Biobehavioral Mechanisms of Glucose Variability

This is an interventional other trial for Diabetes Mellitus, Type 1 focused on measuring Glucose Variability (GV), Continuous Glucose Monitor (CGM), Average Daily Risk Range (ADRR), Self Monitoring Blood Glucose (SMBG) Read More

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 <65 years old.
• HbA1c ≤10% as measured with DCA 2000 or equivalent device.
• Willingness to use lispro (Humalog) insulin for metabolic challenge admission.
• Willingness to perform self-monitoring blood glucose (SMBG) >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 <60 ml/min/1.73 m2.
• Diabetic ketoacidosis in the past 6 months

• Conditions which may increase the risk of induced hypoglycemia such as:

  • uncontrolled coronary artery disease
  • stable or unstable angina
  • episode of chest pain of cardiac etiology with documented Electrocardiography changes or positive troponin levels
  • positive stress test
  • catheterization with coronary blockages >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.