Tag Archives: Type 1 Diabetes

Dexcom G6 Glucose Monitor for Diabetes Cost-Effective in UK | Instant News

Wider use of the UK’s real-time Dexcom G6 continuous glucose monitoring system (RT-CGM) would be cost-effective in the long term, new research suggests.

The analysis is published in the October issue Diabetes Care. The lead author of this article is Stéphane Roze, chief executive of the Vyoo Agency (formerly HEVA HEOR), which conducts a medical cost-effectiveness analysis.

The UK’s National Institute for Health and Care Excellence (NICE) allows real-time use of CGM for people who have it type 1 diabetes who experience it is often severe hypoglycemiahypoglycemia, extreme fear of hypoglycemia, or A1c levels> 9.0% (75 mmol / mol) despite frequent self-monitoring of blood glucose (SMBG).

Up to 25% of people with type 1 diabetes in the United Kingdom meet at least one of these criteria. However, funding is limited, and paying for it yourself is common.

“For type 1 diabetes patients based in the UK, the G6 RT-CGM device was associated with a significant improvement in clinical outcomes and, over the patient’s lifetime, is a cost-effective disease management option relative to SMBG on the basis of a willingness to pay threshold of GBP 20,000 [USD 26,032] per QALY [quality-adjusted life year] obtained, “wrote Roze and colleagues.

Asked for comment, Partha Kar, MD, national special adviser, diabetes, at the UK’s National Health Service (NHS), called the new data “welcome news, and will hopefully help as NICE is currently reviewing evidence surrounding Dexcom.”

Today, says Kar, more people in the UK are using the cheaper 14-day Abbott Libre FreeStyle “flash” glucose monitoring system. The first version of the system, approved in Europe in 2014, did not include alarms for high and low glucose levels. A newer version with an optional alarm, Libre 2, Approved in 2018 but not yet available in the UK. A newer version, Libre 3, recently cleaned for use in Europe.

According to Kar, Libre 2 will arrive in the UK in early 2021. “The NHS is happy to welcome it, when it arrives. We hope Libre 3 will follow soon after,” he said.

New data suggest that Libre may have competition in the UK.

CGM Dexcom Meets the Desire-to-Pay Threshold

The analysis by Roze and colleagues was performed using validated computer simulations that project long-term outcomes for patients with type 1 or type 2 diabetes, including cardiovascular, ophthalmic, and renal complications, as well as peripheral neuropathy, leg ulcers, amputations, and hypoglycemic events.

Patient data used in the model comes from previous data DIAMOND trial, which includes 158 people with type 1 diabetes who received it several times a day insulin injection. The patients were randomly assigned to RT-CGM or SMBG (mean 4.6 tests / day) for 24 weeks. The mean age of the patients was 48 years, the mean duration of diabetes was 20 years, and the mean A1c level was 8.6% (70 mmol / L).

Based on the DIAMOND results, the cost-effectiveness analysis assumes an average A1c reduction of 1.0 percentage points with RT-CGM, vs 0.4 with SMBG. The rate of severe hypoglycemia was 4.2, vs 12.2 per 100 patient years.

This result translates to a 1.49 increase in mean increase in QALYs for RT-CGM compared to SMBG (11.47 vs 9.99).

Over lifetime, this means total average cost was £ 14,234 higher with RT-CGM (£ 102,468 vs £ 88,234), resulting in an additional cost-effectiveness ratio (ICER) of £ 9,558 per QALY earned for RT-CGM vs SMBG.

Most of the higher costs were attributable to the RT-CGM system itself, but savings resulted from improvements in the long-term reduction in complications and hypoglycemic events. At the willingness to pay threshold of £ 20,000, the likelihood that RT-CGM would be considered cost-effective was around 99%.

In a secondary analysis of patients with baseline A1c ≥8.5% (69 mmol / L; mean, 9.1% per 76 mmol / L), use of RT-CGM was associated with an increase of 1.39 QALYs compared to SMBG, and the total lifetime cost on average is £ 13,176 higher than that of SMBG, resulting in an ICER of £ 9,478 / QALY and a 98% probability of being considered cost effective.

“The findings presented here indicate that RT-CGM improves long-term yield relative to SMGD and that initial acquisition costs are at least partially offset by savings due to a reduction in the incidence of long-term complications,” Roze and colleagues wrote.

The sensitivity analysis, they said, “revealed that RT-CGM was most cost-effective in the group of patients who met the NICE eligibility criteria for RT-CGM, in particular, those with high A1c at baseline, FoH. [fear of hypoglycemia], often SHE [severe hypoglycemia episodes], and the use of high-level SMGD. “

The G6 May Be More Cost Effective Than the G4 Used in Diamond Testing

The authors also suggest that the findings may be conservative, as the RT-CGM used in the DIAMOND trial was the older Dexcom G4.

That system has been replaced by the G6, which incorporates an “as soon as possible” warning that allows the user to take action to prevent hypoglycemia.

