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Monday, January 31, 2022

Trial tests strategy to augment response to COVID-19 vaccines in transplant recipients

 A study has begun to assess the antibody response to an additional dose of a COVID-19 mRNA vaccine in kidney and liver transplant recipients, either alone or with a concurrent reduction in immunosuppressive medication. The clinical trial will enroll people for whom two to four doses of a COVID-19 mRNA vaccine did not elicit a detectable antibody response. The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, is sponsoring and funding the Phase 2 trial, called COVID Protection After Transplant–Immunosuppression Reduction, or CPAT-ISR.

“Eliciting a protective immune response to COVID-19 vaccines in some organ transplant recipients continues to be a challenge,” said NIAID Director Anthony S. Fauci, M.D. “We are concerned about protecting everyone from COVID-19 and therefore continue to develop and test new approaches to make vaccination effective for all organ transplant recipients.”

Organ transplant recipients must take lifelong immunosuppressive therapy to prevent organ rejection, and this therapy blunts their immune responses to pathogens and vaccines. Research has shown that many organ transplant recipients do not develop antibodies against SARS-CoV-2, the virus that causes COVID-19, after receiving a primary COVID-19 vaccine regimen. Even after receiving a third dose of a COVID-19 mRNA vaccine, many transplant recipients still fail to produce an antibody response. Those who do develop antibodies tend to have much weaker responses than immunocompetent people. The lack of robust antibody responses, along with a high prevalence of risk factors such as obesity and diabetes, leaves kidney and liver transplant recipients at high risk for SARS-CoV-2 infection and severe COVID-19.

The purpose of the new study is to determine if temporarily reducing immunosuppressive medication taken during the days before and after an additional dose of an mRNA COVID-19 vaccine safely allows for better antibody responses to vaccination in kidney and liver transplant recipients. Research has shown that pausing immunosuppressive medication in people with autoimmune disease can safely improve their antibody responses to vaccinations for both COVID-19 and influenza, suggesting that this approach might also work for some transplant recipients.

The new trial builds on NIAID’s CPAT pilot study, which is assessing the antibody response to a third dose of a COVID-19 mRNA vaccine in kidney transplant recipients. Dorry L. Segev, M.D., Ph.D., leads both trials. Dr. Segev is the associate vice chair for research and the Marjory K. and Thomas Pozefsky professor of surgery and epidemiology at Johns Hopkins University in Baltimore.

The CPAT-ISR trial will take place at approximately 15 transplant centers across the United States. The study team will enroll up to 400 adults ages 18 years or older who received a kidney or liver transplant a year or more prior to enrollment. All participants will have received two to four doses of either the Moderna COVID-19 vaccine or the Pfizer-BioNTech COVID-19 vaccine at least 30 days before enrollment and will have a negative or indeterminate antibody response 30 days or more after the most recent dose. Participants must be taking one of two specific tacrolimus-based immunosuppressive medication regimens and have no recent transplant rejection or change in immunosuppression.

The study team will assign participants at random to one of two groups. One group will receive an additional dose of a COVID-19 mRNA vaccine with no further intervention. The other group will take a reduced dose of their immunosuppressive therapy for five days before and two weeks after receiving an additional dose of a COVID-19 mRNA vaccine. Investigators will measure each participant’s antibody response to vaccination 30 days after the additional vaccine dose. The goal is to determine the proportion of participants who achieve a predefined antibody response at the 30-day mark. The study team will follow participants for one year after enrollment.

More information about the trial, including study site locations and contacts, is available at under study identifier NCT05077254.

CCP May Collect Top American Athletes’ DNA At Beijing Olympics

 by Dorothy Li and Joshua Philipp via The Epoch Times (emphasis ours),

Sealed from the rest of Beijing in a “closed-loop” bubble, over 200 American athletes are receiving daily COVID screening for the Winter Olympics. But some experts worry that U.S. Olympians’ DNA might be collected by the Chinese Communist Party (CCP).

Patricia Adams, executive director of Canada-based non-profit Probe International, said “it’s a very likely possibility” that the CCP will be collecting top-performing athletes’ DNA at the Games.

