Is universal screening for type 1 diabetes around the corner?
The the latest data on universal screening for type 1 diabetes (T1D) is reveiwed in a session at this year’s Annual Meeting of the European Association for the Study of Diabetes (EASD) in Hamburg, Germany (2-6 October). The talk will be given by Dr Emily K. Sims, Associate Professor of Pediatrics, Center for Diabetes and Metabolic Diseases, Indiana University School of Medicine, Indianapolis, IN, USA.
Research by various groups has established that individuals with multiple islet autoantibodies (biomarkers showing that the body is attacking and killing its own insulin producing beta cells in the pancreas) have a near 100% risk of developing T1D over their lifetime (Ziegler et al. JAMA. 2013 Jun 19;309(23):2473-9). Multiple groups including Ezio Bonifacio and colleagues from the TEDDY Consortium (Diabetes Care 2021) and Ghalwash and colleagues from Type 1 Diabetes Intelligence Study Group (The Lancet Diabetes & Endocrinology 2022) have shown that screening for islet auto-antibodies at two ages – 2 and at 5-7 years - would predict most cases of type 1 diabetes that would develop by age 15 years.
Dr Sims will highlight that, although screening programs have previously most often focused on people with family members with T1D (who can have up to 15 times increased risk of developing T1D), most people who develop T1D (85-90%) have no family history of the condition. “Our knowledge of type 1 diabetes has now evolved from thinking it is a disease that suddenly develops, to knowing that it is something that gradually develops, after the appearance of multiple islet-autoantibodies. By screening children and adults to identify individuals with early, presymptomatic stages of disease, we can more accurately predict when they will first need insulin and prevent life-threatening DKA episodes that otherwise frequently occur at diagnosis,” she explains. “Natural history studies have shown us that once someone has reached the threshold of multiple islet autoantibodies, progression occurs similarly in relatives and those with no family history.”
Knowing who is likely to develop T1D will help prevent cases of diabetic ketoacidosis (DKA) that occurs when the body doesn't have enough insulin to allow blood sugar into the cells for use as energy. Instead, the liver breaks down fat for fuel, producing acids called ketones; the build-up of these ketones to dangerous levels causes DKA. These episodes can be dangerous and even fatal, causing a number of uncomfortable symptoms. The symptoms of DKA can be the first sign of T1D in people who haven’t yet been diagnosed.
Various research programs are going on worldwide to establish the best ways of implementing universal screening, including programmes in Germany, the USA, Israel, the UK, and Australia, and a new program (Edent1fi) has just been funded that is going to include multiple new countries in Europe, including the UK, Germany, Poland, Portugal, Italy and the Czech Republic. “These are all research programs. The next steps before universal screening for type 1 diabetes becomes general policy will require guidelines for monitoring and endorsement of screening and monitoring guidelines by applicable societies,” explains Dr Sims. This will also be helped by broader access to disease modifying therapies to impact progression and the need to start insulin injections.
She explains that these research programmes are in many cases working with primary care doctors to obtain blood testing for autoantibodies - while some of them work through newborn screening (genetic testing performed on infant blood spots followed by antibody screening in individuals at higher genetic risk).
Dr Sims says: “The costs of screening, optimal ways to scale it up, and how to connect it with access to disease modifying therapies, such as the monoclonal anti-CD3 antibody that was recently FDA-approved in the US for delay of Stage 3 T1D in individuals meeting criteria for Stage 2 disease (multiple islet autoantibodies and changes in blood sugar), are all still to be worked out. Other important considerations moving forward include reaching traditionally understudied populations and more tailored approaches for individual patients.”
As the question of when we could see universal screening for T1D rolled, Dr Sims concludes: “ I think we will start to see increasing society endorsement of screening and monitoring guidelines over the next five years and that as this occurs, countries will start incorporating screening into routine care for young children at the general practitioner’s office – for example, when children are called for routine childhood vaccinations.” Screening for adults, who can also develop T1D, is less well studied. Although optimal approaches have yet to be clearly elucidated, this population will also likely benefit from identification of early stage disease and the advantages of education, monitoring, and access to therapy.
“Given that we know that individuals without a family history are the most likely to present with new T1D and that once they reach criteria for early stage disease, they are at similar risk to individuals with a family history, universal screening the of general population is key to ultimately allow the most individuals to benefit from access to education, monitoring, and disease modifying therapies.
Dr Sims will also take part in the embargoed press conference taking place at 1200H Noon CEST Hamburg time on Tues 3 Oct, in the Vienna Hall.
To join by zoom, use this link
https://us06web.zoom.us/j/86523053998?pwd=0CxM4PetJCn8K6CbnavJVbp3uIZ3aa.1
For press conference slide presentation, click here
ARTICLE PUBLICATION DATE
3-Oct-2023
COI STATEMENT
Dr Emily Sims, Associate Professor of Pediatrics, Center for Diabetes and Metabolic Disease, Indiana University School of Medicine, Indianapolis, IN, USA. Please e-mail to arrange interview. E) eksims@iu.edu Alternative contact in the EASD Press Room: Tony Kirby T) + 44 7834 385827 E) tony@tonykirby.com This press release is based on session S27 to take place in the Barcelona Hall at the European Association for the Study of Diabetes (EASD) Annual Meeting in Hamburg at 0900H AM CEST on Wednesday 4 October. The presenter is happy to answer any questions. Dr Sims will also take part in the embargoed press conference taking place at 1200H Noon CEST Hamburg time on Tues 3 Oct, in the Vienna Hall. To join by zoom, use this link https://us06web.zoom.us/j/86523053998?pwd=0CxM4PetJCn8K6CbnavJVbp3uIZ3aa.1
For press conference slide presentation, click here
Metabolic signature can help predict which smokers will develop type 2 diabetes
UK Biobank analysis of over 93,000 adults finds that smoking increases the risk of type 2 diabetes in part through its effects on the metabolism
New research being presented at this year’s Annual Meeting of The European Association for the Study of Diabetes (EASD), Hamburg (2-6 Oct) finds that cigarette smoking increases the risk of developing type 2 diabetes in part by affecting a variety of metabolites—small chemicals produced in the processes of metabolism—that circulate in the bloodstream.
