Real-World Outcomes of Patients Starting Intravenous and Transitioning to Subcutaneous Vedolizumab in Inflammatory Bowel Disease.

BACKGROUND: Real-world data on starting intravenous (IV) vedolizumab (VDZ) and transitioning to subcutaneous (SC) treatment in inflammatory bowel disease (IBD) are scarce. AIMS: To assess treatment outcomes of patients with IBD starting IV VDZ and switching to SC VDZ in routine clinical care. METHODS: Adult patients with IBD switching from IV to SC VDZ treatment between 1 March 2020 and 31 December 2021 were identified from the Swedish IBD quality register. The primary outcome was SC VDZ persistence. Secondary outcomes included clinical remission, changes in quality of life (QoL) according to EuroQual 5-Dimensions 5-Levels (EQ-5D-5L) and the Short-Health Scale (SHS) and inflammatory markers, including faecal Calprotectin (FCP). RESULTS: Altogether, 406 patients with IBD (Crohn's disease, n = 181; ulcerative colitis, n = 225) were identified. After a median follow-up of 30 months from starting IV VDZ treatment, the persistence rates were 98%(178/181) in Crohn's disease and 94% (211/225) in ulcerative colitis. Most patients (84%) transitioned during maintenance therapy, and the median follow-up from switch to SC VDZ was 10 months. Compared to baseline, statistically significant improvements were observed in all domains of the SHS, EQ-5D index value and visual analogue scale. Median (interquartile range) FCP concentrations (µg/g) decreased from 459 (185-1001) to 65 (26-227) in Crohn's disease (n = 45; p < 0.001) and from 646 (152-1450) to 49 (20-275) in ulcerative colitis (n = 58; p < 0.001). CONCLUSION: Initiating IV VDZ and switching to SC treatment was associated with high persistence rates and improvements in measures of QoL and FCP. These findings are reassuring for patients who start IV VDZ and switch to SC VDZ.

The importance of factors early in life for development of eating disorders in young people, with some focus on type 1 diabetes.

AIM: Eating disorders have a serious impact on quality of life, especially when combined with Type 1 diabetes. We investigated eating disorders in relation to factors early in life with some focus on Type 1 diabetes. METHODS: Out of 21,700 children born 1st of Oct 1997-1st of Oct 1999 17,055 (78.6%) were included in ABIS (All Babies in southeast Sweden) and 16,415 had adequate questionnaires. ICD-10 diagnosis from The National Patient Register was merged with the ABIS data. RESULTS: In total 247 individuals, 19 boys (7.7%) and 219 girls (92.3%) out of 16,415 (1.5%) developed eating disorders (EDs), 167 (1.0%) Type 1 diabetes of whom 7 (4.2%) also got eating disorders (ED) (OR 3.25 (1.47-7.28); p = 0.04), all of them years after diagnosis of Type 1 diabetes. EDs was associated with high parental education especially in fathers (OR 1.65 (1.09-2.50); p = 0.02) and to at birth anxiety, and depression among mothers. There was no association with the duration of breastfeeding. CONCLUSIONS: Eating disorders are common in girls, with increased risk in high-educated but psychologically vulnerable families. Prevalence is increased in type 1 diabetes. Even modern diabetes treatment needs to be completed with psychological support. LEVEL OF EVIDENCE: Level III: Evidence obtained from well-designed cohort or case-control analytic studies.

Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes.

Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune ß-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.

SARS-CoV-2 and pregnancy outcomes under universal and non-universal testing in Sweden: register-based nationwide cohort study.

