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.

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.

Optimization of a Patient Distribution Framework: Second Wave COVID-19 Preparedness and Challenges in the Amsterdam Region.

To meet surge capacity and to prevent hospitals from being overwhelmed with COVID-19 patients, a regional crisis task force was established during the first pandemic wave to coordinate the even distribution of COVID-19 patients in the Amsterdam region. Based on a preexisting regional management framework for acute care, this task force was led by physicians experienced in managing mass casualty incidents. A collaborative framework consisting of the regional task force, the national task force, and the region's hospital crisis coordinators facilitated intraregional and interregional patient transfers. After hospital admission rates declined following the first COVID-19 wave, a window of opportunity enabled the task forces to create, standardize, and optimize their patient transfer processes before a potential second wave commenced. Improvement was prioritized according to 3 crucial pillars: process standardization, implementation of new strategies, and continuous evaluation of the decision tree. Implementing the novel "fair share" model as a straightforward patient distribution directive supported the regional task force's decisionmaking. Standardization of the digital patient transfer registration process contributed to a uniform, structured system in which every patient transfer was verifiable on intraregional and interregional levels. Furthermore, the regional task force team was optimized and evaluation meetings were standardized. Lines of communication were enhanced, resulting in increased situational awareness among all stakeholders that indirectly provided a safety net and an improved integral framework for managing COVID-19 care capacities. In this article, we describe enhancements to a patient transfer framework that can serve as an exemplary system to meet surge capacity demands during current and future pandemics.

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.

Short versus extended treatment with a carbapenem in patients with high-risk fever of unknown origin during neutropenia: a non-inferiority, open-label, multicentre, randomised trial.

BACKGROUND: Early antibiotic discontinuation has been advocated in haematology patients with fever of unknown origin during chemotherapy-induced neutropenia, but its safety is unknown. We aimed to assess if short treatment with carbapenems is non-inferior to extended treatment. METHODS: This non-inferiority, open-label, multicentre, randomised trial was done in six hospitals in the Netherlands. Adult patients (≥18 years) who were treated with intensive chemotherapy or haematopoietic stem-cell transplantation (HSCT) for a haematological malignancy, and had fever of unknown origin during high-risk neutropenia (<0·5 × 109/L expected for ≥7 days) were eligible. After onset of fever, patients received either 500 mg intravenous imipenem-cilastatin four times a day or 1000 mg intravenous meropenem three times a day. Between 48 h and 72 h of treatment, participants were randomly assigned (1:1) by a computer-generated sequence to receive a short-term (72 h [60-84]; short treatment group) or extended (≥9 days until being afebrile for 5 days or neutrophil recovery; extended treatment group) carbapenem regimen. The composite primary endpoint was treatment failure, defined as recurrent fever or a carbapenem-sensitive infection between day 4 and day 9 and septic shock or respiratory failure or death from day 4 until neutrophil recovery. The study was designed to assess the non-inferiority of the short treatment compared with the extended treatment regimen, with a non-inferiority margin of 10%. The primary outcome was adjudicated by an independent outcome committee, who were masked to treatment allocation, and was analysed in the intention-to-treat and per-protocol populations. The trial is completed and registered with ClinicalTrials.gov, NCT02149329. FINDINGS: Between Dec 1, 2014, and July 1, 2019, 281 patients were included in the intention-to-treat analysis: 144 (51%) patients were assigned to the short treatment group and 137 (49%) to the extended treatment group. Median age was 59 years (IQR 52-65); 109 (39%) patients were women and 172 (61%) were men; 205 (73%) patients received HSCT. In the intention-to-treat analysis, 28 (19%) of 144 patients in the short treatment group versus 21 (15%) of 137 patients in the extended treatment group had treatment failure (adjusted risk difference [ARD] 4·0% [90% CI -1·7% to 9·7%]; p=0·25). In the per-protocol analysis (n=225), 24 (23%) of 104 patients in the short treatment group and 19 (16%) of 121 patients in the extended treatment group had treatment failure (ARD 7·3% [0·3% to 14·9%]; p=0·11). The most common grade 3-5 infection-related adverse events were mucositis (23 [20%] of 114 adverse events in the short treatment group vs 28 [29%] of 98 adverse events in the extended treatment group), fever of unknown origin (20 [18%] vs 16 [16%] events), and bacteraemia (15 [13%] vs 13 [13%] events). The number of serious adverse events were higher in the short treatment group (23 [16%] of 144 patients) than in the extended treatment group (14 [10%] of 137 patients), due to an increased rate of readmission (17 [12%] patients in the short treatment group vs ten [7%] in the extended treatment group). Death before 30 days after neutrophil recovery occurred in five (3%) participants in the short treatment group: two due to progressive leukaemia, two due to candidaemia, and one due to Enterococcus faecium bacteraemia and drug-induced pneumonitis. One (1%) patient died in the extended treatment group due to candidaemia. None of the deaths were related to carbapenem-sensitive infections. INTERPRETATION: Early discontinuation of carbapenem treatment in patients with febrile neutropenia of unknown origin does not result in increased treatment failure. Our study supports short treatment if patients are afebrile after 3 days of carbapenem treatment. However, because secondary analyses suggested that serious adverse events and all-cause mortality occurred more often in patients who are persistantly febrile the short treatment group, we recommend vigilance for non-susceptible pathogens and early resumption of empirical therapy in patients who are deteriorating. FUNDING: The Netherlands Organisation for Health Research and Development and Fonds NutsOhra.

