Relationship between peripheral and intracoronary blood flow in patients with angina and nonobstructive coronary arteries.

Coronary vasomotor dysfunction, an important underlying cause of angina and nonobstructive coronary arteries (ANOCA), encompassing coronary vasospasm, coronary endothelial dysfunction, and/or coronary microvascular dysfunction, is clinically assessed by invasive coronary function testing (ICFT). As ICFT imposes a high burden on patients and carries risks, developing noninvasive alternatives is important. We evaluated whether coronary vasomotor dysfunction is a component of systemic microvascular endothelial and smooth muscle dysfunction and can be detected using laser speckle contrast analysis (LASCA). Forty-three consecutive patients with ANOCA underwent ICFT, with intracoronary acetylcholine, adenosine, and flow measurements, to assess coronary vasomotor dysfunction. Cutaneous microvascular function was assessed using LASCA in the forearm, combined with vasodilators acetylcholine, sodium nitroprusside, and insulin and using EndoPAT, by measuring the reactive hyperemia index (RHI). Of the 43 included patients with ANOCA (79% women, 59 ± 9 yr old), 38 patients had coronary vasomotor dysfunction, including 28 with coronary vasospasm, 26 with coronary endothelial dysfunction, and 18 with coronary microvascular dysfunction, with overlapping endotypes. Patients with and without coronary vasomotor dysfunction had similar peripheral flow responses to acetylcholine, insulin, and RHI. In contrast, coronary vasomotor dysfunction was associated with lower peripheral flow responses to sodium nitroprusside (P < 0.001). An absolute flow response to sodium nitroprusside of 83.95 APU resulted in 86.1% sensitivity and 80.0% specificity for coronary vasomotor dysfunction (area under the ROC curve, 0.883; P = 0.006). In conclusion, this study provides evidence of systemic vascular smooth muscle dysfunction in patients with ANOCA with coronary vasomotor dysfunction and the diagnostic value of peripheral microvascular function testing as a noninvasive tool for detecting coronary vasomotor dysfunction.NEW & NOTEWORTHY This study provides proof of concept that assessment of the peripheral vasculature, particularly vascular smooth muscle cells measured using the LASCA technology holds potential as a noninvasive tool for detecting coronary vasomotor dysfunction. This finding highlights the potential of the LASCA technology in, for example, medication studies for coronary vasomotor dysfunction, especially when investigating whether medication improves vascular function, as repeated peripheral measurements are less invasive than invasive coronary function testing, the current gold standard.

The role of myocardial blood volume in the pathophysiology of angina with non-obstructed coronary arteries: The MICORDIS study.

BACKGROUND: Angina with Non-Obstructed Coronary Arteries (ANOCA) involves abnormal vasomotor responses. While reduced coronary flow is an established contributor to myocardial hypoxia, myocardial blood volume (MBV) independently regulates myocardial oxygen uptake but its role in ANOCA remains unclear. OBJECTIVES: We hypothesized that reduced MBV contributes to ANOCA, and associates with insulin resistance in ANOCA. METHODS: MBV in ANOCA patients was compared to age- and sex-matched healthy controls. ANOCA patients underwent coronary angiography with invasive coronary function testing (CFT) to identify vasospasm and coronary microvascular dysfunction. In all subjects MBV was quantified at baseline, during hyperinsulinemia and during dobutamine-induced stress using myocardial contrast echocardiography (MCE). The hyperinsulinemic-euglycemic clamp was used to assess insulin resistance. RESULTS: Twenty-eight ANOCA patients (21% men, 56.8 ± 8.6 years) and 28 healthy controls (21% men, 56.5 ± 7.0 years) were included. During CFT 11% of patients showed epicardial vasospasm, 39% microvascular vasospasm, 25% coronary microvascular dysfunction, and 11% of patients had a negative CFT. ANOCA patients had significant lower insulin-sensitivity (p < 0.01). During MCE, ANOCA patients showed a significantly lower MBV at baseline (0.388 vs 0.438 mL/mL, p = 0.04), during hyperinsulinemia (0.395 vs 0.447 mL/mL, p = 0.02), and during dobutamine-induced stress (0.401 vs 0.476 mL/mL, p = 0.030). CONCLUSIONS: In ANOCA patients MBV is diminished at baseline, during hyperinsulinemia and dobutamine-induced stress in the absence of differences in microvascular recruitment. These findings support the presence of capillary rarefaction in ANOCA patients. ANOCA patients showed metabolic insulin resistance, but insulin did not acutely alter myocardial perfusion.

