Does size matter? Hospital volume and resource use in paediatric diabetes care.

AIMS: Paediatric diabetes care has become increasingly specialised due to the multidisciplinary approach and technological developments. Guidelines recommend sufficient experience of treatment teams. This study evaluates associations between hospital volume and resource use and hospital expenditure in Dutch children with diabetes. METHODS: Retrospective cohort study using hospital claims data of 5082 children treated across 44 Dutch hospitals (2019-2020). Hospitals were categorised into three categories; small (≥20-100 patients), medium (≥100-200 patients) and large (≥200 patients). All-cause hospitalisations, consultations, technology and hospital expenditure were analysed and adjusted for age, sex, socio-economic status (SES) and hospital of treatment. RESULTS: Fewer hospitalisations were observed in large hospitals compared to small hospitals (OR 0.48; [95% CI 0.32-0.72]; p < 0.001). Median number of yearly paediatrician visits was 7 in large and 6 in small hospitals, the significance of which was attenuated in multilevel analysis (OR ≥7 consultations: 1.89; [95%CI 0.74-4.83]; p = 0.18). Technology use varies between individual hospitals, whereas pump usage and real-time continuous glucose monitoring showed no significant differences between hospital volumes. Mean overall expenditure was highest in medium-sized centres with €6434 per patient (IQR €2555-7955); the difference in diabetes care costs was not significant between hospital patient volumes. CONCLUSIONS: Care provision patterns vary by hospital patient volume. Large hospitals had the lowest hospitalisation rates. The use of diabetes technology was not different between hospital patient volumes. Medium-sized hospitals showed the highest overall expenditure, but diabetes care costs were similar across hospital volumes.

Socio-economic disparities in hospital care among Dutch patients with diabetes mellitus.

AIM: Socio-economic status (SES) influences diabetes onset, progression and treatment. In this study, the associations between SES and use of hospital care were assessed, focusing on hospitalizations, technology and cardiovascular complications. MATERIALS AND METHODS: This was an observational cohort study comprising 196 695 patients with diabetes (all types and ages) treated in 65 hospitals across the Netherlands from 2019 to 2020 using reimbursement data. Patients were stratified in low, middle, or high SES based on residential areas derived from four-digit zip codes. RESULTS: Children and adults with low SES were hospitalized more often than patients with middle or high SES (children: 22%, 19% and 15%, respectively; p < .001, adults: 28%, 25% and 23%; p < .001). Patients with low SES used the least technology: no technology in 48% of children with low SES versus 40% with middle SES and 38% with high SES. In children, continuous subcutaneous insulin infusion (CSII) and real-time continuous glucose monitoring (rtCGM) use was higher in high SES {CSII: odds ratio (OR) 1.54 [95% confidence interval (CI) 1.35-1.76]; p < .001; rtCGM OR 1.39 [95% CI 1.20-1.61]; p < .001} and middle SES [CSII: OR 1.41 (95% CI 1.24-1.62); p < .001; rtCGM: OR 1.27 (95% CI 1.09-1.47); p = .002] compared with low SES. Macrovascular (OR 0.78 (95% CI 0.75-0.80); p < .001) and microvascular complications [OR 0.95 (95% CI 0.93-0.98); p < .001] occurred less in high than in low SES. CONCLUSIONS: Socio-economic disparities were observed in patients with diabetes treated in Dutch hospitals, where basic health care is covered. Patients with low SES were hospitalized more often, used less technology, and adults with high SES showed fewer cardiovascular complications. These inequities warrant attention to guarantee equal outcomes for all.

Do sex differences in paediatric type 1 diabetes care exist? A systematic review.

