Effect of Outdoor Temperature and Air Pollution on the Comparative Safety of Antihyperglycemic Therapies

Diabetes exacts a profound societal cost in terms of morbidity, disability, and mortality. As climate change progresses and further magnifies the negative impacts of extreme outdoor temperatures and air pollution on health, there is urgency in the need for adaptable and personalized diabetes care. Natural environmental factors like extreme temperatures and pollution are known to be associated with serious adverse health outcomes in persons with type 2 diabetes; these include hypoglycemia (very low blood sugar), diabetic ketoacidosis (very high blood ketones), and cardiovascular events (like heart arrhythmias). The most vulnerable and disadvantaged populations tend to be hardest hit by climate change and are least equipped to combat its effects, and there is substantial overlap between these populations and Medicaid recipients. Furthermore, Medicaid recipients are diagnosed with diabetes and hospitalized for diabetes-related adverse health outcomes at higher rates than the general US population.
Personalized diabetes care involves selecting the best therapy based on patient characteristics. Unfortunately, clinical trials comparing diabetes drugs have not examined interactions with outdoor temperature or air pollution, and are underpowered to do so. This presents a major knowledge gap for efforts to incorporate
natural environmental factors into personalized diabetes care. While innovative, the inclusion of environmental factors in clinical decision-making has precedent, and is even anticipated in the treatment of diabetes.
To address this knowledge gap, we recently submitted an R01 application to examine the roles of outdoor temperature and air pollution on the comparative safety of diabetes drugs in persons with type 2 diabetes. We proposed to conduct pharmacoepidemiologic studies by linking federal environmental datasets to Department of Health and Human Services healthcare data for the entire US Medicaid (and Medicare) populations residing in the conterminous US. We proposed to examine the effects of outdoor temperature and air pollution on rates of serious hypoglycemia, diabetic ketoacidosis, and serious arrhythmia, within and among incident users of different diabetes drug classes. Our Quartet application proposes to generate pilot data to bolster an R01 resubmission, recommended by our NIDDK Program Official, by demonstrating proof-of-concept by linking environmental to healthcare data for Medicaid beneficiaries with type 2 diabetes, then using this dataset to: a) examine temperature and pollution variability by beneficiary ZIP code of residence; b) examine rates of the above-named health outcomes by temperature and pollution; and c) demonstrate variability in outcome rates among users of different diabetes drug regimens. These pilot data will enable us to directly respond to summary statement feedback and improve the fundability of our proposed, innovative R01 that would incorporate natural environmental factors to improve health in persons with diabetes.