12:47am Saturday 29 February 2020

Hormone involved in normal digestion may be heart-protective in Type 2 diabetes, SickKids research shows

Cardiovascular disease is the cause of death in up to 80 per cent of people with diabetes.High levels of the blood fats triglyceride and cholesterol are common in diabetics and contribute to higher cardiovascular risk.

GLP-1 is a hormone normally found in the intestine that aids digestion and supports the optimal balance of blood sugar and insulin levels in the body. A research team led by Dr. Khosrow Adeli at The Hospital for Sick Children (SickKids) analyzed the effects of giving rodents with Type 2 diabetes additional amounts of the hormone.

The study found that when the rodents were given additional GLP-1 over a prolonged period, the animals’ lipid (triglyceride) levels decreased significantly, potentially lowering their risk of cardiovascular disease.

Lowering high lipid levels

This positive finding opens the door for more research on GLP-1’s potential to help manage blood lipids in individuals with Type 2 diabetes, says Adeli.  He is Head, Clinical Biochemistry in SickKids’ Paediatric Laboratory Medicine and SickKids Senior Scientist as well as Professor of Laboratory Medicine & Pathobiology and Biochemistry at the University of Toronto’s Faculty of Medicine and a senior scientist at the Banting and Best Diabetes Centre.“If a clinical trial of human blood lipids in diabetes supports the results of our rodent study, the role of GLP-1 could be extended for some Type 2 diabetes patients,” he says.

People who have diabetes face the daily, even hourly challenge of monitoring their blood sugar and insulin levels through dynamic conditions of eating and activity. “When measuring glucose is so front-of-mind, monitoring of triglyceride and cholesterol blood levels is not always a priority for patients or clinicians,” Adeli adds.  “But monitoring and potentially treating high blood lipid levels is a critical long-term aspect of diabetes care.”

Timing is everything

The SickKids study compared lipid levels in rodents who received additional GLP-1 and its sister hormone GLP-2 over 30 minutes versus 120 minutes. Prolonged treatment led to significantly lower blood lipids.

Treatment of Type 2 diabetes sometimes includes medications such as sitagliptin, which prolongs the action of GLP-1 during digestion. It works by inhibiting the enzyme that normally deactivates GLP-1, in turn extending the time that the hormone remains active. Sitagliptin treatment tipped the balance in favor of GLP-1, with marked reductions in blood fats.

“Further research could show whether or not sitagliptin plays an enhanced role in lowering high blood lipids in Type 2 diabetes, prediabetes or metabolic syndrome, and Type 1 or insulin-dependent diabetes,” he says. “This is an important avenue for human research because the rate of death from cardiovascular disease is high among people with diabetes.”

Diabetes: About 90-95 per cent of the diabetes that is diagnosed in approximately 200,000 Canadians a year is Type 2 diabetes, which is usually, but not always, linked with overweight or obesity. Increasingly, Type 2 diabetes is diagnosed among teens and children. In 2011, almost 1.8 million Canadians had diabetes; up to 3.8 million could have diabetes by 2018/19.*

The study was funded by SickKids Foundation and Canadian Institutes for Health Research.

*Public Health Agency of Canada

The intestinal hormone GLP-1

  • Eating triggers the intestine to release the hormone GLP-1 and its sister hormone, GLP-2
  • GLP-1 triggers insulin production while slowing down glucose production during and after eating (the post-prandial state, as opposed to the fasting state)
  • GLP-1 also limits the release of lipids into the blood stream
  • GLP-2 has the paradoxical or opposite effect of stimulating triglyceride production
  • This study in an animal model shows that extending the activity of GLP-1 in the intestine promotes the positive lipid-lowering effect of GLP-1
  • These findings must be confirmed with additional research in humans. Human studies are underway at University Health Network by Dr. Adeli’s collaborator Dr. Gary F. Lewis and his laboratory

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