Diabetes Forecast November 2005

---

FOR TYPE 1

Research Profile

Weak Bones & Type 1:
What's The Connection?
by Terri Kordella

Mari Palta, PhD, hopes to discover exactly how type 1 diabetes contributes to weak bones.	Mari Palta, PhD Occupation Professor of Population Health Sciences, Biostatistics, and Medical Informatics, The University of Wisconsin Professional Focus Epidemiology Outside Interests Gardening, travel, studying and translating foreign languages Research Funding ADA Clinical Research Award

When you think of the complications of diabetes, chances are you think of your heart, eyes, feet, nerves, and kidneys. But type 1 diabetes can affect your bones, too.

For reasons still unknown to science, low bone mineral density is more common in people with type 1 diabetes than in the general population. This translates into a higher risk of fractures and breaks. In fact, people with diabetes have about twice the risk of hip fractures as people who don't have diabetes. The risk is even higher if you are a woman. Women generally have a higher risk than men because women are more likely to develop osteoporosis, a disease characterized by porous bones. But women with diabetes have 7 to 12 times the risk of hip fractures as women who don't have diabetes.

"We don't know exactly what it is about diabetes that causes weak bones," says Mari Palta, PhD, professor of population health sciences, biostatistics, and medical informatics at the University of Wisconsin. "Is it diabetes itself, or, more precisely, poorly controlled diabetes?"

With funding from an American Diabetes Association Clinical Research Award, Palta and her project director and doctoral student, Kirstie Danielson, hope to find out.

Is It In The Blood?

Palta's team will study 100 women between the ages of 18 and 45 who have type 1 and a matched group of their sisters and cousins who don't have diabetes. The women with diabetes are part of the Wisconsin Diabetes Registry Project, an ongoing study of complications in 500 people with type 1. The Registry began in 1987, so the study already has a wealth of information about the women with diabetes, including how well their diabetes is controlled.

"We're going to compare women with diabetes to women without diabetes, but we're also going to compare women with diabetes to each other. We'll compare those with good control to those with poor control," says Palta.

The study design is relatively simple. The participants will visit one of three study centers in Wisconsin for a brief physical, where they will undergo bone density measurements in their heels and wrists and have blood drawn.

Chances are, low bone density will be more common among the women who have diabetes than in their non-diabetic sisters and cousins. But will low bone density also be more common in women with poorly controlled diabetes than in women with well-controlled diabetes? If so, that could indicate a link between high blood glucose and low bone density.

To delve more deeply into the possible link, the researchers will also look for other differences among the participants' blood samples. They are specifically interested in participants' blood levels of vitamin D and a substance called insulin-like growth factor 1 (IGF-1).

"Vitamin D is important in the formation of strong bones," says Palta. "How does diabetes affect vitamin D? Does blood glucose control affect vitamin D? If so, high blood glucose could be interfering with vitamin D in bone formation."

IGF-1 is a growth factor that's "built" a lot like insulin (hence the name insulin-like growth factor). Growth factors stimulate cells to grow and divide, and different growth factors affect different kinds of cells throughout the body. IGF-1 interacts with most cells in the body, but it affects cells in the organs, nerves, skin, cartilage, and bone in particular.

"The more IGF-1 someone has, the higher their bone mineral density," says Danielson. "People with diabetes have low levels of IGF-1, and they often have low bone density." Therefore, low IGF-1 levels related to diabetes may also contribute to low bone density.

"Once we understand the mechanism [of how diabetes affects bone density], it might be possible to come up with a treatment or way of prevention," she adds.