Search

Background: Stroke is increasingly prevalent at younger ages but the risk factors are uncertain. We examined the association between adolescent cognitive function and early-onset stroke., Methods: This was a nationwide population-based cohort study of 1 741 345 Israeli adolescents (42% women) who underwent comprehensive cognitive function tests at age 16-20 years, before mandatory military service, during 1987-2012. Cognitive function (range: 1-9) was categorised as low (1-3, corresponding to IQ score below 89), medium (4-7, IQ score range: 89-118), or high (8-9, IQ score above 118). Participant data were linked to the Israeli National Stroke Registry. Cox proportional hazard models were used to estimate risks for the first occurrence of ischaemic stroke during 2014-2018., Results: During 8 689 329 person-years of follow-up, up to a maximum age of 50 years, 908 first stroke events occurred (767 ischaemic and 141 haemorrhagic). Compared with a reference group of people with high cognitive function, body mass index-adjusted and sociodemographic-adjusted HRs (95% CIs) for early-onset stroke were 1.78 (1.33-2.38) in medium and 2.68 (1.96-3.67) in low cognitive function groups. There was evidence of a dose-response relationship ( P for trend <0.0001) such that one-unit of lower cognitive function z-score was associated with a 33% increased risk of stroke (1.33; 1.23-1.42). These associations were similar for ischaemic stroke but lower for haemorrhagic stroke; persisted in sensitivity analyses that accounted for diabetes status and hypertension; and were evident before age 40 years., Conclusions: Alongside adolescent obesity and hypertension, lower cognitive function may be a risk factor for early-onset stroke., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Prevalence of youth-onset type 2 diabetes (T2D) has increased worldwide, paralleling the rise in pediatric obesity. Occurrence and clinical manifestations vary regionally and demographically., Objectives: We assessed the incidence, and clinical and demographic manifestations of youth-onset T2D in Israel., Methods: In a national observational study, demographic, clinical, and laboratory data were collected from the medical records of children and adolescents, aged 10-18 years, diagnosed with T2D between the years 2008 and 2019., Results: The incidence of youth-onset T2D in Israel increased significantly from 0.63/100,000 in 2008 to 3.41/100,000 in 2019. The study cohort comprised 379 individuals (228 girls [59.7%], 221 Jews [58.3%], mean age 14.7 ± 1.9 years); 73.1% had a positive family history of T2D. Mean body mass index (BMI) z-score was 1.96 ± 0.7, higher in Jews than Arabs. High systolic (≥ 130 mmHg) and diastolic blood pressure (≥ 85 mmHg) were observed in 33.7% and 7.8% of patients, respectively; mean glycosylated hemoglobin (A1c) level at diagnosis was 8.8 ± 2.5%. Dyslipidemia, with high triglyceride (>150 mg/dl) and low HDL-c (<40 mg/dl) levels, was found in 45.6% and 56.5%, respectively. Microalbuminuria and retinopathy were documented at diagnosis, 15.2% and 1.9%, respectively) and increased (36.7% and 4.6%, respectively) at follow-up of 2.9 ± 2.1 years. Criteria of metabolic syndrome were met by 224 (62.2%) patients, and fatty liver documented in 65%, mainly Jews. Psychosocial comorbidity was found in 31%. Treatment with metformin (45.6%), insulin (20.6%), and lifestyle modification (18%) improved glycemic control., Conclusion: Youth-onset T2D in Israel has increased significantly and presents a unique profile., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Neonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes, diagnosed before age 6 months. We aimed to describe the clinical characteristics, molecular genetics, and long-term follow-up of NDM patients from a single pediatric endocrine center in Israel., Methods: Retrospective study (1975-2020) of all patients diagnosed with diabetes before 6 months of age, who tested negative for pancreatic autoantibodies. Medical records were reviewed for demographic, familial and medical history, and clinical and biochemical features; a genetic analysis was performed., Results: Of 24 patients, nine had transient neonatal diabetes (TNDM) and 15 permanent neonatal diabetes (PNDM), of whom five had rare syndromic causes. Genetic etiology was revealed in 87.5% of the NDM cohort, and the most common causes were ABCC8 mutations in TNDM and KCNJ11 and insulin gene mutations in PNDM. The switch from insulin to