[Spurious hypertension in an athletic young man]. / Pseudohypertensie bij een sportieve jonge man.

Isolated systolic hypertension is typical for the elderly, but also occurs in younger adults. Increased pulse wave amplification between the elastic aorta and arteries to the arm can result in a higher peripheral (brachial) blood pressure, while central (aortic) systolic blood pressure is normal. A 21-year-old athletic man was referred because of an arterial blood pressure of 160/85 mmHg. Diagnostic work-up did not reveal secondary hypertension or organ damage such as left ventricular hypertrophy or microalbuminuria. Pulse wave analysis by arterial tonometry showed central blood pressure to be 29 mmHg lower than blood pressure at the brachial artery. This finding suggests 'spurious' or pseudohypertension. Isolated systolic hypertension in athletic young adults can reflect a discrepancy between a blood pressure measured at the upper limb and the 'true' central blood pressure at the central arteries, i.e. pseudohypertension.

Mortality patterns in Dutch diabetes outpatients.

AIM: Diabetes mellitus is a major cause of death. Outpatients with diabetes have more complications than patients in general practice; mortality patterns have only been studied in the total diabetes population. This study aims to assess mortality, causes, and predictors in outpatients with diabetes. MATERIALS AND METHODS: A cohort study, included people with diabetes mellitus from the nationwide Dutch Paediatric and Adult Registry of Diabetes (DPARD) visiting diabetes outpatient clinics in 2016-2020. DPARD data were linked to Statistics Netherlands (CBS), comprising data on mortality, ethnicity and education. All-cause and cardiovascular mortality rates were estimated using Cox proportional hazard regression. RESULTS: During a median follow-up of 3.1 years among 12 992 people with diabetes, mortality rates per 10 000 person-years were 67.7 in adult type 1 diabetes and 324.2 in type 2 diabetes. The major cause of non-cardiovascular death was malignancy. During the pandemic years of influenza (2018) and COVID (2020), mortality rates peaked. Age, smoking and an estimated glomerular filtration rate of <60 ml/min were associated with all-cause mortality. In type 2 diabetes, additional factors were male sex, body mass index <20 kg/m2, diabetes duration <1 year and hypertension. CONCLUSIONS: Mortality among Dutch outpatients with diabetes is high. Smoking and renal failure were associated with mortality in both types. Further focus on early detection and treatment of mortality-associated factors may improve clinical outcomes.

Lifetime and 10-year cardiovascular risk prediction in individuals with type 1 diabetes: The LIFE-T1D model.

AIMS: To develop and externally validate the LIFE-T1D model for the estimation of lifetime and 10-year risk of cardiovascular disease (CVD) in individuals with type 1 diabetes. MATERIALS AND METHODS: A sex-specific competing risk-adjusted Cox proportional hazards model was derived in individuals with type 1 diabetes without prior CVD from the Swedish National Diabetes Register (NDR), using age as the time axis. Predictors included age at diabetes onset, smoking status, body mass index, systolic blood pressure, glycated haemoglobin level, estimated glomerular filtration rate, non-high-density lipoprotein cholesterol, albuminuria and retinopathy. The model was externally validated in the Danish Funen Diabetes Database (FDDB) and the UK Biobank. RESULTS: During a median follow-up of 11.8 years (interquartile interval 6.1-17.1 years), 4608 CVD events and 1316 non-CVD deaths were observed in the NDR (n = 39 756). The internal validation c-statistic was 0.85 (95% confidence interval [CI] 0.84-0.85) and the external validation c-statistics were 0.77 (95% CI 0.74-0.81) for the FDDB (n = 2709) and 0.73 (95% CI 0.70-0.77) for the UK Biobank (n = 1022). Predicted risks were consistent with the observed incidence in the derivation and both validation cohorts. CONCLUSIONS: The LIFE-T1D model can estimate lifetime risk of CVD and CVD-free life expectancy in individuals with type 1 diabetes without previous CVD. This model can facilitate individualized CVD prevention among individuals with type 1 diabetes. Validation in additional cohorts will improve future clinical implementation.

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).

Potency of quality indicators in Dutch and international diabetes registries.