OBJECTIVE: To assess associations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and pregnancy outcomes considering testing policy and test-positivity-to-delivery interval. DESIGN: Nationwide cohort study. SETTING: Sweden. POPULATION: From the Pregnancy-Register we identified 88 593 singleton births, 11 March 2020-31 January 2021, linked to data on SARS-CoV-2-positivity from the Public Health Agency, and information on neonatal care admission from the Neonatal Quality Register. Adjusted odds ratios (aORs) were estimated stratified by testing-policy and test-positivity-to-delivery interval. MAIN OUTCOME MEASURES: Five-minute Apgar score, neonatal care admission, stillbirth and preterm birth. RESULTS: During pregnancy, SARS-CoV-2 test-positivity was 5.4% (794/14 665) under universal testing and 1.9% (1402/73 928) under non-universal testing. There were generally lower risks associated with SARS-CoV-2 under universal than non-universal testing. In women testing positive >10 days from delivery, generally no significant differences in risk were observed under either testing policy. Neonatal care admission was more common (15.3% versus 8.0%; aOR 2.24, 95% CI 1.62-3.11) in women testing positive ≤10 days before delivery under universal testing. There was no significant association with 5-minute Apgar score below 7 (1.0% versus 1.7%; aOR 0.64, 95% CI 0.24-1.72) or stillbirth (0.3% versus 0.4%; aOR 0.72, 95% CI 0.10-5.20). Compared with term births (2.1%), test-positivity was higher in medically indicated preterm birth (5.7%; aOR 2.70, 95% CI 1.60-4.58) but not significantly increased in spontaneous preterm birth (2.3%; aOR 1.12, 95% CI 0.62-2.02). CONCLUSIONS: Testing policy and timing of test-positivity impact associations between SARS-CoV-2-positivity and pregnancy outcomes. Under non-universal testing, women with complications near delivery are more likely to be tested than women without complications, thereby inflating any association with adverse pregnancy outcomes compared with findings under universal testing. TWEETABLE ABSTRACT: Testing policy and time from SARS-CoV-2 infection to delivery influence the association with pregnancy outcomes.

Glycemic control and complications of type 1 diabetes among children in Tanzania.

INTRODUCTION: Knowledge on Type 1 Diabetes (T1D) in sub-Saharan Africa is scarce. This study aimed at assessing microvascular complications of Type 1 diabetes in young patients. METHOD: A retrospective study based on medical recordings from 2010-2016 was done. 604 children and young adults with T1D were recruited from five hospitals with pediatric diabetes clinics. 559 patients aged 2-35 years with known date of birth were included. Clinical data on retinopathy and neuropathy were analyzed. There was no information on renal function/ nephropathy. RESULTS: Most data were missing. There was documentation on HbA1C, plasma glucose and complications in less than half of the patient files. Of those with registered HbA1c values (42.2%), 36% had HbA1c > 12.5%. There was high prevalence of retinopathy (21.5%) and neuropathy (29.4%) in spite of short mean duration of diabetes (6.2 ± 4.1 years). CONCLUSION: Many patients with T1D in Tanzania have poor metabolic control. Microvascular complications are common already after a short duration of diabetes, but the results have to be interpreted with great caution because of study limitations. Better pediatric diabetes care as well as increased awareness of diabetes is needed. Studies in resource-poor countries need careful planning, if possible with prospective design.

LDL cholesterol level as a risk factor for retinopathy and nephropathy in children and adults with type 1 diabetes mellitus: A nationwide cohort study.

BACKGROUND: Microvascular complications are common in people with diabetes, where poor glycaemic control is the major contributor. The aim of this study was to explore the association between elevated LDL cholesterol levels and the risk of retinopathy or nephropathy in young individuals with type 1 diabetes. METHODS: This was a nationwide observational population-based cohort study, including all children and adults with a duration of type 1 diabetes of ≤ 10 years, identified in the Swedish National Diabetes Register between 1998 and 2017. We calculated the crude incidence rates with 95% confidence intervals (CIs) and used multivariable Cox regression to estimate crude and adjusted hazard ratios (HRs) of retinopathy or nephropathy in four LDL cholesterol categories: <2.6 (Reference), 2.6-3.4, 3.4-4.1 and > 4.1 mmol L-1 . RESULTS: In total, 11 024/12 350 (retinopathy/nephropathy, both cohorts, respectively) children and adults (median age 21 years, female 42%) were followed up to 28 years from diagnosis until end of study. Median duration of diabetes when entering the study was 6 and 7 years in the retinopathy and nephropathy cohort, respectively. Median LDL cholesterol was 2.4 mmol L-1 , and median HbA1c level was 61 mmol mol-1 (7.7 %). After multivariable adjustment, the HRs (95% CI) for retinopathy in individuals with LDL cholesterol levels of 2.6-3.4, 3.4-4.1 or > 4.1 mmol L-1 were as follows: 1.13 (1.03-1.23), 1.16 (1.02-1.32) and 1.18 (0.99-1.41), compared with the reference. The corresponding numbers for nephropathy were as follows: 1.15 (0.96-1.32), 1.30 (1.03-1.65) and 1.41 (1.06-1.89). CONCLUSIONS: Young individuals with type 1 diabetes exposed to high LDL cholesterol levels have an increased risk of retinopathy and nephropathy independent of glycaemia and other identified risk factors for vascular complications.

