Effects of Antidiabetic Drugs on Risk Factor Pathways

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Of interest, there is now abundant evidence that insulin-sensitising therapies appear to offer benefits beyond just glucose lowering. Metformin, for example, has positive effects on FFAs, HDL-cholesterol, PAI-1 and vascular function, and may also lower markers of inflammation (Grant, 1995; Grant, 2003; Haffner etal., 2005). Glitazones also benefit each of the above parameters, although their actions on HDL-cholesterol and inflammatory parameters are more pronounced and in addition they tend to raise adiponectin and lower the proportion of small, dense LDL particles (Haffner etal., 2002). By contrast, sulphonylureas have far less and often negligible effects on such markers. Such observations emphasise once again the multiple linkages of insulin resistance on other risk factor pathways. They also concur with the greater benefits of metformin (and to a lesser extent glitazones) on CVD risk (Johnson etal., 2005; Evans etal.,

2006). It is clear that by targeting glucose alone without attention to the many other risk factors in diabetes, CVD risk will be only modestly attenuated (Figure 2.7). Much stronger CVD risk reduction is clearly observed when patients with diabetes have, in addition to glucose control, their lipids and blood pressures targeted (Adler, 2003). That said, it is also clear that CVD risk remains higher in patients with diabetes even when current best therapies are employed. Such findings are in keeping with multiple risk factor abnormalities in diabetes, which can, at present, only be partially attenuated.

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