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Review
. 2011 Fall;8(3):432-40.
doi: 10.1900/RDS.2011.8.432. Epub 2011 Nov 10.

Metabolic memory and individual treatment aims in type 2 diabetes--outcome-lessons learned from large clinical trials

Cristina Bianchi  1 , Stefano Del Prato
Affiliations
Review

Metabolic memory and individual treatment aims in type 2 diabetes--outcome-lessons learned from large clinical trials

Cristina Bianchi et al. Rev Diabet Stud. 2011 Fall.

Abstract

Reducing the burden of long-term complications in type 2 diabetic patients remains a major task, and represents a huge challenge. Whilst tight glycemic control has been shown to reduce the risk of microvascular complications, controversy remains regarding the benefit of intensive treatment in relation to the prevention of cardiovascular events. Recent large trials (including ACCORD, ADVANCE, and VADT) were unable to show a significant impact of glycemic control on cardiovascular events. Also, it has been argued that these trials included patients with a long duration of the disease, and with previous unsatisfactory glycemic control. Chronic exposure to hyperglycemia may cause a kind of negative metabolic memory, and thereby reduce the potential impact of good glycemic control. This concept has been corroborated by the UKPDS which recruited only subjects with newly diagnosed diabetes and without prior cardiovascular events. In these patients, early achievement of glycemic control translated into a long-term reduction of the risk of micro- and macrovascular complications. This observation prompted the UKPDS investigators to propose a positive "glycemic legacy", supporting the need for early and appropriate treatment of hyperglycemia and associated metabolic disturbances. This should be feasible now through the selection of individual targets and personalized pharmacologic treatments. In doing so, the potential risks of intensive treatment might then be avoided.

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Figures

Figure 1
Figure 1. Hazard ratios for major causes of death
Diabetes vs. non-diabetes [1].
Figure 2
Figure 2. Hypothetical representation of the natural history of diabetic patients recruited in the Veteran Administration Diabetes Trial (VADT)
The upper dotted line represents the HbA1c levels over time estimated on the basis of the average glucose profile described in the UKPDS. The lower dotted line represents the ideal time course of glycemic control. The solid line represents the time course of HbA1c in the VADT. Reprinted with permission from [9].
Figure 3
Figure 3. Patient characteristics in large clinical diabetes trials
Compared with the pivotal United Kingdom Prospective Diabetes Study (UKPDS), which enrolled newly diagnosed patients, recent trials have enrolled high-risk patient populations characterized by a longer duration of disease, older age, and more severe hyperglycemia (i.e. higher HbA1c levels) at baseline [5-7].
Figure 4
Figure 4. Treatment goal personalization
Recommedations according to the American Diabetes Association and the American Heart Association [19].
Figure 5
Figure 5. Schematic representation of the HbA1c and ABCD strategies for recently diagnosed patients with type 2 diabetes
* Micro- and macrovascular complications. Adapted from [21].
Figure 6
Figure 6
The 5 finger rule for glycemic target personalization.
See this image and copyright information in PMC

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