Biobehavioral Mechanisms of Glucose Variability

Inclusion Criteria

• Clinical diagnosis of type 1 diabetes mellitus for ≥2 years. For an individual to be enrolled at least one criterion from each list must be met.
• Criteria for documented hyperglycemia (at least 1 must be met):
• Fasting Blood Glucose (BG) ≥126 mg/dL
• 2h Oral Glucose Tolerance Test (OGTT) ≥200 mg/dL
• Hemoglobin (HbA1c) ≥6.5%
• BG ≥200 mg/dL with symptoms
• History of hyperglycemia consistent with diabetes
• Criteria for requiring insulin at diagnosis (1 must be met):
• required insulin at diagnosis and continually thereafter
• no insulin at diagnosis but upon investigator review likely needed insulin (significant hyperglycemia that did not respond to oral agents) and insulin eventually required and used continually
• no insulin at diagnosis but continued hyperglycemia, positive islet cell antibodies - consistent with latent autoimmune diabetes in adults (LADA) and insulin eventually required and used continually
• Use of an insulin pump for at least six months prior to the study.
• Using a bolus calculator with pre-defined parameters for carbohydrate ratio(s), and insulin sensitivity factor(s).
• Signed informed consent.
• Age ≥21 and 4 times/day.
• Willingness to avoid consumption of acetaminophen-containing products during the study.
• Willingness to perform 4 days of outpatient assessment with timed, prepackaged meals and snacks, and >7 SMBGs.

Exclusion Criteria

• Uncontrolled arterial hypertension (resting blood pressure >160/100 mm Hg).
• Impaired hepatic function measured as alanine aminotransferase or aspartate aminotransferase ≥3 times the upper reference limit.
• Impaired renal function: glomerular filtration rate (calc GFR) of 50%
• congestive heart failure
• significant cardiac arrhythmia
• history of a cerebrovascular event
• seizure disorder
• syncope
• adrenal insufficiency
• hypoglycemia-induced migraine within the past year
• neurological disease
• Diabetic complications altering insulin kinetics or food absorption
• Pregnancy, breast-feeding or intention of becoming pregnant.
• Mental incapacity, unwillingness or language barriers precluding adequate understanding or cooperation.
• Psychiatric disorders that would interfere with study tasks (e.g. inpatient psychiatric treatment within 6 months prior to enrollment).
• skin condition that prevents sensor placement on the abdomen or arm.
• Difficulties to operate Continuous Glucose Monitor.
• Uncontrolled thyroid disease: thyroid-stimulating hormone (TSH)>10.
• Bleeding diathesis or dyscrasia.
• Alcohol or drug abuse within 1 year of enrollment by patient history.
• Allergy to components of the CGM sensor.
• Blood donation >473 ml in last 56 days
• Prior noncompliance with study procedures.
• Hematocrit outside of the normal range.
• Magnesium <1.6 mg/dl.
• Potassium <3.4 mmol/L.
• Active enrollment in another clinical trial
• Allergy to or intolerance of insulin lispro (Humalog)
• Anticoagulant therapy other than aspirin.
• Oral steroids.
• Use of acetaminophen-containing medication that cannot be.
• Use of Type 2 Diabetes Mellitus medications: including metformin, sulfonylureas, meglitinides, thiazolidinediones, Dipeptidyl peptidase-4 (DPP-IV) inhibitors, glucagonlike Peptide (GLP-1) agonists and alpha-glucosidase inhibitors.
• Unwillingness to withhold Pramlintide for the duration of the study intervention.