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Carb-matching Bolus vs. Weight-Dependent Partial Bolus on Closed-Loop Glucose Control

Apr 4, 2014

Carbohydrate counting can be difficult for some type 1 diabetes patients. Partial prandial weight-based bolus dosing may be a safe and effective alternative….

For type 1 diabetes patients, single- and dual- hormone closed-loop systems may confer greater overnight glycemic control than conventional insulin pump therapy. A major challenge with these emerging technologies is the closed-loop control of postprandial blood glucose, especially in the morning.

One strategy is to deliver a full bolus-based dose using pre-programmed insulin-to-carbohydrate (I:C) ratios. This strategy may lead to an increased risk of postprandial hypoglycemia without reducing the burden related to carbohydrate counting.

Another strategy avoids prandial boluses, relying solely on a sensor to detect blood glucose changes. While this eliminates the need for carbohydrate counting, it may increase the risk of prolonged hypoglycemia. This is a result of a combination of the lag time associated with the glucose sensor and rapid-acting insulin absorption.

An alternative approach that has the ability to lower the risk of hypo- and hyperglycemia is the partial prandial bolus dose. In a prior study, patients who used this approach achieved favorable postprandial blood glucose control.

In a recent study, researchers compared full carbohydrate-matching boluses with partial boluses while on a dual-hormone closed loop system.

This study was a randomized, crossover study which assessed 12 adults with type 1 diabetes (age 37.5 +/- 9.4 years, BMI 25.6 +/-3.5 kg/m2, HbA1c 7.9 +/- 1.2% and total daily dose 0.6 +/-0.2 Units/kg/day). Participants were on pump therapy for at least 3 months and those with HbA1c greater than 12% were excluded from this study. 

Following an overnight fast, participants received a large, 75 gram carbohydrate breakfast, consisting of bananas, crackers, cereal, milk and cheddar cheese; and having a total of 18.5 grams of protein and 17.7 grams of fat. Participants then received full carbohydrate-matching bolus or a weight-dependent partial bolus.

Partial weight-dependent boluses were calculated at 0.047 Units/kg. Using the aid of a nutritionist, full bolus doses were calculated using personalized insulin to carbohydrate ratios.

Insulin aspart and glucagon were delivered using 2 subcutaneous infusion pumps, at 10 minute intervals, starting at breakfast and lasting over the course of 5 hours. Venous blood samples were collected using the YSI2300 STAT Plus Analyzer at -15, 0, 10, 20, 30, 40, 60, 80, 100, 120, 140, 160, 180, 210, 240, 270 and 300 minutes following breakfast.

On the full bolus visits, fasting glucose levels were 135mg/dL.(7.5 mmol/L) and on partial bolus visits, fasting glucose levels were 128mg/dL.(7.1 mmol/L ) (P = 0.01). These levels increased by 56mg/dL( 3.15 mmol/L) and 128mg/dL>(7.11 mmol/L) at the peak (P = 0.006), for full bolus visits and partial bolus visits, respectively.

Following the full bolus, glucose levels returned to baseline after approximately 2 hours. In the partial bolus visit, glucose returned to baseline at approximately 5 hours.

The incremental AUC was also lower after the full bolus compared to the partial bolus (IAUC, 2.1 mmol/L/h vs 8.3 mmol/L/h,P < 0.001). Basal insulin delivery over 300 min was doubled on the partial bolus visits compared to the full bolus visits (8.05 U [6.74–8.98] vs 3.90 U [3.05–6.81]; P < 0.01).

Overall, the total insulin delivery remained higher on the full bolus visits (14.16 Units [11.06–7.03] vs 11.70 Units [9.81–13.16]; P = 0.03). No hypoglycemic events were observed in the partial bolus visits and a total of 2 hypoglycemic events occurred full bolus visits. On the full bolus and partial bolus visits the average number of glucagon boluses were 2.5 and 0.9, respectively. The size of these glucagon boluses remained virtually identical, however.

A strong negative correlation was found while analyzing the difference in the glucose area under the curve between the 2 interventions and the partial bolus divided by the insulin to carbohydrate ratio – suggesting that an alternative bolus strategy proportional to insulin to carbohydrate ratio may achieve better control compared to a weight-based bolus. In addition, this alternative bolus strategy would allow for the patient to have different partial boluses depending on the time of the day.

Practice Pearls:
  • Carbohydrate counting is a burden for many diabetic patients
  • Although not as effective as full bolus dosing in closed-loop systems, partial prandial weight-based bolus dosing may be a safe and effective alternative
  • More robust studies are necessary to confirm these findings

Haidar A, Farid D, St-Yves A, et al. Post-breakfast closed-loop glucose control is improved when accompanied with carbohydrate-matching bolus compared to weight-dependent bolus. Diabetes Metab. 2014;