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Evolution of the Artificial Pancreas: Components and Integration-CGMs, Insulin, and AP Systems.

The landmark Diabetes Control and Complications Trial (DCCT) showed that glucose control is critical to reducing the risk of diabetes-related complications. This chapter outlines a series of innovations and investigations that followed the DCCT, aimed at minimizing the risk of hypoglycemia while further improving glucose control. The chapter presents an example of innovations in wired enzyme technology that facilitated the movement from capillary glucose monitoring to continuous glucose monitoring (CGM) and ultimately, the first-factory calibrated CGM system. The next glycemic management innovation was to connect CGM data to an insulin pump containing an algorithm able to adjust insulin delivery based on the changing glucose levels and trends. The key features of automated insulin delivery (AID) systems, currently approved in the United States, are presented. The AID summary table includes type of pump, type and function of the insulin delivery algorithm, the data management system, and the indications for use. The next section explores the innovation of alternative routes of insulin delivery to move toward the goal of a fully automated insulin delivery system. The main trials in developing and implementing an implantable intraperitoneal programmable system are summarized. The last section explores if sensor input in addition to glucose levels such as continuous sensing of ketone, lactate, or insulin levels may provide valuable feedback to move us closer to a fully autonomous AID system. Much of this diabetes innovation and investigation work has been supported by the National Institute of Diabetes and Digestive and Kidney Diseases over that last 75 years.

Humans

Acute mild cold exposure with shivering reduces 24 h glucose levels in individuals with type 2 diabetes but not prediabetes.

AIMS/HYPOTHESIS: Repeated cold exposure with shivering has been proposed as a potential strategy to enhance glucose metabolism by increasing energy expenditure and substrate utilisation. However, acute effects/benefits of cold-induced shivering on glucose homeostasis in metabolically compromised individuals are unknown. Here, we aimed to determine whether cold exposure at two different intensities improves 24 h glucose homeostasis in individuals with prediabetes and type 2 diabetes. METHODS: In a randomised crossover trial conducted in the South Limburg/Maastricht region of the Netherlands, men and postmenopausal women with prediabetes (n=12) and stable type 2 diabetes (n=12), aged 40-75 years, body mass index &#x2265;27 and &#x2264;35 kg/m2, non-smoking and sedentary, underwent two whole-body cold exposure sessions using a water-perfused suit. Session order was randomised using an online randomisation tool (randomizer.org); participants were masked to the cold exposure intensity received, but investigators were not. Sessions were designed to elicit ~1.5-fold (mild, 15&#xb0;C) and ~2.5-fold (moderate, 4&#xb0;C) increases in resting metabolic rate (RMR). Continuous glucose monitoring assessed interstitial glucose concentrations over 24 h periods before and after each intervention, with controlled diet and activity. Shivering was confirmed via indirect calorimetry and electromyography. RESULTS: In both study groups and periods, RMR increased significantly vs baseline (p<0.001 for all). In prediabetes, the increase in the final 1 h of cold was 1.53&#xa0;&#xd7;&#xa0;RMR in mild and 1.94&#xa0;&#xd7;&#xa0;RMR in moderate cold. In type 2 diabetes, the increase was 1.57&#xa0;&#xd7;&#xa0;RMR and 2.09&#xa0;&#xd7;&#xa0;RMR in the final 1 h of mild and moderate cold, respectively. In prediabetes, neither mild nor moderate cold exposure altered mean 24 h glucose levels. In contrast, after mild cold exposure the type 2 diabetes group exhibited a significant reduction in mean 24 h glucose levels (-0.6&#xa0;&#xb1;&#xa0;0.5 mmol/l, p=0.003) and fasting glucose (-0.6&#xa0;&#xb1;&#xa0;0.8 mmol/l, p=0.019), as well as an increase in time in normal range (+8.8&#xa0;&#xb1;&#xa0;10.3%, p=0.013) and reduced time in hyperglycaemia (-10.9&#xa0;&#xb1;&#xa0;12.9%, p=0.014). Moderate cold did not significantly affect any of the glucose outcomes in type 2 diabetes. Baseline fasting glucose, age and ALT levels were predictors of the glucose-lowering response, suggesting greater benefits in individuals who have higher baseline glucose levels, are younger and/or have more optimal liver health, i.e. lower ALT. CONCLUSIONS/INTERPRETATION: Acute mild cold exposure with shivering reduced 24 h glucose levels in individuals with type 2 diabetes. No changes were observed in prediabetes. The observed effects appear to depend on baseline metabolic status rather than acute substrate utilisation during cold exposure. These findings support the potential of cold exposure as an adjunct non-pharmacological therapy for type 2 diabetes, although further mechanistic studies and validation in larger cohorts are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT05576025 FUNDING: Dutch Organisation for Knowledge and Innovation in Health, Healthcare and Well-being (ZonMw): 09120012010062.

