NEW YORK (Reuters Health) – Both high and low levels of glycemic control and high HbA1c variability are associated with increased mortality in older people with diabetes, researchers in the UK say.
“In older populations, it is important to consider HbA1c values and trends as a health marker and not as a target,” Dr. Angus Forbes of King’s College London told Reuters Health by email. “The current system of care is biased toward lowering glycemic control, and this may lead to a lack of vigilance in relation to high-risk patients with lower or varying HbA1c levels.”
As reported online April 16 in The Lancet Diabetes and Endocrinology, Dr. Forbes and colleagues studied 54,803 patients age 70 and older from 587 UK primary practices. The analysis included a four-year run-in period (2003-2007) and a five-year followup (2007-2012).
Mean HbA1c was assessed in three models: a baseline mean HbA1c for 2003-06; the mean across the whole follow-up period, and a time-varying yearly updated mean.
A variability score from 0 (lowest) to 100 was calculated based on the number of changes in HbA1c of 0.5% (5.5 mmol/mol) over at least six readings.
During the study period, 30.7% of the women and 33.8% of the men died. The overall mortality rate was 73 per 1,000 person-years for women and 80 per 1,000-person years for men.
The data showed a J-shaped distribution for mortality risk in both sexes, with significant increases with HbA1c values greater than 8% (64 mmol/mol) and less than 6% (42 mmol/mol).
Mortality increased substantially with increasing HbA1c variability in all models, both overall and for men and women separately.
Across the whole follow-up period, the adjusted hazard ratios for patients with a glycemic variability score of 81 to 100 were 2.47 for women and 2.21 for men, compared with those with a score of 0 to 20.
Fitting the mean HbA1c models with the glycemic variability score altered the risk distribution for all models, but most markedly in the model that looked at the entire period; in this analysis, risk was significantly increased only with HbA1c values greater than 9.5% (80 mmol/mol) in women and 9% (75 mmol/mol) in men.
“Both low and high levels of glycemic control were associated with an increased mortality risk, and the level of variability also seems to be an important factor, suggesting that a stable glycemic level in the middle range is associated with lower risk,” the authors state.
“Glycemic variability, as assessed by variability over time in HbA1c, might be an important factor in understanding mortality risk in older people with diabetes,” they conclude.
“As an observational study, these are only associations and further research is required to model the relative benefits of different approaches to glucose management in older people,” Dr. Forbes said. “This work would need to consider the high level of heterogeneity in the population – gender differences, co-morbidity, and most importantly frailty.”
Dr. Hermes Florez, Professor and Division Chief in Epidemiology and Population Health at the University of Miami Health System and author of a related editorial, said, “Efforts will be needed to reduce glycemic variability and prevent hypoglycemia, reducing the development of complications and preserving (older adults’) quality of life.”
“Beyond the information provided by self-monitoring blood glucose data, which has limitations for the assessment of glycemic stability, innovative methods such as continuous glucose monitoring (CGM) may provide more reliable information, including the amplitude and timing of glucose excursions,” he told Reuters Health by email. “However, CGM evaluation may not be readily available in all clinical practices.”
“For now,” he said, “we can consider using the new metric proposed by (the authors) – a score based on the number of changes in HbA1c of 0.5% or higher with scores ranging from 0 to 100.”
Meanwhile, Dr. Florez added, ongoing comparative effectiveness studies “may provide further insight on the appropriate selection of oral agents, injectables and/or insulin therapies for these patients.” He is the Miami principal investigator for one such study, GRADE (https://ift.tt/1dnfpEo).
SOURCE: http://bit.ly/2r7PiMv and http://bit.ly/2r7Q5wX
Lancet Diabetes Endocrinol 2018.
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