Acute and Persistent Prothrombic Effects Observed With Antecedent Hypoglycemia in T2D
Individuals participated in paired hyperinsulinemic-euglycemic and hypoglycemic clamp studies where blood glucose was controlled for 60-minute periods.
Hypoglycemia was associated with early and late prothrombotic changes in the ﬁbrin network in individuals with type 2 diabetes and there was a persistent effect of hypoglycemia on clot density and impaired ﬁbrinolysis that lasted for at least 7 days, according to study findings published in Diabetes Care.
Cardiovascular disease (CVD) is the leading cause of death in individuals with type 2 diabetes, and hypoglycemia has been linked with persistent increases in CV mortality. Studies examining the longer-term effects of hypoglycemia on thrombotic and inﬂammatory markers, however, are limited. In this study, the acute and downstream effects of hypoglycemia on markers of thrombosis risk and inﬂammation were evaluated in 12 individuals with type 2 diabetes who had no history of CVD and 11 control participants.
All individuals participated in paired hyperinsulinemic-euglycemic (glucose 6 mmol/L for two 60-minute periods) and hypoglycemic (glucose 2.5 mmol/L for two 60-minute periods) clamp studies held between 4 and 8 weeks apart to mitigate carryover effects. Characteristics linked with CVD in diabetes, including fibrin clot properties, platelet reactivity, and inﬂammatory markers were measured at baseline, at the end of the 60-minute clamps, after recovery from morning clamps, and on day 1 and day 7 after the euglycemic and hypoglycemic clamps, respectively.
In both groups, euglycemic hyperinsulinemia reduced platelet reactivity and ﬁbrin clot density and improved ﬁbrinolytic efﬁciency. Platelet reactivity and aggregation increased during acute hypoglycemia in both cohorts and resolved at recovery. In the cohort with diabetes, clot lysis times and clot maximum absorbance increased up to day 7 (P =.001 and .002 vs euglycemia, respectively), but in the control group, clots showed limited changes. Fiber network density decreased at day 7 after euglycemia in the group with diabetes, but after hypoglycemia there was an increase in ﬁber network density at day 1 and 7 (both P =.01 for glycemic arm).
“We have identiﬁed potential mechanisms whereby hypoglycemia could increase the risk of [cardiovascular] events during and after an episode and so oppose the beneﬁts of intensive glycemic control,” wrote the researchers.
Chow E, Iqbal A, Walkinshaw E, et al. Prolonged prothrombotic effects of antecedent hypoglycemia in individuals with type 2 diabetes [published online October 16, 2018]. Diabetes Care. doi:10.2337/dc18-0050