CACNA1S mutation-associated dental anomalies: A calcium channelopathy.

OBJECTIVES: To identify the molecular etiology of distinct dental anomalies found in eight Thai patients and explore the mutational effects on cellular functions. MATERIALS AND METHODS: Clinical and radiographic examinations were performed for eight patients. Whole exome sequencing, mutant protein modelling, qPCR, western blot analysis, scratch assays, immunofluorescence, confocal analysis, in situ hybridization, and scanning electron micrography of teeth were done. RESULTS: All patients had molars with multiple supernumerary cusps, single-cusped premolars, and a reduction in root number. Mutation analysis highlighted a heterozygous c.865A>G; p.Ile289Val mutation in CACNA1S in the patients. CACNA1S is a component of the slowly inactivating L-type voltage-dependent calcium channel. Mutant protein modeling suggested that the mutation might allow leakage of Ca2+ or other cations, or a tightening, to restrict calcium flow. Immunohistochemistry analysis showed expression of Cacna1s in the developing murine tooth epithelium during stages of crown and root morphogenesis. In cell culture, the mutation resulted in abnormal cell migration of transfected CHO cells compared to wildtype CACNA1S, with changes to the cytoskeleton and markers of focal adhesion. CONCLUSIONS: The malformations observed in our patients suggest a role for calcium signaling in organization of both cusps and roots, affecting cell dynamics within the dental epithelium.

Low rate of local recurrence detection by rectoscopy in follow-up of rectal cancer.

AIM: The main aim of this study was to examine the effectiveness of rectoscopy for detecting local recurrence of rectal cancer in patients following low anterior resection. METHOD: This was a retrospective study of 201 patients, who underwent low anterior resection for rectal or rectosigmoid cancer between 2007 and 2009 and who were followed up with rigid rectoscopy and imaging. A total of 91 patients were excluded from the analysis for various reasons, leaving 110 patients eligible for analysis. RESULTS: A total of 613 rectoscopies were performed, and 48 biopsies taken. Six local recurrences were detected in the 110 patients, three of which were first detected by rectoscopy and three by CT. Two of the local recurrences were detected outside the follow-up programme because of symptoms: one by rectoscopy and one by CT. Three of 613 (0.5%) rectoscopies led to detection of local recurrence. The sensitivity and specificity of rectoscopy to detect local recurrence was 0.50 and 0.93, respectively. Nineteen distant metastases were detected, and two patients had both local recurrence and distant metastasis. All local recurrences and distant metastases were detected within 48 months of surgery. CONCLUSION: Rigid rectoscopy is poor at detecting local recurrence. Only 3 out of 613 rectoscopies (0.5%) detected local recurrence. Due to extramural growth of some recurrences, the sensitivity is also very low. Based on our results, routine rectoscopy in the surveillance of asymptomatic patients cannot be recommended.

Adrenaline and cortisol levels are lower during nighttime than daytime hypoglycaemia in children with type 1 diabetes.

AIM: We investigated children's counter regulatory hormone profiles during a hyperinsulinaemic hypoglycaemic clamp procedure at day and night. METHODS: In 2013, we assessed the counter regulatory response to hypoglycaemia in eight outpatients with type 1 diabetes, recruited from the Herlev Hospital, Denmark, at a mean age of 9.6 ± 2.3 years. Hyperinsulinaemic 80 mU/m2 /min clamps were performed with a stepwise reduction in plasma glucose from euglycaemia (7-9 mmol/L) to hypoglycaemia (<3.5 mmol/L) and the glucose nadir (≤2.2 mmol/L) during the day and night. Adrenaline, cortisol, glucagon and growth hormone levels were assessed. RESULTS: Adrenaline and growth hormone levels were higher during the day versus the night (p = 0.04 and p = 0.01, respectively). However, at the glucose nadir, the level of adrenaline was lower during the night than the day (0.6 ± 0.2 versus 1.9 ± 0.5 nmol/L, p = 0.016) and cortisol was lower during the day than the night (42 ± 15 versus 319 ± 81 nmol/L, p = 0.016). No differences were demonstrated for glucagon and growth hormone levels based on the same criteria. CONCLUSION: The adrenaline response was blunted during nocturnal iatrogenic hypoglycaemia in our study cohort, and no increase in cortisol levels was demonstrated.

Observation of Quantum-Limited Spin Transport in Strongly Interacting Two-Dimensional Fermi Gases.

