Stacey Divone sees double every time she looks in the mirror. She’s the slightly older of a pair of identical twins born on Christmas Eve 1976, and when she was just 5 years old, Stacey — just like her father — was diagnosed with type 1 diabetes.

Thirty-five years later, her genetic double is still diabetes-free.

“It fascinates me that we share 100% of the same genes, developed in the exact same womb and grew up in the exact same environment, eating the exact same things, having the same father who had type 1 — yet one of us has (T1D) and the other doesn’t,” Stacey says. “The human body is a mysterious thing sometimes.”

So how common is it for one identical twin to have diabetes, and the other not to? The first line of the first study I dug into to answer that question read, “Monozygotic twins are usually discordant for type 1 diabetes.”

Let me translate that into English for you: When it comes to identical twins, usually only one gets diabetes.

How many sets of twins both have diabetes? About a third, according to the literature.

If your identical twin (should you have one) has type 1 diabetes, your risk for developing type 1 yourself is “only” 35%. That’s still a pretty high risk — and there plenty of stories about twins sharing diabetes, like Amylia Grace Yeaman and her sister in Iowa, Ashley and Emily in Pennsylvania, and the Tale of Two Twins in Massachusetts — but it’s by no means a slam-dunk, and two-thirds of sets of identical twins have a D-sibling and a sugar-normal sibling.

Despite the scientific knowledge that type 1 is basically genetic, diabetes researchers have long known that identical twins don’t have the identical risk of developing type 1 diabetes; and this fact has long fueled theories of environmental causes as the root source of type 1 diabetes.

But not so fast. It turns out that identical twins are not so identical after all. We have cancer researchers to thank for this insight, not diabetes researchers.

You Look the Same

Monozygotic twins, commonly called identical twins (like Stacey and her sister) are a pair of babies that came from one egg and one sperm cell. In the womb a pair of such embryos have always been viewed as carbon copies of each other, sharing an identical genetic blueprint. And they do.

At least in the beginning.

But in recent decades, genetic research has shown that the DNA of identical twins diverges over time. These so-called epigenetic changes are powered by environmental factors, and drive the twins farther apart genetically as they explore the world on their separate paths.

But wait, that’s not all.

Once published, each of our individual “books of DNA” mutates all on its own, independently of the epigenetic changes, via so-called somatic mutations, a.k.a. copy errors. Something goes wrong during cell division and the DNA changes.

So the older the twins get, the less identical they become, due to these two types of genetic changes. This is why younger identical twins look more the same than older sets—because the younger pairs actually are more identical.

But it’s more than just looks. Somatic changes have a larger impact on the DNA blueprint than epigenetic changes do, and while most somatic changes seem harmless, it’s now believed that most cancers can be traced to somatic mutations.

Thus the interest in somatic mutations on the part of cancer researchers.

So when do somatic changes start happening? Apparently long before birth. One recent study found that the average pair of identical twins actually has more than 300 genetic differences at birth.

Not so identical after all. Yeah, twins can still pull the wool over elementary school teachers’ eyes with the old switch-a-roo in math class, but apparently diabetes isn’t so easy to fool.

Back to the Drawing Board?

So where does that leave us? Does the fact that identical twins aren’t fully identical make twin research worthless in the diabetes arena? Quite the contrary. Identical twins are still very similar. Consider that a human being has something in the neighborhood of 24,000 genes, and typically around 30% of those differ between any two people. That’s 7,200 differences between you and me, while our “identical” twins might only vary by 300 genes or so, at least at birth. In short: There are a lot fewer differences to sort out between twins. If type 1 diabetes turns out to be purely genetic, looking at the differences between not-quite-identical twins may be the fastest way to find the genes causing type 1 diabetes.

So twin studies continue. In fact, the prestigious Barbara Davis Center for Diabetes at the University of Colorado is currently recruiting D-twins and their “unaffected” co-twins for a study. And beyond trying to sort out the root causes of diabetes itself, researchers at the Barbara Davis Center are also studying other autoimmune diseases that appear in conjunction with diabetes. They are investigating how genes might affect an individual’s response to “preventive agents or treatment aimed at preserving insulin-producing cells.”