Humans

The characteristics of a new glucose sensor for use in an artificial pancreatic beta cell.

A new glucose sensor has been developed for the continuous extracorporeal monitoring of blood glucose concentrations in conjunction with an artificial pancreatic beta cell simulator. This sensor has a rapid ninety percent response time (less than 1 min), is stable for periods of up to 140 hours of accumulated use and can be calibrated without the use of a reference glucose analyzer. Its reliability has been confirmed in over 100 clinical studies. A comparison of this sensor to other glucose sensors designed for artificial pancreatic beta cell devices is made and the sensor is shown to be the most advanced glucose sensor presently available for extracorporeal continuous glucose monitoring in man.

Artificial Organs

Continuous blood glucose monitoring and characteristics of diabetes in patients on maintenance haemodialysis treatment.

The glucose metabolism of diabetes mellitus during maintenance haemodialysis treatment was studied in four patients with endstage renal failure. There was a large day-to-day variation in the predialysis blood glucose levels, which it was difficult to control by adjusting the insulin dose. In spite of very high blood glucose levels, blood lactate and beta-hydroxybutyrate were not elevated. Triglycerides were markedly and constantly elevated, in no apparent association with the predialysis blood glucose level. The patients were shown to release moderate amounts of glucose, beta-hydroxybutyrate and lactate into the dialysate during the dialysis period. A technique of continuous blood glucose monitoring during the haemodialysis period was applied. With this technique blood sugar levels were accurately determined during the whole dialysis period. A rapid drop in the blood glucose level was found in apparent association with an aggravation of symptoms. A very marked tendency to hypoglycaemia was also revealed. It is concluded that the technique is a valuable aid in the proper management of diabetes in these cases.

Adult

Factors Associated With Progression From Level 1 to Level 2 Sensor-Detected Hypoglycaemia in People With Type 1 and Insulin-Treated Type 2 Diabetes: A Post Hoc Analysis From the Hypo-METRICS Study.

AIMS: We investigated the proportion of sensor-detected hypoglycaemic (SDH) events progressing to level 2, and associated variables. MATERIALS AND METHODS: We used data from Hypo-METRICS, which recruited people with type 1 (pwT1D) and insulin-treated type 2 diabetes (pwT2D) with &#x2265;&#x2009;1 hypoglycaemic event in preceding 3&#x2009;months, wearing blinded continuous glucose monitoring devices (CGM), additional to usual monitoring modality, and FitBits for 10&#x2009;weeks. We defined: L1: SDH <&#x2009;3.9&#x2009;mmol/L for &#x2265;&#x2009;15&#x2009;min but &#x2265;&#x2009;3.0&#x2009;mmol/L; L2: SDH <&#x2009;3.9&#x2009;mmol/L with &#x2265;&#x2009;15&#x2009;min of sensor glucose <&#x2009;3.0&#x2009;mmol/L; L2 ratio&#x2009;=&#x2009;L2/(L1&#x2009;+&#x2009;L2), restricted to participants with both event types during the study period. Associations of selected variables on L2 ratio was assessed using beta regression and purposeful variable selection. RESULTS: We analysed 23&#x2009;768 SDH events from 212 pwT1D and 213 pwT2D. PwT1D were predominantly female (53% vs. 42% in T2D, p&#x2009;=&#x2009;0.023) and younger (median age 49 vs. 62&#x2009;years, p&#x2009;<&#x2009;0.001), with a higher L2 ratio (16% vs. 14%, p&#x2009;=&#x2009;0.03). Coefficient of variation (CV), OR&#x2009;=&#x2009;1.07, 95% CI&#x2009;=&#x2009;1.06-1.09 (p&#x2009;<&#x2009;0.001), and mean sensor glucose, OR&#x2009;=&#x2009;1.13, 95% CI&#x2009;=&#x2009;1.08-1.18 (p&#x2009;<&#x2009;0.001) were the principal predictors in T1D and T2D respectively; mean L1-SDH duration, weekly L1-SDH frequency, personal CGM usage, impaired awareness were not. Progression was higher during sleep than wakefulness (21% vs. 11%, p&#x2009;<&#x2009;0.001); L2 ratios during sleep did not differ by awareness status. CONCLUSIONS: Approximately one sixth of SDH events progressed to L2, with a higher proportion in T1D than T2D. The principal determinants were CV in T1D and mean glucose in T2D. Awareness status was not associated with progression risk during sleep.

