Case Study 2: Insulin Clamp, Body Mass Index and Risk of Diabetes

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Case Study 2 Insulin Clamp, Body Mass Index and
Risk of Diabetes

• Moderator Ms. Victoria Pemberton, NIH/NHLBI

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Case Study 2 Insulin Clamp, Body Mass Index
(BMI) and Risk of Diabetes

• Moderator Victoria Pemberton, NIH/NHLBI
• Panelists
• Sandra Alfano, Yale School of Medicine, IRB Chair
  
• Silva Arslanian, University of Pittsburgh,
  Professor of Pediatrics, Director of Pediatric
  Clinical and Translational Research Center (CTSA)
• Sandy Vasan, The Rockefeller University,
  Pediatric Consultant to IRB
• Lisa Teot, University of Pittsburgh, Pediatric
  Pathologist Scientific IRB Member
• Richard Guido, University of Pittsburgh, IRB
  Chairman, Magee-Womens Hospital
• David Asmuth, University of California, Davis,
  IRB Chair
• Description of the case
• The study is designed to determine if an insulin
  clamp plus a combination of lipid profile, blood
  pressure and BMI can accurately predict the
  likelihood of onset of Type 2 diabetes, in
  children 11 years of age with varying BMIs.
• The study procedure involves an overnight fast,
  insertion of two catheters, and heating one hand
  via a heated box or heat pad for the duration of
  the test. Potential risks include hypoglycemia,
  heat burns and complications from the insertion
  of two intravenous catheters.

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Details of Case Study 2

• Objectives Determine the predictive value of
  insulin clamp studies with serum lipid profile,
  blood pressure and BMI for risk of onset of Type
  2 diabetes
• Hypothesis Insulin clamp plus a combination of
  lipid profile, blood pressure and BMI can
  accurately predict the likelihood of onset of
  Type 2 diabetes by age 21
• Population 11 year old children in different BMI
  strata using CDC charts- 5th to 85th percentile
  (normal), 86th to 95th percentile (at risk for
  overweight), gt 95th percentile (overweight)
• Design Single arm with single assessment with
  longitudinal follow up
• Therapeutic Intervention None
• Assessments Insulin clamp studies,
  anthropometric assessment, biochemical laboratory
  studies
• Primary Outcomes
• Association of insulin clamp results with risk
  factors for development of Type 2 diabetes
• Rate and time of onset of Type 2 diabetes by age
  21

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Pediatric Research Regulations Related to the Case

• 45 CFR 46.404 research not involving greater than
  minimal risk
• 45 CFR 46.405 research involving greater than
  minimal risk but presenting the prospect of
  direct benefit to the individual subjects
• 45 CFR 46.406 research involving a minor increase
  over minimal risk and no prospect of direct
  benefit to individual subjects, but likely to
  yield generalizable knowledge about the subjects
  disorder or condition
• 45 CFR 46.407 research not otherwise approvable
  which presents an opportunity to understand,
  prevent or alleviate a serious problem affecting
  the health or welfare of children

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Key Issues for Case Study 2

• How does the panel assess risk in this case?
• Is the risk assessment different between any of
  the subgroups considered for enrollment in this
  study?
• Are there previous studies or additional
  information that might help the panel to assess
  risk in this particular study?
• Does this study require a 407 review?
• Should normal, healthy children be included in
  this study?
• Should children at risk such as overweight be
  included in this study?
• Is it scientifically feasible to include only
  children with a family history of Type 2
  diabetes?
• Are there changes that could be proposed to allow
  this study to be conducted while maintaining its
  scientific value?

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References

• Office for Human Research Protections (OHRP)
  Precursors to Diabetes in Japanese American Youth
  407 Review (2003) http//www.hhs.gov/ohrp/children
  /japanese.html
• Sinaiko, A, Jacobs, D, Steinberg, J, Moran, A,
  Luepker, R, Rocchini, A, and Prineas, R. (2001).
  Insulin resistance syndrome in childhood
  Associations of the euglycemic insulin clamp and
  fasting insulin with fatness and other risk
  factors. J. Peds 139(5)700-707.
• Wendler, D, Belsky, L, Thompson, KM, and Emanuel,
  EJ. (2005). Quantifying the federal minimal risk
  standard Implications for pediatric research
  without a prospect of direct benefit. JAMA
  294826-832.

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Question for the Audience

• Would you approve normal healthy children
  enrolling in this study?
• Individual Yes Votes 9
• Multiple Person Yes Votes 4
• Individual No Votes 26
• Multiple Person No Votes 5