4. Discussion
CIBC, eating behaviors, hyperglycemia, hypoglycemia, insulin-treated diabetes, diabetes
TYPE 1 DIABETES, HYPERGLYCEMIA, HYPOGLYCEMIA, TYPE 2 DIABETES, DIABETES
Glucose trend arrows add important information for appropriate mealtime insulin dosing in patients with intensive insulin-treated diabetes. However, there is still no consensus on adjusting the scheduled dose according to the upward or downward trend arrows available when using CGM.In the absence of evidence, healthcare providers recommend increasing or decreasing the amount of insulin injected before a meal by following algorithms proposed by experts or according to self-reported patient experiences. To our knowledge, this investigation is the first clinical trial evaluating the efficacy and safety of two different algorithms for adjusting mealtime insulin dose based on trend arrows. Among the algorithms available in the literature when the protocol was submitted to the Ethical Committee, we focused on the simple-to-use algorithm adopted in the DirectNet/JDRF study and the more sophisticated algorithm by Ziegler et al.In our study, using a structured approach as on-top therapy for adjusting mealtime insulin doses based on trend arrows improved CGM-derived glucose control and variability measures, with the best results obtained by using the Ziegler algorithm in the subgroup of patients treated with CSII. We believe that flexible insulin administration with CSII, allowing for fractions of units to be delivered as a bolus, can magnify the fine-tuned dose adjustments with the Ziegler algorithm. Notably, the results were obtained without the occurrence of severe hypo- and hyperglycemia and without appreciable differences in the total daily bolus insulin dose possibly due to a more appropriate within-day distribution of mealtime doses. However, the DirectNet/JDRF algorithm can be regarded as a valid alternative for increasing TIR in patients on MDI therapy.Several scientific societies recommend using trend arrows for bolus insulin adjustments for diabetes care [The major strength of our research is the cross-over study design, which eliminates the influence of environmental factors, eating behaviors, and activity level. Notably, the algorithm was added as on-top therapy; that is, patients had adequate glycemic control at baseline, and basal insulin, ICR, and ISF were all optimized before the study.The current study has some limitations. Firstly, we only included adult patients with type 1 diabetes; therefore, the applicability of our findings to type 2 patients on intensive insulin treatment or to pediatric patients is unknown. However, Ziegler and colleagues propose dedicated tables for insulin-dependent type 2 diabetes and children/adolescents with type 1 diabetes, possibly resulting in more flexible insulin dosing and the better control of prandial glucose excursions in these groups of patients.Secondly, we only evaluated the short-term safety and efficacy of the two algorithms. Further research is needed to clarify whether the use of the algorithms may be beneficial in the long term and help patients achieve their desired targets of HbA1c.The interpretation of trend arrows undoubtedly added a layer of complexity when deciding how much insulin to administer before a meal. Any tool facilitating daily dose calculations may result in the more persistent use of dose adjustment algorithms and the long-term improvement of glucose control. In line with this thought, a visual scorecard reporting discrete amounts of insulin units to either add or subtract to the scheduled insulin bolus, such as the Ziegler et al. algorithm, may be more practical than other methods requiring complex calculations (percent dose increase/decrease or recalculation of meal doses based on predicted glucose levels). The development of CGM-informed bolus calculators (CIBC) with automatic trend-based dose adjustments is a further step towards simplifying daily self-management for patients on intensive insulin-based regimens. The feasibility of such an approach has been recently evaluated in a cohort of twenty-five patients with type 1 diabetes on CSII therapy participating in a two-phase, single-arm, prospective, multicenter study conducted in the U.S. At the end of this study, significantly fewer glucose readings of <70 mg/dL at four hours post bolus were found with the CIBC compared to standard bolus calculation without trend-based adjustment (2.1% ± 2.0% vs. 2.8 ± 2.7, In recent years, the development of closed-loop systems providing glucose-responsive algorithm-driven insulin delivery revolutionized the treatment of type 1 diabetes, with ever-growing evidence highlighting their value in improving TIR, especially in the overnight period, without causing an increased risk of hypoglycemia [