Ny metod gör det möjligt att screena för autoimmuna sjukdomar i stor skala
Intresset för att screena för typ 1-diabetes växer i takt med att metoderna blir bättre och nya bromsläkemedel blir tillgängliga för fler patienter. Nu visar ny forskning vid Lunds universitet hur screening för autoimmuna sjukdomar kan göras i stor skala
Ett nytt läkemedel som kan bromsa utvecklingen av typ 1-diabetes har godkänts för användning i USA. Om läkemedlet Teplizumab blir tillgängligt även i Europa kan det ställa nya krav på att sjukvården ska börja screena för sjukdomen. Åke Lernmark är en av de diabetesforskare som har utvecklat screeningmetoder för typ 1-diabetes.
– Om tillgången till bromsläkemedel blir större kommer vi förmodligen att se ett ännu större intresse för att screena för typ 1-diabetes. Vi behöver se till att våra metoder gör det så enkelt och kostnadseffektivt som möjligt att screena för sjukdomen, säger Åke Lernmark, seniorprofessor i experimentell diabetes vid Lunds universitets diabetescentrum.
Jämförde två metoder
Åke Lernmark har tagit fram en metod som mäter diabetesrelaterade autoantikroppar och som för närvarande är en internationell standard. Metoden som kallas RBA (radiobinding assay) mäter diabetesrelaterade autoantikroppar i ett blodprov. Han har nu lett en studie där standardmetoden jämförs med en ny metod som heter ADAP (antibody detection by agglutination-PCR). Den nya metoden ADAP har utvecklats av forskare vid University of California, Berkeley, som är medförfattare till studien.
Forskarna har jämfört de två mätmetoderna på blodprover från omkring 2 500 barn med nydiagnostiserad typ 1-diabetes och en lika stor kontrollgrupp utan sjukdomen och funnit att den nya mätmetoden var lika bra eller bättre än standardmetoden på att definiera vilka barn som är i riskzonen att utveckla typ 1-diabetes. Resultaten stod sig oavsett om analyserna gjordes i Sverige eller USA.
– Vi har lärt oss mycket om hur typ 1-diabetes utvecklas med hjälp av standardmetoden, men vi behöver utveckla bättre screeningmetoder för att de ska kunna användas inom sjukvården. En viktig slutsats av studien är att den nya metoden kan användas för att genomföra storskalig screening för typ 1-diabetes, säger Åke Lernmark.
Storskalig screening
Barnläkaren och forskaren Daniel Agardh leder en forskargrupp vid Lunds universitets diabetescentrum som har screenat skånska barn för de tre autoimmuna sjukdomarna typ 1-diabetes, celiaki och tyreoidit inom ramen för studien TRIAD. Inom studien används både standardmetoden RBA och den nya mätmetoden ADAP.
– En målsättning med projektet är att testa olika metoder som kan användas för storskalig screening av typ 1-diabetes och andra autoimmuna sjukdomar. En fördel med den nya metoden ADAP är att en robot som sköter sig själv kan analysera åttio prover åt gången, i stället för att fyra personer ska göra varje analys manuellt. En nackdel med standardmetoden RBA är att det krävs större mängder blod, säger Daniel Agardh.
I den första delstudien inom TRIAD screenades 2 271 skånska barn för de tre autoimmuna sjukdomarna, typ 1-diabetes, celiaki och tyreoidit, även kallat sköldkörtelinflammation. Forskarna kunde bland annat se att autoantikroppar associerade med typ 1-diabetes, celiaki och tyreodit var vanligare hos barn som hade en förälder eller ett syskon med någon av sjukdomarna.
– Studien ger ökat stöd för att barn med föräldrar eller syskon med någon av sjukdomarna bör screenas för dessa sjukdomar. Problemet med att begränsa screening till barn med familjemedlemmar med någon av sjukdomarna är att vi skulle missa väldigt många barn med någon av sjukdomarna. Risken för att utveckla typ 1-diabetes ökar visserligen om en familjemedlem har sjukdomen, men de flesta som får typ 1-diabetes har ingen nära släkting med sjukdomen, säger Daniel Agardh.
Några droppar blod
De familjer som har deltagit i TRIAD har fått ett test hemskickat och blodprovet har sedan skickats vidare till labb för analys. I höst planerar Daniel Agardh att genomföra en betydligt större screeningstudie inom ramen för TRIAD. När studien påbörjas i höst kommer den nya analysmetoden ADAP användas som huvudmetod.