“It is therefore plausible that the effect of treatment in this analysis in terms of the incidence rate of hypoglycemic, and potentially also FoH. [fear of hypoglycemia], in patients using RT-CGM may have been underestimated, “write the authors.

“The findings presented here provide valuable information to UK-based payers and policymakers regarding the cost-effectiveness of RT-CGM in T1D. [type 1 diabetes], “they concluded.

The study was funded by Dexcom, which paid Roze’s company for the analysis. Kar did not disclose the relevant financial relationships.

Diabetes Care. October 2020; 43: 2411-2417. Abstract

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Single-cell RNA-seq answers key questions in islet cell biology and diabetes research | Instant News

The pancreas is a stomach organ that produces digestive enzymes and hormones that regulate blood sugar levels. This hormone-producing function is localized on the island of Langerhans, which forms a group of various types of endocrine cells.

Among these are beta cells, which produce the hormone insulin which is needed to lower glucose levels (a type of sugar) in our blood, as well as alpha cells, which produce glucagon hormones whose job is to increase glucose levels in the blood.

Type 1 diabetes is a chronic disease where the immune system mistakenly attacks and destroys pancreatic insulin-producing beta cells. Regenerative medicine aims to replenish beta cell mass, and thus support and ultimately replace current insulin replacement therapy.

Changes in island composition, including lack of beta cell function and beta cell dedifference, also contribute to type II diabetes.

Therefore, a deeper understanding of the identity and crosstalk of various islet cell types leads to better characterization of both forms of diabetes and can contribute to the development of new therapeutic concepts.

Single cell transcriptomes are powerful techniques for characterizing cellular identity. Previously, CeMM researchers from the groups Christoph Bock and Stefan Kubicek at CeMM published the first single cell transcriptome from primary human pancreatic islet cells.

Advances in technology have enabled applications for the generation of global single cell atlase human and mouse transcript. Despite this progress, the single cell approach remains technologically challenging given the very small amount of RNA used in the experiment. Therefore, it is important to ensure the quality and purity of the resulting single cell transcriptome.

CeMM researchers in two laboratories who contributed unexpectedly identified high hormone expression in non-endocrine cell types, both in their own dataset and published single cell studies.

They set out to explain whether this would be the result of contamination by RNA molecules, for example from dying cells, and how they could be removed to obtain a more reliable dataset.

Such contamination appears to be present in RNA-seq single cell data from most tissues but is most visible on pancreatic islets. Islet endocrine cells are exclusively devoted to the production of a single hormone, and insulin in beta cells and glucagon in alpha cells is expressed to a higher level than a typical “household” gene.

Thus, the redistribution of these transcripts to other cell types is very clear. Based on these observations, their goal is to develop, validate and apply methods to experimentally determine and computationally eliminate the contamination.

In their investigation, the CeMM researchers used prickly cells of different cell types, both rat and human samples, which they added to their pancreatic islet samples. Importantly, the transcriptomes of these spike cells are fully characterized.

This enables them to internally and accurately control the level of RNA contamination in a single RNA-seq cell, providing that the human transcripts detected in mouse spike-in cells are contaminated RNA.

In this way, they found that the sample had a contamination rate of up to 20%, and was able to determine the contamination in each sample. They then developed a new bioinformatics approach to computationally eliminate contaminated readings from single cell transcriptomes.

Having now obtained the “decontamination” transcriptome, from which false signals have been removed, they proceed to characterize how cellular identities in different cell types respond to treatment with three different drugs.

They found that small molecular blockers of the FOXO1 transcription factor induced dedifferentiation of both alpha and beta cells.

Next, they studied artemeter, which has been found to reduce alpha cell function and can induce insulin production in both in vivo and in vitro studies. Effects of species-specific drug species and cell types.

In alpha cells, a small proportion of cells increase insulin expression and gain aspects of beta cell identity, both in rat and human samples. Importantly, the researchers found that in human beta cells, there was no significant change in insulin expression, whereas in mouse islands, beta cells reduced insulin expression and overall beta cell identity.

This study is the result of interdisciplinary collaboration from the laboratories of Stefan Kubicek and Christoph Bock at CeMM with Patrick Collombat at the Institute of Biology Valrose (France).

This is the first study to apply single cell sequencing to analyze dynamic drug responses in intact isolated tissue, which benefits from the high quantitative accuracy of the decontamination method.

Thus not only provides a new method for single cell decontamination and a very quantitative single cell analysis of drug responses in intact tissue, but also answers current questions that are important in islet cell biology and diabetes research. These findings could open up potential therapeutic avenues for treating type 1 diabetes in the future.


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Heart enlargement related to autoimmunity is associated with the risk of heart failure in type 1 diabetes | Instant News

People with type 1 diabetes, especially those with poor glycemic control, are at a very increased risk for cardiovascular disease than the general population. Even more confusing, in individuals with type 1 diabetes, many cardiovascular risk factors are not in line with known risk factors associated with type 2 diabetes.

