Incidence of Type 1 Diabetes in Relation to Exposure to Rotavirus Infections in Pre- and Postvaccine Birth Cohorts in Finland.

OBJECTIVE: To explore the incidence of type 1 diabetes in children in relation to exposure to rotavirus infections. RESEARCH DESIGN AND METHODS: A nationwide register-based ecological study on the 1995-2015 birth cohorts in Finland compared those born before and after the national implementation of the rotavirus vaccine in 2009. RESULTS: When the prevaccine 2001-2005 birth cohorts were compared with the postvaccine birth cohorts, the number of children exposed to rotavirus infection by the age of 5 years decreased from 2,522 per 100,000 children (2.5%) to 171 per 100,000 children (0.2%), while the incidence of type 1 diabetes in those aged <5 years decreased from 71.5 to 54.4 per 100,000 person-years (incidence rate ratio 0.79, 95% CI 0.71-0.86). CONCLUSIONS: At the population level, a decrease in exposure to rotavirus infections was associated with a decrease in the incidence of type 1 diabetes in young children.

SARS-CoV-2 and type 1 diabetes in children in Finland: an observational study.

BACKGROUND: Some epidemiological studies have suggested an increase in incidence of type 1 diabetes during the COVID-19 pandemic, however the mechanism(s) behind such an increase have yet to be identified. In this study we aimed to evaluate the possible role of the SARS-CoV-2 virus in the reported increase in the rate of type 1 diabetes. METHODS: In this observational cohort study using data from the Finnish Pediatric Diabetes Register (FPDR), we assessed the incidence of type 1 diabetes (number of children with newly diagnosed type 1 diabetes per 100 000 person-years during the pandemic and the reference period) during the first 18 months of the COVID-19 pandemic in children in Finland younger than 15 years old compared with a reference period which included three corresponding pre-pandemic periods also obtained from the FPDR. Children with confirmed monogenic diabetes were excluded. We also compared the phenotype and HLA genotype of the disease between these two cohorts, and analysed the proportion of newly diagnosed people with type 1 diabetes testing positive for SARS-CoV-2 antibodies. FINDINGS: 785 children and adolescents in Finland were diagnosed with type 1 diabetes from March 1, 2020, to Aug 31, 2021. In the reference period, which comprised three similar 18-month terms (from March 1, 2014, to Aug 31, 2015; March 1, 2016, to Aug 31, 2017; and March 1, 2018, to Aug 31, 2019) 2096 children and adolescents were diagnosed. The incidence of type 1 diabetes was 61·0 per 100 000 person-years (95% CI 56·8-65·4) among children younger than 15 years old during the pandemic, which was significantly higher than during the reference period (52·3 per 100 000 person-years; 50·1-54·6). The incidence rate ratio adjusted for age and sex for the COVID-19 pandemic was 1·16 (1·06-1·25; p=0·0006) when compared with the reference period. The children diagnosed during the COVID-19 pandemic had more often diabetic ketoacidosis (p<0·001), had a higher HbA1c (p<0·001), and tested more frequently positive for glutamic acid debarboxylase antibodies at diagnosis (p<0·001) than those diagnosed before the pandemic. There were no significant differences in the distribution of HLA genotypes between the two periods. Only five of those diagnosed during the pandemic (0·9%) of 583 tested positive for infection-induced SARS-CoV-2 antibodies. INTERPRETATION: Children and adolescents diagnosed with type 1 diabetes during the pandemic had a more severe disease at diagnosis. The observed increase in type 1 diabetes incidence during the first 18 months could be a consequence of lockdown and physical distancing rather than a direct effect of SARS-CoV-2 infection. FUNDING: Helsinki University Hospital Research Funds, EU Horizon 2020 (Versatile emerging infectious disease observatory project), Academy of Finland, Sigrid Jusélius Foundation, Jane & Aatos Erkko Foundation, and Medicinska understödsföreningen Liv och Hälsa. TRANSLATIONS: For the Finnish and Swedish translations of the abstract see Supplementary Materials section.

Heterogeneity of Type 1 Diabetes at Diagnosis Supports Existence of Age-Related Endotypes.

OBJECTIVE: Previous findings suggest that there are age-related endotypes of type 1 diabetes with different underlying etiopathological mechanisms in those diagnosed at age <7 years compared with those diagnosed at age ≥13 years. We set out to explore whether variation in demographic, clinical, autoimmune, and genetic characteristics of children and adolescents with newly diagnosed type 1 diabetes support the existence of these proposed endotypes. RESEARCH DESIGN AND METHODS: We used data from the Finnish Pediatric Diabetes Register to analyze characteristics of 6,015 children and adolescents diagnosed with type 1 diabetes between 2003 and 2019. We described and compared demographic data, clinical characteristics at diagnosis, autoantibody profiles, and HLA class II-associated disease risk between three groups formed based on age at diagnosis: <7, 7-12, and ≥13 years. RESULTS: We found significant age-related differences in most of the characteristics analyzed. Children diagnosed at age <7 years were characterized by a higher prevalence of affected first-degree relatives, stronger HLA-conferred disease susceptibility, and higher number of autoantibodies at diagnosis, in particular a higher frequency of insulin autoantibodies, when compared with older children. Those diagnosed at age ≥13 years had a considerably higher male preponderance, higher frequency of glutamic acid decarboxylase autoantibodies, longer duration of symptoms before diagnosis, and more severe metabolic decompensation, reflected, for example, by a higher frequency of diabetic ketoacidosis. CONCLUSIONS: Our findings suggest that the heterogeneity of type 1 diabetes is associated with the underlying disease process and support the existence of distinct endotypes of type 1 diabetes related to age at diagnosis.