Humans

Continuous Intraperitoneal Insulin Infusion for People With Type 1 Diabetes: A Literature Review and International Position Statement.

Achieving glucose targets without hypoglycaemia is the treatment goal in type 1 diabetes. Structured education, intensified insulin injection regimens, continuous glucose monitoring, automated insulin delivery, and ongoing support from a multidisciplinary team all support people with type 1 diabetes to achieve this goal. Despite these advances, significant barriers to achieving optimal management remain. Continuous intraperitoneal insulin infusion has comparable or better glucose outcomes to continuous subcutaneous insulin infusion and may reduce the frequency of hypoglycaemia, including severe episodes. Intraperitoneal insulin may be considered as a treatment modality for children and adults with type 1 diabetes using optimised intensive insulin therapy for whom subcutaneous insulin has failed due to lipoatrophy, -dystrophy or -hypertrophy, local allergy, subcutaneous insulin resistance or co-existing skin conditions. Failure of subcutaneous insulin may result in recurrent or unexplained severe hypoglycaemia or hyperglycaemia. Intraperitoneal insulin may also be considered as a treatment modality for people with type 1 diabetes with severe needle-phobia, and for those being considered for islet cell or pancreatic transplantation, or where transplantation is not available. This paper summarises current intraperitoneal insulin delivery technology, its potential risks and benefits, and an expert position statement. It is intended for use by diabetes specialist healthcare professionals, and as a reference for other healthcare professionals, commissioners, payors, people with diabetes, their carers, and advocates.

Humans

Effects of continuous isomaltulose-containing gummy intake on interstitial glucose and salivary hormones during an 18-hole golf round: a randomized, double-blind controlled pilot study.

BACKGROUND: Golf is a prolonged, moderate-intensity sport requiring sustained physiological stability to manage cumulative stress and maintain performance. Although carbohydrate intake is commonly used to reduce fatigue, rapidly absorbed sugar-induced rapid blood glucose fluctuations may induce volatile arousal and latent metabolic stress. Isomaltulose, a slow-digesting disaccharide, provides a steadier glucose supply compared with sucrose. This exploratory pilot study examined the effects of isomaltulose intake on physiological stress markers, glycemic dynamics, and subjective responses during a competitive 18-hole golf round. METHODS: Twenty-three male collegiate golfers were randomized to either the isomaltulose group (ISO; n&#x2009;=&#x2009;12) or the sucrose group (CON; n&#x2009;=&#x2009;11) in a double-blind controlled trial. Participants consumed gummies containing isomaltulose or sucrose immediately after each hole (12.1 g carbohydrate per hole; total carbohydrate intake: 217.5 g). Primary outcomes were salivary stress markers [cortisol, testosterone, and dehydroepiandrosterone sulfate (DHEAS)] levels. Secondary outcomes included interstitial glucose concentration measured via continuous glucose monitoring, subjective assessments (i.e. sleepiness, relaxation, and concentration), and golf performance (18-hole score). Between-group comparisons at each time point were conducted using planned Welch's t-tests. RESULTS: No significant between-group differences were observed for 18-hole score (p&#x2009;=&#x2009;0.38) or mean interstitial glucose concentration (p&#x2009;=&#x2009;0.20). However, exploratory analyses revealed distinct hormonal variations; salivary DHEAS and testosterone levels were higher in the ISO group during the latter half of the round (p&#x2009;<&#x2009;0.05), whereas both declined in the CON group. Regarding glycemic variability, the ISO group demonstrated a more stable glucose profile with a medium effect size for lower standard deviation (ISO: 14.7&#x2009;&#xb1;&#x2009;1.9 vs. CON: 16.7&#x2009;&#xb1;&#x2009;4.6 mg/dL; d&#x2009;=&#x2009;0.58), although this difference was not significant. Conversely, subjective outcomes diverged; the CON group reported significantly greater subjective arousal (wakefulness and relaxation) (p&#x2009;<&#x2009;0.01) relative to the ISO group. CONCLUSIONS: In conclusion, continuous intake of isomaltulose-containing gummies during an 18-hole golf round was associated with differences in selected physiological markers, including DHEAS and testosterone concentrations. However, these findings were not accompanied by improvements in objective golf performance outcomes compared with sucrose-containing gummies. Isomaltulose may influence glycemic dynamics and hormonal responses during prolonged golf play; however, the practical significance of these effects remains exploratory. Further studies with larger sample sizes and appropriate repeated-measures frameworks are needed to determine whether such physiological changes translate into meaningful performance or recovery benefits.

