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Intensive Therapy Shows Durability Against Mortality in High-Risk Diabetes

Apr 22, 2008

For type 2 diabetes with microalbuminurea, multi-drug treatment with behavior modification reduced the risk of vascular complications and death from cardiovascular and other causes by 29%.

After a 7.8-year interventional study, succeeded by a 5.5-year observational follow-up, the reduction of death at 13.3 years from any cause was reduced by 20% compared with patients given conventional therapy, reported Oluf Pedersen, M.D., of the Steno Therapy Diabetes Center, and colleagues.

The absolute risk of death from cardiovascular causes was reduced by 13% for those receiving intensive therapy, they wrote.

The Steno-2 study, a prospective, randomized, blinded trial, started in 1993 with 160 patients with type 2 diabetes and persistent microalbuminuria. The study had determined that during an average 7.8 years of an intensified multi-targeted intervention, the risk of vascular complications was reduced by half.

There were 130 remaining at the start of the five-year observational follow-up. In the subsequent 5.5 year follow-up until Dec. 31, 2006, the researchers sought to determine whether this approach would affect the rates of any-cause death and death from cardiovascular causes.

The intensified multifactorial intervention in Steno-2 included tight glucose regulation and the use of rennin-angiotensin system blockers regardless of blood pressure. Patients also received low-dose aspirin and lipid-lowering agents along with behavior modification.

The intensified-treatment targets, consistent with the guidelines of the American Diabetic Association, included a glycated hemoglobin level of less than 6.5%, a fasting serum total cholesterol level of less than 175 mg/dL, a fasting serum triglyceride level of less than 150 mg/dL, a systolic blood pressure of less than 130 mm Hg, and a diastolic blood pressure of less than 80 mm Hg.

At the end of the initial study, the structured treatment of patients in the intensive therapy group stopped.
At 13.3-year follow-up (7.8 years of multifactorial intervention and an additional five years of follow-up), 24 patients (30%) in the intensive-therapy group had died, compared with 40 (50%) in the conventional-therapy group (hazard ratio 0.54, 95% confidence interval 0.32 to 0.89, P=0.02). There was no change in the hazard ratio after the formal intervention was stopped.

Nine patients in the intensive-therapy group died from cardiovascular causes, compared with 19 in the conventional-therapy group (P=0.03).

Intensive therapy was associated with a lower risk of death from cardiovascular causes (hazard ratio 0.43, 95% CI 0.19 to 0.94, P=0.04) and a risk reduction of 29% for cardiovascular events (hazard ratio 0.41, 95% CI 0.25 to 0.67, P<0.001). These risk reductions fit with projections from trials involving single risk factors, the researchers said.
Fewer patients in the intensive-therapy group required retinal photocoagulation (relative risk 0.45, 95% CI 0.23 to 0.86, P=0.02).  Few major side effects were reported, the researchers said.

The beneficial effects were seen despite the fact that the significant differences seen in the levels of risk factors for cardiovascular disease between the groups at the end of the interventional study disappeared by the end of the follow-up period. This was largely because of improvements in risk factors in the non-interventional group. The investigators thus attributed the observed success to early as opposed to later intervention.

This study was not designed to identify which elements of intensive diabetes therapy contributed most to the reduction in cardiovascular risk, the researchers wrote.

However, using a risk calculator based on epidemiologic and interventional data, they concluded that the use of statins and antihypertensive drugs might have had the largest effect in reducing cardiovascular risk during the 7.8 years of intervention, with hypoglycemic agents and aspirin the next most important interventions.

The drugs used in this study differed between study groups so that differences in drugs, or their combinations, might have contributed to the long-term outcome, the researchers said.

Adverse effects were not monitored continually, they said. However, few serious adverse effects were reported during regular interviews with patients.

In this respect, they added, it is noteworthy that except for atorvastatin (Lipitor), generic drugs with well-known long-term side effects were prescribed. Whether newer and more expensive diabetes treatments would have additional benefits or risks remains to be determined, they said.

Practice Pearl:
Explain to patients who ask that for high-risk diabetic patients, tight glucose regulation, the use of appropriate drugs, and behavior modification reduced the risk of death from cardiovascular and other causes
Gaede P, et al "Effect of multifactorial intervention on mortality in type 2 diabetes" N Engl J Med 2008; 358: 580-591.


Discovery Leads to Earlier Diagnosis of Type 1 Diabetes: Researchers identify molecular signature in human type 1 diabetes. Researchers at Children’s Research Institute, in Milwaukee, recently made significant discoveries in juvenile diabetes diagnosis.  Led by Martin Hessner, PhD, associate professor, Medical College of Wisconsin, the research team applied a new approach, finding that type 1 diabetes patients during the honeymoon phase create a unique genomic fingerprint.  The research team used a new type of blood test that identifies inflammation associated with type 1 diabetes though a unique genomic fingerprint.  Remarkably, this fingerprint is evident years prior to disease onset.  This discovery offers insight into the pathways responsible for type 1 diabetes.  This fingerprint will be useful in identifying at-risk children earlier in the disease process.  This offers hope for earlier treatment and even delay or prevention of full-blown diabetes.  Journal of Immunology April, 2008


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