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Aims/hypothesisAdvanced glycation end-products (AGEs) may contribute to the development of diabetic neuropathy. In young adults with type 1 diabetes, we aimed to investigate the association between AGEs and cardiovascular autonomic neuropathy (CAN) and distal symmetric polyneuropathy (DSPN).MethodsThis cross-sectional study comprised 151 young adults. CAN was assessed by cardiovascular autonomic reflex tests; lying-to-standing test, deep breathing test (E/I), Valsalva manoeuvre, and heart rate variability indices; and the mean square of the sum of the squares of differences between consecutive R-R intervals and standard deviation of normal-to-normal intervals (SDNN), high- (HF) and low-frequency (LF) power, total frequency power, and the LF/HF ratio. DSPN was assessed by light touch, pain and vibration perception threshold (VPT), neuropathy questionnaires, and objective measures. AGEs were analysed in four groups using z-scores adjusted for relevant confounders and multiple testing: i) “glycolytic dysfunction”, ii) “lipid peroxidation”, iii) “oxidative stress”, and iv) “glucotoxicity”.ResultsA higher z-score of “glycolytic dysfunction” was associated with higher VPT (4.14% (95% CI 1.31; 7.04), p = 0.004) and E/I (0.03% (95% CI 0.01; 0.05), p = 0.005), “lipid peroxidation” was associated with higher LF/HF ratio (37.72% (95% CI 1.12; 87.57), p = 0.044), and “glucotoxicity” was associated with lower SDNN (−4.20% (95% CI −8.1416; −0.0896), p = 0.047). No significance remained after adjustment for multiple testing.Conclusions/interpretationsIn young adults with type 1 diabetes, increased levels of AGEs involving different metabolic pathways were associated with several measures of CAN and DSPN, suggesting that AGEs may play a diverse role in the pathogeneses of diabetic neuropathy.

Plasma clearance of [sup 51]Cr-EDTA is widely used to assess the glomerular filtration rate (GFR) in diabetic nephropathy. Originally, the ratio between the intravenously injected amount of tracer and the total area under the plasma concentration curve was used for the calculation of total [sup 51]Cr-EDTA plasma clearance (C[sub T]). Simplified methods, using the final mono-exponential part of the plasma curve, have been suggested, e.g. four samples, taken 180 to 240 min after injection (C[sub IV]), or using one sample taken at 240 min (C[sub I]). Our aim was to evaluate the agreement between measurements of GFR and rate of in GFR based upon these three methods. Bland & Altman plots were used to illustrate the range of agreement. We investigated 76 insulin-dependent diabetic (IDDM) patients with microalbuminuria or diabetic nephropathy. GFR was measured after a single intravenous injection of 3.7 MBq [sup 51]Cr-EDTA by determining the radioactivity in venous blood samples taken 5, 7, 10, 15, 30, 45, 60, 90, 120, 150, 180, 200, 220,and 240 min after the injection. Rate of decline in GFR was assessed using 12 (6–17) determinations of GFR over a period of time of 8 (4–10) years. Mean (SD) GFR[sub T] was 123 (21) ml·min[sup -1] compared to GFR[sub IV] 123 (21) ml·min[sup -1] (NS) and GFR[sub I] 115 (17) ml·min[sup -1] (p<0.00001). The mean difference (95% limits of agreement) between GFR[sub T] and GFR[sub IV] was + 0.6 (–16.6 to + 17.7) ml·min[sup -1], and between GFR[sub T] and GFR[sub I] + 8.0 (–6.0 to + 22.2) ml·min[sup -1]. The difference between GFR[sub T] and GFR[sub I] was significantly correlated with their mean value (r=0.56, p<0.00001), indicating increasing underestimation by GFR[sub I] with increasing GFR levels. The mean (SD) rate of decline in GFR[sub T] was 2.3 (3.9) ml·min[sup -1]·year[sup -1], compared to a mean rate of decline in GFR[sub IV] of 2.4 (3.6) ml·min[sup -1]·year[sup -1] (NS), and a mean rate of decline in GFR[sub I] of 2.2 (3.5) ml·min[sup -1]·year[sup -1] (NS). The mean difference (95% limits of agreement) between rate of decline in GFR[sub T] and rate of decline in GFR[sub IV] was + 0.16 (–1.59 to + 1.91) ml·min[sup -1]·year[sup -1], and between rate of decline in GFR[sub T] and rate of decline in GFR[sub I] –0.01 (–1.64 to + 1.61) ml·min[sup -1]·year[sup -1], respectively. In conclusion, our cross-sectional study revealed a close agreement between GFR[sub T] and GFR[sub IV] with acceptable limits of agreement (precision), while GFR[sub I] lacked accuracy. However, a close agreement between rate of decline in GFR[sub T] and rate of decline in GFR[sub IV], and between rate of decline in GFR[sub T] and rate of decline in GFR[sub I], with acceptable limits of agreement (precision), suggests that both simplified methods are applicable for long-term follow-up. [ABSTRACT FROM AUTHOR]

Introduction: Quality improvement (QI) curricula are required for clinical disciplines at all training levels. Despite this, faculty educators often feel inadequately prepared to perform QI functions and thus lack the skills necessary to teach QI to learners. We aimed to improve faculty QI skills so they could oversee didactic curricula and experiential QI projects., Methods: We developed a train-the-trainer curriculum for faculty within medicine, nursing, and allied health that was delivered as a 2-hour interactive workshop. Core concepts included QI methodologies, measurement, implementation, and scholarship. Prior to the workshop, attendees completed a baseline knowledge test and a self-assessment of their confidence in teaching QI. Both assessments were repeated 1 month and 6 months postworkshop. Participants also completed a course evaluation., Results: We report on our experience after two workshops with 23 participants total. Baseline median knowledge test percentage correct was 36%. This increased to 77% at 1 month and remained at 57% at 6 months. Self-assessment ratings of QI teaching skills increased consistently from baseline to 1 month to 6 months, with all respondents reporting feeling some confidence or very confident by the end of the study period. The course overall was rated very good or excellent by 91% of attendees., Discussion: A focused QI train-the-trainer curriculum can sustainably improve faculty knowledge and self-ratings of QI teaching skills. Participants rated the interactive 2-hour workshop highly. Its materials can be easily adapted across disciplines and clinical departments to increase the number of faculty competent to facilitate didactic and experiential QI training., (© 2024 Sonstein and Hommel.)

