Novel Biomarker for Development of T2D
Condition: Diabetes Type II
MeSH terms: Diabetes Mellitus, Type 2
Study type: Observational

Summary: 
      The investigators wants to determine if 11β-HSD1 activity will be positively associated, and
      5α-reductase activity negatively associated, with (a) degree of insulin resistance defined by
      the homeostatic model assessment of insulin resistance index (HOMA-IR) and (b) worsening
      glycemic control defined by higher HbA1c and impaired fasting glucose in a group of obese
      children and young adults with or without type 2 diabetes compared to lean children and young
      adults without diabetes. The investigators also want to identify key metabolic signatures
      associated with diabetes using metabolomic profiling.
    

Detailed description: 
      The overarching hypothesis is that increases in whole body 11β-HSD1 activity precede and
      presage the development of type 2 diabetes (T2D) in high-risk obese adolescents, serving as a
      critical determinant of insulin resistance and glucose intolerance. The increase in 11β-HSD1
      activity, in combination with decreases in 5α-reductase activity, will increase tissue
      cortisol production, promoting the development of insulin resistance and the metabolic
      syndrome and predisposing to T2D. The investigators predict that increases in 11β-HSD1
      activity will be detected in obese children prior to the development of insulin resistance
      and glucose intolerance and that the progressive increases in 11β-HSD1 will correlate with
      progressive decreases in insulin sensitivity and glucose tolerance. Given preliminary
      findings, the investigators also predict that increases in 11β-HSD1 will be greater and occur
      earlier in development in males than females. This could establish 11β-HSD1 activity as a
      novel, non-invasive biomarker for progression to, or for development of, glucose intolerance
      and T2D.

      The identification of 11β-HSD1 as a biomarker that predicts T2D would have critical clinical
      import, allowing us to identify obese children and adults at highest risk of metabolic
      decompensation. Studies of 11β-HSD1 in obese subjects with varying degrees of IR and glucose
      intolerance will also narrow critical gaps in the understanding of the pathogenesis of T2D.

      The investigators would like to also validate if urine metabolomic profiling can be used for
      identifying key metabolomic signatures associated with insulin resistance. To that end the
      investigators would like to examine detailed metabolomic profiles in 24 hour and spot urine
      samples.

      The study population will include 50 obese adolescents with T2D, 50 obese adolescents without
      T2D and 50 age, gender, race and pubertal status-matched normal weight controls. The subjects
      will be recruited at the Healthy Lifestyle Program at Duke, Diabetes Clinics at Lenox Baker
      Children's Hospital and Roxboro Clinics.

      Study activities include physical exam and medical history, vitals, laboratory tests (only
      for obese adolescents), urine testing for sugar (only for normal weight adolescents), 24 hour
      urine collection, spot urine collection, body fat content measurement, and food and activity
      questionnaire.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        The study population will include 50 obese adolescents with Type II Diabetes, 50 obese
        adolescents without Type II Diabetes, and age, gender, race and pubertal status-matched
        normal weight controls for urine study and 32 young adults 18-21 years of age obese
        adolescents without T2D and age, gender, race and pubertal status matched normal weight
        controls for OGTT sub-study.
      
Biospecimen description: 
      24 hour urine samples.