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End-stage renal disease (ESRD) is one of the most severe complications in type 1 diabetes. We aimed to estimate the cumulative incidence of ESRD in individuals with childhood-onset type 1 diabetes followed for up to 42 years. Data were... more
End-stage renal disease (ESRD) is one of the most severe complications in type 1 diabetes. We aimed to estimate the cumulative incidence of ESRD in individuals with childhood-onset type 1 diabetes followed for up to 42 years. Data were based on the nationwide, population-based Norwegian Childhood Diabetes Registry and included case patients with new-onset type 1 diabetes (age <15 years) who had received a diagnosis during the periods 1973-1982 and 1989-2012. Follow-up took place until the development of ESRD, death, emigration, or 30 November 2015. We estimated the cumulative incidence of ESRD by linking to the Norwegian Renal Registry. Among the 7,871 patients, representing 147,714 person-years of follow-up, ESRD developed in 103 individuals (1.3%). The mean time from the diagnosis of diabetes to the development of ESRD was 25.9 years (range 12.7-39.1). The cumulative incidence of ESRD was 0.7% (95% CI 0.4-1.0) at 20 years diabetes duration, 2.9% (2.3-3.7) at 30 years duration, ...
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Research Interests: Vitamin D, Medicine, Pregnancy, Humans, Female, and 15 moreYoung Adult, Dietary Supplements, Mothers, Nutritional Status, Clinical Sciences, Genotype, Adult, Single Nucleotide Polymorphism, Fetus, Umbilical Cord, Vitamin D Deficiency, Prenatal Care, Cohort Studies, Paediatrics and reproductive medicine, and Cord
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The Medical Birth Registry of Norway (MBRN) has registered all births in Norway since 1967 and diabetes is registered as a maternal diagnosis. We present original data assessing the validity of the diabetes diagnosis. Among women with... more
The Medical Birth Registry of Norway (MBRN) has registered all births in Norway since 1967 and diabetes is registered as a maternal diagnosis. We present original data assessing the validity of the diabetes diagnosis. Among women with known pre-gestational type 1 diabetes, 97% of births during 1976-1998 (old registration form) were identified as pre-gestational diabetes in the MBRN. For births 1999-2004 (new registration form), 94% were identified as pre-gestational diabetes in the MBRN. Of cases coded as pre-gestational diabetes by the MBRN, 80% were confirmed by the medical record for births during 1998, while more than half of the births incorrectly coded as pre-gestational diabetes really were gestational diabetes. Among births coded as gestational diabetes, 89% were confirmed in the medical record. In conclusion, the sensitivity of the pregestational diabetes diagnosis in the Medical Birth Registry of Norway was very good, particularly in the earlier period, but the information...
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Type 1 diabetes mellitus (T1DM) is an autoimmune disease, where destruction of beta-cells causes insulin deficiency. The incidence of T1DM has increased in the last decades and cannot entirely be explained by genetic predisposition.... more
Type 1 diabetes mellitus (T1DM) is an autoimmune disease, where destruction of beta-cells causes insulin deficiency. The incidence of T1DM has increased in the last decades and cannot entirely be explained by genetic predisposition. Several environmental factors are suggested to promote T1DM, like early childhood enteroviral infections and nutritional factors, but the evidence is inconclusive. Prenatal and early life exposure to environmental pollutants like phthalates, bisphenol A, perfluorinated compounds, PCBs, dioxins, toxicants, and air pollutants can have negative effects on the developing immune system, resulting in asthma-like symptoms and increased susceptibility to childhood infections. In this review the associations between environmental chemical exposure and T1DM development is summarized. Although information on environmental chemicals as possible triggers for T1DM is sparse, we conclude that it is plausible that environmental chemicals can contribute to T1DM developme...