We measure the transport properties of two-dimensional ultracold Fermi gases during transverse demagnetization in a magnetic field gradient. Using a phase-coherent spin-echo sequence, we are able to distinguish bare spin diffusion from the Leggett-Rice effect, in which demagnetization is slowed by the precession of a spin current around the local magnetization. When the two-dimensional scattering length is tuned to be comparable to the inverse Fermi wave vector k_{F}^{-1}, we find that the bare transverse spin diffusivity reaches a minimum of 1.7(6)ℏ/m, where m is the bare particle mass. The rate of demagnetization is also reflected in the growth rate of the s-wave contact, observed using time-resolved spectroscopy. The contact rises to 0.28(3)k_{F}^{2} per particle, which quantifies how scaling symmetry is broken by near-resonant interactions, unlike in unitary three-dimensional systems. Our observations support the conjecture that, in systems with strong scattering, the local relaxation rate is bounded from above by k_{B}T/ℏ.

Increased mortality in a Danish cohort of young people with Type 1 diabetes mellitus followed for 24 years.

AIM: To determine the mortality rate in a Danish cohort of children and adolescents diagnosed with Type 1 diabetes mellitus compared with the general population. METHODS: In 1987 and 1989 we included 884 children and 1020 adolescents aged 20 years and under, corresponding to 75% of all Danish children and adolescents with Type 1 diabetes, in two nationwide studies in Denmark. Those who had participated in both investigations (n = 720) were followed until 1 January 2014, using the Danish Civil Registration System on death certificates and emigration. We derived the expected number of deaths in the cohort, using population data values from Statistics Denmark to calculate the standardized mortality ratio. Survival analysis was performed using Cox proportional hazards model. RESULTS: During the 24 years of follow-up, 49 (6.8%) patients died, resulting in a standardized mortality ratio of 4.8 (95% confidence interval 3.5, 6.2) compared with the age-standardized general population. A 1% increase in baseline HbA1c (1989), available in 718 of 720 patients, was associated with all-cause mortality (hazard ratio = 1.38; 95% confidence interval 1.2, 1.6; P < 0.0001). Type 1 diabetes with multiple complications was the most common reported cause of death (36.7%). CONCLUSION: We found an increased mortality rate in this cohort of children and adolescents with Type 1 diabetes compared with the general population. The only predictor for increased risk of death up to 24 years after inclusion was the HbA1c level in 1989. This emphasizes the importance of achieving optimal metabolic control in young people with Type 1 diabetes.

Retinal vascular geometry and its association to microvascular complications in patients with type 1 diabetes: the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987).

PURPOSE: To examine associations between retinal vascular geometry (tortuosity, branching coefficient [BC] and length-diameter ratio [LDR]) and diabetic proliferative retinopathy (PDR), nephropathy, and peripheral neuropathy in patients with type 1 diabetes mellitus (T1DM). METHODS: A cohort of patients with T1DM participated in a clinical examination in 2011. Blood and urine analyses were done and retinal images taken. PDR was defined as Early Treatment Diabetic Retinopathy Study level 61 or above, nephropathy as albumin-creatinin ratio ≥300 mg/g, and neuropathy as vibration perception threshold >25 Volt. Retinal vessel parameters were measured using semi-automated software. Multiple logistic regressions were performed to investigate correlations between retinal vascular parameters and outcomes. Models were adjusted for other variables (sex, age, duration of diabetes, systolic and diastolic blood pressure, HbA1c, and presence of microvascular complications). Odds ratios were given per standard deviation in retinal vascular parameter. RESULTS: Retinal vascular analyses were performed in 181 patients. Mean age and duration of diabetes were 37.0 years and 29.4 years respectively, and 50.8% were male. Prevalence of PDR, nephropathy, and neuropathy were 26.5%, 6.8%, and 10.1% , respectively. Patients with increased arteriolar BC had a higher risk of nephropathy (OR: 3.10, 95% CI: [1.01-9.54]). Patients with increased venular BC had a higher risk of neuropathy (OR: 2.11, 95% CI: [1.11-4.03]). No associations were found in patients with PDR. CONCLUSIONS: By analyzing the retinal vascular tree in patients with T1DM, we found a higher risk of complications in kidneys and nerves when BC was increased. This might indicate a suboptimal construction of the vascular tree in these patients.

Col2-Cre and tamoxifen-inducible Col2-CreER target different cell populations in the knee joint.

