 1 diabetes and higher body mass index decreased HbA 1c , weight, and insulin requirements with no increased hypoglycemia risk. 94 However, on the basis of results from a study of weekly exenatide that showed similar results, these effects may not be sustained. 51 A meta-analysis of 24 studies including 3377 participants showed that the average HbA 1c decrease from GLP-1 receptor agonists compared with placebo was highest for liraglutide 1.8 mg daily (−0.28%, 95% confidence interval −0.38% to−0.19%) and exenatide (−0.17%, −0.28% to 0.02%). The estimated weight loss from GLP-1 receptor agonists compared with placebo was −4.89 (−5.33 to−4.45) kg for liraglutide 1.8 mg and −4.06 (−5.33 to−2.79) kg for exenatide. 95 No increase in severe hypoglycemia was seen (odds ratio 0.67, 0.43 to 1.04) but therapy was associated with higher levels of nausea. GLP-1 receptor agonist use may be beneficial for weight loss and reducing insulin doses in a subset of patients with type 1 diabetes. GLP-1 receptor agonists are not a recommended treatment option in type 1 diabetes. Semaglutide is being studied in type 1 diabetes in two clinical trials ( NCT05819138 ; NCT05822609 ).
Sodium-glucose cotransporter 2 (SGLT-2), a protein expressed in the proximal convoluted tubule of the kidney, reabsorbs filtered glucose; its inhibition prevents glucose reabsorption in the tubule and increases glucose excretion by the kidney. Notably, the action of these agents is independent of insulin, so this class of drugs has potential as adjunctive therapy for type 1 diabetes. Clinical trials have shown significant benefit in cardiovascular and renal outcomes in type 2 diabetes; therefore, significant interest exists for use in type 1 diabetes. Several available SGLT-2 inhibitors have been studied in type 1 diabetes and have shown promising results with evidence of decreased total daily insulin dosage, improvement in HbA 1c , lower rates of hypoglycemia, and decrease in body weight; however, these effects do not seem to be sustained at one year in clinical trials and seem to wane with time. Despite beneficial effects, increased incidence of diabetic ketoacidosis has been observed in all trials, is a major concern, and is persistent despite educational efforts. 96 97 98 Low dose empagliflozin (2.5 mg) has shown lower rates of diabetic ketoacidosis in clinical trials ( table 2 ). 47 Favorable risk profiles have been noted in Japan, the only market where SGLT-2 inhibitors are approved for adjunctive use in type 1 diabetes. 99 In the US, SGLT-2 inhibitors are approved for use in type 2 diabetes only. In Europe, although dapagliflozin was approved for use as adjunct therapy to insulin in adults with type 1 diabetes, the manufacturer voluntarily withdrew the indication for the drug in 2021. 100 Sotagliflozin is a dual SGLT-1 and SGLT-2 inhibitor that decreases renal glucose reabsorption through systemic inhibition of SGLT-2 and decreases glucose absorption in the proximal intestine by SGLT-1 inhibition, blunting and delaying postprandial hyperglycemia. 101 Studies of sotagliflozin in type 1 diabetes have shown sustained HbA 1c reduction, weight loss, lower insulin requirements, lesser hypoglycemia, and more diabetic ketoacidosis relative to placebo. 102 103 104 The drug received authorization in the EU for use in type 1 diabetes, but it is not marketed there. Although SGLT inhibitors are efficacious in type 1 diabetes management, the risk of diabetic ketoacidosis is a major limitation to widespread use of these agents.
Diabetic ketoacidosis.
Diabetic ketoacidosis is a serious and potentially fatal hyperglycemic emergency accompanied by significant rates of mortality and morbidity as well as high financial burden for healthcare systems and societies. In the past decade, increasing rates of diabetic ketoacidosis in adults have been observed in the US and Europe. 105 106 This may be related to changes in the definition of diabetic ketoacidosis, use of medications associated with higher risk, and admission of patients at lower risk. 107 In a US report of hospital admissions with diabetic ketoacidosis, 53% of those admitted were between the ages of 18 and 44, with higher rates in men than in women. 108 Overall, although mortality from diabetic ketoacidosis in developed countries remains low, rates have risen in people aged >60 and in those with coexisting life threatening illnesses. 109 110 Recurrent diabetic ketoacidosis is associated with a substantial mortality rate. 111 Frequency of diabetic ketoacidosis increases with higher HbA 1c concentrations and with lower socioeconomic status. 112 Common precipitating factors include newly diagnosed type 1 diabetes, infection, poor adherence to insulin, and an acute cardiovascular event. 109
Euglycemic diabetic ketoacidosis refers to the clinical picture of an increased anion gap metabolic acidosis, ketonemia, or significant ketonuria in a person with diabetes without significant glucose elevation. This can be seen with concomitant use of SGLT-2 inhibitors (currently not indicated in type 1 diabetes), heavy alcohol use, cocaine use, pancreatitis, sepsis, and chronic liver disease and in pregnancy 113 Treatment is similar to that for hyperglycemic diabetic ketoacidosis but can require earlier use and greater concentrations of a dextrose containing fluid for the insulin infusion in addition to 0.9% normal saline resuscitation fluid. 114
The diagnosis of diabetic ketoacidosis has evolved from a gluco-centric diagnosis to one requiring hyperketonemia. By definition, independent of blood glucose, a β-hydroxybutyrate concentration >3 mmol/L is required for diagnosis. 115 However, the use of this ketone for assessment of the severity of the diabetic ketoacidosis is controversial. 116 Bedside β-hydroxybutyrate testing during treatment is standard of care in many parts of the world (such as the UK) but not others (such as the US). Concerns have been raised about accuracy of bedside β-hydroxybutyrate meters, but this is related to concentrations above the threshold for diabetic ketoacidosis. 116
Goals for management of diabetic ketoacidosis include restoration of circulatory volume, correction of electrolyte imbalances, and treatment of hyperglycemia. Intravenous regular insulin infusion is the standard of care for treatment worldwide owing to rapidity of onset of action and rapid resolution of ketonemia and hyperglycemia. As hypoglycemia and hypokalemia are more common during treatment, insulin doses are now recommended to be reduced from 0.1 u/kg/h to 0.05 u/kg/h when glucose concentrations drop below 250 mg/dL or 14 mM. 115 Subcutaneous rapid acting insulin protocols have emerged as alternative treatments for mild to moderate diabetic ketoacidosis. 117 Such regimens seem to be safe and have the advantages of not requiring admission to intensive care, having lower rates of complications related to intravenous therapy, and requiring fewer resources. 117 118 Ketonemia and acidosis resolve within 24 hours in most people. 115 To prevent rebound hyperglycemia, the transition off an intravenous insulin drip must overlap subcutaneous insulin by at least two to four hours. 115