Humans

Interaction of melatonin receptor 1B (MTNR1B) genotype and type of breakfast (protein-enriched v carbohydrate-rich) on postprandial glucose response: a randomised crossover trial.

BACKGROUND: The risk allele (G) of MTNR1B rs10830963 has been associated with impaired glucose tolerance, increased fasting glucose and type 2 diabetes (T2D). Late evening eating, when endogenous melatonin levels are elevated, is associated with impaired glucose control in MTNR1B risk carriers. Endogenous melatonin levels remain elevated into the morning so may influence glucose response to breakfast. OBJECTIVE: To investigate the interaction of MTNR1B genotype and type of breakfast on postprandial glucose response in a real-world setting. METHODS: Following an overnight fast, participants consumed either a standard carbohydrate-rich or protein-enriched porridge breakfast. Post-prandial glucose levels were recorded for two hours using a continuous glucose monitor (CGM). One week later, participants repeated the protocol consuming the alternate breakfast. A two-way mixed ANOVA determined the effect of breakfast and genotype on post-prandial glucose levels. RESULTS: Fifty-four adults completed the study. Fasting glucose was significantly higher (p&#x2009;=&#x2009;0.008) in GG (5.53&#x2009;&#xb1;&#x2009;0.43&#x2009;mmol/L) compared to CC or CG participants (5.02&#x2009;&#xb1;&#x2009;0.42 and 5.19&#x2009;&#xb1;&#x2009;0.52&#x2009;mmol/L). Post-prandial iAUC was significantly greater following the carbohydrate-rich breakfast compared to the protein-enriched breakfast (p&#x2009;<&#x2009;0.001). Following the carbohydrate-rich breakfast iAUC was significantly greater in GG participants compared to CC (p&#x2009;=&#x2009;0.026) and CG participants (p&#x2009;=&#x2009;0.029). There was no significant difference between genotype groups following the protein-enriched breakfast (p&#x2009;>&#x2009;0.05). CONCLUSION: The study findings demonstrate, in a relatively young and healthy population, MTNR1B genotype significantly affects markers associated with T2D risk. Personalised genotype-based advice to adjust timing and composition of meals consumed when endogenous melatonin levels are increased may reduce subsequent T2D risk.

Humans

Duration and characteristics of hypoglycemia with once-weekly insulin efsitora alfa versus once-daily basal insulins in adults with type 2 diabetes: Exploratory safety analysis of QWINT 2-4.

