Biobehavioral Mechanisms of Glucose Variability
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      The purpose of this study is to investigate how blood sugar changes in response to insulin
      and what the body does to counter-act low blood sugar in people with Type 1 Diabetes
      Mellitus. Insulin sensitivity is the term used to describe blood sugar changes within the
      body in response to insulin. Greater understanding of insulin sensitivity, particularly how
      the body responds to low blood sugar, will help us to better predict how blood sugar levels
      will change.

      All subjects will receive a liquid mixed-meal and will have their blood sugar response
      monitored in order to study insulin sensitivity. All subjects will receive additional insulin
      injections that are given to cause a low blood sugar in order to understand how the body
      responds to a low blood sugar. All subjects will be closely monitored during the time the
      insulin is given, by frequent checks of blood sugar and constant medical and nursing
      supervision. Details of the visits, tests and procedures are described below. During this
      study, the study team will ask that subjects to use their own insulin pump and own
      glucometer. Subjects will need to use the same glucometer for the entire study. Subjects will
      be provided 1 box of strips. Subjects will be required to use lispro (Humalog) insulin 2-3
      days before your inpatient admission which will be provided free of charge.
    

Detailed description: 
      Glucose variability (GV) in type 1 diabetes (T1DM) is increasingly viewed as a primary marker
      of glycemic control, responsible, along with chronic hyperglycemia reflected by HbA1c, for
      diabetes complications. In this study, we propose to investigate: (i) the time course of
      deterioration of physiological glucoregulatory mechanisms leading to increased GV, and (ii)
      the association of GV with metabolic and behavioral factors such as insulin sensitivity and
      treatment adequacy. Our primary hypothesis is:

      Glucose variability in T1DM is triggered by behavioral events (e.g. meals, insulin injection,
      exercise) that challenge the metabolic system. The timing and the magnitude of the behavioral
      challenges, and the ability of the metabolic mechanisms to absorb these challenges, determine
      the magnitude of GV. This process develops in a certain time frame, and can be accelerated by
      inadequate treatment, or attenuated by precise timing and dosing of bio-behavioral control.
      This study will use a combination of treatment records, continuous glucose monitoring (CGM),
      and an inpatient admission to clarify the relationships between behavioral challenges to the
      metabolic system, physiological glucoregulatory mechanisms, and GV. This study will test the
      following hypotheses:

        1. Suboptimal treatment behavior, e.g. insulin mistiming (early/late meal insulin) or
           unbalanced insulin (higher basal/bolus ratio), is correlated with higher GV and repeated
           hypo- and hyperglycemia; this relationship is mediated by a patients' insulin
           sensitivity;

        2. A metabolic challenge (e.g. consecutive sequence of hypo- and hyperglycemia), will push
           the metabolic system into a transient super-critical state characterized by increased GV
           as defined by the Variability Grid Analysis (VGA) and the Average Daily Risk Range
           (ADRR), which will persist for several days beyond the discontinuation of the challenge.
    

Intervention name(s): Glucose Variability Observation
Intervention type(s): Procedure
Intervention description(s): On the morning of ~Day 17 for a metabolic challenge involving a standardized liquid mixed meal intended to raise the blood glucose approximately 150 mg/dl, followed four hours later by the induction of hypoglycemia with intravenous insulin administration with goal glucose of 55 mg/dl. After carbohydrate rescue, the subject will receive a meal and will be monitored until glucose is stable above 80 mg/dl.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Glucose Variability (GV); Continuous Glucose Monitor (CGM); Average Daily Risk Range (ADRR); Self Monitoring Blood Glucose (SMBG)