Aims/hypothesis Type 2 diabetes is one of the leading causes of death globally and its incidence has increased dramatically over the last two decades. Recent research suggests that loneliness is a possible risk factor for type 2 diabetes. This 20 year follow-up study examined whether loneliness is associated with an increased risk of type 2 diabetes. As both loneliness and type 2 diabetes have been linked to depression and sleep problems, we also investigated whether any association between loneliness and type 2 diabetes is mediated by symptoms of depression and insomnia. Methods We used data from the Trøndelag Health Study (HUNT study), a large longitudinal health study based on a population from central Norway (n=24,024). Self-reports of loneliness (HUNT2 survey, 1995–1997) and data on HbA1c levels (HUNT4 survey, 2017–2019) were analysed to evaluate the associations between loneliness and incidence of type 2 diabetes. Associations were reported as ORs with 95% CIs, adjusted for sex, age and education. We further investigated the role of depression and insomnia as potential mediating factors. Results During the 20 year follow-up period, 4.9% of the study participants developed type 2 diabetes. Various degrees of feeling lonely were reported by 12.6% of the participants. Individuals who felt most lonely had a twofold higher risk of developing type 2 diabetes relative to those who did not feel lonely (adjusted OR 2.19 [95% CI 1.16, 4.15]). The effect of loneliness on type 2 diabetes was weakly mediated by one subtype of insomnia but not by symptoms of depression. Conclusions/interpretation This study suggests that loneliness may be one factor that increases the risk of type 2 diabetes; however, there is no strong support that the effect of loneliness on type 2 diabetes is mediated by depression or insomnia. We recommend that loneliness should be included in clinical guidelines on consultations and interventions related to type 2 diabetes. Graphical abstract

Purpose To characterize the kynurenine pathway, activated during interferon-γ mediated inflammation and cellular (Th1-type) immunity, in Graves` disease (GD) patients with and without thyroid eye disease (TED). Methods We analyzed 34 biomarkers by mass spectrometry in serum samples from 100 patients with GD (36 with TED) and 100 matched healthy controls. The analytes included 10 metabolites and three indices from the kynurenine pathway, six microbiota-derived metabolites, 10 B-vitamers and five serum proteins reflecting inflammation and kidney function. Results GD patients showed significantly elevated levels of seven biomarkers compared with healthy controls (omega squared (ω2) > 0.06, P < 0.01). Out of these seven, the six biomarkers with the strongest effect size were all components of the kynurenine pathway. Factor analysis showed that biomarkers related to cellular immunity and the Th1 responses (3-hydroxykynurenine, kynurenine and quinolinic acid with the highest loading) were most strongly associated with GD. Further, a factor mainly reflecting acute phase response (CRP and serum amyloid A) showed weaker association with GD by factor analysis. There were no differences in biomarker levels between GD patients with and without TED. Conclusion This study supports activation of interferon-γ inflammation and Th1 cellular immunity in GD, but also a contribution of acute phase reactants. Our finding of no difference in systemic activation of the kynurenine pathway in GD patients with and without TED implies that the local Th1 immune response in the orbit is not reflected systemically.

PurposeThe ‘Outcomes & Multi-morbidity in Type 2 Diabetes’ (OMIT) is an observational registry-based cohort of Norwegian patients with type 2 diabetes (T2D) established to study high-risk groups often omitted from randomised clinical trials.ParticipantsThe OMIT cohort includes 57 572 patients with T2D identified via linkage of Norwegian Diabetes Register for Adults and the Rogaland-Oslo-Salten-Akershus-Hordaland study, both offering data on clinical patient characteristics and drug prescriptions. Subsequently these data are further linked to the Norwegian Prescription Database for dispensed medications, the Norwegian Population Register for data on death and migration, Statistics Norway for data on socioeconomic factors and ethnicity and the Norwegian Directorate of Health for data on the general practices and clinical procedures involved in the care of cohort patients. OMIT offers large samples for key high-risk patient groups: (1) young-onset diabetes (T2D at age <40 years) (n=6510), (2) elderly (age >75 years) (n=15 540), (3) non-Western ethnic minorities (n=9000) and (4) low socioeconomic status (n=20 500).Findings to dateOn average, patient age and diabetes duration is 67.4±13.2 and 12.3±8.3 years, respectively, and mean HbA1c for the whole cohort through the study period is 7.6%±1.5% (59.4±16.3 mmol/mol), mean body mass index (BMI) and blood pressure is 30.2±5.9 kg/m2 and 135±16.1/78±9.8 mm Hg, respectively. Prevalence of retinopathy, coronary heart disease and stroke is 10.1%, 21% and 6.7%, respectively.Future plansThe OMIT cohort features 5784 subjects with T2D in 2006, a number that has grown to 57 527 in 2019 and is expected to grow further via repeated linkages performed every third to fifth year. At the next wave of data collection, additional linkages to Norwegian Patient Registry and Norwegian Cause of Death Registry for data on registered diagnoses and causes of death, respectively, will be performed.

Background: This study compares subsequent birth outcomes in migrant women who had already had a child before arriving in Norway with those in migrant women whose first birth occurred in Norway. The aim of this study was to investigate the associations between country of first birth and adverse neonatal outcomes (very preterm birth, moderately preterm birth, post-term birth, small for gestational age, large for gestational age, low Apgar score, stillbirth and neonatal death) in parous migrant and Norwegian-born women. Methods: National population-based study including second and subsequent singleton births in Norway from 1990-2016. Data were retrieved from the Medical Birth Registry of Norway and Statistics Norway. Neonatal outcomes were compared between births to: 1) migrant women with a first birth before immigration to Norway (n=30,062) versus those with a first birth after immigration (n=66,006), and 2) Norwegian-born women with a first birth outside Norway (n=6,205) versus those with a first birth in Norway (n=514,799). Associations were estimated as crude and adjusted odds ratios (aORs) with 95% confidence intervals (CIs) using multiple logistic regression. Results: Migrant women with a first birth before immigrating to Norway had increased odds of adverse outcomes in subsequent births relative to those with a first birth after immigration: very preterm birth (22-31 gestational weeks (gwks); aOR=1.27; CI 1.09-1.48), moderately preterm birth (32-36 gwks; aOR=1.10; CI 1.02-1.18), post-term birth (≥42 gwks; aOR=1.19; CI 1.11-1.27), low Apgar score (<7 at 5 minutes; aOR=1.27; CI 1.16-1.39) and stillbirth (aOR=1.29; CI 1.05-1.58). Similar results were found in the sample of births to Norwegian-born women. Conclusions: The increased odds of adverse neonatal outcomes for migrant and Norwegian-born women who had their first births outside Norway should serve as a reminder of the importance of taking a careful obstetric history in these parous women to ensure appropriate care for their subsequent pregnancies and births in Norway. Keywords: immigration, parous women, neonatal outcomes, obstetric history, predictor

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