Single and Multiple Ascending Doses of MEDI6570 in Subjects With Type 2 Diabetes Mellitus

Inclusion Criteria * In Part A, subjects aged 18 through 65 inclusive at screening. In Part B, male subjects aged 18 through 65 inclusive, and female subjects aged 40 to 65 inclusive, at screening. * Body mass index of 18 to 45 kg/m2. * Subjects with T2DM on stable medical therapy for at least 6 weeks prior to screening with no clinically significant dose change and/or new medications in the recent 6 weeks * Capable of giving written informed consent and adhere to visit/protocol schedule * Female subjects must be of non-childbearing potential, confirmed at screening by one of the following: (a) Postmenopausal, defined as amenorrhea for ≥ 12 months following cessation of all exogenous hormonal treatments, and luteinizing hormone and follicle stimulating hormone (FSH) levels in the postmenopausal range. (b) Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. Tubal ligation is not considered as irreversible surgical sterilization. * Non-sterilized male subjects who are sexually active with a female partner of childbearing potential must use a male condom plus spermicide, and in addition the female partner must use 1 highly effective method of contraception. * In Part B, subjects must meet CTA criteria as follows: (Estimated glomular filtration rate (eGFR) ≥ 60 mL/min/1.73m2. No allergy to iodinated contrast, no history of contrast induced nephropathy or no contraindication to beta blockers or nitroglycerin. No recent pulmonary embolism and must able to hold breath for at least 6 seconds. No history of coronary bypass surgery and no active arrhythmia on day of CTA scan (atrial fibrillation, atrial flutter, frequent premature atrial, or ventricular contractions). * For Part A Cohort 6, subjects must be Japanese (eg, natives of Japan or Japanese Americans), defined as having both parents and four grandparents who are Japanese. This includes second and third generation subjects of Japanese descent whose parents or grandparents are living in a country other than Japan. Exclusion Criteria * History of any clinically important disease or disorder (not including T2DM) which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study. * History or presence of hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism or excretion of drugs. * Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational product, or planned surgical procedure before study completion. * Female subjects who are pregnant and/or currently lactating. * Any clinically important abnormalities in clinical chemistry, hematology, coagulation parameters, or urinalysis results -History of blood dyscrasia, hemostatic disorder, systemic bleeding, or prior trauma that places the subject at a higher risk of bleeding. * History of vascular abnormalities including aneurysms, prior dissections; hx of severe hemorrhage, hematemesis, melena, haemoptysis, severe epistaxis, severe thrombocytopenia, intracranial hemorrhage, rectal bleeding, or major surgery/procedure within 3 months prior to Visit 1; a history suggestive of active peptic ulcer disease; or prior intracranial haemorrhage. -Dual-antiplatelet therapy, anticoagulation therapy or thrombolytic use, in the past month or planned use during the duration of the study. -Chronic aspirin therapy or chronic NSAID therapy. * Clinically significant ECG that may interfere with the interpretation of serial ECG and QT interval changes screening. -Persistent or intermittent complete bundle branch block, incomplete bundle branch block, or intraventricular conduction delay with QRS \> 110 ms. Subjects with QRS \> 110 ms but \< 115 ms are acceptable if there is no evidence of ventricular hypertrophy or pre excitation. -Abnormal vital signs * Hemoglobin A1c\>9.0% measured at screening. HbA1c can be retested once after approximately 4 weeks. * Clinically significant late diabetic complications including symptoms consistent with angina, congestive heart failure, and peripheral arterial disease (claudication), or other complications such as proliferative retinopathy, maculopathy, or gastroparesis. * Any positive result at screening for serum hepatitis B surface antigen, hepatitis C antibody, or human immunodeficiency virus (HIV). * History of cancer in the last 5 years, with the exception of non-melanoma skin cancer. -History of alcohol substance abuse within the past 6 months. A positive drug screen including recreational marijuana will be exclusionary. However, subjects with a documented medical need or prescription may be included at the discretion of the principal investigator. * History of hypersensitivity or ongoing severe allergy or history of hypersensitivity to drugs with a similar chemical structure or calss to MEDI6570. * History of ongoing infection or febrile illness within 30 days prior to Day 1. * Current or previous use of systemic corticosteroids within 28 days prior to screening. * Receipt of any investigational product or use of any biologics within 6 months or 5 half lives prior to screening (whichever is longer), or planned participation in an additional study of an investigational product therapy or biologic prior to end of follow up period.