A collagen formulation mixed with pancreatic cells is the first minimally invasive therapy to successfully reverse type 1 diabetes within 24 hours and maintain insulin independence for at least 90 days, a pre-clinical animal study shows.

The findings suggest that people and dogs with type 1 diabetes could eventually replace daily insulin injections or wearable pumps with a shot every few months.

For diabetic pets, the next step is a pilot clinical study in dogs with naturally occurring type 1 diabetes.

“We plan to account for differences from mouse to human by helping dogs first. This way, the dogs can inform us on how well the treatment might work in humans,” says Clarissa Hernandez Stephens, first author of the work and a graduate researcher in Purdue University’s Weldon School of Biomedical Engineering. Findings appear in the American Journal of Physiology – Endocrinology and Metabolism.

‘No time off’ from diabetes

“With giving my dog shots twice a day, I have to constantly be thinking about where I am and when I need to be home. It greatly affects my work and my personal life,” says Jan Goetz, owner of a diabetic dog named Lexi. “Not having to give these shots would mean freedom.”

Type 1 diabetes affects about one in every 100 companion animals in the US, including dogs and cats, and approximately 1.25 million American children and adults.

David Taylor of Indiana has struggled with type 1 diabetes for almost 50 years.

“A type 1 diabetes diagnosis was my 18th birthday present, and since that first insulin injection, managing diabetes has been my ‘other’ full time job,” Taylor says. “Treatment methods have improved enormously over 50 years, but they still permit no time off for the patient. Receiving an injection every few months would restore the near-normal life to me that I haven’t had as an adult—and I could retire from that full-time diabetes management job.”

Because diabetes in dogs happens similarly in humans, treatment has so far been largely the same: Both need glucose monitoring throughout the day and insulin after meals.

This also means that dogs and humans could potentially benefit from the same cure: A new set of pancreatic cells to replace the clusters of cells, called islets, that aren’t releasing insulin to monitor blood glucose levels.

Still, 20 years of research and clinical trials hasn’t produced an effective islet transplantation therapy because it requires multiple donors; the current method of delivering islets through the portal vein of the liver is too invasive; and the human immune system tends to destroy a large percentage of transplanted islets.

New packaging for islets

The researchers simply changed the islets’ packaging—first, within a solution containing collagen, and second, as an injection through the skin instead of all the way at the liver, saving patients from a nasty procedure.

“Traditionally, we transplant islets in the liver of the animal and never do it under the skin, in large part because the skin doesn’t have the blood flow that the liver has for transporting insulin released by islets. And there are a lot of immune cells in the skin, so chances of rejection are high,” says Raghu Mirmira, professor of pediatrics and medicine and director of the Diabetes Research Center at the Indiana University School of Medicine.

The team removed the need for transplanting in the liver by thoroughly mixing mouse islets, which Mirmira’s lab provided, with the collagen solution. Upon injection just under the skin, the solution solidifies, the body recognizes the collagen, and supplies it with blood flow to exchange insulin and glucose.

“It’s minimally invasive; you don’t have to go to the operating room and have this infusion into the portal vein. It’s as easy as it comes, just like getting a shot,” says Sherry Voytik Harbin, professor of biomedical engineering and basic medical sciences at Purdue.

The researchers tested the effects of the solution between mouse twins and non-twins to check for discrepancies. Initial studies showed if the mouse donor were a twin to the recipient, the diabetic mouse could go at least 90 days without needing another shot. If not twins, the mouse would have normal blood sugar levels for at least 40 days. Nearly all transplanted islets survived either scenario, removing the need for multiple donors to compensate for those killed off by the immune system.

From mice to dogs

As they transition to testing the formulation in naturally diabetic dogs, the researchers will explore the feasibility of transplanting pig islets or stem cells programmed to produce insulin, in hopes that either method will further increase donor availability.

The islet transplantation therapy might also have implications for better treating severe pancreatitis.

Purdue and the Indiana University School of Medicine collaborated on this work through the National Institute of Health T32 Indiana Bioengineering Interdisciplinary Training for Diabetes Research Program.

The collagen formulation is a patented technology. Additional support for the work came from the National Science Foundation Graduate Research; the Indiana University School of Medicine Center for Diabetes and Metabolic Diseases Pilot and Feasibility Program; and the McKinley Family Foundation. The study utilized core services provided by the NIH to the Indiana University School of Medicine.

