Assessment of with sulfonylurea use in type 2 diabetes mellitus: A retrospective cohort study.

AIMS: The utilization of sulfonylurea (SU) for the management of Type 2 Diabetes Mellitus (T2DM) has witnessed a decline, attributed to the rising popularity of alternative medications and uncertainties surrounding the cardiovascular risk profile of SUs. This study aimed to investigate the potential association between SU intake and the incidence of cardiovascular events in patients with T2DM. METHODS: A retrospective cohort study, based on a general practice (GP) registry, was designed, encompassing patients diagnosed with T2DM between 2005 and 2014.Follow-up persisted until the occurrence of a cardiovascular event, loss to follow-up, or until December 31, 2022. Comparative analyses were conducted between patients, receiving SU treatment and those without RESULTS: Data from a cohort comprising 5589 patients revealed that 13 % and 13.1 % of individuals in the comparator group and the SU group, respectively, experienced a cardiovascular event. However, no statistically significant elevation in the risk of cardiovascular events was observed after SU usage. Furthermore, the glycated haemoglobin (HbA1c) levels were significantly higher in the SU group (7.0 % vs. 6.4 %, p < 0.001). CONCLUSIONS: The findings from this study indicate that the use of sulfonylureas SUs is not associated with a statistically significant increase in the risk of cardiovascular events among patients with type T2DM. These results contribute to the ongoing discourse on the safety and efficacy of SU therapy in diabetes management.

Metabolic health in people living with type 1 diabetes in Belgium: a repeated cross-sectional study.

AIMS/HYPOTHESIS: Metabolic abnormalities such as central obesity, insulin resistance, dyslipidaemia and hypertension, often referred to as 'the metabolic syndrome' (or 'combined metabolic abnormalities'), are increasingly being identified in people living with type 1 diabetes, accelerating the risk for CVD. As a result, in recent years, treatment in people living with type 1 diabetes has shifted to improving overall metabolic health rather than glucose control alone. In Belgium, diabetes care for people living with type 1 diabetes is centrally organised. The Initiative for Quality Improvement and Epidemiology in Diabetes, imposed by the Belgian health insurance system, has systematically collected data from patients on intensive insulin therapy treated in all 101 diabetes clinics in Belgium since 2001. The aim of this real-world study is to describe the evolution of treatment and metabolic health, including the prevalence of obesity and combined metabolic abnormalities, in people living with type 1 diabetes over the past 20 years, and to compare the treatment and prevalence of complications between those with and without combined metabolic abnormalities. METHODS: We analysed data on adults (≥16 years old) living with type 1 diabetes, who were diagnosed at age ≤45 years and who had a diabetes duration ≥1 year, collected between 2001 and 2022. The evolution of HbA1c, BMI, LDL-cholesterol, systolic BP, lipid-lowering therapy and antihypertensive therapy over time was analysed. The prevalence of individual and multiple metabolic abnormalities according to various definitions of the metabolic syndrome/combined metabolic abnormalities was analysed, and the association between combined metabolic abnormalities and metabolic health indicators, complications and treatment was investigated in the 2022 data. RESULTS: The final dataset consisted of 26,791 registrations of adults living with type 1 diabetes collected between 2001 and 2022. Although glycaemic and lipid control generally improved over time, the prevalence of obesity strongly increased (12.1% in 2001 vs 21.7% in 2022, p<0.0001), as did the presence of combined metabolic abnormalities (WHO criteria: 26.9% in 2001 vs 42.9% in 2022 in women, p<0.0001; 30.4% in 2001 vs 52.1% in 2022 in men, p<0.0001; WHO criteria without albuminuria: 22.3% in 2001 vs 40.6% in 2022 in women, p<0.0001; 25.1% in 2001 vs 49.2% in 2022 in men, p<0.0001; NCEP-ATPIII criteria: 39.9% in 2005 vs 57.2% in 2022 in women, p<0.0001; 40.8% in 2005 vs 60.9% in 2022 in men, p<0.0001; IDF criteria: 43.9% in 2005 vs 59.3% in 2022 in women, p<0.001; 33.7% in 2005 vs 50.0% in 2022 in men, p<0.0001). People with combined metabolic abnormalities had higher glucose levels compared to those without combined metabolic abnormalities (HbA1c >58 mmol in men: 48.9% vs 36.9%; HbA1c >58 mmol in women: 53.3% vs 41.1%, p<0.0001). People with combined metabolic abnormalities were more often treated with adjunct therapies such as metformin, sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists. In both men and women, the presence of combined metabolic abnormalities was strongly related to the presence of eye complications, peripheral neuropathy, chronic kidney disease and CVD, corrected for age, diabetes duration and HbA1c. CONCLUSIONS/INTERPRETATION: Overweight, obesity and combined metabolic abnormalities are increasingly being identified in people living with type 1 diabetes, further accelerating the risk of microvascular and macrovascular complications. Early identification of the presence of combined metabolic abnormalities should enable therapeutic interventions to be modified towards multifactorial approaches, with attention to education on avoidance of overweight (e.g. dietary counselling) in addition to strict glycaemic control and intensification of use of antihypertensive agents and statins. Use of adjunct therapies in this population as a tool should be explored more thoroughly to reduce risk of complications.

