Investigation Into Effects Upon Counterregulatory Respo...

Investigation Into Effects Upon Counterregulatory Responses to Hypoglycemia During Intensive Treatment of T1DM

Investigation Into Effects Upon Counterregulatory Responses to Hypoglycemia During Intensive Treatment of T1DM

This study is currently recruiting participants.
Verified by Yale University, December 2007

Sponsors and Collaborators: Yale University
Juvenile Diabetes Research Foundation

Information provided by: Yale University
ClinicalTrials.gov Identifier: NCT00580710

Purpose
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
Type 1 Diabetes
Hypoglycemia

MedlinePlus related topics: Diabetes Diabetes Type 1 Hypoglycemia MRI Scans

Drug Information available for: Insulin

U.S. FDA Resources

Study Type: Observational
Study Design: Case Control, Cross-Sectional

Official Title: Investigation Into Effects Upon Counterregulatory Responses to Hypoglycemia During Intensive Treatment of Insulin-Dependent Diabetes Mellitus.

Further study details as provided by Yale University:

Biospecimen Retention: None Retained

Biospecimen Description:

Estimated Enrollment: 45
Study Start Date: August 2001
Estimated Study Completion Date: August 2009

Groups/Cohorts
1
conventionally treated, relatively poorly controlled patients with type 1 diabetes
2
intensively treated, well controlled patients with type 1 diabetes
3
age- and sex- matched non-diabetic control subjects

Detailed 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.

Eligibility
Ages Eligible for Study: 18 Years to 40 Years
Genders Eligible for Study: Both
Accepts Healthy Volunteers: Yes
Sampling Method: Non-Probability Sample

Study Population

The recruited subjects will reflect the gender and ethnic distribution of the Yale and New Haven community. The recruited subjects with type 1 diabetes will reflect the demographics of the clinic population in New Haven. Subject selection is independent of race and sex.

Criteria

Inclusion Criteria:

All subjects:
Age 18-40 years
Body Mass Index < 30
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 ¡Ý 8.5%
Exclusion Criteria:

Pregnancy
History of neurologic or cardiovascular disease
Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00580710

Contacts

Contact: Kathleen Page, MD 203 785 6222 katleen.page@yale.edu

Locations

United States, Connecticut
Yale University School of Medicine Recruiting
New Haven, Connecticut, United States, 06520
Principal Investigator: Robert Sherwin, M.D.

Sponsors and Collaborators

Yale University

Juvenile Diabetes Research Foundation

Investigators

Principal Investigator: Robert Sherwin, M.D. Yale University

More Information

Responsible Party: Yale University School of Medicine ( Robert Sherwin, M.D./Prinicipal Investigator )
Study ID Numbers: #0108012609, JDRF #4-2004-807
First Received: December 19, 2007
Last Updated: December 19, 2007
ClinicalTrials.gov Identifier: NCT00580710
Health Authority: United States: Institutional Review Board