Intensive Blood Sugar Treatment Strategy in Clinical Trial of Diabetes and Cardiovascular Disease Changed

6 February 2008

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health has stopped one treatment within a large, ongoing North American clinical trial of diabetes and cardiovascular disease 18 months early due to safety concerns after review of available data. The study will continue, but it will be slightly modified.

The study is the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study, which has enrolled 10,251 participants.

In the ACCORD study, adults with type 2 diabetes were recruited, especially people at higher risk for diabetes and stroke. These participants were divided into two groups and were treated in one of two ways (depending on which group they were in):

• lowering of blood glucose (sugar) below current recommendations, by intensive methods
  
• lowering of blood glucose (sugar) below current recommendations by a less-intensive method
  

After four years, the participants in the intensive method for lowering blood glucose levels had a slightly higher rate of death than the less-intensive group. The slightly higher death rate concerned the Data and Safety Monitoring Board (DSMB), who advised the research study lead, Elizabeth G. Nabel, M.D to stop the group receiving the higher intensity strategy for lowering blood glucose levels. This means that there is now only one group of participants, those receiving the less-intensive strategy to lower their blood glucose levels.

Of the participants, 257 in the intensive group died, while 203 in the standard treatment group died in the four years of treatment. The study researchers advise that the death rates of both groups (about 3 per 1,000) are lower than in other, similar studies.

The Data and Safety Monitoring Board (DSMB) are an independent advisory group of experts in diabetes, cardiovascular disease, epidemiology, patient care, biostatistics, medical ethics, and clinical trial design that has been monitoring ACCORD since it began.

“A thorough review of the data shows that the medical treatment strategy of intensively reducing blood sugar below current clinical guidelines causes harm in these especially high-risk patients with type 2 diabetes,” said Elizabeth G. Nabel, M.D., director, NHLBI. “Though we have stopped this part of the trial, we will continue to care for these participants, who now will receive the less-intensive standard treatment. In addition, we will continue to monitor the health of all participants, seek the underlying causes for this finding, and carry on with other important research within ACCORD.”



Resources
The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. For Safety, NHLBI Changes Intensive Blood Sugar Treatment Strategy in Clinical Trial of Diabetes and Cardiovascular Disease. Accessed 9 February 2008

Diet and lifestyle critical to recovery from illness

In a study by researchers from the University of Manchester UK, published in the Journal of Nature Genetics on 17 January 2008, it appears that diet and lifestyle play a much bigger role in a person's ability to recover from certain drug therapies, including cancer therapy.

Writing in Nature Genetics, University of Manchester researchers have shown how the nutrients in the environment are critical to the fitness of cells that carry genetic mutations caused by diseases.

The findings for the first time provide a scientific insight into why some people might respond better to certain medications than others and form the foundations for more individualised drug therapy in the future.

The team used baker's yeast — a model organism studied by biologists to reveal molecular processes in higher organisms — to explore the relationship between environment and genetic background.

The large-scale study involved removing one of the two copies of all yeast genes — similar to removing one parent's set of genes in a human — and analysing the resulting fitness under different dietary restrictions.

"If the gene targeted is quantitatively important, you would normally expect the yeast to show a reduction in fitness," said Dr Daniela Delneri, who carried out the research in the University's Faculty of Life Sciences.

"But what we found was that in certain environmental conditions, removing one copy of certain genes actually produced the opposite effect and surprisingly the yeast cells grew more quickly and were healthier."

The team further established that this effect was mainly occurring in genes involved in the proteasome — the quality-control system within the cell that degrades unwanted proteins.

"The proteasome is important as it maintains the equilibrium of the cell," said Dr Delneri. "When this equilibrium is lost it can result in a number of diseases, including cancer, diabetes, Huntingdon's, Alzheimer's and Parkinson's.

"For example, in rapidly-growing cancerous cells the high proteasome activity renders the tumour cells immortal, so drugs that block or inhibit the proteasome's actions are currently used as therapeutic compounds.

"Our study shows that reduced proteasome activity could be either advantageous or damaging to the cell depending on the nutrients available to it in the surrounding environment."

The findings suggest that, ideally, when therapeutic drugs are administered to alter the proteasome activity, the environment — governed by the type of tissue or a person's diet and lifestyle — should be taken into consideration to assure the correct beneficial effect.

University of Manchester Press Release