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

Not Applicable

Completed

Interventions: Procedure: Hyperinsulinemic, euglycemic and hypoglycemic clamp

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
SMBG followed by clamp	Hyperinsulinemic, euglycemic and hypoglycemic clamp	One month of self-monitored blood glucose (SMBG) field data was used to calculate measures of glucose variability and risk of hypoglycemia, while the hyperinsulinemic, euglycemic and hypoglycemic clamp procedure was used to evaluate insulin sensitivity and epinephrine response during induced hypoglycemia.

Primary Outcome Measures

Name	Time	Method
Maximum Epinephrine Response (LBGI Groups)	285 min (time of clamp)	Mean maximum epinephrine response during induced hypoglycemia is the average of subjects' maximum concentration of all epinephrine measurements taken at plasma glucose level lower than 70mg/dL. Low blood glucose index (LBGI) is a metric to calculate the risk for hypoglycemia based on frequency and extent of past events based on SMBG readings. In studies, the LBGI typically accounted for 40-55% of the variance of future significant hypoglycemia in the subsequent 3-6 months. The LBGI has established risk categories: Low Risk, LBGI \< 2.5; Moderate Risk, 2.5 \< LBGI \< 5; and High Risk, LBGI \> 5, indicating an over 10-fold increase in future severe hypoglycemia from the lowest to the highest risk category.

Secondary Outcome Measures

Name	Time	Method
Maximum Epinephrine Response (ADRR Groups)	285 min (time of clamp)	Mean maximum epinephrine response during induced hypoglycemia is the average of subjects' maximum concentration of all epinephrine measurements taken at plasma glucose level lower than 70mg/dL. Average Daily Risk Range (ADRR) is associated with glycemic variability and risk of both hyper- and hypoglycemia. Low Risk, ADRR \< 20; Moderate Risk, 20 \< ADRR \< 40; and High Risk,ADRR \> 40.