The MiniMed™ 780G system includes an advanced hybrid closed loop (AHCL) algorithm that provides both automated basal and correction bolus insulin delivery. The preliminary performance of the system ...in real-world settings was evaluated.
Data uploaded from August 2020 to March 2021 by individuals living in Belgium, Finland, Italy, the Netherlands, Qatar, South Africa, Sweden, Switzerland, and the United Kingdom were aggregated and retrospectively analyzed to determine the mean glucose management indicator (GMI), percentage of time spent within (TIR), below (TBR), and above (TAR) glycemic ranges, system use, and insulin consumption in users having ≥10 days of sensor glucose (SG) data after initiating AHCL. The impact of initiating AHCL was evaluated in a subgroup of users also having ≥10 days of SG data, before AHCL initiation.
Users (
= 4120) were observed for a mean of 54 ± 32 days. During this time, they spent a mean of 94.1% ± 11.4% of the time in AHCL and achieved a mean GMI of 6.8% ± 0.3%, TIR of 76.2% ± 9.1%, TBR <70 of 2.5% ± 2.1%, and TAR >180 of 21.3% ± 9.4%, after initiating AHCL. There were 77.3% and 79.0% of users who achieved a TIR >70% and a GMI of <7.0%, respectively. Users for whom comparison with pre-AHCL was possible (
= 812) reduced their GMI by 0.4% ± 0.4% (
= 0.005) and increased their TIR by 12.1% ± 10.5% (
< 0.0001), post-AHCL initiation. More users achieved the glycemic treatment goals of GMI <7.0% (37.6% vs. 75.2%,
< 0.0001) and TIR >70% (34.6% vs. 74.9%,
< 0.0001) when compared with pre-AHCL initiation.
Most MiniMed 780G system users achieved TIR >70% and GMI <7%, while minimizing hypoglycemia, in a real-world condition.
Summary Background Many patients with advanced type 2 diabetes do not meet their glycated haemoglobin targets and randomised controlled studies comparing the efficacy of pump treatment and multiple ...daily injections for lowering glucose in insulin-treated patients have yielded inconclusive results. We aimed to resolve this uncertainty with a randomised controlled trial (OpT2mise). Methods We did this multicentre, controlled trial at 36 hospitals, tertiary care centres, and referal centres in Canada, Europe, Israel, South Africa, and the USA. Patients with type 2 diabetes who had poor glycaemic control despite multiple daily injections with insulin analogues were enrolled into a 2-month dose-optimisation run-in period. After the run-in period, patients with glycated haemoglobin of 8·0–12·0% (64–108 mmol/mol) were randomly assigned (1:1) by a computer-generated randomisation sequence (block size 2 with probability 0·75 and size 4 with probability 0·25) to pump treatment or to continue with multiple daily injections. Neither patients nor investigators were masked to treatment allocation. The primary endpoint was change in mean glycated haemoglobin between baseline and end of the randomised phase for the intention-to-treat population. This study is registered with ClinicalTrials.gov , number NCT01182493. Findings 495 of 590 screened patients entered the run-in phase and 331 were randomised (168 to pump treatment, 163 to multiple daily injections). Mean glycated haemoglobin at baseline was 9% (75 mmol/mol) in both groups. At 6 months, mean glycated haemoglobin had decreased by 1·1% (SD 1·2; 12 mmol/mol, SD 13) in the pump treatment group and 0·4% (SD 1·1; 4 mmol/mol, SD 12) in the multiple daily injection group, resulting in a between-group treatment difference of −0·7% (95% CI −0·9 to −0·4; −8 mmol/mol, 95% CI −10 to −4, p<0·0001). At the end of the study, the mean total daily insulin dose was 97 units (SD 56) with pump treatment versus 122 units (SD 68) for multiple daily injections (p<0·0001), with no significant difference in bodyweight change between the two groups (1·5 kg SD 3·5 vs 1·1 kg 3·6, p=0·322). Two diabetes-related serious adverse events (hyperglycaemia or ketosis without acidosis) resulting in hospital admission occurred in the pump treatment group compared with one in the multiple daily injection group. No ketoacidosis occurred in either group and one episode of severe hypoglycaemia occurred in the multiple daily injection group. Interpretation In patients with poorly controlled type 2 diabetes despite using multiple daily injections of insulin, pump treatment can be considered as a safe and valuable treatment option. Funding Medtronic.
We theoretically predict and compare with experiments, transitions from spontaneous beating to dynamical entrainment of cardiomyocytes induced by an oscillating, external mechanical probe. In accord ...with recent experiments, we predict the dynamical behavior as a function of the probe amplitude and frequency. The theory is based on a phenomenological model for a non-linear oscillator, motivated by acto-myosin contractility. The generic behavior is independent of the detailed, molecular origins of the dynamics and, consistent with experiment, we find three regimes: spontaneous beating with the natural frequency of the cell, entrained beating with the frequency of the probe, and a "bursting" regime where the two frequencies alternate in time. We quantitatively predict the properties of the "bursting" regime as a function of the amplitude and frequency of the probe. Furthermore, we examine the pacing process in the presence of weak noise and explain how this might relate to cardiomyocyte physiology.
