Restoration of self-awareness of hypoglycemia in adults with long-standing type 1 diabetes: hyperinsulinemic-hypoglycemic clamp substudy results from the HypoCOMPaSS trial.

OBJECTIVE: Impaired awareness of hypoglycemia (IAH) and defective counterregulation significantly increase severe hypoglycemia risk in type 1 diabetes (T1D). We evaluated restoration of IAH/defective counterregulation by a treatment strategy targeted at hypoglycemia avoidance in adults with T1D with IAH (Gold score ≥4) participating in the U.K.-based multicenter HypoCOMPaSS randomized controlled trial. RESEARCH DESIGN AND METHODS: Eighteen subjects with T1D and IAH (mean ± SD age 50 ± 9 years, T1D duration 35 ± 10 years, HbA1c 8.1 ± 1.0% [65 ± 10.9 mmol/mol]) underwent stepped hyperinsulinemic-hypoglycemic clamp studies before and after a 6-month intervention. The intervention comprised the HypoCOMPaSS education tool in all and randomized allocation, in a 2 × 2 factorial study design, to multiple daily insulin analog injections or continuous subcutaneous insulin infusion therapy and conventional glucose monitoring or real-time continuous glucose monitoring. Symptoms, cognitive function, and counterregulatory hormones were measured at each glucose plateau (5.0, 3.8, 3.4, 2.8, and 2.4 mmol/L), with each step lasting 40 min with subjects kept blinded to their actual glucose value throughout clamp studies. RESULTS: After intervention, glucose concentrations at which subjects first felt hypoglycemic increased (mean ± SE from 2.6 ± 0.1 to 3.1 ± 0.2 mmol/L, P = 0.02), and symptom and plasma metanephrine responses to hypoglycemia were higher (median area under curve for symptoms, 580 [interquartile range {IQR} 420-780] vs. 710 [460-1,260], P = 0.02; metanephrine, 2,412 [-3,026 to 7,279] vs. 5,180 [-771 to 11,513], P = 0.01). Glycemic threshold for deterioration of cognitive function measured by four-choice reaction time was unchanged, while the color-word Stroop test showed a degree of adaptation. CONCLUSIONS: Even in long-standing T1D, IAH and defective counterregulation may be improved by a clinical strategy aimed at hypoglycemia avoidance

Accuracy of Continuous Glucose Monitoring During Three Closed-Loop Home Studies Under Free-Living Conditions.

OBJECTIVES: Closed-loop (CL) systems modulate insulin delivery based on glucose levels measured by a continuous glucose monitor (CGM). Accuracy of the CGM affects CL performance and safety. We evaluated the accuracy of the Freestyle Navigator(®) II CGM (Abbott Diabetes Care, Alameda, CA) during three unsupervised, randomized, open-label, crossover home CL studies. MATERIALS AND METHODS: Paired CGM and capillary glucose values (10,597 pairs) were collected from 57 participants with type 1 diabetes (41 adults [mean±SD age, 39±12 years; mean±SD hemoglobin A1c, 7.9±0.8%] recruited at five centers and 16 adolescents [mean±SD age, 15.6±3.6 years; mean±SD hemoglobin A1c, 8.1±0.8%] recruited at two centers). Numerical accuracy was assessed by absolute relative difference (ARD) and International Organization for Standardization (ISO) 15197:2013 15/15% limits, and clinical accuracy was assessed by Clarke error grid analysis. RESULTS: Total duration of sensor use was 2,002 days (48,052 h). Overall sensor accuracy for the capillary glucose range (1.1-27.8 mmol/L) showed mean±SD and median (interquartile range) ARD of 14.2±15.5% and 10.0% (4.5%, 18.4%), respectively. Lowest mean ARD was observed in the hyperglycemic range (9.8±8.8%). Over 95% of pairs were in combined Clarke error grid Zones A and B (A, 80.1%, B, 16.2%). Overall, 70.0% of the sensor readings satisfied ISO criteria. Mean ARD was consistent (12.3%; 95% of the values fall within ±3.7%) and not different between participants (P=0.06) within the euglycemic and hyperglycemic range, when CL is actively modulating insulin delivery. CONCLUSIONS: Consistent accuracy of the CGM within the euglycemic-hyperglycemic range using the Freestyle Navigator II was observed and supports its use in home CL studies. Our results may contribute toward establishing normative CGM performance criteria for unsupervised home use of CL.Juvenile Diabetes Research Foundation (#22-2009-802), Diabetes UK (BDA07/0003549) and Seventh Framework Programme of the European Union (Grant Agreement number 247138) with additional support for the Artificial Pancreas work by National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK085621), Wellcome Strategic Award (100574/Z/12/Z), and National Institute for Health Research Cambridge Biomedical Research Centre.This is the final version of the article. It first appeared from Mary Ann Liebert via http://dx.doi.org/10.1089/dia.2015.006