AIMS: Efsitora is a novel once-weekly basal insulin. Efsitora demonstrated similar efficacy and safety compared with once-daily basal insulin comparators across four phase 3 clinical trials for type 2 diabetes. This exploratory safety analysis further characterizes hypoglycemia events in the efsitora and once-daily treatment groups in three of these trials (QWINT-2, -3, and -4). METHODS: Median duration of hypoglycemia events was assessed with masked continuous glucose monitoring. Incidence of persistent-recurrent (PR) hypoglycemia was assessed by investigators and by a pre-specified algorithm using SMBG e-diary data. Factors contributing to hypoglycemia, characteristics of hypoglycemia, and treatment methods were reported by participants and assessed across groups. RESULTS: Across the three trials, durations of hypoglycemic events for efsitora vs once-daily basal insulin comparators were: Level 1 and 2 [<70&#xa0;mg/dL]: 40-42.5 vs 40&#xa0;min; Level 2 [<54&#xa0;mg/dL]: 35-39.9 vs 35&#xa0;min. Few incidences of PR hypoglycemia were reported for efsitora or once-daily comparators. No major descriptive differences were observed between hypoglycemia contributing factors, characteristics, or treatment methods in efsitora and once-daily treatment groups. CONCLUSIONS: No clinically relevant differences were observed between the duration or characteristics of hypoglycemic events in efsitora and once-daily treatment groups in the QWINT-2, -3, and -4 trials.

Adult

Relationship between participant-reported outcomes, residual beta cell function and metabolic parameters in youth with newly diagnosed type 1 diabetes.

AIMS/HYPOTHESIS: Clinical trials of interventions to preserve beta cell function in new-onset type 1 diabetes frequently employ participant-reported outcome measures (PROMs). However, the expected changes in PROMs scores immediately following diagnosis and their association with residual beta cell function, metabolic markers and continuous glucose monitoring (CGM) are unclear. METHODS: Repeated PROMs including Paediatric Quality of Life Inventory diabetes module (PedsQL) and hypoglycaemia fear survey (HFS) were recorded from participants aged 10-18 years with newly diagnosed type 1 diabetes and their parents in two clinical trials: CLOuD (N=97, hybrid closed loop [HCL] vs multiple daily injections [MDI]) and USTEKID (N=72, ustekinumab immunotherapy vs placebo). Scores were compared with serial mixed meal-stimulated C-peptide levels (AUC C-peptide), HbA1c and CGM data. RESULTS: PedsQL and HFS scores for children/adolescents and their parents showed wide variation between individuals but did not change substantially within individuals over the first 48 months from diagnosis. Baseline scores were highly predictive of scores at 12-48 months (p<0.001). PedsQL scores were higher (better) in those reported by children/adolescents than by their parents (p<0.01). In contrast, HFS scores were higher in parents than children (p<0.001), indicating more fear. Strong correlations were observed between child and parent scores (p<0.001). No significant improvement in these scores was detected following intervention (ustekinumab or HCL). Meta-analysis revealed modest but statistically significant associations between HbA1c and PedsQL (&#x3b2;(std)=-0.11; 95% CI -0.20, -0.03) and HFS (&#x3b2;(std)=0.11; 95% CI 0.00, 0.21), and between CGM time in range and PedsQL (&#x3b2;(std)=0.14; 95% CI 0.03, 0.26) but not HFS (&#x3b2;(std)=-0.05; 95% CI -0.16, 0.06). Beta cell function (AUC C-peptide) was strongly associated with HbA1c (&#x3b2;(std)=-0.29; 95% CI -0.39, -0.20) and CGM time in range (&#x3b2;(std)=0.41; 95% CI 0.30, 0.52). Higher beta cell function showed a trend towards better PedsQL (&#x3b2;(std)=0.11; 95% CI -0.03, 0.25) and lower HFS (&#x3b2;(std)=-0.05; 95% CI -0.17, 0.07) but this did not reach statistical significance. CONCLUSIONS/INTERPRETATION: PedsQL and HFS scores changed little during the first 48 months after diagnosis of type 1 diabetes. These scores showed modest but statistically significant associations with measures of glucose management (HbA1c and CGM time in range), whereas the relationships with residual beta cell function (C-peptide) were weaker and did not reach significance. The modest size of these effects suggests current PROMs capture only limited aspects of the clinical benefit associated with beta cell preservation. Future research should incorporate psychometric instruments that are specifically adapted for young people using modern diabetes technologies and undergoing disease-modifying therapy, to ensure outcomes are meaningfully represented in early-stage type 1 diabetes trials.