off-label sulfonylurea therapy was successful for 5/9 (56%) of the qualifying candidates. Severe hypoglycemia and diabetic ketoacidosis developed in 2 (8%) patients, and chronic diabetes complications in 5 (21%) patients with more than 10 years NDM. At last follow-up, weight and height of all but two syndromic PNDM patients were normal. The median height-SDS of the TNDM subgroup was significantly taller and the mean weight-SDS significantly heavier than those of the PNDM subgroup (-0.52 (-0.67, -0.09) vs. -0.9 (-1.42, -0.3) (p = 0.035) and 0.22 ± 0.69 vs. -0.89 ± 1.21 (p = 0.02), respectively). PNDM patients showed no incremental change in mean weight SDS over the time., Conclusion: The Israeli NDM cohort has clinical and genetic characteristics comparable with other populations. Patients with TNDM were taller and heavier than those diagnosed with PNDM, although both show rapid catch-up growth and reached normal growth parameters. Chronic diabetes complications developed in patients with long-standing NDM., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To evaluate the incidence and severity of ketoacidosis (DKA) at type 1 diabetes diagnosis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic in Israel., Research Design and Methods: A population-based study the product of a national collaboration of Israeli pediatric diabetes centers investigated the presentation of childhood-onset type 1 diabetes. The frequencies of DKA and severe DKA observed during the COVID-19 period from March 15, 2020 (commencement of the first nationwide lockdown) until June 30, 2020 were compared with the same periods in 2019, 2018, and 2017 using multivariable logistic regression, adjusting for age, sex, and socioeconomic position., Results: During the COVID-19 period, DKA incidence was 58.2%, significantly higher than in 2019 (adjusted OR [aOR] 2.18 [95% CI, 1.31-3.60], P = 0.003); 2018 (aOR 2.05 [95% CI, 1.26-3.34], P = 0.004); and 2017 (aOR, 1.79 [95% CI, 1.09-2.93], P = 0.022). The incidence of severe DKA was 19.9%, significantly higher than in 2018 (aOR, 2.49 [95% CI, 1.20-5.19], P = 0.015) and 2017 (aOR, 2.73 [95% CI, 1.28-5.82], P = 0.009). In 2020, admissions and duration of stay in the intensive care unit were higher than in previous years (P = 0.001). During the COVID-19 pandemic, children aged 6-11 years had higher incidences of DKA (61.3% vs. 34.0%, 40.6%, and 45.1%, respectively, P = 0.012), and severe DKA (29.3% vs. 15.1%, 10.9%, and 5.9%, respectively, P = 0.002)., Conclusions: The dramatic increase in DKA at presentation of childhood-onset type 1 diabetes during the COVID-19 pandemic mandates targeted measures to raise public and physician awareness., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Pregnancy and parturition reflect the complex interaction between physiological conditions of the mother and her offspring, and fetal health characteristics may affect maternal health throughout pregnancy and delivery. We aimed to investigate the characteristics of the mother-infant dyad of term infants detected as having congenital hypothyroidism (CH). Methods: A retrospective cohort study of 108,717 term infants delivered liveborn at Lis Maternity and Women's Hospital between 2010 and 2017. Infants were detected by the National Newborn Screening Program as having CH (131, 0.12%). Three years of surveillance in the Pediatric Endocrine Clinic revealed that 65 infants had transient CH and 66 had permanent CH. Data on maternal, pregnancy, delivery, and perinatal characteristics of the mother-infant dyads were retrieved from the hospital's electronic database. Results: Mode of delivery differed: a higher proportion of deliveries of CH infants required vacuum assistance, and more infants with CH were born through a cesarean section compared with the general population ( p  < 0.001). Medication during labor also differed, with higher rates of oxytocin ( p  < 0.001) and antibiotics ( p  = 0.008) administered to mothers of CH infants. A multivariate logistic regression model revealed an increased demand for oxytocin administration during the labor of a CH infant in a hypothyroidism severity-dependent manner, expressed as a threefold risk associated with permanent but not transient CH. Conclusions: Our findings of increased utilization of medical interventions during the labor and delivery of CH infants suggest that the prenatal fetal thyroid function may affect the development and progress of labor and delivery, in response to oxytocin.

