Multiple studies published in recent years have provided evidence that intensive treatment (HgA1c average of 6.4 to 6.9 percent) of hyperglycemia in patients with type 2 diabetes does not in all cases lead to an acceptable balance of benefits to risks. Although important questions remain, the authors of this article say the results of these studies suggest possible changes in therapeutic approach. They present an updated view of challenges and opportunities in treating high-risk patients with type 2 diabetes, drawing mainly on lessons from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study and including some testable hypotheses.
The ACCORD trial consisted of a population with type 2 diabetes and high cardiovascular risks. It was stopped early because of increased mortality in the intensive glycemic treatment group. Further reports have appeared from ACCORD and other studies of high-risk populations, notably the Action in Diabetes and Vascular Disease: Preterax and Diamacron MR Controlled Evaluation (ADVANCE) and the Veterans Affairs Diabetes Trial (VADT). These studies reported the following:
1. Primary cardiovascular outcomes did not improve with intensive glycemic therapy in these high-risk populations.
2. In ACCORD, but not in the other trials, a 22 percent increase in all-cause mortality accompanied intensive glycemic treatment.
3. In a meta-analysis of major trials, a nine percent reduction in major cardiovascular events accompanied intensive glycemic treatment but no significant effect was observed on all-cause mortality or cardiovascular mortality.
4. Nonfatal stroke showed no difference with intensive glycemic therapy.
5. Nonfatal myocardial infarction was reduced with intensive glycemic therapy.
6. Presence of albuminuria showed a clear benefit in intensive therapy in the ACCORD trial.
7. In the ACCORD trial, worsening vision was not reduced, but retinopathy was reduced by 33 percent in the intensive therapy group.
8. After 40 months, brain volume loss was less in the intensive treatment group, as assessed by magnetic resonance imaging. No cognitive differences were found between the groups.
9. High-risk baseline characteristics for increased mortality include HgA1c > 8.5% with prior treatment, hypoglycemia necessitating medical assistance, short life expectancy, and established cardiovascular or microvascular disease.
Overall, mortality increased in high-risks patients in the intensive glycemic group via several proposed mechanisms, including drug effects, weight gain, reductions in hemoglobin A1C diabetes blood test levels, and hypoglycemia. While significant reductions in nonfatal myocardial infarction, albuminuria, brain shrinkage and retinopathy resulted from intensive glycemic control, no benefit occurred in cardiovascular function, renal function, vision and cognition during the three- to five-year follow-up period.
They conclude that these findings do not support abandoning the current recommendations for achieving HgA1c less than 7.0. However, they do suggest the implementation of individualized treatment goals in high-risk patients.