Pediatrics for Parents

The Debate on Diabetes Screening

Janice Arenofsky

When Colby was born, her mother, Jennifer Speth, tested the infant for diabetes. "We did it just for curiosity, never expecting she'd come back as a high risk," says Speth.

Colby is part of a national project called TEDDY (The Environmental Determinants of Diabetes in the Young). Parents are asked to consent to diabetes screening of their newborns; high-risk infants ‚ defined as those who test positive for the genes and have at least one close relative with type 1 diabetes ‚ benefit by close follow-up. (Type 1 diabetes is commonly known as juvenile diabetes.) Participants receive blood tests every three months until age four and then every six months until age 15.

In Colby's case, when the nurse took a drop of blood from her heel for the testing of rare metabolic diseases such as PKU (phenylketonuria), blood was also collected for diabetes screening. Colby's DNA was analyzed, looking for two immune-regulating genes related to diabetes 1: HLA-DR and HLA-DQ. The results suggested that Colby was 100 times more likely than most children to develop juvenile diabetes. "It was a shock," says Speth. "But now we'll know to monitor her."

Speth is grateful for the advance warning for Colby. But would all parents feel the same? This brings up the question, Should newborns be routinely tested for diabetes?

The Great Debate
Many doctors believe screening for type 1 diabetes makes sense due to the increasing prevalence of the disease. The Juvenile Diabetes Research Foundation reports that the rate of juvenile diabetes has risen by 3% to 5% over the past few years.

Scientists don't yet know the reason for the steady growth, but theories abound. Some researchers attribute the increase to a diet of gluten and cow's milk. Others look to viral infections (such as rubella, mumps and coxsackie B4), vaccinations, a germ-free environment, toxic agents and/or psychological stress. Robert Vogt, Ph.D., a scientist at the CDC's Newborn Screening Branch, points to the obesity problem in children.

Another impetus for diabetes screening is the disease's destructiveness. It can cause kidney problems, blindness and even amputations. Early diagnosis, however, can prevent a panicky dash to the ER with a sick baby or child, says Desmond Schatz, MD, a diabetes researcher at the University of Florida in Gainsville. Because "nonspecific" flu-like symptoms often go unrecognized as biomarkers of juvenile diabetes, children sometimes wind up in the ICU, suffering from ketoacidosis toxicity, which can lead to brain swelling. "Anecdotally, we know there are a few deaths each year," says Vogt. "Irreversible brain swelling can lead to a dangerous electrolyte imbalance."

Case In Point
Knowledge translates to power, says Andrew Muir, M.D., a pediatrics professor at the Medical College of Georgia. A clinician with TEDDY, Muir describes the case of a high-risk newborn with a diabetic father. During follow-up visits after the initial testing, the mother noticed that the baby was wetting his diaper frequently. Three months later, the 18-month-old child was diagnosed with diabetes.

In fact, a recent research project known as DAISY (Diabetes Autoimmunity Study in the Young), headed by Jennifer M. Barker, M.D., at the University of Colorado Health Sciences Center, discovered that only one (or 3%) out of 33 at-risk infants who were screened and monitored for the disease needed to be hospitalized. Parents were given a glucometer to measure blood sugar. The control group (also high-risk infants) had a 36% hospitalization rate. The conclusion? Parents alerted to their child's predisposition are more apt to recognize symptoms and avoid a pediatric emergency.

Another reason researchers favor screening in infants and young children is to study diabetes' genetic causes and the prediabetic period better; also, to identify individuals for prevention trials. Currently, TEDDY and its sister project PANDA (Prospective Assessment in Newborns for Diabetes Autoimmunity), both funded by the NIH and other health organizations, screen thousands of newborns in Florida, Georgia and Washington. Other countries also participate.

The Boston-based company PerkinElmer Life and Analytical Sciences reports that autoantibodies can be early predictors of the disease. Tracking this measure is vital, since babies and children do not exhibit the classic symptoms of diabetes until approximately 95% of insulin-producing cells in the pancreas have been destroyed.

Antibody testing of a high-risk child every two years will give parents further clues into their child's predisposition for diabetes. And if two or three tests yield positive results, parents then know their child has a 50:50 risk of developing diabetes. Researchers often give parents glucometers to track their child's daily glucose.

