Objective
The objective of this research is to determine how much reducing high levels of insulin in the blood will improve insulin resistance and blood vessel disease in type 1 diabetes. We will study research participants with type 1 diabetes in two different situations. In one situation, we will measure their insulin resistance and blood vessel health when they are consuming a normal diet and taking the typical amount of insulin each day. In a second situation, we will measure their insulin resistance and blood vessel health when they are consuming a diet lower in carbohydrates. Because patients with type 1 diabetes take less insulin when they consume less carbohydrates, we will see how much taking less insulin improves insulin resistance and blood vessel health.
Background Rationale
Heart disease is the leading cause of death in type 1 diabetes. Despite numerous advancements to improve high blood sugar over the past quarter-century, heart disease continues to cause premature mortality in this condition. Among present-day adolescents with type 1 diabetes, experts estimate the loss in life expectancy is 11 years for males and 13 years for females. The largest contributor to this loss of life expectancy is heart disease. Even patients being treated with the most modern therapy who have blood sugar levels at target still have a 3-fold increased risk for death from a heart attack. The disease process that leads to heart disease begins from a very early point after diagnosis. This research will investigate the early mechanisms that lead to heart disease in type 1 diabetes.
Description of Project
A major focus clinical care in type 1 diabetes centers around injecting insulin to keep blood sugar levels near normal. Maintaining blood sugar numbers close to target is important to prevent long-term consequences of diabetes, including blindness, kidney disease, and limb amputation. Unfortunately, patients whose glucose numbers are at target still have a 3-fold higher risk of serious heart disease compared to individuals who do not have type 1 diabetes. One possible reason for this a condition called insulin resistance, which is consistently found in type 1 diabetes. Insulin resistance is a condition where the body does not use insulin as effectively as it should. Insulin resistance is important because it is closely associated with abnormalities in the blood vessels of the heart. These problems with the blood vessels in the heart often lead to heart attacks, which is the leading cause of death in type 1 diabetes.
This research will help to understand why insulin resistance and blood vessel disease occur in type 1 diabetes, even when blood sugar levels are at target. Our earlier research suggested that high levels of insulin in the blood contribute to insulin resistance in this condition. These high levels of insulin are caused by the need for patients to inject insulin under the skin. After these injections, the body directly absorbs the insulin into the blood stream. Injecting insulin directly into the blood leads to higher insulin levels than would be seen if the same person did not have type 1 diabetes. This research will determine how much lowering these high insulin levels will improve insulin resistance and blood vessel disease in people with type 1 diabetes.
Anticipated Outcome
We anticipate that patients will take 25% less insulin when they are consuming less carbohydrates compared to when they are eating the normal amount of carbohydrates. We further anticipate that this reduction in insulin will be closely related to an improvement in insulin resistance and blood vessel health.
Relevance to T1D
For the first time, this research will show how much lowering the amount of insulin a patient needs to take for their diabetes will improve insulin resistance and blood vessel health. This research has the potential to inform the design of the next generation of insulin analogs and closed loop insulin pumps. Ultimately, it will provide new insight into the metabolic processes that lead to heart disease in type 1 diabetes.