TY - JOUR
T1 - Severe hypoglycemia-induced fatal cardiac arrhythmias are augmented by diabetes and attenuated by recurrent hypoglycemia
AU - Reno, Candace M.
AU - VanderWeele, Jennifer
AU - Bayles, Justin
AU - Litvin, Marina
AU - Skinner, Allie
AU - Jordan, Andrew
AU - Daphna-Iken, Dorit
AU - Fisher, Simon J.
N1 - Publisher Copyright:
© 2017 by the American Diabetes Association.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - We previously demonstrated that insulin-mediated severe hypoglycemia induces lethal cardiac arrhythmias. However, whether chronic diabetes and insulin deficiency exacerbates, and whether recurrent antecedent hypoglycemia ameliorates, susceptibility to arrhythmias remains unknown. Thus, adult Sprague-Dawley ratswere randomized into four groups: 1) nondiabetic (NONDIAB), 2) streptozotocin-induced insulin deficiency (STZ), 3) STZ with antecedent recurrent (3 days) hypoglycemia (∼40-45 mg/dL, 90 min) (STZ+RH), and 4) insulin-treated STZ (STZ+Ins). Following treatment protocols, all rats underwent hyperinsulinemic (0.2 units kg-1 min-1), severe hypoglycemic (10-15 mg/dL) clamps for 3 h with continuous electrocardiographic recordings. During matched nadirs of severe hypoglycemia, rats in the STZ +RH group required a 1.7-fold higher glucose infusion rate than those in the STZ group, consistent with the blunted epinephrine response. Second-degree heart block was increased 12- and 6.8-fold in the STZ and STZ+Ins groups, respectively, compared with the NONDIAB group, yet this decreased 5.4-fold in the STZ+RH group compared with the STZ group. Incidence of third-degree heart block in the STZ+RH group was 5.6%, 7.8-fold less than the incidence in the STZ group (44%). Mortality due to severe hypoglycemia was 5% in the STZ+RH group, 6.2-fold less than that in the STZ group (31%). In summary, severe hypoglycemia- induced cardiac arrhythmias were increased by insulin deficiency and diabetes and reduced by antecedent recurrent hypoglycemia. In this model, recurrent moderate hypoglycemia reduced fatal severe hypoglycemia- induced cardiac arrhythmias.
AB - We previously demonstrated that insulin-mediated severe hypoglycemia induces lethal cardiac arrhythmias. However, whether chronic diabetes and insulin deficiency exacerbates, and whether recurrent antecedent hypoglycemia ameliorates, susceptibility to arrhythmias remains unknown. Thus, adult Sprague-Dawley ratswere randomized into four groups: 1) nondiabetic (NONDIAB), 2) streptozotocin-induced insulin deficiency (STZ), 3) STZ with antecedent recurrent (3 days) hypoglycemia (∼40-45 mg/dL, 90 min) (STZ+RH), and 4) insulin-treated STZ (STZ+Ins). Following treatment protocols, all rats underwent hyperinsulinemic (0.2 units kg-1 min-1), severe hypoglycemic (10-15 mg/dL) clamps for 3 h with continuous electrocardiographic recordings. During matched nadirs of severe hypoglycemia, rats in the STZ +RH group required a 1.7-fold higher glucose infusion rate than those in the STZ group, consistent with the blunted epinephrine response. Second-degree heart block was increased 12- and 6.8-fold in the STZ and STZ+Ins groups, respectively, compared with the NONDIAB group, yet this decreased 5.4-fold in the STZ+RH group compared with the STZ group. Incidence of third-degree heart block in the STZ+RH group was 5.6%, 7.8-fold less than the incidence in the STZ group (44%). Mortality due to severe hypoglycemia was 5% in the STZ+RH group, 6.2-fold less than that in the STZ group (31%). In summary, severe hypoglycemia- induced cardiac arrhythmias were increased by insulin deficiency and diabetes and reduced by antecedent recurrent hypoglycemia. In this model, recurrent moderate hypoglycemia reduced fatal severe hypoglycemia- induced cardiac arrhythmias.
UR - http://www.scopus.com/inward/record.url?scp=85035317726&partnerID=8YFLogxK
U2 - 10.2337/db17-0306
DO - 10.2337/db17-0306
M3 - Article
C2 - 28887311
AN - SCOPUS:85035317726
SN - 0012-1797
VL - 66
SP - 3091
EP - 3097
JO - Diabetes
JF - Diabetes
IS - 12
ER -