The influence of these metabolic changes on diabetes risk appears to be amplified in individuals with genetic susceptibility to type 2 diabetes or insulin resistance.
The analysis of over 93,000 UK Biobank participants also identified a metabolic signature of 131 metabolic traits that can help predict which smokers are more likely to develop type 2 diabetes.
“Our metabolism is constantly changing depending on what we ingest or are exposed to”, says lead author Yuxia Wei from the Karolinska Institutet in Sweden. “Our study is the first to develop a metabolic signature for smoking based on comprehensive metabolomic profiles, and provides new insights into how smoking influences certain metabolites to increase the risk of type 2 diabetes. The findings underscore the importance of refraining from or quitting smoking to prevent diabetes, particularly for individuals with genetic risk factors for diabetes who seem to be more vulnerable to these changes.”
Previous observational evidence suggests that smokers are 20-60% more likely to develop type 2 diabetes, but the underlying mechanisms are unclear.
To address this knowledge gap, researchers used nuclear magnetic resonance spectroscopy (NMR) to analyse hundreds of metabolites in blood samples from 93,722 never, former, and current smokers (aged 37-73 years) without diabetes at the start of the study (2006-10) from the UK biobank—which holds genetic, health, and medical information from approximately half a million British volunteers. Metabolomics data were collected again in 2012-13.
During an average (median) follow-up of 13 years, 1,869 new cases of diabetes were identified.
The observational analysis and causal relationship analysis identified 131 metabolites affected by smoking, including glycoprotein acetyls (an inflammatory biomarker), fatty acids, and lipids, which collectively indicated whether an individual would go on to develop type 2 diabetes.
Compared with people who never smoked, current smoking increased the risk of type 2 diabetes by 73%; and 38% of this excess risk was mediated through the smoking-related metabolic signature (44% in men and 30% in women), after accounting for traditional diabetes risk factors such as age, sex, education level, ethnicity, BMI, physical activity, diet, and family history of diabetes.
For free fatty acids, smoking seemed to lead to higher levels of unhealthy saturated and monosaturated fatty acids, and lower percentages of healthy polyunsaturated ones such as DHA, omega-6 fatty acids, and omega-3 fatty acids (mainly found in seafood). Smoking was also positively associated with metabolites including different lipids in very-low-density lipoproteins (VLDL), triglycerides, and LDL cholesterol (also called ‘bad’ cholesterol), and lower levels of all forms of HDL cholesterol (often know as good cholesterol).
Importantly, the findings indicate that most of the smoking-related metabolic changes are reversible after quitting smoking.
The analysis also found that a high level of the metabolic signature was associated with a 61% higher risk of developing type 2 diabetes compared to a low level.
Genetic susceptibility also made a difference. Individuals with both a high level of the metabolic signature and a high genetic susceptibility to type 2 diabetes were three times as likely to develop the condition as those with low levels of the signature and genetic susceptibility.
The interaction between genetic susceptibility and the metabolic signature enhances their overall impact on type 2 diabetes. As the Wei explains: “The excess risk of developing type 2 diabetes in people with both a high genetic susceptibility and a high level of the signature surpasses what we would expect by simply adding the excess risk in people with only a high genetic susceptibility and the excess risk in people with only a high level of the signature. Our findings suggest that it is even more important for people with high genetic susceptibility to avoid smoking than the general population.”
The researchers further tested and verified the metabolic signature in blood samples from 3,626 participants in the TwinGene Study, a cohort nested in the Swedish Twin Register. They noted that the ability for the metabolic signature to determine risk of type 2 diabetes was highly reproducible despite the fact that individuals living in the UK and Sweden have different dietary habits, lifestyles, and environmental exposures.
“The reproducibility of the findings in the Swedish population indicate the robustness of the approach”, says Wei. “Nevertheless, more than half of the smoking-diabetes link was not explained by the metabolic signature, suggesting that other pathophysiological consequences of smoking play a role in diabetes development. These mechanisms may include the adverse effects of smoking on pancreatic tissue and beta cell function.”
Despite the important findings, the researchers note several limitations of the study, including that smoking status and metabolite levels may have changed during follow-up, which may have influenced the results; and that the study was conducted in people mainly of European origin, so the findings may not be generalisable to other populations.
This work was supported by the Swedish Research Council, FORTE, the Novo Nordisk Foundation, and the China Scholarship Council.
This press release is based on poster presentation 322 at the annual meeting of the European Association for the Study of Diabetes (EASD). The material has been peer reviewed by the congress selection committee. There is no full paper at this stage, but the research has been submitted to a medical journal for publication. The authors are happy to answer any questions.
ARTICLE PUBLICATION DATE
3-Oct-2023
COI STATEMENT
This work was supported by the Swedish Research Council, FORTE, the Novo Nordisk Foundation, and the China Scholarship Council.
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