Adolescent

Diagnostic utility of fasting versus non-fasting blood glucose: contextualising testing strategies-a narrative review.

Diabetes mellitus is a chronic metabolic disorder characterised by impaired glucose homeostasis, resulting in persistent hyperglycaemia. Accurate and prompt diagnosis is essential for early intervention and prevention of long-term complications. Fasting blood glucose levels have traditionally been central to the diagnosis and monitoring of diabetes mellitus. However, growing evidence highlights the clinical relevance of non-fasting glucose measures, including postprandial glucose, random plasma glucose, and glycated haemoglobin (HbA1c) levels. Practical challenges, safety concerns, and evolving insights into glucose physiology have prompted renewed interest in flexible and context-driven approaches to glucose testing. This narrative review examines the physiological basis of fasting and non-fasting glucose regulation and critically evaluates their roles in diabetes screening, diagnosis, and monitoring. It also discusses the strengths and limitations of measuring fasting blood glucose, oral glucose tolerance, HbA1c, random plasma glucose, postprandial glucose, and continuous glucose monitoring. Special attention is given to pre-analytical and practical considerations, patient safety, and the ability of non-fasting measures to capture early metabolic dysfunction and real-world glycaemic exposure. This article reviews evidence supporting the prognostic value of postprandial hyperglycaemia and the expanding role of non-fasting monitoring tools. Non-fasting glucose testing offers substantial advantages in terms of accessibility, safety, and clinical relevance, and is well-suited for population screening and routine diabetes monitoring. Fasting glucose testing remains essential for specific diagnostic and research applications, particularly when strict metabolic standardisation is required. A context-driven framework that prioritises non-fasting approaches while reserving fasting tests for targeted indications provides a balanced and patient-centred strategy for contemporary diabetes care.

Diabetes screening

Effects of time-restricted eating on markers of glucose metabolism and regulation in individuals with prediabetes or type 2 diabetes: a systematic review and meta-analysis of randomised controlled trials.

AIMS/HYPOTHESIS: This systematic review and meta-analysis aimed to investigate the effects of time-restricted eating (TRE) on glucose metabolism and regulation in individuals with prediabetes (fasting blood glucose of 5.6-6.9 mmol/l or HbA1c of 39-47 mmol/mol [5.7-6.4%]) or type 2 diabetes (fasting blood glucose &#x2265;7 mmol/l or HbA1c &#x2265;48 mmol/mol [6.5%]). METHODS: A literature search was performed in MEDLINE, Embase and CENTRAL from inception to 5 August 2025. Moreover, forward and backward citation searches were performed. Eligible studies were RCTs in adults with prediabetes or type 2 diabetes, lasting &#x2265;2 weeks, reporting markers of glucose metabolism and regulation, comparing TRE (&#x2264;12 h eating window) with a non-time-restricted control diet. Studies involving pregnancy, other fasting regimens, or non-peer-reviewed publications were excluded. Data were pooled as weighted mean differences with 95% CIs using random-effects generic inverse variance models in Cochrane Review Manager Web, and results are presented as forest plots. The certainty of evidence was defined using Grading of Recommendations, Assessment, Development and Evaluations methodology, and risk of bias was estimated by using the Revised Cochrane risk-of-bias tool for randomised trials (RoB 2). RESULTS: Out of 2043 records identified through the database search, as well as 1249 from forward and backward citation searches, ten RCTs including 599 participants were included. The mean length of the studies was 4 months, and the eating windows ranged from 4 to 10 h per day. The pooled meta-analysis showed no overall effect of TRE on HbA1c (-3.33 mmol/mol; 95% CI -6.87, 0.20 (-0.30% points; -0.63, 0.02); p=0.06, moderate certainty). Nevertheless, following stratification by subgroups, TRE resulted in a reduction in HbA1c of 0.93 mmol/mol (-1.70, -0.17 [-0.09% points; -0.16, -0.02]; p=0.02) in individuals with prediabetes but not in individuals with type 2 diabetes (-4.68 mmol/mol; -10.08, 0.72 (-0.43% points; -0.92, 0.07); p=0.09). TRE reduced fasting blood glucose in the pooled analysis (-0.30 mmol/l; -0.53, -0.07; p<0.01, moderate certainty) as well as in the subgroup analyses in individuals with prediabetes (-0.14 mmol/l; -0.27, -0.01; p=0.03) and with type 2 diabetes (-0.48 mmol/l; -0.78, -0.17; p<0.01). Moreover, TRE lowered body weight by 1.6 kg (-2.2, -1.0; p<0.001) in the pooled analysis. The evidence was limited by imprecision arising from wide confidence intervals in some of the included studies, which may be due to small sample sizes. Lastly, the effects of TRE on markers of insulin sensitivity, beta cell function and continuous glucose monitoring measurements were inconclusive. CONCLUSIONS/INTERPRETATION: Moderate-certainty evidence indicates that TRE reduces fasting blood glucose but not HbA1c. The subgroup analyses revealed that TRE improved HbA1c and fasting glucose in individuals with prediabetes and improved fasting glucose in individuals with type 2 diabetes. Future large-scale studies should investigate long-term effects of TRE in prevention and treatment of type 2 diabetes. TRIAL REGISTRATION: PROSPERO CRD42024523591 FUNDING: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Three authors (JS, A-DT, THA) are employed at Steno Diabetes Center Copenhagen, a public hospital and research institution under the Capital Region of Denmark, partly funded by a grant from the Novo Nordisk Foundation.

