Home Use of an Artificial Beta Cell in Type 1 Diabetes.

BACKGROUND: The feasibility, safety, and efficacy of prolonged use of an artificial beta cell (closed-loop insulin-delivery system) in the home setting have not been established. METHODS: In two multicenter, crossover, randomized, controlled studies conducted under free-living home conditions, we compared closed-loop insulin delivery with sensor-augmented pump therapy in 58 patients with type 1 diabetes. The closed-loop system was used day and night by 33 adults and overnight by 25 children and adolescents. Participants used the closed-loop system for a 12-week period and sensor-augmented pump therapy (control) for a similar period. The primary end point was the proportion of time that the glucose level was between 70 mg and 180 mg per deciliter for adults and between 70 mg and 145 mg per deciliter for children and adolescents. RESULTS: Among adults, the proportion of time that the glucose level was in the target range was 11.0 percentage points (95% confidence interval [CI], 8.1 to 13.8) greater with the use of the closed-loop system day and night than with control therapy (P<0.001). The mean glucose level was lower during the closed-loop phase than during the control phase (difference, -11 mg per deciliter; 95% CI, -17 to -6; P<0.001), as were the area under the curve for the period when the glucose level was less than 63 mg per deciliter (39% lower; 95% CI, 24 to 51; P<0.001) and the mean glycated hemoglobin level (difference, -0.3%; 95% CI, -0.5 to -0.1; P=0.002). Among children and adolescents, the proportion of time with the nighttime glucose level in the target range was higher during the closed-loop phase than during the control phase (by 24.7 percentage points; 95% CI, 20.6 to 28.7; P<0.001), and the mean nighttime glucose level was lower (difference, -29 mg per deciliter; 95% CI, -39 to -20; P<0.001). The area under the curve for the period in which the day-and-night glucose levels were less than 63 mg per deciliter was lower by 42% (95% CI, 4 to 65; P=0.03). Three severe hypoglycemic episodes occurred during the closed-loop phase when the closed-loop system was not in use. CONCLUSIONS: Among patients with type 1 diabetes, 12-week use of a closed-loop system, as compared with sensor-augmented pump therapy, improved glucose control, reduced hypoglycemia, and, in adults, resulted in a lower glycated hemoglobin level. (Funded by the JDRF and others; AP@home04 and APCam08 ClinicalTrials.gov numbers, NCT01961622 and NCT01778348.).

Bolusing frequency and amount impacts glucose control during hybrid closed-loop.

AIM: To compare bolus insulin delivery patterns during closed-loop home studies in adults with suboptimally [HbA1c 58-86 mmol/mol (7.5%-10%)] and well-controlled [58 mmol/mol (< 7.5%)] Type 1 diabetes. METHODS: Retrospective analysis of daytime and night-time insulin delivery during home use of closed-loop over 4 weeks. Daytime and night-time controller effort, defined as amount of insulin delivered by closed-loop relative to usual basal insulin delivery, and daytime bolus effort, defined as total bolus insulin delivery relative to total daytime insulin delivery were compared between both cohorts. Correlation analysis was performed between individual bolus behaviour (bolus effort and frequency) and daytime controller efforts, and proportion of time spent within and below sensor glucose target range. RESULTS: Individuals with suboptimally controlled Type 1 diabetes had significantly lower bolus effort (P = 0.038) and daily bolus frequency (P < 0.001) compared with those with well-controlled diabetes. Controller effort during both daytime (P = 0.007) and night-time (P = 0.005) were significantly higher for those with suboptimally controlled Type 1 diabetes. Time when glucose was within the target range (3.9-10.0 mmol/L) during daytime correlated positively with bolus effort (r = 0.37, P = 0.016) and bolus frequency (r = 0.33, P = 0.037). Time when glucose was below the target range during daytime was comparable in both groups (P = 0.36), and did not correlate significantly with bolus effort (r = 0.28, P = 0.066) or bolus frequency (r = -0.21, P = 0.19). CONCLUSION: More frequent bolusing and higher proportion of insulin delivered as bolus during hybrid closed-loop use correlated positively with time glucose was in target range. This emphasises the need for user input and educational support to benefit from this novel therapeutic modality.

Impact of injection speed and volume on perceived pain during subcutaneous injections into the abdomen and thigh: a single-centre, randomized controlled trial.