Advanced Hybrid Closed-Loop Therapy Compared With Standard Insulin Therapy Intrapartum and Early Postpartum in Women With Type 1 Diabetes: A Secondary Observational Analysis From the CRISTAL Randomized Controlled Trial.

OBJECTIVE: To determine efficacy and safety of intrapartum and early postpartum advanced hybrid closed-loop (AHCL) therapy compared with standard insulin therapy in pregnant women with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: CRISTAL was a double-arm, open-label, randomized controlled trial performed in Belgium and the Netherlands that assigned 95 pregnant participants with T1D 1:1 to a MiniMed 780G AHCL system (n = 46) or standard insulin therapy (n = 49). This prespecified, secondary observational analysis focused on differences in glycemic control and safety outcomes between participants from the original AHCL group who continued AHCL intrapartum (n = 27) and/or early postpartum (n = 37, until hospital discharge) and those from the original standard insulin therapy group using standard insulin therapy intrapartum (n = 45) and/or early postpartum (n = 34). RESULTS: Of the 43 and 46 participants in the AHCL and standard insulin therapy groups, respectively, completing the trial, 27 (62.8%) in the AHCL group continued AHCL and 45 in the standard insulin therapy group (97.8%) continued standard insulin therapy intrapartum. Compared with standard insulin therapy, intrapartum AHCL was associated with more time in range 3.5-7.8 mmol/L (71.5 ± 17.7% vs. 63.1 ± 17.0%, P = 0.030) and numerically lower time above range >7.8 mmol/L (27.3 ± 17.4% vs. 35.3 ± 17.5%, P = 0.054), without increases in time below range <3.5 mmol/L (1.1 ± 2.4% vs. 1.5 ± 2.3%, P = 0.146). Early postpartum, 37 (86.0%) participants randomized to AHCL continued AHCL, with a median increase in insulin-to-carbohydrate ratios of 67% (interquartile range -14 to 126). Similar tight glycemic control (3.9-10.0 mmol/L: 86.8 ± 6.7% vs. 83.8 ± 8.1%, P = 0.124) was observed with AHCL versus standard insulin therapy. No severe hypoglycemia or diabetic ketoacidosis was reported in either group. CONCLUSIONS: AHCL is effective in maintaining tight glycemic control intrapartum and early postpartum and can be safely continued during periods of rapidly changing insulin requirements.

Health-related quality of life of people with type 1 diabetes: An IMI2 SOPHIA post hoc analysis of FUTURE and ADJUNCT-ONE.

AIM: To characterize and stratify health-related quality of life in individuals with type 1 diabetes (T1D) using body mass index (BMI) and clustering analysis. MATERIAL AND METHODS: Baseline data on individuals with T1D were pooled from two studies. A post hoc analysis of health-related quality of life, measured using the 36-item Short-Form questionnaire, was performed, referenced to the 2010 US general population. Descriptive statistics were presented for the pooled cohort and per BMI category. K-means clustering was performed. One-way analysis of variance was conducted to examine differences in clinical characteristics between clusters. RESULTS: The pooled cohort consisted of 2256 individuals with T1D (age: 45.4 ± 15.0 years, BMI: 26.2 ± 4.6 kg/m2, diabetes duration: 22.7 ± 13.5 years). All quality-of-life domains were slightly lower than 50(the general population's mean), except for vitality. Individuals with a BMI ≥30 kg/m2 reported lower scores for bodily pain, physical functioning, general health, and vitality. A first cluster with a high and a second cluster with a low quality of life were identified, with significant differences in the mental (Cluster 1: 53.8 ± 6.8 vs. Cluster 2: 39.5 ± 10.7; p < 0.001) and physical component summary scores (Cluster 1: 49.6 ± 6.3 vs. Cluster 2: 35.2 ± 12.0; p < 0.001), which exceeded differences found between BMI categories. CONCLUSIONS: In our population of people living with T1D, higher BMI may have adversely impacted physical domains of quality of life, but larger differences between the high- and low-quality-of-life cluster indicate that more factors play a role.

Comparing advanced hybrid closed loop therapy and standard insulin therapy in pregnant women with type 1 diabetes (CRISTAL): a parallel-group, open-label, randomised controlled trial.

