Use of Factory-Calibrated Real-time Continuous Glucose Monitoring Improves Time in Target and HbA1c in a Multiethnic Cohort of Adolescents and Young Adults With Type 1 Diabetes:The MILLENNIALS Study

OBJECTIVEInternational type 1 diabetes registries have shown that HbA1c levels are highest in young people with type 1 diabetes; however, improving their glycemic control remains a challenge. We propose that use of the factory-calibrated Dexcom G6 CGM system would improve glycemic control in this cohort.RESEARCH DESIGN AND METHODSWe conducted a randomized crossover trial in young people with type 1 diabetes (16–24 years old) comparing the Dexcom G6 CGM system and self-monitoring of blood glucose (SMBG). Participants were assigned to the interventions in random order during two 8-week study periods. During SMBG, blinded continuous glucose monitoring (CGM) was worn by each participant for 10 days at the start, week 4, and week 7 of the control period. HbA1c measurements were drawn after enrollment and before and after each treatment period. The primary outcome was time in range 70–180 mg/dL.RESULTSTime in range was significantly higher during CGM compared with control (35.7 ± 13.5% vs. 24.6 ± 9.3%; mean difference 11.1% [95% CI 7.0–15.2]; P < 0.001). CGM use reduced mean sensor glucose (219.7 ± 37.6 mg/dL vs. 251.9 ± 36.3 mg/dL; mean difference −32.2 mg/dL [95% CI −44.5 to −20.0]; P < 0.001) and time above range (61.7 ± 15.1% vs. 73.6 ± 10.4%; mean difference 11.9% [95% CI −16.4 to −7.4]; P < 0.001). HbA1c level was reduced by 0.76% (95% CI −1.1 to −0.4) (−8.5 mmol/mol [95% CI −12.4 to −4.6]; P < 0.001). Times spent below range (<70 mg/dL and <54 mg/dL) were low and comparable during both study periods. Sensor wear was 84% during the CGM period.CONCLUSIONSCGM use in young people with type 1 diabetes improves time in target and HbA1c levels compared with SMBG

Real-World Outcomes of Glucose Sensor Use in Type 1 Diabetes—Findings from a Large UK Centre

From MDPI via Jisc Publications RouterHistory: accepted 2021-11-10, pub-electronic 2021-11-15Publication status: PublishedFlash glucose monitoring (FGM) and real-time continuous glucose monitoring (RT-CGM) are increasingly used in clinical practice, with improvements in HbA1c and time in range (TIR) reported in clinical studies. We aimed to evaluate the impact of FGM and RT-CGM use on glycaemic outcomes in adults with type 1 diabetes (T1DM) under routine clinical care. We performed a retrospective data analysis from electronic outpatient records and proprietary web-based glucose monitoring platforms. We measured HbA1c (pre-sensor vs. on-sensor data) and sensor-based outcomes from the previous three months as per the international consensus on RT-CGM reporting guidelines. Amongst the 789 adults with T1DM, HbA1c level decreased from 61.0 (54.0, 71.0) mmol/mol to 57 (49, 65.8) mmol/mol in 561 people using FGM, and from 60.0 (50.0, 70.0) mmol/mol to 58.8 (50.3, 66.8) mmol/mol in 198 using RT-CGM (p 0.001 for both). We found that 23% of FGM users and 32% of RT-CGM users achieved a time-in-range (TIR) (3.9 to 10 mmol/L) of >70%. For time-below-range (TBR) 4 mmol/L, 70% of RT-CGM users and 58% of FGM users met international recommendations of 4%. Our data add to the growing body of evidence supporting the use of FGM and RT-CGM in T1DM

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Manipulating cocrystal size and morphology using a combination of temperature cycling and additives

A cooling crystallization of benzoic acid and isonicotinamide in ethanol yields the 1:1 cocrystal with an extreme needle-like morphology with an initial mean aspect ratio of ∼10 and a size of ∼64 μm. We demonstrate that the use of suspension temperature cycling in combination with tailor-made additives alleviates such extreme needle-like morphologies and increases the average particle size of this cocrystal material. Temperature cycling of the cocrystal suspensions in ethanol alone reduces the mean aspect ratio from 10 to 3.3 while it increases the average crystal size from 64 to 450 μm. The further addition of low concentrations of benzamide or nicotinamide suppresses the growth rate at the tip of the needle even more, resulting in a more favorable equant morphology. An iterative mechanism in which additives are incorporated in the lattice structure and released during the temperature increase in each cycle is proposed. Thus, the incorporation of an additive at the normally fast growing and potential needle tips and its release during the temperature increase part of the cycle effectively makes an additive action catalytic. The simultaneous use of temperature cycling and tailor-made additives offers a new and effective approach for the elimination of unsatisfactory needle-like crystal morphologies and a small crystal size during the production of a pharmaceutical cocrystal material.This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) and is co-founded under the European Regional Development Fund under Grant Number 12/RC/2275. FC thanks the Crystallize COST Action CM1402 for travel funding of the Short-Term Scientific Mission (STSM). FC gratefully acknowledges the hospitality that he enjoyed as a Visiting researcher during his STSM at the EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation (CMAC) at the University of Strathclyde. JtH, SJU and VS would like to thank EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation (Grant Ref EP/K503289/1) for funding this work. The authors would like to acknowledge that part of this work was carried out in the CMAC National Facility supported by UKRPIF (UK Research Partnership Fund) award from the Higher Education Funding Council for England (HEFCE) (Grant Ref HH13054).2021-11-2

