Insulin is a key hormone which plays a central role in regulating blood glucose. Insulin resistance occurs when the glucose-lowering ability of insulin is impaired. We understand that insulin resistance is a key driver of several serious chronic illnesses in humans including obesity, type 2 diabetes, and metabolic syndrome. The prevalence of these conditions has become an epidemic in recent years. In addition to these common diseases, several rare syndromes of severe insulin resistance have been described. Known subtypes of severe insulin resistance are described below:

Goals of the study

Our goal is to collect detailed phenotypic and genetic information from participants with suspected SIR syndromes by creating a registry and biorepository. This will enable us to correlate genetic information, biochemical anomalies, and clinical phenotypes. This will allow us to study the mechanisms of insulin resistance in different genetic variants, following with potential diagnoses and therapeutics for these rare diseases. First-degree relatives will also be recruited in order to establish segregation of candidate genetic variants.

Study design

The purpose of this study is to establish a registry and biorepository of patients with insulin resistance syndromes due to genetic mutations. Individuals with the condition and their first-degree relatives will be asked to participate. Study assessments include history, physical exam, skin-fold thickness, and smell identification testing. We will collect fasting metabolic labs, and exome/genome sequencing data, and peripheral blood mononuclear cells (PBMCs) or renal epithelial cells (RECs) for the creation of a stem cell line for future research.

Registry of Severe Insulin Resistance Syndromes in Humans diagram.

Eligible participants

Patients are eligible to participate in the study if they are between the ages of 10 and 65 years.

Participants must have a suspected severe insulin resistance syndrome as deemed by their treating physician and include one of the following features:

  • Clinical evidence of severe insulin resistance:
    • Acanthosis nigricans, or
    • History of elevated insulin level > 400 μIU/mL
  • Severe Tall stature:
    • Height greater than 97th percentile for age
  • Severe short stature:
    • Height less than 3rd percentile for age
  • Pseudoacromegaly (at least 2 of the following):
    • Large hands or feet
    • Widely spaced teeth
    • Enlarged tongue
    • Normal IGF-1 and/or growth hormone levels ruling out classical acromegaly

First-degree relatives of those meeting the above criteria are also eligible to participate in the study.

Exclusion criteria

Patients who meet the following criteria cannot participate in the study:

  • Women who are pregnant or breastfeeding
  • Individuals with known bleeding disorders
  • Developmental delays or other health problems that would prevent them from participating in the study

How to register…

If you are interested in participating or have questions please contact:

Stephen Stone, MD
Voice: 314-286-0577