Role of Insulin Action in Psoriasis Pathogenesis

Inclusion Criteria:

Body mass index of 25.0-40.0 kg/m2
Able to understand written and spoken English and/or Spanish
Written informed consent (in English or Spanish) and any locally required authorization (e.g., Health Insurance Portability and Accountability Act) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations.
Diagnosed with plaque psoriasis, documented using Psoriasis Area and Severity Index (PASI)

Glucose metabolism status as follows (determined only retrospectively based on data collected during the study):

For Insulin Sensitive (IS) group:

Hemoglobin A1c < 5.7%, and
Fasting plasma glucose < 95 mg/dL, and
Fasting plasma insulin < 10 μIU/mL

For Insulin Intermediate (II) group:

Hemoglobin A1c < 6.5%, and
Fasting plasma glucose 80-125 mg/dL, and
Fasting plasma insulin 10-14 μIU/mL

For Insulin Resistant (IR) group:

Hemoglobin A1c < 6.5%, and
Fasting plasma glucose 80-125 mg/dL, and
Fasting plasma insulin ≥ 15 μIU/mL

Exclusion Criteria:

Inability to provide informed consent in English or Spanish
Concerns arising at screening visit (any of the following):

Laboratory evidence of diabetes mellitus, either determined during the study or based on previous documentation:

Hemoglobin A1c ≥ 6.5%, and/or
Fasting plasma glucose ≥ 126 mg/dL
Plasma glucose ≥ 200 mg/dL at 2 hours after ingestion of a 75-g oral glucose load
Random plasma glucose ≥ 200 mg/dL associated with typical hyperglycemic symptoms, diabetic ketoacidosis, or hyperglycemic-hyperosmolar state
History of gestational diabetes mellitus

Use of antidiabetic medications within the 90 days prior to screening, including those prescribed for other indications (e.g., weight control, restoration of ovulation in of polycystic ovarian syndrome), including:

• Metformin, thiazolidinediones, sulfonylureas, meglitinides, dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium/glucose cotransporter 2 (SGLT2) inhibitors, amylin mimetics, acarbose, insulin

Clinical concern for absolute insulin deficiency (e.g., type 1 diabetes, pancreatic disease)

Reproductive concerns

i. Women of childbearing potential not using highly effective contraception, defined as:

Surgical sterilization (e.g., bilateral tubal occlusion, bilateral oophorectomy and/or salpingectomy, hysterectomy)
Combined oral contraceptive pills taken daily, including during the study
Intrauterine device (levonorgestrel-eluting or copper) active at the time of the study
Medroxyprogesterone acetate (Depo-Provera®) injection active at the time of the study
Etonogestrel implants (e.g., Implanon®, etc.) active at the time of the study
Norelgestromin/ethinyl estradiol transdermal system (e.g., Ortho-Evra®) active at the time of the study

ii. Women currently pregnant

iii. Women currently breastfeeding

Known, documented history, at the time of screening, of any of the following medical conditions:

i. Bleeding disorders, including due to anticoagulation or use of P2Y12 inhibitors ii. Anemia requiring treatment iii. Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Use of medications associated methemoglobinemia within 48 hours of shave biopsy procedures:

i. Nitrates/nitrites: nitric oxide, nitroglycerin, nitroprusside, nitrous oxide ii. Antineoplastics: cyclophosphamide, flutamide, hydroxyurea, ifosfamide, rasburicase iii. Antibiotics: dapsone, nitrofurantoin, paraaminosalicylic acid, sulfonamides iv. Antimalarials: chloroquine, primaquine v. Anticonvulsants: phenobarbital, phenytoin, valproic acid vi. Others: acetaminophen, metoclopramide, quinine, sulfasalazine

History of severe infection or ongoing febrile illness within 30 days of screening
Any other disease, condition, or laboratory value that, in the opinion of the investigator, would place the participant at an unacceptable risk and/or interfere with the analysis of study data.
Known allergy/hypersensitivity to any component of the medicinal product formulations (including amide anesthetics), IV infusion equipment, plastics, adhesive or silicone, history of infusion site reactions with IV administration of other medicines, or ongoing clinically important allergy/hypersensitivity as judged by the investigator.
Concurrent enrollment in another clinical study of any investigational drug therapy within 6 months prior to screening or within 5 half-lives of an investigational agent, whichever is longer.