Abstract
Diabetes mellitus is increasingly becoming an older person disease due to the increased survival and aging of the population. Previous studies which showed benefits of tight glycemic control and a linear relationship between HbA1c and mortality have largely included younger patients newly diagnosed with diabetes and with less comorbidities. Recent studies, which included older population with diabetes, have shown a U-shaped relationship of increased mortality associated with low HbA1c. The mechanism of such relationship is unclear. There was no direct causal link between low HbA1c and mortality. It appears that malnutrition, inflammation and functional decline are characteristics shared by the populations that showed increased mortality and low HbA1c. In these studies functional status, disability or frailty was not routinely measured. Therefore, although adjustment for comorbidities was made there may be a residual confounding by unmeasured factors such as frailty. Thus, frailty or decline in functional reserve may be the main confounding factor explaining the relationship between increased mortality risk and low HbA1c.
Highlights
MethodsWe have performed a search of Medline and Embase for observational studies from January 1969 to April 2014 using keywords relating to low HbA1c or intensive glycemic control and mortality risk in patients with type 2 diabetes
The evidence suggesting that patients with type 2 diabetes should have their HbA1c less than 7% is largely based on the findings from the United Kingdom Prospective Diabetes Study (UKPDS) which showed that intensive glycemic control (HbA1c 7.0%) reduced the rate of microvascular complications by 25% compared with less tight control (HbA1c 7.9%) reduction of cardiovascular disease did not reach statistical significance (p=0.052) [1]
The second was a retrospective study of 5,815 veterans with heart failure and diabetes which showed that the lowest quintile (HbA1C ≤6.4%) had significantly increased risk of mortality when compared with the middle quintile (7.1% < HbA1c ≤7.8%), hazard ratio (HR) 1.37, 95% CI 1.14 to 1.64, p =0.001 adjusted for potential confounders after 2 years of follow up [32]
Summary
We have performed a search of Medline and Embase for observational studies from January 1969 to April 2014 using keywords relating to low HbA1c or intensive glycemic control and mortality risk in patients with type 2 diabetes. In a community study of 3,153 participants ≥65 years of age, appendicular lean mass loss in men with diabetes was twice that of men without diabetes (3.0% vs 1.5%) and in women with diabetes was 1.8 times that of those without diabetes (3.4% vs 1.9%) over 4 years of follow up The mechanisms explaining these results may be related to reduced muscle protein synthesis due to lower testosterone and insulin like growth factor 1 and increased muscle protein breakdown due to a higher rate of inflammation [24]. The second was a retrospective study of 71,092 patients with type 2 diabetes, mean (SD) age 71.0 (7.4) and 14.6% were >80 years, which showed lower mortality risk for HbA1c levels between 6.0 and 9.0% compared with HbA1c
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