116-OR: Hypoglycemia Leads to a Delayed Increase in Platelet and Coagulation Markers in Subjects with Type 2 Diabetes Treated with Metformin Only—Results from an Experimental Stepwise Hypoglycemic Clamp Study
Authors: ABERER FELIX , PFERSCHY PETER N. , TRIPOLT NORBERT J. , SOURIJ CAREN , KOJZAR HARALD , PRIETL BARBARA , KOFLER SELINA , BRUNNER MARTINA , RIEDL REGINA , NOVAK EVA , OBERMAYER ANNA M. , REITBAUER PHILIPP , STOJAKOVIC TATJANA , AZIZ FAISAL , OULHAJ ABDERRAHIM , PRULLER FLORIAN , SCHARNAGL HUBERT , SOURIJ HARALD 
Published: June 2019

Objective: Although hypoglycemia is associated with increased risk for subsequent cardiovascular events, experimental data investigating the effect of hypoglycemia on coagulation and platelet activation in type 2 diabetes are limited.
Research Design and Methods: This monocentric, open, single arm, trial included 14 subjects with type 2 diabetes (10 male/4 female, age 55±7 years, HbA1c 51±7 mmol/mol, diabetes duration 5±4 years) and metformin treatment only. A stepwise hyperinsulinemic hypoglycemic clamp was performed, aiming to investigate parameters of platelet function during predefined plateaus of hypoglycemia (at 63 and 45 mg/dl, for 30 minutes respectively), 24 hours and 7 days later. Additionally, all subjects underwent a hyperinsulinemic euglycemic clamp experiment.
Results: While platelet activation assessed by light transmittance aggregometry did not significantly increase following a hypoglycemic clamp, flow cytometry based platelet activation assessment demonstrated a significant increase 24 hours (PAC1CD62PCD63pos p&lt;0.01 compared to baseline, and p&lt;0.001 for PAC1CD63Ppos, respectively) and 7 days after the hypoglycemic clamp (p&lt;0.001 for PAC1CD62Ppos, and PAC1CD63Ppos, and p&lt;0.01 for PAC1CD62PCD63pos in comparison to baseline). In addition, coagulation markers like fibrinogen, PAI-1 and factor VIII also increased, with highest levels 24 hours after the hypoglycemic clamp (p&lt;0.001 for fibrinogen and factor VIII and &lt;0.01 for PAI-1). No platelet or coagulation activation was observed during the hyperinsulinemic, euglycemic clamp.
Conclusions: One single event of insulin induced hypoglycemia led to an increase in markers of platelet activation and coagulation, however, the activation occurred with a delay and was evident 24 hours and 7 days after the actual hypoglycemia.

Disclosure
F. Aberer: None. P.N. Pferschy: None. N.J. Tripolt: None. C. Sourij: None. H. Kojzar: None. B. Prietl: None. S. Kofler: None. M. Brunner: None. R. Riedl: None. E. Novak: None. A.M. Obermayer: None. P. Reitbauer: None. T. Stojakovic: None. F. Aziz: None. A. Oulhaj: None. F. Pruller: None. H. Scharnagl: Research Support; Self; Abbott, Amgen Inc. Speaker's Bureau; Self; Sanofi-Aventis Deutschland GmbH. H. Sourij: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Novo Nordisk A/S, Sanofi-Aventis. Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi-Aventis.