Hypoglycemia, a common occurrence in people with type 1 diabetes, is a well appreciated effect of insulin treatment and occurs when blood glucose falls below the normal range. Increased susceptibility to hypoglycemia from exogenous insulin use in people with type 1 diabetes results from multiple factors, including imperfect subcutaneous insulin delivery tools, loss of glucagon within a few years of diagnosis, progressive impairment of the sympatho-adrenal response with repeated hypoglycemic episodes, and eventual development of impaired awareness. In 2017 the International Hypoglycemia Study Group developed guidance for definitions of hypoglycemia; on the basis of this, a glucose concentration of 3.0-3.9 mmol/L (54-70 mg/dL) was designated as level 1 hypoglycemia, signifying impending development of level 2 hypoglycemia—a glucose concentration <3 mmol/L (54 mg/dL). 119 120 At approximately 54 mg/dL, neuroglycopenic hypoglycemia symptoms, including vision and behavior changes, seizures, and loss of consciousness, begin to occur as a result of glucose deprivation of neurons in the central nervous system. This can eventually lead to cerebral dysfunction at concentrations <50 mg/dL. 121 Severe hypoglycemia (level 3), denoting severe cognitive and/or physical impairment and needing external assistance for recovery, is a common reason for emergency department visits and is more likely to occur in people with lower socioeconomic status and with the longest duration of diabetes. 112 Prevalence of self-reported severe hypoglycemia is very high according to a global population study that included more than 8000 people with type 1 diabetes. 122 Severe hypoglycemia occurred commonly in younger people with suboptimal glycemia according to a large electronic health record database study in the US. 123 Self- reported severe hypoglycemia is associated with a 3.4-fold increase in mortality. 124 125
Acute consequences of hypoglycemia include impaired cognitive function, temporary focal deficits including stroke-like symptoms, and memory deficits. 126 Cardiovascular effects including tachycardia, arrhythmias, QT prolongation, and bradycardia can occur. 127 Hypoglycemia can impair many activities of daily living, including motor vehicle safety. 128 In a survey of adults with type 1 diabetes who drive a vehicle at least once a week, 72% of respondents reported having hypoglycemia while driving, with around 5% reporting a motor vehicle accident due to hypoglycemia in the previous two years. 129 This contributes to the stress and fear that many patients face while grappling with the difficulties of ongoing hypoglycemia. 130
Glucagon is highly efficacious for the primary treatment of severe hypoglycemia when a patient is unable to ingest carbohydrate safely, but it is unfortunately under-prescribed and underused. 131 132 Availability of nasal, ready to inject, and shelf-stable liquid glucagon formulations have superseded the need for reconstituting older injectable glucagon preparations before administration and are now preferred. 133 134 Real time CGM studies have shown a decreased hypoglycemic exposure in people with impaired awareness without a change in HbA 1c . 34 135 136 137 138 CGM has shown benefit in decreasing hypoglycemia across the lifespan, including in teens, young adults, and older people. 36 139 Although CGM reduces the burden of hypoglycemia including severe hypoglycemia, it does not eliminate it; overall, such severe level 3 hypoglycemia rates in clinical trials are very low and hard to decipher in the real world. HCL insulin delivery systems integrated with CGM have been shown to decrease hypoglycemia. Among available rapid acting insulins, ultra-rapid acting lispro (lispro-aabc) seems to be associated with less frequent hypoglycemia in type 1 diabetes. 140 141
As prevention of hypoglycemia is a crucial aspect of diabetes management, formal training programs to increase awareness and education on avoidance of hypoglycemia, such as the UK’s Dose Adjustment for Normal Eating (DAFNE), have been developed. 142 143 This program has shown fewer severe hypoglycemia (mean 1.7 (standard deviation 8.5) episodes per person per year before training to 0.6 (3.7) episodes one year after training) and restoration of recognition of hypoglycemia in 43% of people reporting unawareness. Clinically relevant anxiety and depression fell from 24.4% to 18.0% and from 20.9% to 15.5%, respectively. A structured education program with cognitive and psychotherapeutic aspects for changing hypoglycemia related behaviors, called the Hypoglycemia Awareness Restoration Program despite optimized self-care (HARPdoc), showed a positive effect on changing unhelpful beliefs around hypoglycemia and improved diabetes related and general distress and anxiety scores. 144
According to a recent estimate from the International Diabetes Federation, 1.8 million people with type 1 diabetes live in low and middle income countries (LMICs). 2 In many LMICs, the actual burden of type 1 diabetes remains unknown and material resources needed to manage type 1 diabetes are lacking. 145 146 Health systems in these settings are underequipped to tackle the complex chronic disease that is type 1 diabetes. Few diabetes and endocrinology specialist physicians are available owing to lack of specific postgraduate training programs in many LMICs; general practitioners with little to no clinical experience in managing type 1 diabetes care for these patients. 146 This, along with poor availability and affordability of insulin and lack of access to technology, results in high mortality rates. 147 148 149 In developed nations, low socioeconomic status is associated with higher levels of mortality and morbidity for adults with type 1 diabetes despite access to a universal healthcare system. 150 Although global governments have committed to universal health coverage and therefore widespread availability of insulin, it remains very far from realization in most LMICs. 151
Access to technology is patchy and varies globally. In the UST1DX, CGM use was least in the lowest fifth of socioeconomic status. 152 Even where technology is available, successful engagement does not always occur. 153 In a US cohort, lower CGM use was seen in non-Hispanic Black children owing to lower rates of device initiation and higher rates of discontinuation. 154 In many LMICs, blood glucose testing strips are not readily available and cost more than insulin. 151 In resource limited settings, where even diagnosis, basic treatments including insulin, syringes, and diabetes education are limited, use of CGM adds additional burden to patients. Need for support services and the time/resources needed to download and interpret data are limiting factors from a clinician’s perspective. Current rates of CGM use in many LMICs are unknown.
