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Randomized Controlled Trial
. 2019 Jan;42(1):157-163.
doi: 10.2337/dc18-1144. Epub 2018 Nov 19.

Effects of Severe Hypoglycemia on Cardiovascular Outcomes and Death in the Veterans Affairs Diabetes Trial

Stephen N Davis  1 , William Duckworth  2 , Nicholas Emanuele  2 , Rodney A Hayward  2 , Wyndy L Wiitala  2 , Lizy Thottapurathu  2 , Domenic J Reda  2 , Peter D Reaven; Investigators of the Veterans Affairs Diabetes Trial
Affiliations
Randomized Controlled Trial

Effects of Severe Hypoglycemia on Cardiovascular Outcomes and Death in the Veterans Affairs Diabetes Trial

Stephen N Davis et al. Diabetes Care. 2019 Jan.

Abstract

Objective: To determine the risk factors for severe hypoglycemia and the association between severe hypoglycemia and serious cardiovascular adverse events and cardiovascular and all-cause mortality in the Veterans Affairs Diabetes Trial (VADT).

Research design and methods: This post hoc analysis of data from the VADT included 1,791 military veterans (age 60.5 ± 9.0 years) with suboptimally controlled type 2 diabetes (HbA1c 9.4 ± 2.0%) of 11.5 ± 7.5 years disease duration with or without known cardiovascular disease and additional cardiovascular risk factors. Participants were randomized to intensive (HbA1c <7.0%) versus standard (HbA1c <8.5%) glucose control.

Results: The rate of severe hypoglycemia in the intensive treatment group was 10.3 per 100 patient-years compared with 3.7 per 100 patient-years in the standard treatment group (P < 0.001). In multivariable analysis, insulin use at baseline (P = 0.02), proteinuria (P = 0.009), and autonomic neuropathy (P = 0.01) were independent risk factors for severe hypoglycemia, and higher BMI was protective (P = 0.017). Severe hypoglycemia within the past 3 months was associated with an increased risk of serious cardiovascular events (P = 0.032), cardiovascular mortality (P = 0.012), and total mortality (P = 0.024). However, there was a relatively greater increased risk for total mortality in the standard group compared with the intensive group (P = 0.019). The association between severe hypoglycemia and cardiovascular events increased significantly as overall cardiovascular risk increased (P = 0.012).

Conclusions: Severe hypoglycemic episodes within the previous 3 months were associated with increased risk for major cardiovascular events and cardiovascular and all-cause mortality regardless of glycemic treatment group assignment. Standard therapy further increased the risk for all-cause mortality after severe hypoglycemia.

Trial registration: ClinicalTrials.gov NCT00032487.

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References

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