Continuous glucose monitoring in adults with type 2 diabetes: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: Continuous glucose monitoring (CGM) is increasingly used in the treatment of type 2 diabetes, but the effects on glycaemic control are unclear. The aim of this systematic review and meta-analysis is to provide a comprehensive overview of the effect of CGM on glycaemic control in adults with type 2 diabetes. METHODS: We performed a systematic review using Embase, MEDLINE, Web of Science, Scopus and ClinicalTrials.gov from inception until 2 May 2023. We included RCTs investigating real-time CGM (rtCGM) or intermittently scanned CGM (isCGM) compared with self-monitoring of blood glucose (SMBG) in adults with type 2 diabetes. Studies with an intervention duration <6 weeks or investigating professional CGM, a combination of CGM and additional glucose-lowering treatment strategies or GlucoWatch were not eligible. Change in HbA1c and the CGM metrics time in range (TIR), time below range (TBR), time above range (TAR) and glycaemic variability were extracted. We evaluated the risk of bias using the Cochrane risk-of-bias tool version 2. Data were synthesised by performing a meta-analysis. We also explored the effects of CGM on severe hypoglycaemia and micro- and macrovascular complications. RESULTS: We found 12 RCTs comprising 1248 participants, with eight investigating rtCGM and four isCGM. Compared with SMBG, CGM use (rtCGM or isCGM) led to a mean difference (MD) in HbA1c of -3.43 mmol/mol (-0.31%; 95% CI -4.75, -2.11, p<0.00001, I2=15%; moderate certainty). This effect was comparable in studies that included individuals using insulin with or without oral agents (MD -3.27 mmol/mol [-0.30%]; 95% CI -6.22, -0.31, p=0.03, I2=55%), and individuals using oral agents only (MD -3.22 mmol/mol [-0.29%]; 95% CI -5.39, -1.05, p=0.004, I2=0%). Use of rtCGM showed a trend towards a larger effect (MD -3.95 mmol/mol [-0.36%]; 95% CI -5.46 to -2.44, p<0.00001, I2=0%) than use of isCGM (MD -1.79 mmol/mol [-0.16%]; 95% CI -5.28, 1.69, p=0.31, I2=64%). CGM was also associated with an increase in TIR (+6.36%; 95% CI +2.48, +10.24, p=0.001, I2=9%) and a decrease in TBR (-0.66%; 95% CI -1.21, -0.12, p=0.02, I2=45%), TAR (-5.86%; 95% CI -10.88, -0.84, p=0.02, I2=37%) and glycaemic variability (-1.47%; 95% CI -2.94, -0.01, p=0.05, I2=0%). Three studies reported one or more events of severe hypoglycaemia and macrovascular complications. In comparison with SMBG, CGM use led to a non-statistically significant difference in the incidence of severe hypoglycaemia (RR 0.66, 95% CI 0.15, 3.00, p=0.57, I2=0%) and macrovascular complications (RR 1.54, 95% CI 0.42, 5.72, p=0.52, I2=29%). No trials reported data on microvascular complications. CONCLUSIONS/INTERPRETATION: CGM use compared with SMBG is associated with improvements in glycaemic control in adults with type 2 diabetes. However, all studies were open label. In addition, outcome data on incident severe hypoglycaemia and incident microvascular and macrovascular complications were scarce. REGISTRATION: This systematic review was registered on PROSPERO (ID CRD42023418005).

Dual hormone fully closed loop in type 1 diabetes: a randomised trial in the Netherlands - study protocol.

INTRODUCTION: The management of type 1 diabetes (T1DM) has undergone significant advancements with the availability of novel technologies, notably continuous and flash glucose monitoring (CGM and FGM, respectively) and hybrid closed loop (HCL) therapy. The dual hormone fully closed loop (DHFCL) approach with insulin and glucagon infusion has shown promising effects in small studies on glycaemic regulation and quality of life in T1DM. METHODS AND ANALYSIS: The Dual Hormone Fully Closed Loop for Type 1 Diabetes (DARE) study is a non-commercial 12-month open-label, two-arm randomised parallel-group trial. The primary aim of this study is to determine the long-term effects on glycaemic control, patient-reported outcome measurements and cost-effectiveness of the DHFCL compared with usual care, that is, HCL or treatment with multiple daily insulin injections+FGM/CGM. We will include 240 adult patients with T1DM in 14 hospitals in the Netherlands. Individuals will be randomised 1:1 to the DHFCL or continuation of their current care. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Medical Research Ethics Committee NedMec, Utrecht, the Netherlands. Findings will be disseminated through peer-reviewed publications and presentations at local, national and international conferences. TRIAL REGISTRATION NUMBER: NCT05669547.

