The goal of this study is to collect more information from people with plaque psoriasis and to determine if insulin plays a role in the pathogenesis of psoriasis. The main question it aims to answer is if insulin action is preserved or even enhanced in psoriatic lesions despite insulin resistance elsewhere. Participants with plaque psoriasis will have punch biopsies taken of lesional and non-lesional skin after an overnight fast and then during an oral glucose tolerance test. Biopsy specimens will then be assessed for markers of insulin action.
Psoriasis exhibits a clear and robust epidemiologic association with type 2 diabetes mellitus (T2DM). Although T2DM may exacerbate psoriasis and/or complicate its treatment, we do not understand the mechanisms connecting them. As a starting point, psoriasis appears to worsen the insulin resistance (IR) that underlies T2DM. The study investigators hypothesize that the hyperinsulinemia that attempts to compensate for IR retains the ability to drive proliferation of psoriatic lesions. This would set up a vicious cycle in which psoriasis worsens IR, which in turn stimulates insulin hypersecretion that further intensifies psoriasis. In order to test this hypothesis, the investigators must first determine if insulin signaling in psoriatic lesions is actually hyperactive. The investigators therefore propose in this pilot study to elucidate the nature of insulin signaling in psoriasis by measuring phosphorylation of AKT, insulin's key intracellular signaling mediator, in skin biopsies. We will perform shave punch biopsies of lesional and non-lesional skin in overnight-fasted patients with psoriasis who are overweight or obese and therefore at risk of IR. Another set of biopsies will be taken during an oral glucose tolerance test that stimulates endogenous insulin secretion. The investigators expect that AKT phosphorylation will be attenuated in non-lesional skin of patients determined to have IR compared to those who are Insulin Sensitive (IS) or Insulin Intermediate (II), but that AKT phosphorylation will be preserved or even enhanced in lesional skin despite IR. Determining that insulin action is excessive in psoriatic lesions would suggest reducing insulin levels as a novel psoriasis treatment strategy that would also help to spare patients from difficult immunomodulatory treatments.
Study Type
OBSERVATIONAL
Enrollment
10
Participants ingest 75 g of glucose in 10 fl oz aqueous solution (fruit flavored) after an overnight fast. Blood is drawn at baseline (t = 0 min) and at 120 min after ingestion. This test is non-experimental.
Punch biopsies are taken from lesional (psoriatic) and non-lesional skin after an overnight fast and at 120 min after ingestion of glucose during OGTT. This procedure is non-experimental.
Columbia University Irving Medical Center
New York, New York, United States
Skin insulin sensitivity: ratio of phosphorylated to total AKT in skin biopsies
Investigators will perform Western blots on skin biopsies using antibodies to phosphorylated (T308, S473) and total AKT. The ratio of phosphorylated to total AKT will be determined using densitometry of Western blots and/or by enzyme-linked immunosorbent assays (ELISA), each measured in arbitrary units (AU).
Time frame: Up to 120 minutes from the start of OGTT
Serum triglyceride (TG) level during OGTT
Measurement of serum triglyceride level (units: mg/dL) during OGTT. A blood test will be done.
Time frame: During OGTT (up to 120 minutes from start of OGTT)
Serum free fatty acid (FFA) levels during OGTT
Measurement of serum free fatty acid levels (units: mmol/L) during OGTT. A blood test will be done.
Time frame: During OGTT (up to 120 minutes from start of OGTT)
Fasting plasma glucose level
Plasma glucose (units: mg/dL) after an overnight fast (\> 8 hours). A blood test will be done. A healthy (normal) fasting blood glucose level for someone without diabetes is 70 to 99 mg/dL.
Time frame: Before OGTT (baseline = 0 minutes), During OGTT (up to 120 minutes from start of OGTT)
Fasting serum insulin level
Serum insulin (units: μIU/mL) after an overnight fast (\> 8 hours). A blood test will be done. The normal range of fasting insulin varies somewhat between labs, but around 2 to 20 mIU/mL is considered normal by most.
Time frame: Before OGTT (baseline = 0 minutes), During OGTT (up to 120 minutes from start of OGTT)
Fasting serum C-peptide level
Serum C-peptide (units: ng/mL) after an overnight fast (\> 8 hours). A blood test will be done. A normal result of a C-peptide test ranges from 0.5 ng/mL to 2.0 ng/mL (or 0.17 to 0.83 nmol/L).
Time frame: Before OGTT (baseline = 0 minutes), During OGTT (up to 120 minutes from start of OGTT)
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