Role of Insulin Action in Psoriasis Pathogenesis

1. Body mass index of 25.0-40.0 kg/m2
2. Able to understand written and spoken English and/or Spanish
3. 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.
4. Diagnosed with plaque psoriasis, documented using Psoriasis Area and Severity Index (PASI)

5. 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, and
     • 2-hour post-challenge glucose \< 140 mg/dL

   • For Insulin Intermediate (II) group:

     • Hemoglobin A1c \< 6.5%, and
     • Fasting plasma glucose 80-125 mg/dL, and
     • Fasting plasma insulin \< 15 μIU/mL, and
     • 2-hour post-challenge glucose \< 200 mg/dL, and
     • Not otherwise meeting all criteria for the IS group

   • For Insulin Resistant (IR) group:

     • Hemoglobin A1c \< 6.5%, and
     • Fasting plasma glucose 80-125 mg/dL, and
     • Fasting plasma insulin ≥ 15 μIU/mL, and
     • 2-hour post-challenge glucose \< 200 mg/dL

NOTE: Group assignments will be made retroactively, after observational data has been collected. Those not fitting into any of these groups will have their data excluded from further analysis.

Exclusion Criteria:

1. Inability to provide informed consent in English or Spanish

2. 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
3. History of gestational diabetes mellitus

4. 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
5. Clinical concern for absolute insulin deficiency (e.g., type 1 diabetes, pancreatic disease)

6. 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 NOTE: Women not using any of the above forms of birth control may be included if they have a negative urine pregnancy test on the day of the study, before beginning any study procedures.

   ii. Women currently pregnant

   iii. Women currently breastfeeding

7. 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

8. 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

9. History of severe infection or ongoing febrile illness within 30 days of screening
10. 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.

13. 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.

14. 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.