Study of Serum Markers for Cardiovascular Risk in Obese Youth and Impact of Lifestyle and Medication Intervention

Summary

In Protocol #2, we will select 30 obese pubertal and 30 obese prepubertal subjects with an abnormal cytokine profile (i.e. fibrinogen and/or hsCRP concentration greater than or equal to 2 Standard Deviations (SD) above the mean established in our lab for lean controls in Protocol #1). They will be randomly assigned to either lifestyle intervention (diet/exercise) or diet/exercise plus metformin for 6 months. After the 6 month evaluation the subjects will cross over the treatment arms, i.e., those that were doing diet/exercise intervention only will add metformin, those that were doing the diet/exercise plus metformin will discontinue the metformin and continue with diet/exercise changes only. Intrahepatic fat contents will be measured as well. The investigators hypothesize that obese children in these age groups will have increased cardiovascular risk related to their obese state before reaching the currently defined criteria of metabolic syndrome. The investigators hypothesize that these cardiovascular risks can be reduced with lifestyle and drug interventions.

Timeline

Start

2003-11

Primary completion

2009-05

Completion

2011-09

Publications

• Results Mauras N, Delgiorno C, Kollman C, Bird K, Morgan M, Sweeten S, Balagopal P, Damaso L. Obesity without established comorbidities of the metabolic syndrome is associated with a proinflammatory and prothrombotic state, even before the onset of puberty in children. J Clin Endocrinol Metab. 2010 Mar;95(3):1060-8. doi: 10.1210/jc.2009-1887. Epub 2010 Jan 8.
• Results Rynders C, Weltman A, Delgiorno C, Balagopal P, Damaso L, Killen K, Mauras N. Lifestyle intervention improves fitness independent of metformin in obese adolescents. Med Sci Sports Exerc. 2012 May;44(5):786-92. doi: 10.1249/MSS.0b013e31823cef5e.
• Results Mauras N, DelGiorno C, Hossain J, Bird K, Killen K, Merinbaum D, Weltman A, Damaso L, Balagopal P. Metformin use in children with obesity and normal glucose tolerance--effects on cardiovascular markers and intrahepatic fat. J Pediatr Endocrinol Metab. 2012;25(1-2):33-40. doi: 10.1515/jpem-2011-0450.
• Benson M, Hossain J, Caulfield MP, Damaso L, Gidding S, Mauras N. Lipoprotein subfractions by ion mobility in lean and obese children. J Pediatr. 2012 Dec;161(6):997-1003. doi: 10.1016/j.jpeds.2012.05.060. Epub 2012 Jul 20.

Drugs

Indications