European dermatology forum: Updated guidelines on the use of extracorporeal photopheresis 2020 - Part 2.

BACKGROUND: Following the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma published in 1983, this technology has received continued use and further recognition for additional earlier as well as refractory forms. After the publication of the first guidelines for this technology in the JEADV in 2014, this technology has maintained additional promise in the treatment of other severe and refractory conditions in a multidisciplinary setting. It has confirmed recognition in well-known documented conditions such as graft-vs.-host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection including lung, heart and liver and to a lesser extent inflammatory bowel disease. MATERIALS AND METHODS: In order to further provide recognized expert practical guidelines for the use of this technology for all indications, the European Dermatology Forum (EDF) again proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. All authors had the opportunity to review each contribution as it was added. RESULTS AND CONCLUSION: These updated 2020 guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion. The guidelines were divided into two parts: PART I covers Cutaneous T-cell lymphoma, chronic graft-vs.-host disease and acute graft-vs.-host disease, while PART II will cover scleroderma, solid organ transplantation, Crohn's disease, use of ECP in paediatric patients, atopic dermatitis, type 1 diabetes, pemphigus, epidermolysis bullosa acquisita and erosive oral lichen planus.

Direct oral anticoagulant use and risk of severe COVID-19.

BACKGROUND: Hypercoagulability and thromboembolism are prominent features of severe COVID-19, and ongoing anticoagulant use might be protective. METHODS: We conducted a nationwide register-based cohort study in Sweden, February through May, 2020, to assess whether ongoing direct oral anticoagulant (DOAC) use was associated with reduced risk of hospital admission for laboratory-confirmed COVID-19, or a composite of intensive care unit (ICU) admission or death due to laboratory-confirmed COVID-19. RESULTS: DOAC use (n = 103 703) was not associated with reduced risk of hospital admission for COVID-19 (adjusted hazard ratio [aHR] [95% confidence interval] 1.00 [0.75-1.33] vs. nonuse atrial fibrillation comparator [n = 36 875]; and aHR 0.94 [0.80-1.10] vs. nonuse cardiovascular disease comparator [n = 355 699]), or ICU admission or death due to COVID-19 (aHRs 0.76 [0.51-1.12], and 0.90 [0.71-1.15], respectively). CONCLUSION: Ongoing DOAC use was not associated with reduced risk of severe COVID-19, indicating that prognosis would not be modified by early outpatient DOAC initiation.

European dermatology forum - updated guidelines on the use of extracorporeal photopheresis 2020 - part 1.

BACKGROUND: Following the first investigational study on the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma published in 1983, this technology has received continued use and further recognition for additional earlier as well as refractory forms. After the publication of the first guidelines for this technology in the JEADV in 2014, this technology has maintained additional promise in the treatment of other severe and refractory conditions in a multi-disciplinary setting. It has confirmed recognition in well-known documented conditions such as graft-versus-host disease after allogeneic bone marrow transplantation, systemic sclerosis, solid organ transplant rejection including lung, heart and liver and to a lesser extent inflammatory bowel disease. MATERIALS AND METHODS: In order to further provide recognized expert practical guidelines for the use of this technology for all indications, the European Dermatology Forum (EDF) again proceeded to address these questions in the hands of the recognized experts within and outside the field of dermatology. This was done using the recognized and approved guidelines of EDF for this task. All authors had the opportunity to review each contribution as it was added. RESULTS AND CONCLUSION: These updated 2020 guidelines provide at present the most comprehensive available expert recommendations for the use of extracorporeal photopheresis based on the available published literature and expert consensus opinion. The guidelines are divided in two parts: PART I covers cutaneous T-cell lymphoma, chronic graft-versus-host disease and acute graft-versus-host disease while PART II will cover scleroderma, solid organ transplantation, Crohn's disease, use of ECP in paediatrics practice, atopic dermatitis, type 1 diabetes, pemphigus, epidermolysis bullosa acquisita and erosive oral lichen planus.