The PRolaCT studies - a study protocol for a combined randomised clinical trial and observational cohort study design in prolactinoma.

BACKGROUND: First-line treatment for prolactinomas is a medical treatment with dopamine agonists (DAs), which effectively control hyperprolactinaemia in most patients, although post-withdrawal remission rates are approximately 34%. Therefore, many patients require prolonged DA treatment, while side effects negatively impact health-related quality of life (HRQoL). Endoscopic transsphenoidal resection is reserved for patients with severe side effects, or with DA-resistant prolactinoma. Surgery has a good safety profile and high probability of remission and may thus deserve a more prominent place in prolactinoma treatment. The hypothesis for this study is that early or upfront surgical resection is superior to DA treatment both in terms of HRQoL and remission rate in patients with a non-invasive prolactinoma of limited size. METHODS: We present a combined randomised clinical trial and observational cohort study design, which comprises three unblinded randomised controlled trials (RCTs; PRolaCT-1, PRolaCT-2, PRolaCT-3), and an observational study arm (PRolaCT-O) that compare neurosurgical counselling, and potential subsequent endoscopic transsphenoidal adenoma resection, with current standard care. Patients with a non-invasive prolactinoma (< 25 mm) will be eligible for one of three RCTs based on the duration of pre-treatment with DAs: PRolaCT-1: newly diagnosed, treatment-naïve patients; PRolaCT-2: patients with limited duration of DA treatment (4-6 months); and PRolaCT-3: patients with persisting prolactinoma after DA treatment for > 2 years. PRolaCT-O will include patients who decline randomisation, due to e.g. a clear treatment preference. Primary outcomes are disease remission after 36 months and HRQoL after 12 months. DISCUSSION: Early or upfront surgical resection for patients with a limited-sized prolactinoma may be a reasonable alternative to the current standard practice of DA treatment, which we will investigate in three RCTs and an observational cohort study. Within the three RCTs, patients will be randomised between neurosurgical counselling and standard care. The observational study arm will recruit patients who refuse randomisation and have a pronounced treatment preference. PRolaCT will collect randomised and observational data, which may facilitate a more individually tailored practice of evidence-based medicine. TRIAL REGISTRATION: US National Library of Medicine registry (ClinicalTrials.gov) NCT04107480 . Registered on 27 September 2019, registered retrospectively (by 2 months).

Fully Closed Loop Glucose Control With a Bihormonal Artificial Pancreas in Adults With Type 1 Diabetes: An Outpatient, Randomized, Crossover Trial.

OBJECTIVE: To demonstrate the performance and safety of a bihormonal (insulin and glucagon) artificial pancreas (AP) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS: In this outpatient, randomized, crossover trial, 2-week fully closed loop glucose control (AP therapy) was compared with 2-week open loop control (patient's normal insulin pump therapy with a glucose sensor if they had one). RESULTS: A total of 23 patients were included in the analysis. Time in range (70-180 mg/dL [3.9-10 mmol/L]) was significantly higher during closed loop (median 86.6% of time [interquartile range 84.9-88.5]) compared with open loop (53.9% [49.7-67.2]; P < 0.0001). CONCLUSIONS: Compared with insulin pump therapy, the bihormonal AP provided superior glucose control, without meal or exercise announcements, and was safe in adults with type 1 diabetes.

SUGAR-DIP trial: oral medication strategy versus insulin for diabetes in pregnancy, study protocol for a multicentre, open-label, non-inferiority, randomised controlled trial.