OBJECTIVE: Collagen type 2 (Col2)-Cre or tamoxifen-inducible Col2-CreER transgenic mouse lines have been used for studies to explore the cellular and molecular pathogenesis of osteoarthritis (OA). The purpose of this study is to investigate whether the targeted cells are the same or different in the two mouse lines. METHODS: We crossed tamoxifen inducible Col2-CreER and Col2-Cre mice with Rosa tdTomato reporter mice and analyzed the labeling patterns at different time points. RESULTS: In the Col2-CreER mice, 90.8 [95% confidence interval (CI) (88.3, 93.2)] and 82.8 (77.4, 88.3) % of the articular surface cells are Tomato positive when tamoxifen was administered at 2 and 2.5 weeks of age and strong activity was observed even 4.5 months after injection. However, 46.0 (32.8, 59.1) and 22.2 (11.7, 32.6) % of the surface cells were Tomato positive when tamoxifen was administered at 3 and 4 weeks of age, respectively. Little to no Tomato activity in the articular surface cells was observed when tamoxifen was administered at 8 weeks of age. At any stage of tamoxifen injection, the Tomato activity was detected in growth plate and epiphyseal bone in addition to articular chondrocytes, but little in endosteum and not in the synovium and ligament. In contrast, the targeted tissues in the Col2-Cre mouse line were articular cartilage, growth plate, meniscus, endosteum, ligament, bone and synovium. CONCLUSIONS: This study demonstrates that the pattern of targeted cells in the inducible Col2-CreER mice are partially overlapping with but different from that of targeted cells in Col2-Cre mice and the pattern varies dependent on when tamoxifen is administered.

Optimum bolus wizard settings in insulin pumps in children with Type 1 diabetes.

AIM: To evaluate current insulin pump settings in an optimally regulated paediatric population using bolus wizard. METHODS: We used a retrospective study design to analyse data from 124 children on insulin pump therapy who had optimum HbA1c levels [< 59 mmol/mol (< 7.5%)] and no history of severe hypoglycaemic events. Bolus wizard settings were used to calculate the insulin to carbohydrate factors and insulin sensitivity factors. Multiple regression analysis was used to analyse the variables associated with the calculation factors. RESULTS: Insulin to carbohydrate factor varied from 276 in the youngest group to 424 in the oldest group, and increased according to age. Insulin sensitivity factor was highest in the group aged 6 to < 12 years, with a value of 125. Age, amount of carbohydrates, number of boluses per day and insulin per kg were all significantly associated with both calculation factors. Furthermore, duration of insulin pump treatment was significantly associated with insulin sensitivity factor and percentage bolus/basal was significantly associated with insulin to carbohydrate factor. Gender, diabetes duration and BMI were not associated with any of the calculation factors. CONCLUSION: Optimum insulin pump settings at pump initiation depend on both insulin requirements and use of the pump. Settings need to be individualized because the standardized calculation factors are not constant for children. There is a need to develop specific age- and insulin dose-dependent calculation factors.

Regulation of adipogenesis and osteogenesis in mesenchymal stem cells by vascular endothelial growth factor A.

Understanding the mechanisms by which bone marrow mesenchymal stem cells (BMSCs) differentiate into bone-forming osteoblasts and marrow adipocytes is crucial to develop strategies for the treatment of several bone diseases. Age-related bone loss resulting in osteopenia and osteoporosis has been associated with reduced numbers of osteoblasts and increased numbers of adipocytes, likely originating from differentiation defects in BMSCs. Although many factors involved in the complex regulation of osteoblast and adipocyte cell lineages have previously been identified, their functional interactions in the context of BMSC differentiation and maintenance of bone homeostasis during ageing are unknown. Recent discoveries have provided important new insights into the mechanisms by which the nuclear envelope protein lamin A and vascular endothelial growth factor A (VEGF) mutually control BMSC fate. Particularly interesting is the finding that VEGF in this context functions as an intracellular protein, unaffected by neutralizing antibodies, and not as a secreted growth factor. These insights may not only facilitate the identification of new targets for treating bone diseases but also lead to improved design of tissue engineering approaches aimed at stimulating bone regeneration and repair.

Long-term incidence of vitrectomy and associated risk factors in young Danish patients with Type 1 diabetes: the Danish Cohort of Paediatric Diabetes 1987.

