Reply to Freckmann et al. Comment on "Hochfellner et al. Accuracy Assessment of the GlucoMen® Day CGM System in Individuals with Type 1 Diabetes: A Pilot Study. Biosensors 2022, 12, 106".

We thank Dr. Freckmann et al. [...].

Accuracy Assessment of the GlucoMen® Day CGM System in Individuals with Type 1 Diabetes: A Pilot Study.

The aim of this study was to evaluate the accuracy and usability of a novel continuous glucose monitoring (CGM) system designed for needle-free insertion and reduced environmental impact. We assessed the sensor performance of two GlucoMen® Day CGM systems worn simultaneously by eight participants with type 1 diabetes. Self-monitoring of blood glucose (SMBG) was performed regularly over 14 days at home. Participants underwent two standardized, 5-h meal challenges at the research center with frequent plasma glucose (PG) measurements using a laboratory reference (YSI) instrument. When comparing CGM to PG, the overall mean absolute relative difference (MARD) was 9.7 [2.6-14.6]%. The overall MARD for CGM vs. SMBG was 13.1 [3.5-18.6]%. The consensus error grid (CEG) analysis showed 98% of both CGM/PG and CGM/SMBG pairs in the clinically acceptable zones A and B. The analysis confirmed that GlucoMen® Day CGM meets the clinical requirements for state-of-the-art CGM. In addition, the needle-free insertion technology is well tolerated by users and reduces medical waste compared to conventional CGM systems.

Insulin induces a progressive increase in the resistance of subcutaneous tissue to fluid flow: Implications for insulin pump therapy.

AIM: To determine the effect of insulin on the resistance of subcutaneous tissue to the flow of infusion fluids. MATERIALS AND METHODS: Thirty subjects with type 1 diabetes wore two Accu-Chek Spirit Combo insulin pumps with Accu-Chek FlexLink infusion sets (Roche Diabetes Care, Mannheim, Germany) for 7 days. One pump was filled with insulin aspart (Novo Nordisk, Bagsvaerd, Denmark) and used for continuous subcutaneous insulin infusion (CSII). The other pump was filled with insulin diluting medium (IDM; Novo Nordisk) and used to deliver IDM subcutaneously at rates identical to those employed for CSII. Both infusion sites were assessed daily by measuring the pressure required to infuse various bolus amounts of IDM. RESULTS: On day 1, maximum pressure (Pmax ) and tissue flow resistance (TFR; calculated from measured pressure profiles) were similar for both infusion sites (P > 0.20). During the subsequent study days, the Pmax and TFR values observed at the IDM infusion site remained at levels comparable to those seen on day 1 (P > 0.13). However, at the site of CSII, Pmax and TFR progressively increased with CSII duration. By the end of day 7, Pmax and TFR reached 25.8 */2.11 kPa (geometric mean */geometric standard deviation) and 8.64 */3.48 kPa*s/µL, respectively, representing a remarkable 3.5- and 20.6-fold increase relative to the respective Pmax and TFR values observed on day 1 (P < 0.001). CONCLUSION: Our results suggest that insulin induces a progressive increase in the resistance of subcutaneous tissue to the introduction of fluid; this has important implications for the future design of insulin pumps and infusion sets.

Efficient and safe glycaemic control with basal-bolus insulin therapy during fasting periods in hospitalized patients with type 2 diabetes using decision support technology: A post hoc analysis.