INTRODUCTION: In women with gestational diabetes mellitus (GDM) requiring pharmacotherapy, insulin was the established first-line treatment. More recently, oral glucose lowering drugs (OGLDs) have gained popularity as a patient-friendly, less expensive and safe alternative. Monotherapy with metformin or glibenclamide (glyburide) is incorporated in several international guidelines. In women who do not reach sufficient glucose control with OGLD monotherapy, usually insulin is added, either with or without continuation of OGLDs. No reliable data from clinical trials, however, are available on the effectiveness of a treatment strategy using all three agents, metformin, glibenclamide and insulin, in a stepwise approach, compared with insulin-only therapy for improving pregnancy outcomes. In this trial, we aim to assess the clinical effectiveness, cost-effectiveness and patient experience of a stepwise combined OGLD treatment protocol, compared with conventional insulin-based therapy for GDM. METHODS: The SUGAR-DIP trial is an open-label, multicentre randomised controlled non-inferiority trial. Participants are women with GDM who do not reach target glycaemic control with modification of diet, between 16 and 34 weeks of gestation. Participants will be randomised to either treatment with OGLDs, starting with metformin and supplemented as needed with glibenclamide, or randomised to treatment with insulin. In women who do not reach target glycaemic control with combined metformin and glibenclamide, glibenclamide will be substituted with insulin, while continuing metformin. The primary outcome will be the incidence of large-for-gestational-age infants (birth weight >90th percentile). Secondary outcome measures are maternal diabetes-related endpoints, obstetric complications, neonatal complications and cost-effectiveness analysis. Outcomes will be analysed according to the intention-to-treat principle. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Utrecht University Medical Centre. Approval by the boards of management for all participating hospitals will be obtained. Trial results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NTR6134; Pre-results.

Acceptance of the Artificial Pancreas: Comparing the Effect of Technology Readiness, Product Characteristics, and Social Influence Between Invited and Self-Selected Respondents.

BACKGROUND: Psychosocial factors that may affect acceptance of artificial pancreas (AP) systems have been investigated in small sample sizes of highly motivated, self-selected persons with type 1 diabetes (T1DM) with a focus on product characteristics. We aimed to develop a valid survey to investigate the association of technology readiness and social influence with AP acceptance in a larger sample, including both self-selected and invited respondents with T1DM. METHODS: An online survey was developed based on established questionnaires. Intention to use the AP was chosen as measure of AP acceptance. T1DM patients who signed up themselves for scientific research into AP systems represented the self-selected group, while patients treated at a teaching hospital represented the invited group. Questionnaire values were compared using independent t-tests and regression analyses. RESULTS: The developed survey showed reliability and validity. The survey was completed by 425 self-selected and 109 invited persons. Intention to use the AP was high in both groups, but was significantly higher among self-selected respondents. In both groups, intention to use the AP was most strongly related to product compatibility, followed by product complexity, technology readiness, and product usefulness among invited respondents; and followed by product usefulness and technology innovativeness among self-selected respondents. CONCLUSIONS: Product characteristics have a stronger relationship with AP acceptance than technology readiness, while social influence does not seem to be associated with AP acceptance. As the (strength of) factors differ between self-selected and invited persons, researchers and product developers should be cautious when relying on self-selected persons with T1DM in the design, development, and testing of AP systems.

Web-based cognitive behavioural therapy blended with face-to-face sessions for chronic fatigue in type 1 diabetes: a multicentre randomised controlled trial.

BACKGROUND: Fatigue in type 1 diabetes is prevalent and persistent, but so far, no evidence-based treatments are available. We aimed to investigate the efficacy of cognitive behavioural therapy (CBT) in reducing fatigue severity in patients with type 1 diabetes. METHODS: We did a multicentre randomised controlled trial at one university medical centre and four large teaching hospitals in the Netherlands. Eligible patients were aged 18-70 years and had type 1 diabetes for at least 1 year and chronic fatigue for at least 6 months. We randomly assigned patients (1:1) to CBT or waiting list using computer-generated blocked randomisation, stratified by type of enrolment. The CBT intervention (Dia-Fit) was given for 5 months in blended form, consisting of face-to-face and web-based sessions. The primary outcome was fatigue severity assessed 5 months after randomisation, directly after the intervention or waiting list period, with the Checklist Individual Strength fatigue severity subscale. Secondary outcomes were functional impairment (assessed with the total score of the Sickness Impact Profile-8), glycaemic control (HbA1c), and glucose variability. Analyses were done by intention to treat. This trial is registered with the Nederlands Trial Register, number NTR4312. FINDINGS: Between Feb 6, 2014, and March 24, 2016, we randomly assigned 120 eligible patients to either CBT (n=60) or waiting list (n=60), all of whom were included in the intention-to-treat analyses. Compared with patients in the waiting list group, those in the CBT group had significantly lower fatigue severity scores (mean difference 13·8, 95% CI 10·0-17·5; p<0·0001) and significantly lower scores for functional impairment (mean difference 513, 95% CI 340-686; p<0·0001) after 5 months. HbA1c and glucose variability did not change after treatment and there was no difference between groups. Five patients in the CBT group and seven in the waiting list group reported adverse events; none were deemed to be related to the study intervention. INTERPRETATION: Although our findings need to be confirmed in larger and longer-term studies, they suggest that CBT can effectively reduce fatigue severity and functional impairment in type 1 diabetes. FUNDING: Dutch Diabetes Research Foundation (Diabetes Fonds).

