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1 July 2009

Residual risk of microvascular complications of diabetes: is intensive multitherapy the solution?

Professor Paola Fioretto

Member of the R3i International Steering Committee
Professor Paola Fioretto Microvascular diabetic complications impact substantially on patient quality of life and confer a significant economic burden on healthcare systems. In the US, diabetes is the leading cause of blindness, end-stage renal disease and non-traumatic limb amputations. Tight glycemic and blood pressure control are mandatory to prevent microvascular complications; however, current standards of care do not eliminate the risk.

Taking nephropathy as example, the UKPDS and, more recently, the ADVANCE trial have demonstrated the efficacy of tight glycemic control in preventing the development of microalbuminuria and the progression to overt nephropathy. Reduction in mean blood pressure, especially when obtained using angiotensin II receptor blockers or angiotensin converting enzyme inhibitors, prevents the development and slows the progression of nephropathy. However, in the UKPDS, despite good glycemic and blood pressure control, 29% developed microalbuminuria and 7% progressed to macroalbuminuria. In the Steno-2 study, which randomized 160 type 2 diabetic patients with microalbuminuria, over a 7.8 yr follow-up, intensive multifactorial intervention with aggressive treatment of glycemia, blood pressure and dyslipidemia was associated with reduced progression from microalbuminuria to overt diabetic nephropathy. However, nephropathy developed in 20% of intensively treated patients. Overall, these data suggest the existence of high residual risk for nephropathy.

There is growing evidence that lipid abnormalities may be implicated in the development and progression of diabetic nephropathy; indeed, both elevated triglycerides and low HDL are independent risk factors. In the UKPDS, triglycerides were independently associated with microalbuminuria and macroalbuminuria. With respect to the development of renal insufficiency (eGFR<60 ml/min), low HDL was shown to increase risk by nearly 3-fold. Correction of atherogenic dyslipidemia might therefore provide additional benefit.

In conclusion, there is an urgent need to address the issue of microvascular residual risk in diabetes and to define optimal strategies for reducing this risk. Identifying those factors most relevant to microvascular residual risk is currently being addressed by an ongoing R3i multinational epidemiological study.