AIM: To evaluate the efficacy and safety of basal-bolus insulin therapy in managing glycaemia during fasting periods in hospitalized patients with type 2 diabetes. MATERIALS AND METHODS: We performed a post hoc analysis of two prospective, uncontrolled interventional trials that applied electronic decision support system-guided basal-bolus (meal-related and correction) insulin therapy. We searched for fasting periods (invasive or diagnostic procedures, medical condition) during inpatient stays. In a mixed model analysis, patients' glucose levels and insulin doses on days with regular food intake were compared with days with fasting periods. RESULTS: Out of 249 patients, 115 patients (33.9% female, age 68.3 ± 10.3 years, diabetes duration 15.1 ± 10.9 years, body mass index 30.1 ± 5.4 kg/m2 , HbA1c 69 ± 20 mmol/mol) had 194 days with fasting periods. Mean daily blood glucose (BG) was lower (modelled difference [ModDiff]: -0.5 ± 0.2 mmol/L, P = .006), and the proportion of glucose values within the target range (3.9-10.0 mmol/L) increased on days with fasting periods compared with days with regular food intake (ModDiff: +0.06 ± 0.02, P = .005). Glycaemic control on fasting days was driven by a reduction in daily bolus insulin doses (ModDiff: -11.0 ± 0.9 IU, P < .001), while basal insulin was similar (ModDiff: -1.1 ± 0.6 IU, P = .082) compared with non-fasting days. Regarding hypoglycaemic events (BG < 3.9 mmol/L), there was no difference between fasting and non-fasting days (χ2 0.9% vs. 1.7%, P = .174). CONCLUSIONS: When using well-titrated basal-bolus insulin therapy in hospitalized patients with type 2 diabetes, the basal insulin dose does not require adjustment during fasting periods to achieve safe glycaemic control, provided meal-related bolus insulin is omitted and correction bolus insulin is tailored to glucose levels.

Survival assessment of the extended-wear insulin infusion set featuring lantern technology in adults with type 1 diabetes by the glucose clamp technique.

Maintaining good glycaemic control with the same infusion set for longer than 3 days may improve the quality of life of insulin pump users. The aim of the current study was to assess the efficacy and safety of the novel, extended-wear infusion set over 7 days of wear in adults with type 1 diabetes. Sixteen participants completed three identical 8-hour euglycaemic clamp experiments on Days 1, 4 and 7 of infusion set wear. Between the experiments, the participants were discharged home for routine diabetes management while wearing the same extended-wear infusion set throughout the study. Time to reach the maximum glucose infusion rate (TGIRmax ) on Day 7 was reduced by 67% compared with Day 1 (p < .001). The corresponding area under the glucose infusion rate curve (AUCGIR ) was comparable for the first 2 h of the clamp (p = .891) but decreased by 28% over time (p < .008). While the extent of insulin absorption decreased with prolonged wear, it was accompanied by an increase in insulin absorption rate. The infusion set survival rate was 100% without leakages, occlusion alarms, severe hypoglycaemia or ketoacidosis. The extended-wear infusion set proved safe and effective during prolonged wear in real-life conditions.

Development of a Single-Site Device for Conjoined Glucose Sensing and Insulin Delivery in Type-1 Diabetes Patients.

OBJECTIVE: Diabetes patients are increasingly using a continuous glucose sensor to monitor blood glucose and an insulin pump connected to an infusion cannula to administer insulin. Applying these devices requires two separate insertion sites, one for the sensor and one for the cannula. Integrating sensor with cannula to perform glucose sensing and insulin infusion through a single insertion site would significantly simplify and improve diabetes treatment by reducing the overall system size and the number of necessary needle pricks. Presently, several research groups are pursuing the development of combined glucose sensing and insulin infusion devices, termed single-port devices, by integrating sensing and infusion technologies created from scratch. METHODS: Instead of creating the device from scratch, we utilized already existing technologies and introduced three design concepts of integrating commercial glucose sensors and infusion cannulas. We prototyped and evaluated each concept according to design simplicity, ease of insertion, and sensing accuracy. RESULTS: We found that the best single-port device is the one in which a Dexcom sensor is housed inside a Medtronic cannula so that its glucose sensitive part protrudes from the cannula tip. The low degree of component modification required to arrive at this configuration allowed us to test the efficiency and safety of the device in humans. CONCLUSION: Results from these studies indicate the feasibility of combining commercial glucose sensing and insulin delivery technologies to realize a functional single-port device. SIGNIFICANCE: Our development approach may be generally useful to provide patients with innovative medical devices faster and at reduced costs.