AIMS/HYPOTHESIS: Sex differences are present in cardiovascular care and in outcomes among adults with type 1 diabetes mellitus, which typically commences in childhood. Whether sex influences care and outcomes in childhood is not known. This systematic review provides an overview of sex differences in children with type 1 diabetes, focusing on patient and disease characteristics, treatment, comorbidities and complications. METHODS: Literature in MEDLINE up to 15 June 2021 was searched, using the terms diabetes mellitus, sex characteristics, sex distribution, children and/or adolescents. All primary outcome studies on children with type 1 diabetes that mentioned a sex difference in outcome were included, with the exception of qualitative studies, case reports or case series. Studies not pertaining to the regular clinical care process and on incidence or prevalence only were excluded. Articles reporting sex differences were identified and assessed on quality and risk of bias using Joanna Briggs Institute critical appraisal tools. Narrative synthesis and an adapted Harvest plot were used to summarise evidence by category. RESULTS: A total of 8640 articles were identified, rendering 90 studies for review (n=643,217 individuals). Studies were of observational design and comprised cohort, cross-sectional and case-control studies. Most of the included studies showed a higher HbA1c in young female children both at diagnosis (seven studies, n=22,089) and during treatment (20 out of 21 studies, n=144,613), as well as a steeper HbA1c increase over time. Many studies observed a higher BMI (all ages, ten studies, n=89,700; adolescence, seven studies, n=33,153), a higher prevalence of being overweight or obese, and a higher prevalence of dyslipidaemia among the female sex. Hypoglycaemia and partial remission occurred more often in male participants, and ketoacidosis (at diagnosis, eight studies, n=3561) and hospitalisation was more often seen in female participants. Most of the findings showed that female participants used pump therapy more frequently (six studies, n=211,324) and needed higher insulin doses than male participants. Several comorbidities, such as thyroid disease and coeliac disease, appeared to be more common in female participants. All studies reported lower quality of life in female participants (15 studies, n=8722). Because the aim of this study was to identify sex differences, studies with neutral outcomes or minor differences may have been under-targeted. The observational designs of the included studies also limit conclusions on the causality between sex and clinical outcomes. CONCLUSIONS/INTERPRETATION: Sex disparities were observed throughout diabetes care in children with type 1 diabetes. Several outcomes appear worse in young female children, especially during adolescence. Focus on the cause and treatment of these differences may provide opportunities for better outcomes. REGISTRATION: This systematic review is registered in PROSPERO (CRD42020213640).

Fasting and meal-stimulated serum C-peptide in long-standing type 1 diabetes mellitus.

AIMS: This study aims to evaluate the stability of C-peptide over time and to compare fasting C-peptide and C-peptide response after mixed-meal tolerance test (MMTT) at T90 or T120 with C-peptide area under the curve (AUC) in long-standing type 1 diabetes. METHODS: We included 607 type 1 diabetes individuals with diabetes duration >5 years. C-peptide concentrations (ultrasensitive assay) were collected in the fasting state, and in a subpopulation after MMTT (T0, just prior to, T30-T60-T90-T120, 30-120 min after ingestion of mixed-meal) (n = 168). Fasting C-peptide concentrations (in n = 535) at Year 0 and Year 1 were compared. The clinical determinants associated with residual C-peptide secretion and the correspondence of C-peptide at MMTT T90 / T120 and total AUC were assessed. RESULTS: A total of 153 participants (25%) had detectable fasting serum C-peptide (i.e ≥ 3.8 pmol/L). Fasting C-peptide was significantly lower at Year 1 (p < 0.001, effect size = -0.16). Participants with higher fasting C-peptide had a higher age at diagnosis and shorter disease duration and were less frequently insulin pump users. Overall, 109 of 168 (65%) participants had both non-detectable fasting and post-meal serum C-peptide concentrations. The T90 and T120 C-peptide values at MMTT were concordant with total AUC. In 17 (10%) individuals, C-peptide was only detectable at MMTT and not in the fasting state. CONCLUSIONS: Stimulated C-peptide was detectable in an additional 10% of individuals compared with fasting in individuals with >5 years of diabetes duration. T90 and T120 MMTT measurements showed good concordance with the MMTT total AUC. Overall, there was a decrease of C-peptide at 1-year follow-up.

Healthcare expenditure and technology use in pediatric diabetes care.