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Research Interests: Asthma, Medicine, Norway, Prospective studies, Pregnancy, and 15 moreHumans, Child, Female, Tandem Mass Spectrometry, Risk factors, High Performance Liquid Chromatography, Questionnaires, Adult, Public health systems and services research, Odds ratio, Respiratory Tract Infections, Risk Factors, Confidence Interval, Case Control Studies, and Paediatrics and reproductive medicine
High prevalences of vitamin D deficiency have been reported in non-Western immigrants moving to Western countries, including Norway, but there is limited information on vitamin D status in infants born to immigrant mothers. We aimed to... more
High prevalences of vitamin D deficiency have been reported in non-Western immigrants moving to Western countries, including Norway, but there is limited information on vitamin D status in infants born to immigrant mothers. We aimed to describe the vitamin D status and potentially correlated factors among infants aged 6 weeks and their mothers with Pakistani, Turkish or Somali background attending child health clinics in Norway. Eighty-six healthy infants and their mothers with immigrant background were recruited at the routine 6-week check-up at nine centres between 2004 and 2006. Venous or capillary blood was collected at the clinics from the mother and infant, and serum separated for analysis of 25-hydroxyvitamin D (s-25(OH)D) and intact parathyroid hormone (s-iPTH). The mean maternal s-25(OH)D was 25·8 nmol/l, with 57 % below 25 nmol/l and 15 % below 12·5 nmol/l. Of the mothers, 26 % had s-iPTH>5·7 pmol/l. For infants, mean s-25(OH)D was 41·7 nmol/l, with 47 % below 25 nmol/l...
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Many types of vitamin supplements are available on the market, but little is known about whether cholecalciferol obtained from fat-containing capsules differs in bioavailability from that of solid tablets. Our objective was to test... more
Many types of vitamin supplements are available on the market, but little is known about whether cholecalciferol obtained from fat-containing capsules differs in bioavailability from that of solid tablets. Our objective was to test whether 4 weeks of daily supplementation with 10 μg cholecalciferol given as a fish oil capsule produces a larger increase in serum 25-hydroxyvitamin D (s-25(OH)D) concentration compared with the same dose of cholecalciferol given as a multivitamin tablet. A total of seventy-four healthy subjects aged 19–49 years were initially included and fifty-five of these completed the study and fulfilled the inclusion criteria. After completing a self-administered questionnaire about diet and sunshine exposure and having a non-fasting venous blood sample drawn, participants were randomised to receive daily multivitamin tablets (n 28) or fish oil capsules (n 27), each containing equal doses of cholecalciferol. A second blood sample was drawn after 28 d. Mean baseline...
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Research Interests: Adolescent, Medicine, Muscle strength, Norway, Humans, and 15 moreInternal Medicine, Minority Groups, Placebo, Female, Male, Dietary Supplements, Placebos, Ethnic Groups, Clinical Sciences, Vitamin, Middle Aged, Adult, Randomized Controlled Trial, Confidence Interval, and Paediatrics and reproductive medicine
Research Interests: Epidemiology, Peer Review, Medicine, Humans, Diabetes mellitus, and 15 moreFemale, Cohort Study, Birth Order, Meta Analysis, Maternal Age, Peer reviewed, Odds ratio, Medicine and Health Sciences, Observational Study, Case Control Study, Confidence Interval, Case Control Studies, Child preschool, confounding, and Incidence Rate
Research Interests: Medicine, Logistic Regression, Norway, Humans, Diabetes mellitus, and 15 moreFemale, Male, Confidence intervals, Dietary Supplements, Clinical Sciences, Odds ratio, First Year, Breast feeding, Cod Liver Oil, Case Control Study, Confidence Interval, Eicosapentaenoic Acid, Docosahexaenoic Acid, Case Control Studies, and Insulin dependent diabetes mellitus
Research Interests: Adolescent, Cardiovascular disease, Ischaemic heart disease, Humans, Child, and 15 moreDiabetes mellitus, Female, Male, Cohort Study, Infant, Cohort, Clinical Sciences, Longitudinal Studies, Early Detection, Adult, General Population, Age of Onset, Cohort Studies, Child preschool, and Cause of death
Research Interests: Incidence Geometry, Adolescent, Medicine, Norway, Humans, and 15 moreChild, Internal Medicine, Diabetes mellitus, Cox Regression, Diabetic Retinopathy, Cohort Study, Incidence, Clinical Sciences, Adult, Public health systems and services research, Proportional hazards model, Cumulative Incidence, Relative Risk, Child preschool, and Paediatrics and reproductive medicine
Research Interests: Obstetrics, Adolescent, Medicine, Logistic Regression, Norway, and 15 moreMaternal Mortality, Pregnancy, Population, Humans, Female, Male, Infant, Clinical Sciences, Adult, Infant Mortality, First Year, Perinatal mortality, Cross Sectional Studies, Pre Eclampsia, and Paediatrics and reproductive medicine