As an additional benefit, the test results can also be a red flag for celiac disease, a chronic digestive disorder that often precedes type 1 diabetes, according to a recent study in Pediatrics (May 2004).

On The Other Hand
But some scientists say universal screening is premature. The test is not 100% accurate and, with its "low predictive value," according to Vogt, generates many false positives. For one thing, babies with the HLA genes do not necessarily develop diabetes.

The same applies to babies with autoantibodies to pancreatic cells. This second screening test measures the amounts of glutamate decarboxylase (GAD), tyrosine phosphatase (IA2) and autoantibodies against insulin (IAA). "The risk level needs to be more specific and precise," says Muir. "So far," he adds, "the most exact measure scientists can supply is that a child has a one in seven chance of developing juvenile diabetes."

In an effort to improve the worldwide accuracy of laboratory tests, the CDC and the Immunology of Diabetes Society take part in DASP (Diabetes Autoantibody Standardization Program). The goal is to encourage laboratories to evaluate the newest technologies for specificity and sensitivity. Forty-seven laboratories in 17 countries participate in this program

Still, detractors protest that the tests heighten anxiety among parents. However, studies also show that the anxiety appears to decrease over time and varies widely with the mother's educational level, ethnic group and marital status.

Another negative experts point out is that if testing does not take place within the context of a research study with appropriate follow up, parents tend to forget their child's risk level. Less monitoring of symptoms takes place. "If parents live near a city with a diabetes research program, I recommend that high-risk infants and children participate," says Muir. "But if I lived in a small town, say in Utah, I wouldn't bother testing."

According to Muir, bottom line, the tests are far from foolproof. Eighty-five percent of children who develop diabetes do not have a close relative with the disease or any other genetic link. Conversely, a large percentage of high-risk children show autoantibodies, but never develop diabetes. The up side to this weak genetic link is that since fewer genes are involved, there is, according to Vogt, a better chance of finding the disease's genetic causes.

Screening For Success
The biggest downside to universal screening is the current lack of "intervention" or prevention trials. But, as the saying goes, the times are changing. In the 1990s, prevention trials using insulin failed. However, in 2002 researchers at Columbia University successfully used a drug ‚ a monoclonal antibody ‚ to slow the progression of diabetes. The drug lengthened the time patients produced their own insulin, improving their overall health with minimal side effects.

Although not strictly an "intervention," TRIGR (Trial to Reduce Insulin Dependent Diabetics in the Genetically at Risk) studies high-risk infants to see if diet is an environmental trigger. International in scope, TRIGR will run to 2007. Its 40 centers in the United States, Canada, Europe and Australia will analyze the effects of a standard cow's milk formula on infants versus a hydrolyzed milk. (For more information, call 1-888-STOP-T1D or go to www.trigrnorthamerica.org.)

Experts say that as prevention trials become available in the next five years, various health organizations such as the March of Dimes will exert pressure on state legislatures to support universal diabetes screening.

What To Do
Meanwhile, parents of high-risk newborns should stay abreast of new prevention trials. Also, watch for symptoms of diabetes ‚ thirst and frequent urination; and consider breastfeeding (according to Harvard Medical School, breast fed infants face a lower risk of infection and diseases, including diabetes).

Parents with extremely high-risk newborns (both parents have diabetes) may want to consider HLA typing or testing for autoantibodies. Talk this over with your child's doctor and/or endocrinologist. Although this testing is not routine and therefore is expensive, your doctor or hospital can send a blood sample to any one of several U.S. laboratories who perform these tests, such as the Mayo Clinic in Rochester, Minnesota.

A Last Word
While the debate about diabetes screening in newborns is raging, laboratory technology is quietly and rapidly improving. Currently, 55 laboratories in 17 countries are experimenting with automated fluorescent DNA sequencing, radioimmunoassay and remote monitoring to develop better diagnostic technologies. Laboratories not only consider accuracy but also cost-effectiveness.

Janice Arenofsky writes health/medical articles for many national venues, including LET'S LIVE, THE MEDICAL POST, VIM & VIGOR, BABYZONE.COM and PARENTING. She lives in Scottsdale, Arizona.