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.

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.).

Spectrum of Diabetes Research does not Reflect Patients' Scientific Preferences: A Longitudinal Evaluation of Diabetes Research Areas 2010-2013 vs. a Cross-sectional Survey in Patients with Diabetes.

OBJECTIVE: To compare the proportions and trends in the distribution of research topics as presented during the annual meetings 2010-2013 of the European Association for the Study of Diabetes (EASD) to patients' preferences. METHODS: Longitudinal evaluation of EASD research areas 2010-2013 divided into 9 main categories and compared with a cross-sectional survey in 918 people (652 with patients with diabetes, 205 relatives, 61 others interested), who had allocated their preferences to the same 9 topics. RESULTS: "Development, pathophysiology and prevention of diabetes" was the primary category of interest for 25% of patients, 19% preferred "transplantation and cell therapy" and 16% "blood glucose measurement, devices and artificial pancreas". During the 4 years of abstract investigation 50% or more of total research activities was constantly dedicated to "pathophysiology and prevention of diabetes", less than 2% to "transplantation and cell therapy" and 2.8-4.3% to "blood glucose measurement, devices and artificial pancreas". The average proportion of EASD research related to "blood-glucose lowering therapy without insulin" and "insulin therapy" corresponded with the proportion of research patients would like to see (12.0 vs. 12.5%, and 6.9 vs. 4.7%, respectively). The majority, however, was commercially funded. Non-commercial research was not closer correlated to patients' preferences. CONCLUSION: The distribution of research topics over the last 4 years as measured by the distribution of accepted EASD abstracts does not reflect what patients and their relatives want to have investigated. Better patient involvement and a reassessment of non-commercial funding strategies might help create more valuable research.

How do patients' preferences compare to the present spectrum of diabetes research?

OBJECTIVE: To compare patients' preferences in diabetes research to the current scientific research spectrum as presented during annual meetings of the European Association for the Study of Diabetes (EASD). METHODS: After dividing all scientific activities in diabetes research into 9 main fields, a questionnaire was published in a popular German weekly news magazine, inviting diabetic patients to express their research preferences. Thereafter, all abstracts accepted for publication at 2 recent EASD meetings were allocated to one of these research fields. RESULTS: In May and July 2011 the questionnaire was answered by 652 patients with diabetes, 205 relatives and 61 other persons interested. The most important research fields were "development, pathophysiology and prevention of diabetes" (25.6%), "transplantation and cell therapy" (19.4%) and "blood glucose measurement and artificial pancreas" (16.5%). The most often covered topic of the 2,645 EASD abstracts was "development, pathophysiology and prevention" (46.3%), followed by "diabetes complications in man" (17.5%) and "special situations, training, psychology, treatment- and care structures" (10.5%). CONCLUSION: Views of diabetic patients and their relatives regarding their preferred research fields may differ when compared to current scientific activity in diabetology. Diabetic patients and their relatives should be involved in the weighting and selection of research topics more often.

Insulin aspart has a shorter duration of action than human insulin over a wide dose-range.

AIMS: Regular human insulin (RHI) at high doses shows prolongation of its duration of action potentially leading to late postprandial hypoglycaemia. This study compared late metabolic activity (4-12 and 6-12 h post-dosing) and duration of action (time to reach late half-maximal activity) over a range of doses between insulin aspart (IAsp) and RHI. METHODS: Pharmacokinetic and pharmacodynamic properties of subcutaneous IAsp and RHI (6, 12 and 24 (I)U) were compared in 16 healthy subjects in this double-blind, randomized, six-way crossover glucose clamp study. RESULTS: With increasing doses of both insulins, metabolic activity, insulin exposure, maximum metabolic effect and maximum serum insulin concentration increased linearly. Late metabolic activity was lower for IAsp than RHI at all doses, reaching statistical significance (p < 0.05) for 12 and 24 (I)U. Likewise, IAsp had a shorter duration of action at all doses (p < 0.01) and reached time to 80% of total metabolic activity earlier at doses of 12 and 24 (I)U (p < 0.05). IAsp, compared with RHI, showed a higher maximum metabolic effect at 12 and 24 (I)U (p < 0.0001) and a stronger early metabolic activity for all three doses (p < 0.05). CONCLUSIONS: IAsp showed a shorter duration of action and, particularly with doses of 12 and 24 (I)U, less late metabolic activity than RHI. These properties might contribute to the lower incidence of hypoglycaemia observed with IAsp versus RHI in clinical trials as lower late metabolic activity should decrease the risk of late postprandial hypoglycaemia.

[The length of hospital stay in patients with acute coronary syndrome is reduced by establishing a chest pain unit]. / Reduktion der stationären Verweildauer bei Patienten mit akutem Koronarsyndrom durch Einrichtung einer Chest Pain Unit.