Humans

Continuous monitoring and control of plasma glucose during operation for removal of insulinomas.

A glucose-controlled insulin and glucose infusion system (Biostator system, Miles Laboratories Inc., Elkhart, Ind.) was used during operation for removal of four suspected insulinomas. In two patients the Biostator system continuously monitored plasma glucose levels and, through a computer-controlled feedback mechanism, automatically infused insulin or glucose as needed. In this way plasma glucose could be kept at approximately 110 mg/dl throughout the procedure. In one patient a rise in insulin infusion rate and a fall in glucose infusion rate followed removal of the tumor. In the other, absence of these findings was consistent with the clinical suspicion that the source of hypoglycemia had not been removed. In two other patients the Biostator system continuously monitored the patient's plasma glucose, without feedback-controlled administration of insulin or glucose. This demonstrated that, in these patients, tumor manipulation and removal did not lead to severe hypoglycemia, and thus eliminated any need to prophylactically infuse large amounts of glucose. Successful tumor removal was followed by a rise in blood glucose levels in both of these individuals. The glucose-controlled insulin and glucose infusion system appears to be a useful instrument for intraoperative management of patients with suspected insulinomas.

Adenoma, Islet Cell

Technology choice, glycemic control and patient-reported outcome measures in adults with type 1 diabetes: A randomized crossover trial comparing a smart insulin pen with an automated insulin delivery system (EBIACE-1).

AIMS: To compare glycemic outcomes and patient-reported outcome measures (PROMs) between smart insulin pens (SIP) and an automated insulin delivery (AID) system in adults with type 1 diabetes (T1D), and to identify individuals able to maintain near-optimal glycemic control using SIP. METHODS: EBIACE-1 was a randomized, open-label, crossover trial including 31 adults with T1D. Participants received SIP (InPen&#x2122;) and AID (MiniMed&#x2122; 780G) for 6&#xa0;months each. Co-primary outcomes were time in range (TIR 70-180 mg/dL) and HbA1c. Treatment effects were assessed using longitudinal models in intention-to-treat (ITT) and per-protocol (PP) analyses. Predictors of near-optimal glycemic control with SIP were evaluated using multivariable logistic regression. RESULTS: AID improved glycemic control versus SIP, with higher TIR (81&#xa0;% vs 66&#xa0;%; +15&#xa0;%, 95&#xa0;% CI 10-19; P&#xa0;<&#xa0;0.001) and lower HbA1c (6.9&#xa0;% [52&#xa0;mmol/mol] vs 7.3&#xa0;% [56&#xa0;mmol/mol]; -0.4&#xa0;%, 95&#xa0;% CI&#xa0;-&#xa0;0.6 to&#xa0;-&#xa0;0.3; P&#xa0;<&#xa0;0.001). Near-optimal glycemic control with SIP was achieved by 12 of 26 participants (46&#xa0;%). In exploratory analyses, higher baseline diabetes-related life interference was associated with a lower probability of achieving this outcome. CONCLUSIONS: AID provides superior glycemic control, although nearly half of participants achieved near-optimal control with SIP, supporting a personalized approach to technology selection.

