Clinical Implications of the DREAM Study: Response to Kanat

Because impaired fasting glucose (IFG) in the DREAM study (1) was defined at the time of recruitment as a fasting plasma glucose (FPG) concentration of ≥6.1 to <7.0 mmol/l (110–125 mg/dl), Dr. Kanat (2) raises the possibility that patients with FPG levels of 5.6–6.0 mmol/l (100–109 mg/dl), which fall within the more recent American Diabetes Association definition of IFG (3), might not respond similarly to rosiglitazone. This seems unlikely, since these subjects have less of an abnormality of glucose homeostasis than those who fulfill the older criterion. Furthermore, there are two bits of evidence against his contention. In the Diabetes Prevention Program (DPP) (4), subjects were selected with FPG concentrations as low as 5.3 mmol/l (95 mg/dl) and responded to the drug and lifestyle interventions. Second, in the same study (5), before the troglitazone (Rezulin) arm was discontinued, the response in subjects receiving this drug for up to 1.5 years (mean 0.9) was even better than in those undergoing the intensive lifestyle intervention and was similar to the response seen with rosiglitazone in the DREAM study (1). Whether thiazolidinediones actually delay the development of type 2 diabetes, as troglitazone seemed to do in women with gestational diabetes (6), or simply treat rising glycemia, as seemed to be the case in the troglitazone arm of the DPP (5), is not clear. Perhaps the follow-up evaluation of the subjects in the DREAM study will shed light on this important question.