Investigation Into the Effects Upon Brain Response to Change in Circulating Glucose Levels in Diabetes Mellitus

Type 1 Diabetes Clinical Trial

Official title:

Investigation Into the Effects Upon Brain Response to Change in Circulating Glucose Levels in Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00580710
• Other study ID #: 0108012609
• Secondary ID: 2R01DK020495-37
• Status: Completed
• Start date: August 2001
• Est. completion date: November 1, 2018

Study information

• Verified date: April 2022
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 164
• Est. completion date: November 1, 2018
• Est. primary completion date: November 1, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

• All subjects:

• on a weight maintaining diet

• ability to read and speak English fluently

• For All Type 1 Diabetics all of the above inclusion criteria AND C-peptide negative AND no evidence of neuropathy or proliferative retinopathy

• Only for Type 1 Diabetics in the intensively treated group: HbA1c < 7.5% AND documented hypoglycemia at least once per week over at least 4 weeks of frequent daily self monitoring

• Only for Type 1 Diabetics in the conventionally treated group:HbA1c = 8.5%

• Age 18-40 years in the groups 1,2, and 3. Age 18-50 in groups arm 2 obese and control.

• BMI <30 in the groups 1,2, and 3; BMI >18.4 but < or = 25 in the arm control group; and BMI > or = 30kg/m2 in the obese group.

Exclusion Criteria:

• Pregnancy

• History of neurologic or cardiovascular disease

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Hypoglycemia
• Type 1 Diabetes

Locations

Country	Name	City	State
United States	Yale University School of Medicine	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brain response to blood glucose levels	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.	4 to 8 weeks