In health, the blood glucose (BG) level is internally regulated through insulin release from the pancreas that counterbalances carbohydrate intakes from food, drinks, etc. Since patients with Insulin Dependent Diabetes Mellitus (IDDM) are unable to produce a sufficient amount of insulin, this internal self-regulation is disrupted. The standard daily control of IDDM involves multiple insulin injections which lower BG. However, this external BG control is still not nearly as good as the internal self-regulation: too little insulin results in chronic high BG levels which too much insulin can cause hypoglycemia. Recent studies have demonstrated that the most effective long-term control of IDDM is the strict maintenance of BG levels within a normal range through intensive insulin therapy.

Detailed results of its effects are presented by the Diabetes Control and Complications Trial and its European counterpart: chronic high BG levels were proven to cause many complications in multiple body systems over time, while too much insulin resulted in hypoglycemia. Without immediate treatment hypoglycemia can rapidly progress to severe hypoglycemia (SH), a condition defined as low BG resulting in stupor, seizure or unconsciousness that precludes self-treatment.

On one side, intensive therapy is the best long-term treatment of IDDM, on the other hand, it was associated with at least a threefold increase in SH. Since SH could result in accidents, coma and even death, patients and health care providers are often discouraged from pursuing intensive therapy. Consequently, hypoglycemia has been identified as the major barrier to improved glycemic control. In short, patients with IDDM face a life-long clinical optimization problem: to maintain strict glycemic control without increasing risk for hypoglycemia.

A bio-mathematical problem, associated with this optimization, is to create a measure, based on multiple BG readings, that quantifies both trends: towards chronically high BG levels and towards increased risk for hypoglycemia.

The following studies investigate bio-behavioral aspects and treatment strategies related to these issues:

"Bio-behavioral Irregularity and Control of IDDM" Principal Investigator: Boris Kovatchev, Ph.D.

This is an interdisciplinary study that creates bio-mathematical models, advanced data analysis methods, individual assessment protocols and standardized output for evaluation of biological and behavioral irregularity factors associated with IDDM.

Funding Agency: NIH/NIDDK, R01 DK51562-03

"Severe Hypoglycemia: Risks and Prevention" Principal Investigator: Daniel J. Cox, Ph.D.

This study evaluates biological and psychological parameters that differentiate patients who have Type I diabetes with either a recent history of no, or multiple, episodes of severe hypoglycemia. It develops and evaluates a psychosocial intervention - reducing the occurrence of severe hypoglycemia without compromising the glycemic control.

Funding Agency: NIH/NIDDK R01 DK28288-15

"Use of the Memory Meter to Predict Severe Hypoglycemia and Assess Glycosylated Hemoglobin"

Creates methods for assessment of the glycemic control of patients with IDDM based on blood glucose self-monitoring data.

Funding Agency: Lifescan, Inc., Milpitas, CA