We review a theoretical, coarse-grained description for cardiomyocytes calcium dynamics that is motivated by experiments on RyR channel dynamics and provides an analogy to other spontaneously ...oscillating systems. We show how a minimal model, that focuses on calcium channel and pump dynamics and kinetics, results in a single, easily understood equation for spontaneous calcium oscillations (the Van-der-Pol equation). We analyze experiments on isolated RyR channels to quantify how the channel dynamics depends both on the local calcium concentration, as well as its temporal behavior ("adaptation"). Our oscillator model analytically predicts the conditions for spontaneous oscillations, their frequency and amplitude, and how each of those scale with the small number of relevant parameters related to calcium channel and pump activity. The minimal model is easily extended to include the effects of noise and external pacing (electrical or mechanical). We show how our simple oscillator predicts and explains the experimental observations of synchronization, "bursting" and reduction of apparent noise in the beating dynamics of paced cells. Thus, our analogy and theoretical approach provides robust predictions for the beating dynamics, and their biochemical and mechanical modulation.
IntroductionFor many people with type 1 diabetes who struggle to achieve glycaemic control with multiple daily injections of insulin (MDI) plus self-monitoring of blood glucose, MDI plus ...intermittently scanned continuous glucose monitoring (IS-CGM) or real-time continuous glucose monitoring (RT-CGM), or insulin administration using insulin pump therapy represent optimised care in many regions. Through technological advances an advanced hybrid closed loop (AHCL) system has been developed; studies of incremental effects relative to MDI plus IS-CGM are lacking.Methods and analysisThe Advanced Hybrid Closed Loop study in Adult Population with Type 1 Diabetes (ADAPT) study is a multinational, prospective, open-label, confirmatory and exploratory randomised controlled trial to examine outcomes with the MiniMed 670G version 4.0 AHCL system (with an equivalent algorithm and commercialised as the MiniMed 780G system, referred to as AHCL) relative to MDI plus IS-CGM in adults with baseline HbA1c≥8.0%. An exploratory cohort will compare AHCL with MDI plus RT-CGM. The study will be conducted in approximately 124 adults on MDI plus either IS-CGM or RT-CGM for at least 3 months prior to screening. The primary endpoint will be the difference in mean HbA1c change from baseline to 6 months between the AHCL and the MDI plus IS-CGM arms. Secondary endpoints will include proportion of time spent in hypoglycaemic, euglycaemic and hyperglycaemic ranges.Ethics and disseminationThe ADAPT study will be conducted in accordance with the requirements of the Declaration of Helsinki and local laws and regulations, and has been approved by ethics committees. The trial will provide valuable information on the incremental benefits that may be provided by AHCL for patients failing to achieve glycaemic targets on MDI plus IS-CGM or RT-CGM and form a basis for health economic evaluations to support market access.Trial registration numberNCT04235504; Pre-results.
Aim
To evaluate the effect of a one-year use of an advanced hybrid closed-loop (AHCL) system on the quality of life, level of anxiety, and level of self-efficacy in adults with type 1 diabetes (T1D) ...previously treated with multiple daily injections (MDI) and naïve to advanced diabetes technology
Methods
A total of 18 participants of a previously published 3-month randomized trial (10 men, 8 women; age 40.9 ± 7.6 years) who were switched directly from MDI/BMG to AHCL completed 12 months of MiniMed 780G™system use (a 3-month randomized trial followed by a 9-month follow-up phase). At month 6 of the study, patients were switched from the sensor GS3 (Continuous Glucose Monitoring) system, powered by Guardian™ Sensor 3) to GS4. Quality of life was assessed using the Polish validated version of the ‘QoL-Q Diabetes’ questionnaire. The level of anxiety was evaluated with the use of the State-Trait Anxiety Inventory (STAI). Self-efficacy was assessed with the General Self-Efficacy Scale (GSES). Results were obtained at baseline and at the end of the study.