AIMS: To examine the long-term incidence of vitrectomy in young people with Type 1 diabetes. METHODS: We prospectively studied 324 people with Type 1 diabetes who participated in baseline examinations in 1995. Surgical history was obtained from the Danish National Patient Registry in April 2012. RESULTS: During the 17-year study period, 39 people (12.0%) underwent vitrectomy at least once. The mean age and diabetes duration at first vitrectomy were 29.8 and 22.9 years, respectively, and 64.1% of the participants were men. In multivariable Cox regression analysis, baseline age (hazard ratio 0.81 per 1 year increase), BMI (hazard ratio 1.21 per 1 kg/m(2) increase), HbA1c (hazard ratio 1.72 per 1% increase) and diabetic retinopathy (hazard ratio 2.85 and 6.07 for mild and moderate/severe diabetic retinopathy vs none, respectively) were independent predictors of vitrectomy (P < 0.05 for all variables). CONCLUSIONS: Vitrectomy is a relatively common procedure in young people with Type 1 diabetes, with poor glycaemic control being the strongest modifiable risk factor.

Insulin pump treatment; increasing prevalence, and predictors for better metabolic outcome in Danish children and adolescents with type 1 diabetes.

AIMS: Few studies have looked at nationwide data for insulin pump treatment. Since 1996 the Danish Childhood Diabetes Registry (DanDiabKids) has collected data on all Danish diabetic patients aged 0-15 yr. The purpose of this study is to evaluate the prevalence of continuous subcutaneous insulin infusion (CSII) use among Danish children with diabetes and to compare metabolic control in CSII-treated children and adolescents to those treated with MDI. MATERIALS AND METHODS: The Registry collects on a yearly basis data on insulin regimen, central measured hemoglobin A1c (HbA1c), and demographic data on all patients. In the period 2005-2011, 2983 young patients (1721 males) with diabetes were followed in the Registry. Mean observation period was 5.11 yr [standard error (SE) 0.09]. In the total period 1846 patients were treated with MDI and 1493 changed from MDI to CSII. In 2005, less than 5% of children were treated with CSII whereas the percentage of children on CSII increased to approximately 50% in 2011. The patients were divided into age groups, <5 yr, 5-10 yr, and > 15 yr. RESULTS: HbA1c was significantly higher in MDI-treated children, +5.29 (CI 95% 4.29; 6.29 mmol/mol). HbA1c in all age groups was significantly lower in CSII-treated patients, and longitudinally HbA1c continued to be lower in all age groups. In multivariate analysis, a low HbA1c at CSII start, centers with more than 100 pump patients, a more recent year of diabetes onset, a higher number of self-monitoring of blood glucose (SMBG) measurements, a higher number of daily boluses, and a higher percentage of bolus insulin were all related to a lower HbA1c. CONCLUSION: The percentage of children on pumps (CSII) is CSII treatment is associated with a significantly lower Hba1c, achieved just after treatment initiation. In the following years there is a parallel rise in HbA1c in both MDI as well as in MDI treated patients. Patients coming from larger clinics, and patients measuring more blood glucose values and taking more boluses have a better metabolic control.

Prevalence and predictors of severe hypoglycemia in Danish children and adolescents with diabetes.

OBJECTIVE: To investigate the prevalence of severe hypoglycemia in Danish children and adolescents with type 1 diabetes and to pinpoint predictors of this acute complication in children on modern treatment modalities. RESEARCH DESIGN AND METHODS: The study is based on data from DanDiabKids, a national diabetes register for children and adolescents. The register contains data on patients with type 1 diabetes with an ascertainment rate of 99%. Data from 3320 patients aged 0-18 yr was included in the study period from 1998 to 2009 and analyzed using a negative binomial model. RESULTS: One thousand nine hundred and ninety-nine episodes of severe hypoglycemia in 867 patients were registered conferring an overall incidence of severe hypoglycemia of 15.1 [95% confident interval (CI): 13.8; 16.4] per 100 patient years. This remained unchanged during the study period. Duration of diabetes, age and treatment in centers managing less than 100 patients significantly increased the risk of severe hypoglycemia (p < 0.001). Patients on insulin pump therapy had a 42% reduced risk of severe hypoglycemia compared with pen treated patients (p = 0.01). Patients treated with five or more daily insulin injections had a 31% (95% CI: 17; 49) reduced risk of severe hypoglycemia compared to patients on fewer daily injections (p = 0.015). CONCLUSIONS: Despite improvements in metabolic control over a decade the prevalence of severe hypoglycemic events remained unchanged. More intensive treatments such as insulin pump therapy and multiple daily injections on a national level seems to be a protective factor for developing severe hypoglycemia up to 2009.

Microaneurysm count as a predictor of long-term progression in diabetic retinopathy in young patients with type 1 diabetes: the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987).