BACKGROUND: Diabetes mellitus is one of the most common chronic diseases in childhood. With more advanced care options including ever-evolving technology, allocation of resources becomes increasingly important to guarantee equal care for all. Therefore, we investigated healthcare resource utilization, hospital costs, and its determinants in Dutch children with diabetes. METHODS: We conducted a retrospective, observational analysis with hospital claims data of 5,474 children with diabetes mellitus treated in 64 hospitals across the Netherlands between 2019-2020. RESULTS: Total hospital costs were €33,002,652 per year, and most of these costs were diabetes-associated (€28,151,381; 85.3%). Mean annual diabetes costs were €5,143 per child, and treatment-related costs determined 61.8%. Diabetes technology significantly increased yearly diabetes costs compared to no technology: insulin pumps € 4,759 (28.7% of children), Real-Time Continuous Glucose Monitoring € 7,259 (2.1% of children), and the combination of these treatment modalities € 9,579 (27.3% of children). Technology use increased treatment costs significantly (5.9 - 15.3 times), but lower all-cause hospitalisation rates were observed. In all age groups, diabetes technology use influenced healthcare consumption, yet in adolescence usage decreased and consumption patterns changed. CONCLUSIONS: These findings suggest that contemporary hospital costs of children with diabetes of all ages are driven primarily by the treatment of diabetes, with technology use as an important additive factor. The expected rise in technology use in the near future underlines the importance of insight into resource use and cost-effectiveness studies to evaluate if improved outcomes balance out these short-term costs of modern technology.

How low is really low? Comparison of two C-peptide assays to establish residual C-peptide production in type 1 diabetes.

INTRODUCTION: C-peptide is an important marker to assess residual insulin production in individuals with type 1 diabetes (T1D). The accuracy and detection limits of C-peptide assays are important to detect C-peptide microsecretion and to reliably observe changes over time in these people. We compared and verified two commercially available assays able to measure C-peptide in the picomolar range. METHODS: The ultrasensitive Mercodia enzyme-linked immunosorbent C-peptide assay (ELISA) was compared with the Beckman immunoradiometric assay (IRMA) for C-peptide, assessing reproducibility (coefficient of variation [CV]), limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoQ). RESULTS: For both assays within-run and between-run variation were high at the low (around the detection limit) C-peptide concentration range, with CVs of around 40%. LoB values for the ultrasensitive ELISA and the IRMA were 1.3 and 0.16 pmol/L respectively. LoD values were 2.4 and 0.54 pmol/L respectively. LoQ values were 9.7 and 3.8 pmol/L respectively. Only the IRMA met the specifications claimed by the manufacturer. CONCLUSIONS: The IRMA provided the lowest threshold for quantification of serum C-peptide. LoQ of commercially available assays should be established in-house before applying them in research studies and clinical trials in which low C-peptide levels have clinical or scientific relevance.

International comparison of glycaemic control in people with type 1 diabetes: an update and extension.

AIMS: To update and extend a previous cross-sectional international comparison of glycaemic control in people with type 1 diabetes. METHODS: Data were obtained for 520,392 children and adults with type 1 diabetes from 17 population and five clinic-based data sources in countries or regions between 2016 and 2020. Median HbA1c (IQR) and proportions of individuals with HbA1c < 58 mmol/mol (<7.5%), 58-74 mmol/mol (7.5-8.9%) and ≥75 mmol/mol (≥9.0%) were compared between populations for individuals aged <15, 15-24 and ≥25 years. Logistic regression was used to estimate the odds ratio (OR) of HbA1c < 58 mmol/mol (<7.5%) relative to ≥58 mmol/mol (≥7.5%), stratified and adjusted for sex, age and data source. Where possible, changes in the proportion of individuals in each HbA1c category compared to previous estimates were calculated. RESULTS: Median HbA1c varied from 55 to 79 mmol/mol (7.2 to 9.4%) across data sources and age groups so a pooled estimate was deemed inappropriate. OR (95% CI) for HbA1c < 58 mmol/mol (<7.5%) were 0.91 (0.90-0.92) for women compared to men, 1.68 (1.65-1.71) for people aged <15 years and 0.81 (0.79-0.82) aged15-24 years compared to those aged ≥25 years. Differences between populations persisted after adjusting for sex, age and data source. In general, compared to our previous analysis, the proportion of people with an HbA1c  < 58 mmol/l (<7.5%) increased and proportions of people with HbA1c ≥ 75 mmol/mol (≥9.0%) decreased. CONCLUSIONS: Glycaemic control of type 1 diabetes continues to vary substantially between age groups and data sources. While some improvement over time has been observed, glycaemic control remains sub-optimal for most people with Type 1 diabetes.

Differences in retinopathy prevalence and associated risk factors across 11 countries in three continents: A cross-sectional study of 156,090 children and adolescents with type 1 diabetes.