Decreased Incidence of Type 1 Diabetes in Young Finnish Children.

OBJECTIVE: The incidence of type 1 diabetes has been rising for decades, particularly among young children. Between 2006 and 2011, the incidence rate (IR) reached a plateau in Finland. In this observational, register-based cohort study, we assess recent trends in the disease rate in Finnish children. RESEARCH DESIGN AND METHODS: Based on data from the Finnish Pediatric Diabetes Register, we studied the incidence of type 1 diabetes among children younger than 15 years of age between 2003 and 2018. We assessed sex-specific IRs per 100,000 person-years (PY) by 4-year time periods in three age-groups (0.50-4.99, 5.00-9.99, and 10.00-14.99 years). RESULTS: Among the 7,871 children with newly diagnosed type 1 diabetes, the median age at diagnosis increased from 7.88 to 8.33 years (P = 0.001), while the overall IR decreased from 57.9/100,000 PY in 2003-2006 to 52.2/100,000 PY in 2015-2018, yielding an IR ratio (IRR) of 0.90 (95% CI 0.85-0.96, P = 0.001). This decline was mainly due to the decrease in the youngest age-group (IRR 0.77 [95% CI 0.68-0.87]; P < 0.001), being significant both among boys and girls. In the middle age-group, a significant decrease was observed only among girls. No changes were observed in the oldest children. CONCLUSIONS: The incidence of type 1 diabetes decreased among young Finnish children between 2003 and 2018. Current findings imply that environmental factors driving the immune system toward islet autoimmunity are changing in young children.

Effect of carboxymethylcellulose and hyaluronate solutions on jejunal healing in horses.

OBJECTIVE: To compare a double-layer inverting anastomosis with a single-layer appositional anastomosis, coated with either 1% sodium carboxymethylcellulose (SCMC) or 0.4% sodium hyaluronate (HA) solutions, in the small intestine of horses with respect to anastomotic healing and adhesion formation. ANIMALS: 18 adult horses. PROCEDURE: Midline celiotomy and end-to-end jejunal anastomoses were performed. In control group horses (n = 6), a double-layer inverting anastomosis coated with sterile lactated Ringer's solution was performed. In treatment group horses, a single-layer appositional anastomosis was performed that was coated with 1% carboxymethylcellulose solution (SAA + SCMC group horses, 6) or 0.4% hyaluronate solution (SAA + HA group horses, 6). An additional 500 mL of the respective treatment solution was applied to the jejunal serosal surface, and 2 jejunal serosal abrasion sites were created. Horses were euthanatized 10 days after surgery. Anastomoses and abdominal adhesions were evaluated grossly. Anastomotic healing was evaluated on the basis of bursting wall tension. RESULTS: Bursting wall tension was significantly greater in SAA + SCMC group horses, compared with control group horses. All intestinal segments failed at a point distant to the anastomosis. Significantly fewer adhesions were found at the abrasion sites of SAA + HA group horses, compared with control group horses. No differences were found in adhesion formation at the anastomotic sites among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Coating a single-layer appositional jejunal anastomosis with SCMC or HA solutions does not adversely affect anastomotic healing. Application of 0.4% HA solution to the serosal surface of the jejunum significantly decreases the incidence of experimentally induced intra-abdominal adhesion formation in horses.

Antepartum findings and obstetric aspects in pregnancies followed by neonatal persistent hyperinsulinemic hypoglycemia.

In this study we report antepartum and obstetric findings in cases of persistent hyperinsulinemic hypoglycemia of infancy (PHHI). The study is retrospective and covers the years 1983 to 1994, when there were 9 infants treated for PHHI in the region of the University Hospital of Kuopio. One of the mothers had gestational diabetes mellitus and one had insulin-dependent diabetes mellitus (IDDM). There were signs of fetal distress in cardiotocography (CTG) in 3 of 9 cases prenatally and in 3 of 9 cases intrapartum (33%). There were 5 premature deliveries (56%) and 5 cesarean sections (56%) in this series. Five neonates (56%) were macrosomic and one delivery was complicated by shoulder dystocia. Three neonates (33%) had a 1-minute Apgar score of <6, but there were no cases at 5 minutes. In cases of fetal macrosomia without a maternal diabetic problem amniocentesis may be carried out after 34 weeks of gestation to assay amniotic fluid insulin, C-peptide and erythropoietin to reveal rare cases of PHHI where there may be problems of fetal hypoxemia similar to those in diabetic pregnancies.