BACKGROUND: Diabetes mellitus forms a slow pandemic. Cardiovascular risk and quality of diabetes care are strongly associated. Quality indicators improve diabetes management and reduce mortality and costs. Various national diabetes registries render national quality indicators. We describe diabetes care indicators for Dutch children and adults with diabetes, and compare them with indicators established by registries worldwide. METHODS: Indicator scores were derived from the Dutch Pediatric and Adult Registry of Diabetes Indicator sets of other national diabetes registries were collected and juxtaposed with global and continental initiatives for indicator sets. RESULTS: This observational cohort study included 3738 patients representative of the Dutch diabetic outpatient population. The Dutch Pediatric and Adult Registry of Diabetes harbors ten quality indicators comprising treatment volumes, HbA1c control, foot examination, insulin pump therapy, and real-time continuous glucose monitoring. Worldwide, nine national registries record quality indicators, with great variety between registries. HbA1c control is recorded most frequently, and no indicator is reported among all registries. CONCLUSIONS: Wide variety among quality indicators recorded by national diabetes registries hinders international comparison and interpretation of quality of diabetes care. The potential of quality evaluation will be greatly enhanced when diabetes care indicators are aligned in an international standard set with variation across countries taken into consideration.

[Glycemia reduction in type 2 diabetes patients with low cardiovascular risk]. / Patiënten met type 2-diabetes en een laag cardiovasculair risico.

In persons with type 2 diabetes without established cardiovascular complications data are lacking on the comparative effectiveness of commonly used glucose-lowering medications, when added to metformin, with respect to glycemic outcomes as well as microvascular and cardiovascular disease outcomes. The GRADE trial compared the ability of four glucose-lowering remedies to achieve and maintain a defined glycated hemoglobin target and to protect the participant from microvascular and macrovascular complications. In this article, we comment on the relevance of this trial with specific attention for the notion that GLP-1 receptor agonists seem to have a primary preventive effect.

Effects of COVID-19 on diabetes care among dutch diabetes outpatients.

AIMS: The COVID-19 pandemic impacted diabetes care by reducing diabetes outpatient visits and diabetes-related screening due to allocation of healthcare resources. Yet the impact of COVID-19 on diabetes outpatients has not been extensively evaluated. This study aimed to assess the effect of the COVID-19 pandemic on diagnostics and intermediate outcomes of outpatient diabetes care pre- and during COVID. METHODS: This observational cohort study included 8,442 diabetes patients in the Dutch Pediatric and Adult Registry of Diabetes (DPARD) visiting diabetes outpatient clinics in 2019 and 2021. A mixed-effects regression analysis was used to examine differences in target achievement of HbA1c, BMI, blood pressure, LDL-cholesterol, eGFR, and the difference in mean HbA1c between 2019 and 2020 among n = 1,426 outpatients who visited in both years. Analyses were adjusted for age, sex, and BMI. RESULTS: A 22.7% (21.6-23.8%, p < 0.001) decline in outpatient volume was observed during the pandemic (2020). BMI, lipid spectrum, kidney function, and HbA1c were assessed less frequently in 2020 than in 2019. In 2020, compared to 2019, the median HbA1c level increased by 2.2% (1.0 mmol/mol, p = 0.035) and the percentages of patients with known HbA1C meeting targets below 10, 8, 7% (86, 64, and 53 mmol/mol) decreased by 0.5%, 1.7% and 1.4%, respectively. Target blood pressure ≤ 130/80 mmHg was achieved more often in 2020 (15.0% versus 18.3%, p = 0.018), while HbA1c ≤ 86 mmol/mol was achieved less (89.3% versus 87.1%, p = 0.001), among diabetes outpatients seen in both 2019 and 2020. In patients visiting both years, HbA1c was 2.3% (1.9 mmol/l, 95% CI 1.2-2.5, p < 0.001) lower during the pandemic than in the prepandemic (2019). CONCLUSIONS: The COVID pandemic was associated with a marked reduction in patient volume in diabetes outpatient care among five hospitals. Among patients who received outpatient care both before and during the pandemic period, HbA1c control and blood pressure control enhanced during the pandemic. Re-evaluation of current diabetes outpatient care organization is warranted to ensure optimal diabetes care in future times.

[Round Table Diabetes Care: a collaboration for appropriate care]. / Samen met de patiënt bepalen wat passende zorg is.

The provision of appropriate care is the cornerstone of the Integrated Care Agreement (IZA) in the Netherlands. Appropriate care is presented as a way of working together to ensure that everyone continues to have access to reimbursed and good quality health care in the future. A method that has been successfully used within the diabetes field since 2016 and has taken shape as the Round Table Diabetes Care. The current article describes this approach.

[Prevalence and drug treatment of people with type 2 diabetes mellitus and a very high risk of cardiovascular disease]. / Diabetes type 2 én een hoog risico op hart- en vaatziekten.