Aims: Children with chronic diseases were unable to receive their usual care during COVID-19 lockdown. We assessed the feasibility and impact of telehealth visits on the time-in-range (TIR) of paediatric individuals with type 1 diabetes (T1D)., Methods: An observational multicentre real-life study. Patients scheduled for an in-clinic visit during the lockdown were offered to participate in a telehealth visit. Sociodemographic, clinical, continuous glucose monitor and pump data were recorded 2 weeks prior and 2 weeks after telehealth visit. The primary endpoint was change in relative-TIR, i.e. change in TIR divided by the percent of possible change (∆TIR/(100-TIRbefore)*100)., Results: The study group comprised 195 individuals with T1D (47.7% males), mean±SD age 14.6 ± 5.3 years, and diabetes duration 6.0 ± 4.6 years. Telehealth was accomplished with 121 patients and their parents (62.0%); 74 (38.0%) did not transfer complete data. Mean TIR was significantly higher for the two-week period after the telehealth visit than for the two-week period prior the visit (62.9 ± 16.0, p < 0.001 vs. 59.0 ± 17.2); the improvement in relative-TIR was 5.7±26.1%. Initial higher mean glucose level, lower TIR, less time spent at <54 mg/dl range, longer time spent at 180-250 mg/dl range, higher daily insulin dose, and single-parent household were associated with improved relative-TIR. Multiple regression logistic analysis demonstrated only initial lower TIR and single-parent household were significant, odds ratio: -0.506, (95%CI -0.99,-0.023), p=0.04 and 13.82, (95%CI 0.621, 27.016), p=0.04, respectively., Conclusions: Paediatric and young adult patients with T1D benefited from a telehealth visit during COVID-19. However, this modality is not yet suitable for a considerable proportion of patients.

Aim: To explore corticosteroid prescription practices and knowledge among paediatricians., Methods: The Paediatricians Corticosteroids Survey, a cross-sectional, web-based survey distributed to Israeli paediatricians between February and July 2018., Results: Three hundred and forty-nine paediatricians (105 general paediatricians, 207 subspecialists and 37 paediatric endocrinologists) participated. Two hundred and three (58.2%) had >10 years of paediatric clinical experience and treated >60 patients/wk on average, 175/318 (55%) prescribed corticosteroids to >10% of their patients. On knowledge items, 11/266 (4.1%) responded 'not sure' when tapering of steroids is required, 22/268 (8.2%) to what 'stress dose' meant and 27/268 (10.1%) when a stress dose is required. Multivariate linear analysis showed higher scores were associated with training in paediatric endocrinology (β = 2.271, P = 0.032); medical practice only in a subspecialty (β = 1.909, P = 0.041) or in both general paediatrics and a subspecialty (β = 2.023, P = 0.014), compared to general paediatrics alone and medical studies in Israel (β = 1.059, P = 0.035). Overall, 96.2% thought continued medical education (CME) sessions would be helpful., Conclusion: Our findings suggest that despite clinical experience with corticosteroid usage, respondents demonstrated gaps in knowledge for potentially life-threatening situations. Corticosteroid-based CME programs are warranted to improve paediatricians' knowledge and patient management., (©2020 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Aims: Disparities in health outcomes in pediatric type 1 diabetes (T1D) based on race/ethnicity and socioeconomic position (SEP) have been reported. We compared T1D characteristics