Strategies for earlier detection of type 1 diabetes in children

An estimated 1.8 million people in the United States, or nearly 1 in 250 children and 1 in 200 adults, have type 1 diabetes. One-third of children with type 1 diabetes are diagnosed when they develop diabetic ketoacidosis (DKA), which is not only life-threatening in the short term but is associated with poor long-term glycemic control. First-degree relatives are 15 times as likely as the general population to have type 1 diabetes, and the American Diabetes Association recommends testing them for pancreatic islet autoantibodies to predict whether they will develop the disease. In a prospective study, children previously identified as being at high risk of type 1 diabetes based on autoantibodies had a low incidence of DKA (3.3%) at the time of diagnosis.

Not only does the presence of islet autoantibodies have prognostic significance, selected patients may be eligible for teplizumab (Tzield), a monoclonal antibody approved by the U.S. Food and Drug Administration in 2022 to delay the onset of type 2 diabetes in high-risk individuals. An international randomized, placebo-controlled trial tested a 14-day intravenous infusion of teplizumab in 76 nondiabetic relatives of patients with type 1 diabetes (including 55 children 8 to 17 years of age) with two or more autoantibodies and impaired glucose tolerance. The intervention group had a median time to diagnosis of type 1 diabetes of 48.4 months, compared with 24.4 months in the placebo group. A subsequent trial showed that teplizumab preserves β-cell function in patients with newly diagnosed type 1 diabetes but does not improve clinical outcomes.

Teplizumab’s exceptionally high price ($13,850 per vial; $194,000 for a 14-day course) and limited benefits—delaying type 1 diabetes onset for an average of 2 years—means that other strategies are needed to improve outcomes in at-risk children. Notably, 80% of patients with type 1 diabetes have no affected relatives. However, it is not known whether screening the general population for type 1 diabetes with genetic or autoantibody tests would lead to more benefits than harms.

One alternative to population-wide screening is using machine learning to predict type 1 diabetes in primary care. A June 2024 study in The Lancet used electronic health records from more than 2 million children in Wales to develop and validate a predictive algorithm for type 1 diabetes based on 26 symptoms, history elements, and timing of primary care visits. When the algorithm was set to generate an electronic alert at 10% of visits, 7 in 10 children with type 1 diabetes would have triggered an alert in the 90 days before diagnosis and been diagnosed an average of 9 days earlier. Fewer alerts (e.g., 5% of visits) reduced the number of early diagnoses. Although the researchers asserted that implementing the algorithm would “substantially reduce the proportion of patients with new-onset type 1 diabetes presenting in [DKA],” they acknowledged that further studies are needed to test the feasibility of this strategy and its relationship to “alert fatigue” and clinician burnout in practice.

**

This post first appeared on the AFP Community Blog.

Vaccines protect patients from complications of measles, RSV, and COVID-19

August is National Immunization Awareness Month, when public and private health organizations are encouraged to highlight the benefits of vaccines for patients of all ages. In a recent webinar, Centers for Disease Control and Prevention (CDC) Director Mandy Cohen, MD, MPH, discussed how primary care can support federal vaccine efforts, from participating in the national Vaccines for Children program to pre-ordering annual influenza and COVID-19 vaccines to eliciting questions patients and parents may have about vaccines.

Recent publications have reinforced the protective effects of vaccines against complications of measles, respiratory syncytial virus (RSV), and COVID-19. In an American Family Physician editorial, Dr. Doug Campos-Outcalt alerted family physicians to this year’s measles resurgence and its association with a small decline (95% to 93%) in the percentage of kindergarten-age children who have received two doses of measles, mumps, and rubella (MMR) vaccine. Measles is a highly contagious illness that is not free from complications, as some people believe:

Before the introduction of the measles vaccine in 1963, there were an estimated 3 million to 4 million cases of measles each year, leading to 48,000 hospitalizations, 1,000 cases of encephalitis, and 400 to 500 deaths.

