• Defining the Metabolic Syndrome: Experience in Adult Studies (Steven Haffner, UTHSCSA)

• Definitions in Children and Adolescents (Darrel Wilson, Stanford):

Overview of various definitions in children/adolescents, differences in prevalence rates based on various definitions; examine what might be driving differences in prevalence rates among various definitions.

• U.S. Prevalence of Metabolic Syndrome in Children and Adolescents (Earl Ford, CDC; Steve Cook, Rochester):

National prevalence of the metabolic syndrome in children and adolescents; mean levels of components of metabolic syndrome (with age on X-axis) stratified by sex (one graph) and race-ethnicity.

• Maturation Considerations in Defining the Metabolic Syndrome (Shumei Sun, Wright State)

• Obese white and African-American youth; outcomes include insulin sensitivity, glucose tolerance, beta-cell function, lipid partitioning, adipokines, etc. (Sonia Caprio, Yale)

• Normal weight and obese white and African-American youth; outcomes include insulin sensitivity, glucose tolerance, cellular adhesion molecules as vascular markers, etc. (Silva Arslanian, Pittsburgh)

• Obese Hispanic youth; outcomes include insulin sensitivity, glucose tolerance, acanthosis nigricans, etc. (Michael Goran, USC)

• LRC: Clinical cohorts tracked for 30 years (John Morrison, Cincinnati)

• Fels Study: White cohort tracked from early childhood through middle age; outcomes include adult metabolic syndrome, type 2 diabetes, CVD, heart failure; will present both prospective and retrospective analyses (Shumei Sun, Wright State)

• CARDIA: Adults tracked from age 18 to 45 years; retrospective analysis (Kiang Liu, Northwestern)

• Bogalusa (Gerry Berenson, Tulane)

A grid of components, cutoffs used, disease outcomes, strength of prediction, etc., will be developed for participants to use during this session

• LRC (John Morrison)

• Fels (Shumei Sun)

• Waist vs. BMI-- NGHS (John Morrison)

• Fasting Insulin-- Fels (Shumei Sun)

• CRP--NHANES (Earl Ford/Steve Cook)

• Factor Analysis to define Metabolic Syndrome (Elizabeth Goodman, Brandeis)

• A cross-sectional study of 4,000 Columbian children (Martha Cruz UTEP)

NIH Staff:
T. Huang, NICHD
G. Grave, NICHD
P. Savage, NHLBI
E. Obarzanek, NHLBI
C. Loria, NHLBI
R. Kavey, NHLBI
B. Linder, NIDDK
M. Horlick, NIDDK
S. Groft, ORD

Work to Date
A group of 23 leading scientists was convened to evaluate new evidence to support a common working research definition of the metabolic syndrome (MetS) in children and adolescents.  In addition, 8 NIH staff members from NICHD, NHLBI, and NIDDK contributed to the development of the scientific program and were part of the expert panel (see participant list for individual names).

The panel was convened primarily to evaluate results from a series of new analyses using existing data sets, which program staff at NICHD designed and supervised.  Five sets of the analyses were done through contracts.  One data set was analyzed by program staff within NICHD.  Four other studies presented results that were recently published or submitted for publication.

In brief, the main analyses conducted in preparation for the workshop were:

1. Examining different cutoffs of metabolic components in childhood in relation to corresponding adult components;
2. Examining different cutoffs of metabolic components in childhood in relation to adult MetS and clinical precursors of disease that were precisely measured in childhood;
3. Examining different definitions of the MetS (with varying constituent cutoffs) in relation to adult MetS.

As evidenced by the results presented, MetS in childhood increases the risk for adult MetS as well as incidents of type 2 diabetes (T2D) and cardiovascular disease (CVD) over and beyond any individual metabolic component.  This fact, along with results from multiple factor analyses, suggests that the clustering of metabolic risk factors is unequivocal.

Due to the controversial debate surrounding the MetS in adults, the panel spent a considerable amount of time deciding whether a common definition of the MetS in children was necessary.  At the conclusion of the meeting, however, the majority of panelists decided that MetS as a concept was unlikely to fade within the scientific community and that in order to make studies comparable, a common language was important to establish a baseline of reference.  In addition, though most MetS-affected children are obese, not all obese children develop the MetS.  Thus, there is interest in being able to identify which obese children are metabolically at risk.  The consensus on the need for a working research definition in the pediatric population was a major accomplishment of this workshop.

Summary of Workshop
The expert panel agreed on the need for a pediatric definition of the different metabolic risk factors amid the ongoing debate over the validity and value of the MetS in adults.  To achieve that goal, the panel recommended additional items that need to be addressed over the next year. Specifically, the panel called for the following analyses:

1. Replicating the analyses from the Lipid Research Clinic/Princeton Follow-up Study and Fels Study with T2D and CVD as outcomes.  Running these analyses also in the Bogalusa Heart Study, the Muscatine Study, and possibly the National Growth and Health Study (NGHS, adult MetS as outcome only).  Exploring the possibility of combining some data sets.
2. Examining the stability of MetS phenotypes during childhood and adolescence.  
3. Adapting the international obesity definition approach (IOTF) to waist circumference (WC) using NHANES data.
4. Further examining the role of WC versus WC/height versus BMI percentile in relation to adult T2D and CVD outcomes. 

Subsequent to the workshop, the NICHD has issued four contracts with investigators from the Fels Study, the Muscatine Study, the Bogalusa Heart Study, and NHANES to begin these analyses.  In addition, an intramural-extramural agreement within NICHD is allowing for the conduct of analyses using the Princeton Study, NGHS, and part of Bogalusa Heart Study.  Dr. Huang is working closely with all investigators to determine the proper statistical steps.  A statistical core consisting of NICHD staff and a few expert members from the panel has been formed to oversee the analyses.

We hope to accomplish three things in the next 12 months:

1. Submit the collection of papers based on recent analyses across the various studies along with a preface summarizing the workshop in December 2006.
2. Complete the new analyses and reconvene the panel by the end of FY2007. 
3. Submit an executive summary with a basic working definition of the MetS in children and adolescents following the next conference.