OBJECTIVE: To examine the prevalence, time trends, and risk factors of diabetic retinopathy (DR) among youth with type 1 diabetes (T1D) from 11 countries (Australia, Austria, Denmark, England, Germany, Italy, Luxemburg, Netherlands, Slovenia, United States, and Wales). SUBJECTS AND METHODS: Data on individuals aged 10-21 years with T1D for >1 year during the period 2000-2020 were analyzed. We used a cross-sectional design using the most recent year of visit to investigate the time trend. For datasets with longitudinal data, we aggregated the variables per participant and observational year, using data of the most recent year to take the longest observation period into account. DR screening was performed through quality assured national screening programs. Multiple logistic regression models adjusted for the year of the eye examination, age, gender, minority status, and duration of T1D were used to evaluate clinical characteristics and the risk of DR. RESULTS: Data from 156,090 individuals (47.1% female, median age 15.7 years, median duration of diabetes 5.2 years) were included. Overall, the unadjusted prevalence of any DR was 5.8%, varying from 0.0% (0/276) to 16.2% between countries. The probability of DR increased with longer disease duration (aORper-1-year-increase  = 1.04, 95% CI: 1.03-1.04, p < 0.0001), and decreased over time (aORper-1-year-increase  = 0.99, 95% CI: 0.98-1.00, p = 0.0093). Evaluating possible modifiable risk factors in the exploratory analysis, the probability of DR increased with higher HbA1c (aORper-1-mmol/mol-increase-in-HbA1c  = 1.03, 95% CI: 1.03-1.03, p < 0.0001) and was higher among individuals with hypertension (aOR = 1.24, 95% CI: 1.11-1.38, p < 0.0001) and smokers (aOR = 1.30, 95% CI: 1.17-1.44, p < 0.0001). CONCLUSIONS: The prevalence of DR in this large cohort of youth with T1D varied among countries, increased with diabetes duration, decreased over time, and was associated with higher HbA1c, hypertension, and smoking.

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.

Serum hepcidin concentrations in relation to iron status in children with type 1 diabetes.

Chronic low-grade inflammation in type 1 diabetes (T1D) might increase hepcidin synthesis, possibly resulting in functional iron deficiency (FID). We hypothesized that in T1D children with FID, hepcidin concentrations are increased compared to those with normal iron status and those with absolute iron deficiency (AID). We evaluated hepcidin concentrations in T1D children in relation to iron status, and investigated whether hepcidin is useful in assessing FID. A cross-sectional study was conducted. FID was defined as elevated zinc protoporphyrin/heme ratio and/or red blood cell distribution width, and AID as low serum ferritin concentration. Post-hoc analyses with different definitions of FID were performed, using transferrin saturation and reticulocyte hemoglobin content. Serum hepcidin concentrations were measured using mass-spectrometry. The IRODIAB-study is registered at www.trialregister.nl (NTR4642). This study included 215 T1D children with a median age of 13.7 years (Q1-Q3: 10.1-16.3). The median (Q1-Q3) hepcidin concentration in patients with normal iron status was 1.8 nmol/l (0.9-3.3), in AID-patients, 0.4 nmol/l (0.4-0.4) and in FID-patients, 1.6 nmol/l (0.7-3.5). Hepcidin concentrations in FID-patients were significantly higher than in AID-patients (p < 0.001). Irrespective of FID-definition used, hepcidin concentrations did not differ between FID-patients and patients with normal iron status. This might be explained by the influence of various factors on hepcidin concentrations, and/or by differences in response of iron parameters over time. Single hepcidin measurements do not seem useful in assessing FID in T1D children. Multiple hepcidin measurements over time in future studies, however, might prove to be more useful in assessing FID in children with T1D.

Clinical and genetic correlates of islet-autoimmune signatures in juvenile-onset type 1 diabetes.

