Type 1 diabetes (T1D) can seem to strike out of the blue, yet it has been known for decades that autoantibodies that destroy insulin-making pancreatic islets are often present months, even years, before symptoms emerge. A simple blood test can identify people with asymptomatic early-stage T1D, which creates opportunities to prevent a potentially fatal complication of the disease and even delay the onset of its symptoms by several years. However, until recently, clinicians lacked a framework for managing patients with early-stage T1D. How should they be monitored to optimize outcomes?

Answers to this critical question are included in a new “consensus guidance”—meaning it’s based on expert opinion and research data in the absence of clinical trials—co-published in Diabetes Care and Diabetologia in June 2024.¹ Written by an international panel in partnership with the American Diabetes Association and other major organizations, the landmark publication offers recommendations for managing adult and pediatric patients who test positive for islet autoantibodies, but have not yet advanced to Stage 3 (insulin-dependent) T1D.

“There are a lot of people walking around out there with positive autoantibodies who are in what we now call early-stage type 1 diabetes,” says Anastasia Albanese-O’Neill, PhD, APRN, associate vice president of community screening and clinical trial education at Breakthrough T1D (breakthrought1d.org, formerly called JDRF) and a coauthor of the guidelines. “When a person has a positive autoantibody test result, as clinicians, we want to know: What is our plan of care? Until now, there really wasn’t clear guidance.” This is especially key as the population of patients diagnosed with early-stage T1D continues to grow, just as more new treatment options may become available. “This is a pivotal moment in the care of type 1 diabetes,” says Albanese-O’Neill.

Why screening matters

The ability to identify asymptomatic patients who have early-stage T1D is possible thanks to the discovery of islet autoantibodies. Data from prospective studies show that a child with two autoantibodies has an 85% chance of developing Stage 3 T1D within 15 years. For a child with three AAs, the likelihood of being diagnosed with Stage 3 T1D is 92% over the same time frame, and it’s all but certain that these patients will develop the disease at some point in their lifetimes.¹

The creation of screening tools for these AAs led to the development of a staging system that describes the phases of T1D based on the number of islet autoantibodies the patient has, their glycemic status and the presence of diabetes symptoms.¹ Stages are defined as the following:

• At risk (pre-Stage 1): a single autoantibody or transient autoantibodies, but normal blood glucose and no symptoms.
• Stage 1: ≥2 autoantibodies, but normal blood glucose and no symptoms.
• Stage 2: ≥2 autoantibodies and glucose intolerance or dysglycemia (fasting glucose 100-125 mg/dL, 2-hour postprandial glucose 140-199 mg/dL and A1C 5.7-6.4%) and no symptoms.
• Stage 3: clinical (insulin-dependent) T1D, marked by ≥2 autoantibodies and persistent hyperglycemia with symptoms (e.g., polyuria, polydipsia, weight loss).

Currently, screening for autoantibodies is primarily reserved for children and adults who are most likely to develop Stage 3 T1D due to a family history of the disease, which carries a 15-fold increased risk. However, about 90% of all people who develop T1D do not have a family history, meaning they are unlikely to undergo screening and may not be diagnosed until they develop symptoms and have Stage 3 T1D.² “Screening programs for early-stage type 1 diabetes are expanding around the world,” says Albanese-O’Neill, noting that the Italian Parliament unanimously passed legislation in 2023 that introduced a national screening program for T1D (and celiac disease) for all children ages 1 to 17.³ “Our long-term goal is population-level screening, but we’re not there yet,” she says. Close monitoring of patients diagnosed with early-stage T1D would have several important benefits, including:

Preventing DKA. Diabetic ketoacidosis (DKA) is the most common cause of diabetes-related death among children with T1D and carries an increased risk of serious complications such as cerebral edema and cognitive deficits.⁴ Rates of DKA at diagnosis have been reported as high as 62%, but drop to as low as 4% among monitored patients.² Preventing DKA at diagnosis not only can save lives, but evidence suggests it may also improve long-term glycemic control.⁵

“We know, based on evidence from global screening programs, that we can prevent DKA at diagnosis,” says Albanese-O’Neill. She emphasizes that monitoring for progression of disease, as well as educating patients and families about how to recognize and respond to persistent thirst, frequent urination and other harbinger symptoms, can slash DKA risk.