A web-based cognitive behaviour therapy for chronic fatigue in type 1 diabetes (Dia-Fit): study protocol for a randomised controlled trial.

BACKGROUND: Fatigue is frequently reported by patients with type 1 diabetes mellitus. A recent study showed that 40 % of patients experienced severe fatigue that lasted for more than six months and was accompanied by substantial impairments in daily functioning. Currently, there is no effective treatment available for chronic fatigue in patients with type 1 diabetes. Cognitive behaviour therapy aimed at cognitions and behaviours that perpetuate fatigue is effective in reducing fatigue in other chronic diseases. Recent research showed that these cognitions and behaviours are also potential determinants of fatigue in type 1 diabetes. We designed Dia-Fit, a web-based cognitive behaviour therapy for severe and chronic fatigue in patients with type 1 diabetes. This patient-tailored intervention is aimed at reducing fatigue by changing cognitions and behaviours assumed to maintain fatigue. The efficacy of Dia-Fit will be investigated in this study. METHODS/DESIGN: A randomised controlled trial will be conducted in 120 patients with type 1 diabetes who are chronically and severely fatigued. Patients will be randomised to a treatment or waiting list group. The treatment group will receive Dia-Fit, a blended care therapy consisting of up to eight internet modules and face-to-face sessions with a therapist during a five-month period. The treatment will be tailored to the fatigue-maintaining cognitions and behaviours that are relevant for the patient and are determined at baseline. The waiting list group will receive Dia-Fit after a waiting period of five months. The primary outcome measure is fatigue severity. Secondary outcome measures are functional impairment and glucose control determined by haemoglobin A1c and blood glucose variability. DISCUSSION: To our knowledge, this is the first study investigating the efficacy of a cognitive behavioural intervention for chronic fatigue in patients with type 1 diabetes. TRIAL REGISTRATION: Dutch trial register NTR4312 (10 December 2013).

Feasibility of a portable bihormonal closed-loop system to control glucose excursions at home under free-living conditions for 48 hours.

BACKGROUND: This study assessed the feasibility of a portable bihormonal closed-loop system at home. SUBJECTS AND METHODS: Sixteen pump-treated patients with type 1 diabetes received 48 h of closed-loop therapy with a telemonitored insulin- and glucagon-delivering closed-loop system and 48 h of patient-managed open-loop therapy. RESULTS: Owing to technical problems in five cases, only 11 patients could be analyzed. Whereas median (interquartile range) glucose levels were not significantly different during Day 1 of open-loop control (OL1) from closed-loop control (CL1) (8.27 [0.83] mmol/L vs. 8.84 [1.47] mmol/L; P=0.206), they were significantly lower during Day 2 of closed-loop control (CL2) versus open-loop control (OL2) (7.70 [2.29] mmol/L vs. 8.84 [0.87] mmol/L; P=0.027). Time spent in euglycemia (3.9-10 mmol/L) was comparable with 67.2% (38.5%) in OL1 versus 79.2% (16.9%) in CL1 (P=0.189) and 66.0% (29.8%) in OL2 versus 76.5% (23.9%) in CL2 (P=0.162). Time spent in hypoglycemia (<3.9 mmol/L) was comparable on Day 1 of control (OL1, 0.68% [8.68%]; CL1, 2.08% [7.61%]; P=0.593) but significantly higher during Day 2 of control (OL2, 0.00% [11.07%]; CL2, 2.8% [9.8%]; P=0.0172) (P=0.017). CONCLUSIONS: Bihormonal closed-loop control is feasible at home, with comparable time in euglycemia to open-loop control and significantly lower median glucose levels on Day 2 of control at the expense of more time in hypoglycemia, albeit still at a very low percentage of time.

