Perioperative Stress Hyperglycemia in General and Vascular Surgery Patients

Phase 4

Terminated

Conditions: Hyperglycemia Stress

Interventions: Drug: Dulaglutide
Drug: Placebo
Device: Continuous glucose monitor (CGM), blinded

Registration Number: NCT04862234

Lead Sponsor: Emory University

Brief Summary: Hyperglycemia is seen in approximately 30% of patients who do not have a history of diabetes and undergo general surgery. Hyperglycemia in this setting is associated with increased risk of postoperative complications. The purpose of this study is to investigate risk factors for developing high sugars during the time of surgery, and if these high sugars can be prevented by the use of an injectable diabetes medication (dulaglutide) prior to surgery.

Detailed Description: Stress hyperglycemia (SH), defined as a blood glucose \>140 mg/dl in hospitalized patients without a prior history of diabetes mellitus (DM) is associated with increased risk of complications and mortality compared to patients with normoglycemia and with known history of DM. Increased counterregulatory hormones (cortisol, glucagon, epinephrine, growth hormone), free fatty acids, inflammation and oxidative stress are likely involved in the pathogenesis of impaired insulin secretion and action leading to stress hyperglycemia. However, no prospective studies have comprehensively examined preoperative glycemic control profiles and their association with the incidence, clinical predictors and underlying mechanisms of SH in general surgical patients. Accordingly, the researchers propose a prospective study investigating clinical, metabolic and inflammatory/oxidative stress biomarker profiles leading to SH. This study will use continuous glucose monitoring (CGM) technology to fully characterize the onset, duration and severity of SH during the perioperative period.

Given the association between stress hyperglycemia and poor hospital outcomes, this study aims to determine if the prevention of stress hyperglycemia is feasible with the single administration of a weekly glucagon-like peptide-1 receptor agonist (GLP-1 RA), a common medication used to treat patients with established diabetes. In addition, the researchers will explore the role of beta-cell function, insulin resistance, and inflammation on the pathogenesis of stress hyperglycemia.

The goals of this study are to: 1) conduct an extensive analysis of preoperative glycemic control and its relationship to clinical, metabolic and biomarker profiles of SH in a high-risk population, and 2) conduct a pilot randomized controlled trial to prospectively determine if single dose use of dulaglutide can improve perioperative glycemic control compared to insulin administration (standard-of-care). Patients qualifying for the study will be approached at their preoperative clinic visit and invited to participate in the prospective observational study arm (Aim 1), and in the interventional trial for prevention of SH with dulaglutide (Aim 2) if they meet inclusion criteria based on oral glucose tolerance testing (OGTT) or lab testing performed for Aim 1. Within 72 hours prior to planned surgery, consented patients will present to the clinical research center (CRC) to undergo evaluation with OGTT and lab testing with CGM placement. Those patients with OGTT or lab results consistent with a diagnosis of prediabetes or newly diagnosed diabetes will be asked if they would like to participate in Aim 2. Patients consenting to participate in Aim 2 will be randomized to receive a subcutaneous injection of dulaglutide 0.75 mg or placebo during the CRC visit, and glycemic control parameters will be followed postoperatively during surgical admission (up to 14 days). In addition to the above, baseline and postoperative levels of serum inflammatory and oxidative stress markers will be obtained to provide further information regarding beta-cell function and insulin resistance in relation to the development of stress hyperglycemia.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 16

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dulaglutide	Dulaglutide	Participants randomized to receive dulaglutide within 72 hours prior to a planned surgery.
Dulaglutide	Continuous glucose monitor (CGM), blinded	Participants randomized to receive dulaglutide within 72 hours prior to a planned surgery.
Placebo	Placebo	Participants randomized to receive a placebo to match dulaglutide within 72 hours prior to a planned surgery.
Placebo	Continuous glucose monitor (CGM), blinded	Participants randomized to receive a placebo to match dulaglutide within 72 hours prior to a planned surgery.

Primary Outcome Measures

Name	Time	Method
Percentage of Time in Target Glucose Range (70-140 mg/dL) by CGM	During hospitalization (up to 5 days postoperatively)	The percentage of time in the target glucose range of 70-140 mg/dL, as measured by a continuous glucose monitor (CGM) data was determined.

Secondary Outcome Measures

Name	Time	Method
Perioperative Insulin Requirements	During hospitalization (up to 5 days postoperatively)	Perioperative insulin requirements will be assessed as the total daily insulin dose.
Percentage of Time in Hyperglycemia (Glucose>140 mg/dL)	During hospitalization (up to 5 days postoperatively)	The percentage of time in hyperglycemia with glucose\>140 mg/dL will be examined.
Percentage of Time in Hypoglycemia (Glucose <40 mg/dL)	During hospitalization (up to 5 days postoperatively)	The percentage of time in hypoglycemia with glucose \<40 mg/dL will be examined.
Mean Daily Glucose Values	During hospitalization (up to 5 days postoperatively)	The mean daily glucose values, as measured by both point of care (POC) glucose testing and CGM data, will be examined.
Maximum Daily Glucose Values	During hospitalization (up to 5 days postoperatively)	The maximum daily glucose values, as measured by both POC glucose testing and CGM data, will be examined.
Percentage of Time in Hyperglycemia (Glucose>180 mg/dL)	During hospitalization (up to 5 days postoperatively)	The percentage of time in hyperglycemia with glucose\>180 mg/dL will be examined.
Percentage of Time in Hypoglycemia (Glucose <70 mg/dL)	During hospitalization (up to 5 days postoperatively)	The percentage of time in hypoglycemia with glucose \<70 mg/dL will be examined.
Percentage of Time in Hypoglycemia (Glucose <54 mg/dL)	During hospitalization (up to 5 days postoperatively)	The percentage of time in hypoglycemia with glucose \<54 mg/dL will be examined.
Mean Onset of Stress Hyperglycemia During the Postoperative Period	During hospitalization (up to 5 days postoperatively)	The mean onset time of stress hyperglycemia during the postoperative period by CGM data will be examined.
Mean Duration of Stress Hyperglycemia During the Postoperative Period	During hospitalization (up to 5 days postoperatively)	The mean duration of stress hyperglycemia during the postoperative period by CGM data will be examined.
Change in Plasma Cortisol Level	Baseline, 48 to 72 hours postoperatively	Samples will be collected prior to surgery and 48 to 72 hours after surgery to assess inflammatory and oxidative stress biomarkers.
Change in Level of Free Fatty Acids (FFA)	Baseline, 48 to 72 hours postoperatively	Samples will be collected prior to surgery and 48 to 72 hours after surgery to assess inflammatory and oxidative stress biomarkers.
Change in High Sensitivity C-reactive Protein (hsCRP) Level	Baseline, 48 to 72 hours postoperatively	Samples will be collected prior to surgery and 48 to 72 hours after surgery to assess inflammatory and oxidative stress biomarkers.
Change in Tumor Necrosis Factor-alpha (TNF-α) Level	Baseline, 48 to 72 hours postoperatively	Samples will be collected prior to surgery and 48 to 72 hours after surgery to assess inflammatory and oxidative stress biomarkers.
Change in Adiponectin Level	Baseline, 48 to 72 hours postoperatively	Samples will be collected prior to surgery and 48 to 72 hours after surgery to assess inflammatory and oxidative stress biomarkers.
Change in Level of Thiobarbituric Acid Reactive Substances (TBARS)	Baseline, 48 to 72 hours postoperatively	Samples will be collected prior to surgery and 48 to 72 hours after surgery to assess inflammatory and oxidative stress biomarkers.