Delaying the onset of symptoms. Close monitoring can identify patients who progress from Stage 1 T1D to Stage 2 T1D, making them a candidate for treatment with a monoclonal antibody that preserves beta-cell function and delays the onset of clinical (Stage 3) T1D by 2 years, on average.^6,7 Approved by the FDA for adults and children ages 8 and older with Stage 2 T1D, the novel agent is the first treatment capable of altering the course of the disease.⁸ “We now have an approved therapy that delays the onset of type 1 diabetes,” says Albanese-O’Neill. “This represents a paradigm change.” The recent approval may only be the beginning of a new era of T1D therapeutics, as several novel treatments that could also delay the onset of disease are under investigation in clinical trials.

Screening: the basics

Clinicians should establish a monitoring program for patients diagnosed with early-stage T1D. The autoantibodies to screen for include:

• GAD65 (glutamic acid decarboxylase 65)
• IA-2 (islet antigen 2)
• IAA (insulin autoantibody)
• ZnT8 (zinc transporter 8)

To confirm early-stage (1 or 2) T1D, follow the “rule of twos”: The patient must have at least two different antibodies in two confirmed tests using two different blood samples. (A patient with a single autoantibody is not formally staged, but is considered “at risk.”)¹

Some patients’ insurance may cover the cost of screening, while free programs are available to many people with a family history at trialnet.org and to all children ages 1 to 17 at Autoimmunity Screening for Kids (askhealth.org), operated by the Barbara Davis Center for Diabetes at the University of Colorado.

Coding note:
Three new ICD codes for monitoring unspecified presymptomatic T1D, Stage 1 T1D and Stage 2 T1D will become available on October 1, 2024.⁹

Who monitors after a diagnosis?

“Monitoring should take place wherever there is sufficient expertise for it to happen,” says Albanese-O’Neill. Pediatricians and primary care providers routinely monitor and treat various conditions, so it’s reasonable to assume that practitioners who educate themselves can also monitor early-stage T1D, according to the guidelines. However, the document encourages partnership with specialists and recommends that patients with Stage 2 T1D be referred to a diabetologist/endocrinologist to discuss treatment options and their individualized risk for progression to clinical T1D.¹ Clinicians can also get answers about screening for autoantibodies, what test results mean and other critical T1D information from Autoimmunity Screening for Kids (asktheexperts.org/for-providers).

What monitoring method?

Clinicians have many options for tracking the progression of early-stage T1D, including an oral glucose tolerance test (OGTT), random glucose test, A1C test, continuous glucose monitoring and self-monitoring of blood glucose. “The OGTT is the gold standard, especially for staging patients. It gives us the most information,” says Albanese-O’Neill. “But what’s clinically feasible?” She explains that the international panel could not reach consensus on recommending monitoring methods, so the guidance spells out the pros and cons of each, leaving clinicians latitude on choosing what makes sense for their patient and clinical environment. Albanese-O’Neill notes that Breakthrough T1D is funding research to evaluate monitoring methods in early-stage T1D.

How often to monitor?

Young children tend to have more rapid disease progression and thus require more frequent monitoring. The recommended monitoring schedule is based on age, autoantibody status and stage, specifically:¹

At risk or pre-Stage 1 (positive for single autoantibody)

• Children under 3 years: Autoantibody and metabolic monitoring every 6 months. If there’s no progression after 3 years, stop monitoring and counsel family about potential symptoms and DKA awareness.
• Children 3 years and older: Same as above, but monitor annually.

Stage 1 (positive for multiple autoantibodies and normal glycemia)

• Children under 3 years: Check A1C every 3 months.
• Children 3 to 9 years: Check A1C every 6 months.
• Children 10 to 17 years: Check A1C once a year.

A longitudinal A1C increase of 10% or more (for example, from 5% to 5.5%) indicates increased risk of progression to Stage 3 T1D within 1 year.