Clostridium difficile infection and risk of Parkinson's disease: a Swedish population-based cohort study.

BACKGROUND AND PURPOSE: Gastrointestinal inflammation has been implicated in Parkinson's disease (PD). The aim of this study was to examine whether individuals with a history of Clostridium difficile infection (CDI) are at elevated risk of PD. METHODS: We performed a population-based cohort study using Swedish national register data. Adults aged ≥35 years were identified from the Swedish Population and Housing Census 1990 and followed during the period 1997-2013. Diagnoses of CDI and PD were extracted from the National Patient Register. Associations of CDI history with PD risk were estimated using Cox proportional hazards regression. We also explored whether the association differed by the source of CDI diagnosis (inpatient vs. outpatient), presence of recurrent infections, and pre-infection use of antibiotics. RESULTS: Amongst the study population (N = 4 670 423), 34 868 (0.75%) had a history of CDI. A total of 165 and 47 035 incident PD cases were identified from individuals with and without CDI history, respectively. Across the entire follow-up, a 16% elevation of PD risk was observed among the CDI group [hazard ratio 1.16, 95% confidence interval (CI)1.00-1.36], which was mainly driven by increased PD risk within the first 2 years after CDI diagnosis (hazard ratio 1.38, 95% CI 1.12-1.69). In longer follow-up, CDI was not associated with subsequent PD occurrence. This temporal pattern of CDI-PD associations was generally observed across all CDI subgroups. CONCLUSIONS: Clostridium difficile may be associated with an increased short-term PD risk, but this might be explained by reverse causation and/or surveillance bias. Our results do not imply that CDI history affects long-term PD risk.

Decrease in primary but not in secondary abdominal surgery for Crohn's disease: nationwide cohort study, 1990-2014.

BACKGROUND: Treatment of patients with Crohn's disease has evolved in recent decades, with increasing use of immunomodulatory medication since 1990 and biologicals since 1998. In parallel, there has been increased use of active disease monitoring. To what extent these changes have influenced the incidence of primary and repeat surgical resection remains debated. METHODS: In this nationwide cohort study, incident patients of all ages with Crohn's disease, identified in Swedish National Patient Registry between 1990 and 2014, were divided into five calendar periods of diagnosis: 1990-1995 and 1996-2000 with use of inpatient registries, 2001, and 2002-2008 and 2009-2014 with use of inpatient and outpatient registries. The cumulative incidence of first and repeat abdominal surgery (except closure of stomas), by category of surgical procedure, was estimated using the Kaplan-Meier method. RESULTS: Among 21 273 patients with Crohn's disease, the cumulative incidence of first abdominal surgery within 5 years of Crohn's disease diagnosis decreased continuously from 54·8 per cent in 1990-1995 to 40·4 per cent in 1996-2000 (P < 0·001), and again from 19·8 per cent in 2002-2008 to 17·3 per cent in 2009-2014 (P < 0·001). Repeat 5-year surgery rates decreased from 18·9 per cent in 1990-1995 to 16·0 per cent in 1996-2000 (P = 0·009). After 2000, no further significant decreases were observed. CONCLUSION: The 5-year rate of surgical intervention for Crohn's disease has decreased significantly, but the rate of repeat surgery has remained stable despite the introduction of biological therapy.