BACKGROUND: Advanced hybrid closed loop (AHCL) therapy can improve glycaemic control in pregnant women with type 1 diabetes. However, data are needed on the efficacy and safety of AHCL systems as these systems, such as the MiniMed 780G, are not currently approved for use in pregnant women. We aimed to investigate whether the MiniMed 780G can improve glycaemic control with less hypoglycaemia in pregnant women with type 1 diabetes. METHODS: CRISTAL was a double-arm, parallel-group, open-label, randomised controlled trial conducted in secondary and tertiary care specialist endocrinology centres at 12 hospitals (11 in Belgium and one in the Netherlands). Pregnant women aged 18-45 years with type 1 diabetes were randomly assigned (1:1) to AHCL therapy (MiniMed 780G) or standard insulin therapy (standard of care) at a median of 10·1 (IQR 8·6-11·6) weeks of gestation. Randomisation was done centrally with minimisation dependent on baseline HbA1c, insulin administration method, and centre. Participants and study teams were not masked to group allocation. The primary outcome was proportion of time spent in the pregnancy-specific target glucose range (3·5-7·8 mmol/L), measured by continuous glucose monitoring (CGM) at 14-17 weeks, 20-23 weeks, 26-29 weeks, and 33-36 weeks. Key secondary outcomes were overnight time in target range, and time below glucose range (<3·5 mmol/L) overall and overnight. Analyses were conducted on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov (NCT04520971). FINDINGS: Between Jan 15, 2021 and Sept 30, 2022, 101 participants were screened, and 95 were randomly assigned to AHCL therapy (n=46) or standard insulin therapy (n=49). 43 patients assigned to AHCL therapy and 46 assigned to standard insulin therapy completed the study. At baseline, 91 (95·8%) participants used insulin pumps, and the mean HbA1c was 6·5% (SD 0·6). The mean proportion of time spent in the target range (averaged over four time periods) was 66·5% (SD 10·0) in the AHCL therapy group compared with 63·2% (12·4) in the standard insulin therapy group (adjusted mean difference 1·88 percentage points [95% CI -0·82 to 4·58], p=0·17). Overnight time in the target range was higher (adjusted mean difference 6·58 percentage points [95% CI 2·31 to 10·85], p=0·0026), and time below range overall (adjusted mean difference -1·34 percentage points [95% CI, -2·19 to -0·49], p=0·0020) and overnight (adjusted mean difference -1·86 percentage points [95% CI -2·90 to -0·81], p=0·0005) were lower with AHCL therapy than with standard insulin therapy. Participants assigned to AHCL therapy reported higher treatment satisfaction. No unanticipated safety events occurred with AHCL therapy. INTERPRETATION: In pregnant women starting with tighter glycaemic control, AHCL therapy did not improve overall time in target range but improved overnight time in target range, reduced time below range, and improved treatment satisfaction. These data suggest that the MiniMed 780G can be safely used in pregnancy and provides some additional benefits compared with standard insulin therapy; however, it will be important to refine the algorithm to better align with pregnancy requirements. FUNDING: Diabetes Liga Research Fund and Medtronic.

Evidence-based interventions for identifying candidate quality indicators to assess quality of care in diabetic foot clinics: a scoping review.

BACKGROUND: Foot ulcers in people with diabetes are a serious complication requiring a complex management and have a high societal impact. Quality monitoring systems to optimize diabetic foot care exist, but a formal and more evidence-based approach to develop quality indicators (QIs) is lacking. We aimed to identify a set of candidate indicators for diabetic foot care by adopting an evidence-based methodology. METHODS: A systematic search was conducted across four academic databases: PubMed, Embase CINAHL and Cochrane Library. Studies that reported evidence-based interventions related to organization or delivery of diabetic foot care were searched. Data from the eligible studies were summarized and used to formulate process and structure indicators. The evidence for each candidate QI was described in a methodical and transparent manner. The review process was reported according to the "Preferred Reported Items for Systematic reviews and Meta-Analysis" (PRISMA) statements and its extension for scoping reviews. RESULTS: In total, 981 full-text articles were screened, and 322 clinical studies were used to formulate 42 candidate QIs. CONCLUSIONS: An evidence-based approach could be used to select candidate indicators for diabetic foot ulcer care, relating to the following domains: wound healing interventions, peripheral artery disease, offloading, secondary prevention, and interventions related to organization of care. In a further step, the feasibility of the identified set of indicators will be assessed by a multidisciplinary panel of diabetic foot care stakeholders.

Evaluation of Glucose Metrics in Adults with Type 1 Diabetes Switching to Insulin Glargine 300 U/mL: A Retrospective, Propensity-Score Matched Study.

Objectives: To study real-world effect of switching to Insulin Glargine 300 U/mL (Gla-300) on glucose metrics in people with type 1 diabetes. Methods: This retrospective secondary-use study compared 151 adults who switched to Gla-300 from first-generation long-acting insulins (Switchers) to 281 propensity-score matched controls (Non-switchers) who continued first-generation long-acting insulins. Primary endpoint was difference in time in range (TIR) evolution. A fictive "switching" date was assigned to Non-switchers to facilitate between-group comparisons. Results: In the period before switching, TIR decreased numerically for people in whom Gla-300 was eventually initiated (-0.05%/month [-0.16 to 0.07]), while it increased for matched controls (0.08%/month [0.02 to 0.015]; between-group difference P = 0.047). After Gla-300-initiation, Switchers had similar TIR increase compared to Non-switchers (P = 0.531). Switchers used higher basal dose than before switch (Δ0.012 U/[kg·d] [0.006 to 0.018]; P < 0.0001). Conclusion: In real-life, Gla-300 was typically initiated in people where TIR was decreasing, which was reversed after switch using slightly higher basal insulin dose. ClinicalTrials: ClinicalTrials.gov number NCT05109520.