Stage 2 (positive for multiple autoantibodies and dysglycemia)

• Monitor A1C every 3 months, regardless of the child’s age.

A longitudinal A1C increase of 10% or more from the date autoantibodies were confirmed indicates possible progression to Stage 3 T1D. In such cases, an OGTT should be performed to determine whether initiation of insulin is warranted.

The guidelines recommend similar but less-frequent monitoring for adults 18 and older who are at risk for or have Stage 1 or 2 T1D. Pregnant women with known autoantibodies should be tested during and after their term.¹

—by Tim Gower

While some issues are systemic, there is still much you can do to help ensure early diagnosis and optimal glycemic control in this vulnerable population.

The overall incidence of type 1 diabetes (T1D) in the United States is rising, but it’s accelerating the fastest in minority populations, including the Hispanic community, where it’s increasing at a rate of about 4% per year compared with 0.7% among non-Hispanic White persons.¹ What’s more, data report growing disparities between the Hispanic and non-Hispanic White populations, including the following:

• Hispanic people are more than twice as likely to live below the poverty level, and low income is associated with worse outcomes in T1D.^2,3
• Hispanic youth have significantly higher rates of potentially fatal diabetic ketoacidosis (DKA) at or near diagnosis of T1D.⁴
• Hispanic young people with T1D have worse glycemic control, even after accounting for their socioeconomic status.²
• People of Hispanic heritage are three times more likely to lack health insurance.⁵

Fortunately, clinicians can help Hispanic children with T1D overcome disparities by developing a bond of trust with patients and their families, says pediatric endocrinologist Susanne M. Cabrera, MD, of Children’s Wisconsin in Milwaukee, and an Associate Professor at the Medical College of Wisconsin. “If you don’t look like your patients or you don’t speak their language, you may be at somewhat of a disadvantage and will probably have to work a little bit harder to gain their trust,” says Dr. Cabrera. “But that doesn’t mean that if you’re not Hispanic you can’t take really great care of Hispanic patients. It just means that you need to show sincere interest and put the work in. Patients pick up on kindness and consistency.” Here, Dr. Cabrera shares strategies to help clinicians deliver the best care to Hispanic patients with T1D.

Beware of bias and assumptions

Common misbeliefs and biases about T1D can contribute to worse outcomes in the Hispanic population and other minority groups, says Dr. Cabrera. “Type 1 diabetes has historically been thought of as a condition that only affected Caucasians. As a result, there may be assumptions made by providers that Hispanic individuals presenting with prediabetes or diabetes symptoms or laboratory values are likely to have type 2 diabetes, and we don’t need to think about type 1,” she says. “That’s a lingering stereotype that we really need to dispel. Type 1 diabetes affects everyone.”

Meanwhile, another common pitfall in clinical settings is assuming that a child who has overweight or obesity and hyperglycemia has type 2 diabetes (T2D) instead of T1D, says Dr. Cabrera. “Children with undiagnosed type 1 diabetes are reflective of the U.S. population, meaning that they can be overweight or have obesity,” she says, adding that some can even have evidence of acanthosis nigricans, a skin condition more classically suggestive of T2D. “The overlap of phenotype between type 1 diabetes and type 2 diabetes can make proper diagnosis more difficult, but this is critical, since the treatment of type 1 is always insulin, whereas treatment of type 2 is non-insulin medications and lifestyle changes.” If a clinician assumes T2D and does not start insulin in a patient with T1D, the child is not adequately treated and could develop DKA, Dr. Cabrera notes.

She adds that a relative lack of awareness about T1D in the Hispanic community, which is more familiar with T2D, can contribute to the high rates of problems such as DKA at diagnosis in this population. That’s all the more reason for clinicians to have an appropriate level of what she calls “clinical suspicion” of T1D and to be certain they are not letting assumptions guide decision-making. Her message to clinicians: “Check your biases at the door.”