ANTECEDENTES: El tratamie nto de pacientes con enfermedad de Crohn ha evolucionado en las últimas décadas con un uso cada vez mayor de medicamentos inmunomoduladores desde 1990 y tratamientos biológicos desde 1998. Al mismo tiempo, ha aumentado la utilidad de la vigilancia activa de la enfermedad. Hasta qué punto estos cambios han influido en la incidencia de la resección quirúrgica primaria y repetida sigue siendo objeto de debate. MÉTODOS: Estudio de cohortes a nivel nacional de pacientes incidentes con enfermedad de Crohn de todas las edades identificados en el registro sueco nacional de pacientes entre 1990-2014, que se dividió en cinco períodos de diagnóstico: 1990-1995 y 1996-2000 con el uso de registros de pacientes hospitalizados, 2001, y 2002-2008 y 2009-2014 con uso de registros de pacientes ambulatorios y hospitalizados. Se estimó la incidencia acumulada de la primera cirugía abdominal y de las cirugías abdominales subsiguientes (excepto el cierre de estomas), por categoría de procedimiento quirúrgico, mediante el método de Kaplan-Meier. RESULTADOS: Entre 21.273 pacientes con enfermedad de Crohn, la incidencia acumulada de la primera cirugía abdominal durante los 5 años posteriores al diagnóstico de la enfermedad disminuyó continuamente del 54,8% en la cohorte 1990-1995 al 40,4% en la cohorte 1996-2000 (P < 0,001) y nuevamente del 19,8% en cohorte 2002-2008 al 17,3% en la cohorte 2009-2014 (P < 0,001). Las tasas cirugías iterativas a los 5 años disminuyeron de 18,9% en la cohorte 1990-1995 a 16,0% en la cohorte 1996-2000 (P = 0,017). Después del 2000, no se observaron más disminuciones significativas. CONCLUSIÓN: La tasa de intervención quirúrgica a los 5 años para la enfermedad de Crohn ha disminuido significativamente, pero la cirugía iterativa se ha mantenido estable a pesar de la introducción de la terapia biológica.

The risk of epilepsy in children with celiac disease: a population-based cohort study.

BACKGROUNDAND PURPOSE: The purpose was to estimate the risk of epilepsy in a cohort of young individuals with celiac disease (CD) compared to that of matched references. METHODS: The cohort consisted of 213 635 individuals born during 1989-2011 and residing in Friuli-Venezia Giulia (Italy). 1215 individuals affected by CD and 6075 reference individuals matched by sex and age were identified. Epilepsy was defined by means of hospital diagnosis or drug prescriptions. Conditional logistic regression was used to estimate the odds ratios (ORs) of having epilepsy amongst individuals with CD, before CD diagnosis and in the entire period, compared with those of their matched references. Cox regression was used to calculate the hazard ratios for epilepsy diagnosed after CD diagnosis. Different definitions of epilepsy were used for sensitivity analyses. RESULTS: Thirty-one (2.6%) individuals with CD and 78 (1.3%) reference individuals had epilepsy [adjusted OR 2.03; 95% confidence interval (CI) 1.33-3.10]. The risk of epilepsy was increased prior to CD (adjusted OR 2.29; 95% CI 1.33-3.94), with similar estimates after CD diagnosis (adjusted hazard ratio 1.96; 95% CI 0.95-4.02). The increased risk of epilepsy was not explained by a peak in epilepsy diagnosis just around CD diagnosis. Sex stratification found a significantly higher risk of epilepsy amongst female individuals with CD. Sensitivity analyses confirmed the positive association between CD and epilepsy. CONCLUSION: Children and youths with CD were at increased risk of epilepsy. Patients with epilepsy without a clear etiology should be screened for CD since an early diagnosis and treatment might improve the response to antiepileptic therapies.

Incidence, prevalence and clinical manifestations at onset of juvenile diabetes in Tanzania.