– Det kommer att underlätta för deltagarna som bara behöver bidra med några droppar blod. Vi hoppas att vår metod med hemmatestning kan användas inom sjukvården i framtiden, för att öka deltagandet och sänka kostnaderna för nationella screeningprogram. De flesta som deltar i våra studier är tacksamma för att möjligheten finns. Det ger förutsättningar att ställa om kosten om barnet visar sig ha celiaki. Om barnet visar sig ha odiagnostiserad typ 1-diabetes finns det möjlighet att sätta in insulinbehandling i tidigt skede, vilket minskar risken för komplikationer på kort och lång sikt, säger Daniel Agardh.
Länkar till vetenskapliga publikationer:
”Childhood screening for type 1 diabetes comparing automated multiplex Antibody Detection by Agglutination-PCR (ADAP) with single plex islet autoantibody radiobinding assays” eBioMedicine, June 2024.
”Home capillary sampling and screening for type 1 diabetes, celiac disease, and autoimmune thyroid disease in a Swedish general pediatric population: the TRIAD study”, Frontiers in Pediatrics, april 2024.
Text: PETRA OLSSON
Nyhet från Lunds universitet, Press release,
från Vetenskap & Hälsa
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Most diabetes care and education specialists follow guidance on type 1 diabetes screening
Key takeaways:
- Most respondents to a small survey said they follow ADA recommendations for type 1 diabetes screening.
- One-third of respondents said they did not have knowledge about using teplizumab to delay type 1 diabetes.
Most diabetes care and education specialists said they believe it is important to screen for presymptomatic type 1 diabetes, though some said they had limited knowledge regarding teplizumab-mzwv, according to a presenter.
Researchers presented findings from a small cross-sectional survey focused on type 1 diabetes screening and prevention at the Association of Diabetes Care and Education Specialists annual meeting. Most respondents were neutral or agreed with the American Diabetes Association’s 2024 Standard of Care recommendations regarding type 1 diabetes staging and screening, and the majority agreed that they had knowledge of teplizumab-mzwv (Tzield, Provention Bio).
However, Jennifer Clements, PharmD, FCCP, FADCES, BCPS, CDCES, BCACP, BC-ADM, clinical professor and director of pharmacy education at the University of South Carolina College of Pharmacy, said, some respondents were not confident with the use of teplizumab-mzwv and response to the survey was small.
“It would be great to have more real-world perspective on teplizumab,” Clements told Healio. “As individuals become more knowledgeable on the medication and perhaps gain clinical experience, it would be important to share best practices.”
Diabetes care and education specialists were invited to complete a 20-quesiton survey on the screening and staging of type 1 diabetes and the role of teplizumab-mzwv in treating presymptomatic type 1 diabetes. The survey was conducted over a 6-week period. After filling out demographic information, participants provided their response to statements on a 5-point Likert scale. Responses to each statement were strongly disagree, disagree, neutral, agree and strongly agree.
The majority of diabetes care and education specialists responding to a survey said they agree with following recommendations for type 1 diabetes screening.
“It would be great to have more real-world perspective on teplizumab,” Clements told Healio. “As individuals become more knowledgeable on the medication and perhaps gain clinical experience, it would be important to share best practices.”
Of the 21 diabetes care and education specialists who completed the survey, 81% had 11 or more years of practice experience and 61.9% worked in ambulatory or outpatient care. Of the respondents, 61.9% said 25% or less of their patient population had type 1 diabetes. Twelve of the respondents said 76% or more of the patient population at their practice were adults.
The majority of respondents were neutral, agreed or strongly agreed that they promote screening for presymptomatic type 1 diabetes, stage individuals with type 1 diabetes based on their characteristics and diagnostic criteria, and suggest or make referrals to a specialized center for further evaluation based on the 2024 ADA Standards of Care. Eight respondents disagreed or strongly disagreed about referring patients to a specialized center.
“It was encouraging to see most respondents agreeing with the importance of type 1 diabetes screening,” Clements said. “The recommendations are clear and should be considered for implementation into clinical practice, regardless of the setting.”
Of the participants, 66.7% agreed or strongly agreed that they have the knowledge to support the role of teplizumab-mzwv to delay symptomatic type 1 diabetes, though 19% disagreed and 14.2% strongly disagreed with the statement. The responses were similar when participants were asked whether they had the knowledge to promote teplizumab-mzwv to delay type 1 diabetes among people aged 8 years and older with stage 2 type 1 diabetes.
“There was a small sample size, so it does not clearly determine if respondents are or are not familiar with teplizumab-mzwv,” Clements said. “However, there may be diabetes care and education specialists who have not gained clinical experience with this medication based on clinical setting, patient populations or other reasons.”
The majority of respondents agreed or strongly agreed that they understood statements about the need for two positive pancreatic islet antibodies to prescribe teplizumab-mzwv, the need for a complete blood count and liver enzyme tests, the administration of teplizumab-mzwv and the cost.