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Research Interests: Demography, Incidence Geometry, Norwegian, Adolescent, Medicine, and 15 moreNorway, Population, Humans, Child, Female, Male, Poisson regression, Infant, Incidence, Clinical Sciences, Newborn Infant, Public health systems and services research, Type 2 Diabetes Mellitus, Child preschool, and Paediatrics and reproductive medicine
OBJECTIVE The aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized... more
OBJECTIVE The aim if the study was to investigate whether children born to older mothers have an increased risk of type 1 diabetes by performing a pooled analysis of previous studies using individual patient data to adjust for recognized confounders. RESEARCH DESIGN AND METHODS Relevant studies published before June 2009 were identified from MEDLINE, Web of Science, and EMBASE. Authors of studies were contacted and asked to provide individual patient data or conduct prespecified analyses. Risk estimates of type 1 diabetes by maternal age were calculated for each study, before and after adjustment for potential confounders. Meta-analysis techniques were used to derive combined odds ratios and to investigate heterogeneity among studies. RESULTS Data were available for 5 cohort and 25 case-control studies, including 14,724 cases of type 1 diabetes. Overall, there was, on average, a 5% (95% CI 2–9) increase in childhood type 1 diabetes odds per 5-year increase in maternal age (P = 0.006...
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Research Interests: Obstetrics, Pediatrics, Risk, Norwegian, Medicine, and 15 moreNorway, Pregnancy, Population, Humans, Diabetes mellitus, Female, Newborn Infant, Public health systems and services research, Odds ratio, Retrospective Studies, Type 2 Diabetes Mellitus, Offspring, Congenital abnormalities, Socioeconomic Factors, and Paediatrics and reproductive medicine
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Background and aim Genetic markers are established as predictive of type 1 diabetes, but unknown early life environment is believed to be involved. Umbilical cord blood may reflect perinatal metabolism and exposures. We studied whether... more
Background and aim Genetic markers are established as predictive of type 1 diabetes, but unknown early life environment is believed to be involved. Umbilical cord blood may reflect perinatal metabolism and exposures. We studied whether selected polar metabolites in cord blood contribute to prediction of type 1 diabetes. Methods Using a targeted UHPLC-QQQ-MS platform, we quantified 27 low-molecular-weight metabolites (including amino acids, small organic acids, and bile acids) in 166 children, who later developed type 1 diabetes, and 177 random control children in the Norwegian Mother, Father, and Child cohort. We analyzed the data using logistic regression (estimating odds ratios per SD [adjusted odds ratio (aOR)]), area under the receiver operating characteristic curve (AUC), and k-means clustering. Metabolites were compared to a genetic risk score based on 51 established non-HLA single-nucleotide polymorphisms, and a 4-category HLA risk group. Results The strongest associations fo...
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Research Interests: Obstetrics, Statistics, Epidemiology, Obesity, Type 2 Diabetes, and 15 moreMedicine, Gestational diabetes, Pregnancy, Child, Diabetes mellitus, Cohort Study, Mothers, Body Mass Index, Parents, Public health systems and services research, Parent, Type, Weight Gain, Gestational Weight Gain, and Maternal Obesity
Iron overload due to environmental or genetic causes have been associated diabetes. We hypothesized that prenatal iron exposure is associated with higher risk of childhood type 1 diabetes. In the Norwegian Mother and Child cohort study... more
Iron overload due to environmental or genetic causes have been associated diabetes. We hypothesized that prenatal iron exposure is associated with higher risk of childhood type 1 diabetes. In the Norwegian Mother and Child cohort study (n = 94,209 pregnancies, n = 373 developed type 1 diabetes) the incidence of type 1 diabetes was higher in children exposed to maternal iron supplementation than unexposed (36.8/100,000/year compared to 28.6/100,000/year, adjusted hazard ratio 1.33, 95%CI: 1.06-1.67). Cord plasma biomarkers of high iron status were non-significantly associated with higher risk of type 1 diabetes (ferritin OR = 1.05 [95%CI: 0.99-1.13] per 50 mg/L increase; soluble transferrin receptor: OR = 0.91 [95%CI: 0.81-1.01] per 0.5 mg/L increase). Maternal but not fetal HFE genotypes causing high/intermediate iron stores were associated with offspring diabetes (odds ratio: 1.45, 95%CI: 1.04, 2.02). Maternal anaemia or non-iron dietary supplements did not significantly predict ty...