Adult

[Late hypoglycaemia in chemical diabetes. Abnormalities of pancreatic glucagon secretion and effect of pectine (author's transl)].

Nineteen patients suffering from chemical diabetes either with (group A, ten cases) or without (group B, nine cases) reactive hypoglycaemia were included in the study and compared with seven control (group C). The following variables were measured over a 5 hour period during a standard oral glucose tolerance test (OGTT): (i) blood glucose by continuous monitoring; (ii) plasma insulin and glucagon levels by radioimmunoassay. Furthermore, in five diabetics of group A, the data from the standard OGTT were compared with those from a pectin-supplemented OGTT (9 g per square meter of body surface). Although the insulin response was similar glucagon levels were significantly higher (45.1 +/- 11.8 pmol/l) (p less than 0.01) in group B than in group A (9.6 +/- 1.3) and C (8.1 +/- 1.4 at 30 minutes). The high glucagon levels noted in group B may explain the absence of reactive hypoglycaemia. The pectin supplementation improved the OGTT pattern by blunting the blood glucose peak (p less than 0.05), and avoiding the reactive hypoglycaemia (p less than 0.01). The addition of pectin did not produce any significant effect on the insulin response while a significant increase in glucagon concentrations (p less than 0.05) was observed beyond the 150th minute. Therefore, the data suggest that pectin may improve the OGTT pattern by increasing the glucagon response in the late period of the test. The development of postprandial reactive hypoglycaemia seldom coincides with a plasma glucagon peak, while the absence of reactive hypoglycaemia tends to be associated with high levels of glucagon, as is the case in overt diabetes mellitus.

Adult

The artificial beta cell (Biostator) in the adjustment of instable diabetics--results after 20 months.

In 55 poorly controlled insulin-dependent diabetics, we tried to discover criteria for an improvement of metabolism by means of the "artificial beta-cell" (Biostator). To this end, during the first 24 h of hospitalization, blood glucose was monitored continuously under conventional insulin therapy (monitoring period). Insulin requirement was determined during the next 24 h by the artificial beta-cell (feedback period). Corrections of diabetes regimen were made with reference to the insulin consumption during the feedback period and to the extent of the postprandial blood sugar increases and decreases during the monitoring period. The resulting new diabetes regimen led to a significant improvement of the daily blood sugar profiles.

Artificial Organs

Dual-approach analysis of gut microbiome in patients with type 1 diabetes and diabetic kidney disease.

BACKGROUND: Type 1 diabetes (T1D) is a multifactorial autoimmune disease mediated by genetic, epigenetic, and environmental factors. Diabetic kidney disease (DKD) is a major complication of diabetes mellitus which affects 30-40% of T1D patients. Increasing evidence suggests the significant role of the microbiome in the progression of both T1D and DKD. MATERIALS AND METHODS: Here we recruited 76 T1D patients and 22 healthy controls and combined data from sigmoid colon biopsy samples analysed with V3-V4 region amplification of 16S rRNA gene and shotgun metagenomics data obtained from faecal samples. Additionally, we compared T1D patients with and without progression of DKD. RESULTS: We observed significant differences within both sample types at various taxonomic and functional levels. T1D patient microbiota detected using biopsy samples had a lower abundance of the Bacteroides genus when compared to healthy controls. Significantly, despite only a few taxonomic differences patients with and without DKD progression were vastly different at the functional pathway level within the faecal samples - we observed 2 and 61 enriched pathways in these groups. respectively, with several of these pathways linked to the mediation of renal function. CONCLUSION: Altogether, we present novel data about microbial signatures relevant to T1D and DKD progression, which partly supports previous data and also presents possible tissue type or population-specific elements. DKD progression is characterized with significant differences within the functional level of the gut microbiome.

Humans