Combination therapy with exenatide decreases the dapagliflozin-induced changes in brain responses to anticipation and consumption of palatable food in patients with type 2 diabetes: A randomized controlled trial.

AIMS: Sodium-glucose cotransporter-2 inhibitors induce less weight loss than expected. This may be explained by sodium-glucose cotransporter-2 inhibitor-induced alterations in central reward- and satiety circuits, leading to increased appetite and food intake. Glucagon-like peptide-1 receptor agonists reduce appetite and body weight because of direct and indirect effects on the brain. We investigated the separate and combined effects of dapagliflozin and exenatide on the brain in response to the anticipation and consumption of food in people with obesity and type 2 diabetes. MATERIALS AND METHODS: As part of a larger study, this was a 16 week, double-blind, randomized, placebo-controlled trial. Subjects with obesity and type 2 diabetes were randomized (1:1:1:1) to dapagliflozin 10 mg with exenatide-matched placebo, exenatide twice-daily 10 µg with dapagliflozin-matched placebo, dapagliflozin plus exenatide, or double placebo. Using functional magnetic resonance imaging, the effects of treatments on brain responses to the anticipation of food and food receipt were assessed after 10 days and 16 weeks. RESULTS: After 10 days, dapagliflozin increased activation in right amygdala and right caudate nucleus in response to the anticipation of food, and tended to decrease activation in right amygdala in response to actual food receipt. After 16 weeks, no changes in brain activation were observed with dapagliflozin. Dapagliflozin plus exenatide reduced activation in right caudate nucleus and amygdala to the anticipation of food, and decreased activation in the right amygdala in response to food receipt after 16 weeks. CONCLUSIONS: The dapagliflozin-induced changes in brain activation may contribute to the discrepancy between observed and expected weight loss with dapagliflozin. Exenatide blunted the dapagliflozin-induced changes in brain activation, which may contribute to the additional weight loss with combined treatment.