Home use of closed loop insulin delivery improves overnight glucose control in adults with type 1 diabetes: A four-week multicentre randomised crossover study

This is the author accepted manuscript and will be embargoed until 16/12/14. The final published version can be found here: http://www.thelancet.com/journals/landia/article/PIIS2213-8587(14)70114-7/fulltext#article_upsell.Background: We assessed whether overnight home use of automated closed loop insulin delivery (artificial pancreas) improves glucose control. Methods: We studied 24 adults with type 1 diabetes in a multicentre crossover study design comparing four weeks of overnight closed loop using a model predictive control algorithm to direct insulin delivery, with four weeks of insulin pump therapy in which participants used real-time display of continuous glucose monitoring independent of their pumps as control. Primary outcome was time when glucose was in the target range of 3•9 and 8•0mmol/l between midnight to 07:00. Analyses were by intention to treat. Trial registration ClinicalTrials.gov NCT01440140. Findings: Closed loop was utilised over median 8•3 (interquartile range 6•0, 9•6)hours on 555nights (86%). Proportion of time when overnight glucose was in target range was significantly higher during closed loop compared to control by 13•5% (95% CI, 7•3-19•7; p<0•001). Mean overnight glucose (8•2±0•9 vs. 9•0±1•3mmol/l; p=0•005) and time spent above target (44•3%±11•9 vs. 57•1%±15•6; p=0•001) were significantly lower during closed loop. Time spent below target was low and comparable [1•8%( 0•6, 3•6) vs. 2•1%(0•7, 3•9);p=0•28]. Lower mean overnight glucose was brought about by increased overnight insulin delivery [6•4 (4•5, 8•1) vs. 4•9 (3•7, 6•3)units;p<0•001) without changing the total daily insulin amount [34•5 (29•3, 48•4) vs. 35•4 (29•7, 45•2)units;p=0•32]. No severe hypoglycaemia episodes occurred during control period and two during closed loop not related to algorithm instructions. Interpretation: Unsupervised overnight closed loop at home is feasible and may improve glucose control in adults with type 1 diabetes

Factors associated with glycemic control during free-living overnight closed-loop insulin delivery in children and adults with type 1 diabetes

Unsupervised free-living overnight home use of closed-loop insulin delivery is feasible, safe, and effective in adolescents1 and adults2 with type 1 diabetes, but outcomes vary between individuals. Understanding factors influencing glucose outcomes may help to identify vulnerable populations, guide design of future studies, and lead to enhanced control algorithms.Funding for these studies was received from the JDRF (#22-2009-802) and Diabetes UK (BDA07/0003549), with additional support for the Artificial Pancreas work by National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK085621), Wellcome Strategic Award (100574/Z/12/Z), and National Institute for Health Research Cambridge Biomedical Research Centre.This is the final version of the article. It was first available from Sage via http://dx.doi.org/10.1177/193229681560443