Engage effectively with the community

If you have a significant population of Hispanic patients, consider hiring a staff member who speaks Spanish, ideally, someone who comes from or knows the community you’re serving. “The more providers you have on staff who can relate to your patients, either by language or shared culture, the better care you’re going to deliver,” says Dr. Cabrera. In addition, she says, “Prioritize making sure that all take-home educational materials are properly translated for Spanish speakers.” Dr. Cabrera also recommends establishing relationships with diabetes care providers in your area. “That can go far in developing trust and promoting the most seamless care for your patients,” says Dr. Cabrera. And while it may not be possible for some practices, Dr. Cabrera encourages healthcare providers to attend community events. For example, her clinic sends a contingent to Milwaukee’s Mexican Fiesta every summer to meet with community members and talk about the importance of T1D screening and other aspects of diagnosing and treating the disease.

Encourage use of diabetes technology

Using technological innovations such as continuous glucose monitoring (CGM) and insulin pumps can significantly improve glycemic control in T1D, yet the benefits of these devices are not equally shared among different racial groups in the U.S. For example, a survey published in the Journal of Clinical Endocrinology and Metabolism found that Hispanic young adults with T1D were less than half as likely to have used CGM compared with non-Hispanic White persons in the same age group.⁶

Here again, Dr. Cabrera feels that providers’ unconscious biases about different racial groups may interfere with clinical judgment when recommending T1D management strategies, making them less likely to suggest tech-based tools to some groups. While dealing with insurance and device companies can be challenging to navigate, she says, all patients and families interested in using tech to control T1D deserve access. “We’ve got to make sure that we’re offering the best care to everyone and not making assumptions about what certain people can handle,” says Dr. Cabrera. Keep this in mind: As of May 2023, Medicaid coverage in 45 states and the District of Columbia provided some form of coverage for CGM.⁷

Discuss screening for early-stage T1D—when the time is right

Screening for islet autoantibodies that destroy insulin-producing pancreatic islets can confirm a diagnosis of T1D, but has other important benefits for patients and their families, notes Dr. Cabrera. Siblings, parents and children of a person diagnosed with T1D have up to a 15-fold increased risk for developing the disease themselves as compared with the general population. Screening can identify family members with early-stage T1D before it causes Stage 3 (insulin-dependent) T1D, making them potential candidates for therapy that delays the onset by several years. Knowing that a person has autoantibodies could also make them eligible for clinical trials of new therapies that may have similar benefits.

However, talking about screening with patients and family members of someone with T1D can be a sensitive matter and must be handled with care, says Dr. Cabrera. “This is a conversation best had once the dust has settled and the initial shock of the diagnosis has abated,” she says. It’s first essential to acknowledge that a T1D diagnosis is stressful and will have an impact on the family and their day-to-day life. Equally important, Dr. Cabrera says, is to recognize that when one child receives a diagnosis of T1D, it can be anxiety-provoking and stressful for the parents to consider the possibility that their other children might have the disease, too.

When the time feels right, be direct and simply ask the parents or caregivers of a child diagnosed with T1D if they’re interested in having the patient’s siblings tested to see if they may be at increased risk of developing T1D. “It’s good to ask what their thoughts are about screening so any misconceptions or concerns can be addressed in a thoughtful and compassionate way,” says Dr. Cabrera. Also, be prepared for different reactions from families when you bring up screening their other children. “Some will actively pursue testing, while others say they would never want to know,” says Dr. Cabrera.

In general, screening for risk is advisable if the family finds themselves persistently worrying that other siblings may have T1D. You may also need to discuss screening more than once. “Many families are not ready the first time they hear about it but become more open and receptive over time,” says Dr. Cabrera. Keeping the conversation about screening open is important, especially as new treatments and clinical trials become available. You can take a similar approach to discussing early-stage screening with parents who have T1D but not their children, whose risk for the disease is increased as well.

Promote access to therapies that delay onset of T1D

Patients 8 years and older who have undergone screening and are determined to have Stage 2 T1D are candidates for a monoclonal antibody that delays the onset of insulin-dependent T1D by roughly 2 years. (For more on this, click here.) However, along with getting insurance coverage, practical matters may also pose a challenge for some families, says Dr. Cabrera, noting that receiving the drug requires infusions on 14 consecutive days.