Mechanisms underlying the blood pressure lowering effects of dapagliflozin, exenatide, and their combination in people with type 2 diabetes: a secondary analysis of a randomized trial.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) lower blood pressure (BP). When SGLT2i and GLP-1RA are combined, synergistic effects on BP have been observed. The mechanisms underlying these BP reductions are incompletely understood. The aim of this study was to assess the mechanisms underlying the BP reduction with the SGLT2i dapagliflozin, GLP-1RA exenatide, and dapagliflozin-exenatide compared with placebo in people with obesity and type 2 diabetes. METHODS: Sixty-six people with type 2 diabetes were randomized to 16 weeks of dapagliflozin 10 mg/day, exenatide 10 µg twice daily, dapagliflozin-exenatide, or placebo treatment. The effect of treatments on estimates of: (1) plasma volume (calculated by Strauss formula, bioimpedance spectroscopy, hematocrit, (2) autonomic nervous system activity (heart rate variability), (3) arterial stiffness (pulse wave applanometry), (4) systemic hemodynamic parameters including peripheral vascular resistance, cardiac output and stroke volume (all derived from non-invasively systemic hemodynamic monitoring), and (5) natriuresis (24-hour urine collection) were assessed after 10 days and 16 weeks of treatment. RESULTS: After 10 days, dapagliflozin reduced systolic BP (SBP) by - 4.7 mmHg, and reduced plasma volume. After 16 weeks, dapagliflozin reduced SBP by - 4.4 mmHg, and reduced sympathetic nervous system (SNS) activity. Exenatide had no effect on SBP, but reduced parasympathetic nervous system activity after 10 days and 16 weeks. After 10 days, dapagliflozin-exenatide reduced SBP by - 4.2 mmHg, and reduced plasma volume. After 16 weeks, dapagliflozin-exenatide reduced SBP by - 6.8 mmHg, and the reduction in plasma volume was still observed, but SNS activity was unaffected. CONCLUSIONS: The dapagliflozin-induced plasma volume contraction may contribute to the initial SBP reduction, while a reduction in SNS activity may contribute to the persistent SBP reduction. Dapagliflozin-exenatide resulted in the largest decrease in SBP. The effect on plasma volume was comparable to dapagliflozin monotherapy, and SNS activity was not reduced, therefore other mechanisms are likely to contribute to the blood pressure lowering effect of this combination, which need further investigation. Trial registration Clinicaltrials.gov, NCT03361098.

Effects of Dapagliflozin and Combination Therapy With Exenatide on Food-Cue Induced Brain Activation in Patients With Type 2 Diabetes.

CONTEXT: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) cause less weight loss than expected based on urinary calorie excretion. This may be explained by SGLT2i-induced alterations in central reward and satiety circuits, leading to increased appetite and food intake. Glucagon-like peptide-1 receptor agonists are associated with reduced appetite and body weight, mediated by direct and indirect central nervous system (CNS) effects. OBJECTIVE: We investigated the separate and combined effects of dapagliflozin and exenatide on the CNS in participants with obesity and type 2 diabetes. METHODS: This was a 16-week, double-blind, randomized, placebo-controlled trial. Obese participants with type 2 diabetes (n = 64, age 63.5 ±â€…0.9 years, BMI 31.7 ±â€…0.6 kg/m2) were randomized (1:1:1:1) to dapagliflozin 10 mg with exenatide-matched placebo, exenatide twice daily 10 µg with dapagliflozin-matched placebo, dapagliflozin and exenatide, or double placebo. Using functional MRI, the effects of treatments on CNS responses to viewing food pictures were assessed after 10 days and 16 weeks of treatment. RESULTS: After 10 days, dapagliflozin increased, whereas exenatide decreased CNS activation in the left putamen. Combination therapy had no effect on responses to food pictures. After 16 weeks, no changes in CNS activation were observed with dapagliflozin, but CNS activation was reduced with dapagliflozin-exenatide in right amygdala. CONCLUSION: The early increase in CNS activation with dapagliflozin may contribute to the discrepancy between observed and expected weight loss. In combination therapy, exenatide blunted the increased CNS activation observed with dapagliflozin. These findings provide further insights into the weight-lowering mechanisms of SGLT2i and GLP-1 receptor agonists.

Kidney hemodynamic profile and systemic vascular function in adults with type 2 diabetes: Analysis of three clinical trials.