They [CCP] are doing the testing every day … and [there’s] absolutely no oversight over the use of the products that they’re getting,” Adams said during a Jan. 26 webinar on EpochTV’s “Unmasking Communist China” program.

In the online event, Stephen Yates, chief executive of consultancy firm DC International Advisory, spoke of the threat posed by the Chinese regime’s mass collection of personal information and health data. U.S. officials and experts have previously sounded the alarm that Beijing is amassing a large database that includes Americans’ personal and health information, which could be used to enhance artificial intelligence systems and fields of medicine, as well as assist in espionage and military operations.

The danger, Yates said, lies in the CCP using the mass data set for unethical purposes.

“China has weaponized artificial intelligence and a lot of other studies of the human process in ways that civilized countries wouldn’t even allow, so we don’t have any way to really know what this dark window of the future might be,” he said.

According to Yates, CCP may use the massive data set to give their athletes a competitive advantage or increase opportunities for psychological warfare.

The Winter Olympics is set to open in Beijing on Feb 4. The diplomatic boycotts announced by the United States and a spate of other countries, which is meant to hold the communist regime accountable for its human rights violations in Xinjiang, don’t keep athletes from competing at the Games.

The U.S. athletes arrived in Beijing on the evening of Jan. 28, and were sent straight to hotels situated in a closed-loop system surrounded by wire fences. Everyone in the bubble can only leave via special vehicles, and staff in full protective suits carry out mouth swabs on them every day.

A security guard stands guard at a hotel parking in Beijing on January 29, 2022. (KIRILL KUDRYAVTSEV/AFP via Getty Images)

In the online event, Adams suggested that the CCP may “get rid of an American who’s the likely winner of the gold” through what she described as “nefarious means using false positive COVID test.”

Beijing’s Olympic organizers on Jan. 29 denied reports that they may potentially manipulate COVID test results, saying that the tests are up to international standards, according to state media China Daily.

Adams said that “at the end of the day, it’s all being done by the Chinese government, and nobody really knows what’s going to happen to the data.”

She noted the problem is “nobody trusts the Chinese government.”

“The Chinese government has demonstrated to the world over and over and over again that they don’t follow rules. They follow their own rules. They don’t follow international rules. They don’t follow treaties that they’ve signed.”

The CCP’s known record of cyber espionage has led several countries, including the United States, UK, and Canada to tell their athletes to bring a burner phone for the Games. Cyber security experts warned that Beijing 2022, a compulsory health app for the Games, may spy on users through encryption flaws.

“I think that athletes are very, very nervous. And they’re not happy,” said Adams.

Did NYC Testing Numbers Drop Due To COVID Fatigue Or At-Home Tests?

 Everyone has their pandemic pastime. What’s Francine Ricchi’s? Tracking the lengths of COVID testing lines.

For more than a year, the Boerum Hill resident has done laps around her Brooklyn neighborhood almost daily, tallying the number of people waiting to get their noses swabbed and then posting to her Twitter account.

On her most recent trips, though, Ricchi has seen a change in the testing sites along her route. During past waves, she has watched lines grow and dwindle, as community transmission rises and falls. And sure enough, as cases skyrocketed in December, she documented queues of more than 100 people waiting to get tested.

But even though the daily number of New York City cases has still been enormously high — day after day larger than the peak once recorded in April 2020 – Ricchi said testing lines have become ghost towns.

“It was mostly documenting different locations showing there was no line at opening time,” she said. On January 26th, when the daily average case rate was 5,054, “there was really nobody. At one location, there were two people. We’re definitely in this period where demand for tests has dropped off.”

City data supports Ricchi’s findings. As COVID cases have come down from their omicron summit, so too have tests, which is to be expected.

But official PCR testing numbers have been cut nearly in half over two weeks. Last year, a similar drop took six months. It’s the sharpest drop over the shortest time ever recorded during the pandemic.

 PCR testing numbers have been cut nearly in half over two weeks. Last year, a similar drop took six months. 

