GENETIC PREDICTORS OF THIAZOLIDINEDIONE RESPONSE

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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. Pioglitazone (Actos) is approved by the Food and Drug Administration (FDA) and is used for the treatment of type 2 diabetes. People differ in the way they respond to pioglitazone. It is an effective medication for some people, but it does not work as well in other people. This may be a result of differences in the amount of pioglitazone in the blood. This may be due to differences in the way the drug is broken-down in the body. The way a medication is broken-down in the body may be affected by a person s genetic make-up (or DNA). The purpose of the first part of this clinical study is to determine if a person s genetic make-up affects the amount of pioglitazone in the blood and the blood sugar-lowering response to pioglitazone. This study will be undertaken in people with type 2 diabetes. The second part of this clinical study is looking at how a person s genetics affects drug interactions. The drug interaction that will be studied is pioglitazone and gemfibrozil (Lopid). Gemfibrozil is a popular cholesterol-lowering medication. When given in combination with pioglitazone, gemfibrozil increases the blood levels of pioglitazone. However, this effect is not consistent among all people. Some people have much larger increases in pioglitazone blood levels than other people. The purpose of this study is to see if genetics influences the extent to which gemfibrozil increases pioglitazone blood levels. This study will be undertaken in healthy people without type 2 diabetes.