AIMS/HYPOTHESIS: Heterogeneity in individuals with type 1 diabetes has become more generally appreciated, but has not yet been extensively and systematically characterised. Here, we aimed to characterise type 1 diabetes heterogeneity by creating immunological, genetic and clinical profiles for individuals with juvenile-onset type 1 diabetes in a cross-sectional study. METHODS: Participants were HLA-genotyped to determine HLA-DR-DQ risk, and SNP-genotyped to generate a non-HLA genetic risk score (GRS) based on 93 type 1 diabetes-associated SNP variants outside the MHC region. Islet autoimmunity was assessed as T cell proliferation upon stimulation with the beta cell antigens GAD65, islet antigen-2 (IA-2), preproinsulin (PPI) and defective ribosomal product of the insulin gene (INS-DRIP). Clinical parameters were collected retrospectively. RESULTS: Of 80 individuals, 67 had proliferation responses to one or more islet antigens, with vast differences in the extent of proliferation. Based on the multitude and amplitude of the proliferation responses, individuals were clustered into non-, intermediate and high responders. High responders could not be characterised entirely by enrichment for the highest risk HLA-DR3-DQ2/DR4-DQ8 genotype. However, high responders did have a significantly higher non-HLA GRS. Clinically, high T cell responses to beta cell antigens did not reflect in worsened glycaemic control, increased complications, development of associated autoimmunity or younger age at disease onset. The number of beta cell antigens that an individual responded to increased with disease duration, pointing to chronic islet autoimmunity and epitope spreading. CONCLUSIONS/INTERPRETATION: Collectively, these data provide new insights into type 1 diabetes disease heterogeneity and highlight the importance of stratifying patients on the basis of their genetic and autoimmune signatures for immunotherapy and personalised disease management.

Raising the Cut-Off Level of Anti-Tissue Transglutaminase Antibodies to Detect Celiac Disease Reduces the Number of Small Bowel Biopsies in Children with Type 1 Diabetes: A Retrospective Study.

OBJECTIVE: To study the optimal cut-off value for anti-tissue transglutaminase type 2 IgA antibodies (TG2A) in serum to select for diagnostic small bowel biopsies for celiac disease in children with type 1 diabetes mellitus. STUDY DESIGN: Children with type 1 diabetes mellitus with elevated TG2A titers and duodenal biopsies performed during the course of their diabetes treatment were included. Anti-endomysial antibodies were recorded if present. The optimal TG2A cut-off value, expressed as the ratio between obtained value and upper limit of normal (ULN), was determined using receiver operating characteristic curve analysis and compared with the cut-off value used in the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines in terms of sensitivity, specificity, positive and negative predictive value. RESULTS: We included 63 children. The optimal cut-off value for performing biopsies is demonstrated to be 11 times the ULN. Raising the cut-off value from 3 times the ULN to 11 times the ULN changed sensitivity from 96% to 87% and increased specificity from 36% to 73%, increased the positive predictive value from 88% to 94% and lowered negative predictive value from 67% to 53%. The percentage of normal histology was decreased from 12% to 6%. CONCLUSIONS: Increasing the TG2A cut-off value for performing duodenal biopsies in children with type 1 diabetes mellitus and suspected celiac disease leads to a substantial reduction of unnecessary biopsies. We advocate to adapt the European Society for Pediatric Gastroenterology, Hepatology and Nutrition 2012 guidelines for this group of children, including monitoring patients with TG2A levels of less than 11 times the ULN over time.

Detection and quantification of beta cells by PET imaging: why clinical implementation has never been closer.

In this issue of Diabetologia, Alavi and Werner ( https://doi.org/10.1007/s00125-018-4676-1 ) criticise the attempts to use positron emission tomography (PET) for in vivo imaging of pancreatic beta cells, which they consider as 'futile'. In support of this strong statement, they point out the limitations of PET imaging, which they believe render beta cell mass impossible to estimate using this method. In our view, the Alavi and Werner presentation of the technical limitations of PET imaging does not reflect the current state of the art, which leads them to questionable conclusions towards the feasibility of beta cell imaging using this approach. Here, we put forward arguments in favour of continuing the development of innovative technologies enabling in vivo imaging of pancreatic beta cells and concisely present the current state of the art regarding putative technical limitations of PET imaging. Indeed, far from being a 'futile' effort, we demonstrate that beta cell imaging is now closer than ever to becoming a long-awaited clinical reality.

Iron status and its association with HbA1c levels in Dutch children with diabetes mellitus type 1.