AIMS: Glomerular hyperfiltration plays a key role in the pathophysiology of diabetic kidney disease (DKD). Mechanisms underlying this adverse hemodynamic profile are incompletely understood. We hypothesized that systemic vascular pathology, including endothelial dysfunction and arterial stiffness, relates to glomerular hyperfiltration indicated by filtration fraction (FF). METHODS: Baseline data of three trials of overweight adults with type 2 diabetes (TD2, n = 111) with relatively well preserved kidney function were analyzed. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and FF, were assessed with gold-standard clearance techniques. Systemic vascular resistance (SVR), an indicator of endothelial dysfunction, and pulse pressure (PP), a measure of arterial stiffness, were derived from continuous beat-to-beat monitoring. RESULTS: SVR related negatively to GFR (ß: -0.382, p < 0.001) and ERPF (ß: -0.475, p < 0.001), and positively to FF (ß:0.369, p < 0.001). Associations between SVR, ERPF and FF persisted after multivariable adjustments.. PP was negatively related to ERPF (ß: -0.252, p = 0.008), and positively to FF (ß: 0.257, p = 0.006), of which the latter remained significant in multivariable regression. CONCLUSION: Parameters of systemic vascular pathology, including endothelial dysfunction and arterial stiffness, relate to an adverse kidney hemodynamic profile characterized by glomerular hyperfiltration, which predisposes to the development of DKD.

Postprandial renal haemodynamic effects of the dipeptidyl peptidase-4 inhibitor linagliptin versus the sulphonylurea glimepiride in adults with type 2 diabetes (RENALIS): A predefined substudy of a randomized, double-blind trial.

AIM: To determine the effect of the dipeptidyl peptidase-4 inhibitor linagliptin on postprandial glomerular hyperfiltration compared with the sulphonylurea glimepiride in adults with type 2 diabetes (T2D). MATERIALS AND METHODS: In this predefined substudy within a randomized, double-blind, parallel-group, intervention trial, overweight people with T2D without renal impairment were treated with once-daily linagliptin 5 mg (N = 10) or glimepiride 1 mg (N = 13) as an add-on to metformin for 8 weeks. After a standardized liquid protein-rich meal, the glomerular filtration rate (GFR) and effective renal plasma flow were determined by inulin and para-aminohippuric acid clearance, respectively, based on timed urine sampling. Intrarenal haemodynamics were estimated using the Gomez equations. Glucoregulatory/vasoactive hormones, urinary pH and fractional excretions (FE) of sodium, potassium and urea were measured. RESULTS: Compared with glimepiride, linagliptin increased the postprandial filtration fraction (FF; mean difference 2.1%-point; P = .016) and estimated glomerular hydraulic pressure (mean difference 3.0 mmHg; P = .050), and tended to increase GFR (P = .08) and estimated efferent renal arteriolar resistance (RE ; P = .08) from baseline to week 8. No differences in FE were noted. Glimepiride reduced HbA1c more than linagliptin (mean difference -0.40%; P = .004), without between-group differences in time-averaged postprandial glucose levels. In the linagliptin group, change in FF correlated with change in mean arterial pressure (R = 0.807; P = .009) and time-averaged mean glucagon (R = 0.782; P = .008), but not with changes in glucose, insulin, intact glucagon-like peptide-1, renin or FENa . Change in glucagon was associated with change in RE (R = 0.830; P = .003). CONCLUSIONS: In contrast to our hypothesis, compared with glimepiride, linagliptin does not reduce postprandial hyperfiltration, yet appears to increase FF after meal ingestion by increasing blood pressure or RE .

Experience of the Coronavirus Disease (COVID-19) Patient Care in the Amsterdam Region: Optimization of Acute Care Organization.

The coronavirus disease (COVID-19) pandemic causes a large number of patients to simultaneously be in need of specialized care. In the Netherlands, hospitals scaled up their intensive care unit and clinical admission capacity at an early stage of the pandemic. The importance of coordinating resources during a pandemic has already been emphasized in the literature. Therefore, in order to prevent hospitals from being overwhelmed by COVID-19 admissions, national and regional task forces were established for the purpose of coordinating patient transfers. This review describes the experience of Regionaal Overleg Acute Zorg (ROAZ) region Noord-Holland Flevoland, in coordinating patient transfers in the Amsterdam region. In total, 130 patient transfers were coordinated by our region, of which 73% patients were transferred to a hospital within the region. Over a 2-month period, similarities regarding days with increased patient transfers were seen between our region and the national task force. In parallel, an increased incidence in hospital admissions in the Netherlands was observed. During a pandemic, an early upscale (an increase in surge spaces) of hospital admission capacity is imperative. Furthermore, it is preferred to establish national and regional task forces, coordinated by physicians experienced and trained in handling crisis situations, adhering full transparency regarding hospital admission capacity.

