Sofia Carlsson

Research problem and specific questionsType 2 diabetes (T2D) is a common, chronic disease that increases the risk of cardiovascular disease and shortens life expectancy. T2D was formerly known as “old-age diabetes” but is now increasingly affecting adolescents and young adults (&lt

40 years). In Sweden, the prevalence of early-onset T2D doubled between 2006 and 2021. The risk is highest among people with a foreign origin or low education and is increasing fastest in young women. This is an alarming trend because the earlier the disease develops, the higher the risk of serious complications and shortened life expectancy. Moreover, developing T2D at a young age may negatively affect family formation, professional life and pregnancy outcomes. Preventing early-onset T2D requires knowledge of the factors influencing the risk of developing the disease, and factors that increase the risk of complications and reduced life chances for those affected.  International research on early-onset T2D is limited, and Swedish research almost non-existent. The aim of this project is to fill key knowledge gaps regarding the risk factors and consequences of early-onset T2D. Specifically, we will:RISK FACTORS: elucidate heritability and identify risk factors (pre- and perinatal factors, individual and contextual socioeconomic factors, ethnic origin, childhood/adolescent diseases, lifestyle factors).CONSEQUENCES: study mortality, cardiovascular disease, pregnancy outcomes and socio-economic consequences and identify prognostic factors (inadequate treatment, mental and somatic co-morbidity, glucose control and metabolic risk factors, lifestyle and socio-economic and demographic factors).Data and methodsWe have created a database consisting of the entire Swedish population and collected information from nine national registries over a 40-year period. This allows us to identify all those who developed T2D diabetes in Sweden since the 1990s, map exposures before diagnosis and follow their prognosis. We have identified kinship ties within the cohort and can thus combine traditional cohort design with family-based design and compare people who developed T2D with their siblings without diabetes with respect to possible risk factors and different health and socioeconomic outcomes. In this way, confounding can be minimized. We will also conduct focus group interviews with young people with T2D to generate hypotheses and deepen the interpretations of the results obtained.Societal relevance and utilisationT2D in young people is a significant public health threat, with a strong social gradient. The proposed project is the most comprehensive of its kind and has the potential to significantly increase knowledge about T2D and its determinants and consequences among young people in Sweden. The results can be used to identify vulnerable groups in need of targeted interventions, improve primary and secondary prevention and inform policy makers. Thereby, the study can contribute to improved public health and reduced health inequalities. The results will be communicated in the form of scientific articles and via reports and seminars aimed at authorities responsible for public health and care such as the Public Health Agency of Sweden and the National Board of Health and Welfare, as well as regional public health and healthcare planners and providers. We will also publish in professional journals to reach the clinical profession and communicate with patient organizations, such as the Swedish Diabetes Association and write articles in patient magazines.Plan for project realisationThe project is being carried out at Karolinska Institutet by a team with expertise in all aspects of the project (epidemiology, biostatistics, sociology, obstetrics, endocrinology and cardiology). Most of the data is available, and preliminary analyses show that the feasibility is high. Funding is sought for analysis, report writing, focus group interviews and communication of research results.

Diabetes is a chronic disease affecting 1/5 swedes during their lifetime, associated with CVD and reduced life expectancy. With a finer classification of diabetes, opportunities arise for better assessment of factors influencing onset and prognosis, which may lead to improved prevention. This project involves subtypes within the broad categories T1D and T2D

LADA– a common form of autoimmune diabetes, newly proposed subtypes of T2D- including a severe insulin resistant and a severe insulin deficient type, and adult onset T1D. We aim to provide new knowledge on the interplay environmental vs. genetic factors influences in the aetiology of these largely unexplored subtypes of diabetes. To this aim, we are conducting the world´s largest study of LADA, the ESTRID-study, with incident cases of LADA and T2D subtypes and clinical, genetic and environmental information. The Norwegian HUNT-study, European Epic-InterAct and UK biobank, which includes adult onset T1D, will be used for extensions and replication. We will use Mendelian Randomization design for causal inference. ESTRID and HUNT are linked to national registers allowing us to follow patients from diagnosis and assess the prognostic role of clinical, genetic and lifestyle factors. The aim is to identify factors increasing the risk of autoimmune diabetes in adults and different forms of T2D and factors contributing to poor prognosis. Such knowledge is central future efforts to prevent diabetes and its consequences.