Diabetes Technology & Therapeutics

The artificial pancreas (AP) has the potential to improve glycemic control in adolescents. This article presents the first evaluation in adolescents of the Zone Model Predictive Control and Health Monitoring System (ZMPC+HMS) AP algorithms, and their first evaluation in a supervised outpatient setting with frequent exercise.

Adolescents with type 1 diabetes underwent 3 days of closed-loop control (CLC) in a hotel setting with the ZMPC+HMS algorithms on the Diabetes Assistant platform. Subjects engaged in twice-daily exercise, including soccer, tennis, and bicycling. Meal size (unrestricted) was estimated and entered into the system by subjects to trigger a bolus, but exercise was not announced.

Ten adolescents (11.9–17.7 years) completed 72 h of CLC, with data on 95 ± 14 h of sensor-augmented pump (SAP) therapy before CLC as a comparison to usual therapy. The percentage of time with continuous glucose monitor (CGM) 70–180 mg/dL was 71% ± 10% during CLC, compared to 57% ± 16% during SAP (P = 0.012). Nocturnal control during CLC was safe, with 0% (0%, 0.6%) of time with CGM <70 mg/dL compared to 1.1% (0.0%, 14%) during SAP. Despite large meals (estimated up to 120 g carbohydrate), only 8.0% ± 6.9% of time during CLC was spent with CGM >250 mg/dL (16% ± 14% during SAP). The system remained connected in CLC for 97% ± 2% of the total study time. No adverse events or severe hypoglycemia occurred.

The use of the ZMPC+HMS algorithms is feasible in the adolescent outpatient environment and achieved significantly more time in the desired glycemic range than SAP in the face of unannounced exercise and large announced meal challenges.

We aimed to compare closed-loop glucose control for people with type 1 diabetes undertaking high-intensity interval exercise (HIIE) versus moderate-intensity exercise (MIE).

Adults with type 1 diabetes established on insulin pumps undertook HIIE and MIE stages in random order during automated insulin delivery via a closed-loop system (Medtronic). Frequent venous sampling for glucose, lactate, ketones, insulin, catecholamines, cortisol, growth hormone, and glucagon levels was performed. The primary outcome was plasma glucose <4.0 mmol/L for ≥15 min, from exercise commencement to 120 min postexercise. Secondary outcomes included continuous glucose monitoring and biochemical parameters.

Twelve adults (age mean ± standard deviation 40 ± 13 years) were recruited; all completed the study. Plasma glucose of one participant fell to 3.4 mmol/L following MIE completion; no glucose levels were <4.0 mmol/L for HIIE (primary outcome). There were no glucose excursions >15.0 mmol/L for either stage. Mean (±standard error) plasma glucose did not differ between stages pre-exercise; was higher during exercise in HIIE than MIE (11.3 ± 0.5 mmol/L vs. 9.7 ± 0.6 mmol/L, respectively; P < 0.001); and remained higher until 60 min postexercise. There were no differences in circulating free insulin before, during, or postexercise. During HIIE compared with MIE, there were greater increases in lactate (P < 0.001), catecholamines (all P < 0.05), and cortisol (P < 0.001). Ketones increased more with HIIE than MIE postexercise (P = 0.031).

Preliminary findings suggest that closed-loop glucose control is safe for people undertaking HIIE and MIE. However, the management of the postexercise rise in ketones secondary to counter-regulatory hormone-induced insulin resistance observed with HIIE may represent a challenge for closed-loop systems.

Fasting Ramadan carries a high risk for patients with type 1 diabetes (T1DM). Data on the optimum insulin regimen in these patients are limited.

To compare glucose profiles in patients with T1DM who use continuous subcutaneous insulin infusion (CSII) compared with those who use multiple daily injections (MDI) insulin regimen during Ramadan fast. The primary outcome was rates of hypoglycemia. Other outcomes included glycemic control, number of days needed to break fasting, and acute glycemic complications.

Patients with T1DM who were on CSII or MDI and decided to fast Ramadan were recruited. Glucose data collected using self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) were compared in the two groups, CSII and MDI, and glucose control was assessed by measuring serum fructosamine levels.

A total of 156 patients were recruited, 61 on CSII and 95 on MDI. There was no difference in the rate of mild hypoglycemia <4.4 mmol/L (<80 mg/dL) (8.6% ± 6.1% in the CSII group and 9.85% ± 9.34% in the MDI group, P = 0.96). The mean rate of severe hypoglycemia <2.7 mmol/L (<50 mg/dL) was also not different in both groups (0.99% ± 1.7% in the CSII group compared to 1.7% ± 4.7% in the MDI group, P = 0.23). There was no difference in glycemic control as measured by fructosamine levels or the number of days that patients have to stop fasting. Glucose variability was significantly better in CSII group (SMBG; standard deviation [SD] 66.9 ± 15.3 vs. 76.9 ± 29.9, P = 0.02) (CGM; SD 68.1 ± 19.6 vs. 78.7 ± 24.9, P = 0.04). No diabetic ketoacidosis was reported in either group.

In patients with T1DM who fast Ramadan, there was no difference in rates of hypoglycemia or hyperglycemia between CSII and MDI. However, CSII was associated with less glucose variability.

Postprandial (PP) control remains a challenge for closed-loop (CL) systems. Few studies with inconsistent results have systematically investigated the PP period.