DPARD: rationale, design and initial results from the Dutch national diabetes registry.

BACKGROUND: Treatment of diabetes mellitus has majorly improved over the past century, however, the disease burden is high and its prevalence still expanding. Further insight in the diabetes population is imperative to improve the quality of diabetes care by enhancement of knowledge-based diabetes management strategies. To this end, in 2017 a Dutch nationwide consortium of diabetologists, paediatric endocrinologists, and diabetes patients has founded a national outpatient diabetes care registry named Dutch Pediatric and Adult Registry of Diabetes (DPARD). We aim to describe the implementation of DPARD and to provide an overview of the characteristics of patients included during the first 2 years. METHODS: For the DPARD cohort with long-term follow-up of observational nature, hospital data are gathered directly from electronic health records and securely transferred and stored. DPARD provides weekly updated clinical information on the diabetes population care on a hospital-level benchmarked against the national average. RESULTS: Between November 2017 and January 2020, 20,857 patients were included from 8 (11%) Dutch hospitals with a level of care distribution representative of all diabetic outpatients in the Netherlands. Among patients with known diabetes type, 41% had type 1 diabetes, 51% type 2 diabetes, and 8% had diabetes due to other causes. Characteristics of the total patient population were similar to patients with unknown diabetes classification. HbA1c levels decreased over the years, while BMI levels showed an increase over time. CONCLUSIONS: The national DPARD registry aims to facilitate investigation of prevalence and long-term outcomes of Dutch outpatients with diabetes mellitus and their treatment, thus allowing for quality improvement of diabetes care as well as allowing for comparison of diabetes care on an international level.

A Case of Silicone and Sarcoid Granulomas in a Patient with "Highly Cohesive" Silicone Breast Implants: A Histopathologic and Laser Raman Microprobe Analysis.

Foreign body giant cell (FBGC) reaction to silicone material in the lymph nodes of patients with silicone breast implants has been documented in the literature, with a number of case reports dating back to 1978. Many of these case reports describe histologic features of silicone lymphadenopathy in regional lymph nodes from patients with multiple sets of different types of implants, including single lumen smooth surface gel, single lumen textured surface gel, single lumen with polyethylene terephthalate patch, single lumen with polyurethane coating, and double lumen smooth surface. Only one other case report described a patient with highly-cohesive breast implants and silicone granulomas of the skin. In this article, we describe a patient with a clinical presentation of systemic sarcoidosis following highly cohesive breast implant placement. Histopathologic analysis and Confocal Laser Raman Microprobe (CLRM) examination were used to confirm the presence of silicone in the axillary lymph node and capsular tissues. This is the first report where chemical spectroscopic mapping has been used to establish and identify the coexistence of Schaumann bodies, consisting of calcium oxalate and calcium phosphate minerals, together with silicone implant material.

Kidney hemodynamic function in men and postmenopausal women with type 2 diabetes and preserved kidney function.