“If we want to be equitable and reduce barriers to different groups, it’s really important to think through ways in which you can get these infusions done,” Dr. Cabrera says. Scheduling treatment during the summer allows children to avoid missing school, she notes, yet getting transportation to an infusion center daily for 2 weeks can be difficult for some families at any time of year. Dr. Cabrera’s clinic has been able to overcome that barrier by having traveling nurses visit patients in their homes to administer the infusions.

Suggest participation in clinical trials

Even though we have seen an increase in the incidence of type 1 diabetes among non-Hispanic Black and Hispanic children, we haven’t seen an increased participation of these groups in screening and clinical trials,” says Anastasia Albanese-O’Neill, PhD, APRN, associate vice president of community screening and clinical trial education at Breakthrough T1D (breakthrought1d.org, formerly called JDRF). In fact, while Hispanic people make up about 19% of the U.S. population, they only constitute 11.6% of participants in U.S.-based diabetes clinical trials, according to a study in Diabetologia.^8,9

Concerns about past abuses such as the infamous U.S. Public Health Service Syphilis Study at Tuskegee are often cited to explain underrepresentation of people of color in clinical trials. Yet a 2022 survey by the Pew Research Center found that well over half of Hispanic people in the United States (58%) consider clinical trials important, which is close to the portion of White people (67%) who feel the same.¹⁰ Lower participation in trials by Hispanic people and other minority communities is just as likely due to lack of information and challenges with access—something as simple as not having a way to get to a clinical site, says Dr. Cabrera. “It’s really important to think about social structures that might leave certain segments of the community out of research. We need to ask what we can do as researchers to make sure that studies are accessible and available to everyone,” stresses Dr. Cabrera.

One solution that clinicians can recommend to Hispanic patients eliminates the language barrier that may keep them from finding a trial. Beyond Type 1, a nonprofit organization, now offers a search engine for T1D clinical trials for people whose primary language is Spanish (visit beyondtype1.org/research-trials).

—by Tim Gower

Data show that diabetes-related distress is common in families of school-age children with type 1 diabetes (T1D).^1-3 Marked by the unrelenting emotional and behavioral challenges of living with diabetes or caring for someone with the disease, diabetes distress is distinct from other mental health conditions. “At its heart, it’s about feeling out of control with diabetes,” says William Polonsky, PhD, CDCES, President of the Behavioral Diabetes Institute and Associate Clinical Professor at the University of California, San Diego. “And it’s understandable. The day you develop it, the universe has given you a new job in addition to all the other demands you have, and you get to do it for the rest of your life.”

Not surprisingly, a recent study found that about 65% of adolescents with T1D suffer from diabetes distress, including feelings of sadness and anger about having the disease and feeling unsupported by family and friends.⁴ However, parents are vulnerable too, with 60% reporting at least one serious concern related to their child’s care, such as feeling upset when their child’s T1D management is off track, feeling like the “diabetes police” and worrying about the short- and long-term medical complications for their child.^1,2

That’s a concern, as parental diabetes distress is a strong predictor of a child’s A1C over time.^3,4 What’s more, when parents’ emotional challenges continue as their child grows older, it compounds the difficulties that many adolescents with T1D experience.⁵ Unfortunately, data from the Type 1 Diabetes Exchange reflects this, with only 17% of patients 18 and younger consistently achieving the recommended A1C target of 7% or less.⁶

The bottom line: As a pediatric healthcare provider, you play a major role in helping patients and their families overcome diabetes distress—and ultimately improving management of T1D throughout a young patient’s life. Here are strategies to accomplish that:

Establish trust

Clinicians who forge strong partnerships with patients and their parents can help them overcome obstacles to effective T1D management, notes Joanna Mitri, MD, MS, Medical Director, Global Education and Advisory Care, Joslin Diabetes Center; Assistant Professor, Harvard Medical School. An important early step in building a relationship with families is to recognize and address concerns parents have about the diagnosis. “When a child or adolescent receives a type 1 diabetes diagnosis, parents may feel shock, guilt, anxiety or uncertainty,” says Dr. Mitri. “For many parents, the challenge is how to stay actively engaged in their child’s diabetes management while at the same time encouraging their independence. They worry how their child can balance their social life and their ability to manage type 1 diabetes, both emotionally and practically,” she says. “To assist parents in coping, I focus on providing comprehensive education about T1D and its management. I ask parents how much involvement they desire in their child’s care. Empowering their child to take charge brings reassurance and eases parents’ concerns.”