between Eritrean status-less children living in Israel and native-born Israeli children., Methods: This observational study compared 7 Eritrean and 28 Israeli children (< 8 years old at T1D diagnosis) who were diagnosed in a single diabetes center during 2015-2019. Sociodemographic and diabetes-related data from diagnosis until the last clinic visit were retrieved from their medical files., Results: At diagnosis, the mean age was 4.8 ± 2.2 years, 17 (48.6%) had diabetic ketoacidosis with a mean HbA1c level of 10.5 ± 2.1% (91.3 mmol/mol) and 29 (82.9%) had ≥ 2 pancreatic autoantibodies. The mean T1D duration of follow-up was 2.7 ± 1.4 years. Overall glycemic control during follow-up (> 6 months from diagnosis, mean number of samples 10.6 ± 5.2) was good, with mean, best, and peak HbA1c levels of 7.4 ± 0.8% (57.4 mmol/mol), 6.7 ± 0.7% (49.7 mmol/mol), and 8.1 ± 1.1% (65 mmol/mol), respectively. Thirty-two children (91.4%) used continuous glucose monitoring devices (CGMs), and the mean time from diagnosis to CGM initiation was 10.8 ± 14.1 months. CGM metrics: time CGM active: 95.4 ± 3.8%, mean glucose level: 170.0 ± 27.0 mg/dl (9.4 mmol/L), time-in-range: 56.4 ± 14.7%, time-below-range: 5.5 ± 5.7%, and time-above-range: 38.6 ± 16.1%. Diabetes-related parameters at diagnosis and during follow-up were similar between groups. Eritrean children had significantly lower SEPs (P < 0.001) and parental education levels (P < 0.001). Correlations between SEP and diabetes parameters and SEP and growth parameters were not significant., Conclusions: Eritrean status-less children in Israel achieved glycemic targets similar to those of Israeli children, perhaps reflecting uniformity in the standard of care and CGM usage.

Background: In Israel, coronary heart disease mortality rates are significantly higher among the Arab population than the Jewish population. Dyslipidemia prevention should begin in childhood., Objectives: To identify sociodemographic disparities in the preventive health measurement of lipid profile testing and lipoprotein levels among Israeli children and adolescents., Methods: A cross-sectional analysis of 1.2 million children and adolescents insured by Clalit Health Services between 2007 and 2011 was conducted using sociodemographic data and serum lipid concentrations., Results: Overall, 10.1% individuals had undergone lipid testing. Those with male sex (odds ratio [OR] = 0.813, 95% confidence interval [95%CI] 0.809-0.816), Arab ethnicity (OR = 0.952, 95%CI 0.941-0.963), and low socioeconomic status (SES) (OR = 0.740, 95%CI 0.728-0.752) were less likely to be tested. By 2010, differences among economic sectors narrowed and Arab children were more likely to be tested (OR = 1.039, 95%CI 1.035-1.044). Girls had higher total cholesterol, triglyceride, low-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels compared to boys (P < 0.001). Jewish children had higher cholesterol and low-density and high-density lipoprotein-cholesterol, as well as lower triglyceride levels than Arabs (P < 0.001). Children with low SES had lower cholesterol, low-density and high-density lipoprotein-cholesterol, and non-high-density lipoprotein-cholesterol levels (P < 0.001)., Conclusions: We found that boys, Arab children, and those with low SES were less likely to be tested. Over time there was a gradual reduction in these disparities. Publicly sponsored healthcare services can diminish disparities in the provision of preventive health among diverse socioeconomic groups that comprise the national population.