Inequities in the availability of and access to certain insulin formulations continue to plague diabetes care. 155 In developed countries such as the US, rising costs have led to insulin rationing by around 25% of people with type 1 diabetes. 156 LMICs have similar trends while also remaining burdened by disproportionate mortality and complications from type 1 diabetes. 155 157 With the inclusion of long acting insulin analogs in the World Health Organization’s Model List of Essential Medicines in 2021, hope has arisen that these will be included as standard of care across the world. 158 In the past, the pricing of long acting analogs has limited their use in resource poor settings 159 ; however, their inclusion in WHO’s list was a major step in improving their affordability. 158 With the introduction of lower cost long acting insulin biosimilars, improved access to these worldwide in the future can be anticipated. 160
Making insulin available is not enough on its own to improve the prognosis for patients with diabetes in resource poor settings. 161 Improved healthcare infrastructure, better availability of diabetes supplies, and trained personnel are all critical to improving type 1 diabetes care in LMICs. 161 Despite awareness of limitations and barriers, a clear understanding of how to implement management strategies in these settings is still lacking. The Global Diabetes Compact was launched in 2021 with the goal of increasing access to treatment and improving outcomes for people with diabetes across the globe. 162
Monitoring systems.
The ability to measure urinary or more recently blood ketone concentrations is an integral part of self-management of type 1 diabetes, especially during acute illness, intermittent fasting, and religious fasts to prevent diabetic ketoacidosis. 163 Many people with type 1 diabetes do not adhere to urine or blood ketone testing, which likely results in unnecessary episodes of diabetic ketoacidosis. 164 Noting that blood and urine ketone testing is not widely available in all countries and settings is important. 1 Regular assessment of patients’ access to ketone testing (blood or urine) is critical for all clinicians. Euglycemic diabetic ketoacidosis in type 1 diabetes is a particular problem with concomitant use of SGLT-2 inhibitors; for this reason, these agents are not approved for use in these patients. For sick day management (and possibly for the future use of SGLT-2 inhibitors in people with type 1 diabetes), it is hoped that continuous ketone monitoring (CKM) can mitigate the risks of diabetic ketoacidosis. 165 Like CGM, the initial CKM device measures interstitial fluid β-hydroxybutyrate instead of glucose. CKM use becomes important in conjunction with a hybrid closed loop insulin pump system and added SGLT-2 inhibitor therapy, where insulin interruptions are common and hyperketonemia is frequent. 166
Perhaps the greatest technological challenge to date has been the development of non-invasive glucose monitoring. Numerous attempts have been made using strategies including optics, microwave, and electrochemistry. 167 Lack of success to date has resulted in healthy skepticism from the medical community. 168 However, active interest in the development of non-invasive technology with either interstitial or blood glucose remains.
In the immediate future, two weekly basal insulins, insulin icodec and basal insulin Fc, may become available. 169 Studies of insulin icodec in type 1 diabetes are ongoing (ONWARDS 6; NCT04848480 ). How these insulins will be incorporated in management of type 1 diabetes is not yet clear.
Currently available AID systems use only a single hormone, insulin. Dual hormone AID systems incorporating glucagon are in development. 170 171 Barriers to the use of dual hormone systems include the need for a second chamber in the pump, a lack of stable glucagon formulations approved for long term subcutaneous delivery, lack of demonstrated long term safety, and gastrointestinal side effects from glucagon use. 74 Similarly, co-formulations of insulin and amylin (a hormone co-secreted with insulin and deficient in people with type 1 diabetes) are in development. 172
As our understanding of the immunology of type 1 diabetes expands, development of the next generation of immunotherapies is under active pursuit. Antigen specific therapies, peptide immunotherapy, immune tolerance using DNA vaccination, and regulatory T cell based adoptive transfer targeting β cell senescence are all future opportunities for drug development. Combining immunotherapies with metabolic therapies such as GLP-1 receptor agonists to help to improve β cell mass is being actively investigated.
The quest for β cell replacement methods is ongoing. Transplantation of stem cell derived islets offers promise for personalized regenerative therapies as a potentially curative method that does away with the need for donor tissue. Since the first in vivo model of glucose responsive β cells derived from human embryonic stem cells, 173 different approaches have been attempted. Mesenchymal stromal cell treatment and autologous hematopoietic stem cells in newly diagnosed type 1 diabetes may preserve β cell function without any safety signals. 174 175 176 Stem cell transplantation for type 1 diabetes remains investigational. Encapsulation, in which β cells are protected using a physical barrier to prevent immune attack and avoid lifelong immunosuppression, and gene therapy techniques using CRISPR technology also remain in early stages of investigation.