In the most recent week for which complete data is available, about 86,700 New Yorkers got a PCR COVID test each day. That’s down from an early-January apex of almost 133,300 such tests per day. Antigen tests are trending in much the same way.

For comparison, during the winter wave a year ago, daily testing doubled from October to January, peaking at an average of 69,000 PCR tests. This tally didn’t shrink back to its original level until June.

City-run COVID sites are doing less than half as much testing now as they were in early January, said Dr. Ted Long, a primary care physician and executive director of the New York City Test & Trace Corps.

“​​As omicron was under better control and people started to see cases were no longer sharply rising, the impetus to get tested also went down a bit across the city,” Long said. He added that record numbers of New Yorkers sought to get tested before traveling to see family over the last winter holiday, as recommended by city health officials. After the break, that demand cooled off.

CityMD, a local urgent care chain, is administering 40% fewer COVID tests than at the height of the omicron testing crush, said Matt Gove, a spokesperson for the private health care provider.

Did Official Numbers Drop Due To COVID Fatigue Or At-Home Tests?

Frustrations over slow turnaround times might also be dissuading people from seeking tests.

Turnaround times took a hit around the start of the holiday season, and the issues persisted for some providers through the first half of January. In the run-up to Christmas, CityMD needed five-plus days on average to return test results. The urgent care chain shuttered 19 of its approximately 150 offices in December, citing staffing challenges. All have since reopened.

Other private health providers faltered, too. Jessica Benmen, a 27-year-old East Village resident, got results on January 27th from a COVID test she’d taken at a Labworq location on December 31st — a whopping 28 days earlier.

New York State Attorney General Letitia James sent the Brooklyn-based testing company a warning letter in December demanding that it report accurate turnaround times for its COVID-19 tests. Labworq is one of a half dozen companies to receive such warnings, the others being ClearMD HealthLabQSameday HealthEZ Test NY and Keep Health Safe,

“I’d forgotten that I even did it,” Benmen said, “It’s almost worse that they sent it to me this late.”

Citywide, turnaround times haven’t yet fully returned to their pre-omicron speed, but they have rebounded from early January, when less than 60% of tests came back within two days. Now, more than three-quarters of tests return results within 48 hours, according to data compiled by the New York City health department.

CityMD is now returning PCR tests in two or three days, Gove said, and turnaround times are even quicker at municipal-run sites. More than 80% of tests come back within 24 hours, Long said. He chalked the speed up to their pandemic response lab, which processes tests conducted at city sites.

Benmen, who gets tested before seeing friends and family, has experienced the improvement firsthand. Most tests she takes come back quickly, but she also says she's now using rapid tests more often. The holiday season's long lines and waits made rapid tests a more convenient option for New Yorkers who could get their hands on the limited supplies.

But home tests aren't counted in the city's official records, so it's hard to tell whether New Yorkers are actually getting tested less frequently — or simply switching over to rapid tests taken at home. When asked why the city hadn't incorporated at-home tests into its recordkeeping, a spokesperson told WNYC/Gothamist to contact the New York State Department of Health for an answer.

The New York State Department of Health said the decision was up to New York City officials.

"Local health departments have launched their own portals for at-home test tracking and approval by the Department is not required," state health department spokesperson Erin Silk wrote in an email, citing the examples of Warren and Tompkins counties.

Long said the city has distributed more than 8 million at-home test kits, 6.6 million of which went to New York City schools. The city began handing out the kits in mid-December. Assuming the free at-home kits have experienced the same average positivity rate as the city’s PCR testing since then, at least 1.7 million cases could have been potentially missed by recordbooks.

Francine Ricchi said that while short lines are less likely to make a splash with her Twitter followers, she'll keep documenting her local testing sites.

"Documenting zero people on line is just as important as documenting 50 or 60 waiting at open," she said. She also enjoys the excuse to go outside.

"It's a good morning routine for me to get up and get moving," Ricchi added. "Little bit of exercise. It's not a bad way to start your day."