[Artificial pancreas for automated glucose control]. / Kunstpancreas voor geautomatiseerde glucoseregulatie.

Strict glucose control is important for patients with diabetes mellitus in order to prevent complications. However, many patients find it difficult to achieve the recommended HbA1c level. The possibility of hypoglycaemia plays an important role in this. The artificial pancreas automates glucose control, improving glucose levels without increasing hypoglycaemic events. The required insulin dose is calculated and administered on the basis of continuous glucose measurements, taking over a large part of the treatment from the patient. Several research groups are working on making this technique suitable for home use. It is expected that the artificial pancreas will become available in the near future. However, effectiveness and safety will have to be investigated in long-term studies. A large number of insulin-dependent patients with diabetes could be eligible for this treatment.

Feasibility of a bihormonal closed-loop system to control postexercise and postprandial glucose excursions.

BACKGROUND: The aim of this pilot study was to test the feasibility of a bihormonal (glucagon and insulin) closed-loop (CL) system by challenging the system with two meals and 30 min exercise. METHODS: Ten patients with type 1 diabetes treated with continuous subcutaneous insulin infusion underwent a standardized protocol on three different occasions: 40 g carbohydrate breakfast followed 2 h later by 30 min of moderate-intensity exercise, followed 1.5 h later by a standardized 60 g carbohydrate lunch. An open-loop (OL) day served as control, the first CL day as tuning experiment, and the second CL day to compare with OL. RESULTS: The overall mean venous glucose was similar: 9 (5.4-13.5) mmol/liter in OL versus 8.7 (6.4-11.0) mmol/liter in CL, p = .74. The postbreakfast glucose concentrations tended to be lower in OL than in CL [9.5 (4.3-13.3) versus 11.4 (7-16.2) mmol/liter; p = .07] and higher in OL than in CL postlunch [9.4 (6.0-14.9) versus 7.7 (5.5-9.0) mmol/liter,p = .15]. The postexercise glucose concentrations were similar in OL and CL: 7.5 (4.6-13) versus 8.2 (5.5-13.1) mmol/liter; p = .45. In those patients coming in with baseline glucose above 7 mmol/liter, there was initial overinsulinization in CL. During OL, two hypoglycemic episodes occurred compared with four hypoglycemic episodes in three participants during CL. Glucagon seemed mostly effective in preventing hypoglycemia. CONCLUSIONS: Overall, CL glucose control was comparable to OL control, but there was overinsulinization in those patients with baseline glucose above 7 mmol/liter.

Insulin glulisine compared to insulin aspart and to insulin lispro administered by continuous subcutaneous insulin infusion in patients with type 1 diabetes: a randomized controlled trial.

BACKGROUND: In a previous pilot study comparing insulin glulisine (GLU) with insulin aspart (ASP) administered by continuous subcutaneous insulin infusion (CSII), GLU-treated patients did show a trend toward fewer catheter occlusions compared with ASP-treated patients. Here we performed a randomized open-label, three-way crossover, controlled multicenter study comparing GLU with ASP and insulin lispro (LIS). METHODS: Subjects with type 1 diabetes were allocated to one of three treatment orders-GLU-ASP-LIS, ASP-LIS-GLU, or LIS-GLU-ASP-with each insulin used for 13 weeks. The study was designed to demonstrate the superiority of GLU over ASP and LIS on unexplained hyperglycemia and/or perceived infusion set occlusion. A prespecified P value of 0.025 was considered significant to correct for multiple testing. RESULTS: Percentages of subjects with at least one unexplained hyperglycemia and/or infusion set occlusion were not significantly different between GLU and ASP (68.4% [62.7-74.1%] vs. 62.1% [56.2-68.1%], P = 0.04) and GLU and LIS (68.4% [62.7-74.1%] vs. 61.3% [55.4-67.3%], P = 0.03). No differences were seen in hemoglobin A1c at end point, most points of the seven-point glucose curves, severe hypoglycemia, and symptomatic ketoacidosis. The overall rate of hypoglycemia with a plasma glucose level below 70 mg/dL per patient-year was significantly different between GLU and ASP (73.84 vs. 65.01, P = 0.008) and GLU and LIS (73.84 vs. 62.69, P < 0.001). Insulin doses remained unchanged during the trial. CONCLUSIONS: GLU was not superior to ASP and LIS with no significant difference seen among GLU, ASP, and LIS in CSII use with respect to unexplained hyperglycemia and/or perceived catheter set occlusion. GLU was associated with a higher frequency of symptomatic hypoglycemia, possibly because of slight overdosing, as previous trials suggested lower insulin requirements when GLU is initiated in type 1 diabetes.

