Investigation Into the Effects Upon Brain Response to Change in Cirucating Glose Levels in Diabetes Mellitus
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|ClinicalTrials.gov Identifier: NCT00580710|
Recruitment Status : Recruiting
First Posted : December 27, 2007
Last Update Posted : January 17, 2018
This study is designed to investigate the effects of diabetes mellitus and its treatment upon the body's responses to low blood glucose (blood sugar) levels. Diabetes is a medical condition in which blood glucose can rise very high. Treatment of diabetes mellitus involves giving insulin (a hormone), which can occasionally cause blood glucose to fall too low. The body responds to low glucose levels by producing a number of hormones, which act against the insulin to help correct the low blood glucose. These hormones also provide symptoms which warn that the glucose is falling too far. These protective warnings by the body may be different in people with diabetes. We want to test whether this also means that diabetes changes the sensitivity of brain function to a lowering of blood glucose levels. In order to answer this question, we need to compare the response of people with diabetes with the response of people who do not have diabetes.
The plan of the study is to lower the subject's blood glucose using insulin, while measuring what changes occur in brain function using what is called functional magnetic resonance imaging (fMRI).
|Condition or disease|
|Type 1 Diabetes Hypoglycemia|
Previous studies have shown that a person with type 1 diabetes is less likely to suffer the long term microvascular complications of diabetes (eye, kidney and nerve damage) if they strive to achieve as near normal a blood glucose as possible. Unfortunately the tighter the blood glucose control is, the more likely the subject is to suffer episodes of hypoglycemia. Hypoglycemia is often the aspect of diabetes management most feared by people with diabetes and may cause more anxiety than the threat of advanced complications.
For many people with diabetes the problem of hypoglycemia is compounded by the development of the syndrome of hypoglycemia unawareness. One aspect of hypoglycemia unawareness is impairment of the hormones normally released as blood glucose falls. Hypoglycemia triggers a release of such insulin antagonists as epinephrine, norepinephrine, glucagon, growth hormone and cortisol. These hormones act synergistically with the autonomic nervous system to raise blood glucose, counteracting insulin and restoring normoglycemia. These homeostatic mechanisms are also responsible for some of the early symptoms of low blood glucose, providing a warning to insulin-treated diabetics as glucose falls. A number of studies including research from this unit have established that strict metabolic control is associated with impairment of the normal counterregulatory response to hypoglycemia and a loss of hypoglycemia awareness.
The brain is central to the recognition of hypoglycemia and the coordination of the counterregulatory response. Neural tissue depends mainly on glucose for its energy supply. As circulating glucose falls beneath the level needed to maintain glucose transport across the blood-brain barrier, a variety of defense mechanisms are activated, including symptoms of cognitive dysfunction. However, the precise nature and causes of the adverse CNS effects of hypoglycemia are not well understood.
Functional magnetic resonance imaging (fMRI) provides a tool to measure the effects of hypoglycemia on the patterns and magnitudes of neuronal activation in the human brain, in both normal and diabetic subjects.
|Study Type :||Observational|
|Estimated Enrollment :||250 participants|
|Official Title:||Investigation Into the Effects Upon Brain Response to Change in Cirucating Glose Levels in Diabetes Mellitus|
|Study Start Date :||August 2001|
|Estimated Primary Completion Date :||August 2020|
|Estimated Study Completion Date :||August 2020|
conventionally treated, relatively poorly controlled patients with type 1 diabetes
intensively treated, well controlled patients with type 1 diabetes
age- and sex- matched non-diabetic, normal weight (BMI > or = 18.5 but < or = 25 kg/m2) control subjects
obese individuals defined as BMI > or = 30kg/m2
type 2 diabetics
Type 2 diabetics on diet only or diet and Metformin
type 1 diabetes unaware
Type 1 diabetics unaware of hypoglycemic symptoms
type 1 diabetes aware
Type 1 diabetics aware of hypoglycemic symptoms
- Brain response to blood glucose levels [ Time Frame: 4 to 8 weeks ]Brain response is operationally defined as: fMRI BOLD signal to detect differences in brain activation in response to changes in glucose levels taken between 4 to 8 weeks after subject enrollment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00580710
|Contact: Renata D Belfort-DeAguiar, MD||203 785 email@example.com|
|United States, Connecticut|
|Yale University School of Medicine||Recruiting|
|New Haven, Connecticut, United States, 06520|
|Principal Investigator: Robert Sherwin, M.D.|
|Principal Investigator:||Robert Sherwin, M.D.||Yale University|