Counter-Regulatory Impairment and the Effect of Microvascular Insulin Transfer in Type 1 Diabetes Mellitus (BPK003)

The researchers plan to test the following hypothesis:

A good level of glucose control in Type 1 Diabetes Mellitus (T1DM) is dependent on two levels of feedback from the body:

1. the transport of insulin through small blood vessels: suggesting that hypoglycemia leads to increased insulin sensitivity which then causes recurrent hypoglycemia;
2. the endocrine level, defined as insulin-glucose interaction and hormonal counter-regulation.

The researchers plan to investigate the relationships between hypoglycemia, insulin transport, and counter-regulation. This study will ultimately lead to a better understanding of risk for recurrent hypoglycemia.

Adults with type 1 diabetes

• Pitsillides AN, Anderson SM, Kovatchev B. Hypoglycemia risk and glucose variability indices derived from routine self-monitoring of blood glucose are related to laboratory measures of insulin sensitivity and epinephrine counterregulation. Diabetes Technol Ther. 2011 Jan;13(1):11-7.
• Chan A, Barrett EJ, Anderson SM, Kovatchev BP, Breton MD. Muscle microvascular recruitment predicts insulin sensitivity in middle-aged patients with type 1 diabetes mellitus. Diabetologia. 2012 Mar;55(3):729-36. Epub 2011 Dec 14. PubMed PMID: 22167126.

Inclusion Criteria:

• Participated in and satisfied all of the inclusion criteria of NCT00315939
• 18 years of age or older
• Have Type 1 Diabetes Mellitus defined by American Diabetes Association criteria or judgment of physician
• Since our major goal is the investigation of hypoglycemia, we will preferentially recruit patients with a history of severe hypoglycemia/moderate hypoglycemia anticipating that approximately (~) half of the recruited subjects will have had two or more severe or moderate hypoglycemia episodes in the past 12 months

Exclusion Criteria:

• Age < 18
• Pregnancy
• Use of oral steroids
• Hematocrit < 36% (females); < 38% (males)
• Symptomatic heart disease (e.g., history of myocardial infarction, history of coronary bypass or stenting procedure, angina, episode of chest pain of cardiac etiology with documented EKG changes, positive stress test or catheterization with coronary blockages > 50%)
• History of an ischemic cerebrovascular event
• Active substance abuse
• Psychosis
• Mental retardation
• Severe depression