medwireNews: The excess mortality risk associated with high or very low glycated hemoglobin (HbA1c) values is modified by glycemic variability in diabetes patients aged 70 years or more, shows an analysis of The Health Improvement Network (THIN) database.
Glycemic variability had a negative survival effect regardless of whether the variability resulted in increasing or decreasing HbA1c, although the researchers note that “the risk seems to be greater in the direction of intensification (ie, reducing HbA1c).”
In younger populations, decreasing HbA1c, especially from a high level, would be expected to reduce the risk for complications and mortality, but in this study the reverse was observed. For example, women with glycemic variability scores outside of the range the researchers considered to represent stable glycemia had a 2.47-fold increased mortality risk if their HbA1c levels were overall decreasing, but a smaller 1.82-fold increased risk if they were increasing.
Rather than using the standard deviation of HbA1c levels or other commonly used markers of variability, Angus Forbes (King’s College London, UK) and co-workers used a score based on the number of times patients had a clinically significant change in HbA1c (≥0.5%; ≥5.5 mmol/mol).
Speaking to medwireNews about the findings, Kevin Fernando, a general practitioner from North Berwick Health Centre, UK, noted that the adverse effect of falling HbA1c levels is “something unique to this older, more frail population.”
This effect likely even applies in patients with high baseline HbA1c, he said. “From my own experience, it’s always the higher the baseline, the bigger the fall, and there’s no doubt in an older, frailer patient they can’t tolerate those big falls very well.”
Falling glucose levels increase a patient’s risk for hypoglycemia and physical falls, he explained, and acute reductions may also worsen diabetic neuropathy and retinopathy, again increasing a patient’s risk for a fall.
The study is published in The Lancet Diabetes & Endocrinology. It used data obtained from the UK THIN primary care database for 28,017 women aged an average of 79 years, of whom 30.7% died during follow-up, and 26,786 men aged an average of 77 years, of whom 33.8% died.
Both women and men had an increased mortality risk if their HbA1c levels were above 8% (64 mmol/mol) or below 6% (42 mmol/mol), compared with levels between these thresholds. The researchers saw the strongest effects in a model that used the average of patients’ mean HbA1c for each year of follow-up, so representing long-term average glycemic control.
Among people whose diabetes had lasted at least 5 years, mortality also rose with increasing glycemic variability score. Accounting for glycemic variability had the effect of reducing the impact of high HbA1c levels, so that the excess mortality risk only occurred at levels above about 9.5% in women and 9.0% in men. At the bottom end of the scale, it raised the HbA1c threshold for increased mortality risk in men to around 7.0%, and strengthened the negative effects of levels below 6.0% so that women and men had respective 25% and 30% increases in mortality risk, up from a corresponding 15% and 22% if variability was not considered.
Fernando observed that the findings tie in with the recent spate of publications showing that older patients with diabetes are often overtreated, potentially causing harm. But recommendations to individualize diabetes treatment have been based largely on expert opinion, whereas this paper quantifies what doctors have long suspected, he said.
However, he stressed that treatment decisions should be based more on functional status than actual age. “Yes, we’ve got this evidence base, but if that patient that’s sat in front of me is 80 [but] still darting around the world, and you still expect them to be around in 10 years’ time, there is a rationale to still treat them a little bit tighter to try and prevent onset of microvascular and macrovascular complications.”
Conversely, “a lot of these more frailer individuals benefit far more from, say, slightly tighter blood pressure or even lipid control rather than tighter glycemic control.”
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