Aims/hypothesis: As a result of early loss of the glucagon response, adrenaline is the primary counter-regulatory hormone in type 1 diabetes. Diminished adrenaline responses to hypoglycaemia due to counter-regulatory failure are common in type 1 diabetes, and are probably induced by exposure to recurrent hypoglycaemia, however, the metabolic effects of adrenaline have received less research attention, and also there is conflicting evidence regarding adrenaline sensitivity in type 1 diabetes. Thus, we aimed to investigate the metabolic response to adrenaline and explore whether it is modified by prior exposure to hypoglycaemia., Methods: Eighteen participants with type 1 diabetes and nine healthy participants underwent a three-step ascending adrenaline infusion during a hyperinsulinaemic-euglycaemic clamp. Continuous glucose monitoring data obtained during the week before the study day were used to assess the extent of hypoglycaemia exposure., Results: While glucose responses during the clamp were similar between people with type 1 diabetes and healthy participants, plasma concentrations of NEFAs and glycerol only increased in the group with type 1 diabetes (p<0.001). Metabolomics revealed an increase in the most common NEFAs (p<0.01). Other metabolic responses were generally similar between participants with type 1 diabetes and healthy participants. Exposure to hypoglycaemia was negatively associated with the NEFA response; however, this was not statistically significant., Conclusions/interpretation: In conclusion, individuals with type 1 diabetes respond with increased lipolysis to adrenaline compared with healthy participants by mobilising the abundant NEFAs in plasma, whereas other metabolic responses were similar. This may suggest that the metabolic sensitivity to adrenaline is altered in a pathway-specific manner in type 1 diabetes., Trial Registration: ClinicalTrials.gov NCT05095259., (© 2024. The Author(s).)

Aims: Many adults with type 1 diabetes do not achieve recommended glycemic goals despite intensive insulin therapy using insulin pumps. The aim of this study was to explore associations between clinical and psychosocial factors and HbA1c in insulin pump users to identify and prioritize areas for potential intervention., Methods: A questionnaire-based survey covering clinical and psychosocial aspects of life with type 1 diabetes was distributed to all adult (≥ 18 years) insulin pump users in the Capital Region of Denmark. Responses were combined with data from medical records and national registries. Associations with HbA1c were modeled using regression-based machine learning., Results: Of 1,591 invited individuals, 770 (48.4%) responded to the survey. Mean HbA1c among responders was 7.3% (56 mmol/mmol), and 35.6% had an HbA1c < 7.0% (53 mmol/mol). Six factors were significantly associated with HbA1c: diabetes duration (0.006% (0.1 mmol/mol) lower HbA1c per 1-year increase in diabetes duration); education (0.4% (4.3 mmol/mol) lower HbA1c with long higher education vs. primary school); insulin type (0.2% (2.2 mmol/mol) lower HbA1c with ultra-rapid-acting insulin vs. rapid-acting insulin); hypoglycemia awareness status (0.2% (2.2 mmol/mol) lower HbA1c with complete unawareness vs. full awareness); insulin device satisfaction (0.2% (2.7 mmol/mol) lower HbA1c per 1-point increase in Insulin Device Satisfaction Survey score); and diabetes distress (0.3% (3.1 mmol/mol) higher HbA1c per 1-point increase in Type 1 Diabetes Distress Scale score)., Conclusions: This study identified several associations between clinical and psychosocial factors and HbA1c that may be considered when developing interventions targeted people with type 1 diabetes., (© 2023. The Author(s).)

Lemnaceae are small freshwater plants with extraordinary high growth rates. We aimed to test whether this correlates with a more efficient photosynthesis, the primary energy source for growth. To this end, we compared photosynthesis properties of the duckweed Lemna minor and the terrestrial model plant Arabidopsis thaliana . Chlorophyll fluorescence analyses revealed high similarity in principle photosynthesis characteristics; however, Lemna exhibited a more effective light energy transfer into photochemistry and more stable photosynthesis parameters especially under high light intensities. Western immunoblot analyses of representative photosynthesis proteins suggested potential post-translational modifications in Lemna proteins that are possibly connected to this. Phospho-threonine phosphorylation patterns of thylakoid membrane proteins displayed a few differences between the two species. However, phosphorylation-dependent processes in Lemna such as photosystem II antenna association and the recovery from high-light-induced photoinhibition were not different from responses known from terrestrial plants. We thus hypothesize that molecular differences in Lemna photosynthesis proteins are associated with yet unidentified mechanisms that improve photosynthesis and growth efficiencies. We also developed a high-magnification video imaging approach for Lemna multiplication which is useful to assess the impact of external factors on Lemna photosynthesis and growth.

Aims: Insulin pump self-management is important for glycaemic outcomes. We aimed to investigate associations between self-management factors and HbA1c., Methods: Adult insulin pump users with type 1 diabetes (n = 770) completed an online questionnaire. The latest HbA1c and demographics were extracted from national registries. Associations between HbA1c and self-management (use of advanced features, timing of infusion set change, timing of meal bolus, data-upload and pump settings adjustments) were investigated using backward selected linear regression models., Results: Of the 699 responders eligible for this study, 60% were women; the median age and diabetes duration were 49 and 25 years, respectively. Significant associations with HbA1c were found for changing infusion set every 0-4 days relative to 5-10 days (-5 mmol/mol (-0.4%), p = 0.003), and for never/rarely missing a bolus (-6 mmol/mol (-0.5%), p < 0.001) relative to often missing a bolus. Timing insulin 10-15 min before meal relative to after meal start was also associated with lower HbA1c (-3 mmol/mol (-0.3%), p = 0.023). Self-adjusting pump settings showed the strongest association with lower HbA1c (-6 mmol/mol (-0.6%), p < 0.001) relative to health care professionals doing all adjustments., Conclusion: Self-adjusting insulin pump settings, optimal timing and few omissions of meal boluses, and timely change of infusion set are associated with lower HbA1c., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: Pre-procedural fasting (nil per os [NPO]) is a commonly implemented protocol to prevent aspiration during certain diagnostic and therapeutic procedures. However, evidence suggests aspiration risk is quite low. Current guidelines support a reduced fasting duration before procedures necessitating anesthesia or sedation, but many health systems persist in the use of NPO past midnight., Objective: We aimed to reduce the use of NPO p MN before inpatient diagnostic and therapeutic procedures necessitating anesthesia or sedation by 50% within 6 months., Design, Setting and Participants: We performed a quality improvement initiative at a single academic health system in Southeast Texas. We include the experience of patients of all ages across 4 affiliated hospitals (one main academic hospital and three community satellite hospitals)., Intervention: An interprofessional team was convened to review best practices and oversee this quality improvement initiative. Diagnostic imaging protocols previously requiring NPO were amended to reflect evidence-based fasting requirements. A pre-procedure clear liquid diet was also implemented., Main Outcome and Measures: We describe the steps to implementation, feasibility of implementation as described through key process measures, and the safety of implementation (balancing measures)., Results: NPO requirements were removed from 70% of existing diagnostic imaging and therapeutic orders. After these amended protocols and the implementation of a pre-procedure clear liquid diet, we displayed an immediate 50% reduction in NPO past midnight usage. Further stakeholder engagement/education and targeted interventions reduced NPO past midnight usage to only 33% of pre-procedural diet orders. Surgery remains the most common indication for continued use of NPO. Aspiration events and procedural delays were rare., (© 2023 Society of Hospital Medicine.)