Future acceptance of an artificial pancreas in adults with type 1 diabetes.

BACKGROUND: The purpose of this study was to examine future acceptance of an artificial pancreas (AP) and its perceived usefulness, ease of use, and trust in the device. METHODS: A questionnaire, based on the Technology Acceptance Model, was developed to examine future acceptance with its determinants and intention to use the AP. One hundred thirty-two patients with diabetes type 1 treated with insulin pump therapy completed the questionnaire. Using factor analysis and reliability analysis, the number of items was reduced from 34 to 15. RESULTS: The response rate was 66%. The subjects had a mean age of 43 years, and 34% were male. Almost 75% had the intention to use an AP. There were high scores on perceived usefulness (expected improvement of glucose control: 35.6% moderately agreed and 53% strongly agreed), perceived ease of use (expectation that the AP can be easily handled: 33.3% moderately agreed and 53.8% strongly agreed), and trust (administration of correct insulin dose and reliability of glucose measurement: 40.9% and 38.9% moderately agreed, whereas 32.6% and 28.2% strongly agreed, respectively). CONCLUSIONS: A newly developed questionnaire examining the acceptance of an AP indicated that most patients with continuous subcutaneous insulin infusion-treated type 1 diabetes have the intention to use an AP system and have a positive attitude toward perceived usefulness, ease of use, and trust.

Exercise in closed-loop control: a major hurdle.

BACKGROUND: People with type 1 diabetes mellitus (T1DM) are at risk for exercise-induced hypoglycemia. Prevention of such hypoglycemia in a closed-loop setting is a major challenge. Markers for automated detection of physical activity could be heart rate (HR) and body acceleration counts (AC). Correlations between HR, AC, and glucose concentrations before and after moderate intensity exercise were examined in T1DM patients during open- loop control. METHOD: Eleven T1DM subjects treated with an insulin pump performed moderate intensity exercise of 30 min. Glucose profiles, insulin concentrations, HR, and acceleration were measured. RESULTS: Mean (range) glucose decrease during exercise was 1.4 (0 to 3.3) mmol/liter. The mean increase in HR was 45.2 beats per minutes (15 to 106 bpm). Mean increase in AC was 18,000 (3,000 to 25,000). No correlations were seen between the glucose drop and HR or AC. A trend was observed between the increase in HR and increase in AC. CONCLUSION: Moderate intensity exercise resulted in increased HR and body AC while it decreased glucose concentrations but, in this real-time setting, no association could be demonstrated between the glucose decrease and increase in HR or AC.

Premeal injection of rapid-acting insulin reduces postprandial glycemic excursions in type 1 diabetes.

OBJECTIVE: To assess the effect of three premeal timings of rapid-acting insulin on postprandial glucose excursions in type 1 diabetes. RESEARCH DESIGN AND METHODS: Ten subjects participated in a three-way randomized crossover trial. Mean ± SD age was 45.5 ± 12.1 years, A1C was 8.55 ± 1.50%, duration of diabetes was 23.8 ± 7.8 years, and duration of continuous subcutaneous insulin infusion therapy was 8.5 ± 6.1 years. Insulin aspart was administered at 30, 15, or 0 min before mealtime. RESULTS: Area under the curve was lower in the -15 stratum (0.41 ± 0.51 mmol/l/min) than that in the -30 stratum (1.89 ± 0.72 mmol/l/min, P = 0.029) and 0 stratum (2.11 ± 0.66 mmol/l/min, P = 0.030). Maximum glucose excursion was lower in the -15 stratum (4.77 ± 0.52 mmol/l) than that in the -30 (6.48 ± 0.76 mmol/l, P = 0.025) and 0 stratum (6.93 ± 0.76 mmol/l, P = 0.022). Peak glucose level was lower in the -15 stratum (9.26 ± 0.72 mmol/l) than that in the -30 stratum (11.74 ± 0.80 mmol/l, P = 0.007) and the 0 stratum (12.29 ± 0.93, P = 0.009). Time spent in the 3.5-10 mmol/l range was higher in the -15 stratum (224.5 ± 25.0 min) than that in the 0 stratum (90.5 ± 23.2 min, P = 0.001). There was no significant difference in occurrence of glucose levels <3.5 mmol/l between strata (P = 0.901). CONCLUSIONS: Administration of rapid-acting insulin analogs 15 min before mealtime results in lower postprandial glucose excursions and more time spent in the 3.5-10.0 mmol/l range, without increased risk of hypoglycemia.