Cost-utility analysis of Dexcom G6 real-time continuous glucose monitoring versus FreeStyle Libre 1 intermittently scanned continuous glucose monitoring in adults with type 1 diabetes in Belgium.

AIMS/HYPOTHESIS: The aim of this study was to assess the long-term cost-effectiveness of Dexcom G6 real-time continuous glucose monitoring (rtCGM) with alert functionality compared with FreeStyle Libre 1 intermittently scanned continuous glucose monitoring (isCGM) without alerts in adults with type 1 diabetes in Belgium. METHODS: The IQVIA CORE Diabetes Model was used to estimate cost-effectiveness. Input data for the simulated baseline cohort were sourced from the randomised ALERTT1 trial (ClinicalTrials.gov. REGISTRATION NO: NCT03772600). The age of the participants was 42.9 ± 14.1 years (mean ± SD), and the baseline HbA1c was 57.8 ± 9.5 mmol/mol (7.4 ± 0.9%). Participants using rtCGM showed a reduction in HbA1c of 3.6 mmol/mol (0.36 percentage points) based on the 6-month mean between-group difference. In the base case, both rtCGM and isCGM were priced at €3.92/day (excluding value-added tax [VAT]) according to the Belgian reimbursement system. The analysis was performed from a Belgian healthcare payer perspective over a lifetime time horizon. Health outcomes were expressed as quality-adjusted life years. Probabilistic and one-way sensitivity analyses were used to account for parameter uncertainty. RESULTS: In the base case, rtCGM dominated isCGM, resulting in lower diabetes-related complication costs and better health outcomes. The associated main drivers favouring rtCGM were lower HbA1c, fewer severe hypoglycaemic events and reduced fear of hypoglycaemia. The results were robust under a wide range of one-way sensitivity analyses. In models where the price of rtCGM is €5.11/day (a price increase of 30.4%) or €12.34/day (a price increase of 214.8%), rtCGM was cost-neutral or reached an incremental cost-effectiveness ratio of €40,000 per quality-adjusted life year, respectively. CONCLUSIONS/INTERPRETATION: When priced similarly, Dexcom G6 rtCGM with alert functionality has both economic and clinical benefits compared with FreeStyle Libre 1 isCGM without alerts in adults with type 1 diabetes in Belgium, and appears to be a cost-effective glucose monitoring modality. Trial registration ClinicalTrials.gov NCT03772600.

A multidisciplinary Delphi consensus to define evidence-based quality indicators for diabetic foot ulcer care.

BACKGROUND: Valid measures to assess quality of care delivered to patients with diabetes suffering from diabetic foot ulcer (DFU) are scarce. This study aimed to achieve consensus on relevant and feasible quality indicators (QIs) among stakeholders involved in DFU care and was conducted as the second part of a Belgian QI selection study that sought to identify QIs for DFU care. METHODS: A stakeholder panel, including caregivers from primary care and specialized disciplines active in diabetic foot care as well as a patient organization representative, was recruited. By using the RAND/UCLA Appropriateness Method, stakeholders were asked to rate a list of 42 candidate evidence-based indicators for appropriateness through a 9-point Likert scale. QIs were classified based on the median ratings and the disagreement index, calculated by the inter-percentile range adjusted for symmetry. RESULTS: At the end of a three-phase process, 17 QIs were judged as appropriate. Among them, five were not previously described, covering the following topics: integration of wound care specialty in the multidisciplinary team, systematic evaluation of the nutritional status of the patient, administration of low-density lipoprotein-cholesterol lowering medication and protocolized care (implementation of care and prevention management protocols). CONCLUSIONS: The identified evidence-based QIs provide an assessment tool to evaluate and monitor quality of care delivered to DFU patients. Future research should focus on their complementarity with the existing QIs and their implementation in clinical practice.

Assessment and management of diabetes-related foot infection according to the new International Working Group on the Diabetic Foot guidelines 2023-Multidisciplinary grand rounds.

Diabetes-related foot disease is a serious and common complication for people with diabetes mellitus. The gold standard care for a person with diabetes-related foot disease is the involvement of a multidisciplinary foot team engaged in evidence-based care. To date, there are seven International Working Group on the Diabetic Foot (IWGDF) guidelines published to assist healthcare providers in managing diabetes-related foot disease around the world. This review discusses the acute management of diabetes-related foot infection with insights from experts of various specialities (internal medicine, infectious disease, vascular surgery, radiology) with a discussion on the implementation of IWGDF guidelines in real life practice and the challenges that healthcare providers may face.