The progression of kidney disease may differ between sexes in type 2 diabetes (T2D), with previous studies reporting a slower decline in women. Glomerular hyperfiltration is a key factor driving the kidney function decline. The current study aimed to investigate the differences in kidney hemodynamic function between men and women with T2D. A cross-sectional analysis of pooled data from three studies compared kidney hemodynamic function between men and postmenopausal women with T2D without overt nephropathy. The outcome measures were glomerular filtration rate (GFR; inulin clearance), effective renal plasma flow (ERPF; p-aminohippurate clearance), filtration fraction (GFR/ERPF), and renal vascular resistance (RVR; mean arterial pressure/renal blood flow). Glomerular hydraulic pressure (PGLO) as well as afferent and efferent vascular resistance were estimated by Gomez formulae. Sex differences were assessed with linear regression models adjusted for systolic blood pressure, glucose, use of renin-angiotensin system blockers, and body mass index. In total, 101 men [age: 63 (58-68) yr, body mass index: 31.5 ± 3.9 kg/m2, GFR: 111 ± 18 mL/min, HbA1c: 7.4 ± 0.7%] and 27 women [age: 66 (62-69) yr, body mass index: 30.9 ± 4.5 kg/m2, GFR: 97 ± 11 mL/min, HbA1c: 7.1 ± 0.5%] were included. GFR was higher in men versus women [11.0 mL/min (95% confidence interval: 3.6, 18.4)]. Although statistically nonsignificant, PGLO trended higher in men [1.9 mmHg (95% confidence interval: -0.1, 4.0)], whereas RVR [-0.012 mmHg/L/min (95% confidence interval: -0.022, -0.002)] and afferent vascular resistance were lower [-361 dyn/s/cm5 (95% confidence interval: -801, 78)]. In conclusion, in adults without overt nephropathy, GFR was higher in men compared with women. PGLO also trended to be higher in men. Both findings are possibly related to afferent vasodilation and suggest greater prevalence of hyperfiltration. This could contribute to accelerated GFR loss over time in men with T2D.NEW & NOTEWORTHY In adults with type 2 diabetes, men had higher markers of hyperfiltration, which could potentially explain the accelerated progression of diabetic kidney disease in men compared with women.

The value of ambulatory blood pressure measurement to detect masked diastolic hypotension in older patients treated for hypertension.

OBJECTIVE: assess how many patients with low ambulatory diastolic blood pressure (DBP) are not identified when relying on office DBP alone, and thus have 'masked diastolic hypotension'. DESIGN: cross-sectional, retrospective cohort study. SETTING: academic hospital. SUBJECTS: 848 patients treated for hypertension who received ambulatory blood pressure monitoring (ABPM). METHODS: cut-off value between on- and off-target systolic blood pressure (SBP): 140 mmHg. Cut-off for low office and/or ambulatory DBP: DBP ≤ 70 mmHg. 'Masked diastolic hypotension' was defined as office DBP > 70 mmHg and mean ambulatory DBP ≤ 70 mmHg. RESULTS: mean age of the sample was 60 ± 13 years, 50% was female, 37% had diabetes, 42% preexisting cardiovascular disease (CVD), mean office blood pressure (BP) was 134/79 mmHg. In all patients (n = 848), low office DBP was present in n = 84(10%), while n = 183(22%) had low ambulatory DBP. In all patients with normal-to-high office DBP (n = 764), n = 122(16%) had 'masked diastolic hypotension'. In this group, ambulatory DBP was 14-19 mmHg lower than office DBP. Patients with low ambulatory DBP were older, had more (cardiovascular) comorbidities, and used more (antihypertensive) drugs. Antihypertensive drugs were lowered or discontinued in 30% of all patients with 'masked diastolic hypotension' due to side effects. CONCLUSIONS: 'masked diastolic hypotension' is common among patients treated for hypertension, particularly in older patients with CVD (e.g. coronary artery disease, diabetes), patient groups in which the European Society of Cardiology/Hypertension guideline advises to prevent low DBP. Although it remains to be examined at which BP levels the harms of low DBP outweigh the benefits of lowering SBP, our observations are aimed to increase awareness among physicians.

Liraglutide and sitagliptin have no effect on intestinal microbiota composition: A 12-week randomized placebo-controlled trial in adults with type 2 diabetes.