We aimed to evaluate the glycemic effect and detect any predictors of improved time-in-range (TIR) in persons with type 1 diabetes after initiating hybrid closed-loop (HCL) treatment with MiniMed 670G in a 12-month retrospective observational study. Before starting HCL treatment, the 62 participants followed a Steno-developed training program; 7 participants (6.5%) discontinued the HCL therapy; the remaining 55 (58% female) had an age (mean ± standard deviation) of 45.6 ± 12.6 years and diabetes duration of 28.2 ± 10.9 years. After 12 months' HCL therapy, glycated hemoglobin A1c decreased from 7.4% +0.7% to 7.1% +0.5%, TIR increased from 59.3% ± 13.5% to 72% ± 9.3%, time in 54-70 mg/dL (3.0-3.9 mM) decreased from 2.4% ± 2.0% to 1.4% ± 1.0%, and time in 180-250 mg/dL (10.0-13.9 mM) decreased from 26.4% ± 8.3% to 20.8% ± 5.5%, all P  < 0.001. Improvement in TIR was significantly associated with lower total daily insulin dose, higher amount of total carbohydrate, and more time spent in Auto Mode. Our findings support the promising results on glycemic outcomes seen with HCL treatment.

Background: The Accreditation Council for Graduate Medical Education (ACGME) requires training in quality improvement (QI) yet many programs struggle to incorporate appropriate content. Small fellowship programs may find it particularly difficult, limited by a lack of well-trained faculty. We report on the feasibility and effectiveness of a consolidated curriculum for subspecialty fellowship programs., Methods: Two QI experts were identified to design a curriculum. Interactive didactic sessions were created to guide development and implementation of fellow QI projects. All projects culminated in abstract/poster presentation., Results: Seven of 10 eligible fellowships participated. Twenty-four projects were completed with 70% reaching improvement in process measures. Trainees improved confidence in 11 of 12 QI domains. Program directors stated enhancement in QI education with 100% recommending program continuation., Conclusions: Consolidating teaching efforts with existing QI experts can lead to an effective QI curriculum for fellowship programs. This model can be expanded to other graduate medical education trainees as a means to increase QI proficiency., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Importance: The increased hospital mortality rates from non-SARS-CoV-2 causes during the SARS-CoV-2 pandemic are incompletely characterized., Objective: To describe changes in mortality rates after hospitalization for non-SARS-CoV-2 conditions during the COVID-19 pandemic and how mortality varies by characteristics of the admission and hospital., Design, Setting, and Participants: Retrospective cohort study from January 2019 through September 2021 using 100% of national Medicare claims, including 4626 US hospitals. Participants included 8 448 758 individuals with non-COVID-19 medical admissions with fee-for-service Medicare insurance., Main Outcomes and Measures: Outcome was mortality in the 30 days after admission with adjusted odds generated from a 3-level (admission, hospital, and county) logistic regression model that included diagnosis, demographic variables, comorbidities, hospital characteristics, and hospital prevalence of SARS-CoV-2., Results: There were 8 448 758 non-SARS-CoV-2 medical admissions in 2019 and from April 2020 to September 2021 (mean [SD] age, 73.66 [12.88] years; 52.82% women; 821 569 [11.87%] Black, 438 453 [6.34%] Hispanic, 5 351 956 [77.35%] White, and 307 218 [4.44%] categorized as other). Mortality in the 30 days after admission increased from 9.43% in 2019 to 11.48% from April 1, 2020, to March 31, 2021 (odds ratio [OR], 1.20; 95% CI, 1.19-1.21) in multilevel logistic regression analyses including admission and hospital characteristics. The increase in mortality was maintained throughout the first 18 months of the pandemic and varied by race and ethnicity (OR, 1.27; 95% CI, 1.23-1.30 for Black enrollees; OR, 1.25; 95% CI, 1.23-1.27 for Hispanic enrollees; and OR, 1.18; 95% CI, 1.17-1.19 for White enrollees); Medicaid eligibility (OR, 1.25; 95% CI, 1.24-1.27 for Medicaid eligible vs OR, 1.18; 95% CI, 1.16-1.18 for noneligible); and hospital quality score, measured on a scale of 1 to 5 stars with 1 being the worst and 5 being the best (OR, 1.27; 95% CI, 1.22-1.31 for 1 star vs OR, 1.11; 95% CI, 1.08-1.15 for 5 stars). Greater hospital prevalence of SARS-CoV-2 was associated with greater increases in odds of death from the prepandemic period to the pandemic period; for example, comparing mortality in October through December 2020 with October through December 2019, the OR was 1.44 (95% CI, 1.39-1.49) for hospitals in the top quartile of SARS-CoV-2 admissions vs an OR of 1.19 (95% CI, 1.16-1.22) for admissions to hospitals in the lowest quartile. This association was mostly limited to admissions with high-severity diagnoses., Conclusions and Relevance: The prolonged elevation in mortality rates after hospital admission in 2020 and 2021 for non-SARS-CoV-2 diagnoses contrasts with reports of improvement in hospital mortality during 2020 for SARS-CoV-2. The results of this cohort study suggest that, with the continued impact of SARS-CoV-2, it is important to implement interventions to improve access to high-quality hospital care for those with non-SARS-CoV-2 diseases.