Context: Growth hormone (GH) treatment of short healthy children is based on the belief that short stature is associated with psychosocial problems and a diminished quality of life., Objective: To determine the impact of GH therapy on psychosocial well-being and the ability of psychological metrics to define short stature-related distress., Methods: Sixty prepubertal boys with idiopathic short stature (age: 10.0 ± 1.4 years, height-SDS: -2.38 ± 0.3) were enrolled in this 4-year intervention study (1-year double-blinded, randomized, placebo-controlled [GH/placebo-2:1] and 3-year open-labelled GH therapy). Explicit (conscious/voluntary) psychological metrics (Pediatric Quality of Life Inventory [PedsQL], Silhouette Apperception Test [SAT], Rosenberg Self-Esteem Scale [RSES], Child Behavior Checklist [CBCL]) and implicit (unconscious/involuntary) psychological metrics (Single-Category Implicit Association Test for height [SC-IAT-H], Height Perception Picture Test [HPPT]). Psychosocial evaluations were performed at study entry, after 1 and 4 years., Results: At study entry, PedsQL of boys with idiopathic short stature was lower than Israeli norms (P = 0.001). After 1-year blinded intervention, only the GH-treated boys improved their actual and anticipated adult height perception (SAT, P < 0.001 and P = 0.022) with reduced short stature-related distress (SC-IAT-H, P < 0.001). At study end, RSES and SC-IAT-H improved significantly (P < 0.001), with no change in PedsQL and CBCL., Conclusions: Our finding of improved psychosocial functioning only in the GH-treated boys after 1-year blinded intervention suggests that it was the GH therapy, rather than being enrolled in a clinical trial, which contributed to the outcome. Long-term open-labelled GH treatment significantly improved height perception and self-esteem. Future studies are needed to fully assess the relevance of complementing the routinely used explicit self-report measures with the implicit measures., (© 2019 John Wiley & Sons Ltd.)

Aims: Nutrition and sleep are prerequisites for linear growth and we addressed the under-researched role of sleep in this equation., Methods: This was a prospective randomised, double-blinded, placebo-controlled study of nutritional supplements in 164 healthy lean, short, prepubertal children with 83 in the supplement group and 81 in the placebo group. From November 2010 to November 2013, we focussed on children aged three to nine years referred for specialist growth assessments to the Schneider Children's Medical Center, Israel. Progress was assessed using anthropometric measurements, sleep questionnaires and three-day food diaries at baseline and after the six-month intervention., Results: Children in the supplement group who took at least 50% of the recommended dose had shorter sleep latency than those who did not (p = 0.046). Children who fell asleep in less than 15 minutes had significantly improved standard deviation scores for weight (0.25 ± 0.34 versus 0.07 ± 0.36, p = 0.044) and height (0.09 ± 0.13 versus 0.03 ± 0.13, p = 0.057) than those who took longer to fall asleep. Positive correlations were found between mean sleep duration and caloric and macronutrient intake per kilogram., Conclusion: Adequate nutritional intake was associated with better sleep patterns and may enhance linear growth., (©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Context: Central precocious puberty (CPP) may have clinical implications in adulthood., Objective: To assess the prevalence of obesity, metabolic outcome (hyperlipidemia, diabetes, and hypertension), and malignancy rate of former CPP women between the third and fifth decades of life., Design: This was a case control study of a historical cohort using the computerized database of a health management organization., Setting: The setting was the Institute for Endocrinology and Diabetes, Schneider Children's Medical Center of Israel, and Clalit Health Services., Participants: The study group comprised of 142 CPP women aged 27-50 years [100 GnRH analog (GnRHa) treated; 42 untreated]. The control group comprised of 413 women randomly matched for age, year of birth, and community clinic (283 for the GnRHa treated; 130 for the untreated)., Methods: Extracted from the database were demographic data, medical history, medications dispensed, recorded anthropometric measurements, vital signs, and laboratory data., Results: At young adulthood, body mass index (percentile and distribution) of treated and untreated former CPP women was comparable to that of their respective controls. Elevated body mass index at presentation was a risk factor for obesity in adulthood in the GnRHa-treated group (r = 0.257; P = .01). The prevalence of metabolic comorbidities (16 vs 13.4%; 21.4 vs 24.6%) and malignancy rate (1.0 vs 1.5%; 4.8 vs 1.5%) were similar in the former CPP women and their controls, with no significant difference between CPP groups., Conclusion: CPP (treated or untreated) is not associated with increased risk of obesity, metabolic derangements, or cancer morbidities in young adulthood. The finding that the health status of former CPP women is similar to that of the general population is reassuring.