Postprandial glycemic excursions with the use of a closed-loop platform in subjects with type 1 diabetes: a pilot study.

BACKGROUND: The aim of this study was to evaluate the efficacy of a proportional derivative algorithm closed-loop system to control postprandial glucose concentrations in subjects with type 1 diabetes. METHODS: Six subjects treated with continuous subcutaneous insulin infusion received a standardized meal on three days. The first day served as control, the second day as learning experiment for the algorithm, and the third day to compare the closed loop to the control day. Venous blood glucose was measured as reference until 300 min postprandially. The artificial pancreas platform consisted of a subcutaneous continuous glucose monitor (CGM), the GlucoDay S (Menarini Diagnostics), two D-Tron+ pumps (Disetronic Medical Systems) for subcutaneous insulin, and glucagon administration connected to a personal computer. RESULTS: One subject was excluded due to technical failure of the CGM. Two of five subjects were male, mean age was 50.8 years (range 38-60), and mean hemoglobin A1c was 8.7% (range 7.0-12.2). The mean postprandial venous blood glucose concentration of day 1 was 205 mg/dl (range 94-265 mg/dl) compared with 128 mg/dl (range 128-158 mg/dl) on day 3 (p = .14). Percentage of time spent in euglycemia postprandially on day 1 was 31% versus 60% on day 3 (p = .08). Time spent below 3.9 mmol/liter (70 mg/dl) was 19% on day 1 compared with 11% on day 3 (p = 1.0). Time above 10 mmol/liter (180 mg/dl) on day 1 was 60% versus 29% on day 3 (p = .22). CONCLUSION: The artificial pancreas provided comparable postprandial glycemic control to usual care.

Patients' perception and future acceptance of an artificial pancreas.

BACKGROUND: Little is known of patient acceptance of an artificial pancreas (AP). The purpose of this study was to investigate future acceptance of an AP and its determinants. METHODS: Patients with type 1 diabetes treated with insulin pump therapy were interviewed using questions based on the technology acceptance model and completed the diabetes treatment and satisfaction questionnaire (DTSQ). RESULTS: Twenty-two adults with type 1 diabetes participated. Half of the patients were followed in a university hospital, and the others were under treatment in an affiliated teaching hospital. Half of the patients were male. The mean DTSQ score was 29 (range 23-33). The AP was perceived as likely to be useful. Perceived advantages were a stable glucose regulation, less need for self-monitoring of blood glucose, relief of daily concerns, and time saving. Participants were confident in their capability to use the system. Although many participants (58%) had been reluctant to start continuous subcutaneous insulin infusion, the majority (79%) felt they would have no barriers to start using the AP. Trust in the AP was related to the quality of glucose control it would provide. Almost everyone expressed the intention to use the new system when available, even if it would initially not cover 24/24 hours. CONCLUSION: The overall attitude on the AP was positive. Intention to use was dependent on trust in the AP, which was related to the quality of glucose control provided by the AP.

Concurrent splenic peliosis and vascular Ehlers-Danlos syndrome.

This case report describes concurrent splenic peliosis and vascular Ehlers-Danlos syndrome (EDS) in a 59-year-old male patient. After splenic rupture due to peliosis, the complicated postoperative period hinted at the possibility of vascular EDS. This diagnosis was confirmed by genetic testing, which revealed a novel point mutation in the COL3A1 gene, c.2545G-->C, leading to a codon encoding for arginine instead of glycine (p.Gly849Arg). In addition, a histological diagnosis of splenic peliosis could be established.