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HbA1c and Survival In Diabetes: Mystery Unveiled?

by Nithin Jayan on  September 30, 2010 at 3:39 PM Health In Focus   - G J E 4
An HbA1c threshold of 7·5% may correspond to the lowest death rate. 'Low and high mean HbA1c values were associated with increased all-cause mortality and cardiac events'

Glycated haemoglobin (HbA1c) has been the gold standard for therapeutic target in diabetes management ever since its introduction in the 1980s. "The lower the HbA1c the better" was the dictum. Just like any other scientific principle, the concept is now highlighted with confusion.

Three questions popped up:

What is the target HbA1c?

How tight should intensive glycaemic control be?

Who are most likely to benefit from intensive control?

What is the target HbA1c?

Measurement of glycated haemoglobin (HbA1c) is used to assess long-term glycemic control ( or blood glucose level in blood). It is a reflection of the glycemic history over the previous 2-3 months. The suggested goal in the management of Diabetes Mellitus is to achieve 'an A1C as close to normal as possible without significant hypoglycaemia.' The target HbA1c had been suggested to be less than 7% (in general). An Intensive or tight glycaemic control meant Hb1Ac levels as low as 6.5% or even 6%. This is achieved by a combination of multiple oral drugs, insulin and stringent lifestyle modifications.

New research studies now suggests that a too high or too low value of HbA1c is harmful in people with type 2 diabetes. A recent report published in the leading journal Lancet states that '10% of patients with the lowest Hba1c values (<6.7%) had a higher death rate than all but the highest top 10% who had a HbA1c of >9.9%.' An HbA1c threshold of 7·5% may correspond to the lowest death rate.

What are the benefits of intensive control?

It is known that an Intensive or tight glycaemic control reduces the long-term risk of microvascular complications e.g. retinopathy, nephropathy and neuropathy, in people with type 2 diabetes. This can however take a long time to display apparent benefits. The utility in the reduction of macrovascular complications, i.e. coronary artery disease, stroke and peripheral vascular disease is not known.

What are the risks of intensive control?

Inducing a rapid decrease in HbA1c can cause:

Hypoglycaemia

Weight gain (especially with insulin or sulphonylureas)

Chance of increased risk of mortality

The patient also finds it difficult. The treatment causes undue stress and frustration ultimately leading to decreased patient compatibility. Older people with a long duration of diabetes and who are at high cardiovascular risk may be at particular risk of harm from intensive control.

Who are most likely to benefit from intensive control?

People who are younger

Newly diagnosed with type 2 diabetes

Have low cardiovascular risk

It seems all these three requirements need to be satisfied to make a person eligible to reap benefits from intensive control diabetes. The practical feasibility is, obviously, limited owing to a 'late diagnosis of diabetes.'

The benefit of early intervention has not been questioned yet! Fortunately, no controversies exist apparently. Control of postprandial glucose (PPG) and Glucose Variability seems to require more attention.

To conclude, this is what Lancet said, 'Low and high mean HbA1c values were associated with increased all-cause mortality and cardiac events'. An HbA1c threshold of 7·5% may correspond to the lowest death rate.

Diabetes guidelines should hence need revision to include a minimum HbA1c value.

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