Publications by authors named "Lernmark Ake"

Context: When clinically stable, patients with A-β+ Ketosis-Prone Diabetes (KPD) manifest unique markers of amino acid metabolism. Biomarkers differentiating KPD from type 1 (T1D) and type 2 diabetes (T2D) during hyperglycemic crises would accelerate diagnosis and management.

Objective: Compare serum metabolomics of KPD, T1D and T2D patients during hyperglycemic crises, and utilize Classification and Regression Tree (CART) modeling to distinguish these forms of diabetes.

View Article and Find Full Text PDF

The goal of the TEDDY (The Environmental Determinants of Diabetes in the Young) study is to elucidate factors leading to the initiation of islet autoimmunity (first primary outcome) and those related to progression to type 1 diabetes mellitus (T1DM; second primary outcome). This Review outlines the key findings so far, particularly related to the first primary outcome. The background, history and organization of the study are discussed.

View Article and Find Full Text PDF

Aims/hypothesis: The aim of this work was to explore molecular amino acids (AAs) and related structures of HLA-DQA1-DQB1 that underlie its contribution to the progression from stages 1 or 2 to stage 3 type 1 diabetes.

Methods: Using high-resolution DQA1 and DQB1 genotypes from 1216 participants in the Diabetes Prevention Trial-Type 1 and the Diabetes Prevention Trial, we applied hierarchically organised haplotype association analysis (HOH) to decipher which AAs contributed to the associations of DQ with disease and their structural properties. HOH relied on the Cox regression to quantify the association of DQ with time-to-onset of type 1 diabetes.

View Article and Find Full Text PDF

Aims: The study aims were to determine autoantibodies associated with type 1 diabetes (T1D), celiac disease (CD) and autoimmune thyroid disease (AITD) in individuals living with type 2 diabetes (T2D) compared to T1D and matched controls.

Methods: Individuals with T1D and T2D were randomly identified in health-care registers. Blood was collected through home-capillary sampling and autoantibodies associated with either T1D against glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A), CD against tissue transglutaminase (tTGA) or AITD against thyroid peroxidase (TPOA) were determined in an automated, multiplex Antibody Detection by Agglutination-PCR (ADAP) assay.

View Article and Find Full Text PDF

It is oftentimes the case in studies of disease progression that subjects can move into one of several disease states of interest. Multistate models are an indispensable tool to analyze data from such studies. The Environmental Determinants of Diabetes in the Young (TEDDY) is an observational study of at-risk children from birth to onset of type-1 diabetes (T1D) up through the age of 15.

View Article and Find Full Text PDF

Context: Autoantibodies to thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) define preclinical autoimmune thyroid disease (AITD), which can progress to either clinical hypothyroidism or hyperthyroidism.

Objective: We determined the age at seroconversion in children genetically at risk for type 1 diabetes.

Methods: TPOAb and TgAb seropositivity were determined in 5066 healthy children with human leukocyte antigen (HLA) DR3- or DR4-containing haplogenotypes from The Environmental Determinants of Diabetes in the Young (TEDDY) study.

View Article and Find Full Text PDF
Article Synopsis
  • The study aimed to investigate whether oral insulin can postpone the onset of stage 3 type 1 diabetes (T1D) in patients who have stage 1 or 2 T1D and specific genetic markers (HLA DR4-DQ8) or elevated IA-2 autoantibodies.
  • Researchers used advanced genetic testing on 546 participants to analyze the connection between genetic factors and autoantibody levels prior to treatment, utilizing Cox regression to assess the effectiveness of oral insulin.
  • Findings revealed that oral insulin significantly decreased the T1D onset in participants with high IA-2A levels, particularly among those carrying the HLA DR4-DQ8 haplotype, indicating a specific endotype of T1D
View Article and Find Full Text PDF

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programs are being increasingly emphasized. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb+) children and adults who are at risk for (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in nonspecialized settings.

View Article and Find Full Text PDF

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb) children and adults who are at risk of (confirmed single IAb) or living with (multiple IAb) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings.

View Article and Find Full Text PDF

Context: The 2 peaks of type 1 diabetes incidence occur during early childhood and puberty.

Objective: We sought to better understand the relationship between puberty, islet autoimmunity, and type 1 diabetes.

Methods: The relationships between puberty, islet autoimmunity, and progression to type 1 diabetes were investigated prospectively in children followed in The Environmental Determinants of Diabetes in the Young (TEDDY) study.

View Article and Find Full Text PDF

Aims/hypothesis: Delivery by Caesarean section continues to rise globally and has been associated with the risk of developing type 1 diabetes and the rate of progression from pre-symptomatic stage 1 or 2 type 1 diabetes to symptomatic stage 3 disease. The aim of this study was to examine the association between Caesarean delivery and progression to stage 3 type 1 diabetes in children with pre-symptomatic early-stage type 1 diabetes.

Methods: Caesarean section was examined in 8135 children from the TEDDY study who had an increased genetic risk for type 1 diabetes and were followed from birth for the development of islet autoantibodies and type 1 diabetes.