AIM: Preclinical data suggest that treatment with either glucagon-like peptide (GLP)-1 receptor agonists or dipeptidyl peptidase (DPP)-4 inhibitors could change the intestinal microbiome and thereby contribute to their beneficial (cardio)metabolic effects. Therefore, our study aimed to investigate the effects of these agents on microbiota composition in adults with type 2 diabetes (T2D). METHODS: A total of 51 adults with T2D (mean ± SD: age 62.8 ± 6.9 years, BMI 31.8 ± 4.1 kg/m2, HbA1c 7.3 ± 0.6%) treated with metformin and/or sulphonylureas were included in the 12-week randomized, double-blind trial. Patients were given the GLP-1 receptor agonist liraglutide (1.8 mg sc) or the DPP-4 inhibitor sitagliptin (100 mg), or matching placebos, once daily for 12 weeks. Faecal samples were collected at baseline and at 12 weeks after the start of the intervention. Microbiota analyses were performed by 16S rRNA gene-sequencing analysis. Bile acids were measured in faeces and plasma. RESULTS: Liraglutide decreased HbA1c by 1.3% (95% CI: -1.7 to -0.9) and tended to reduce body weight (-1.7 kg, 95% CI: -3.6 to 0.3), but increased faecal secondary bile acid deoxycholic acid. Sitagliptin lowered HbA1c by 0.8% (95% CI: -1.4 to -0.4) while body weight remained stable (-0.8 kg, 95% CI: -2.7 to 1.0), but increased faecal levels of cholic acid, chenodeoxycholic acid and ursodeoxycholic acid. However, neither liraglutide nor sitagliptin affected either alpha or beta diversity of the intestinal microbiota, nor were changes in microbial composition related to clinical parameters. CONCLUSION: These data suggest that the beneficial effects of liraglutide and sitagliptin on glucose metabolism, body weight and bile acids, when used as add-on therapies to metformin or sulphonylureas, are not linked to changes in the intestinal microbiota (NCT01744236).

National diabetes registries: do they make a difference?

AIMS: The global epidemic of diabetes mellitus continues to expand, including its large impact on national health care. Measuring diabetes outcomes and their causes of variation highlights areas for improvement in care and efficiency gains; large registries carry this potential. By means of a systematic review, we aimed to give an overview of national registries worldwide by quantifying their data and assessing their influence on diabetes care. METHODS: The literature on MEDLINE up to March 31, 2020, was searched, using keywords diabetes mellitus, national, registry, registration, and/or database. National disease-specific registries from corresponding articles were included. Database characteristics and clinical variables were obtained. All registries were compared to the ICHOM standard set of outcomes. RESULTS: We identified 12 national clinical diabetes registries, comprising a total of 7,181,356 diabetic patients worldwide. Nearly all registries recorded weight, HbA1c, lipid profile, and insulin treatment; the recording of other variables varied to a great extent. Overall, registries corresponded fairly well with the ICHOM set. Most registries proved to monitor and improve the quality of diabetes care using guidelines as a benchmark. The effects on national healthcare policy were more variable and often less clear. CONCLUSIONS: National diabetes registries confer clear insights into diagnostics, complications, and treatment. The extent to which registries influenced national healthcare policy was less clear. A globally implemented standard outcome set has the potential to improve concordance between national registries, enhance the comparison and exchange of diabetes outcomes, and allocate resources and interventions where most needed.

The Value of Artificial Intelligence in Laboratory Medicine.

OBJECTIVES: As laboratory medicine continues to undergo digitalization and automation, clinical laboratorians will likely be confronted with the challenges associated with artificial intelligence (AI). Understanding what AI is good for, how to evaluate it, what are its limitations, and how it can be implemented are not well understood. With a survey, we aimed to evaluate the thoughts of stakeholders in laboratory medicine on the value of AI in the diagnostics space and identify anticipated challenges and solutions to introducing AI. METHODS: We conducted a web-based survey on the use of AI with participants from Roche's Strategic Advisory Network that included key stakeholders in laboratory medicine. RESULTS: In total, 128 of 302 stakeholders responded to the survey. Most of the participants were medical practitioners (26%) or laboratory managers (22%). AI is currently used in the organizations of 15.6%, while 66.4% felt they might use it in the future. Most had an unsure attitude on what they would need to adopt AI in the diagnostics space. High investment costs, lack of proven clinical benefits, number of decision makers, and privacy concerns were identified as barriers to adoption. Education in the value of AI, streamlined implementation and integration into existing workflows, and research to prove clinical utility were identified as solutions needed to mainstream AI in laboratory medicine. CONCLUSIONS: This survey demonstrates that specific knowledge of AI in the medical community is poor and that AI education is much needed. One strategy could be to implement new AI tools alongside existing tools.