A little glycemic control goes a long way, according to 10-year followup data from the United Kingdom Prospective Diabetes Study (UKPDS).

The results showed patients with newly diagnosed type 2 diabetes benefit over the long term from several years of tight control of blood glucose levels, but the same can’t be said for tight management of blood pressure.

The UKPDS randomly assigned 4,209 of these patients to receive conventional therapy (dietary restriction) or intensive glucose-lowering therapy (sulfonylurea or insulin or, in overweight patients, metformin). In addition, 1,148 patients who also had hypertension were randomly assigned to tight or less-tight blood pressure control regimens.

Initial results over a median 10-year followup showed intensive glucose therapy was associated with a reduced risk of microvascular complications, but only the overweight patients on metformin had the additional benefits of a reduction in myocardial infarction risk and all-cause mortality.

Between-group differences in glycosylated hemoglobin levels were lost in the first year after the study ended and differences in blood pressure disappeared within two years. But the latest followup results show that a decade later, tight glucose control was associated with a continued reduction in microvascular complications as well as newly apparent reductions in the risks of myocardial infarction and death from any cause.

In the sulfonylurea-insulin group, relative reductions in risk persisted at 10 years for any diabetes-related endpoint (9%) and microvascular disease (24%). Risk reductions for myocardial infarction (15%) and death from any cause (13%) emerged over time.

In the metformin group, significant risk reductions persisted for any diabetes-related endpoint (21%), myocardial infarction (33%) and death from any cause (27%).

In contrast, the blood pressure arm of the study showed that the significant risk reductions seen during the trial for any diabetes-related endpoint, diabetes-related death and microvascular disease were not sustained during post-trial followup. A statistically significant 50% reduction in the risk for peripheral vascular disease emerged over time, but the number of patients who suffered this complication was small.

“Optimal blood-pressure control is of major importance in reducing the risks of microvascular and macrovascular disease in patients with type 2 diabetes but must be maintained if these benefits are to be sustained,” wrote lead author Dr. Rury Holman of the Oxford Centre for Diabetes, Endocrinology and Metabolism, and colleagues.

The authors contrasted their long-term results in newly diagnosed patients with recently reported data suggesting that tight glucose control does not decrease macrovascular complications over the short term in patients with long-standing type 2 diabetes, and may even be harmful.

The Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial showed a significant reduction only in major microvascular events (14%) at a median followup of five years, driven mainly by a reduction in the risk for new or worsening nephropathy. And the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was stopped early (at 3.5 years) because of an unexplained higher rate of death from any cause in the group assigned to tight glucose control.

About one-third of the patients in the ADVANCE and ACCORD trials had a history of macrovascular disease, compared with only 7.5% in the UKPDS.

References:
Holman RR, Paul SK, Bethel MA, et al. 10-year followup of intensive glucose control in type 2 diabetes.

N Engl J Med. 2008 Sep 10. (Early online publication.)

Holman RR, Paul SK, Bethel MA, et al. Long-term followup after tight control of blood pressure in type 2 diabetes. N Engl J Med. 2008 Sep 10. (Early online publication.)