Influence of state reopening policies in COVID-19 mortality



By the end of May 2020, all states in the US have eased their COVID-19 mitigation measures. Different states adopted markedly different policies and timing for reopening. An important question remains in how the relaxation of mitigation measures is related to the number of casualties. To address this question, we compare the actual data to a hypothetical case in which the mitigation measures are left intact using a projection of the data from before mitigation measures were eased. We find that different states have shown significant differences between the actual number of deaths and the projected figures within the present model. We relate these differences to the states different policies and reopening schedules. Our study provides a gauge for the effectiveness of the approaches by different state governments and can serve as a guide for implementing best policies in the future. According to the Pearson correlation coefficients we obtained, the face mask mandate has the strongest correlation with the death count than any other policies we considered.

In a break with federal guidelines, San Francisco allows second COVID-19 booster for all J&J takers

 Last week, Julia Ma did something the majority of people in the United States can't – she got an authorized second COVID-19 booster shot after one dose of Johnson & Johnson's vaccine.

Ma's J&J shot was followed five months later by a Pfizer-BioNTech booster dose. Her third shot, another Pfizer, put her on par with 86 million Americans who’ve had three doses of either the Pfizer or Moderna COVID-19 vaccine, as a two-dose series plus a booster. 

Only J&J recipients who are immunocompromised are authorized by the federal government to get a single initial shot and two boosters.

But this month the San Francisco Department of Public Health sanctioned a second booster dose for everyone who got J&J as their first shot, making it the only known place in America where a third shot is officially allowed for those with normal immune protection.

Ma, 37, said because she’s fully vaccinated she’s not terribly worried about COVID-19, but she’s hoping to travel next month and wanted to make sure she wouldn’t be a vector for others while omicron surged.

“I don't want my vax status to be a barrier to that," she said. "I opted for the J&J initially because I liked that it was only one shot, but I sometimes feel like the CDC guidelines forget about J&J recipients.”

An accommodation for J&J recipients

San Francisco's Department of Health described the third dose as “an accommodation” based on recent studies that found a third dose of an mRNA COVID-19 vaccine, such as from Pfizer and Moderna, is needed to induce adequate protection as immunity wanes. The third dose reduces symptomatic infection, hospitalization and severe outcomes from the omicron variant.

The second booster is only available to residents of San Francisco or people who got their initial J&J vaccination there.

"San Francisco’s Department of Public Health has always been a vanguard of the way things should be from a scientific perspective," said Dr. Peter Chin-Hong, a professor of medicine and infectious disease at the University of California, San Francisco.

In a release, the department said while the research so far has focused on people whose vaccines were either from Pfizer or Moderna, “We believe that similar studies in persons whose primary series was a single J&J vaccine dose would yield similar results showing that three doses are needed for optimal protection.”

Such studies are not available in part because so few people have gotten the J&J vaccine. In the United States, 119 million people have been fully vaccinated with Pfizer, 74 million with Moderna and 16 million with J&J, said Chin-Hong.

“While there’s understandable frustration with the absence of data, I’m not a fan of the decision to wing it ahead of data,” said Dr. Kelly Moore, chief executive officer of, which educates health care professionals about U.S. vaccine recommendations

Current recommendations

A single booster two months after the initial J&J shot was authorized by federal regulators in October. The Centers for Disease Control and Prevention recommends it be one of the mRNA vaccines.

mix and match vaccine study published last week in the New England Journal of Medicine found the highest levels of antibodies for J&J recipients were produced when it was followed by an mRNA vaccine.

“If you get as your second dose of either Moderna or Pfizer, you’re going to get much higher antibody levels and we have a good sense that higher antibody levels are advantageous,” said Dr. William Schaffner, a professor and infectious disease expert at the Vanderbilt University School of Medicine in Nashville, Tennessee.

For people who got either Pfizer or Moderna, a booster is recommended five months after the last dose of their original two-dose series. Multiple studies show for people who got an mRNA vaccine, three doses of vaccine were much more protective against getting omicron than two.

Yale study of 37,877 people in Connecticut who got PCR COVID-19 tests between Dec. 12 and 26 found those who’d gotten two mRNA doses five months ago had omicron positivity rates of 4.2% while people who’d had a third (booster) shot had positivity rates of 2.2%.

