Investigation Into the Effects Upon Brain Response to Change in Circulating Glucose Levels in Diabetes Mellitus
Condition: Type 1 Diabetes; Hypoglycemia
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia
Study type: Observational

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).
    

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.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
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.
      
Keywords: type 1 diabetes; hypoglycemia; magnetic resonance imaging