BACKGROUND: Providing prompt and appropriate therapy, combined with the increased economic requirements of treating patients with acute coronary syndrome (ACS), places high demands on the emergency department. The aim of the present analysis is to evaluate to what extent establishing a dedicated chest pain unit (CPU) influences the length of hospital stay in ACS patients. METHODS: Patients presenting with suspected ACS between 05/2004 and 05/2006 to either the emergency department (ED) or the newly established CPU were retrospectively analyzed. The CPU became functional in July 2005. Data were obtained according to standardized procedures based on patient charts and all available clinical information. RESULTS: A total of 247 patients were treated in the ED and 765 in the CPU. In the ED patient group 29 (11.7%) were diagnosed with ST elevation myocardial infarction (STEMI), 38 (15.4%) with non-ST elevation myocardial infarction (NSTEMI) and 15 (6.1%) with unstable angina pectoris (UAP), while ACS could be excluded in 165 (66.8%) patients. Patients treated in the CPU showed a higher percentage of ACS with 75 (9.8%) STEMI, 128 (16.7%) NSTEMI and 136 (17.8%) UAP patients; ACS could be excluded in 426 (55.7%) patients. The median length of hospital stay was shorter in ACS patients treated in the CPU at 5.0 days compared to 8.0 days if admitted to the ED (p<0.001). No difference in length of hospital stay was observed in UAP patients, whereas in STEMI patients admitted to the ED the time was longer at 8.0 days compared to 7.0 days if admitted to the CPU (p=0.042). A reduction from 8.0 to 6.0 days in the length of hospital stay if admitted to the CPU compared to the ED could be observed (p=0.002) in NSTEMI patients. CONCLUSIONS: Establishing a chest pain unit with optimized diagnostic and structural processes is associated with reduced lengths of hospital stay in patients with ACS treated according to current guidelines and recommendations.

How pharmacokinetic and pharmacodynamic principles pave the way for optimal basal insulin therapy in type 2 diabetes.

This pedagogical review illustrates the differences between pharmacokinetic (PK) and pharmacodynamic (PD) measures, using insulin therapy as the primary example. The main conclusion is that PD parameters are of greater clinical significance for insulin therapy than PK parameters. The glucose-clamp technique, the optimal method for determining insulin PD, is explained so that the reader can understand the important studies in the literature. Key glucose-clamp studies that compare two basal insulin analogues - insulin glargine and insulin detemir - to Neutral Protamine Hagedorn insulin and to each other are then presented. The review further explains how PD parameters have been translated into useful clinical concepts and simple titration algorithms for everyday clinical practice. Finally, the necessity of overcoming patient and/or physician barriers to insulin therapy and providing continuing education and training is emphasised.

Insulin glulisine has a faster onset of action compared with insulin aspart in healthy volunteers.

AIM: Because of its zinc-free formulation insulin glulisine (GLU) might have a faster onset of action than other short-acting analogues. We compared the pharmacokinetics and pharmacodynamics of GLU with those of insulin aspart (ASP). METHODS: Twelve healthy subjects, aged 18-65 years, participated in this randomized, double-blind, crossover trial. Subjects received 0.2 U/kg GLU or ASP under euglycaemic glucose-clamp conditions. RESULTS: GLU showed a significantly higher early metabolic effect (area under the glucose infusion rate (GIR) curve in the first 30 min AUC-GIR (0-)30↓ min 30.3 ± 26.4 vs. 16.2 ± 18.4 mg/kg, P = 0.0421) than ASP, an earlier onset of action (time to 10% of GIR (max) (GIR (max)-t (10%)) 9 vs. 17 min, P = 0.0146) and a faster absorption (shorter times to 10% and 20% of INS (max,) P = 0.0005 each). CONCLUSIONS: As demonstrated previously versus lispro, GLU, the only analogue formulated without zinc, also has an earlier onset of action than ASP.

[Cortisone level and emotional support by key figures in patients with bronchial asthma]. / Kortisonbild und emotionale Unterstützung durch Schlüsselfiguren bei Patienten mit Asthma bronchiale.

In a subgroup of patients with bronchial asthma, irrational fears of cortisone medication can be observed beyond justified worries about side-effects. A cortisone image which involves overemphasizing the threatening aspects of cortisone, often underlies noncompliant illness behaviour. In the present study, cortisone image and subjectively experienced emotional support by a key figure was investigated in 62 patients, all of whom had participated in the Düsseldorf Asthma treatment and teaching programme (ATTP). The data show that patients having a supportive relationship with their key figures are less likely to experience threatening aspects of cortisone. The findings are discussed in light of psychoanalytic object relations theory.

[Negative cortisone attitude in patients with bronchial asthma]. / Negatives Kortisonbild bei Patienten mit Asthma bronchiale.

Patients with bronchial asthma often exhibit irrational fears of cortisone medication beyond justified worries about side-effects. A negative cortisone image, which means overemphasizing the damaging and threatening aspects of cortisone, often underlies non-compliant illness behaviour. In the present study, cortisone image was investigated in 54 patients with bronchial asthma before and after participation in the Düsseldorf Asthma treatment and teaching programme (ATTP) and one year later. By participating in ATTP, a significant reduction of the negative cortisone image and thus a more realistic view of cortisone could be achieved in most patients. This effect was also evident at the follow-up examination one year later. On the other hand, persistence of a negative cortisone image in a subgroup of patients turned out to be a potent predictor of later non-compliant illness behaviour. Psychological implications of a persistent negative cortisone image are discussed.