Until recently, no specific guidelines for management of type 1 diabetes existed and management guidance was combined with consensus statements developed for type 2 diabetes. Table 6 summarizes available guidance and statements from various societies. A consensus report for management of type 1 diabetes in adults by the ADA and European Association for the Study of Diabetes became available in 2021; it covers several topics of diagnosis and management of type 1 diabetes, including glucose monitoring, insulin therapy, and acute complications. Similarly, the National Institute for Health and Care Excellence also offers guidance on management of various aspects of type 1 diabetes. Consensus statements for use of CGM, insulin pump, and AID systems are also available.
Guidelines in type 1 diabetes
Type 1 diabetes is a complex chronic condition with increasing worldwide prevalence affecting several million people. Several successes in management of type 1 diabetes have occurred over the years from the serendipitous discovery of insulin in 1921 to blood glucose monitoring, insulin pumps, transplantation, and immunomodulation. The past two decades have seen advancements in diagnosis, treatment, and technology including development of analog insulins, CGM, and advanced insulin delivery systems. Although we have gained a broad understanding on many important aspects of type 1 diabetes, gaps still exist. Pivotal research continues targeting immune targets to prevent or delay onset of type 1 diabetes. Although insulin is likely the oldest of existing modern drugs, no low priced generic supply of insulin exists anywhere in the world. Management of type 1 diabetes in under resourced areas continues to be a multifaceted problem with social, cultural, and political barriers.
ADA—American Diabetes Association
AID—automated insulin delivery
BGM—blood glucose monitoring
CGM—continuous glucose monitoring
CKM—continuous ketone monitoring
DCCT—Diabetes Control and Complications Trial
DIY—do-it-yourself
FDA—Food and Drug Administration
GADA—glutamic acid decarboxylase antibody
GLP-1—glucagon-like peptide 1
GRS—genetic risk scoring
HbA1c—glycated hemoglobin
HCL—hybrid closed loop
LADA—latent autoimmune diabetes of adults
LMIC—low and middle income country
PAKT—pancreas after kidney transplant
RCT—randomized controlled trial
SGLT-2—sodium-glucose cotransporter 2
SPKT—simultaneous pancreas-kidney transplant
What future new technologies can be helpful in management of type 1 diabetes?
How can newer insulin delivery methods benefit people with type 1 diabetes?
What is the role of disease modifying treatments in prevention and delay of type 1 diabetes?
Is there a role for sodium-glucose co-transporter inhibitors or glucagon-like peptide 1 receptor angonists in the management of type 1 diabetes?
As the population with type 1 diabetes ages, how should management of these people be tailored?
How can we better serve people with type 1 diabetes who live in under-resourced settings with limited access to medications and technology?
A person with lived experience of type 1 diabetes reviewed a draft of the manuscript and offered input on important aspects of their experience that should be included. This person is involved in large scale education and activism around type 1 diabetes. They offered their views on various aspects of type 1 diabetes, especially the use of adjuvant therapies and the burden of living with diabetes. This person also raised the importance of education of general practitioners on the various stages of type 1 diabetes and the management aspects. On the basis of this feedback, we have highlighted the burden of living with diabetes on a daily basis.
Series explanation: State of the Art Reviews are commissioned on the basis of their relevance to academics and specialists in the US and internationally. For this reason they are written predominantly by US authors
Contributors: SS and IBH contributed to the planning, drafting, and critical review of this manuscript. FNK contributed to the drafting of portions of the manuscript. All three authors are responsible for the overall content as guarantors.
Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: SS has received an honorarium from Abbott Diabetes Care; IBH has received honorariums from Abbott Diabetes Care, Lifescan, embecta, and Hagar and research support from Dexcom and Insulet.
Provenance and peer review: Commissioned; externally peer reviewed.
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April 27, 2023
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by Silvia Cernea Clark, Rice University
For the well over 700 million people around the globe living with type 1 diabetes, getting a host immune system to tolerate the presence of implanted insulin-secreting cells could be life-changing.
Rice University bioengineer Omid Veiseh and collaborators identified new biomaterial formulations that could help turn the page on type 1 diabetes treatment, opening the door to a more sustainable, long-term, self-regulating way to handle the disease.
To do so, they developed a new screening technique that involves tagging each biomaterial formulation in a library of hundreds with a unique "barcode" before implanting them in live subjects.
According to the study in Nature Biomedical Engineering , using one of the alginate formulations to encapsulate human insulin-secreting islet cells provided long-term blood sugar level control in diabetic mice. Catheters coated with two other high-performing materials did not clog up.
"This work was motivated by a major unmet need," said Veiseh, a Rice assistant professor of bioengineering and Cancer Prevention and Research Institute of Texas scholar. "In type 1 diabetes patients , the body's immune system attacks the insulin-producing cells of the pancreas. As those cells are killed off, the patient loses the ability to regulate their blood glucose."
For decades, scientists labored toward what Veiseh called a "'holy grail" goal of housing islet cells inside a porous matrix made out of a protective material that would allow the cells to access oxygen and nutrients without getting clobbered by the host's immune system.
However, materials with optimal biocompatibility proved very hard to find, due in part to screening constraints. On one hand, immune system response to a given implanted biomaterial can only be assessed in a live host.