OBJECTIVE: Dutch diabetes guidelines have been updated to incorporate specific therapies with cardiovascular and kidney outcomes benefit in type 2 diabetes patients (T2D) at very high risk for cardiorenal complications. This is part of a comprehensive approach to reduce the risk of diabetes-related complications, including management of glycemia, blood pressure, and lipids. The current study examines the prevalence of T2D at very high cardiorenal risk and the deployment of evidence-based approaches to lower this risk. DESIGN: Cross-sectional, observational study. METHOD: A representative population) with T2D in primary care (N= 64,224) was selected from the PHARMO Data Network. A very high risk of CVD was defined as: 1) established CVD, 2) CKD with (very) high cardiovascular risk and 3) heart failure. Drug treatment was determined according to prescriptions in 2019. RESULTS: 25,901 subjects with T2D had a very high risk of CVD (mean age 73.3 years; 42% female). Established CVD, CKD with (very) high cardiovascular risk, and heart failure were observed in 82%, 26% and 22% of patients, respectively. Low-dose salicylates, lipid-lowering and blood pressure-lowering medication were used by 39%, 70% and 69%, respectively. Glucose-lowering medication use included metformin (53%), sulfonylurea-derivatives (24%), and insulin (19%). 2% of the population used a SGLT2 inhibitor or GLP1-receptor agonist. CONCLUSION: 40% of people with DM2 have a very high risk of CVD. Although our findings reflect the recommendations of the previous treatment guideline for DM2, they also show that the new guideline has significant implications for the treatment of a large proportion of people with DM2.

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.

Glucose variability and mood in people with type 1 diabetes using ecological momentary assessment.

OBJECTIVE: Mood fluctuations related to blood glucose excursions are a commonly reported source of diabetes-distress, but research is scarce. We aimed to assess the relationship between real-time glucose variability and mood in adults with type 1 diabetes (T1D) using ecological momentary assessments. METHODS: In this prospective observational study, participants wore a masked continuous glucose monitor and received prompts on their smartphone 6 times a day to answer questions about their current mood (Profile Of Mood States (POMS)-SF (dimensions: Anxiety, Depressive symptoms, Anger, Fatigue, Vigor)) for 14 days. Mixed model analyses examined associations over time between daily Coefficient of Variation (CV) of blood glucose and mean and variability (CV) of POMS scores. Further, within-person differences in sleep and nocturnal hypoglycemia were explored. RESULTS: 18 people with T1D (10 female, mean age 44.3 years) participated. A total of 264 out of 367 days (70.2%) could be included in the analyses. No overall significant associations were found between CV of blood glucose and mean and CV of POMS scores, however, nocturnal hypoglycemia moderated the associations between CV of blood glucose and POMS scales (mean Fatigue Estimate 1.998, p < .006, mean Vigor Estimate -3.308, p < .001; CV Anger Estimate 0.731p = 0.02, CV Vigor Estimate -0.525, p = .006). CONCLUSION: We found no overall relationship between real-time glycemic variability and mood per day. Further research into within-person differences such as sleep and nocturnal hypoglycemia is warranted.

The health and budget impact of sodium-glucose co-transporter-2 inhibitors (SGLT2is) in The Netherlands.

OBJECTIVES: Type-2 Diabetes mellitus (T2DM) increases both the patient risk of cardiovascular disease (CVD) and renal outcomes, such as chronic kidney disease (CKD). Recent clinical trials of the glucose-lowering drug-class of sodium-glucose co-transporter-2 inhibitors (SGLT2is) have shown benefits in preventing CVD events and progression of CKD, leading to an update of the Dutch T2DM treatment guideline for patients at risk. The aim of this study is to assess the health and economic impact of the guideline-recommended utilization of SGLT2is in the Netherlands. METHODS: The patient population at risk was determined by multiplying Dutch T2DM prevalence rates with the total numbers of inhabitants of the Netherlands in 2020. Subsequently, two analyses, comparing a treatment setting before and after implementation of the new guideline for SGLT2is, were conducted. Clinical and adverse event rates in both settings as well as direct healthcare costs were sourced from the literature. Total costs were calculated by multiplying disease prevalence, event rates and costs associated to outcomes. One-time disutilities per event were included to estimate the health impact. The potential health and economic impact of implementing the updated guideline was calculated. RESULTS: Using a 5-year time horizon, the guideline-suggested utilization of SGLT2is resulted in a health impact equal to 4835 quality adjusted life years gained (0.0031 per patient per year) and €461 million cost-savings. The costs of treatment with SGLT2is were €813 million. Hence the net budget impact was €352 million for the total Dutch T2DM population, which translated to €0,57 per patient per day. CONCLUSION: SGLT2is offer an option to reduce the number of CVD and CKD related events and associated healthcare costs and health losses in the Netherlands. Further research is needed to include the benefits of improved T2DM management options from a broader societal perspective.HighlightsThe glucose-lowering drug-class of sodium-glucose co-transporter-2 inhibitors (SGLT2is) has shown benefits in preventing cardiovascular events and progression of kidney disease in patients with type-2 diabetes leading to a revision of the respective Dutch treatment guideline.The 5-year budget impact of the adoption of SGLT2is in the new treatment guideline was equal to €352 million or €0.57 per patient per day, with a total of 4385 quality adjusted life years gained.The introduction of SGLT2is for Dutch type-2 diabetes patients has the potential to substantially reduce the number of cardiovascular as well as renal disease events and related healthcare costs while also delivering a health benefit.