Impact of diabetes on medical costs in the pre- and postoperative year of lower extremity amputations in Belgium.

AIMS: To compare the medical costs of individuals undergoing lower extremity amputation (LEA) in Belgium with those of amputation-free individuals. METHODS: Belgian citizens undergoing LEAs in 2014 were identified. The median costs per capita in euros for the 12 months preceding and following minor and major LEAs were compared with those of matched amputation-free individuals. RESULTS: A total of 3324 Belgian citizens underwent LEAs (2295 minor, 1029 major), 2130 of them had diabetes. The comparison group included 31,716 individuals. Amputation was associated with high medical costs (individuals with diabetes: major LEA €49,735, minor LEA €24,243, no LEA €2,877 in the year preceding amputation; €45,740, €21,445 and €2,284, respectively, in the post-amputation year). Significantly higher costs were observed in the individuals with (versus without) diabetes in all groups. This difference diminished with higher amputation levels. Individuals undergoing multiple LEAs generated higher costs (individuals with diabetes: €39,313-€89,563 when LEAs preceded index amputation; €46,629-€92,877 when LEAs followed index amputation). Individuals dying in the year after a major LEA generated remarkably lower costs. CONCLUSIONS: LEA-related medical costs were high. Diabetes significantly impacted costs, but differences in costs diminished with higher amputation levels. Individuals with multiple amputations generated the highest costs.

The impact of diabetes on mortality rates after lower extremity amputation.

OBJECTIVE: To assess the impact of diabetes, amputation level, sex and age on mortality rates after lower extremity amputation (LEA) in Belgium, and to assess temporal trends in one-year survival rates from 2009 to 2018. METHODS: Nationwide data on individuals who underwent minor and major LEA from 2009 to 2018 were collected. Kaplan-Meier survival curves were constructed. A Cox regression model with time-varying coefficients was used to estimate the likelihood of mortality after LEA in individuals with or without diabetes. Matched amputation-free individuals with or without diabetes were used for comparison. Time trends were analysed. RESULTS: Amputations 41,304 were performed: 13,247 major and 28,057 minor. Five-year mortality rates in individuals with diabetes were 52% and 69% after minor and major LEA, respectively (individuals without diabetes: 45% and 63%, respectively). In the first six postoperative months, no differences in mortality rates were found between individuals with or without diabetes. Later, hazard ratios (HRs) for mortality in individuals with diabetes (compared with no diabetes) after minor LEA ranged from 1.38 to 1.52, and after major LEA from 1.35 to 1.46 (all p ≤ 0.005). Among individuals without LEA, HRs for mortality in diabetes (versus no diabetes) were systematically higher compared to the HRs for mortality in diabetes (versus no diabetes) after minor and major LEA. One-year survival rates did not change for individuals with diabetes. CONCLUSIONS: In the first six postoperative months, mortality rates after LEA were not different between individuals with or without diabetes; later, diabetes was significantly associated with increased mortality. However, as HRs for mortality were higher in amputation-free individuals, diabetes impacts mortality less in the minor and major amputation groups relative to the comparison group of individuals without LEA.

PAI-BEL: a Belgian multicentre survey of primary adrenal insufficiency.

Objective: Primary adrenal insufficiency (PAI) is a rare disease with an increasing prevalence, which may be complicated by life-threatening adrenal crisis (AC). Good quality epidemiological data remain scarce. We performed a Belgian survey to describe the aetiology, clinical characteristics, treatment regimens, comorbidities and frequency of AC in PAI. Methods: A nationwide multicentre study involving 10 major university hospitals in Belgium collected data from adult patients with known PAI. Results: Two hundred patients were included in this survey. The median age at diagnosis was 38 years (IQR 25-48) with a higher female prevalence (F/M sex ratio = 1.53). The median disease duration was 13 years (IQR 7-25). Autoimmune disease was the most common aetiology (62.5%) followed by bilateral adrenalectomy (23.5%) and genetic variations (8.5%). The majority (96%) of patients were treated with hydrocortisone at a mean daily dose of 24.5 ± 7.0 mg, whereas 87.5% of patients also received fludrocortisone. About one-third of patients experienced one or more AC over the follow-up period, giving an incidence of 3.2 crises per 100 patient-years. There was no association between the incidence of AC and the maintenance dose of hydrocortisone. As high as 27.5% of patients were hypertensive, 17.5% had diabetes and 17.5% had a diagnosis of osteoporosis. Conclusion: This study provides the first information on the management of PAI in large clinical centres in Belgium, showing an increased frequency of postsurgical PAI, a nearly normal prevalence of several comorbidities and an overall good quality of care with a low incidence of adrenal crises, compared with data from other registries.

Closed-loop insulin delivery in pregnant women with type 1 diabetes (CRISTAL): a multicentre randomized controlled trial - study protocol.

