Severe hypoglycemia ‘marker rather than cause’ for longer-term type 2 diabetes mortality risk
medwireNews: Severe hypoglycemia in people with type 2 diabetes is associated with later mortality from a wide range of causes, including those for which there is no obvious underlying mechanism, say researchers.
“However, regardless of the nature of the association, from a prognostic perspective our study identifies a group of patients with type 2 diabetes at a very high risk of death,” emphasize Francesco Zaccardi and study co-authors from the University of Leicester in the UK.
The team used UK Clinical Practice Research Datalink to identify 74,610 adults with type 2 diabetes, 388 (0.5%) of whom had at least one hospital admission for hypoglycemia. People who had severe hypoglycemia events were older, on average, than those who did not, at 73.9 versus 67.7 years, were more likely to be in the most socioeconomically deprived quintile (21.9 vs 15.0%), more frequently had cardiovascular disease (CVD) including myocardial infarction, heart failure, and stroke, and were more often using insulin (35.3 vs 6.6%).
During a median follow-up of 7.1 years, the mortality rate was markedly higher in people with a history of severe hypoglycemia, at 60.8% versus 25.0%, corresponding to 132 versus 40 deaths per 1000 person–years.
Researchers have proposed that hypoglycemia may “predispose an individual to long-term CVD events through direct (i.e. ECG abnormalities) and indirect (i.e. platelet abnormalities) mechanisms,” explain Zaccardi and team.
However, only 17.5% of people with hypoglycemia died of CVD events, with 7.0% dying of cancer, and the highest event rate of 36.3% was accounted for by other causes, the most common of these being unspecified dementia, unspecified pneumonia and unspecified bronchopneumonia, vascular dementia, and chronic obstructive pulmonary disease with acute lower respiratory infection.
In unadjusted analyses, the researchers found the increased risk for CVD mortality in people with versus without hypoglycemia to be “moderate,” with 5-year absolute differences ranging from 3.6% to 4.7% according to age.
For cancer, the 5-year mortality difference ranged from a 1.4% absolute reduction to a 7.1% increase in people with hypoglycemia versus those without. And for other causes of death, people with hypoglycemia had a consistently increased risk, ranging from 5.0% to 20.9%.
The researchers say that the apparent effect of hypoglycemia on non-CVD causes of death, for which there is no obvious mechanism, suggests that its effect on long-term mortality risk is by and large non-causal.
Moreover, the association between hypoglycemia and mortality weakened when the team adjusted for a range of potential confounders, including medication and comorbidities, so that for example the overall 21% absolute increase in the 5-year risk for death from any cause in a 60-year-old with hypoglycemia reduced to 11%.
“Rather, severe hypoglycaemia is very likely a marker of frailty, which is causally associated with a higher risk of death,” Zaccardi and colleagues write in Diabetologia.
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