Scientists have proposed a new therapy for type 2 diabetes. If proven effective, the therapy could help some people discontinue insulin treatment.
Scientists have proposed a new therapy for the treatment of type 2 diabetes, with a proof-of-concept study showing positive initial results. If effective, the therapy may mean that some people can stop taking insulin treatment.
The authors of the research presented their findings at UEG Week Virtual 2020, a conference organized by United European Gastroenterology, a professional nonprofit organization for specialists in digestive health.
Type 2 diabetes
According to the National Institute of Diabetes and Digestive and Kidney Diseases, a person may have type 2 diabetes when their blood sugar is too high.
People gain blood sugar, or blood glucose, mainly from the food they eat. Insulin helps cells access this glucose to use as energy. However, for a person with type 2 diabetes, either their body does not make enough insulin or their cells do not respond to insulin correctly.
This then means that the glucose in their blood increases, which can lead to complications of diabetes, such as heart and kidney disease, visual impairment, and loss of sensation in the limbs. The higher the blood glucose over time, the higher the risk of these complications.
According to the Centers for Disease Control and Prevention (CDC), about 1 in 10 adults in the United States have diabetes, and 90–95% of these individuals have type 2 diabetes.
Doctors typically recommend lifestyle changes, such as being more physically active and eating a more healthful diet, to treat type 2 diabetes, as well as medications to manage a person’s blood pressure and blood glucose levels.
Insulin treatment may be necessary if a person is unable to maintain their blood sugar at normal levels. This treatment can take the form of injections, pens, pumps, or inhalers. It encourages the cells in a person’s body to absorb more blood sugar.
However, people’s perception of the side effects of insulin treatment can be quite pronounced. As a result, doctors may be less likely to prescribe insulin, and, when they do, people may not take it regularly.
Consequently, therapies that can avoid these perceived side effects may be valuable in ensuring that people keep up with their prescribed treatment and avoid risking serious health issues.
Proof of concept
In this context, the researchers behind the present study used a novel technique that scientists first reported using in humans in 2016. Based on those preliminary results, it seemed promising.
The technique is called duodenal mucosal resurfacing (DMR). The duodenum is the first part of a person’s small intestine. DMR involves lifting the mucosal layer of the duodenal to allow the ablation of the revealed area using heated water — a process that removes the cells in the targeted area.
The researchers who developed the DMR technique were trying to replicate the positive impact that bariatric surgery (gastric bypass) has on blood sugar levels with a less invasive technique.
Studies of how bariatric surgery improves blood sugar control have concluded that there is a direct effect from the duodenum in addition to the weight loss that results from bariatric surgery.
DMR can take place in an outpatient setting and is minimally invasive. It involves an endoscope catheter to gain access to the duodenal.
The direct effect of the small intestine on glucose control appears to come from the presence of intraepithelial lymphocyte T cells. These are nestled between the gut cells involved in the absorption of nutrients from food.
Mice without these cells are protected from obesity and heart disease, even when eating a high fat diet.
These intraepithelial lymphocytes reduce the amount of a gut hormone called GLP-1. Therefore, in the current study, the researchers added regular doses of a GLP-1 agonist called liraglutide on day 14.
They did so to counteract the reduced amount of this essential lean, antidiabetic hormone. The study participants also received lifestyle counseling to help reduce their blood sugar levels.
The study involved 16 participants with type 2 diabetes receiving insulin treatment. Of the participants who received the DMR therapy with liraglutide, 12 (75%) were able to stop using insulin and maintain their blood sugar control after 6 months.
Promising initial results
The study participants also saw a variety of benefits to their metabolism.
The participants’ HbA1c readings, which determine a person’s glucose control, had all reduced to below 7.5%. After 12 months, this fell further to 6.7%.
Those who responded to the treatment saw a reduction in their body mass index from an average of 29.8 kilograms per square meter (kg/m2) before the study started to 25.5 kg/m2 12 months after the study. Fat in the participants’ livers reduced from 8.1% to 4.6% after 6 months.
Even for the participants who still needed insulin, the required amount reduced from an average of 35 units per day to 17 units per day after 12 months.
According to Dr. Suzanne Meiring, a researcher at the Amsterdam University Medical Center, the Netherlands, and co-lead of the study,
“A single endoscopic DMR ablation with GLP-1 drugs and lifestyle counseling can lead to discontinuation of insulin therapy in a subset of patients with type 2 diabetes while improving their blood glucose control and overall metabolic health.”
“Many patients with type 2 diabetes are very happy to be able to discontinue insulin therapy, since insulin therapy comes with weight gain and hypoglycemic events.”
Further research needed
It is important to note that this is a very small proof-of-concept study. The researchers presented it as a conference paper, and, therefore, few details are available in the public domain for scrutiny.
The intervention combined two innovative treatments. No details of any side effects of the two treatments (DMR and GLP-1 agonist) are available. While promising, there is a need for larger trials to confirm the results.
Importantly, precisely how and why the therapy appears to work is not yet clear.
The scientists believe that it may work because the mucosal cells that the DMR therapy affects undergo changes in response to unhealthful diets that can promote insulin resistance.
“Based on the results of this study, a large international randomized controlled trial, called Revita T2Di Pivotal, will soon start to further investigate its effectiveness in greater numbers,” says Dr. Meiring.