Better knowledge on incidence, prevalence and clinical manifestations is needed for planning diabetes care in Sub Saharan Africa. AIMS: To find a crude incidence/prevalence of diabetes in children and young adults in a low resource setting, classify the diabetes and audit the health record keeping. METHODS: A retrospective observational study based on medical recordings 2010-2016. Target population was children and adolescent registered in Changing Diabetes in Children (CDiC) or Life for a Child (LFAC) programs for children with T1DM and diagnosed at 5 diabetes clinics in three geographical regions of Tanzania. 604 patients' files were available from five hospitals. RESULTS: 336/604 files covered patients <15 years of age at diagnosis. The prevalence of diabetes <15 years of age ranged from 10.1 to 11.9 per 100,000 children and the annual incidence 1.8-1.9/100,000 children, with peak incidence at 10-14 years. A lot of data were missing. The great majority of the patients presented with typical signs and symptoms of T1D, 83.7% with plausible ketoacidosis (DKA). CONCLUSIONS: Diabetes incidence and prevalence is still low. T1D seems to dominate with very high frequency of DKA at diagnosis. Increased awareness of diabetes both in health care and community is needed.

Toxic metals in cord blood and later development of Type 1 diabetes.

The incidence of type 1 diabetes (T1D) has increased explained by changes in environment or lifestyle. In modern society dissemination of heavy metals has increased. As the autoimmune process usually starts already, we hypothesized that exposure to toxic metals during fetal life might contribute to development of T1D in children. We analysed arsenic (AS), aluminium (Al), cadmium (Cd), lithium (Li), mercury (Hg), lead (Pb), in cord blood of 20 children who later developed T1D (probands), and in 40 age-and sex-matched controls. Analysis of heavy metals in cord blood was performed by ALS Scandinavia AB (Luleå, Sweden) using the 'ultrasensitive inductively coupled plasma sector field mass spectrometry method' (ICP-SFMS) after acid digestion with HNO3. Most children had no increased concentrations of the metals in cord blood. However, children who later developed T1D had more often increased concentrations (above limit of detection; LOD) of aluminium (p = 0.006) in cord blood than the non-diabetic controls, and also more often mercury and arsenic (n.s). Our conclusion is that exposure to toxic metals during pregnancy might be one among several contributing environmental factors to the disease process if confirmed in other birth cohort trials.

Investigating fetal growth restriction and perinatal risks in appropriate for gestational age infants: using cohort and within-sibling analyses.

OBJECTIVE: Fetal growth restriction refers to fetuses that fail to reach their growth potential. Studies within siblings may be useful to disclose fetal growth restriction in appropriate for gestational age (AGA) infants. We analysed associations between birthweight percentiles and perinatal risks in AGA infants, using both population-based and within-sibling analyses. DESIGN: Population-based cohort study. SETTING AND SAMPLE: Using nation-wide Swedish registries (1987-2012), we identified 2 134 924 singleton AGA births (10th-90th birthweight percentile for gestational age), of whom 1 377 326 were full siblings. METHODS: Unconditional Poisson regression was used for population analyses, and conditional (matched) Poisson regression for within-sibling analyses. We estimated associations between birthweight percentiles and stillbirth, neonatal mortality, and morbidity, using incidence rate ratios (IRRs) with 95% confidence intervals (CIs). RESULTS: Stillbirth and neonatal mortality risks declined with increasing birthweight percentiles, but the declines were larger in within-sibling analyses. Compared with the reference group (40th to <60th percentile), IRRs (95% CIs) of stillbirth for the lowest and highest percentile groups (10th to <25th and 75th-90th percentiles, respectively) were 1.87 (1.72-2.03) to 0.76 (0.68-0.85) in population analysis and 2.60 (2.27-2.98) and 0.43 (0.36-0.50) in within-sibling analysis. Neonatal morbidity risks in term non-malformed infants with low birthweight percentiles were generally only increased in within-sibling analyses. CONCLUSION: Using birthweight information from siblings may help to define fetal growth restriction in AGA infants. TWEETABLE ABSTRACT: Size of siblings helps to detect growth-restricted infants with seemingly normal birthweights.

Systematic review with meta-analysis: the prevalence of coeliac disease in patients with osteoporosis.