Children with diabetes mellitus (DM) type 1 may be at risk for iron deficiency (ID) although this has been little studied. ID is either an absolute (depleted iron stores) or a functional (restricted iron stores due to chronic inflammation) deficiency each requiring a different therapeutic approach. Unfortunately, absolute ID is often not distinguished from functional ID. Furthermore, iron-deficient anemia may influence hemoglobin A1c (HbA1c) levels. We aimed to determine the prevalence and type of ID and investigate its association with HbA1c levels in pediatric DM type 1 patients. We performed a two-center prospective observational study in which the iron status of Dutch children with DM type 1 was determined during a regular check-up. Absolute ID and functional ID were found in 13/227 (5.7%) and 100/214 (47%) patients, respectively, while only 15/113 (13%) patients also had anemia. HbA1c levels in patients with and without a deprived iron status (absolute or functional) were not significantly different (65 ± 17 vs. 65 ± 16 mmol/mol, p = 0.815). CONCLUSION: Functional, but not absolute, ID was common in Dutch pediatric DM type 1 patients. HbA1c levels were not associated with ID, which can be explained by the relatively mild deprived iron status in our patients. TRIAL REGISTRATION: NTR4642 What is Known: • Iron deficiency is either an absolute (depleted iron stores) or a functional (restricted iron stores due to chronic inflammation) deficiency each requiring a different therapeutic approach. • Children with diabetes mellitus type 1 may be at risk for both types of iron deficiency and this can influence their hemoglobin A1c levels although this has been little studied. What is New: • In Dutch children with diabetes mellitus type 1, functional, but not absolute iron deficiency, is common and should not be treated with iron replacement therapy. • Hemoglobin A1c levels were not associated with iron deficiency, probably due to the relatively mild deprived iron status in our patients.

Increased skin autofluorescence of children and adolescents with type 1 diabetes despite a well-controlled HbA1c: results from a cohort study.

BACKGROUND: Early identification of children and adolescents with type 1 diabetes at high risk for development of complications is important, as early intervention may prevent further deterioration. Here we investigate the applicability of assessing skin advanced glycation end products (sAGEs) by skin autofluorescence (SAF) as a potential surrogate risk marker. METHODS: This study included a cross-sectional analysis of SAF in 77 patients with type 1 diabetes mellitus and 118 healthy controls across age categories (11-12, 13-14, 15-16, and 17-19 years old). In patients, the impact of current and historical glycated hemoglobin (HbA1c) values, age, and duration of diabetes on SAF was studied in a retrospective cohort study and analyzed with multivariable analyses. RESULTS: SAF was significantly and similarly higher in patients when compared with controls across all age categories (P ≤0.009). For patients, age, duration of diabetes, and current and historical HbA1c were associated with SAF in univariate analysis. Multivariate analysis showed no association between HbA1c and SAF. A subgroup of patients with a HbA1c-within-target (≤7.5 %/59 mmol/mol) were observed to have high SAF. CONCLUSION: Children and adolescents with type 1 diabetes show higher SAF than controls. The presumed correlation of high HbA1c with high SAF does not exist in all patients. Thus, use of this non-invasive measure may provide a surrogate marker for diabetic complications, additional to HbA1c.

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.

Cohort profile: the 'Biomarkers of heterogeneity in type 1 diabetes' study-a national prospective cohort study of clinical and metabolic phenotyping of individuals with long-standing type 1 diabetes in the Netherlands.

PURPOSE: The 'Biomarkers of heterogeneity in type 1 diabetes' study cohort was set up to identify genetic, physiological and psychosocial factors explaining the observed heterogeneity in disease progression and the development of complications in people with long-standing type 1 diabetes (T1D). PARTICIPANTS: Data and samples were collected in two subsets. A prospective cohort of 611 participants aged ≥16 years with ≥5 years T1D duration from four Dutch Diabetes clinics between 2016 and 2021 (median age 32 years; median diabetes duration 12 years; 59% female; mean glycated haemoglobin (HbA1c) 61 mmol/mol (7.7%); 61% on insulin pump; 23% on continuous glucose monitoring (CGM)). Physical assessments were performed, blood and urine samples were collected, and participants completed questionnaires. A subgroup of participants underwent mixed-meal tolerance tests (MMTTs) at baseline (n=169) and at 1-year follow-up (n=104). Genetic data and linkage to medical and administrative records were also available. A second cross-sectional cohort included participants with ≥35 years of T1D duration (currently n=160; median age 64 years; median diabetes duration 45 years; 45% female; mean HbA1c 58 mmol/mol (7.4%); 51% on insulin pump; 83% on CGM), recruited from five centres and measurements, samples and 5-year retrospective data were collected. FINDINGS TO DATE: Stimulated residual C-peptide was detectable in an additional 10% of individuals compared with fasting residual C-peptide secretion. MMTT measurements at 90 min and 120 min showed good concordance with the MMTT total area under the curve. An overall decrease of C-peptide at 1-year follow-up was observed. Fasting residual C-peptide secretion is associated with a decreased risk of impaired awareness of hypoglycaemia. FUTURE PLANS: Research groups are invited to consider the use of these data and the sample collection. Future work will include additional hormones, beta-cell-directed autoimmunity, specific immune markers, microRNAs, metabolomics and gene expression data, combined with glucometrics, anthropometric and clinical data, and additional markers of residual beta-cell function. TRIAL REGISTRATION NUMBER: NCT04977635.