Photosynthesis needs to run efficiently under permanently changing illumination. To achieve this, highly dynamic acclimation processes optimize photosynthetic performance under a variety of rapidly changing light conditions. Such acclimation responses are acting by a complex interplay of reversible molecular changes in the photosynthetic antenna or photosystem assemblies which dissipate excess energy and balance uneven excitation between the two photosystems. This includes a number of non-photochemical quenching processes including state transitions and photosystem II remodeling. In the laboratory such processes are typically studied by selective illumination set-ups. Two set-ups known to be effective in a highly similar manner are (i) light quality shifts (inducing a preferential excitation of one photosystem over the other) or (ii) dark-light shifts (inducing a general off-on switch of the light harvesting machinery). Both set-ups result in similar effects on the plastoquinone redox state, but their equivalence in induction of photosynthetic acclimation responses remained still open. Here, we present a comparative study in which dark-light and light-quality shifts were applied to samples of the same growth batches of plants. Both illumination set-ups caused comparable effects on the phosphorylation of LHCII complexes and, hence, on the performance of state transitions, but generated different effects on the degree of state transitions and the formation of PSII super-complexes. The two light set-ups, thus, are not fully equivalent in their physiological effectiveness potentially leading to different conclusions in mechanistic models of photosynthetic acclimation. Studies on the regulation of photosynthetic light acclimation, therefore, requires to regard the respective illumination test set-up as a critical parameter that needs to be considered in the discussion of mechanistic and regulatory aspects in this subject., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hommel, Liebers, Offermann and Pfannschmidt.)

Introduction: Insulin pump therapy can improve quality of life and glycaemic outcomes for many people with type 1 diabetes (T1D). The multidimensional Steno Tech Survey study aims to investigate why some insulin pump users do not achieve treatment goals. In this article, we present the study design and analyse differences in population characteristics between responders and non-responders., Methods: In June 2020, all 1591 insulin pump users (≥ 18 years) in the Capital Region of Denmark were invited to participate in an online questionnaire that evaluated several dimensions of insulin pump self-management and psychosocial health. Demographic, socioeconomic and clinical characteristics, including age, sex and HbA1c, of the cohort were identified via national registries. Predictors of questionnaire response/non-response were explored with logistic regression analysis., Results: In the full study population, 58% were female, median age was 42 years and median HbA1c was 58 mmol/mol (7.5%); 30% had HbA1c < 53 mmol/mol (7.0%). In total, 770 individuals (48%) responded to the questionnaire. Logistic regression analysis showed that 50+ years of age (odds ratio [OR] = 2.3, 95% confidence interval [CI]: 1.4-3.8), female sex (OR = 1.3, CI: 1.02-1.6), being married (OR = 1.8, CI: 1.3-2.4) and having long higher education (OR = 1.6, CI: 1.004-2.5) were significantly associated with a higher likelihood of responding to the survey; the opposite was found for HbA1c from 64 to < 75 mmol (8.0-9.0%) (OR = 0.6, CI: 0.4-0.8) and HbA1c ≥ 75 mmol/mol (≥ 9.0%) (OR = 0.2, CI: 0.1-0.3)., Conclusions: The established Steno Tech cohort enables future analysis of a range of psychosocial and behavioural aspects of insulin pump self-management. Interpretation and generalization of findings should consider observed differences between responders and non-responders., (© 2021. The Author(s).)

Importance: Continuity in primary care is associated with improved outcomes, but less information is available on the association of continuity of care in the hospital with hospital complications., Objective: To assess whether the number of hospitalists providing care is associated with subsequent hospital complications and length of stay., Design, Setting, and Participants: This retrospective cohort study used multilevel logistic regression models to analyze Medicare claims for medical admissions from 2016 to 2018 with a length of stay longer than 4 days. Admissions with multiple charges on the same day from a hospitalist or an intensive care unit (ICU) stay during hospital days 1 to 3 were excluded. The data were accessed and analyzed from November 1, 2020, to April 30, 2021., Exposures: The number of different hospitalists who submitted charges during hospital days 1 to 3., Main Outcomes and Measures: Overall length of stay and transfer to ICU or a new diagnosis of drug toxic effects on hospital day 4 or later., Results: Among the 617 680 admissions, 362 376 (58.7%) were women, with a mean (SD) age of 80.2 (8.4) years. In 306 037 admissions (49.6%), the same hospitalist provided care on days 1 to 3, while 2 hospitalists provided care in 274 658 admissions (44.5%), and 3 hospitalists provided care in 36 985 admissions (6.0%). There was no significant association between the number of different hospitalists on days 1 to 3 and either length of stay or subsequent ICU transfers. Admissions seeing 2 or 3 hospitalists had a slightly greater adjusted odds of subsequent new diagnoses of drug toxic effects (2 hospitalists: odds ratio [OR], 1.04; 95% CI, 1.02-1.07; 3 hospitalists: OR, 1.07; 95% CI, 1.03-1.12)., Conclusions and Relevance: There was little evidence that receiving care from multiple hospitalists was associated with worse outcomes for patients receiving all their general medical care from hospitalists.

Background: Carbohydrate counting and use of automated bolus calculators (ABCs) can help reduce HbA 1c in type 1 diabetes but only limited evidence exists in type 2 diabetes. We evaluated the efficacy of advanced carbohydrate counting (ACC) and use of an ABC compared with manual insulin bolus calculation (MC) in persons with type 2 diabetes. Materials and Methods: A 24-week open-label, randomized clinical study was conducted in 79 persons with type 2 diabetes treated with basal-bolus insulin (mean age 62.5 ± 9.6 years, HbA 1c 8.7% ± 1.0% [72 ± 11 mmol/mol], diabetes duration 18.7 ± 7.6 years). Participants were randomized 1:1 into two groups: ABC group received training in ACC and use of an ABC; MC group received training in ACC and manual calculation of insulin bolus. Participants wore blinded continuous glucose monitors for 6 days at baseline and at study end. Primary endpoint was change in HbA 1c . Results: After 24 weeks, HbA 1c decreased 0.8% (8.8 mmol/mol) in ABC group and 0.8% (9.0 mmol/mol) in MC group with no between-group difference ( P  = 0.96) and without increase in time in hypoglycemic range (sensor glucose <3.9 mmol/L). Glycemic variability decreased significantly in both groups, whereas the total insulin dose and body mass index (BMI) remained unchanged during the study. Treatment satisfaction increased significantly in both groups after 24 weeks. Conclusion: ACC is an effective, low-cost tool to reduce HbA 1c and glycemic variability in persons with basal-bolus insulin-treated type 2 diabetes without increase in hypoglycemia or BMI. Similar effects were seen with use of an ABC and with use of manual bolus calculation. Trial registration: ClinicalTrials.gov NCT02887898.