LOFIT (Lifestyle front Office For Integrating lifestyle medicine in the Treatment of patients): a novel care model towards community-based options for lifestyle change-study protocol.

BACKGROUND: A healthy lifestyle is indispensable for the prevention of noncommunicable diseases. However, lifestyle medicine is hampered by time constraints and competing priorities of treating physicians. A dedicated lifestyle front office (LFO) in secondary/tertiary care may provide an important contribution to optimize patient-centred lifestyle care and connect to lifestyle initiatives from the community. The LOFIT study aims to gain insight into the (cost-)effectiveness of the LFO. METHODS: Two parallel pragmatic randomized controlled trials will be conducted for (cardio)vascular disorders (i.e. (at risk of) (cardio)vascular disease, diabetes) and musculoskeletal disorders (i.e. osteoarthritis, hip or knee prosthesis). Patients from three outpatient clinics in the Netherlands will be invited to participate in the study. Inclusion criteria are body mass index (BMI) ≥25 (kg/m2) and/or smoking. Participants will be randomly allocated to either the intervention group or a usual care control group. In total, we aim to include 552 patients, 276 in each trial divided over both treatment arms. Patients allocated to the intervention group will participate in a face-to-face motivational interviewing (MI) coaching session with a so-called lifestyle broker. The patient will be supported and guided towards suitable community-based lifestyle initiatives. A network communication platform will be used to communicate between the lifestyle broker, patient, referred community-based lifestyle initiative and/or other relevant stakeholders (e.g. general practitioner). The primary outcome measure is the adapted Fuster-BEWAT, a composite health risk and lifestyle score consisting of resting systolic and diastolic blood pressure, objectively measured physical activity and sitting time, BMI, fruit and vegetable consumption and smoking behaviour. Secondary outcomes include cardiometabolic markers, anthropometrics, health behaviours, psychological factors, patient-reported outcome measures (PROMs), cost-effectiveness measures and a mixed-method process evaluation. Data collection will be conducted at baseline, 3, 6, 9 and 12 months follow-up. DISCUSSION: This study will gain insight into the (cost-)effectiveness of a novel care model in which patients under treatment in secondary or tertiary care are referred to community-based lifestyle initiatives to change their lifestyle. TRIAL REGISTRATION: ISRCTN ISRCTN13046877 . Registered 21 April 2022.

Gender gaps in type 1 diabetes care.

AIMS: Diabetes mellitus is one of the largest global health concerns of recent times. Women with diabetes mellitus have a higher excess risk of all-cause mortality and more vascular events than men. Focusing on type 1 diabetes, this could be caused by gender inequalities in delivered diabetes care. This study aims to assess gender differences in type 1 diabetes outpatient care, particularly diagnostics and outcomes. METHODS: This cross-sectional cohort study included all adult type 1 diabetes patients in the Dutch Pediatric and Adult Registry of Diabetes (DPARD) visiting diabetes outpatient clinics between 2016-2021. The frequency of process measurements, including physical examination and laboratory testing, was assessed among both sexes after adjustment for age and body mass index. Gender differences in eGFR ≥ 60, BMI-, and control in blood pressure and LDL-cholesterol were evaluated. Hospital variation in achieving HbA1c targets of 53 mmol/mol and median HbA1c were assessed. Cardiovascular risk scores were calculated in men and women using the Systematic Coronary Risk Evaluation (SCORE) European low-risk chart. RESULTS: Our study showed a 17% higher odds of reaching weight control and a 23% lower odds of achieving blood pressure targets in men than women. Gender-skewed cardiovascular mortality risk scores were found. Gender disparities in outcomes appear not to be caused by gender-biased attitudes in healthcare professionals since no gender differences were found in the performance of process measurements in type 1 diabetes care. In addition, hospitals appear to vary by extent of gender differences in achieving a target HbA1c of 53 mmol/mol. CONCLUSION: Gender equality exists in the diagnostic process of diabetes care. However, differences in weight control, blood pressure control, and cardiovascular mortality risk scores remain between both sexes, most likely due to multifactorial causes. Indications for interhospital variation in gender disparities in HbA1c control exist. Further focus on performance of process measurements between hospitals may identify areas for improvement of gender-skewed outcomes to further enhance Dutch diabetes care for both sexes.

