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 \<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.