Biobehavioral Mechanisms of Glucose Variability

Study start date: April 1, 2013

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.