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Master of Public Health

Evaluation of Weight Change and Hypoglycemia as Mediators in the Association between Insulin Use and Death

AUTHORS

Min JY , Hackstadt AJ , Griffin MR , Greevy RA , Chipman J , Grijalva CG , Hung AM , Roumie CL , . Diabetes, obesity & metabolism. 2019 8 2; ().

ABSTRACT

AIMS: To evaluate whether weight change or hypoglycemia mediated the association between insulin use and death.

MATERIALS AND METHODS: In a retrospective cohort of Veterans who filled a new prescription for metformin and added insulin or sulfonylurea (2001-2012), we assessed change in body mass index (BMI) and hypoglycemia during the first 12 months of treatment intensification. Cox proportional hazards models compared the risk of death between treatment groups. Using the difference method, we estimated the indirect effect and proportion mediated through each mediator. A sensitivity analysis assessed mediators in the first 6 months of intensified therapy.

RESULTS: Among 28,892 patients surviving 12 months, deaths per 1000 person-years were 15.4 for insulin users and 12.9 for sulfonylurea users (hazard ratio [HR] 1.20, 95% confidence interval [CI] 0.87,1.64). Change in BMI and hypoglycemia mediated 13% (-98, 98) and -1% (-37, 71) of this association, respectively. Among 30,214 patients surviving 6 months, deaths per 1000 person-years were 34.8 for insulin users and 21.3 for sulfonylurea users (HR 1.66, 95% CI 1.28, 2.15). Change in BMI and hypoglycemia mediated 9% (1, 23) and 0% (-9, 4) of this association, respectively.

CONCLUSIONS: We observed an increased risk of death among metformin users intensifying treatment with insulin versus sulfonylurea and surviving 6 months of intensified therapy, but not among those surviving 12 months. This association was mediated in part by weight change. This article is protected by copyright. All rights reserved.

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