Why don’t these wounds close? Blame a perfect storm of diabetic complications, such as reduced blood flow, neuropathy and impaired signaling between cells. According to research by Denisa Wagner, PhD, of Boston Children’s Hospital’s Program in Cellular and Molecular Medicine, a poorly understood feature of our immune system’s neutrophils may be one more ingredient in the storm.
About half of people with diabetes develop peripheral neuropathy. The most common form, small-fiber neuropathy, generally starts in the feet, causing pain, odd sensations like pricks and “pins and needles,” and—the most worrisome feature—a loss of sensation that can increase the chance of ulcers and infections.
In some cases, that may lead to the need for amputation—as happened with my diabetic great-grandfather whose numbed feet, unbeknownst to him, got too close to the fire.
While there are some treatments to reduce pain, there’s nothing that restores sensation. Nor do any existing treatments address the underlying cause of the neuropathy: the degeneration or dysfunction of the endings of the sensory neurons in the skin.
In parts of the developing world, especially remote, rural areas, it’s not unusual for people with diabetes to ignore their symptoms until they’ve collapsed and need immediate care. By the time they see a doctor, their blood sugar levels might be so high as to cause diabetic ketoacidosis (DKA), where the body starts breaking down fats and proteins, turning their blood acidic and leaving them extremely dehydrated.
For many, it won’t be the first such episode. But for some, it can be the last.
Stories like this are increasingly common across large swaths of the developing world—as Diane Stafford, MD, an endocrinologist from Boston Children’s Hospital, discovered when she traveled to Kigali, Rwanda, through the Human Resources for Health program.
Research shows that gastric bypass surgery, aside from inducing weight loss, resolves type 2 diabetes. Though weight loss and improved diabetes often go hand-in-hand, patients who undergo gastric bypass usually end up seeing an improvement in their type 2 diabetes even before they lose weight.
But why? To investigate, a research team led by Nicholas Stylopoulos, MD, of Boston Children’s Hospital’s Division of Endocrinology, spent a year studying rats and observed that after gastric bypass surgery, the way in which the small intestine processes glucose changes. They saw the intestine using and disposing of glucose, and showed that it thereby regulates blood glucose levels in the rest of the body, helping to resolve type 2 diabetes.
Basically, as the team reported recently in Science, the small intestine—widely believed to be a passive organ—is actually a major contributor to the body’s metabolism.
For decades, patients have managed their type 1 diabetes by injecting themselves with insulin to regulate the glucose in their blood. While this form of medical management addresses the immediate danger of low insulin levels, long-term complications associated with diabetes, like heart and kidney diseases, still threaten more than 215,000 children currently living with the disease in the United States.
“Insulin injections can manage hyperglycemia by reducing the patient’s glucose levels, but it is not the cure,” says Paolo Fiorina, MD, PhD, of the Nephrology Division at Boston Children’s Hospital.
Fiorina is currently involved in new research targeting a molecular pathway that triggers diabetes in the first place—potentially providing a permanent cure. It could potentially change the face of diabetes treatment in children.
We humans are sharing creatures. We talk about ourselves, what we think, what we know. If we weren’t like this, cocktail parties would be really boring, and Facebook and Twitter wouldn’t exist.
Nor would health care. At the most basic level, health care relies on give-and-take between patients and doctors—patients sharing their symptoms and concerns with doctors, and doctors sharing their knowledge with patients.
The same holds true for public health. Prevention and control efforts require lots of patients and doctors to share information so that public health agencies know where to target their resources.
But the give-and-take in public health is often slow and cannot always detect conditions or complications at rates that reflect reality. And usually it’s one-way—from the patient or public to surveyors.
When children return home from the hospital after surgery, parents can be overwhelmed by the written information and instructions for follow-up. At the MIT Media Lab’s Health and Wellness Hackathon earlier this year, the focus was on empowering patients to take an active role in their health. As my colleague Brian Rosman described, our team from Boston Children’s Hospital attended and spent two weeks developing “Ralph,” a mobile application for managing post-operative care that incorporates an avatar and features of gaming to engage and motivate children to follow their regimen. I was one of the primary programmers for our group.
We won third place, working alongside five other talented teams. Here are some snapshots of what they were up to — helping patients manage asthma, diabetes, pain, cardiac rehab and more.
Recent research on Type 1 diabetes has begun focusing on prevention: Studies indicate that children start developing diabetes-related autoantibodies sometimes years before they develop clinical diabetes requiring insulin shots. The autoantibodies are an indicator of insulitis – a precursor condition in which the insulin-producing islets in the pancreas become inflamed and infiltrated with white blood cells.
In animal models, immune-suppressing drugs have been shown to blunt this attack by curbing the number of white blood cells circulating in the body. That reduces the need for insulin treatment – but at a high cost: Given systemically, the high doses needed to suppress the immune attack cause kidney toxicity, reduce the ability to fight infections, and decrease the body’s ability to respond to insulin.
People who rely on protein-based drugs often have to endure IV hookups or frequent injections, sometimes several times a week. And protein drugs – like Factor VIII and Factor IX for patients with hemophilia, alpha interferon for hepatitis C, interferon beta for multiple sclerosis — are very expensive.
What if they could be made by people’s own bodies?
Combining tissue engineering with gene therapy, researchers at Children’s Hospital Boston showed that it’s possible to get blood vessels, made from genetically engineered cells, to secrete drugs on demand directly into the bloodstream. They proved the concept recently in the journal Blood, reversing anemia in mice with engineered vessels secreting erythropoietin (EPO).
This technology could potentially deliver other protein drugs,
While it’s not yet clear what this means for patients with either disease, the findings help untangle some very perplexing data about human genetics and diabetes risk, and could change doctors’ thinking about the treatment of both conditions down the road.
Scientists have long known that cancerous and healthy cells don’t use sugar in the same ways.