Friday May 22 2009
The study looked at intense treatment to lower blood sugar
“Tighter control of blood sugar levels in people with diabetes may cut their risk of heart problems,” BBC News has reported. The news service said a study pooling data on 33,000 people with type 2 diabetes has shown that intensive control of blood sugar levels cuts heart attacks by 17% and heart disease by 15%.
This well designed study has shown that medication-based intensive care can reduce the risk of heart attacks, but, unsurprisingly, it also increases the risk of episodes where blood sugar falls too low. Intensive blood sugar control targets may not be appropriate for all patients, and can be difficult to achieve.
All people with type 2 diabetes will normally be assessed by their GP, with initial treatment being based on dietary control, followed by diabetes medication if necessary. The most appropriate medication is often selected based on a patient’s particular characteristics and medical history. Diabetics should never alter their blood sugar control regimen themselves, and should always discuss any possible changes with the medical staff directing their treatment.
Where did the story come from?
This research was carried out by Dr Kausik K Ray and colleagues from the Universities of Cambridge and Glasgow, and Addenbrooke’s Hospital in Cambridge. There was no funding source for this study, but the researchers were supported by grants from the British Heart Foundation, the Gates Cambridge Trust and the Overseas Research Studentship Awards Scheme. Some of the authors reported that they had previously received honoraria from various drug companies for giving lectures and acting as members of advisory boards. The study was published in the peer-reviewed medical journal The Lancet.
What kind of scientific study was this?
This was a systematic review and meta-analysis pooling the results of randomised controlled trials (RCTs) on people with type 2 diabetes, comparing the rates of death and cardiovascular events for groups controlling their blood sugar using standard treatment or intensive treatment. The aim of intensive treatment is to achieve a lower blood sugar level than usually aimed for with standard treatment.
The researchers report that RCTs have shown that intensive blood sugar control reduces the risk of adverse small blood vessel events, such as eye problems and poor kidney function (which are more common in diabetics). However, they have not consistently found that it reduces risk of cardiovascular adverse events (large blood vessel disease).
The researchers suggest that this may have been because, individually, the trials were too small to detect an effect and, therefore, they wanted to pool the data from the individual trials to see if there was an effect.
The researchers used databases of medical and scientific literature, expert recommendations and journal article references to find RCTs that compared intensive control with standard blood sugar control in diabetics.
The marker used to determine how well blood sugar levels are being controlled in the long-term is called HbA1c. Improving blood sugar control lowers this measurement. The researchers only included studies where there was a significant difference in HbA1c between the intensive control and standard control groups during follow-up, that is, those trials where intensive control was successfully improving blood sugar control.
They also restricted the studies in their analysis to those that included people whose diabetes was stable, those that looked at cardiovascular event(s) as their main outcome(s) and those that gave enough information about the specific, relevant outcomes.
The researchers extracted information from the included trials, including data on HbA1c measurements, all deaths, deaths from heart attack, non-fatal heart attacks, strokes and any side effects of treatment. Two researchers independently extracted data from each trial to ensure that the data were accurate.
The authors then used statistical methods to pool these results and look at whether intensive control affected these outcomes compared with standard control. They also used statistical methods to look at whether the results from the trials were significantly different from each other, which would suggest that the trials differed in some important way and that it might not be appropriate to pool them all together.
What were the results of the study?
The researchers identified five RCTs that matched their inclusion criteria, which together provided data on 33,040 people with type 2 diabetes.
These RCTs tested different methods of intensive and standard control. Intensive control usually involved a combination of different diabetic medications, while standard treatment was defined as a “half-dose of intensive treatments” in one RCT, “current medication” in one trial, “dietary control” in another and not further defined for two RCTs.
People receiving intensive blood sugar control had HbA1c measurements that were on average 0.9% lower than those receiving standard control.
Across all five RCTs there were 2,892 deaths, 2,318 cases of coronary heart disease (fatal and non-fatal heart attacks), 1,497 non-fatal heart attacks and 1,127 strokes. This was over a follow-up of 163,000 person years (across all participants).
In the intensive control group there were 10 non-fatal heart attacks per 1,000 person-years compared with about 12 per 1,000 person-years in the standard control group.
This means that if 200 people from each group were followed for five years, there would be 10 non-fatal heart attacks in the intensive control group, compared with 12 in the standard control group. This equates to a 17% reduction in the odds of having a non-fatal heart attack for those in the intensive control group (odds ratio [OR] 0.83, 95% confidence interval [CI] 0.77 to 0.93).
In the intensive control group there were around 14 coronary heart disease events per 1,000 person-years, compared with approximately 17 events per 1,000 person-years in the standard control group. This means that if 200 people from each group were each followed for five years, there would be 14 coronary heart disease events in the intensive control group compared with 17 in the standard control group. This meant that intensive control also reduced the odds of coronary heart disease by 15% (OR 0.83, 95% CI 0.77 to 0.93).
However, intensive control did not affect the risk of stroke or of death from any cause.
As expected, more people receiving intensive control (38.1%) had an episode where their blood sugar fell too low (a hypoglycaemic episode) than those receiving standard control (28.6%). Twice as many people in the intensive control group (2.3%) had a severe hypoglycaemic episode than in the standard control group (1.2%). People receiving intensive control gained an average of 2.5kg more weight than those on standard treatment by the end of the study.
What interpretations did the researchers draw from these results?
The researchers conclude that intensive blood sugar control “significantly reduces coronary events without an increased risk of death” in diabetics when compared with standard blood sugar control. However, they also point out that the optimum blood sugar control targets, and methods of achieving these, might differ in different populations.
What does the NHS Knowledge Service make of this study?
This well designed study has illustrated that if intensive control is used successfully it can reduce the risk of heart attacks. However, there are a number of points to note:
- The risk of having a heart attack was quite low in both groups and, therefore, the difference in risk between the groups was also small. If 200 people used intensive treatment for five years, this would prevent three heart attacks compared with if they used standard control over the same period.
- Two of the included RCTs used drugs called glitazones as part of intensive control treatment. Studies have suggested that these drugs increase the risk of heart failure. Although, overall, this review found no significant increase in heart failure with intensive control, statistical tests showed that the results of the individual trials were significantly different from each other, and that this was likely to be due to an increased risk in heart failure with the glitazones.
- The studies included in this review used differing methods of intensive control, and it is not possible to say which method is best. Also, with standard treatment it was unclear exactly what medications were being used.
All people with type 2 diabetes will normally be assessed by their GP and initially treated through dietary control, with oral diabetic medications commenced as necessary. The most appropriate medication is often selected based on an individual patient’s characteristics and comorbidity. All patients will then be followed up regularly, with the aim of keeping their blood sugar at a controlled level and monitoring for any complications or need for a change in treatment.
Intensive drug control may not be appropriate for all people with type 2 diabetes, and can be difficult to achieve. The review also showed that it increases the risk of episodes where blood sugar falls too low. Diabetics should never alter their blood sugar control regimen themselves, and should always first discuss any possible changes with the healthcare professionals in charge of their treatment.