Metabolic Phenotyping During Stress Hyperglycemia in Cardiac Surgery Patients

Stress hyperglycemia is common in the perioperative period and is associated with increased
risk of death postoperatively. Counterregulatory hormones and inflammatory mediators appear
to modulate the acute biological response to stress; however, the pathophysiological pathways
that result in stress hyperglycemia and its link to poor clinical outcomes are not well
understood. At least half of non-Diabetes Mellitus (DM) patients undergoing cardiac surgery
develop stress hyperglycemia shown to be an independent risk factor of morbidity and
mortality. The current approach to treat hyperglycemia with insulin has major limitations
including high resource utilization and high risk of hypoglycemia.The main goals of the study
are to examine baseline and postoperative metabolic profiles of non-diabetic CABG patients
with stress hyperglycemia and to study the effect of a long-acting GLP-1 RA on the prevention
of stress-hyperglycemia and modulation of metabolic stress during cardiac surgery.

The Study will be conducted in 2 Parts. The First part of the study aims to provide new
insights into the mechanisms underlying the metabolic and inflammatory responses to surgical
stress The first part is a nested case control study.The Second part of the study will
examine whether exposure to a long acting glucagon like peptide-1 receptor agonist (GLP-1
RA), dulaglutide can improve glycemic control and ameliorate the inflammatory response to
acute surgical stress. This study is a randomized study with assignment to either dulaglutide
or placebo two to three days prior to surgery in non-Diabetes Mellitus obese patients (BG<126
mg/dL, HbA1c <6.5%, BMI >30, age> 50 years) undergoing CABG surgery.The study ultimately
wants to provide evidence to support the use of novel therapies to prevent and manage stress
hyperglycemia in the inpatient setting.

Inclusion Criteria:

- Males or females between the ages of 50 and 80 years and BMI ≥30mg/kg2 undergoing
elective CABG surgery

- No previous history of diabetes or hyperglycemia.

Exclusion Criteria:

- Hyperglycemia (BG>125 mg/dl or HbA1c > 6.5%) or previous treatment with antidiabetic
agents;

- impaired renal function (GFR < 30 ml/min) or clinically significant hepatic failure;

- subjects with gastrointestinal obstruction expected to require gastrointestinal
suction;

- patients with clinically relevant pancreatic or gallbladder disease;

- treatment with oral or injectable corticosteroid;

- mental condition rendering the subject unable to understand the possible consequences
of the study;

- pregnancy or breastfeeding at time of enrollment.