Research Interests: Type 2 Diabetes, Medicine, Pregnancy, General, Diabetes mellitus, and 4 moreFerritin, Odds ratio, Offspring, and R
Studies on vitamin D status during pregnancy and risk of type 1 diabetes (T1D) lack consistency, and are limited by small sample sizes or single measures of 25-hydroxyvitamin D (25(OH)D). We investigated whether average maternal 25(OH)D... more
Studies on vitamin D status during pregnancy and risk of type 1 diabetes (T1D) lack consistency, and are limited by small sample sizes or single measures of 25-hydroxyvitamin D (25(OH)D). We investigated whether average maternal 25(OH)D plasma concentrations during pregnancy are associated with risk of childhood T1D. In a case-cohort design, we identified 459 children with T1D and a random sample (n = 1,561) from the Danish National Birth Cohort (n = 97,127) and Norwegian Mother and Child Cohort Study (n = 113,053). Participants were born between 1996 and 2009. The primary exposure was the estimated average 25(OH)D concentration based on serial samples from the first trimester until delivery, and umbilical cord plasma. We estimated hazard ratios using weighted Cox regression adjusting for multiple confounders. The adjusted hazard ratio for T1D per 10 nmol/L increase in the estimated average 25(OH)D concentration was 1.00 (95% confidence interval: 0.90, 1.10). Results were consistent...
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Our aim was to study the relation between the duration of full and any breastfeeding and risk of type 1 diabetes. We included two population-based cohorts of children followed from birth (1996-2009) to 2014 (Denmark) or 2015 (Norway). We... more
Our aim was to study the relation between the duration of full and any breastfeeding and risk of type 1 diabetes. We included two population-based cohorts of children followed from birth (1996-2009) to 2014 (Denmark) or 2015 (Norway). We analyzed data from a total of 155,392 children participating in the Norwegian Mother and Child Cohort Study (MoBa) and the Danish National Birth Cohort (DNBC). Parents reported infant dietary practices when their child was 6 and 18 months old. The outcome was clinical type 1 diabetes, ascertained from nationwide childhood diabetes registries. Hazard ratios (HRs) were estimated using Cox regression. Type 1 diabetes was identified in 504 children during follow-up, and the incidence of type 1 diabetes per 100,000 person-years was 30.5 in the Norwegian cohort and 23.5 in the Danish cohort. Children who were never breastfed had a twofold increased risk of type 1 diabetes compared with those who were breastfed (HR 2.29 [95% CI 1.14-4.61] for no breastfeed...
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Type 1 diabetes and celiac disease result from misdirected immune mediated destruction of host cells, and are among the most common chronic diseases in children. Despite changes in incidence over the past 3 decades, little is known about... more
Type 1 diabetes and celiac disease result from misdirected immune mediated destruction of host cells, and are among the most common chronic diseases in children. Despite changes in incidence over the past 3 decades, little is known about non-genetic risk factors (except for dietary gluten for celiac disease). Norway is among the countries in the world with the highest incidence of these two diseases. We describe here plans and study design for the PAGE study (Prediction of Autoimmune diabetes and celiac disease in childhood by Genes and perinatal Environment). PAGE is a sub-study within the Norwegian Mother and Child Cohort study, including follow-up of more than 100,000 pregnancies. Children who develop type 1 diabetes or celiac disease are identified via linkage to the Norwegian Patient Register and the Norwegian Childhood Diabetes Registry, with complementing information from questionnaires. The overall aim is to test hypotheses about potential non-genetic risk factors for type 1...