BACKGROUND: Despite increasing use of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII, insulin pumps) in type 1 diabetes (T1D) in pregnancy, achieving recommended pregnancy glycaemic targets (3.5-7.8 mmol/L or 63-140 mg/dL) remains challenging. Consequently, the risk of adverse pregnancy outcomes remains high. Outside pregnancy, hybrid closed-loop (HCL) insulin delivery systems have led to a paradigm shift in the management of T1D, with 12% higher time in glucose target range (TIR) compared to conventional CSII. However, most commercially available HCL systems are currently not approved for use in pregnancy. This study aims to evaluate the efficacy, safety and cost-effectiveness of the MiniMed™ 780G HCL system (Medtronic) in T1D in pregnancy. METHODS: In this international, open-label, randomized controlled trial (RCT), we will compare the MiniMed™ 780G HCL system to standard of care (SoC) in T1D in pregnancy. Women aged 18-45 years with T1D diagnosis of at least one year, HbA1c ≤ 86 mmol/mol (≤ 10%), and confirmed singleton pregnancy up to 11 weeks 6 days will be eligible. After providing written informed consent, all participants will wear a similar CGM system (Guardian™ 3 or Guardian™ 4 CGM) during a 10-day run-in phase. After the run-in phase, participants will be randomised 1:1 to 780G HCL (intervention) or SoC [control, continuation of current T1D treatment with multiple daily injections (MDI) or CSII and any type of CGM] stratified according to centre, baseline HbA1c (< 53 vs. ≥ 53 mmol/mol or < 7 vs. ≥ 7%), and method of insulin delivery (MDI or CSII). The primary outcome will be the time spent within the pregnancy glucose target range, as measured by the CGM at four time points in pregnancy: 14-17, 20-23, 26-29, and 33-36 weeks. Prespecified secondary outcomes will be overnight TIR, time below range (TBR: <3.5 mmol/L or < 63 mg/dL), and overnight TBR. Other outcomes will be exploratory. The planned sample size is 92 participants. The study will end after postpartum discharge from hospital. Analyses will be performed according to intention-to-treat as well as per protocol. DISCUSSION: This large RCT will evaluate a widely used commercially available HCL system in T1D in pregnancy. Recruitment began in January 2021 and was completed in October 2022. Study completion is expected in May 2023. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04520971. Registration date: August 20, 2020. https://clinicaltrials.gov/ct2/show/NCT04520971.

Sustained Impact of Intermittently Scanned Continuous Glucose Monitoring on Treatment Satisfaction and Severe Hypoglycemia in Adults with Type 1 Diabetes (FUTURE): An Analysis in People with Normal and Impaired Awareness of Hypoglycemia.

Objective: Nationwide reimbursement of intermittently scanned continuous glucose monitoring (isCGM) was introduced in Belgium (2016). This real-world observational study investigates the impact of isCGM over 24 months on adults with type 1 diabetes with impaired or normal awareness of hypoglycemia (IAH or NAH). Methods: We included 1905 people who started first-generation 14-day FreeStyle Libre (without alerts). Sixteen percent had IAH. Primary endpoint was evolution of quality of life (QOL); secondary endpoints were evolution of severe hypoglycemia, work absenteeism, glycated hemoglobin (HbA1c), and sensor-measured outcomes. Results: At baseline, people with IAH (n = 308) had significantly worse QOL than people with NAH (n = 1594). Only people with IAH improved on the hypoglycemia fear survey-worry subscale after 24 months (22.8 [95% confidence interval: 21.4-24.2] at baseline; 20.6 [19.0-22.1] at 24 months, P = 0.002). For both groups, Diabetes Treatment Satisfaction Scale improved over 24 months (IAH: +3.1 [2.1-4.1], P < 0.001; NAH: +2.3 [1.9-2.7], P < 0.001), whereas general QOL, diabetes distress, and HbA1c remained stable. People with IAH showed the strongest decline in work absenteeism and severe hypoglycemia (36.4% having an event 6 months before isCGM initiation; 16.0% having an event during last 6 months of follow-up, P < 0.001), with similar observations for hypoglycemia hospitalization and hypoglycemia coma. Over 24 months, people with IAH spent more time in hypoglycemia, but less time in hyperglycemia than people with NAH. Conclusion: These data show sustained improvement of severe hypoglycemia, work absenteeism, and hypoglycemia fear after isCGM reimbursement, mostly driven by people with IAH. Together with improved treatment satisfaction, irrespective of hypoglycemia awareness level, isCGM without alerts is a valuable tool under long-term real-world conditions. Clinical Trial Registration number: NCT02898714.

Effect of switching from intermittently scanned to real-time continuous glucose monitoring in adults with type 1 diabetes: 24-month results from the randomised ALERTT1 trial.

