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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
A previous single-center study established a mathematical model for predicting the adult height (AH) in girls with idiopathic central precocious puberty (CPP).
To perform internal and external ...validations by comparing the actual AH to the calculated AH established by this model and to update it.
The original formula, calculated AH (cm) = 2.21 (height at initial evaluation, SD) + 2.32 (target height, SD) - 1.83 (luteinizing hormone/follicle-stimulating hormone peaks ratio) + 159.68, was established in a sample of 134 girls (group 4) and was applied to additional girls with CPP seen in the same center (group 1, n = 35), in Germany (group 2, n = 43) and in the Netherlands (group 3, n = 72). This formula has been updated based on these extended data, and both versions are available at the following location: http://www.kamick.org/lemaire/med/girls-cpp15.html.
Despite the differences among the 4 groups in terms of their characteristics at the initial evaluation and the percentages of patients treated with the gonadotropin-releasing hormone analogue, they have similar calculated and actual AHs. The actual AHs are 162.2±7.0, 163.0±7.6, 162.4±7.7 and 162.1±5.6 cm in groups 1 to 4, respectively. They are highly correlated with the AHs calculated by the formula established in the original group (group 4), with R at 0.84, 0.67 and 0.69 in groups 1 to 3, respectively. When the actual AHs and the AHs predicted by the Bayley and Pinneau method are compared, the R is 0.76, 0.51 and 0.64 in groups 1 to 3, respectively. The absolute differences between actual AHs and the calculated AHs are greater than 1 SD (5.6 cm) in 15%, 35% and 28% of the patients in groups 1 to 3, respectively.
This study validates and updates the previously established formula for predicting AH in girls with CPP. This updated formula can help clinicians to make treatment decisions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Restoration of immune tolerance may halt progression of autoimmune diseases. Tolerogenic dendritic cells (tolDC) inhibit antigen-specific proinflammatory T-cells, generate antigen-specific regulatory ...T-cells and promote IL-10 production
, providing an appealing immunotherapy to intervene in autoimmune disease progression.
A placebo-controlled, dose escalation phase 1 clinical trial in nine adult patients with long-standing type 1 diabetes (T1D) demonstrated the safety and feasibility of two (prime-boost) vaccinations with tolDC pulsed with a proinsulin peptide. Immunoregulatory effects were monitored by antigen-specific T-cell assays and flow and mass cytometry.
The tolDC vaccine induced a profound and durable decline in pre-existing autoimmune responses to the vaccine peptide up to 3 years after therapy and temporary decline in CD4 and CD8+ T-cell responses to other islet autoantigens. While major leukocyte subsets remained stable, ICOS
CCR4
TIGIT
Tregs and CD103
tissue-resident and CCR6
effector memory CD4
T-cells increased in response to the first tolDC injection, the latter declining thereafter below baseline levels.
Our data identify immune correlates of mechanistic efficacy of intradermally injected tolDC reducing proinsulin autoimmunity in T1D.
ObjectivesCardiovascular disease (CVD) is a precarious complication of type 1 diabetes (T1D). Alongside glycaemic control, lipid and blood pressure (BP) management are essential for the prevention of ...CVD. However, age-specific differences in lipid and BP between individuals with T1D and the general population are relatively unknown.DesignCross-sectional study.SettingSix diabetes outpatient clinics and individuals from the Lifelines cohort, a multigenerational cohort from the Northern Netherlands.Participants2178 adults with T1D and 146 22 individuals without diabetes from the general population.Primary and secondary outcome measuresTotal cholesterol, low-density lipoprotein cholesterol (LDL-cholesterol), systolic BP (SBP) and diastolic BP (DBP), stratified by age group, glycated haemoglobin category, medication use and sex.ResultsIn total, 2178 individuals with T1D and 146 822 without diabetes were included in this study. Total cholesterol and LDL-cholesterol were lower and SBP and DBP were higher in individuals with T1D in comparison to the background population. When stratified by age and medication use, total cholesterol and LDL-cholesterol were lower and SBP and DBP were higher in the T1D population. Men with T1D achieved lower LDL-cholesterol levels both with and without medication in older age groups in comparison to women. Women with T1D had up to 8 mm Hg higher SBP compared with the background population, this difference was not present in men.ConclusionsLipid and BP measurements are not comparable between individuals with T1D and the general population and are particularly unfavourable for BP in the T1D group. There are potential sex differences in the management of LDL-cholesterol and BP.
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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Samenvatting
De snelle technologische ontwikkelingen in de diabeteszorg zorgen voor betere uitkomsten, maar ook voor een toename van dataverkeer tussen patiënt en zorgverleners. De noodzaak voor die ...verbetering van uitkomsten wordt beschreven. De stappen die daartoe zijn gezet en die nog kunnen worden gezet, zijn aan de inzet van deze technologie verbonden. Daarbij moet en kan ook de diabeteszorg worden veranderd, waardoor er op nieuwe wijze continuïteit in contacten en coaching komt en traditionele zorg (3-4 x per jaar een consult) verandert naar nieuwe virtuele en automatische vormen. Daarvoor is een verandering nodig: in plaats van dat elk contact vanuit één patiënt of behandelaar wordt gestart, wordt op basis van de glucosedata populatiemanagement van diabetes verricht. Daarbij wordt op basis van zorggegevens een (continue) triage verricht en wordt direct persoonsgerichte zorg aangeboden aan mensen die problemen ervaren of risico hebben op problemen. De combinatie van diabetestechnologie en populatiemanagementmethoden wordt aan de hand van het ontwikkelde CloudCare-systeem toegelicht.
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.
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.
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.
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
IntroductionCardiovascular disease (CVD) is the leading cause of mortality in individuals with type 1 diabetes mellitus (T1DM). Cardiovascular risk management is therefore essential in the management ...of individuals with T1DM. This study describes the performance of lipid and blood pressure management in individuals with T1DM using three guidelines.Research design and methodsIndividuals ≥18 years with T1DM, treated with insulin for ≥1 year, visiting Diabeter or the University Medical Center Groningen between January 1, 2018 and December 31, 2018, were included. Lipid and blood pressure management were examined using the Dutch, American Diabetes Association (ADA) and National Institute for Health and Care Excellence (NICE) guidelines. Concordance of recommended and prescribed lipid-lowering (LLM) or antihypertensive medication (AHM) was assessed per guideline and 10-year age groups. Achievement of treatment targets was assessed for those prescribed medication.ResultsA total of 1855 individuals with T1DM were included. LLM and AHM was prescribed in 19% and 17%, respectively. In individuals recommended LLM, this was prescribed in 22%–46% according to Dutch, ADA or NICE guideline recommendations. For individuals recommended AHM, this was prescribed in 52%–75%. Recommended and actual prescription of LLM and AHM increased over age for all three guidelines. However, discordance between treatment recommendation and medication prescribed was higher in younger, compared with older, age groups. Low-density lipoprotein-cholesterol targets were achieved by 50% (without CVD) and 31% (with CVD) of those prescribed LLM. The blood pressure target was achieved by 46% of those prescribed AHM.ConclusionThis study suggests that there is undertreatment of lipid and blood pressure according to guideline recommendations, particularly in younger age groups. Treatment targets are not met by most individuals prescribed medication, while guidelines recommendations differ considerably. We recommend to investigate the factors influencing undertreatment of lipid and blood pressure management in individuals with T1DM.
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.
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.
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.
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.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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