Aim: The aim of the study was to evaluate the association between C-peptide levels, glycaemic variability and hypoglycaemia in patients with insulin-treated type 2 diabetes (T2D)., Methods: A total of 98 patients with T2D treated with basal-bolus insulin were enrolled in a cross-sectional study. Glycaemic variability and hypoglycaemia were assessed from continuous glucose monitoring (CGM) data recorded over 6 days: Glycemic variability was assessed by calculating the mean coefficient of variation (CV), while hypoglycemia was defined as sensor glucose levels ≤ 3.9 mmol/L or < 3.0 mmol/L. Fasting C-peptide and fasting glucose were measured on day 1., Results: Low levels of fasting C-peptide correlated with higher CV (r = -0.53, P < 0.0001). In a multivariate regression model with HbA 1c , body mass index, diabetes duration and total daily insulin dose, only C-peptide was significantly associated with CV. Patients with ≥ 1 episode of hypoglycaemia had significantly lower median C-peptide levels than patients without hypoglycaemia (274 (136-620) pmol/L vs. 675 (445-1013) pmol/L, respectively; P = 0.0004). Also, 17 patients clinically diagnosed with T2D had detectable glutamic acid decarboxylase (GAD) antibodies (≥ 5 U/mL). These GAD-positive patients had significantly lower fasting C-peptide, higher CV and greater frequency of hypoglycaemia than GAD-negative patients., Conclusion: In patients with insulin-treated T2D, low levels of C-peptide are associated with greater glycaemic variability and higher risk of hypoglycaemia, suggesting that C-peptide levels should be taken into consideration when optimizing insulin treatment and assessing hypoglycaemia risk., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Background: In a 4-month follow-up survey, we examined whether treatment with continuous subcutaneous insulin infusion (CSII) and/or continuous glucose monitoring (CGM) in adults with type 1 diabetes was associated with sustained skin problems and whether skin problems were associated with diabetes-related emotional distress., Research Design and Methods: A total of 111 adult patients completed a follow-up questionnaire concerning skin problems as a result of CSII and/or CGM use. The questionnaire included a patient-reported outcome measure, the Problem Areas in Diabetes (PAID) scale., Results: Current visible skin problems caused by CSII or CGM use were reported by 51 (46.0%) participants, in 34 (66.7%) of whom skin problems had been reported more than 4 months earlier. Seventy-two (64.9%) participants reported skin problems as a result of CSII use, whereas 38 (74.5%) reported skin problems owing to CGM use at some time. Itching was the most prevalent complaint. CSII-related itching was associated with a mean PAID score >20 (P = 0.01), and patients with more than one skin problem had an increased PAID score compared with those with one or no skin problems (P = 0.006)., Conclusions: More than half patients treated with CSII, CGM, or both had experienced skin problems during 4 months of follow-up that were associated with increased diabetes burden. Skin problems represent a persistent health issue affecting diabetes-specific emotional distress.

Polyketide synthases (PKSs) occur in many bacteria, fungi and plants. They are highly versatile enzymes involved in the biosynthesis of a large variety of compounds including antimicrobial agents, polymers associated with bacterial cell walls and plant pigments. While harmful algae are known to produce polyketide toxins, sequences of the genomes of non-toxic algae, including those of many green algal species, have surprisingly revealed the presence of genes encoding type I PKSs. The genome of the model alga Chlamydomonas reinhardtii (Chlorophyta) contains a single type I PKS gene, designated PKS1 (Cre10.g449750), which encodes a giant PKS with a predicted mass of 2.3 MDa. Here, we show that PKS1 is induced in 2-day-old zygotes and is required for their development into zygospores, the dormant stage of the zygote. Wild-type zygospores contain knob-like structures (~50 nm diameter) that form at the cell surface and develop a central cell wall layer; both of these structures are absent from homozygous pks1 mutants. Additionally, in contrast to wild-type zygotes, chlorophyll degradation is delayed in homozygous pks1 mutant zygotes, indicating a disruption in zygospore development. In agreement with the role of the PKS in the formation of the highly resistant zygospore wall, mutant zygotes have lost the formidable desiccation tolerance of wild-type zygotes. Together, our results represent functional analyses of a PKS mutant in a photosynthetic eukaryotic microorganism, revealing a central function for polyketides in the sexual cycle and survival under stressful environmental conditions., (© 2018 The Authors. The Plant Journal published by John Wiley & Sons Ltd and Society for Experimental Biology.)

Background: In the future, widespread use of closed-loop infusion (artificial pancreas) systems to treat type 1 diabetes (T1D) may significantly improve glycemic control and enhance treatment flexibility. However, the infusion sets and plasters necessary for these treatments can cause dermatological complications that may hamper the spread of the new technology; few studies have investigated these complications in adults. The aim of this study was to describe the dermatological complications associated with continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) in adults., Methods: A total of 118 adult patients from two different diabetes clinics completed a questionnaire concerning the dermatological complications associated with their CSII and/or CGM treatment, other treatment variables, duration of diabetes, allergies, skin care, and other pathologies., Results: CGM or CSII use was associated with current eczema, scars, and wounds. In total, 34% of CSII users and 35% of CGM users currently had one or more skin lesions due to the use of these devices. We found no significant association with glycated hemoglobin (HbA1c) levels, a history of atopic dermatitis, or other skin pathologies. However, multivariate analysis revealed associations with a history of atopy and CSII-associated dermatological complications., Conclusions: Dermatological complications were present in one in every three patients and represent a significant challenge to using CSII and CGM to treat adults with T1D. Prospective studies on the causes of these complications will be required to develop preventive strategies and ensure that optimal diabetes treatment approaches that take advantage of the latest technology can be implemented.

