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Introduction: Severe hypoglycemia is associated with an increased risk of cardiovascular (CV) death, and platelet responses to hypoglycemia (hypo) have been described. The impact of a transient severe hypo versus prolonged less severe hypo is unclear. Methods: 2 hypo studies were compared; firstly, in 18 subjects (type 2 diabetes (T2D) : 8 controls) blood glucose lowered to 3.5mmoL/L (90mg/dL) for 1-hour; secondly, in 46 subjects (23 T2D: 23 controls) blood glucose lowered to Results: In T2D, from baseline to hypo, differences were seen for 4 PRPs, three showing increased percent change in study-2 (plasminogen activator inhibitor-1 (PAI-1) , platelet glycoprotein VI (PGVI) and Tissue factor) , one showing increased percent change in study-1 (CD40 ligand (CD40LG)) ; at 24-hours in T2D, percent change for CD40LG remained increased, together with von Willebrand factor (vWF) , in study-2. In controls, from baseline to hypo, differences were seen for four PRPs, three showing increased percent change in study-2 (PAI-1, CD40LG and Protein S) , one showing increased percent change in study-1 (vWF) ; at 24-hours in controls, percent change for Protein S remained increased in study-2, whilst percent change for vWF and plasminogen were increased in study-1. Conclusion: Thrombogenic potential was enhanced in T2D versus controls, as evidenced by an increased thrombogenic protein expression profile in both mild and severe hypoglycemia, that showed persistent changes at 24-hours in severe hypo. Disclosure A. Moin: None. H. Kahal: None.

Introduction: Heat shock proteins (HSPs) protect against protein misfolding, contribute to diabetes-induced complications and are affected by hypoglycemia. Misfolded proteins are degraded by ubiquination through UBE2L3/UBE2N proteins. Methods: Two prospective case-control induced hypoglycemia studies were compared: Study1, hypoglycemic clamp to 2.8mmol/l(50mg/dl) for 1-hour, 17 subjects (T2D(n=10); controls(n=7));Study2, hypoglycemic clamp to 2.0mmol/l(36mg/dl) transiently, 46 subjects (T2D(n=23); controls(n=23)).Blood sampling: baseline, hypoglycemia and 24-hours; Somalogic proteomic analysis of HSPs was undertaken. Results: HSP changes were seen in both studies separately; however, percentage-change baseline to hypoglycemia differed between studies for seven of 19 HSP panel proteins, with notable changes in Study 1: elevated levels in controls at hypoglycemia for TLR4:MD-2(p=0.01) and CD274(p=0.04), and at 24-hours for MAPKAPK5(p=0.047); elevated levels in T2D at hypoglycemia for DNAJB1(p=0.01), STIP1(p=0.01), UBE2L3(p=0.01) and UBE2N(p=0.001) (Figure1). Conclusion: Milder-prolonged hypoglycaemia caused greater HSP changes than severe-acute hypoglycaemia for HSPs protective against protein misfolding and for increasing UBE2L3/UBE2N degradation proteins in T2D, suggesting hypoglycemic duration may cause greater cell damage than severity. Disclosure A. Moin: None. A. S. Atkin: None. H. Kahal: None. A. Al-qaissi: None. T. Sathyapalan: Research Support; Self; Abbott, Eli Lilly and Company, Novo Nordisk. S. Atkin: None. A. E. Butler: None.

Objective: Hypoglycemia is a common complication of tighter glucose control regimens in type 2 diabetes (T2D) and may increase the risk of dementia, Alzheimer’s disease being the most common form. We measured amyloid-related proteins during induced hypoglycemia in a cohort of subjects with and without T2D, hypothesizing that these protein levels would be further elevated during hypoglycemia in T2D subjects. Methods: A prospective, parallel study was conducted in individuals with T2D (n=23) and controls (n=22). Hypoglycaemia ( Results: No changes from baseline in serum levels of the four amyloid-related proteins were seen in subjects with or without T2D, either at the time of hypoglycemia or at 24-hours post-clamp. Conclusions: Induced hypoglycemia is not associated with a significant increase in serum levels of amyloid-related proteins. Thus, no clear mechanistic link based on serum proteins between T2D-related hypoglycemic episodes and Alzheimer’s disease emerged from this study, although it is important to consider that protein levels in the cerebrospinal fluid may differ. Disclosure A. Moin: None. T. Sathyapalan: Research Support; Self; Amgen, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S. Other Relationship; Self; Ipsen Biopharmaceuticals. S. Atkin: None. A.E. Butler: None.