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Type 1 diabetes mellitus is one of the most common chronic diseases with onset in childhood, but environmental risk factors have not been convincingly established. To test whether increased growth during the first year of life is... more
Type 1 diabetes mellitus is one of the most common chronic diseases with onset in childhood, but environmental risk factors have not been convincingly established. To test whether increased growth during the first year of life is associated with higher risk of childhood-onset type 1 diabetes. This is a cohort study using information from 2 population-based cohort studies in Norway and Denmark, the Norwegian Mother and Child Cohort Study (MoBa) and the Danish National Birth Cohort (DNBC), of children born between February 1998 and July 2009. The current study was conducted between November 2014 and June 2015. Change in weight and length from birth to age 12 months. Unadjusted and adjusted hazard ratios (HRs) of type 1 diabetes, classified based on nationwide childhood diabetes registers, obtained using Cox proportional hazards regression. A total of 99 832 children were included in the study, with 59 221 in MoBa (51.2% boys and 48.8% girls; mean age at end of follow-up, 8.6 years [ra...
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OBJECTIVE We aimed to study the association of breast-feeding duration and age at the introduction of solid foods with the risk of islet autoimmunity and type 1 diabetes in genetically susceptible children. RESEARCH DESIGN AND METHODS... more
OBJECTIVE We aimed to study the association of breast-feeding duration and age at the introduction of solid foods with the risk of islet autoimmunity and type 1 diabetes in genetically susceptible children. RESEARCH DESIGN AND METHODS Newborns were recruited from the Norwegian general population during 2001–2007. After genetic screening of nearly 50,000 newborns, 908 children with the high-risk HLA genotype were followed up with blood samples and questionnaires at age 3, 6, 9, and 12 months and then annually. Complete infant diet data were available for 726 children. RESULTS Any breast-feeding for 12 months or longer predicted a decreased risk of developing type 1 diabetes compared with any breast-feeding for less than 12 months before and after adjusting for having a first-degree relative with type 1 diabetes, vitamin D supplementation, maternal education, sex, and delivery type (hazard ratio 0.37 [95% CI 0.15–0.93]). Any breast-feeding for 12 months or longer was not associated wi...
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Research Interests: Biology, Autoimmunity, Innate immunity, Medicine, Multidisciplinary, and 15 moreHumans, Infant, PLoS one, Intestines, Genotype, Single Nucleotide Polymorphism, Time Factors, Odds ratio, Feces, Type 2 Diabetes Mellitus, islets of Langerhans, Case Control Studies, Cohort Studies, Enterovirus, and Viral Load
Human enterovirus (HEV) infections can be asymptomatic or cause only mild illness; recent evidence may implicate HEV infection in type 1 diabetes mellitus and myocarditis. Here, we report the molecular characterization of HEV obtained in... more
Human enterovirus (HEV) infections can be asymptomatic or cause only mild illness; recent evidence may implicate HEV infection in type 1 diabetes mellitus and myocarditis. Here, we report the molecular characterization of HEV obtained in serial monthly collections from healthy Norwegian infants. A total of 1,255 fecal samples were collected from 113 healthy infants beginning at age 3 months and continuing to 28 months. The samples were analyzed for HEV nucleic acid by real-time PCR. Fifty-eight children (51.3%) had HEV infections. One hundred forty-five positive samples were typed directly by nucleotide sequencing of the VP1 region. HEV-A was detected most frequently, with an overall prevalence of 6.8%. HEV-B was present in 4.8% of the samples and HEV-C in only 0.2% of the samples. No poliovirus or HEV-D group viruses were detected. Twenty-two different serotypes were detected in the study period: the most common were EV71 (14.5%), CAV6 (10.5%), CAV4 (8.9%), E18 (8.9%), and CBV3 (7....
Research Interests: Biology, Medicine, Clinical Microbiology, Biological Sciences, Humans, and 15 moreChronic Disease, Clinical, Infant, Neuromuscular Disease, Feces, Neonatal Sepsis, Base Sequence, Asymptomatic, Epidemiologic Studies, Nucleic Acid, Enterovirus, Molecular Sequence Data, Child preschool, Nucleotide sequence, and Medical and Health Sciences
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Research Interests: Adolescent, Medicine, Breastfeeding, Birth Weight, Gestational diabetes, and 15 moreCaesarean Section, Humans, Child, Diabetes mellitus, Female, Infant, Birth Order, Clinical Sciences, Maternal Age, Gestational Age, Case Control Study, Literature Search, Age of Onset, Child preschool, and confounding
OBJECTIVE—We have investigated age-period-cohort effects and spatial and temporal trends for the incidence of type 1 diabetes among 0- to 14-year-old children in Norway. RESEARCH DESIGN AND METHODS—We included children with the diagnosis... more
OBJECTIVE—We have investigated age-period-cohort effects and spatial and temporal trends for the incidence of type 1 diabetes among 0- to 14-year-old children in Norway. RESEARCH DESIGN AND METHODS—We included children with the diagnosis of type 1 diabetes in Norway during 1973–1982 and 1989–2003. We studied age, calendar period, and birth cohort effects using Poisson regression, including Holford's method of parameterization, to model the dependencies between age, period, and cohort effects. To study spatiotemporal clustering of cases, we used spatial scan statistics. RESULTS—The overall incidence rate for the study population <15 years of age was 22.7 cases per 100,000 (95% CI 22.1–23.4), showing an average annual increase of 1.2% (95% CI 0.7–1.5%) during the study period. One specific area with 30% increased incidence rates was identified in the southern part of Norway during 1976–1980 (P = 0.001). Also, children born during 1964–1966 in a specific region in the southern p...