Background: Young people often struggle to self-manage type 1 diabetes during the transition from childhood to adulthood. Mobile health (mHealth) apps may have the potential to support self-management, but evidence is limited and randomized controlled trials are needed., Objective: We assessed whether the mHealth app "Young with Diabetes" improved young people's self-management measured by glycated hemoglobin (HbA 1c ) and three self-reported psychometric scales., Methods: Young people (14-22 years) with inadequate glycemic control and their parents were enrolled in a randomized controlled trial and assigned either to Young with Diabetes and usual care (Young with Diabetes group) or to usual care alone (control). Young with Diabetes use was monitored; functions included a chat room, contact the health care provider, reminders, tips, information about the diabetes department and type 1 diabetes topics, carbohydrate counting, and a parents' section. Outcomes included HbA 1c and three self-reported psychometric scales: Perceived Competence in Diabetes Scale; Health Care Climate Questionnaire; and Problem Areas In Diabetes care survey. Data were collected at baseline and at 2, 7, and 12 months., Results: A total of 151 young people were randomized (Young with Diabetes group=76, control=75) and 49 parents agreed to participate. At 12 months, HbA 1c was significantly higher (4.1 mmol/mol; 0.4 %) in the Young with Diabetes group, compared to the control group (P=.04); this finding did not occur when comparing app users (Young with Diabetes use ≥5 days) with nonusers. Young people used Young with Diabetes on a mean of 10.5 days. They spent the most time chatting about alcohol and searching for information about sex. Most young people and half of the parents reported that Young with Diabetes helped them. More than 80% would recommend Young with Diabetes to peers., Conclusions: Young with Diabetes did not improve HbA 1c , but it may be a useful complement to self-management. Qualitative evaluation is needed to explore benefits and shortcomings of Young with Diabetes. Health care providers should address young peoples' knowledge about sensitive topics, provide them with peer support, and be aware of parents' need for information about how to support., Trial Registration: ClinicalTrials.gov NCT02632383; https://clinicaltrials.gov/ct2/show/NCT02632383 (Archived by WebCite at http://www.webcitation.org/6zCK2u7xM)., (©Pernille Castensøe-Seidenfaden, Gitte Reventlov Husted, Andreas Kryger Jensen, Eva Hommel, Birthe Olsen, Ulrik Pedersen-Bjergaard, Finn Kensing, Grete Teilmann. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 26.06.2018.)

Background: Young people with type 1 diabetes often struggle to self-manage their disease. Mobile health (mHealth) apps show promise in supporting self-management of chronic conditions such as type 1 diabetes. Many health care providers become involved in app development. Unfortunately, limited information is available to guide their selection of appropriate methods, techniques, and tools for a participatory design (PD) project in health care., Objective: The aim of our study was to develop an mHealth app to support young people in self-managing type 1 diabetes. This paper presents our methodological recommendations based on experiences and reflections from a 2-year research study., Methods: A mixed methods design was used to identify user needs before designing the app and testing it in a randomized controlled trial. App design was based on qualitative, explorative, interventional, and experimental activities within an overall iterative PD approach. Several techniques and tools were used, including workshops, a mail panel, think-aloud tests, and a feasibility study., Results: The final mHealth solution was "Young with Diabetes" (YWD). The iterative PD approach supported researchers and designers in understanding the needs of end users (ie, young people, parents, and health care providers) and their assessment of YWD, as well as how to improve app usability and feasibility. It is critical to include all end user groups during all phases of a PD project and to establish a multidisciplinary team to provide the wide range of expertise required to build a usable and useful mHealth app., Conclusions: Future research is needed to develop and evaluate more efficient PD techniques. Health care providers need guidance on what tools and techniques to choose for which subgroups of users and guidance on how to introduce an app to colleagues to successfully implement an mHealth app in health care organizations. These steps are important for anyone who wants to design an mHealth app for any illness., (©Pernille Castensøe-Seidenfaden, Gitte Reventlov Husted, Grete Teilmann, Eva Hommel, Birthe Susanne Olsen, Finn Kensing. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 23.10.2017.)

Aims and Objectives: To explore and describe the experiences of adolescents and their parents living with type 1 diabetes, to identify their needs for support to improve adolescents' self-management skills in the transition from child- to adulthood., Background: Adolescents with type 1 diabetes often experience deteriorating glycaemic control and distress. Parents are important in adolescents' ability to self-manage type 1 diabetes, but they report anxiety and frustrations. A better understanding of the challenges adolescents and parents face, in relation to the daily self-management of type 1 diabetes, is important to improve clinical practice., Design: A qualitative explorative study using visual storytelling as part of individual interviews., Methods: A purposive sample of nine adolescents and their parents (seven mothers, six fathers) took photographs illustrating their experiences living with type 1 diabetes. Subsequently, participants were interviewed individually guided by participants' photographs and a semistructured interview guide. Interviews were analysed using thematic analysis., Results: Four major themes were consistent across adolescents and their parents: (1) striving for safety, (2) striving for normality, (3) striving for independence and (4) worrying about future. Although adolescents and parents had same concerns and challenges living with type 1 diabetes, they were experienced differently. Their thoughts and feelings mostly remained isolated and their concerns and challenges unsolved., Conclusions: The concerns and challenges adolescents and their parents face in the transition from child- to adulthood are still present despite new treatment modalities. Parents are fundamental in supporting the adolescents' self-management-work; however, the parties have unspoken concerns and challenges., Relevance to Clinical Practice: Healthcare providers should address the parties' challenges and concerns living with type 1 diabetes to diminish worries about future including fear of hypoglycaemia, the burden of type 1 diabetes and the feeling of being incompetent in diabetes self-management. It is important to focus on supporting both adolescents and their parents, and to provide a shared platform for communication., (© 2016 John Wiley & Sons Ltd.)