The J&J vaccine is still highly protective against severe COVID-19 disease and death, which has always been the goal of all three vaccines.

A study of 20 J&J recipients by researchers at Harvard who developed the one-shot vaccine found people from different parts of the world who received it were protected against severe disease regardless of the virus variant.

In a statement, Johnson & Johnson said "A growing body of evidence demonstrates that our vaccine provides protection when administered as a single dose for an efficient response to the pandemic and as a booster dose at least two months after primary vaccination to protect against symptomatic COVID-19."

COVID questions?: Your coronavirus resource guide

The company points to a South African study conducted while the omicron variant was dominant there that found one J&J shot followed by a J&J booster was 85% effective against COVID-19 related hospitalization.

Dr. Anthony Fauci. a top health adviser to President Biden, has said that while there’s much more data available on Pfizer and Moderna vaccines, the protection provided by J&J plus one booster appears to be parallel.

“I do think Johnson & Johnson is right that two doses are going to be good to avoid severe outcomes," said Dr. Sten Vermund, dean of the Yale School of Public Health.

But while an initial dose plus a boost is good, it still doesn’t answer the question of optimizing dosing, he said.

“If I were a J&J recipient, I would welcome a two-dose mRNA booster, which would be a grand total of three doses,” he said.

Should J&J have been two doses?

Many scientists think J&J should have been a two-dose vaccine from the beginning, which would make its booster the third in the series, just like the mRNA vaccines.

Scientifically it makes sense, said Chin-Hong. Multiple vaccines against other diseases fit into this category, priming and then reminding the immune system.

“Measles, mumps, rubella, hepatitis B, the human papillomavirus, it’s always a similar formula," he said. "You have a one-two vaccination punch, you wait a while and then you remind the immune system.”

The CDC could authorize a third J&J shot if it chose to, but the question hasn't been brought to its Advisory Committee on Immunization Practices said Schaffner, who sits on the committee.

"An additional dose, a third dose for the initial J&J recipients, has not been proposed as a near-team discussion for that group," he said. 

Some J&J recipients have managed workarounds, said Chin-Hong. “I’ve spoken to parents with college-aged kids who’ve gotten a J&J shot in another state, and then when they came home they got an additional shot,” he said.

Other workarounds may be inadvertently on the horizon. 

Selena Burke lives in Hilton Head, South Carolina. She got the J&J vaccine as her first shot, followed by a Pfizer booster Oct. 27. She’d like to get another booster next month, when she’s five months out, but can’t because it’s not currently allowed

But soon, pharmacists in her state might not be able to ask if she’s been previously vaccinated. A proposed law there would make it a criminal offense for any public, private or nonprofit entity to ask anyone their vaccination status, with possible fines up to $14,000 or a year’s jail time.

“Then maybe I could get the second Pfizer shot,” Burke said.

Meridian Bioscience Gets Additional NIH Award to Develop Viral Respiratory Test

 Meridian Bioscience Inc. on Monday said it received an award from the National Institute of Health Rapid Acceleration of Diagnostics initiative to help research, develop and produce the company's Revogene molecular viral respiratory diagnostic testing panel.

Meridian said the Revogene respiratory panel will simultaneously detect SARS-CoV-2, respiratory synovial virus, and influenza A/B infections.

Meridian said the $2.5 million in additional funding follows an original $5.5 million award. The funding is provided as part of an NIH initiative to speed technologies for Covid-19 testing, the company said.

1 in 3 People Misinterprets Home COVID Tests

 Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I'm Dr F. Perry Wilson of the Yale School of Medicine.

Imagine that you are unvaccinated, 45 years old, and otherwise healthy. Recently, you spent more than 10 minutes less than 6 feet apart from someone who turned out to have COVID. Currently, you are feeling sick with a cough, fever, and muscle aches. You've also lost your sense of smell.

But here's the wrinkle. You take a rapid, at-home COVID test, and it comes back negative.


What do you do?

That very question was put to 338 individuals in this week's study, appearing in JAMA Internal Medicine.