View Article and Find Full Text PDF
Article Synopsis
  • The study examines the effectiveness of a new automated multiplex Antibody Detection by Agglutination-PCR (ADAP) method for diagnosing type 1 diabetes compared to traditional single-plex radiobinding assays (RBA).
  • It analyzed various autoantibodies in nearly 10,000 participants, aiming to establish diagnostic thresholds for identifying different stages of type 1 diabetes.
  • Results showed ADAP had higher sensitivity and comparable specificity to RBA, suggesting it may be a more effective diagnostic tool for detecting multiple autoantibodies in type 1 diabetes.
View Article and Find Full Text PDF

Objective: To explore associations of HLA class II genes (HLAII) with the progression of islet autoimmunity from asymptomatic to symptomatic type 1 diabetes (T1D).

Research Design And Methods: Next-generation targeted sequencing was used to genotype eight HLAII genes (DQA1, DQB1, DRB1, DRB3, DRB4, DRB5, DPA1, DPB1) in 1,216 participants from the Diabetes Prevention Trial-1 and Randomized Diabetes Prevention Trial with Oral Insulin sponsored by TrialNet. By the linkage disequilibrium, DQA1 and DQB1 are haplotyped to form DQ haplotypes; DP and DR haplotypes are similarly constructed.

View Article and Find Full Text PDF
Article Synopsis
  • - The study aimed to evaluate anxiety, depression, and quality of life (QoL) among individuals with type 1 (T1D) and type 2 diabetes (T2D) compared to matched controls during the COVID-19 pandemic's second wave.
  • - Researchers collected data from 203 T1D and 413 T2D individuals, along with 282 controls, through questionnaires on mental health, QoL, and blood samples to assess coronavirus antibody levels.
  • - Findings indicated that younger individuals and health issues were linked to higher anxiety and depression, with T1D showing a greater SARS-CoV-2 NCP infection rate, potentially due to factors like age and employment status.
View Article and Find Full Text PDF

Purpose: The aim was to study the association between dietary intake of B vitamins in childhood and the risk of islet autoimmunity (IA) and progression to type 1 diabetes (T1D) by the age of 10 years.

Methods: We followed 8500 T1D-susceptible children born in the U.S.

View Article and Find Full Text PDF

The type 1 diabetes community is coalescing around the benefits and advantages of early screening for disease risk. To be accepted by healthcare providers, regulatory authorities and payers, screening programmes need to show that the testing variables allow accurate risk prediction and that individualised risk-informed monitoring plans are established, as well as operational feasibility, cost-effectiveness and acceptance at population level. Artificial intelligence (AI) has the potential to contribute to solving these issues, starting with the identification and stratification of at-risk individuals.

View Article and Find Full Text PDF

Although the genetic basis and pathogenesis of type 1 diabetes have been studied extensively, how host responses to environmental factors might contribute to autoantibody development remains largely unknown. Here, we use longitudinal blood transcriptome sequencing data to characterize host responses in children within 12 months prior to the appearance of type 1 diabetes-linked islet autoantibodies, as well as matched control children. We report that children who present with insulin-specific autoantibodies first have distinct transcriptional profiles from those who develop GADA autoantibodies first.

View Article and Find Full Text PDF

Objective: To investigate gastrointestinal infection episodes (GIEs) in relation to the appearance of islet autoantibodies in The Environmental Determinants of Diabetes in the Young (TEDDY) cohort.

Research Design And Methods: GIEs on risk of autoantibodies against either insulin (IAA) or GAD (GADA) as the first-appearing autoantibody were assessed in a 10-year follow-up of 7,867 children. Stool virome was characterized in a nested case-control study.

View Article and Find Full Text PDF

Objective: To study the interaction among HLA genotype, early probiotic exposure, and timing of complementary foods in relation to risk of islet autoimmunity (IA).

Research Design And Methods: The Environmental Determinants of Diabetes in the Young (TEDDY) study prospectively follows 8,676 children with increased genetic risk of type 1 diabetes. We used a Cox proportional hazards regression model adjusting for potential confounders to study early feeding and the risk of IA in a sample of 7,770 children.

View Article and Find Full Text PDF
Article Synopsis
  • A committee evaluated the scientific evidence and developed evidence-based recommendations for laboratory tests used in diagnosing and managing diabetes mellitus, which were reviewed by various professional organizations.
  • Diagnosis of diabetes is primarily based on elevated glucose levels in blood or Hb A1c measurements, while patients can monitor their glycemic control using self-testing methods.
  • The guidelines highlight several testing methods, stating that some analytes currently offer minimal clinical value and are not recommended for use in practice.
View Article and Find Full Text PDF

Background: Numerous laboratory tests are used in the diagnosis and management of diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially.

Approach: An expert committee compiled evidence-based recommendations for laboratory analysis in screening, diagnosis, or monitoring of diabetes.

View Article and Find Full Text PDF

Background: Numerous laboratory tests are used in the diagnosis and management of diabetes mellitus. The quality of the scientific evidence supporting the use of these assays varies substantially.

Approach: An expert committee compiled evidence-based recommendations for laboratory analysis in screening, diagnosis, or monitoring of diabetes.

View Article and Find Full Text PDF