Clements said more information is needed to explain best practices for type 1 diabetes screening and teplizumab-mzwv use.
SOURCE
Clements J, et al. P-218. Presented at: ADCES24; Aug, 9-12, 2024; New Orleans.
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New Data Shed Light on Type 1 Diabetes Male Predominance
ADRID, Spain — New research sheds light on the male predominance in type 1 diabetes, finding that the risk between men and women diverges around age 10 years.
Data from more than 200,000 first-degree relatives of people with type 1 diabetes who were screened for type 1 diabetes risk in the TrialNet program showed that "there's a clear interaction with age and male sex being a risk factor. At the age of ten in girls, there seems to be this tipping point where the risk of type of diabetes dramatically reduces," lead investigator Richard Oram, MD, of the Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, United Kingdom, told Medscape Medical News.
There was a steep decline in 5-year type 1 diabetes risk in women who were screened and positive for type 1 diabetes-related autoantibodies prior to age 10 years compared to after 10 years. In contrast, among men the risk of progression remained steady as age at screening increased. The reasons for this aren't clear, but the age of 10 years "goes with puberty, so it raises the question as to whether these are puberty-related changes," Oram said.
This study looks at both type 1 diabetes risk and onset specifically by age and gender. The first author, Exeter PhD student Erin L. Templeman, told Medscape Medical News, "In childhood, the prevalence is very similar in type 1 diabetes between males and females. It's later on that we see that the diversion in the expression." She cited a 2008 study as one of several finding the gender difference. But that study examined people aged 15-34 and only at type 1 diabetes onset. "We wanted to explore this further," she said.
As of now few people without first-degree relatives who have type 1 diabetes are being screened, although there are now guidelines for managing those who are and who screen positive.
However, Oram said, "I think the takeaway would be that boys seem to get more type 1 diabetes after the age of 10. If you do a screening study at the age of 10 or later, you would expect more boys to be positive than girls."
Asked to comment, William Hagopian, MD, PhD, Clinical Professor of Medicine, University of Washington, Seattle, told Medscape Medical News, "it is intriguing that the lower risk in females seems to appear near the age of menarche, and earlier menarches are now observed in some populations. However, the latter connection is speculative and requires further investigation. In any case, working out the mechanisms underlying the observed differences in early-stage disease progression by sex may yield important clues about the early development of the disease and how to interrupt it."
Males More Likely to Screen Positive, and to Progress With Just One Autoantibody
Among the 235,765 relatives of people with type 1 diabetes screened and after adjustment for confounders, the proportion who screened positive for at least one autoantibody was 5.0% in women vs 5.4% in men, a significant difference (P < .001). And of those, men were more likely to screen positive for more than one autoantibody, 2.6% vs just 1.8% in women (P < .001).
Among those positive for a single autoantibody, men were more likely to progress to type 1 diabetes within 5 years (21% vs 14% in women, P < .001). However, among those with at least two autoantibodies, the risk of progression to clinical type 1 diabetes (stage III) was similar. Among those with stage I type 1 diabetes (at least two autoantibodies but normoglycemia), progression occurred in 38% of both men and women. And for those with stage II type 1 diabetes (at least two autoantibodies and dysglycemia), progression to type 1 diabetes occurred in 59% of men and 57% of women, not significantly different.
"Once you hit stage I or stage II, male sex is no longer a risk factor for progression. Male sex is a risk factor for getting type 1 diabetes but not for the speed the train is going once you've left the station and you already have it," Oram commented.
Hagopian, who is also senior research professor of pediatrics, Indiana University, Indianapolis, said that the finding of gender difference appearing to be largely due to progression of single islet autoantibody positivity to clinical disease is "new and important." He noted that people who are positive for a single autoantibody have a much lower risk of progressing to type 1 diabetes, about 15-40%, compared with > 90% for those with multiple autoantibodies, "but the former is still high enough to warrant follow-up. These findings begin to provide a way, perhaps along with type of islet autoantibody, family history, genetics, and other factors, to inform prognosis and guide monitoring intensity of these single islet autoantibody positive individuals."
Oram pointed out that the sex difference in type 1 diabetes doesn't often emerge in some of the major epidemiologic studies investigating risk factors because gender is adjusted for in the analysis. "Sometimes we look for really clever mechanisms in disease, and we don't stop to think about some really obvious but kind of slightly perplexing observations that have been there for years…It highlights that we don't always consider sex as a variable in scientific studies as well as we should do."
These findings will be presented on September 10, 2024, at the annual meeting of the European Association for the Study of Diabetes.
From diabetespro.com
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