AIM: The aim of this study was to assess pain associated with subcutaneous injection into the abdomen and thigh of different combinations of injection speeds and volumes. METHODS: The study was a single-centre, one-visit, double-blinded, randomized controlled trial in 82 adults with type 1 or type 2 diabetes receiving daily injections of insulin or glucagon-like peptide-1 (GLP-1) agonists. Participants received 17 subcutaneous injections (12 in abdomen, 5 in thigh) of saline at different injection speeds (150, 300 and 450 µl/s), with different volumes (400, 800, 1200 and 1600 µl), and two needle insertions without any injection. Pain was evaluated on a 100-mm visual analogue scale (VAS) (0 mm no pain, 100 mm worst pain) and on a yes/no scale for pain acceptability. RESULTS: Injection speed had no impact on injection pain (p = 0.833). Injection of larger volumes caused significantly more pain [VAS least square mean differences 1600 vs. 400 µl, 7 · 2 mm (95% confidence interval - CI; 4.6-9.7; p < 0.0001); 1600 vs. 800 µl, 7.2 mm (4.4-10.0; p < 0.0001); 1200 vs. 400 µl, 3.5 mm (0.4-6.6; p = 0.025) and 1200 vs. 800 µl, 3.6 mm (0.4-6.7; p = 0.027)]. Significantly more pain occurred in the thigh versus the abdomen [9.0 mm (6.7-11.3; p < 0.0001)]. CONCLUSIONS: Injection speed had no effect on injection pain, whereas higher injection volumes caused more pain. The results of this study may be of value for guiding patients to use the appropriate injection site and technique to reduce their injection pain. Furthermore, these findings may have important implications for the development of new injection devices and drug formulations for clinical practice.

Plasma glucose and hypoglycaemia following exercise in people with Type 1 diabetes: a comparison of three basal insulins.

AIM: The aim of this study was to compare the effects of exercise on plasma glucose excursions when using each of three basal insulins in people with Type 1 diabetes. RESEARCH DESIGN AND METHODS: This was a multinational, open-label, randomized, three-period, crossover clinical trial. People with Type 1 diabetes [n = 51, age 39 +/- 10 (+/- sd) years, 67% men] managed with mealtime plus basal insulin regimens, were exercised for 30 min, 5 h after the last mealtime and basal insulin injection when using insulin detemir, insulin glargine or neutral protamine Hagedorn (NPH) insulin. RESULTS: There were no significant differences in the plasma glucose excursions during or for 150 min after exercise. During 30 min exercise, five (11%) participants on insulin detemir developed minor hypoglycaemia, six (12%) for NPH and 18 (38%) for glargine. From the end of exercise to 150 min, five (11%) on insulin detemir developed minor hypoglycaemia, seven (14%) for NPH and nine (19%) for glargine. In total, from start of exercise to 150 min after exercise, 10 (21%) participants on insulin detemir experienced minor hypoglycaemia as compared with 13 (27%) for NPH and 27 (57%) for glargine (P < 0.001 glargine vs. detemir and NPH). Maximum plasma cortisol levels were lower on detemir and NPH than glargine. CONCLUSIONS: Insulin detemir was associated with less hypoglycaemia than insulin glargine but not NPH insulin in relatively well-controlled people with Type 1 diabetes during and after exercise.

Inhaled insulin as adjunctive therapy in subjects with type 2 diabetes failing oral agents: a controlled proof-of-concept study.

AIM: This controlled proof-of-concept study investigated inhaled insulin (INH) as adjunctive therapy to existing oral antidiabetic agents in subjects with type 2 diabetes. METHODS: Twenty-four subjects with type 2 diabetes [19 men and 5 women, 56.1 +/- 6.6 years, body mass index 32.7 +/- 4.2 kg/m(2), glycosylated haemoglobin (HbA1c) 8.4 +/- 0.8% (mean +/- s.d.)] inadequately controlled by metformin and/or sulfonylureas were randomized to receive additional therapy with either INH administered preprandially using a metered-dose inhaler (MDI), or insulin glargine (GLA) injected subcutaneously at bedtime for 4 weeks. Both inhaled and injected insulin doses were titrated to predefined blood glucose (BG) targets. RESULTS: INH and GLA improved metabolic control to a similar extent. Mean daily BG decreased by 2.8 mmol/l in the INH group (p < 0.001) and by 2.4 mmol/l in the GLA group (p < 0.001). Accordingly, fasting BG (-2.7 vs. -3.6 mmol/l for INH vs. GLA), preprandial- and 2-h postprandial BG, HbA1c (-1.23 vs. -1.05%), body weight (-1.9 vs. -2.3 kg) and serum fructosamine were similarly and significantly reduced in both groups (p < 0.05). Triglycerides decreased significantly with INH (-1.15 micromol/l; p < 0.001) but not with GLA [-0.52 micromol/l; not significant (NS)]. Incidence rates of adverse events did not differ significantly, and there were no indications of respiratory tract irritation. CONCLUSIONS: In subjects with type 2 diabetes inadequately controlled by oral agents, preprandial administration of INH delivered by a MDI provided a comparable metabolic control to bedtime GLA and did not show any safety concerns during a 4-week treatment. These results warrant a more extensive investigation of preprandial treatment with INH in longer term studies.