Aims: The purpose of this secondary analysis of the StenoABC Study was to identify determinants of the changes in HbA1c observed after training of people with type 1 diabetes in advanced carbohydrate counting (ACC) and automated bolus calculator (ABC) use, and further to investigate psychosocial effects of these insulin dosing approaches., Methods: Validated diabetes-specific questionnaires were used to assess diabetes treatment satisfaction, problem areas in diabetes, fear of hypoglycemia and diabetes dependent quality of life before and one year after the training. In addition, numeracy was tested (using a non-validated test developed specifically for this study) and behavioral measures (number of daily blood glucose measurements and self-reported use of ACC) were obtained. Associations between change in HbA1c and these measures plus sex, age, diabetes duration and BMI were tested., Results: Numeracy was the only baseline predictor of yearly change in HbA1c identified. Higher levels of numeracy were associated with greater reductions in HbA1c (P=0.031). No associations between change in HbA1c and the behavioral measures investigated were found, nor were any clinically relevant associations between changes in HbA1c and questionnaire scores. Treatment satisfaction increased in all users of ACC (P<0.001). People who also used an ABC reported significantly lower levels of fear of hypoglycemia than people who practiced ACC without such device (P=0.005)., Conclusions: Improvements in HbA1c after training in ACC were inversely related to numeracy. Use of an ABC did not compensate for poor numeracy skills. However, device use reduced fear of hypoglycemia compared with ACC without ABC use., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aims: To describe and compare changes in glycaemic control in young people with Type 1 diabetes over time between the last 2 years in paediatric care and the first 2 years in adult care and to identify risk factors for poor glycaemic control., Methods: Our retrospective cohort study followed participants aged 14-22 years from 2 years before to 2 years after transfer from paediatric to adult care. Changes in glycaemic control were calculated using repeated measurements. We adjusted for gender, age at diabetes onset, age at transfer, duration of diabetes at transfer, gap (amount of time) between last paediatric and first adult visit, comorbidity, learning disability and/or mental health conditions and family structure. We examined associations between acute hospital admissions, low visit attendance rate, loss to follow-up and baseline HbA 1c level., Results: Among 126 participants, the mean HbA 1c level was 80 mmol/mol (9.4%) pre-transfer but decreased by an average of 3 mmol/mol (0.3%) each year post-transfer (P = 0.005). Young people with a learning disability and/or a mental health condition had worse glycaemic control (P = 0.041) and the mean HbA 1c of those with divorced parents was 14 mmol/mol (1.2%) higher (P = 0.014). Almost one-third of participants were admitted to the hospital for acute diabetes care. Low visit attendance rate, high baseline HbA 1c level, learning disability and/or mental health conditions and divorced parents predicted acute hospital admissions., Conclusions: Glycaemic control improved significantly after transfer to adult care, but the mean HbA 1c level remained high. Future interventions should focus on young people with divorced parents, those with a learning disability and/or mental health condition and those who do not attend clinical visits to improve HbA 1c levels and thereby reduce hospitalization rates., (© 2017 Diabetes UK.)

Aims: To test whether concomitant use of an automated bolus calculator for people with Type 1 diabetes carrying out advanced carbohydrate counting would induce further improvements in metabolic control., Methods: We conducted a 12-month, randomized, parallel-group, open-label, single-centre, investigator-initiated clinical study. We enrolled advanced carbohydrate counting-naïve adults with Type 1 diabetes and HbA 1c levels 64-100 mmol/mol (8.0-11.3%), who were receiving multiple daily insulin injection therapy. In a 1:1-ratio, participants were randomized to receive training in either advanced carbohydrate counting using mental calculations (MC group) or advanced carbohydrate counting using an automated bolus calculator (ABC group) during a 3.5-h group training course. For 12 months after training, participants attended a specialized diabetes centre quarterly. The primary outcome was change in HbA 1c from baseline to 12 months., Results: Between August 2012 and September 2013, 168 participants (96 men and 72 women) were recruited and randomly assigned to the MC group (n = 84) and the ABC group (n = 84). Drop-out rates were 23.8 and 21.4%, respectively (P = 0.712); 130 participants completed the study. The baseline HbA 1c was 75 ± 9 mmol/mol (9.0 ± 0.8%) in the MC group and 74 ± 8 mmol/mol (8.9 ± 0.7%) in the ABC group. At 12 months, change in HbA 1c was significant within both groups: MC group: -2 mmol/mol (95% CI -4 to -1) or -0.2% (95% CI -0.4 to -0.1; P = 0.017) and ABC group: -5 mmol/mol (95% CI -6 to -3) or -0.5% (95% CI -0.6 to -0.3; P < 0.0001), but HbA 1c reductions were significantly greater in the ABC group (P = 0.033). No episodes of severe hypoglycaemia were reported., Conclusions: People with Type 1 diabetes initiating advanced carbohydrate counting obtained significantly greater HbA 1c reductions when guided by an automated bolus calculator (NCT02084498)., (© 2016 Diabetes UK.)