"The problem is the immune response needs to be investigated inside the body of these diabetic mice, not in a test tube ," said Boram Kim, a graduate student in the Veiseh lab and co-lead author on the study. "That means that if you want to screen these hundreds of alginate molecules, then you need to have hundreds of animal test subjects. Our idea was to screen for hundreds of biomaterials at the same time, in the same test subject."
On the other hand, different biomaterial formulations look the same, making it impossible to identify high-performing ones in the absence of some telltale trait. This made testing more than one biomaterial per host unfeasible.
"They are different materials but they look the same," Veiseh said. "And once they are implanted in the body of a test subject and then taken out again, we cannot distinguish between the materials and we would be unable to identify which material formulation worked best."
To overcome these constraints, Veiseh and collaborators came up with a way to tag each alginate formulation with a unique 'barcode' that allowed them to identify the ones that performed best.
"We paired each modified biomaterial with human umbilical vein endothelial cells (HUVEC) from a different donor," Kim said.
"The HUVEC cells, because they come from unique donors, act as a barcode that allows us to tell what material was used initially," Veiseh added. "The winners are the ones that have live cells in them. Once we found them, we sequenced the genome of those cells and figured out which material was paired with it. That's how we uncovered the greatest hits."
Trials are underway for stem cell-derived islet cell use in diabetic patients. However, current islet treatments require immunosuppression, making it a taxing way to treat type 1 diabetes.
"Currently, in order to use implanted islet cells in diabetic patients, you have to suppress the entire immune system, just as if you were trying to do an organ transplant," Veiseh said. "That comes with a lot of complications for the patient."
"They can develop cancer, they can't fight infections, so, for the vast majority of patients, it's better to actually do the insulin therapy where they inject themselves. With this biomaterial-encapsulation strategy, no immunosuppression is needed."
Placing actual HUVEC cells inside the biomaterial capsules increased the likelihood that the host immune system would detect a foreign presence. This makes the experiment more robust than simply testing for immune response to the biomaterials alone.
"We wanted to test a library of these materials, with the selection pressure of having cells inside the beads that makes it harder for the material to not get noticed by the immune system," Veiseh said. "There's a lot of interest from all the islet cell manufacturers to be able to get rid of immunosuppression and instead use these alginate hydrogel matrices to protect the implanted cells."
The new high-throughput "barcoding" approach can be deployed to screen for other medical applications using fewer live test subjects.
"That actually feeds into a lot of other projects in my lab where we're doing biologic production from cells for other disease indications," Veiseh said. "The same modifications can be applied to all types of materials that go into the body. This is not limited only to cell transplantation. The technology we developed can be paired with a lot of different device concepts."
"For instance, some diabetic patients use automated pump systems to self-administer insulin. The catheters on those pump systems have to be replaced every few days because they get clogged. We were able to show that coating the catheters with these new materials prevented clogging."
"With this new cell-based barcoding technology, biomaterials research just got an unprecedented boost that will accelerate the translation to clinically applicable products, and make it more affordable," said Dr. José Oberholzer, a transplant surgeon and bioengineer at the University of Virginia.
"This is a real paradigm shift. With this method, we can now screen hundreds of biomaterials at once and select those that the human body does not reject. We can protect cellular grafts from the assaults of the immune system, without the need for immunosuppressive medications," Oberholzer added.
Former Rice bioengineering professor and current NuProbe U.S. CEO David Zhang noted that " high-throughput DNA sequencing has revolutionized many biomedical fields."
"I am pleased to work with Omid to enable the development of improved biomaterials using my team's expertise in DNA sequencing," added Zhang, who was a co-investigator on the grant. "These improved biomaterials can enable durable implanted cell therapies to function as living drug factories, and can have a positively disruptive impact on patients with a variety of chronic diseases."
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Continued type 2 diabetes guidance derived from the niddk-supported grade study.
NIDDK-supported research from the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study , which compared the ability of four type 2 diabetes medications to maintain blood glucose (sugar) over time when paired with metformin, presented new follow-up findings emphasizing a need for individualized blood glucose treatment in the long-term management of type 2 diabetes . Across 10 additional analyses of GRADE data, researchers have now identified differences in medication acceptance, quality of life, insulin secretion, mortality, and other outcomes among the four previously studied second-line medications. Researchers observed individual patient characteristics were associated with the achievement of lower and higher average blood glucose levels over time. For example, researchers found that early intensification of diabetes treatment among older patients (≥58 years) was not associated with negative outcomes ( hypoglycemia or treatment failure), and younger individuals (<58 years) overall, were less likely to maintain blood glucose control over time. These follow-up analyses show clinicians can select second-line treatments based on patient characteristics. Moreover, these characteristics can be used to identify people who are not meeting glycemic goals and who may benefit from treatment intensification. The GRADE report collection was published in Diabetes Care in April.
Researchers from NIDDK, NIH’s National Institute of Allergy and Infectious Diseases (NIAID), and the NIH Clinical Center detected signs of early coronary artery disease in asymptomatic, middle-aged people living with HIV (PLWH). Coronary artery disease develops at younger ages and presents differently in PLWH compared to people who are HIV-negative, making early intervention difficult. Using MRI imaging and electrocardiography, researchers measured coronary artery thickness, an early sign of coronary artery disease, and diastolic function, the ability of the heart muscle to relax, in 74 PLWH with no history of cardiovascular disease and compared the results with those of a group of 25 matched controls. The researchers reported increased coronary artery thickness in PLWH was associated with impaired diastolic function (impaired heart muscle activity) and duration of exposure to the anti-retroviral therapy didanosine. The study, which was published in Radiology: Cardiothoracic Imaging in April, uncovers an avenue for early heart disease intervention for PLWH and demonstrates a need for additional research on how HIV affects the heart.