It's an important question. With free test kits being sent to millions of homes around the country, and with the Biden administration committing to get more home tests onto store shelves, there's about to be a lot more home testing. And that means people need to know what to do with the results.

Now, for our hypothetical scenario — an unvaccinated individual with a recent, close COVID contact who has symptoms consistent with COVID — the recommendations are quite clear: Quarantine, regardless of what the rapid test says, and get yourself a PCR test.

How would the survey respondents, 64% of whom had college educations by the way, fare?

Not too great.


Those who were assigned to read the FDA-authorized instructions included with the Ellume at-home COVID test got the answer wrong 36% of the time.

And when you look at those instructions, you can see why.


If your test is negative, the authorized instructions say, you are unlikely to have COVID-19 but may have had it previously, and you could get an antibody test to figure that out.

This is just not correct. In fact, while the rapid tests continue to be able to detect Omicron, there are convincing data to suggest that the tests turn positive later in the course of disease than with prior variants.

In fact, this language might be worse than no instructions at all. Among individuals presented with no information on how to interpret the tests, only 21% got it wrong.


The authors also provided a third option: an information sheet designed with decision theory principles in mind that makes it very clear what to do with a negative test based on whether you've had a COVID exposure, and whether you've had symptoms.


Just 4% of folks got the decision to quarantine wrong when presented with this enhanced set of patient instructions.

Some good news: There wasn't much confusion after a positive test — everyone knew they should isolate regardless of the instructions they were presented. But this study raises a real concern for an off-target effect of the "tests for everyone" program — false reassurance.

Understanding how to interpret any medical test requires knowing two things: how sensitive the test is at detecting the disease of interest, and how likely you were to have the disease before you tested (the pretest probability). When the pretest probability is high, negative results need to be taken with a large grain of salt, particularly if the test of interest might not be perfectly sensitive.

Sensitivity of at-home COVID tests are quite variable, and more so for Omicron, as this preprint shows.


The FDA acknowledged the reduced sensitivity of antigen tests in the face of Omicron in a December statement, recommending that, among those with symptoms of COVID, a negative home test should be followed by a definitive PCR test.

In other words, if it looks like COVID and sounds like COVID, treat it as COVID — regardless of what a line on a piece of cardboard says.

What this means is that in the coming weeks, more and more people will be testing themselves for COVID. Those that test positive generally know what to do. Those that test negative may not. Healthcare providers need to get the word out that these home tests are great as an initial screen, or to use as a check before visiting a high-risk individual, but PCR tests are better if you have new symptoms. Patient instructions of the type that the authors designed here might go a long way to get that message out.

To be fair, not all home tests do as bad a job of explaining the meaning of a negative test as the Ellume instructions do. The FDA-authorized instructions for the BinaxNow test and the iHealth Covid test — which seems to be the one many people have received in the mail — clearly state that you may still be infectious if you have a negative test.


All in all, I think it's a great thing that we are getting tests into the hands of more people. Knowledge is power. It just might take a modicum of effort, or better design of instructional cards, to teach everyone how to use that power wisely.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale's Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at

Does Using A1c to Diagnose Diabetes Miss Some Patients?

 The introduction of A1c as an option for diagnosing type 2 diabetes over a decade ago may have resulted in underdiagnosis, new research indicates.

In 2011, the World Health Organization (WHO) advised that A1c measurement, with a cutoff value of 6.5%, could be used to diagnose diabetes. The American Diabetes Association had issued similar guidance in 2010.

Prior to that time, the less-convenient 2-hour oral glucose tolerance test (OGTT) and fasting blood glucose (FBG) were the only recommended tests. While WHO made no recommendations for interpreting values below 6.5%, the ADA designated 5.7%-6.4% as prediabetes.

The new study, published online in The Lancet Regional Health-Europe, showed that the incidence of type 2 diabetes in Denmark had been increasing prior to the 2012 adoption of A1c as a diagnostic option but declined thereafter. And all-cause mortality among people with type 2 diabetes, which had been dropping, began to increase after that time.  