BACKGROUND: Earlier studies have produced highly varying risk estimates for the prevalence of coeliac disease (CD) in osteoporosis. AIMS: To investigate the prevalence of CD among individuals with osteoporosis. METHODS: We conducted a systematic review of articles published in PubMed, Medline or EMBASE through May 2017 to identify studies looking at prevalence of CD in patients with osteoporosis. Search terms included "coeliac disease" combined with "fractures", "bone disease", "bone density", "densitometry", "osteoporos*", "osteomal*", "osteodys" or "dexa" or "dxa" or "skelet". Non-English papers with English-language abstracts were included. We used fixed-effects inverse variance-weighted models, and tested heterogeneity through subgroup analysis as well as through meta-regression. RESULTS: We identified eight relevant studies, comprising data from 3188 individuals with osteoporosis. Of these, 59 individuals (1.9%) had CD. A weighted pooled analysis demonstrated biopsy-confirmed CD in 1.6% (95% CI = 1.1%-2.0%) of individuals with osteoporosis. The heterogeneity was moderate (I2  = 40.1%), and influenced by the underlying CD prevalence in the general population. After adding four studies (n = 814) with CD defined as positive tissue transglutaminase or endomysial antibodies, the pooled prevalence was comparable (1.6%; 95% CI = 1.2%-2.0%). CONCLUSIONS: About 1 in 62 individuals with osteoporosis, or 1.6%, have biopsy-verified CD. This prevalence is comparable to that in the general population. These findings argue against routinely screening patients with osteoporosis for CD, which is contrary to current guideline recommendations. Additional studies are needed to determine the true utility of such screening programs.

Insulin-Like Growth Factor-1 at Diagnosis and during Subsequent Years in Adolescents with Type 1 Diabetes.

BACKGROUND: Type 1 diabetes (T1D) in adolescents is associated with alterations in the insulin-like factor system probably caused both by a deranged metabolism and insulinopenia in the portal vein. OBJECTIVE: To study how the circulating IGF-1 is affected at diagnosis and during subsequent years in adolescents with T1D. METHODS: Ten girls and ten boys with type 1 diabetes (T1D), aged 13.0 ± 1.4 (mean ± SD) years at diagnosis, took part in the study. Blood samples were drawn at diagnosis and after 3, 9, 18, and 48 months. HbA1c, total IGF-1, and C-peptide were measured. RESULTS: At diagnosis, the patients had high HbA1c, low IGF-1, and measurable C-peptide. After the start of insulin treatment, maximal improvement in glycemic control and IGF-1 occurred within 3 months and then both tended to deteriorate, that is, HbA1c to increase and IGF-1 to decrease. C-peptide decreased with time, and after 4 years, half of the patients were C-peptide negative. At diagnosis, C-peptide correlated positively to IGF-1 (r = 0.50; p < 0.03). C-peptide correlated negatively with insulin dose (U/kg) after 18 and 48 months from diagnosis (r = -0.48; p < 0.03 and r = -0.72; p < 0.001, resp.). CONCLUSIONS: In conclusion, our results show that in newly diagnosed adolescents with type 1 diabetes and deranged metabolism, the IGF-1 level is low and rapidly improves with insulin treatment but later tends to decrease concomitantly with declining endogenous insulin secretion.

The Better Diabetes Diagnosis (BDD) study - A review of a nationwide prospective cohort study in Sweden.

The incidence of type 1 diabetes (T1D) in Sweden is one of the highest in the world. However, the possibility of other types of diabetes must also be considered. In addition, individuals with T1D constitute a heterogeneous group. A precise classification of diabetes is a prerequisite for optimal outcome. For precise classification, knowledge on the distribution of genetic factors, biochemical markers and clinical features in individuals with new onset of diabetes is needed. The Better Diabetes Diagnosis (BDD), is a nationwide study in Sweden with the primary aim to facilitate a more precise classification and diagnosis of diabetes in order to enable the most adequate treatment for each patient. Secondary aims include identification of risk factors for diabetes-related co-morbidities. Since 2005, data on almost all children and adolescents with newly diagnosed diabetes in Sweden are prospectively collected and including heredity of diabetes, clinical symptoms, levels of C peptide, genetic analyses and detection of autoantibodies. Since 2011, analyses of HLA profile, autoantibodies and C peptide levels are part of clinical routine in Sweden for all pediatric patients with suspected diagnosis of diabetes. In this review, we present the methods and main results of the BDD study so far and discuss future aspects.