Prevalence of and Reasons for Discontinuation of Continuous Subcutaneous Insulin Infusion in People with Type 1 Diabetes: A Systematic Review.

The introduction of continuous subcutaneous insulin infusion in clinical care has led to more optimal glycemic and quality-of-life outcomes, compared with multiple daily injections (MDI). Despite this, some insulin pump users revert back to MDI. The aim of this review was to include the most recent rates of insulin pump discontinuation among people with type 1 diabetes and to identify reasons for and factors associated with discontinuation. A systematic literature search was conducted using the Embase.com, MEDLINE (via OVID), PsycINFO, and CINAHL databases. Titles and abstracts of eligible publications were screened, and baseline characteristics of the included studies were extracted, as were variables in the context of insulin pump use. Data were synthesized into themes: indications for insulin pump initiation, persons with type 1 diabetes (PWD)-reported reasons for, and factors associated with insulin pump discontinuation. A total of 826 eligible publications were identified and 67 were included. Discontinuation percentages ranged from 0% to 30% (median 7%). The most frequently mentioned reasons for discontinuation were wear-related issues (e.g., device attached to the body, interference with daily activities, discomfort, affected body image). Related factors included hemoglobin A1c (HbA1c) (17%), issues with following treatment recommendations (14%), age (11%), gender (9%), side effects (7%), and comorbidity- and complication-related factors (6%). Despite many developments in insulin pump technology, discontinuation rates and PWD-reported reasons for and factors associated with insulin pump discontinuation in more recent studies were comparable to earlier reviews/meta-analyses. Continuation of insulin pump treatment depends on a knowledgeable and willing health care provider (HCP) team and a close match with PWDs' wishes and needs.

Type 1 diabetes management: Room for improvement.

AIMS/HYPOTHESIS: Optimal diabetes care and risk factor management are important to delay micro- and macrovascular complications in individuals with type 1 diabetes (T1D). Ongoing improvement of management strategies requires the evaluation of target achievement and identification of risk factors in individuals who do (or do not) achieve these targets. METHODS: Cross-sectional data were collected from adults with T1D visiting six diabetes centers in the Netherlands in 2018. Targets were defined as glycated hemoglobin (HbA1c) <53 mmol/mol, low-density lipoprotein-cholesterol (LDL-c) <2.6 mmoL/L (no cardiovascular disease [CVD] present) or <1.8 mmoL/L (CVD present), or blood pressure (BP) <140/90 mm Hg. Target achievement was compared for individuals with and without CVD. RESULTS: Data from 1737 individuals were included. Mean HbA1c was 63 mmol/mol (7.9%), LDL-c was 2.67 mmoL/L, and BP 131/76 mm Hg. In individuals with CVD, 24%, 33%, and 46% achieved HbA1c, LDL-c, and BP targets respectively. In individuals without CVD these percentages were 29%, 54%, and 77%, respectively. Individuals with CVD did not have any significant risk factors for HbA1c, LDL-c, and BP target achievement. In comparison, individuals without CVD were more likely to achieve glycemic targets if they were men and insulin pump users. Smoking, microvascular complications, and the prescription of lipid-lowering and antihypertensive medication were negatively associated with glycemic target achievement. No characteristics were associated with LDL-c target achievement. Microvascular complications and antihypertensive medication prescription were negatively associated with BP target attainment. CONCLUSION: Opportunities for improvement of diabetes management exist for the achievement of glycemic, lipid, and BP targets but may differ between individuals with and without CVD.