Results
Significant increase in QoL was reported in the global score (p=0.02, Cohen d=0.61) and in as many as 11 out of 23 analyzed areas of life: being physically active (p=0.02, Cohen d = 0.71); feeling well (p<.01, Cohen d = 0.73); feeling in control of my body (p<.01, Cohen d = 0.72); looking good (p<.01, Cohen d = 1.07); working (p<.01, Cohen d = 1.12); sleeping (p=0.01, Cohen d = 0.66); eating as I would like (p<.01, Cohen d = 0.79); looking after or being useful to others (p= 0.02, Cohen d = 0.65); being active with pets/animals (p<.01, Cohen d = 0.95); being spontaneous (p=0.02, Cohen d = 0.67); and doing “normal” things (p=0.02, Cohen d = 0.67). Both state (p=0.04, Cohen d = 0.56) and trait (p=0.02, Cohen d = 0.60) anxiety decreased while the general self-efficacy increased (p=0.03, Cohen d = 0.76). No participant stopped the use of the pump.
Conclusion
Adult patients with T1D previously treated with MDI and naïve to modern technologies experienced significant improvement in their psychological well-being after transitioning to the AHCL system after 12 months of treatment.
Abstract Our aim was to investigate the reliability of ultra-short HRV in patients with DM. A good correlation was found between the 1 minute and 5 minute parameters for maximal-RR, minimal-RR, ...average-RR, SDNN, RMSSD, pNN50, and total power. Also, a good correlation between 10 second and 5 minute parameters was found for maximal-RR, minimal-RR, average-RR, and RMSSD. We suggest that certain ultra-short HRV parameters can be used efficiently in DM patients for autonomic evaluation.
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is a complicated condition genetically, clinically, and treatment wise. Genetically, there are numerus mutations with different ...effect on enzyme activity that make genetic diagnosis a challenge. Clinically, there are a wide range of presentations from asymptomatic patients to the severe life-threatening classic CAH. Both an asymptomatic heterozygote and a mildly affected non-classical patient can carry a ‘severe’ mutation and endow it to their offspring. We present a case of non-classic CAH and discuss the problematic relations between biochemical and genetic diagnosis. By integrating the seemingly contradicting literature, we provide a new simple tool to assess the risk of such patients to give birth to a child with classic CAH.
Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency varies clinically from asymptomatic or mild disease (non-classic), through ‘simple virilizing’ type, to a severe life-threatening condition (classic) due to adrenal insufficiency.‘Classic’ CAH patient must harbor two ‘severe’ mutations, one on each of the alleles of the 21OH gene.Prevention of the birth of a child with classic disease is a challenge as the heterozygote carrier of ‘severe’ mutation is usually asymptomatic with normal biochemical tests, and a ‘non-classic’ patient can still carry a ‘severe’ mutation.Genetic diagnosis is a challenge, as there are numerus mutations including deletions, intronic mutations, double and triple mutations, and pseudogenes.In this article, we provide a new simple tool to assess the risk of a couple to give birth to a child with ‘classic’ disease.
To assess whether the socioeconomic and stereotypical barriers for the adoption of advanced diabetes technologies can be overcome in the underprivileged children and their families in India, ...predominantly from the rural areas, by providing insulin pump therapy (CSII) to deserving patients.
All patients were selected from the type 1 diabetes mellitus (T1DM) database of the Kovai Medical Center and Hospital, Coimbatore. Sixteen people with type 1 diabetes (PWD) were chosen due to poor control or an urgent situation like pregnancy or renal failure. Demographic data along with variables such as age, sex, time of diagnosis of T1DM, duration of CSII therapy, total daily insulin dose, hypoglycaemias, hospitalisations, glycosylated haemoglobin pre- and post-pump were collected. The glycosylated haemoglobin values were collected at 3, 6 and 12 months, post-CSII hypoglycaemia was defined as self-reported hypoglycaemia by the patient.
During 12 month follow-up, all 16 PWD were using the insulin pump with significant reductions in HbA1c from 11.4% at baseline to 8.0% (
< 0.001) and 7.6% at the end of 3 and 6 months, respectively.
Our results indicate that the CSII therapy without prejudice can lead to significant reductions in glycaemic control, hospitalisations and quality of life. This pilot work will help us lobby government policy makers to ensure policy changes that help the underprivileged with T1DM in India.
Dopaminergic neurons are specialized cells in the substantia nigra, tasked with dopamine secretion. This secretion relies on intracellular calcium signaling coupled to neuronal electrical activity. ...These neurons are known to display spontaneous calcium oscillations
and
, even in synaptic isolation, controlling the basal dopamine levels. Here we outline a kinetic model for the ion exchange across the neuronal plasma membrane. Crucially, we relax the assumption of constant, cytoplasmic sodium and potassium concentration. We show that sodium-potassium dynamics are strongly coupled to calcium dynamics and are essential for the robustness of spontaneous firing frequency. The model predicts several regimes of electrical activity, including tonic and 'burst' oscillations, and predicts the switch between those in response to perturbations. 'Bursting' correlates with increased calcium amplitudes, while maintaining constant average, allowing for a vast change in the calcium signal responsible for dopamine secretion. All the above traits provide the flexibility to create rich action potential dynamics that are crucial for cellular function.
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