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OBJECTIVE—An increasing incidence rate of childhood-onset type 1 diabetes has been described in several countries, particularly among the youngest children, and the Nordic countries have consistently been shown to have the highest... more
OBJECTIVE—An increasing incidence rate of childhood-onset type 1 diabetes has been described in several countries, particularly among the youngest children, and the Nordic countries have consistently been shown to have the highest incidence rates. An increasing incidence had previously been reported in Norway for 1973–1982, together with regional variation within the country. The aim of this study was to test whether there has been an increasing incidence of type 1 diabetes and a continued regional variation among children aged <15 years in Norway during 1989–1998. RESEARCH DESIGN AND METHODS—As a part of the activities of the National Childhood Diabetes Registry of Norway and the EURODIAB study, a 10-year prospective, nationwide case registration of type 1 diabetes was done among children aged <15 years. RESULTS—A total of 1,867 new case subjects (1,009 boys and 858 girls) were identified. The total incidence rate was 22.4 per 100,000 person-years (95% CI 21.5–23.5). The inci...
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OBJECTIVE—The aim of this study was to test whether symptoms of maternal infections during pregnancy and indicators of postnatal infections predict development of islet autoimmunity in children at genetically increased risk of type 1... more
OBJECTIVE—The aim of this study was to test whether symptoms of maternal infections during pregnancy and indicators of postnatal infections predict development of islet autoimmunity in children at genetically increased risk of type 1 diabetes. RESEARCH DESIGN AND METHODS—A total of 871 children with type 1 diabetes-associated HLA genotypes born in Denver, Colorado, and 391 siblings or offspring of individuals with type 1 diabetes referred from clinics in the Denver metropolitan area were enrolled soon after birth and seen in the clinic at age ≤15 months. Information on indicators of infection was collected by structured interviews soon after birth and at ages 3–15 months. Clinic visits were scheduled at ages 9, 15, and 24 months, and yearly thereafter. The outcome was positivity for one or more islet autoantibodies (to GAD65, insulin, or IA-2/ICA512) at two or more consecutive visits. During a mean follow-up of 4.2 years, 52 children developed islet autoimmunity. RESULTS—Children wh...
Research Interests: Diabetes, Autoimmunity, Type 2 Diabetes, Medicine, Early Childhood, and 15 morePregnancy, Humans, Diabetes mellitus, Female, Male, Gastroenteritis, Infant, Risk factors, Respiratory Tract Infections, Risk Factors, Type 2 Diabetes Mellitus, Predictive value of tests, Diabetes Care, islets of Langerhans, and Medical and Health Sciences
Previous studies indicate reduced risk of type 1 diabetes after intake of vitamin D supplements during pregnancy or early childhood. We aimed to test whether lower maternal serum concentrations of 25-hydroxy-vitamin D (25-OH D) during... more
Previous studies indicate reduced risk of type 1 diabetes after intake of vitamin D supplements during pregnancy or early childhood. We aimed to test whether lower maternal serum concentrations of 25-hydroxy-vitamin D (25-OH D) during pregnancy were associated with an increased risk of childhood-onset type 1 diabetes. In this case-control study nested within a cohort of 29,072 women in Norway, 25-OH D levels were measured using a radioimmunoassay on samples from late pregnancy in 109 women delivering a child who developed type 1 diabetes before 15 years of age (case subjects) and from 219 control women. Dividing the levels of maternal 25-OH D into quartiles, there was a trend toward a higher risk of type 1 diabetes with lower levels of vitamin D during pregnancy. The odds of type 1 diabetes was more than twofold higher for the offspring of women with the lowest levels of 25-OH D compared with the offspring of those with levels above the upper quartile. Given future replication in in...