Improved Effectiveness of Immediate Continuous Glucose Monitoring in Hypoglycemia-Prone People with Type 1 Diabetes Compared with Hypoglycemia-Focused Psychoeducation Following a Previous Structured Education: A Randomized Controlled Trial.

Objective: Stepped-care has been suggested in the management of patients with problematic hypoglycemia and impaired awareness of hypoglycemia (IAH), initially with psychoeducational programs based on blood glucose awareness training, progressing to diabetes technology in those with persisting need. We examined the clinical effectiveness of stepped-care starting with HypoAware and adding continuous glucose monitoring (CGM) as needed, versus immediate CGM in type 1 diabetes patients with problematic hypoglycemia despite previous structured education in insulin adjustment. Research Design and Methods: A randomized controlled trial (N = 52, mean age 53, 56% females). The stepped-care group attended HypoAware. If a severe hypoglycemic event (SHE) had occurred or IAH was still present after 6 months, CGM was initiated. The control group started immediate CGM. Primary endpoint was the number of participants with self-reported SHE. Secondary outcomes, evaluated at 6 and 12 months, were glycated hemoglobin (HbA1c), the number of participants with IAH time below range (TBR; <54 mg/dL), and patient-reported outcomes (PROs). Results: At 6 months, the number of patients reporting SHE had decreased significantly more in the CGM group: -39% (P < 0.05). HbA1c decreased more in the CGM group (-0.47 percentage-points, P < 0.05). IAH was restored in 31% of patients in both groups. TBR (<54 mg/dL) was lower in the CGM group (-2.4 percentage-points, P < 0.05). In the stepped-care group, 93% started CGM/intermittently scanned CGM. At 12 months, the number of patients reporting SHE was still higher in the stepped-care group. No differences were found in PROs. Conclusions: Immediate start of CGM is more effective than a hypoglycemia-focused reeducation program in reducing SHE risk and attaining glycemic targets in individuals with problematic hypoglycemia and IAH despite previous education in insulin dose adjustment. Trial registration: Netherlands Trial Register, NL64474.029.18.

Estimation of glomerular filtration rate for drug dosing in patients with very high or low body mass index.

An accurate estimated glomerular filtration rate (eGFR) is essential in drug dosing. This study demonstrates the limitations of indexed (ml/min/1.73 m2 ) and de-indexed (ml/min) eGFR based drug dosing in patients with obesity or underweight. This systematic study aimed to determine the most appropriate approach to estimate the GFR for standardized eGFR based drug dosing in these patients. (Raw) data of 12 studies were selected to investigate the accuracy and bias of both the indexed and de-indexed estimations of the Modification of Diet in Renal Disease (MDRD) study equation and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI), and of the Cockcroft-Gault (CG) in patients with obesity or underweight. Accuracy was calculated as the proportion of eGFR values within 30% of the measured GFR (P30) using an inert tracer (e.g., iohexol, inulin, 51 Cr-EDTA, or iothalamate clearance). An accuracy of at least 80% was considered acceptable. GFR values estimated with the CG, MDRD, and CKD-EPI differ significantly within a patient with obesity or underweight regardless of whether it is indexed or de-indexed. All studies, with two exceptions, show that all three equations are inaccurate for patients with underweight or class II obesity (P30: 55%-94%). De-indexing eGFR improves not or modestly the accuracy, and mostly remains below the 80% (P30: 62%-100%). CG was highly inaccurate in obese and underweight patients (P30: 7%-82%). Although these results show that CG is obsolete, the accuracy of MDRD and CKD-EPI is low in patients with obesity or underweight and de-indexing is not the solution. Better education and more accurate methods for appropriate drug dosing (e.g., measured GFR with inert tracer, therapeutic drug monitoring, or 24-h creatinine clearance) are recommended.