Exciting stuff.

Fraternal Twins, Unite!

Just to be clear here, the genetic research to date has not focused on fraternal twins, because they are actually two different individuals who came from two separate eggs, but just happened to be in the womb together. As separate individuals, their risk of sharing diabetes would be the same as any (non-twin) siblings.

But of course being born and growing up in lockstep, fraternal twins still have a very special bond with each other.

We know many of these pairings in the Diabetes Community, including the famous Singer Twins, Mollie and Jackie, who happen to have a mom and aunt by the same names who are also twins and happen to all be part of a country band, MJ2. Mollie is the T1 peep diagnosed at age 4 and has a blog called Cure Moll, while her sister Jackie is a sugar-normal. For the record, they’re fraternal twins.

In response our query about her twin relationship, Mollie shares the following:

“I think this is an important topic to write on. Even though we’re fraternal and not identical twins, Jackie has gone through extensive testing over the years to see if she carried the R Protein. She’s also always been one of my strongest advocates, which is why we started the Diabetic Angels community together, and have always been a team, even though she doesn’t have diabetes. But maybe because we’re twins, Jackie is very knowledgeable about diabetes and stays informed regarding new management techniques and research. She always says if she were ever diagnosed, she wouldn’t be overly concerned because she knows exactly what to do and how to do it… meaning she would be right on a CGM and pump. The other thing Jackie has said since she was a child is that if she could, she ‘would take my diabetes for me.’ That really is very much a ‘twin thing.'”

Twin Type 2s

Meanwhile, diabetes twin research isn’t limited just to those of us with type 1. Swedish researchers recently published the results of a study that followed over 4,000 pairs of twins over a six-year period starting in 1998. They selected identical twins with different BMIs to try to understand the effect of increased weight on health. At the study’s end they announced that they had confirmed one long-held belief about weight and health, and made one confounding discovery.

Not too surprisingly, they say, the heavier twins had increased risk of type 2 diabetes, but the lighter twin actually had a higher risk of heart attack, overturning the long-held belief that weight is an independent heart attack risk.

But is type 2 really as simple as the right genes plus weight? Maybe not.

A smaller study (also from Sweden) suggests that T2D isn’t that simple after all. The study looked at 14 sets of twins, in which one in each pair had type 2 diabetes and the other did not, focused on the genes. It found there were differences in the genes that control fat and glucose metabolism between the twin with type 2 diabetes and the sugar-normal twin.

Not Clones, After All

It may turn out that the subtle differences between “identical” twins will be more valuable to our understanding of both types of diabetes than if identical twins were truly identical. While the early differences between “identical” twins may prove over time to weaken the environmental origins theories behind the cause of diabetes, modern twin studies looking at subtle differences between the genetic blueprints of similar people might allow us to determine the role that genes play in the development of diabetes.

For example, take the diabetes research that the Divone Sisters have been a part of.

In 2012, Stacey and her twin signed up for the groundbreaking diabetes genetic project Trialnet to get a better understanding of their “identical,” yet not identical DNA.

“The test results confirmed what we already knew: my sister and I are identical twins,” Stacey shares. “We were also tested for a number of auto-antibodies for things like type 1 diabetes, celiac disease and Addison’s disease. My m1AA auto antibody level was way elevated, obviously since I have type 1. Everything else for me was at normal levels, thankfully. My sister showed normal levels for everything, including type 1.”

Like the majority of “identical” twins, Stacey’s sister was just different enough from Stacey, genetically, to duck the diabetes bullet. Even though their dad had lived with type 1, only one of the sisters have followed in those pancreatically-challenged footsteps.

“This was such a relief, I’m sure to both of us, but for me especially,” says Stacey, who blogs over at The Girl With The Portable Pancreas. “Even though I’ve lived with it for 35 years, I never would want to see her have to live with it, too.” 

I guess twins don’t really share everything after all. Which is heartening, in some ways…