PURPOSE: To investigate microaneurysm (MA) count as a predictor of long-term progression of diabetic retinopathy (DR) in young patients with type 1 diabetes mellitus (T1DM). METHODS: We examined 185 patients with T1DM at baseline (1995) and at follow-up (2011). At baseline, mean age and duration of diabetes were 20.6 and 12.9 years, respectively. Two-field (1995) and seven-field (2011) fundus photographs were taken in accordance with the European Diabetes Study Group (EURODIAB) and the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, respectively. DR was graded in accordance to the ETDRS protocol, allowing for non-standard photography at baseline. Baseline MAs were counted; patients without DR and those with MAs only were included. Multivariable logistic regressions were performed to investigate MA-count as a predictor of two-step progression, progression to proliferative DR (PDR), and incident diabetic macula edema (DME). RESULTS: We included 138 patients (138 eyes). Of these, 58 had no retinopathy and 80 had MAs only. At follow-up, rates of two-step progression of DR, progression to PDR and incident DME were 52.9, 21.7, and 10.1 %, respectively. In logistic regression models, MA count was able to predict progression to PDR (OR: 1.51 per MA; 95 % CI: [1.04-2.20]) and DME (OR: 1.69 per MA; 95 % CI: [1.05-2.77]), but not two-step progression (OR 0.91 per MA, 95 % CI: [0.64-1.31]). CONCLUSIONS: In younger patients with T1DM, MA count predicts long-term incidence of PDR and DME. This demonstrates that early DR is a warning sign of late retinopathy complications and that the number of MAs is an important factor for long-term outcome.

Cognitive remediation combined with an early intervention service in first episode psychosis.

OBJECTIVE: This randomised clinical trial assessed the effects of a 16-week cognitive remediation programme (NEUROCOM) combined with an early intervention service (EIS) vs. EIS alone. METHOD: One hundred and seventeen patients with first episode psychosis were randomly assigned to 4 months cognitive remediation combined with EIS vs. EIS alone. Statistical analysis of effect was based on intention to treat. RESULTS: A total of 98 patients (83.8%) participated in post-training assessments at 4 months and 92 (78.6%) in 12-month follow-up assessments. No effects were found on the primary outcome measure functional capacity. At the post-training assessment, the intervention group had improved significantly on Rosenberg Self-Esteem Scale (Cohen's d=0.54, P=0.01), Positive and Negative Symptoms Scale (PANSS), General Psychopathology Scale (Cohen's d=0.51, P=0.05) and the verbal learning domain (Cohen's d=0.46, P=0.02). At follow-up assessment, the intervention group retained the significant improvements on the verbal learning domain (Cohen's d=0.58, P<0.05). Furthermore, significant improvements were observed on the working memory domain (Cohen's d=0.56, P=0.01) and PANSS positive symptoms (Cohen's d=0.44, P=0.04), while improvement on the composite score was marginally significant (Cohen's d=0.34, P=0.05). CONCLUSION: In accordance with other cognitive remediation programmes, this programme demonstrates some immediate and long-term effect on cognitive functioning, symptoms and self-esteem.

Diabetic ketoacidosis at the onset of type 1 diabetes is associated with future HbA1c levels.

AIMS/HYPOTHESIS: We investigated the long-term impact of diabetic ketoacidosis (DKA) at onset on metabolic regulation and residual beta cell function in a Danish population with type 1 diabetes. METHODS: The study is based on data from DanDiabKids, a Danish national diabetes register for children. The register provides clinical and biochemical data on patients with type 1 diabetes diagnosed in 1996-2009 and then followed-up until 1 January 2012. Repeated-measurement models were used as statistical methods. RESULTS: The study population comprised 2,964 children <18 years. The prevalence of DKA at diagnosis was 17.9%. Of the total subjects, 8.3% had mild, 7.9% had moderate and 1.7% had severe DKA. DKA (moderate and severe) was associated with increased HbA1c (%) levels (0.24; 95% CI 0.11, 0.36; p = 0.0003) and increased insulin dose-adjusted HbA1c (IDAA1c, 0.51; 95% CI 0.31, 0.70; p < 0.0001) during follow-up, after adjustment for covariates. Children without a family history of diabetes were more likely to present with DKA (19.2% vs 8.8%, p < 0.0001); however, these children had a lower HbA1c (%) level over time (-0.35; 95% CI -0.46, -0.24; p < 0.0001). Continuous subcutaneous insulin infusion (CSII) was associated with a long-term reduction in HbA1c, changing the effect of DKA, after adjustment for covariates (p < 0.0001). CONCLUSIONS/INTERPRETATION: DKA at diagnosis was associated with poor long-term metabolic regulation and residual beta cell function as assessed by HbA1c and IDAA1c, respectively; however, CSII treatment was associated with improvement in glycaemic regulation and residual beta cell function, changing the effect of DKA at onset in our population.