BACKGROUND: Comparing Continuous With Flash Glucose Monitoring In Adults With Type 1 Diabetes (ALERTT1) examined whether switching from first-generation intermittently scanned continuous glucose monitoring (isCGM) without alerts to real-time continuous glucose monitoring (rtCGM) with alert functionality offers additional benefits to adults with type 1 diabetes. The extension of the randomised ALERTT1 trial assessed the effect of switching from isCGM to rtCGM up to 24 months. METHODS: In this 6-month, double-arm, parallel-group, non-masked, randomised, controlled trial, done across six hospitals in Belgium, 254 adults aged 18 years or older with type 1 diabetes previously using isCGM were randomly assigned (1:1) to rtCGM with alerts (intervention; n=127) or isCGM without alerts (control; n=127). Upon completion of the 6-month trial, the control group switched to rtCGM (is-rtCGM group), and the intervention group continued rtCGM (rt-rtCGM group). The extension focused on within-group changes in time in range (TIR; 3·9-10·0 mmol/L; primary outcome), HbA1c, time in clinically significant hypoglycaemia (<3·0 mmol/L), and Hypoglycaemia Fear Survey worry (HFS-worry) score (all prespecified key secondary outcomes). Mean within-group change versus the start of rtCGM is reported, with a positive value referring to a lower value at start of rtCGM. This trial is registered at ClinicalTrials.gov (NCT03772600). FINDINGS: 119 participants were assigned to the is-rtCGM group of whom 112 (94%) completed the 24-month trial, and 123 participants were assigned to the rt-rtCGM group of whom 117 (95%) completed the 24-month trial. TIR increased from 51·8% (95% CI 49·1-54·5) at start of rtCGM (month 6) to 63·5% (60·7-66·3) at month 12 in the is-rtCGM group, and remained stable up to month 24 (change 11·7 percentage points [pp] [9·4-14·0; p<0·0001). In the rt-rtCGM group, TIR increased from 52·5% (95% CI 49·8-55·1) at start of rtCGM (month 0) to 63·0% (60·3-65·8) at month 12, also remaining stable up to month 24 (change 10·5 pp [8·2-12·8]; p<0·0001). HbA1c decreased from 7·4% (57 mmol/mol; month 6) to 6·9% (52 mmol/mol) at month 24 (change -0·54 pp [95% CI -0·64 to -0·44]; -5 mmol/mol [95% CI -6 to -4]; p<0·0001) in the is-rtCGM group, and from 7·4% (57 mmol/mol; month 0) to 7·0% (53 mmol/mol) at month 24 (change -0·43 pp [95% CI -0·53 to -0·33]; -4 mmol/mol [95% CI -5 to -3]; p<0·0001) in the rt-rtCGM group. The change in HFS-worry score was -2·67 (month 24 vs month 6; p=0·0008) in the is-rtCGM group and -5·17 points (month 24 vs month 0; p<0·0001) in the rt-rtCGM group. Time in clinically significant hypoglycaemia was unchanged in both groups after month 12. Severe hypoglycaemia decreased from 31·0 to 3·3 per 100 patient-years after switching to rtCGM. INTERPRETATION: Glycaemic control and hypoglycaemia worry improved significantly up to 24 months after switching from isCGM without alerts to rtCGM with alerts, supporting the use of rtCGM in the care of adults with type 1 diabetes. FUNDING: Dexcom.

Decoding foot deformity and joint-destruction pathways in diabetes: Emerging insights from in-vivo foot joint kinetic measures.

BACKGROUND: A comprehensive insight into the effect of longstanding diabetes mellitus and neuropathy on foot joint kinetics during walking is lacking. Our goal was to assess the in-vivo kinetics of major foot joints in persons with diabetes. METHODS: Three groups, matched for age, sex and walking speed were recruited in this study: 1) people with diabetic peripheral neuropathy, 2) people with diabetes without peripheral neuropathy, and 3) control subjects without diabetes. Participants were instrumented with retroreflective markers on both feet and lower limbs and underwent a barefoot gait analysis using a state-of-the-art multi-segment kinetic foot modelling approach in order to provide accurate joint loading measures at the ankle, midtarsal, tarso-metatarsal and hallux joints. FINDINGS: The group with neuropathy showed reduced ankle peak plantarflexion angular velocity compared to the control group (P = 0.002). Both groups with diabetes showed a significantly reduced midtarsal peak plantarflexion angular velocity, peak power generation and positive work compared to the control group (p < 0.01). Groups showed significant differences with respect to the tarsometatarsal peak dorsiflexion (p = 0.006) and plantarflexion angular velocity (P < 0.05). INTERPRETATION: This study shows that both diabetes groups have similar joint loading and power absorption capacity but seem to lose their power generation capacity especially at the midtarsal joint. This loss of power generation capacity and the resulting decreased net mechanical work of the foot potentially embodies a foot that poorly supplements the body's mechanical energy during push-off. This phenomenon may cause excessive tissue stresses that contribute to foot deformity and joint-destruction mechanisms.

The Impact of Baseline User Characteristics on the Benefits of Real-Time Versus Intermittently Scanned Continuous Glucose Monitoring in Adults With Type 1 Diabetes: Moderator Analyses of the ALERTT1 Trial.