Dr. Myra Lipes, Investigator in the Immunobiology Section at the Joslin Diabetes Center at Harvard Medical School, has worked for more than a decade to understand what causes an increased risk of cardiovascular disease in patients with type 1 diabetes and what can be done about that.

Heart failure in particular has recently been recognized as an important type 1 complication with a national register-based study that shows a tenfold increase in the risk of heart failure in individuals with poor glycemic control. In addition, there is a higher case fatality rate in type 1 diabetes than in type 2 diabetes, which suggests different mechanisms for heart failure might be involved in type 1 diabetes.

Myra Lipes, Investigator in the Immunobiology Section at the Joslin Diabetes Center at Harvard Medical School

Given the burden of heart failure in type 1 diabetes, early identification of patients with certain risks is very important.

New research from Dr.’s lab Lipes in Joslin showed that in people with type 1 diabetes without known cardiovascular disease, the presence of autoantibodies to cardiac muscle protein is associated with evidence of cardiac magnetic resonance imaging (CMR) that shows an increase in left ventricular volume (the main heart pumping chamber), increased muscle mass and reduced pumping function (ejection fraction), a feature associated with a higher risk of failure in the general population. This new study was published in Circulation.

Antibodies are usually produced by the immune system and circulate in the blood, playing an important role in the body’s defense against infection. In people who tend to be autoimmune, the body misidentifies its own protein as a threat and attack. This is what happens with type 1 diabetes – the immune system thinks the pancreatic beta cells are the invaders and destroy them. In this situation, antibodies are called autoantibodies. So, it might not be too surprising that this type 1 diabetes complication also involves an incorrect immune response to heart muscle cells.

Previous studies conducted by Dr. Lipes has shown that a mouse model of type 1 diabetes develops dilated cardiomyopathy (weakened heart muscle) and premature heart failure associated with the presence of autoantibodies directed against cardiac muscle protein. His group also showed that poor glycemic control in patients with type 1 diabetes – but not in those with type 2 diabetes – was associated with cardiac autoimmunity. Unexpected findings are similar rates of cardiac autoantibodies in patients with type 1 diabetes, who are young and without diabetes complications, and a cohort of heart failure with Chagas cardiomyopathy, which is thought to be caused by chronic inflammation of the heart muscle (“myocarditis”), increasing the likelihood of dysfunction myocardial associated subclinical autoimmune in type 1 diabetes “said Dr. Lipes.

In this study, Lipes wanted to determine whether the widening cardiac phenotype seen in mouse models and Chagas patients was also present in people with type 1 diabetes who have this circulating autoantibody. He and his team used data collected from participants involved in the Diabetes Control and Complications (DCCT) study post-Diabetes Epidemiology Intervention and Complications (EDIC) follow-up studies, and consisted of people who had type 1 diabetes for an average of 28 year. As part of this study, participants were imaged with CMR, a gold standard noninvasive imaging technique to assess the structure and function of the heart.

“In this study, we measured autoantibodies against cardiac muscle protein in blood samples taken from CMR imaging in 892 EDIC participants without known cardiovascular disease,” Lipes said. “And then we examined where the presence of heart antibodies was associated with CMR evidence of myocardial dysfunction.”

They found that although recent A1c levels were similar in participants with and without cardiac autoantibodies, the presence of cardiac autoantibodies identified patients with worse glycemic control in the past, indicating that cardiac autoantibodies were a marker of long-term glycemic exposure. In addition, they found that CMR scanning of people with two or more autoantibodies showed an enlarged heart. They sorted patients into categories based on the number of circulating autoantibodies, which indicates that people with more of these specific autoantibodies have clearer changes in the heart. This finding did not weaken after adjusting for traditional cardiovascular risk factors, suggesting this change was mainly due to cardiac autoimmunity.

They know from previous research that the heart can have structural and functional changes related to the metabolic problems of diabetes itself; However, this relationship is relatively simple. For example, higher A1C levels are associated with slightly smaller left ventricular volume that is not clinically significant. But this research shows that higher A1C levels can trigger additional autoimmune responses that damage the heart in different and clearer ways that lead to enlargement and worse function, features that are known to be associated with a higher risk of heart failure.

“This points to a new process that involves the heart and is associated with poor glycemic control in type 1 diabetes,” Lipes said.

Because cardiac autoantibodies can be detected in a simple blood test, this study opens new avenues for detecting potential heart failure in patients with type 1 diabetes.

“Given the high burden of heart failure in type 1 diabetes, heart antibodies can allow early identification of people at higher risk of heart failure,” Lipes said. “And, of course, understanding the main causes of heart failure is important because it can lead to therapeutic approaches that are targeted at improving outcomes in these patients.”


Journal reference:

Sousa, G.R., et al. (2020) Cardiac Immunity Associated with Subclinical Myocardial Dysfunction in Type 1 Diabetes Mellitus Patients. Circulation. doi.org/10.1161/CIRCULATIONAHA.119.044539.


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