Although not technically a vaccine, the monoclonal antibody nirsevimab was approved by the U.S. Food and Drug Administration in July 2023 for the prevention of RSV bronchiolitis in infants younger than 12 months. A prospective, matched case-control study examined the real-world effectiveness of nirsevimab in preventing hospitalization for RSV bronchiolitis in France during the 2023-2024 season, before that country’s implementation of maternal RSV vaccination. Nirsevimab was 83% protective against hospitalization for RSV-associated illness and reduced pediatric intensive care unit admissions by 70%.

COVID-19 vaccines have been shown to reduce the risk of infections and hospitalizations; however, there have been conflicting data about whether they are protective against postacute sequelae of SARS-CoV-2 (PASC, also known as long COVID). An analysis of a national primary care registry found that breathing difficulties, fatigue, and sleep disturbances often persist after having COVID-19. A large U.S. Department of Veterans Affairs case-control study showed that the rate of PASC decreased during the pre-Delta, Delta, and Omicron eras of COVID-19 and was significantly lower among vaccinated people after vaccines became available. Of the overall decrease in PASC, researchers estimated that 28% was attributable to viral changes and 72% attributable to vaccines.

**

This post first appeared on the AFP Community Blog. Although it's hard to put a price on the suffering and deaths prevented by vaccines, an analysis published last week estimated that during the past 30 years in the U.S., childhood immunizations have produced a net savings of $540 billion in direct costs and $2.7 trillion in societal costs.

The case for supporting more American immigrants, not less

As a senior faculty member at a medical school and now a residency program, I'm used to writing letters of recommendation (LOR) for students, residents, and junior faculty applying for promotions. A few years ago, I received a LOR request from a fellow (a physician who has completed residency and is pursuing specialized training) whom I'd never met before and who wasn't applying for faculty position or promotion. Instead, this foreign-born physician was applying to stay in the U.S. The reason he was asking me to support his application is that one of my papers had cited one of his research studies. As a "well-known physician and researcher in the field of Family Medicine," I could testify to the importance of his contribution to medical science in this country. He hoped to extend his visa in the EB-2 National Interest Waiver category, which requires that applicants "have an advanced degree or extraordinary ability and prove their work can significantly contribute to the US economy." I wrote the LOR, and though I did not hear back about the outcome, I recently Googled his name and was pleased to see that he was able to complete his training and is now an attending physician at a respected medical institution.

The contribution of international medical graduates (IMGs) to the U.S. physician workforce is, and has always been, substantial. My late grandfather (a neuropsychiatrist), uncle (an emergency medicine physician) and aunt (an ophthalmologist), all attended medical school in China before immigrating to the U.S. to teach and practice medicine. According to a recent article in JAMA, "there are currently more than 230,000 licensed IMGs who graduated from more than 2000 different medical schools in 169 countries." Some of these IMGs were immigrants like my relatives, while others were U.S. citizens who attended medical schools outside of the U.S. (most often in the Caribbean). Since U.S. medical school graduates tend to settle and practice in urban areas and enter higher-paying medical subspecialties, IMGs fill essential gaps in primary care and underserved rural areas - though a recent study suggested that fewer of them are choosing to do so.

This year's race for the Republican Presidential nomination, which concluded with the nomination of Donald Trump for the third election in a row, had the distinction of including two candidates who are the children of Indian immigrants: Nikki Haley and Vivek Ramaswamy. Both candidates, sensitive to the prevailing anti-immigrant sentiment in the GOP, were careful to note that their parents were "legal immigrants," presumably in contrast to the thousands of "illegals" migrating across the Mexican border. There are, of course, well-established pathways for highly educated foreign-born persons like their parents and mine to enter and remain in the U.S. That influx of talented doctors, scientists, engineers, and others is essential to maintaining America's technological preeminence.

But the U.S. doesn't just need highly educated professionals - it also needs factory laborers, construction workers, farm workers, nannies, housecleaners, and other working-class professions that don't qualify for EB-2 National Interest Waivers. Even if "mass deportation" of tens of millions of undocumented immigrants living in the U.S. was possible - and contrary to popular belief, the Biden administration expelled more migrants (2.8 million) during its first two years than Trump did during his entire 4-year term - it would result in wholesale economic disaster. What America needs isn't a way to get rid of more immigrants who are holding useful jobs and making our country better; instead, as I wrote ten years ago, it needs to create more legal pathways to citizenship that don't require a LOR from a professor of family medicine.