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Elevated C-reactive protein (CRP) levels have previously been described before the onset of type 2 diabetes and gestational diabetes. We hypothesized that inflammation, as reflected by elevated CRP levels, can help predict development of... more
Elevated C-reactive protein (CRP) levels have previously been described before the onset of type 2 diabetes and gestational diabetes. We hypothesized that inflammation, as reflected by elevated CRP levels, can help predict development of islet autoimmunity or type 1 diabetes. Children at risk for type 1 diabetes and followed in the Diabetes Autoimmunity Study of the Young (DAISY) had blood samples drawn and frozen serum saved at various intervals after birth. CRP was measured using a high-sensitivity sandwich enzyme immunoassay. Islet autoantibodies (IAs) were measured using biochemical immunoassays. Elevations in CRP concentrations were significantly more frequent (P < 0.01) in children who later developed type 1 diabetes (8 of 16 children) than in children negative for IAs at their last testing (3 of 26). Children with one or more positive IA were more likely to have elevated CRP concentrations (15 of 36) than IA-negative children (3 of 26; P < 0.01). The finding of elevated...
Research Interests: Endocrinology, Diabetes, Inflammation, Autoimmunity, Type 2 Diabetes, and 13 moreMedicine, Humans, Child, Internal Medicine, Diabetes mellitus, C reactive protein, Reproducibility of Results, Biological markers, Disease Progression, Type 2 Diabetes Mellitus, Autoantibodies, Medical and Health Sciences, and prediabetic state
OBJECTIVE To investigate whether enterovirus infections predict progression to type 1 diabetes in genetically predisposed children repeatedly positive for islet autoantibodies. RESEARCH DESIGN AND METHODS Since 1993, the Diabetes and... more
OBJECTIVE To investigate whether enterovirus infections predict progression to type 1 diabetes in genetically predisposed children repeatedly positive for islet autoantibodies. RESEARCH DESIGN AND METHODS Since 1993, the Diabetes and Autoimmunity Study in the Young (DAISY) has followed 2,365 genetically predisposed children for islet autoimmunity and type 1 diabetes. Venous blood and rectal swabs were collected every 3–6 months after seroconversion for islet autoantibodies (against GAD, insulin, or insulinoma-associated antigen-2 [IA-2]) until diagnosis of diabetes. Enteroviral RNA in serum or rectal swabs was detected using reverse transcriptase PCR with primers specific for the conserved 5′ noncoding region, detecting essentially all enterovirus serotypes. RESULTS Of 140 children who seroconverted to repeated positivity for islet autoantibodies at a median age of 4.0 years, 50 progressed to type 1 diabetes during a median follow-up of 4.2 years. The risk of progression to clinical...
Research Interests: Immunology, Diabetes, Autoimmunity, Adolescent, Medicine, and 15 morePathophysiology, Humans, Child, Diabetes mellitus, Infant, Time Factors, Disease Progression, Islet, Proportional Hazards Models, Autoantibodies, islets of Langerhans, Enterovirus, Seroconversion, Child preschool, and Medical and Health Sciences
Summary OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES Metabolic diseases, host responses, cancer, autoinflammatory diseases, allergy. The hypothesis that under some circumstances enteroviral infections can lead to... more
Summary OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES Metabolic diseases, host responses, cancer, autoinflammatory diseases, allergy. The hypothesis that under some circumstances enteroviral infections can lead to type 1 diabetes (T1D) was proposed several decades ago, based initially on evidence from animal studies and sero-epidemiology. Subsequently, enterovirus RNA has been detected more frequently in serum of patients than in control subjects, but such studies are susceptible to selection bias and reverse causality. Here, we review critically recent evidence from human studies, focusing on longitudinal studies with potential to demonstrate temporal association. Among seven longitudinal birth cohort studies, the evidence that enterovirus infections predict islet autoimmunity is quite inconsistent in our interpretation, due partially, perhaps, to heterogeneity in study design and a limited number of subjects studied. An association between enterovirus and r...