Ask the right questions

There are several validated tools to assess how well patients and families are coping (available at behavioraldiabetes.org). For example, the Type 1 Diabetes Distress Scale is an instrument developed by Polonsky and other experts to assess patients of all ages. There is also the PAID-T assessment geared to teens. In general, patients rate their distress on a scale of 1 (not at all) to 5 (a great deal). Those who score a 2 are considered to have a moderate level of distress, while those who score 3 or more have a high level of distress. A simple way to gauge distress in patients is to ask:

1. Do you feel overwhelmed by the demands of living with diabetes?
2. Do you feel you’re often failing with your diabetes routine?

In addition, there is a Parent Diabetes Distress Scale (PARENT-DDS) that assesses parents with children who have T1D. Questions to ask parents include:

1. Do you feel overwhelmed by the responsibilities you take on to manage your child’s diabetes?
2. Do you worry that you’re not doing enough or that others will blame you if your child’s diabetes is not well controlled?

Note: Families with a child diagnosed with early-stage T1D will have unique concerns and challenges. For more insight, see sidebar below.

Foster feelings of hope

Polonsky emphasizes the importance of staying positive. “If you feel like the disease is going to get you no matter what you do, why bother doing anything?” he says. Instead, empower them to take charge. “Hope is evidence-based,” stresses Polonsky. “With good effort and care, odds are good that patients can live a long and healthy life. Tell patients and their parents, ‘We can work together to manage this and avoid complications.’ Remind them regularly.”

Have separate visits as the child grows older

While parents will be present with younger children at most office visits, it’s important for clinicians to schedule one-on-one time with adolescents. “That allows the patient to talk about any issues they may want to address specifically with their healthcare provider,” says Dr. Mitri, noting that this will help patients see their clinician as their advocate and encourage them to discuss problems they may be less likely to reveal to a parent. Such conversations can also help teens become comfortable speaking openly with other healthcare providers, which will be essential when a young person eventually transitions to adult care for T1D.

Check in with teens often

Many individuals with T1D experience increasing A1C levels in late adolescence and early adulthood.^6,7 This is also the time when patients report the highest levels of diabetes distress. A recent study examined how diabetes stressors affected T1D management in adolescents. Study participants were asked to record their diabetes stressors and self-management in daily diaries and also record their daily blood glucose values. Results showed that on days when participants reported higher diabetes stressors, they reported lower self-care and higher blood glucose levels.⁷

This underscores the importance of diabetes distress screening to identify adolescents at risk. Patients who are struggling may benefit from a referral to a counselor who specializes in adolescent T1D, advises Dr. Mitri (the American Diabetes Association publishes a list of such providers at my.diabetes.org/health-directory). She also notes that this age group often benefits from continuous glucose monitoring, which can encourage them to check their glucose levels more frequently on their smartphones with fewer fingerstick tests.

—by Morgan Meissner

Special thanks to our medical reviewer:

Rachel Pessah-Pollack, MD, FACE, Clinical Associate Professor, Division of Endocrinology, Diabetes & Metabolism, NYU School of Medicine, NYU Langone

Maria Lissandrello, Senior Vice President, Editor-In-Chief; Lori Murray, Associate Vice President, Executive Editor; Lindsay Bosslett, Associate Vice President, Managing Editor; Jodie Gould, Senior Editor; Madeleine Beckman, Senior Editor; Joana Mangune, Editorial Manager; Erica Kerber, Vice President, Creative Director; Suzanne Augustyn, Senior Art Director;  Rachel Pres, Senior Director, Digital Production

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