In an NIDDK study comparing thermoregulation (ability to maintain a constant internal body temperature) between women and men 18 to 35 years old, researchers found heat generation and loss were regulated similarly among both groups, despite variation in body shape and size. Data was collected from 16 women and 12 men at a range of temperatures (63 – 88°F) in a whole-room indirect calorimeter under controlled conditions (clothing, diet, and physical activity) to compare inter-individual variation in metabolic activity (energy use) at cold temperatures.
The researchers hypothesized that, if women were less thermally adapted to the cold than men, thermogenesis (heat production) in the group would increase above baseline at warmer temperatures. Study results showed women increased metabolic activity at cooler temperatures on average than the men (21.9 ± 1.3°C vs. 22.9 ± 1.2°C), which was attributed to increased body insulation associated with higher percentage of body fat.
The researchers did not find sex-based differences in other secondary measurements collected, including self-reported thermal comfort, muscle electrical activity, and brown fat glucose (sugar) uptake. These results suggest body temperature regulation is primarily influenced by both body size and composition, dispelling commonly held beliefs regarding differences in how men and women physically respond to the cold. This research was conducted at the NIH Clinical Center Metabolic Clinical Research Unit and published in the Proceedings of the National Academy of Sciences (PNAS) in April.
Research partially funded by NIDDK identified bacteria species that break down cholesterol in the gut, which may lower cholesterol and heart disease risk. Researchers analyzed the microbial genome in stool samples of more than 1,400 participants in the NIH-supported Framingham Heart Study using a deep-learning algorithm. The team discovered that people with higher levels of certain bacteria, including a species called Oscillibacter , had lower levels of cholesterol. They validated this observation by growing and feeding cholesterol to Oscillibacter strains grown from the stool samples. The bacteria broke the cholesterol into smaller molecules that don’t raise the risk of cardiovascular disease. Another bacterium, Eubacterium coprostanoligenes , was also associated with lower cholesterol and had a synergistic effect with the Oscillibacter bacteria. The study was published in April in Cell and appeared in NIH’s Research Matters .
In a new study, NIDDK researchers looked at how the body responds to fasting, or not eating anything for a period of time. Study participants stayed in a special room that could accurately measure how much energy their bodies were using. After consuming a normal diet for three days, the participants went through two 24-hour sessions in this room. In one session, they ate normally. In the other, they fasted. For the 24 hours after each session, the participants could eat as much as they wanted from a variety of foods in refrigerated vending machines.
The researchers found that people who have trouble switching between burning carbohydrates and burning fat during fasting (metabolic inflexibility) tend to eat more calories after the fasting period, compared to people who can more easily switch between these fuel sources. This finding suggests that the ability to be "metabolically flexible" and adapt one’s fuel usage may be an important factor in overeating and weight gain. The study, which was led by scientists in NIDDK’s Phoenix Epidemiology and Clinical Research Branch, was published in April as an “Editor’s Choice” selection in Obesity .
In an NIDDK-funded randomized study of patients with chronic kidney disease, type 2 diabetes, and hypertension, researchers investigated whether embedding practice facilitators into primary care practices would decrease hospitalizations when compared to standard of care clinics. The study included more than 11,000 patients from 141 primary care clinics.
Researchers concluded that more preventative cardiovascular, diabetic, and chronic kidney disease care was delivered in clinics with practice facilitators than in standard of care clinics; however, the embedded practice facilitator approach did not reduce hospitalizations at one year. Secondary outcomes (emergency department visits, readmissions, cardiovascular events, dialysis, or death) were also not significantly different between the two study groups. The risk of an adverse event was similar in both groups as well. The study, which published in the New England Journal of Medicine in April, suggests that more understanding is needed to effectively deliver guideline-directed therapies to this population.
A recent NIDDK-supported study from Cornell University sheds light on a new role of retinoic acid, a metabolite of vitamin A, in the development of chronic kidney disease (CKD). Signs of late-stage CKD include progressive fibrosis and proximal tubules damage. Researchers found in a mouse model that retinoic acid receptors (RARα), particularly those within the proximal tubules, are crucial for the normal development of kidneys and their ongoing health. Deletion of RARα resulted in increased inflammation, interstitial fibrosis, and decreased kidney function over several months, reflecting features of CKD in people. Of note, female responses to the deletion of RARα in models were greater than in males, providing opportunity to study the diseases mechanisms in females in the CKD models. Researchers then restored RARα levels by administering retinoic acid, which reduced fibrosis in previous studies. The research appeared in the Proceedings of the National Academy of Sciences (PNAS) in February and points to potential innovative approaches to therapies for CKD.
In a new NIDDK-supported study, a team from Northwestern University introduced a wireless implantable device to continuously monitor bladder function. Researchers created an ultrathin stretchable sensor that encircles the bladder and measures mechanical strain as the bladder fills or empties in real time. Data gathered by the sensor is sent to a smartphone or tablet via Bluetooth. Published in April in the Proceedings of the National Academy of Sciences , the device holds promise for people with disrupted bladder signaling, which can result from bladder cancer, paralysis, spina bifida, or invasive bladder procedures, as current tests that assess lower urinary tract function provide snapshot measurements only. The implantable wireless system functioned for 30 days following implantation in rodent models and up to 8 weeks in nonhuman primate models, indicating a promising alternative for monitoring bladder function and the potential for enhancing patient care.
