A Downhill Battle: Maintaining Healthy Bones in Diabetes

A study from ENDO 2019 shows that postmenopausal women with diabetes can form new bone with walking after a meal either uphill or downhill, despite the poor bone quality associated with diabetes and a lack of the estrogen needed to prompt bone formation.

Diabetes remains one of the biggest global health problems and is the sixth leading cause of death. In the U.S., according to the American Diabetes Association and the Centers for Disease Control and Prevention, the number of diabetes diagnoses has more than doubled during the last two decades, as the population has aged and become overweight or obese. That’s more than 30 million people, and a quarter of them are not aware that they have the disease. Another 84 million have prediabetes, with 90% of those people unaware of their status.

An unusual new study presented at ENDO 2019 examines this perplexing condition, specifically how postmenopausal women with diabetes can boost their bone health by doing one simple thing: Walking downhill after meals!

In this study, Katarina T. Borer, PhD, of the University of Michigan in Ann Arbor, and team looked at aspects of exercise like timing of meals and amount of mechanical loading in women with diabetes and their effects on bone remodeling. Knowing from previous studies that downhill walking is a better bone-loading exercise than uphill walking, even though uphill walking requires greater exertion from a cardiovascular point of view, Borer decided to test that phenomenon in 15 postmenopausal women with diabetes.

“When you walk uphill, even though it seems like more effort, you aren’t loading your bones, because gravity is pulling you down and you are walking up. As far as timing of meals and exercise goes, I’m very convinced that timing is very important for many things.” – Katarina T. Borer, PhD, University of Michigan, Ann Arbor, Michigan

“Basically, downhill walking loads the feet much more than uphill walking.” Borer explains. “When you walk downhill, you add your force, the effort of going down to the gravity. When you walk uphill, even though it seems like more effort, you aren’t loading your bones, because gravity is pulling you down and you are walking up. As far as timing of meals and exercise goes, I’m very convinced that timing is very important for many things.”

Fueling Up

The reason Borer chose diabetic women to study is because of the inherently poor quality of their bone. Increased bone mineral density (BMD) is seen in people who have increased body mass index to support the heavier weight, which is typically good for preservation of the bone and protection against fracture. Although there is a close correlation between overweight/obesity and diabetes, so we would expect patients with diabetes to also have stronger bones, that’s not the case.

“Even though women with diabetes are usually heavy and often have normal BMD, they break their bones more readily, so there’s something wrong with the quality of their bones,” Borer says. “That was the idea that guided me to say, ‘okay, I know that mechanical loading is very important in healthy women, so let’s look at diabetic women who have altered quality of bone’.” Their postmenopausal status also negatively affects their BMD due to the absence of estrogen.

For the five-trial experiment, two groups of women spent 40 minutes exercising on either an uphill or downhill treadmill (with a 6º slope uphill or downhill), either within an hour before or an hour after eating each of two daily meals. Researchers measured foot loading with specialized mechanosensitive insoles. They also measured participants’ glucose and insulin levels hourly to look for markers of bone formation and resorption in the blood. “The question I ultimately had,” Borer says, “was, ‘does the bone respond, despite diabetic bone abnormalities and lack of estrogen?’ Because with aging you mostly resorb your bone, and diabetes reduces bone quality. There’s less evidence that you can form bone as you grow older.”

To back up for a moment, similar experiments have been conducted on women without diabetes, including by Borer and team, from which researchers gleaned some important information about timing. Downhill walking or running showed positive effects on bone shortly after eating but not before eating.

“The simple concept is that when you eat, you absorb sugar and amino acids and fats and so on, so if you exercise shortly afterward, your muscles — and in this particular case — your bones will have regularly available circulating nutrients,” Borer explains. “But if you do the reverse, exercising before eating, then you have to mobilize stored fuels, and that is a different ball game — the fuels are not readily available. What’s interesting about bone is that it responds to loading only very briefly, then it goes into a refractory period for about six to eight hours, where you can exercise yourself until you’re blue in the face, but nothing happens regarding bone’s sensitivity to loading.”

Turning On Bone Growth

Her findings with the cohort of postmenopausal women with diabetes offer a lot of hope. “In my study, the women exercising within an hour of eating had the best outcome, which is an increase in the marker of bone formation, but if they exercised on an empty stomach, it didn’t do anything — it was the same as if they were sedentary,” Borer says. “And these were diabetic women, with multiple bone quality issues.”

Although how diabetes impairs bone quality is not completely understood, it is hypothesized that the free radicals and inflammation associated with diabetes impair bone formation in some way. Another is that due to insulin resistance in diabetes, insulin cannot move sugar into muscles and possibly into bones as efficiently as in healthy people. In the absence of nutrients, the bone deteriorates.

Despite these hurdles, researchers found significant increase in the markers of type 1 procollagen, which is the substrate for bone. “It was really very surprising,” she says, “that diabetic women who have two obstacles (postmenopausal without estrogen and poor bone quality) responded with a very nice peak of bone formation when exercising effectively — loading their bones efficiently — after eating.”

“Women exercising within an hour of eating had the best outcome, which is an increase in the marker of bone formation, but if they exercised on an empty stomach, it didn’t do anything — it was the same as if they were sedentary. And these were diabetic women, with multiple bone quality issues.” – Katarina T. Borer, PhD, University of Michigan, Ann Arbor, Michigan

Parenthetically, this peak was not seen after the second meal and exercise episode, due to the extended bone refractory period. Interestingly, though, with uphill exercise, a peak was seen after the second episode but not the first for reasons that are unclear.

This is potentially very good news. Borer agrees: “Most osteoporosis drugs on the market protect only against bone resorption. The assumption behind pharmacological development is that bone in older people cannot grow,” she says. “My study shows that it can; it’s just that you have to know how to turn it on.”

Her team hopes to undertake a longer-term study of at least eight months to measure bone formation more directly.

—Horvath is a freelance writer based in Baltimore, Md. She wrote about new obesity research from ENDO 2019 in the October issue.