Manipulating cocrystal size and morphology using a combination of temperature cycling and additives

A cooling crystallization of benzoic acid and isonicotinamide in ethanol yields the 1:1 cocrystal with an extreme needle-like morphology with an initial mean aspect ratio of ∼10 and a size of ∼64 μm. We demonstrate that the use of suspension temperature cycling in combination with tailor-made additives alleviates such extreme needle-like morphologies and increases the average particle size of this cocrystal material. Temperature cycling of the cocrystal suspensions in ethanol alone reduces the mean aspect ratio from 10 to 3.3 while it increases the average crystal size from 64 to 450 μm. The further addition of low concentrations of benzamide or nicotinamide suppresses the growth rate at the tip of the needle even more, resulting in a more favorable equant morphology. An iterative mechanism in which additives are incorporated in the lattice structure and released during the temperature increase in each cycle is proposed. Thus, the incorporation of an additive at the normally fast growing and potential needle tips and its release during the temperature increase part of the cycle effectively makes an additive action catalytic. The simultaneous use of temperature cycling and tailor-made additives offers a new and effective approach for the elimination of unsatisfactory needle-like crystal morphologies and a small crystal size during the production of a pharmaceutical cocrystal material.This publication has emanated from research supported in part by a research grant from Science Foundation Ireland (SFI) and is co-founded under the European Regional Development Fund under Grant Number 12/RC/2275. FC thanks the Crystallize COST Action CM1402 for travel funding of the Short-Term Scientific Mission (STSM). FC gratefully acknowledges the hospitality that he enjoyed as a Visiting researcher during his STSM at the EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation (CMAC) at the University of Strathclyde. JtH, SJU and VS would like to thank EPSRC Centre for Innovative Manufacturing in Continuous Manufacturing and Crystallisation (Grant Ref EP/K503289/1) for funding this work. The authors would like to acknowledge that part of this work was carried out in the CMAC National Facility supported by UKRPIF (UK Research Partnership Fund) award from the Higher Education Funding Council for England (HEFCE) (Grant Ref HH13054).peer-reviewed2021-11-2

Impact of COVID-19 lockdown on flash and real-time glucose sensor users with type 1 diabetes in England

AimsPeople with type 1 diabetes (T1D) face the daily task of implementing self-management strategies to achieve their glycaemic goals. The UK COVID-19 lockdown has had an impact on day-to-day behaviour, which may affect diabetes self-management and outcomes. We assessed whether sensor-based outcomes pre- and during lockdown periods were different in a cohort of glucose sensor users with T1D.MethodsData were collected from Freestyle Libre (FSL) or Dexcom G6 sensor users who remotely shared their data with the diabetes clinic web platform. Sensor metrics according to international consensus were analysed and compared between pre-lockdown period and 2 and 3 weeks into lockdown (periods 1 and 2).ResultsTwo hundred and sixty-nine T1D patients (baseline HbA1c 57 ± 14 mmol/mol) were identified as FSL (n = 190) or Dexcom G6 (n = 79) users. In patients with sensor use > 70% (N = 223), compared to pre-lockdown period percentage TIR 3.9–10 mM (TIR) significantly increased during period 1 (59.6 ± 18.2 vs. 57.5 ± 17.2%, p = 0.002) and period 2 (59.3 ± 18.3 vs. 57.5 ± 17.2%, p = 0.035). The proportion of patients achieving TIR ≥ 70% increased from 23.3% pre-lockdown to 27.8% in period 1 and 30.5% in period 2. A higher proportion also achieved the recommended time below and above range, and coefficient of variation in periods 1 and 2. Dexcom G6 users had significantly lower % time below range (< 3.9 mM) compared to FSL users during both lockdown periods (period 1: Dexcom G6 vs. FSL: 1.8% vs. 4%; period 2: 1.4% vs. 4%, p < 0.005 for both periods).ConclusionSensor-based glycaemic outcomes in people with T1D in the current cohort improved during COVID-19 lockdown, which may be associated with positive changes in self-management strategies. Further work is required to evaluate long-term sustainability and support

Real-World Outcomes of Glucose Sensor Use in Type 1 Diabetes—Findings from a Large UK Centre

Flash glucose monitoring (FGM) and real-time continuous glucose monitoring (RT-CGM) are increasingly used in clinical practice, with improvements in HbA1c and time in range (TIR) reported in clinical studies. We aimed to evaluate the impact of FGM and RT-CGM use on glycaemic outcomes in adults with type 1 diabetes (T1DM) under routine clinical care. We performed a retrospective data analysis from electronic outpatient records and proprietary web-based glucose monitoring platforms. We measured HbA1c (pre-sensor vs. on-sensor data) and sensor-based outcomes from the previous three months as per the international consensus on RT-CGM reporting guidelines. Amongst the 789 adults with T1DM, HbA1c level decreased from 61.0 (54.0, 71.0) mmol/mol to 57 (49, 65.8) mmol/mol in 561 people using FGM, and from 60.0 (50.0, 70.0) mmol/mol to 58.8 (50.3, 66.8) mmol/mol in 198 using RT-CGM (p 70%. For time-below-range (TBR) < 4 mmol/L, 70% of RT-CGM users and 58% of FGM users met international recommendations of <4%. Our data add to the growing body of evidence supporting the use of FGM and RT-CGM in T1DM