BACKGROUND: ALERTT1 showed that switching from intermittently scanned continuous glucose monitoring (isCGM) without alerts to real-time CGM (rtCGM) with alert functionality improved time in range (TIR; 70-180 mg/dL), glycated hemoglobin (HbA1c), time <54 mg/dL, and Hypoglycemia Fear Survey version II worry subscale (HFS-worry) score after six months in adults with type 1 diabetes (T1D). Moderator analyses aimed to identify certain subgroups that would benefit more from switching to rtCGM than others. METHODS: Post hoc analyses of ALERTT1 evaluated the impact of 14 baseline characteristics on the difference (delta) in mean TIR, HbA1c, time <54 mg/dL, and HFS-worry score at six months between rtCGM and isCGM. Therefore, the delta was allowed to depend on each of these variables by including interactions in the moderator analysis model. Analyses were performed separately for each variable; variables with P < .10 in the univariable analysis were combined into a single model. RESULTS: Univariable analyses showed no dependency of delta TIR, HbA1c, or time <54 mg/dL on variables other than CGM type. Only delta HFS-worry score depended on baseline HbA1c (P = .0059), indicating less worries with rtCGM in people with baseline HbA1c <6.5% or ≥8%. Given P < .10 for dependency of delta TIR on insulin therapy type (favoring multiple daily injections), baseline HbA1c, and baseline TIR, these variables were combined into a multivariable analysis; interactions were not statistically significant. CONCLUSIONS: Except for HFS-worry score, no interactions between 14 baseline characteristics and the six-month intervention effect of rtCGM on TIR, HbA1c, or time <54 mg/dL were observed, supporting the conclusion of ALERTT1 that switching from isCGM without alerts to rtCGM with alert functionality is beneficial for a wide range of people with T1D.

Bottom-up approach to build a 'precision' risk factor classification for diabetic foot ulcer healing. Proof-of-concept.

AIMS: Diabetic foot ulcers (DFU) have a complex multifactorial pathophysiology. It is crucial to identify essential prognostic variables to streamline therapeutic actions and quality-of-care audits. Although SINBAD and University of Texas (UT), the most frequently used prognostic classification systems, were prospectively validated, not all individual parameters were shown to have consistent associations with healing. In this study, we used a bottom-up approach relying on robust methods to identify independent predictors of DFU healing. METHODS: 1,664 DFU patients were included by 34 Belgian diabetic foot clinics (DFCs). Twenty-one patient- and foot-related characteristics were recorded at presentation. Predictors of healing were identified using multivariable Cox proportional hazard regression. Multivariable models were built using backward regression with multiple imputation of missing values and bootstrapping. RESULTS: Five essential independent variables were identified: presentation delay, history of minor amputation, ulcer location, surface area and ischemia. This 5 variable-model showed a better performance compared to models based on existing classification systems. CONCLUSIONS: A bottom-up approach was used to build a prognostic classification for DFU healing based on large databases. It offers new insights and allows to tailor the classification to certain clinical settings. These 5 parameters could be used as a 'precision classification' for specialized DFCs.

Temporal trends in major, minor and recurrent lower extremity amputations in people with and without diabetes in Belgium from 2009 to 2018.

AIMS: This study assessed temporal trends in the incidence of lower extremity amputations (LEA) in Belgium from 2009 to 2018, and subsequent secondary amputation rates. METHODS: Nationwide data on LEA were collected. Sex- and age-adjusted annual incidence rates were calculated. Time trends were analysed in negative binomial models. The incidence of secondary interventions, defined as either any ipsilateral reamputation or any contralateral amputation, was studied with death as competing risk. RESULTS: 41 304 amputations were performed (13 247 major, 28 057 minor). In individuals with diabetes, the amputation rate (first amputation per patient per year) decreased from 143.6/100.000 person-years to 109.7 (IRR 0.97 per year, 95 %CI 0.96-0.98, p < 0.001). The incidence of major LEAs decreased from 56.2 to 30.7 (IRR 0.93, 95 %CI 0.91-0.94, p < 0.001); the incidence of minor amputations showed a non-significant declining trend in women (54.3 to 45.0/100 000 person years, IRR 0.97 per year, 95 %CI 0.96-0.99), while this remained stable in men with diabetes (149.2 to 135.3/100 000 person years, IRR 1.00 per year, 95 %CI 0.98-1.01). In individuals without diabetes, the incidence of major amputation didn't change significantly, whereas minor amputation incidence increased (8.0 to 10.6, IRR 1.04, 95 %CI 1.03-1.05, p < 0.001). In individuals with diabetes, one-year secondary intervention rates were high (31.3% after minor, 18.4% after major LEA); the incidence of secondary amputations didn't change. CONCLUSIONS: A significant decline in the incidence rate of major LEA was observed in people with diabetes. This decline was not accompanied by a significant rise in minor LEA. The incidence of secondary interventions remained stable.