A.) shows a schematic illustration of the technology and envisioned clinical use case. Following a partial bladder cystectomy, the system continuously monitors filling and voiding dynamics through a soft, stretchable strain gauge that encircles the bladder and a companion wireless module that streams data to an external device using standard Bluetooth Low Energy (BLE) communication protocols. The resulting information provides insights to aid in care decisions associated with postoperative recovery and healing, potential complications due to infections, and other processes. B.), present schematic illustrations and a photograph of the strain gauge and its helical interconnection to the wireless base station, respectively. A critical feature of the gauge is that it avoids any significant mechanical constraint on the natural processes of filling and voiding of the bladder, through the use of ultrathin, low modulus designs. The device exploits a silicone elastomer with low cross-linking density (Ecoflex 00-30), with a sensing region that contains particles of conducting carbon at loading levels slightly above the threshold for percolation electrical transport (16–18). The system can be designed as either a permanent implant for chronic monitoring or as a temporary device based on bioresorbable materials, specifically on poly(octamethylenemaleate (anhydride) citrate) (POMaC) and tungsten (W) particles (19–22). In this latter iteration, the strain gauge dissolves and disappears in the body to eliminate device load on the bladder after a period of clinical need (C.). D.) shows the relative change in resistance of such a bioresorbable strain gauge following injection of saline into a bladder mimic at three different rates. E.) illustrate the process of accelerated dissolution in phosphate-buffered saline (PBS, pH = 7.4) at 75 °C. The focus of the following description is on the permanent version of the device.
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By Elizabeth Cooney June 21, 2024
O RLANDO — Twelve people with type 1 diabetes who received a therapy derived from stem cells were able to produce enough of their own insulin to maintain healthy blood glucose levels 90 days later, Vertex Pharmaceuticals said Friday. All but one reduced or eliminated the need to inject insulin over those three months and three people followed for one year no longer needed to inject insulin at all.
Researchers say the study marks a promising approach that could one day relieve some people with type 1 diabetes of the need for daily insulin injections.
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“These cells clearly work,” said Jay Skyler, an endocrinologist at the University of Miami Miller School of Medicine who was not involved in the study.
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Elizabeth Cooney is a cardiovascular disease reporter at STAT, covering heart, stroke, and metabolic conditions.
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Type 1 diabetes (also known as diabetes mellitus) is an autoimmune disease in which immune cells attack and destroy the insulin-producing cells of the pancreas. The loss of insulin leads to the inability to regulate blood sugar levels. Patients are usually treated by insulin-replacement therapy.
RNA-sequencing data from NK-like CD57 + and PD-1 + CD8 + exhausted-like T cell populations linked to beneficial immunotherapy response in autoimmune patients suggest shared clonal relationships with each other and with common precursor populations.
Many studies identified an increase in the incidence of type 1 diabetes mellitus (T1DM) during the COVID-19 pandemic, but other reports do not support this association. This Review addresses the issue of the involvement of SARS-CoV-2 infection in the development of T1DM using evidence from epidemiological, clinical and experimental studies.
Patient educators and nurses can demonstrate the real-life use of health technologies.
Activation of innate immunity has been linked to the progression of type 1 diabetes. A study now shows that overexpression of METTL3, a writer protein of the m 6 A machinery that modifies mRNA, restrains interferon-stimulated genes when expressed in pancreatic β-cells, identifying it as a promising therapeutic target.
One hundred years after the Nobel prize was bestowed on Banting and McLeod for the ‘discovery’ of insulin, we are again seeing major evolutions in the management of type 1 diabetes mellitus, with the prospect of achieving disease control beyond mere management now becoming real. Here, we discuss the latest, most notable developments.
Designed for all health care professionals who provide clinical care and education for people with diabetes, the Clinical Update Conference (CUC) encompasses three days of engagement, education, and connection. Attendees learn practical guidance from diabetes care experts on the latest evidence and newest clinical practice recommendations and are a part of the first in-depth discussion on what’s new in the annually updated Standards of Care in Diabetes—with an emphasis on application.
2025 Clinical Update Conference January 31–February 2, 2025 Omni Orlando Resort at ChampionsGate Orlando, Florida and virtually
Stay Updated!
The 2024 CUC was held February 2–4 at the Omni Orlando Resort at ChampionsGate in Orlando, FL and virtually.
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In addition, the report provides an update on the Pathway to Stop Diabetes® (Pathway) program, which pairs talented early-career scientists with mentorship from world-renowned diabetes scientists to drive research innovation free from traditional project constraints. This year, through the Pathway program, ADA dedicated over $4.8 million ...
For Harvard Stem Cell Institute Co-Director and Xander University Professor Douglas Melton, whose lab pioneered the science behind the therapy, the trial marked the most recent turning point in a decades-long effort to understand and treat the disease. In a conversation with the Gazette, Melton discussed the science behind the advance, the ...
The objectives of our study were to update national trends in risk-factor control in U.S. adults with diabetes, assess trends in treatment, and identify population subgroups most likely to have ...
Methods. In this trial involving participants with type 2 diabetes of less than 10 years' duration who were receiving metformin and had glycated hemoglobin levels of 6.8 to 8.5%, we compared the ...
Diabetes describes a group of metabolic diseases characterized by high blood sugar levels. Diabetes can be caused by the pancreas not producing insulin (type 1 diabetes) or by insulin resistance ...
Type 2 diabetes mellitus, the most frequent subtype of diabetes, is a disease characterized by high levels of blood glucose (hyperglycaemia). It arises from a resistance to and relative deficiency ...
The American Diabetes Association and the European Association for the Study of Diabetes convened a panel to update the previous consensus statements on th. ... 17 Diabetes Centre, Clinical Research and Evidence-Based Medicine Unit, Aristotle University Thessaloniki, Thessaloniki, Greece.
I. Introduction. Diabetes mellitus, a metabolic disease defined by elevated fasting blood glucose levels due to insufficient insulin production, has reached epidemic proportions worldwide (World Health Organization, 2020).Type 1 and type 2 diabetes (T1D and T2D, respectively) make up the majority of diabetes cases with T1D characterized by autoimmune destruction of the insulin-producing ...
