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HeConnection-CureFor the first time, scientists at the Toronto General Hospital Research Institute have shown that an experimental bariatric surgery can lower blood sugar levels in rats with type 1 diabetes.

A team led by Dr. Tony Lam and Dr. Danna Breen, a post- doctoral fellow in the lab of Dr. Lam, used a rat model to study novel nutrient-sensing signals in the jejunum, located in the middle of the intestine. Dr. Lam and his team demonstrate that duodenal-jejunal bypass surgery activates novel nutrient-sensing signals in the jejunum and rapidly lowers blood sugar levels in non-obese rats with uncontrolled diabetes. DJB surgery is a type of bariatric surgery which excludes the duodenum and proximal jejunum, the first section of the small intestine, and instead redirects food into the distal jejunum, the middle to last section of the intestine. This latter section of the intestine, as demonstrated by Dr. Lam and his team, can sense glucose and signal to the brain to let the liver know that it must lower glucose production, leading to better control of blood sugar in the diabetic rats.

The study showed for the first time that a surgical intervention induces a rapid glucose-lowering effect in non-obese type 1 uncontrolled diabetic rats, independent of a reduction in food intake and body weight as well as changes in blood insulin levels.

“We report that shortly after a meal, the influx of nutrients into the jejunum of DJB surgical diabetic rats activates novel sensing mechanisms to lower blood sugar levels. Importantly, this occurs in the presence of insulin-deficiency and is independent of weight loss,” says Dr. Lam, who holds The John Kitson McIvor (1915 — 1942) Endowed Chair in Diabetes Research and the Canada Research Chair in Obesity at the Toronto General Research Institute and the University of Toronto. He is also Associate Director of Research at the Banting and Best Diabetes Centre at the University of Toronto.

Currently, patients with Type 1 diabetes lower their glucose through insulin injections (usually several times a day) and must regularly monitor blood glucose levels. High or uncontrolled glucose levels (hyperglycemia) can result in damage to eyes, nerves and kidneys and increase the risk of heart attack, stroke, blindness, erectile dysfunction, foot problems and amputations. Many laboratories around the world are in a race to find alternative and effective ways in which to lower and better control glucose levels because of the severe complications which can result from high sugar levels.

Dr. Lam’s laboratory is a world pioneer in exploring the role of the gut in regulating blood sugar. “The gut is an easier and therefore more promising therapeutic target in regulating blood sugar than the brain or liver, due to their potential side effects,” says Dr. Danna Breen, who is the lead author in the study. Dr. Breen adds that this type of surgery may potentially have therapeutic value in lowering glucose (sugar) levels in non-obese individuals with type 2 or 1 diabetes, but that many more years of future studies are required to determine whether this approach is effective and safe in humans who have diabetes.

In healthy individuals, insulin is a hormone whose primary role is to regulate blood sugar. It is produced by cells located on the pancreas in response to sugar intake, and it acts to bring blood sugar to appropriate levels, allowing the body to have the energy it needs to function properly. In persons with type 1 diabetes, the pancreas does not produce insulin, resulting in elevated blood sugar levels due to lack of insulin which cannot signal to the liver to reduce sugar production. People with type 1 diabetes need to take daily insulin shots and carefully monitor their blood sugar levels.

“If new medicines or surgical interventions can be developed that stimulate this sensing mechanism in the gut, we may have an effective and alternative way of slowing down the body’s production of sugar, thereby lowering blood sugar levels in diabetes,” says Dr. Lam.

Studies reported in the New England Journal of Medicine this year have challenged medical therapy as the prevailing method of treating patients with type 2 diabetes. Two studies reported that bariatric surgery induced remission in severely obese patients with type 2 diabetes, and was associated with significant improvement in metabolic control over and above medical therapy, both conventional and intensive.

Working with rats, Drs. Lam, Breen and colleagues designed and performed a series of elegant experiments on two different groups of rats: rats whose insulin-producing pancreatic islet cells were destroyed by toxins; and genetically-altered rats which experienced spontaneous autoimmune destruction of islet cells — similar to what happens in humans with type 1 diabetes.

Non-obese rats induced with uncontrolled diabetes or autoimmune type 1 diabetes had an experimental DJB surgery, a variation of the Roux-en-Y gastric bypass, the most common surgical method currently used to treat obese patients. Two days after DJB surgery, blood sugars were normal in the insulin-deficient diabetic rats.

Health-e-Solutions comment: The most important thing in this study, in my opinion, is to see the clear and compelling link between the gut and blood glucose metabolism. We are convinced that the gut is vital in the control of type 1 and type 2 diabetes, and therefore it is vital to manage the types of food we eat. It is also becoming increasingly clear that the health of our gut microbiome is critically important to our whole body health.

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