Objective: To evaluate the effect of group-based diabetes dialogue meetings (DDMs) on diabetes distress, perceived competence and glycaemic control., Methods: Patients with type 1 diabetes (T1D) were invited to DDMs with peers and healthcare professionals. The impact of participation was evaluated by change in diabetes distress measured by Problem Areas in Diabetes (PAID), diabetes competence measured by Perceived Competence in Diabetes (PCD), change in HbA1c before and one year after the DDMs., Results: 120 patients with T1D participated in at least one DDM: 75% female, mean age 50 years (range 21-76), mean diabetes duration 23 years (range 0-64); 39% of all participants had a baseline PAID score≥33, indicating high levels of distress. After one year, both PAID (from 30.4±16.6 to 27.4±17.1; n=81, p=0.03), and mean HbA1c (61.6±10.2 to 58.8±9.9; n=120, p<0.0001) had improved significantly. PCD showed no change. Meanwhile, the benefit from participating was rated high with a median of four out of five and the major gain being the possibility to share experiences with peers., Conclusion: Group-based DDMs were highly appreciated by participants and associated with significant improvements in diabetes distress and HbA1c., Practice Implications: DDMs target a large group of patients using few staff resources., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To investigate changes in retinal metabolism, function, structure and morphology in relation to initiation of insulin pump therapy (continuous subcutaneous insulin infusion, CSII)., Methods: Visual acuity, retinopathy level, dark adaptation kinetics, retinal and subfoveal choroidal thickness, macular perfusion velocities, retinal vessel diameters and blood oxygen saturations were measured at baseline and after 1, 4, 16, 32 and 52 weeks in 31 patients with type 1 diabetes who started CSII and 20 patients who continued multiple daily insulin injections (MDI)., Results: One year of CSII reduced haemoglobin A1c (HbA1c ) by 1.6% (17.8 mmol/mol) compared with 0.3% (3.1 mmol/mol) in the MDI group (p < 0.0001). Central retinal thickness increased by 1.5% in the CSII group (within-group p = 0.0098; between-group p = 0.063) without producing macular oedema. No detectable change was found in any other primary outcome measure. The proportion of patients with retinopathy worsening did not differ between groups. At baseline, longer disease duration was associated with higher retinal artery oxygen saturation (p = 0.014) and lower macular venous perfusion velocity (p = 0.045)., Conclusion: One year of CSII led to an HbA1c reduction relative to continued MDI and a small increase in retinal thickness but not to early retinopathy worsening or to changes in retinal vascular, structural or functional characteristics. Longer duration of type 1 diabetes appears to be associated with lower macular venous perfusion velocity and higher retinal artery oxygen saturation. The latter could potentially reflect cumulative glycaemia., (© 2016 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Chloroplasts are the sunlight-collecting organelles of photosynthetic eukaryotes that energetically drive the biosphere of our planet. They are the base for all major food webs by providing essential photosynthates to all heterotrophic organisms including humans. Recent research has focused largely on an understanding of the function of these organelles, but knowledge about the biogenesis of chloroplasts is rather limited. It is known that chloroplasts develop from undifferentiated precursor plastids, the proplastids, in meristematic cells. This review focuses on the activation and action of plastid RNA polymerases, which play a key role in the development of new chloroplasts from proplastids. Evolutionarily, plastids emerged from the endosymbiosis of a cyanobacterium-like ancestor into a heterotrophic eukaryote. As an evolutionary remnant of this process, they possess their own genome, which is expressed by two types of plastid RNA polymerase, phage-type and prokaryotic-type RNA polymerase. The protein subunits of these polymerases are encoded in both the nuclear and plastid genomes. Their activation and action therefore require a highly sophisticated regulation that controls and coordinates the expression of the components encoded in the plastid and nucleus. Stoichiometric expression and correct assembly of RNA polymerase complexes is achieved by a combination of developmental and environmentally induced programmes. This review highlights the current knowledge about the functional coordination between the different types of plastid RNA polymerases and provides working models of their sequential expression and function for future investigations., (© The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Given the increasing use of silver nanoparticles (Ag NP) by the food and food packaging industries, this study investigated potential consequences of Ag NP ingestion in intestinal epithelial C2BBe1 cells. Treatment of proliferating cells (<10,000 cells/cm(2)) with 0.25 μg/cm(2) (1.25 μg/mL) of 23 nm Ag NP for 24 h induced 15% necrotic cell death and an 80% reduction in metabolic activity and decreased the GSH/GSSG ratio, indicating oxidative stress. G2/M phase cell cycle arrest and complete inhibition of cell proliferation was also induced by Ag NP treatment. Simulated in vitro digestion of Ag NP prior to cell exposure required the use of slightly higher doses to induce the same toxicity, likely due to slower Ag dissolution. Treatment of cells with silica, titania, and ZnO NP partially inhibited cell proliferation, but inhibition at low doses was unique to Ag NP. These data suggest that Ag NP induces oxidative stress, cell cycle arrest, and the inhibition of cell proliferation. However, toxicity and induction of oxidative stress were not observed in confluent cells (>100,000 cells/cm(2)) treated with 10 μg/cm(2) (40-50 μg/mL) Ag NP, indicating that these cells are less sensitive to Ag NP., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aim: To explore and illustrate how the Guided Self-Determination-Youth method influences the development of life skills in adolescents with type 1 diabetes supported by their parents and healthcare providers., Background: Evidence-based methods that accomplish constructive cooperation between adolescents with poorly controlled type 1 diabetes, their parents and healthcare providers are needed. We adjusted an adult life skills intervention comprising reflection sheets and advanced communication for use by adolescent-parent-professional triads in outpatient visits., Design: A qualitative realistic evaluation design comprising eight context-mechanism-outcome configurations directed the analysis of the Guided Self-Determination-Youth's influence on adolescent-parent-professional triads to evaluate what worked for whom, how and in what circumstances. Thirteen adolescents aged 13-18 years diagnosed with type 1 diabetes for ≥1 year and having poor glycaemic control participated together with 17 parents and eight healthcare providers. Data were collected from December 2009-March 2012 and consisted of digitally recorded outpatient Guide Self-Determination-Youth visits collected during the intervention period (11·5-24·5 months) and semi-structured interviews at 6-month follow-up., Findings: Emerging life skills in adolescents were identified as: (1) developing new relatedness with healthcare providers and parents; (2) becoming decision makers in their own lives with diabetes; and (3) growing personally. Reflection sheets combined with healthcare providers' advanced communication were central to promoting mutual problem-solving., Conclusion: A life skills approach turned outpatient visits into person-specific visits with improved cooperation patterns in the triads. Combining reflection sheets and advanced communication skills supported adolescents in beginning a process of developing life skills., (© 2014 John Wiley & Sons Ltd.)

To investigate the impact of continuous glucose monitoring (CGM) on health-related quality of life (HRQOL), treatment satisfaction (TS) medical resource use, and indirect costs in the SWITCH study. SWITCH was a multicentre, randomized, crossover study. Patients with type 1 diabetes (n = 153) using continuous subcutaneous insulin infusion (CSII) were randomized to a 12 month sensor-On/Off or sensor-Off/On sequence (6 months each treatment), with a 4-month washout between periods. HRQOL in children and TS in adults were measured using validated questionnaires. Medical resource utilization data were collected. In adults, TS was significantly higher in the sensor-On arm, and there were significant improvements in ratings for treatment convenience and flexibility. There were no clinically significant differences in children's HRQOL or parents' proxy ratings. The incidence of severe hypoglycaemia, unscheduled visits, or diabetes-related hospitalizations did not differ significantly between the two arms. Adult patients made fewer telephone consultations during the sensor-On arm; children's caregivers made similar numbers of telephone consultations during both arms, and calls were on average only 3 min longer during the sensor-On arm. Regarding indirect costs, children with >70 % sensor usage missed fewer school days, compared with the sensor-Off arm (P = 0.0046) but there was no significant difference in the adults days of work off. The addition of CGM to CSII resulted in better metabolic control without imposing an additional burden on the patient or increased medical resource use, and offered the potential for cost offsets.