Making insulin-resistant cells more sensitive to insulin is another goal of novel therapeutics for diabetes. In preclinical research, insulin sensitivity has been improved with gene therapy ...
Learn about early diabetes symptoms, diabetic diet information, diabetes care, type 1 diabetes, insulin resistance and type 2 diabetes. Read the latest medical research on diabetes.
A team has developed the most comprehensive epidemiological dataset for youth diabetes and prediabetes research, derived from extensive National Health and Nutrition Examination Survey (NHANES ...
The American Diabetes Association's 2024 Scientific Sessions in Orlando assembled the top experts in diabetes care and research, revealing groundbreaking discoveries and innovations. This summary digs into the key highlights, offering valuable insights for people in the diabetes community. Disease-Modifying Agents
The American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), Joint British Diabetes Societies for Inpatient Care (JBDS), American Association of Clinical Endocrinology (AACE), and Diabetes Technology Society (DTS) convened a panel of internists and diabetologists to update the ADA consensus statement on hyperglycemic crises in adults with diabetes, published ...
The American Diabetes Association (ADA) is the nation's leading voluntary health organization fighting to bend the curve on the diabetes epidemic and help people living with diabetes thrive. For 83 years, the ADA has driven discovery and research to treat, manage, and prevent diabetes while working relentlessly for a cure.
Recent Advances. ADA-funded researchers use the money from their awards to conduct critical diabetes research. In time, they publish their findings in order to inform fellow scientists of their results, which ensures that others will build upon their work. Ultimately, this cycle drives advances to prevent diabetes and to help people burdened by it.
At the Diabetes Research Institute and Foundation, we have one goal: to find a cure for diabetes. Read the latest DRI news and press releases. For media inquiries and requests for interviews with leading experts in the field of diabetes research, please contact: Michael Myers Chief Communications Officer. Paulina Castro
Nanotechnology in diabetes research has played several roles in improving the outcome of diabetic management in diabetics through the deployment of novel nanotechnology ... Bakay M., Pandey R., Hakonarson H. Genes involved in type 1 diabetes: An update. Genes. 2013; 4:499-521. doi: 10.3390/genes4030499. [PMC free article] [Google ...
Subcutaneous semaglutide and risk of kidney disease progression in type 2 diabetes (June 2024) In a trial evaluating subcutaneous semaglutide (1 mg weekly) versus placebo in over 3500 adults with type 2 diabetes (mean age 67 years, mean A1C 7.8 percent) and chronic kidney disease (CKD; mean estimated glomerular filtration rate [eGFR] 47 mL/min ...
Type 1 diabetes is an autoimmune condition resulting in insulin deficiency and eventual loss of pancreatic β cell function requiring lifelong insulin therapy. Since the discovery of insulin more than 100 years ago, vast advances in treatments have improved care for many people with type 1 diabetes. Ongoing research on the genetics and immunology of type 1 diabetes and on interventions to ...
Potential mechanisms, informed by preclinical research, for the increased risk of type 2 diabetes mellitus are discussed. ... Type 1 diabetes mellitus (T1DM) can be predicted, and immune therapy ...
Nanny Natalia Mulyani Soetedjo, Hikmat Permana, Timotius Ivan Hariyanto, Marshell Tendean, ... Ketut Suastika. Article 111630. View PDF. Article preview. Read the latest articles of Diabetes Research and Clinical Practice at ScienceDirect.com, Elsevier's leading platform of peer-reviewed scholarly literature.
Rice University bioengineer Omid Veiseh and collaborators identified new biomaterial formulations that could help turn the page on type 1 diabetes treatment, opening the door to a more sustainable ...
NIDDK-supported research from the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study, which compared the ability of four type 2 diabetes medications to maintain blood glucose (sugar) over time when paired with metformin, presented new follow-up findings emphasizing a need for individualized blood glucose ...
TUESDAY, June 25, 2024 (HealthDay News) -- An experimental stem cell therapy can essentially cure type 1 diabetes by restoring insulin production in some patients, early clinical trial results show.
ORLANDO — Twelve people with type 1 diabetes who received a therapy derived from stem cells were able to produce enough of their own insulin to maintain healthy blood glucose levels 90 days ...
RSS Feed. Type 1 diabetes (also known as diabetes mellitus) is an autoimmune disease in which immune cells attack and destroy the insulin-producing cells of the pancreas. The loss of insulin leads ...
SAVE THE DATE! 2025 Clinical Update Conference. January 31-February 2, 2025. Omni Orlando Resort at ChampionsGate. Orlando, Florida and virtually. Stay Updated! The 2024 CUC was held February 2-4 at the Omni Orlando Resort at ChampionsGate in Orlando, FL and virtually. Updates related to the ADA Clinical Update Conference.
The online version of the Standards of Care now includes any research updates or policy changes that are approved throughout 2022. The complete, annotated Standards of Care, which includes updates made today, can be accessed online at Diabetes Care. The Abridged Standards of Medical Care in Diabetes has also been updated and can be accessed ...
American Diabetes Association ® Names Three Awardees for $4.875 Million in 2019 Pathway to Stop Diabetes Research Grants - February 15, 2019. Three ADA Pathway Grant Awardees' Collaborative Breakthrough: Analysis Describing the Genetic Link Between Beta (β) Cell Function and Type 2 Diabetes Published in Cell Reports - January 15, 2019.
The six-year study included 1,255 adults—563 with type 1 diabetes and 692 without diabetes. The researchers assessed diet using a food frequency questionnaire, which obtains dietary information ...