To compare a new CL algorithm with current pump therapy (open loop [OL]) in the PP glucose control in type 1 diabetes (T1D) subjects.

A crossover randomized study was performed in two centers. Twenty T1D subjects (F/M 13/7, age 40.7 ± 10.4 years, disease duration 22.6 ± 9.9 years, and A1c 7.8% ± 0.7%) underwent an 8-h mixed meal test on four occasions. In two (CL1/CL2), after meal announcement, a bolus was given followed by an algorithm-driven basal infusion based on continuous glucose monitoring (CGM). Alternatively, in OL1/OL2 conventional pump therapy was used. Main outcome measures were as follows: glucose variability, estimated with the coefficient of variation (CV) of the area under the curve (AUC) of plasma glucose (PG) and CGM values, and from the analysis of the glucose time series; mean, maximum (C_max), and time to C_max glucose concentrations and time in range (<70, 70–180, >180 mg/dL).

CVs of the glucose AUCs were low and similar in all studies (around 10%). However, CL achieved greater reproducibility and better PG control in the PP period: CL1 = CL2<OL1<OL2 (PG_mean 123 ± 47 and 125 ± 44 vs. 152 ± 53 and 159 ± 54 mg/dL) and C_max OL 217.1 ± 67.0 mg/dL versus CL 183.3 ± 63.9 mg/dL, P < 0.0001. Time-in-range was higher with CL versus OL (80% vs. 64%; P < 0.001). Neither the time below 70 mg/dL (CL 6.1% vs. OL 3.2%; P > 0.05) nor the need for oral glucose was significantly different (CL 40.0% vs. OL 22.5% of meals; P = 0.054).

This novel CL algorithm effectively and consistently controls PP glucose excursions without increasing hypoglycemia. Study registered at ClinicalTrials.gov: study number NCT02100488.

Managing type 1 diabetes (T1D) in young children presents challenges to families and caregivers. Pump therapy may reduce challenges and benefit glycemic control. However, pump use is not universal; parent-reported reasons for lack of uptake are not well described.

Parents of children <7, with T1D for ≥1 year, in the T1D Exchange registry completed surveys capturing demographic and clinical characteristics, as well as barriers to pump use. Data from pump users were compared to nonusers, and barriers were analyzed among parents who received pump recommendations, but decided against uptake.

Young children (N = 515) from 41 sites were identified (mean age 5.2 ± 1.2 years, diabetes duration 2.4 ± 1.0 years, 46% female, and 78% Non-Hispanic White). Overall glycemic control was suboptimal (HbA1c 8.1% ± 1.0%). The majority were pump users (64%, n = 331; nonusers 36%, n = 184). Pump users had longer T1D duration (2.5 ± 1.1 years vs. 2.2 ± 1.0 years, P = 0.001), were more likely to have annual household incomes ≥$75,000 (62% vs. 36%, P < 0.001), have a parent with college education or higher (70% vs. 45%, P < 0.001), perform more frequent blood glucose monitoring (7.5 ± 2.5 times/day vs. 6.5 ± 2.3 times/day, P < 0.001), and use continuous glucose monitoring (CGM) (45% vs. 13%, P < 0.001). Only income, education, frequency of blood glucose monitoring, and CGM use remained significant in a multivariate model including age, sex, ethnicity, and duration of diabetes. Barriers to pump uptake included concerns with physical interference, therapeutic effectiveness, and to a lesser extent, financial burden.

These findings provide an opportunity to address potentially modifiable parent-reported barriers to pump uptake through education and behavioral intervention.

Exercise causes glycemic disturbances in individuals with type 1 diabetes (T1D). Continuous moderate-intensity aerobic exercise (CON) generally lowers blood glucose (BG) levels and often leads to hypoglycemia. In comparison, circuit-based exercise (CIRC) may attenuate the drop in BG. The goal of this study is to contrast the effects of basal insulin suspension at the onset of two different forms of exercise (CON vs. CIRC).

Twelve individuals (six men and six women) with T1D on insulin pump therapy were recruited for the study. All participants completed a maximal aerobic fitness test and two 40-min exercise sessions, consisting of either continuous treadmill walking or a circuit workout. Basal insulin infusion was stopped at the onset of exercise and resumed in recovery. After providing an initial reference value, volunteers were blinded to their [BG] and were asked to estimate their levels during exercise.

Oxygen consumption (47.5 ± 7.5 vs. 54.5 ± 13.5 mL·kg⁻¹·min⁻¹, P = 0.03) and heart rate (122 ± 20 vs. 144 ± 20 bpm, P = 0.003) were lower in CON vs. CIRC. Despite the lower workload, BG levels dropped more with CON vs. CIRC (delta BG = −3.8 ± 1.5 vs. −0.5 ± 3.0 mmol/L for CON vs. CIRC, respectively, P = 0.001). Participants were able to estimate their BG more accurately during CON (r = 0.83) vs. CIRC (r = 0.33) based on a regression analysis.

Despite a lower intensity of exercise, with full basal insulin suspension at the start of exercise, CON results in a larger drop in BG vs. CIRC. These findings have implications for single hormone-based artificial pancreas development for exercise. While this study does not negate the importance of frequent capillary BG monitoring during exercise, it does suggest that if persons are knowledgeable about their pre-exercise BG levels, they can accurately perceive the changes in BG during CON, but not during CIRC.