GI News special report Tight glucose control and heart disease Earlier this year, we reported that part of a major US clinical trial (ACCORD) had been halted when researchers checking interim results found that more people receiving intensive glucose lowering therapy died (257 deaths) compared with those getting the standard treatment (203 deaths). Half of the deaths in the intensive-control group were from heart disease – what the treatment was intended to prevent.
What happened next? The first papers on the ACCORD trial and an Australian study (ADVANCE) have now been published in the New England Journal of Medicine.
ACCORD and ADVANCE were both big trials (over 10,000 and 11,000 participants respectively) and long term (3.5–5 years). The researchers wanted to see whether intensive blood glucose control (with drugs not diet and lifestyle) would dramatically reduce the number of heart attacks and stroke in high risk people with long established type 2 diabetes. The studies were designed to bring the participants’ average A1c down to 6% or even less (the average A1c level in people without diabetes falls between 3.5 and 5.5%).
Although the ADVANCE study shows clear benefits of intensive blood glucose control in reducing kidney disease risk, the ‘most compelling message from both studies is that near normal glycemic control for a median of 3.5 to 5 years does not reduce cardiovascular events within that timeframe’ report Drs Dluhy and McMahon writing in an editorial in the same issue of the journal.
A couple of big differences in the two studies stand out. Participants in ACCORD had a very rapid rate of decline in their blood glucose levels (1.4% within 4 months in their A1c). In ADVANCE, the decline was a gradual one – 0.5% at 6 months and 0.6% at 12 months.
There were also differences in weight gain. ACCORD volunteers gained an average of 3.5 kg and more than 27% of them piled on over 10 kg. Average weight gain in the ADVANCE trial compared with the standard therapy group was much less – 0.7 kg. ‘The weight gain may not be a trivial point, since achieving glycemic control with such an aggressive drug strategy is clearly not equivalent to achieving such control through lifestyle changes (i.e. nutritional therapy and increased physical activity)’ writes Dr William Cefalu in an accompanying editorial.
So, what’s the take-home message for health professionals and people with type 2 diabetes?
Drs Dluhy and McMahon conclude: ‘The most appropriate target for glycated hemoglobin (A1c) should remain 7%, though lower individualized targets may be appropriate when the focus is primary prevention of macrovascular (heart) disease … Clinicians caring for patients with diabetes should continue to focus on smoking cessation, dietary and exercise counseling, blood-pressure control, and providing aspirin and a statin to a greater extent than achieved even in the ADVANCE and ACCORD studies. For now, rather than changing our current glycemic target, we may best serve our patients with type 2 diabetes by implementing programs to help more of them reach the currently recommended goals.’
In the last decade, research has yielded overwhelming evidence that lifestyle changes such as a healthy eating plan and increasing exercise make a real difference in the risk of developing type 2 diabetes and in the quality of health of those who already have it. In addition, mounting evidence shows that reducing your post-meal glucose rises is at least as important as hitting your target A1c when it comes to avoiding complications of type 2 diabetes including heart attacks. That’s why the International Diabetes Federation now urges people with type 2 diabetes to focus on healthy eating, physical activity and weight control to manage their diabetes and to keep their 2-hour post-meal blood glucose levels under 7.8 mmol/L (140 mg/dL).
Preventing diabetes – how long do lifestyle interventions last? Several studies around the world have shown that three out of five people with pre-diabetes (impaired glucose tolerance) can prevent or at least delay getting type 2 diabetes by making lifestyle changes such as increasing their activity level, eating a healthier diet and achieving a modest weight loss (5–10 kg). Major clinical trials in USA, China, India, Finland and Japan have shown that ‘lifestyle interventions’ with group or individual counseling are very effective in helping people change their diet and get more exercise. The question is, how long do the ‘intervention’ benefits last when the professional support ends and you are on your own? A recent report in the Lancet suggests that a period of active lifestyle intervention can produce a significant reduction in the incidence of diabetes over the long term.
In 1986, 577 adults with impaired glucose tolerance from 33 clinics in China were randomly assigned to either a control group or to one of three lifestyle intervention groups (diet, exercise, or diet plus exercise). The study participants who followed a healthy diet (drinking less alcohol, eating more vegetables and losing weight if they were overweight or obese) and exercise (increasing leisure time physical activity) regime significantly delayed the development of diabetes for the six years of the ‘active intervention’ period compared with those in the control group. What about the long term? When researchers followed up 568 of the original 577 study participants in 2006 they found that:
435 people had developed type 2 diabetes – including 93% of the control group and 80% of the combined intervention groups.
The onset of diabetes was significantly delayed among those who had been in the intervention groups, they had spent an average of 3.6 fewer years with diabetes than those in the control group.
Fewer people from the intervention groups who had diabetes were on insulin.
‘There were 33.2 million people with impaired glucose tolerance in China in 2003,’ write the researchers, ‘and this is expected to increase to 54.3 million by 2025. Small group and lifestyle counseling in high-risk individuals at community facilities is likely to be effective if aimed more broadly at the Chinese population … at a more global level, widespread adoption of such interventions offers the prospect that projected increases in type 2 diabetes could be attenuated.’
The ‘sweet tooth’ gene A new study by University of Toronto researchers published in Physiological Genomics reports that people with a specific genetic variation in the GLUT2 (glucose transporter type 2) gene which controls glucose entry into the cells consistently consume more sugary foods. ‘Certainly environmental factors can influence the foods that we like and dislike,’ says lead researcher Ahmed El-Sohemy. ‘But what this line of research demonstrates is that there is also a biological or a genetic basis for some of our likes and dislikes.’ El-Sohemy and his colleagues studied two large groups of volunteers, who completed detailed records of their daily diet. Analyzing blood samples, they found that people with a different form of GLUT2 consumed ‘between 20 and 30 grams of sugar extra ... every day’ he says. ‘It was about the equivalent amount of sugar that you would find in a regular sweetened can of soda.’
The GLUT2 gene is known to work in the pancreas. Other researchers have studied it in the brains of mice and ‘it turns out this gene is also turned on in regions of the brain that control appetite,’ says El-Sohemy. ‘Taken together, our findings show that a genetic variation in GLUT2 is associated with habitual consumption of sugars, suggesting an underlying glucose-sensing mechanism that regulates food intake.’
GI Group: For more detailed findings, check out the University of Toronto press release.
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