Background: The protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene encodes lymphoid tyrosine phosphatase (LYP), which is expressed primarily in lymphoid tissues. The functional but geographically highly variable PTPN22 single-nucleotide polymorphisms (SNPs), particularly c.1858C>T, contribute to the onset and progression of autoimmunity-associated diseases and facilitate the expression of disease-associated autoantibodies. In Central Europe, 17-25% of patients with monogenic diabetes (maturity-onset diabetes of the young, MODY) transiently express islet cell autoantibodies., Methods: We addressed the links between the functional and geographically variable PTPN22 SNPs with MODY manifestation and the expression of islet cell autoantibodies in 276 MODY patients who originated from four regions (the Czech Republic, Israel, Japan and Brazil)., Results: The frequency of PTPN22 polymorphisms in the MODY patients was similar to those in geographically matched healthy populations, with the exception of c.788G>A, the minor allele frequency of which was significantly elevated in the Czech hepatocyte nuclear factor 1-α (HNF1A) MODY patients [odds ratio (OR) 4.8, 95% confidence interval (CI) 2.2-10.7] and the Brazilian MODY patients (OR 8.4, 95% CI 1.8-39.1). A barely significant increase in the c.788G>A minor allele was also detected in the islet cell autoantibody-positive Czech MODY patients. However, c.788A behaves as a loss-of-function mutant in T cells, and thus protects against autoimmunity., Conclusions: MODY patients (including islet cell autoantibody-positive cases) do not display any increase in autoimmunity-associated PTPN22 alleles. The absence of autoimmunity-associated PTPN22 alleles was also demonstrated in latent autoimmune diabetes in adults, which suggests that the slow kinetics of the onset of autoantibodies is subject to a regulation that is different from that experienced in type 1 diabetes and other autoimmune disorders., (© 2015 S. Karger AG, Basel.)

Background: Maturity-onset diabetes of the young (MODY) is characterized by an autosomal dominant mode of inheritance; a primary defect in insulin secretion with non-ketotic hyperglycemia, age of onset under 25 yr; and lack of autoantibodies. Heterozygous mutations in glucokinase (GCK) are associated with mild fasting hyperglycemia and gestational diabetes mellitus while homozygous or compound heterozygous GCK mutations result in permanent neonatal diabetes mellitus. Given that both the Israeli-Arabic and the various Israeli-Jewish communities tend to maintain ethnic seclusion, we speculated that it would be possible to identify a relatively narrow spectrum of mutations in the Israeli population., Objective: To characterize the genetic basis of GCK-MODY in the different ethnic groups of the Israeli population., Subjects: Patients with clinically identified GCK-MODY and their first degree family members., Methods: Molecular analysis of GCK was performed on genomic DNA using polymerase chain reaction, denaturing gradient gel electrophoresis (DGGE), and sequencing. Bioinformatic model was preformed using the NEST program., Results: Mutations in GCK were identified in 25 families and were all family-specific, except c.616A>C. p.T206P. This mutation was identified in six unrelated families, all patients from a Jewish-Ashkenazi descent, thus indicating an ethno-genetic correlation. A simple, fast, and relatively cheap DGGE/restriction-digestion assay was developed., Conclusions: The high incidence of the mutant allele in GCK-MODY patients of Jewish-Ashkenazi descent suggests a founder effect. We propose that clinically identified GCK-MODY patients of Jewish-Ashkenazi origin be first tested for this mutation., (© 2011 John Wiley & Sons A/S.)