Unusual increase of psittacosis in southern Sweden linked to wild bird exposure, January to April 2013.

Free-living wild birds worldwide act as reservoir for Chlamydia psittaci, but the risk of transmission to humans through contact with wild birds has not been widely documented. From 12 January to April 9 2013, a total of 25 cases of psittacosis were detected in southern Sweden, about a threefold increase compared with the mean of the previous 10 years. A matched case-control study investigating both domestic and wild bird exposure showed that cases were more likely than controls to have cleaned wild bird feeders or been exposed to wild bird droppings in other ways (OR: 10.1; 95% CI: 2.1-47.9). We recommend precautionary measures such as wetting bird feeders before cleaning them, to reduce the risk of transmission of C. psittaci when in contact with bird droppings. Furthermore, C. psittaci should be considered for inclusion in laboratory diagnostic routines when analysing samples from patients with atypical pneumonia, since our findings suggest that psittacosis is underdiagnosed.

A type X collagen mutation causes Schmid metaphyseal chondrodysplasia.

The expression of type X collagen is restricted to hypertrophic chondrocytes in regions undergoing endochondral ossification, such as growth plates. The precise function of type X collagen is unknown but the tissue-specific expression prompted us to examine the gene in hereditary disorders of cartilage and bone growth (osteochondrodysplasias). We have identified a 13 base pair deletion in one type X collagen allele segregating with autosomal dominant Schmid metaphyseal chondrodysplasia in a large Mormon kindred (lod score = 18.2 at theta = 0). The mutation produces a frameshift which alters the highly conserved C-terminal domain of the alpha 1(X) chain and reduces the length of the polypeptide by nine residues. This mutation may prevent association of the mutant polypeptide during trimer formation, resulting in a decreased amount of normal protein.

Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause cherubism.

Cherubism (MIM 118400) is an autosomal dominant inherited syndrome characterized by excessive bone degradation of the upper and lower jaws followed by development of fibrous tissue masses, which causes a characteristic facial swelling. Here we describe seven mutations in the SH3-binding protein SH3BP2 (MIM 602104) on chromosome 4p16.3 that cause cherubism.

The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy: a randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this multicentre, randomised, controlled crossover study was to determine the efficacy of adding continuous glucose monitoring (CGM) to insulin pump therapy (CSII) in type 1 diabetes. METHODS: Children and adults (n = 153) on CSII with HbA(1c) 7.5-9.5% (58.5-80.3 mmol/mol) were randomised to (CGM) a Sensor On or Sensor Off arm for 6 months. After 4 months' washout, participants crossed over to the other arm for 6 months. Paediatric and adult participants were separately electronically randomised through the case report form according to a predefined randomisation sequence in eight secondary and tertiary centres. The primary outcome was the difference in HbA(1c) levels between arms after 6 months. RESULTS: Seventy-seven participants were randomised to the On/Off sequence and 76 to the Off/On sequence; all were included in the primary analysis. The mean difference in HbA(1c) was -0.43% (-4.74 mmol/mol) in favour of the Sensor On arm (8.04% [64.34 mmol/mol] vs 8.47% [69.08 mmol/mol]; 95% CI -0.32%, -0.55% [-3.50, -6.01 mmol/mol]; p < 0.001). Following cessation of glucose sensing, HbA(1c) reverted to baseline levels. Less time was spent with sensor glucose <3.9 mmol/l during the Sensor On arm than in the Sensor Off arm (19 vs 31 min/day; p = 0.009). The mean number of daily boluses increased in the Sensor On arm (6.8 ± 2.5 vs 5.8 ± 1.9, p < 0.0001), together with the frequency of use of the temporary basal rate (0.75 ± 1.11 vs 0.26 ± 0.47, p < 0.0001) and manual insulin suspend (0.91 ± 1.25 vs 0.70 ± 0.75, p < 0.018) functions. Four vs two events of severe hypoglycaemia occurred in the Sensor On and Sensor Off arm, respectively (p = 0.40). CONCLUSIONS/INTERPRETATION: Continuous glucose monitoring was associated with decreased HbA(1c) levels and time spent in hypoglycaemia in individuals with type 1 diabetes using CSII. More frequent self-adjustments of insulin therapy may have contributed to these effects.