PHARMACOGENETICS OF PRO 12ALA PPAR-GAMMA-2

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this protocol is to determine why some individuals do not respond well to thiazolidinediones, a class of antidiabetic drugs. These drugs work by improving the sensitivity of the body to insulin. Subjects will be recruited on the basis of their genotype, as it is believed that a particular variant (Pro 12Ala PPAR-gamma-2) may cause a blunted response to these drugs. Subjects with impaired glucose tolerance (a precursor of diabetes) will be recruited and treated with rosiglitazone, a thiazolidinedione. Insulin sensitivity will be tested before and after a 12 week treatment with rosiglitazone, both in terms of glucose uptake an inhibition of lipolysis (fat breakdown). Likewise, gene expression in fat and muscle will be studies before and after treatment. The protocol concludes with a 12 week didactic weight management program.