Aims: To determine whether the frequency and severity of diabetic ketoacidosis and the clinical characteristics of children at diagnosis of Type 1 diabetes mellitus have changed over the past decades among patients under surveillance of a tertiary paediatric centre., Methods: In three time-periods, 75 (1986-1987), 86 (1996-1997) and 245 (2006-2007) patients at mean age 10.1 ± 4.7 years (0.6-20.0) were diagnosed with new-onset Type 1 diabetes. Data on clinical characteristics and laboratory evaluation at diagnosis retrieved from the patients' files . Comparative analysis was performed between the three time periods., Results: The frequency of diabetic ketoacidosis at diagnosis was 40% in 1986-1987, 41.8% in 1996-1997 and 29.4% in 2006-2007; the last rate was significantly lower (P=0.04). No significant differences in the proportions of patients with severe or moderate diabetic ketoacidosis were found over time. Mean weight standard deviation score significantly increased from -0.72 ± 1.8 in 1986-1987 to -0.27 ± 1.2 in 2006-2007 (P<0.05), while percentage weight loss (∼6.5%) before diagnosis remained unchanged. In 2006-2007 a higher proportion of children had glucose testing at the community clinic before diagnosis, than in the earlier years (73.1 vs. 59.6%, P=0.003)., Conclusions: The overall frequency of diabetic ketoacidosis in children with newly diagnosed Type 1 diabetes has decreased in the past decade, although the degree of metabolic decompensation has remained unchanged., (© 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.)

Background: Type 1 diabetes (T1D) patients are at risk for additional autoimmune diseases (AID)., Objective: To compare the characteristics of associated autoimmunity among familial (parent-offspring and sib-pair) subgroups and sporadic T1D patients., Patients and Methods: Data regarding AID in T1D patients and their nuclear family members were extracted from medical files of 121 multiplex T1D families (58 parent-offspring, 63 sib-pairs) and 226 sporadic controls followed between 1979 and 2008., Results: The prevalence of associated autoimmunity was similar in familial and sporadic cases (33.6 vs. 32.7%). The frequency of additional AID and percentage of patients with two or more coexistent AID were significantly higher among sib-pairs than parent-offspring (p = 0.05 and p = 0.04, respectively). The median time elapsed between diagnosis of T1D and occurrence of additional autoimmunity tended to be shorter in the sib-pairs. Only in familial cases did a positive autoimmune family background predict the development of coexistent autoimmunity (OR = 2.11, CI [1.0, 4.49] p = 0.05)., Conclusions: Among sib-pairs with T1D, the higher prevalence of additional AID, the increased number of diseases per person, and the relatively earlier appearance of associated AID suggest an increased susceptibility for coexistent autoimmunity in this subgroup. Positive family history for autoimmunity in multiplex T1D families increased their risk for co-occurrence of AID., (Copyright © 2011 S. Karger AG, Basel.)

Background: Familial type 1 diabetes mellitus (T1D) comprises parent-offspring and sib-pair subgroups., Objective: To compare the demographic and clinical characteristics in the two subgroups at diagnosis and evaluate the differences between index cases and second affected family members., Methods: Retrieved from our institutional registry of new T1D cases for the years 1979-2008 were a cohort of 194 familial cases (87 parent-offspring, 107 sib-pairs); 133 sporadic cases matched by age, gender, and year of diagnosis were selected as controls. Extracted from their medical files were demographic data, family background, clinical and laboratory findings., Results: The parent-offspring subgroup was characterized by male preponderance (p = 0.009). At diagnosis parents were significantly older than their offspring (p < 0.001) and probands were significantly younger than their affected siblings (p = 0.03). Clinical symptoms and metabolic decompensation were similar in the familial subgroups. Diabetic ketoacidosis (DKA) rate and hemoglobin A1c (HbA1c) levels were lower in second affected family members in both parent-offspring (p = 0.05 and p < 0.001) and sib-pair subgroups (p < 0.001, for both parameters). Consanguinity and T1D were more frequent in the extended family of familial than sporadic cases (p < 0.001 and p = 0.012, respectively) with no difference between the two subgroups., Conclusions: The genetic background for T1D would appear to differ not only between familial and sporadic cases but also between parent-offspring and sib-pair subgroups. Whereas differences in age of onset are attributable to both genetic and environmental factors, the less severe clinical manifestations in second affected family members may result from increased awareness or a less aggressive disease process.