47-OR: Acute Fluctuations in Plasma Glucose Affect Echocardiographic-Derived Measures of Systolic Function in Patients with Type 1 Diabetes

Abstract

Insulin treatment in patients with type 1 diabetes (T1D) causes rapid and large fluctuations in plasma glucose (PG) concentrations, and patients with T1D and poor glycemic control have an increased risk of cardiovascular disease including heart failure. We evaluated echocardiographic changes in cardiac function during experimental hypoglycemia and rebound hyperglycemia in patients with T1D. Patients with T1D (age 52.8±11.4 years, HbA1c 7.5±0.8% [57.6±8.9 mmol/mol], BMI 25.7±3.1 kg/m2) underwent two clamp days in random order. Both clamp days included three steady-state phases: 1) a 45-min hyperinsulinemic euglycemic phase (PG=6 mmol/L); 2) a 60-min hyperinsulinemic hypoglycemic phase (PG=2.5 mmol/L), and 3) a 60-min recovery phase in either hyperglycemia or euglycaemia (Clamp A: PG: 20 mmol/L; Clamp B: PG: 6 mmol/L). Cardiac function was evaluated with echocardiography at each phase by a blinded observer. Acute hypoglycemia increased left ventricular ejection fraction (LVEF) (absolute change, Clamp A: 6.5% [5.0;8.1], P=0.0001; Clamp B: 6.2% [4.6;7.9], P<0.0001) and global longitudinal strain (GLS) (absolute change, Clamp A: -3.1% (-4.5;-1.6), P<0.001; Clamp B: -3.5% (-4.6;-2.3), P<0.0001) from baseline. In Clamp A during hyperglycemia, LVEF and GLS were increased compared to baseline euglycemia (5.0% [3.2;6.8] (P<0.0001) and 2.1% [-3.7;-0.6] (P<0.01), respectively). An increase in LVEF was also observed in the recovery phase in Clamp B despite normalization of PG for 60 min (2.1% [0.5;3.8], P<0.05). In the recovery phase, LVEF was greater during hyperglycemia in Clamp A (2.9% [1.0;4.7], P<0.01) compared to euglycaemia in Clamp B. In conclusion, our findings suggest that acute fluctuations in PG affect echocardiographic-derived measures of systolic function in patients with T1D. Disclosure C. R. Andreasen: None. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker’s Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S. T. Vilsbøll: Consultant; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Gilead Sciences, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk, Sanofi, Sun Pharmaceutical Industries Ltd. A. Andersen: None. P. G. Hagelqvist: None. K. U. Abelin: None. J. V. Lauritsen: None. P. G. Jørgensen: Speaker’s Bureau; Self; AstraZeneca. S. Engberg: None. J. J. Holst: Consultant; Self; Novo Nordisk, Other Relationship; Self; Antag Therapeutics, Bainan Biotech, MSD Corporation, Novo Nordisk, Other Relationship; Spouse/Partner; Antag Therapeutics, Bainan Biotech, Synklino ApS. U. Pedersen-bjergaard: Advisory Panel; Self; Novo Nordisk A/S, Sanofi-Aventis, Consultant; Self; Abbott, Speaker’s Bureau; Self; Novo Nordisk A/S. Funding Novo Nordisk Foundation (NNF17SA0031406)