Higher BMI a Strong Predictor Of Intraoperative Insulin Resistance

If the so-called “obesity paradox,” the theory that obesity may be protective under certain conditions, does indeed exist, it is not apparent with respect to intraoperative insulin resistance during coronary artery bypass graft (CABG) surgery, Canadian researchers have concluded. They found a linear negative relationship between body mass index (BMI) and insulin sensitivity during the procedure, opening the door to more postoperative adverse events in obese and morbidly obese patients.

Although previous studies have reported better outcomes in overweight and obese patients than normal-weight patients (Diabetes Care 2013;36 [suppl 2]:S276-S281), the association between obesity and morbidity and mortality after major surgery remains unclear, reported Yosuke Nakadate, MD, an attending anesthesiologist in McGill University Health Centre, in Montreal.

The investigators were spurred by prior research demonstrating that the degree of intraoperative insulin resistance is a predictor of adverse events (J Clin Endocrinol Metab 2010;95[9]:4338-4344). In that trial involving 143 nondiabetic and 130 diabetic patients scheduled for elective cardiac surgery, it was found that for every 1 mg/kg per minute decrease in insulin sensitivity, the incidence of major complications increased significantly. Indeed, diabetic patients with poor glycemic control had a significantly greater incidence of major complications and minor infections than those with better glycemic control.

The researchers studied individuals scheduled for elective CABG, valve surgery or a combination of both between May 2008 and June 2015 at their institution. Patients undergoing off-pump CABG or procedures with anticipated deep hypothermic circulatory arrest were excluded.

A Continuum of Weight

All patients received a standardized IV anesthesia regimen consisting of sufentanil and midazolam supplemented with inhaled sevoflurane. Insulin sensitivity was assessed by the hyperinsulinemic-euglycemic clamp technique during cardiac surgery. The investigators used the dextrose infusion rate during steady-state conditions before cardiopulmonary bypass as an indicator of insulin sensitivity.

“Patients were divided into diabetic and nondiabetic patients, and were then classified into one of five groups based on BMI,” Dr. Nakadate said. The groups were:

• underweight (BMI <18.5 kg/m²);
• normal weight (BMI 18.5-25 kg/m²);
• overweight (BMI 25-30 kg/m²);
• obese (BMI 30-35 kg/ m²); and
• morbidly obese (BMI >35 kg/m²).

As Dr. Nakadate reported at the 2017 annual meeting of the Canadian Anesthesiologists’ Society (abstract 272918), 401 patients completed the study and 134 were diabetic. The investigators found a negative correlation for BMI and intraoperative insulin sensitivity, independent of the presence of diabetes mellitus. Indeed, insulin sensitivity in nondiabetic underweight and normal-weight patients was higher than in their overweight, obese and morbidly obese counterparts.

Moreover, diabetic patients in the underweight, normal-weight and overweight groups also showed greater insulin sensitivity than obese and morbidly obese diabetic patients. Perhaps not surprisingly, diabetic patients were on average less insulin sensitive than nondiabetic patients in all weight groups.

“In summary,” Dr. Nakadate said, “we demonstrated that higher BMI is a strong predictor of intraoperative insulin resistance. Taking into account our previous study, which demonstrated that intraoperative insulin resistance is a predictor of worse postoperative outcomes, this study suggests that obesity may be a risk factor for worse outcomes.”

According to Boris Mraovic, MD, the trial adds to the growing body of evidence on the importance of perioperative insulin sensitivity and glucose control.

“It is probably most important in cardiac surgery because the stress of surgery increases insulin resistance, and cardiac surgery is one of the most stressful surgeries,” he said. Dr. Mraovic is an associate professor of clinical anesthesiology at the University of Missouri School of Medicine, in Columbia.

“BMI and insulin resistance as risk factors for morbidity and mortality are well established, as they are components of metabolic syndrome,” Dr. Mraovic added. “This study showed a direct linear correlation of BMI and insulin sensitivity, proving that even moderate increases in BMI—as a risk factor for perioperative morbidity/mortality—should not be ignored.”

Dr. Mraovic recommended preoperative carbohydrate loading as one way to improve perioperative insulin sensitivity, a strategy whose benefit is established in enhanced recovery after major abdominal surgeries and in cardiac surgery.

“Would decreasing BMI and improving insulin sensitivity before elective surgery improve outcomes after cardiac surgery?” Dr. Mraovic asked. “That is still unknown and remains to be investigated.”

—Michael Vlessides