Lower A1cs and Renal Outcomes in Type 2 Diabetes?
Lower A1cs and Renal Outcomes in Type 2 Diabetes?
Coca SG, Ismail-Beigi F, Haq N, Krumholz HM, Parikh CR
Arch Intern Med. 2012;172:761-769
This systematic review and meta-analysis by Coca and colleagues examined whether intensive glycemic control was associated with better clinically relevant renal outcomes among patients with type 2 diabetes. The investigators evaluated 7 trials involving 28,065 adults who were followed for 2-15 years. Their criteria were as follows:
The surrogate endpoints were development of microalbuminuria and macroalbuminuria. The clinical endpoints included doubling of the serum creatinine level, end-stage renal disease (ESRD), and death from renal disease.
The included trials were the Kumamoto Study, 2 arms of the UKPDS, the VA Diabetes Feasibility Trial, ACCORD, ADVANCE, and VADT. Compared with conventional control, intensive glucose control reduced the risk for microalbuminuria (risk ratio [RR], 0.86; 95% CI, 0.76-0.96) and macroalbuminuria (RR, 0.74; 95% CI, 0.65-0.85) but not doubling of the serum creatinine level (RR, 1.06; 95% CI, 0.92-1.22), ESRD (RR, 0.69; 95% CI, 0.46-1.05), or death from renal disease (RR, 0.99; 95% CI, 0.55-1.79). Compared with the surrogate renal endpoints of microalbuminuria (23%) and macroalbuminuria (5%), the pooled cumulative incidence of doubling of the serum creatinine level, ESRD, and death from renal disease was low (< 4%, < 1.5%, and < 0.5%, respectively).
Following the inability of intensive glycemic control to reduce cardiovascular disease (CVD) risk in the ACCORD, ADVANCE, and VADT trials, there were concerns that clinicians and patients might begin to discount glucose control as a diabetes goal; As a result, the American Diabetes Association (ADA), the American College of Cardiology Foundation, and the American Heart Association issued a joint statement reaffirming that lowering A1c to below or around 7% was desirable for the reduction of microvascular disease risk. A1c of about 7% remains the recommendation of the ADA, although just-published guidelines encourage less stringent goals depending on the patient.
There is an important distinction between the goal of "below or around" 7% and the tight glycemic control or intensive therapy interventions that were tested in the studies included in the systematic review conducted by Coca and colleagues. Overall, the findings do not seem to support an A1c goal much below 7%, if that. Although reducing risk for microalbuminuria and macroalbuminuria is certainly desirable, the meta-analysis results were driven by ACCORD and ADVANCE, each of which achieved median A1c of about 6.5%. In light of the mortality risk found in ACCORD and supporting information from an observational analysis suggesting a U-shaped relationship between A1c and mortality, the trade-off of lower microvascular risk for higher CVD risk hardly seems worthwhile. Furthermore, the hard clinical endpoints analyzed in the present study did not show a benefit from tight glycemic control, although they trended in that direction. The trend did not become significant primarily because the prevalence of these endpoints was relatively low. So again, because CVD (and mortality) in diabetes is a much more common problem, the trade-off of kidney disease risk reduction for increased CVD risk might not be worthwhile. The ADA goal of A1c levels below or around 7% and the patient-centered considerations allowing for higher A1c levels in specific patients appear to be the appropriate approach.
Abstract
Role of Intensive Glucose Control in Development of Renal End Points in Type 2 Diabetes Mellitus: Systematic Review and Meta-analysis
Coca SG, Ismail-Beigi F, Haq N, Krumholz HM, Parikh CR
Arch Intern Med. 2012;172:761-769
Study Summary
This systematic review and meta-analysis by Coca and colleagues examined whether intensive glycemic control was associated with better clinically relevant renal outcomes among patients with type 2 diabetes. The investigators evaluated 7 trials involving 28,065 adults who were followed for 2-15 years. Their criteria were as follows:
participants were randomly assigned to intensive vs standard glycemic control;
the study assessed progression or development of kidney disease as either a primary or surrogate outcome; and
involved only participants with stable disease and was conducted in the outpatient setting.
The surrogate endpoints were development of microalbuminuria and macroalbuminuria. The clinical endpoints included doubling of the serum creatinine level, end-stage renal disease (ESRD), and death from renal disease.
The included trials were the Kumamoto Study, 2 arms of the UKPDS, the VA Diabetes Feasibility Trial, ACCORD, ADVANCE, and VADT. Compared with conventional control, intensive glucose control reduced the risk for microalbuminuria (risk ratio [RR], 0.86; 95% CI, 0.76-0.96) and macroalbuminuria (RR, 0.74; 95% CI, 0.65-0.85) but not doubling of the serum creatinine level (RR, 1.06; 95% CI, 0.92-1.22), ESRD (RR, 0.69; 95% CI, 0.46-1.05), or death from renal disease (RR, 0.99; 95% CI, 0.55-1.79). Compared with the surrogate renal endpoints of microalbuminuria (23%) and macroalbuminuria (5%), the pooled cumulative incidence of doubling of the serum creatinine level, ESRD, and death from renal disease was low (< 4%, < 1.5%, and < 0.5%, respectively).
Viewpoint
Following the inability of intensive glycemic control to reduce cardiovascular disease (CVD) risk in the ACCORD, ADVANCE, and VADT trials, there were concerns that clinicians and patients might begin to discount glucose control as a diabetes goal; As a result, the American Diabetes Association (ADA), the American College of Cardiology Foundation, and the American Heart Association issued a joint statement reaffirming that lowering A1c to below or around 7% was desirable for the reduction of microvascular disease risk. A1c of about 7% remains the recommendation of the ADA, although just-published guidelines encourage less stringent goals depending on the patient.
There is an important distinction between the goal of "below or around" 7% and the tight glycemic control or intensive therapy interventions that were tested in the studies included in the systematic review conducted by Coca and colleagues. Overall, the findings do not seem to support an A1c goal much below 7%, if that. Although reducing risk for microalbuminuria and macroalbuminuria is certainly desirable, the meta-analysis results were driven by ACCORD and ADVANCE, each of which achieved median A1c of about 6.5%. In light of the mortality risk found in ACCORD and supporting information from an observational analysis suggesting a U-shaped relationship between A1c and mortality, the trade-off of lower microvascular risk for higher CVD risk hardly seems worthwhile. Furthermore, the hard clinical endpoints analyzed in the present study did not show a benefit from tight glycemic control, although they trended in that direction. The trend did not become significant primarily because the prevalence of these endpoints was relatively low. So again, because CVD (and mortality) in diabetes is a much more common problem, the trade-off of kidney disease risk reduction for increased CVD risk might not be worthwhile. The ADA goal of A1c levels below or around 7% and the patient-centered considerations allowing for higher A1c levels in specific patients appear to be the appropriate approach.
Abstract
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