"Our findings suggest that fewer patients have been diagnosed with [type 2 diabetes] since A1c testing was introduced as a convenient diagnostic option. We may thus be missing a group with borderline increased A1c values that is still at high metabolic and cardiovascular risk," write Jakob S. Knudsen, MD, of the Department of Clinical Epidemiology, Aarhus University Hospital, Denmark, and colleagues.

Therefore, Knudsen told Medscape Medical News, clinicians should "consider testing with FBG or OGTT when presented with borderline A1c values."

The reason for the increase in mortality after incident type 2 diabetes diagnosis, he said, "is that the patients who would have reduced the average mortality are no longer diagnosed...This does not reflect that we are treating already diagnosed patients any worse, rather some patients are not diagnosed."

But M. Sue Kirkman, MD, emeritus professor of medicine at the University of North Carolina at Chapel Hill, who was part of the writing group for the 2010 ADA guidelines, isn't convinced.

"This is an interesting paper, but it is a bit hard to believe that a change in WHO recommendations would have such a large and almost immediate impact on incidence and mortality. It seems likely that …factors [other] than just the changes in recommendations for the diagnostic test account for these findings," she said.

Kirkman pointed to new data just out from the US Centers for Disease Control and Prevention (CDC) on January 26 that don't show evidence of a higher proportion of people in the United States who have undiagnosed diabetes, "which would be expected if more cases were being 'missed' by A1c."

She added that the CDC incidence data "show a continuing steady rate of decline in incidence that began in 2008, before any organizations recommended using A1c to screen for or diagnose diabetes." Moreover, "there is evidence that type 2 diabetes incidence has fallen or plateaued in many countries since 2006, well before the WHO recommendation, with most of the studies from developed countries."

But Knudsen also cited other data, including a study that showed a drop or stabilization in diagnosed diabetes incidence in high-income countries since 2010.

"That study concluded that the reasons for the declines in the incidence of diagnosed diabetes warrant further investigation with appropriate data sources, which was a main objective of our study," write Knudsen and coauthors.

Knudsen told Medscape Medical News: "We are not the first to make the point that this sudden change is related to A1c introduction...but we are the first to have the data to clearly show that is the case."

Diabetes Incidence Dropped but Mortality Rose After 2010

The population-based longitudinal study used four Danish medical databases and included 415,553 patients treated for type 2 diabetes for the first time from 1995-2018 and 2,060,279 matched comparators not treated for diabetes.  

From 1995 until the 2012 introduction of A1c as a diagnostic option, the annual standardized incidence rates of type 2 diabetes more than doubled, from 193 per 100,000 population to 396 per 100,000 population, at a rate of 4.1% per year.

But from 2011 to 2018, the annual standardized incidence rate declined by 36%, to 253 per 100,000 population, a 5.7% annualized decrease.

The increase prior to 2011 occurred in both men and women and in all age groups, while the subsequent decline was seen primarily in the older age groups. The all-cause mortality risk within the first year after diabetes diagnosis was higher than subsequent 1-year mortality risks and not different between men and women.

From the periods 1995-1997 to 2010-2012, the adjusted mortality rate among those with type 2 diabetes decreased by 44%, from 72 deaths per 1000 person-years to 40 deaths per 1000 person-years (adjusted mortality rate ratio, 0.55). After that low level in 2010-2012, mortality increased by 27% to 48 per 1000 person-years (adjusted mortality rate ratio 0.69 compared with 1995-1997).  

The reversed mortality trend after 2010-2012 was due almost entirely to the increase in the first year after diabetes diagnosis, Knudsen and colleagues note.

According to Kirkman, "A1c is strongly predictive of complications and mortality. That plus its ease of use and the fact that more people may be screened mean it's still a good option. But for any of these tests, people who are slightly below the cut-point should not be considered normal or low risk."

Indeed, Knudsen and colleagues say, "These findings may have implications for clinical practice and suggest that a more multifactorial view of metabolic risk is needed."

Knudsen and Kirkman have reported no relevant financial relationships.

Lancet Reg Health Eur. Published online January 1, 2022. Full text