Cholesterol Lowering and Residual Risk in Diabetes, Type 1

Participants will receive weekly injections of PCSK9i (evolocumab) plus daily, oral pills of atorvastatin or ezetimibe for 1 month.

Participants will undergo blood draw, and optional vascular studies that include:

• Glycocalyx testing (A non-invasive test where a video microscope camera is placed under the tongue to capture images of the movement of red blood cells as they travel through the micro-blood vessels)
• PET/CT for vascular imaging - to assess any inflammation of blood vessels and to evaluate increased metabolism in related tissues, and
• Endothelial cell collection before cholesterol reduction and 1-month after cholesterol reduction to measure any genetic changes in in the endothelial cells before and after collection

Glycemic Variability (GV), the amount one's blood sugar changes throughout the day, will be analyzed from continuous glucose monitoring (CGM) data.

Inclusion criteria

• Participants with previous diagnosis of T1D (as defined by American Diabetes Association or judgment of physician for at least 1 year)

• American Diabetes Association Criteria for diagnosis of diabetes (Must meet at least 1 of the following criteria):

• i. FPG ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 hours, OR;
• ii. 2-h PG ≥200 mg/dL (11.1 mmol/L) during OGTT. The test should be performed using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water, OR;
• iii. A1C ≥6.5% (48 mmol/mol), OR;
• iv. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dL (11.1 mmol/L), AND;
• History of T1D (due to autoimmune β-cell destruction, usually leading to absolute insulin deficiency, including latent autoimmune diabetes of adulthood). Autoimmune markers include islet cell autoantibodies and autoantibodies to GAD (glutamic acid decarboxylase, GAD65), insulin, the tyrosine phosphatases islet antigen 2 (IA-2) and IA-2β, and zinc transporter 8, OR;
• Diagnosis of T1D and confirmed by review of records by 2 separate clinical members of the study team
• Age ≥ 18 & < 90
• LDL-C >100mg/dl
• Able and willing to provide written informed consent for the study

Exclusion criteria

• Established cardiovascular disease on antithrombotic therapy
• Triglycerides >400mg/dl
• Use of a PCSK9 inhibitor
• Recent infection in the past 30 days
• Any hospitalization in the past 30 days
• Use of immunosuppressive therapy
• Use of any antithrombotic therapy
• Use of aspirin
• Use of NSAID within the past 72 hours
• Pregnancy
• Anemia (hemoglobin < 9 g/dl) or thrombocytopenia (platelet count <75), or thrombocytosis (platelet count >600)
• A history of hemorrhagic diathesis
• Chronic kidney disease (CrCl < 30ml/min)
• T2D, monogenic diabetes syndromes, or diabetes in the context of disease of the exocrine pancreas (such as pancreatitis, trauma or pancreatectomy, neoplasia, cystic fibrosis, hemochromatosis)