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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Yale University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT00580710
First received: December 19, 2007
Last updated: January 28, 2014
Last verified: January 2014
  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

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Investigation Into Effects Upon Counterregulatory Responses to Hypoglycemia During Intensive Treatment of Insulin-dependent Diabetes Mellitus.

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Brain response to blood glucose levels [ Time Frame: 4 to 8 weeks ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 250
Study Start Date: August 2001
Estimated Study Completion Date: August 2018
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts
conventionally treated
conventionally treated, relatively poorly controlled patients with type 1 diabetes
intensively treated
intensively treated, well controlled patients with type 1 diabetes
non-diabetic, non-obese control subjects
age- and sex- matched non-diabetic, normal weight (BMI > or = 18.5 but < or = 25 kg/m2) control subjects
obese 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

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 50 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:
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Contacts
Contact: Renata D Belfort-DeAguiar, MD 203 785 6222 glucose.studies@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
Investigators
Principal Investigator: Robert Sherwin, M.D. Yale University
  More Information

No publications provided

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00580710     History of Changes
Other Study ID Numbers: #0108012609, JDRF #4-2004-807
Study First Received: December 19, 2007
Last Updated: January 28, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
type 1 diabetes
hypoglycemia
magnetic resonance imaging

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on July 20, 2014