Source: Purdue University

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Insurance ‘churn’ poses serious risks for diabetes patients

One in four working-age adults with type 1 diabetes had at least one gap of at least 30 days in their private health insurance, within an average of a three-year period, according to a new study.

For a million American adults, living with type 1 diabetes means a constant need for insulin medication, blood sugar testing supplies, and specialized care, to keep them healthy and prevent a crisis that could end up in an emergency room, a hospital bed, or death.

“Type 1 diabetes requires intensive daily management, in order to simply remain alive…”

A temporary loss of coverage had a sizable impact on the patients’ use of health care once they got insurance again. After a gap of 30 days or more, adults with type 1 diabetes were five times more likely to end up in an emergency room, hospital, or urgent care center than in the period before the interruption.

Insurance gaps also increased patients’ rolling-average blood sugar levels, or HbA1c, measurements, indicating a lower level of control during the gap. Higher levels can increase the risk of long-term diabetes complications. Questionnaires showed those who had an insurance gap reported less satisfaction with their lives and worse health status. Overall, one-fourth of working age adults with type 1 diabetes in the United States indicated that their health was fair or poor.

The new study is the first to look at the impacts of health insurance “churn”—a term for moving in and out of different health insurance plans—on people with type 1 diabetes using data from private insurance companies.

“Type 1 diabetes requires intensive daily management, in order to simply remain alive, so interruptions to care and coverage of insulin and supplies can pose a major risk,” says Mary A. M. Rogers, a researcher at the University of Michigan Medical School who led the study. “While we expected gaps in coverage to affect health in some way, the size of the effect and the frequency of gaps were striking.”

Rogers notes that the changing nature of Americans’ work lives—with multiple jobs of shorter duration and rising “gig” employment based on short-term contracts instead of permanent jobs—makes the study especially timely.

In addition, the proportion of private employers offering health insurance has been declining; in 2016, only 45 percent of private-sector employers offered it.

Meanwhile, more working-age adults are living—and working—with chronic conditions which were diagnosed in their childhood. Years ago, such conditions might have been disabling or life-threatening but they now can be managed through improvements in medical care.

A recent study Rogers led estimates that 27,000 children and teens, and 37,000 working-age adults are newly diagnosed with type 1 diabetes each year in the United States. The exact causes of this autoimmune disease are not yet known and the disease has no cure.

The study used anonymous data from the Clinformatics Data Mart database from January 2001 to mid-2015, which the Institute for Healthcare Policy and Innovation at the university purchased. It focused on adults ages 19 to 64 who had type 1 diabetes. Of the 168,612 adults studied, 40,897 had at least one interruption in their health insurance coverage of 30 days or more.

The results of the study indicated that people in their 20s and 30s with type 1 diabetes were more likely than those in their 40s, 50s, and early 60s to experience a gap in coverage. In addition, those in the north central and southern part of the country were more likely to have a gap than those living in the northeast or west.

After an interruption in insurance, adults with type 1 diabetes used more acute care services—from an urgent care center, emergency room, ambulance or hospital. Their use of acute care services was four to seven times higher than in the time period before the interruption. After a gap of 31 to 60 days, adults with type 1 diabetes were 5.25 times more likely to use such services. After a gap of 91 to 120 days, they were 7.19 times as likely.

“These acute care services are costly, and largely preventable with regular self-care guided by a primary care physician or an endocrinologist—a specialist who treats patients with diabetes,” says Rogers, who is a research associate professor in the internal medicine department at the university. “While we did not examine direct costs, each emergency visit or hospitalization can easily cost thousands of dollars.”

Patients with type 1 diabetes also have to deal with the rising cost of insulin, which has more than tripled in the past two decades.

Cancer patients with insurance still face huge costs

Rogers notes that the availability of individual insurance plans and Medicaid expansion plans under the Affordable Care Act has broadened the kinds of insurance available to adults who do not receive insurance through their job.

“Our study provides evidence of fragmented care for adults with type 1 diabetes in the United States,” says Rogers. “Such gaps in health care have been noticed for people who go in and out of Medicaid coverage, but we report that it also occurs in adults who have private health insurance. We know that providing continuity of care is important for patients with diabetes and is associated with lower mortality.”

“This problem is not going away. If anything, fragmented care is likely to increase with projected trends. Yet access to medical care is essential for life for people with type 1 diabetes. Providing access to medical services for people with chronic conditions is a problem that America has not yet fully resolved,” Rogers concludes.

The study appears in Health Affairs.

Additional authors are also from the University of Michigan.

Source: University of Michigan

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