Background/Objectives: Individuals with type 2 diabetes have an increased risk of pancreatic cancer (PC), yet early detection markers remain limited. We examined associations between routinely measured serum biomarkers and subsequent PC risk in this population. Methods: Using the Swedish AMORIS cohort, 101,051 individuals aged ≥50 years at diabetes diagnosis with newly diagnosed type 2 diabetes (1969-2019) were analysed. Ten biomarkers, including liver enzymes, inflammatory markers, renal function, and lipid profiles, were assessed. The primary analysis focused on measurements within ±1 year of the diabetes diagnosis (n = 13,190; Cohort 1). Sensitivity analyses considered broader windows: -3, -5, and -10 years before diagnosis to +1 year after, and from the diagnosis to the end of the follow-up (Cohorts 2-5). Multivariable Cox models adjusted for age and sex were applied. Results: During a mean follow-up of 15.9 years, 192 individuals developed PC. In primary analysis, higher alkaline phosphatase was associated with increased PC risk (HR: 1.16, 95% CI: 1.09-1.24 per 1 SD increase). Higher creatinine was associated with reduced PC risk (HR: 0.55, 95% CI: 0.36-0.83 per 1 SD increase), while haptoglobin (HR: 1.20, 95% CI: 0.97-1.49 per 1 SD increase) suggested a modest positive association. Patterns were consistent across sensitivity analyses. Conclusions: In individuals ≥ 50 years with newly diagnosed type 2 diabetes, higher ALP and lower creatinine were independently associated with increased PC risk before and after diabetes diagnosis, while haptoglobin showed a modest positive association. As these biomarkers are routine laboratory panels, their potential to support risk stratification in primary care requires further evaluation within established risk-prediction frameworks.

To investigate whether antidiabetic drugs have a biological basis to be repurposed in PD prevention, we applied a drug target Mendelian randomization framework to assess associations between genetic variation in antidiabetic drug targets and PD risk or age at onset (AAO). Instrumental variables (IVs) were derived from GWAS summary statistics on fasting glucose (FG), glycated hemoglobin (HbA1c), and gene expression data from GTEx. Apart from SGLT2 inhibitors, all other antidiabetic drugs of interest could be instrumented through our methods. Positive and negative control analyses were carried out to validate 20 IVs in the FG arm and 23 IVs in the HbA1c arm. DPP-4 inhibitors failed the positive control. GWAS summary statistics for PD risk and AAO data were sourced from the IPDGC and COURAGE-PD consortia, resulting in 42 083 cases/457 090 controls for risk and 37 103 PD cases for AAO. MR analyses showed no significant associations across consortia or in meta-analysis. These findings do not support a causal role of genetic variation in antidiabetic drug targets in PD risk or AAO.

BACKGROUND:The global prevalence of type 2 diabetes has nearly doubled between 1990 and 2020. Genetic susceptibility confers increased risk of type 2 diabetes, but environmental exposures could modify this risk. We aimed to investigate how societal changes have affected the prevalence of type 2 diabetes in people with high and low genetic susceptibility, using chronological time as an indicator for these changes. METHODS:This longitudinal, population-based study included observations from four surveys from the HUNT study between 1984 and 2019, for participants aged 20-79 years. Diabetes was indicated by self-report and by non-fasting glucose or HbA1c in secondary analyses. We used a polygenic score for type 2 diabetes including more than 1 100 000 genetic variants to approximate genetic susceptibility. We used generalised estimating equations to estimate diabetes prevalence for the top and bottom deciles of the polygenic score at each timepoint, allowing for three-way interaction between time, polygenic score category, and 20-year age group. To explore underlying mechanisms, we did similar analyses for incidence by polygenic score category and 10-year mortality by diabetes status. FINDINGS:The study included 198 312 observations from 86 194 individuals. 45 654 (53·0%) of 86 194 participants were female and 40 540 (47·0%) were male. From the mid-1980s to the late 2010s, diabetes prevalence increased by 0·4 percentage points (pp; 95% CI 0·1-0·7) among the bottom decile of the polygenic score, 3·0 pp (2·7-3·2) among the mid-80%, and 9·1 pp (8·0-10·1) among the top decile. The difference in diabetes prevalence between the top and bottom deciles of genetic susceptibility increased over time for all age groups. Findings were similar when laboratory measurements were added to define hyperglycaemia. Additional analyses suggested an increasing diabetes incidence in participants aged 20-39 years in the top decile of genetic susceptibility, and improved diabetes survival from 1996-2006 to 2007-17. INTERPRETATION:Our findings suggest an increasing gap in diabetes prevalence between the most and least genetically susceptible. This suggests that people with a high genetic susceptibility to type 2 diabetes could be especially affected by a diabetogenic environment and highlights the need for public health measures. FUNDING:The study was funded by The Liaison Committee for education, research and innovation in Central Norway.

Aims/hypothesisThe role of red meat in type 1 diabetes risk remains unclear. We examined whether maternal and early-life red meat intake is associated with the development of type 1 diabetes and whether such associations are modified by genetic susceptibility.MethodsWe analysed data from 15,717 children participating in the All Babies In Southeast Sweden (ABIS) cohort, followed for type 1 diabetes diagnosis via national registers until the age of 24-26 years. Dietary intake was assessed through food frequency questionnaires during pregnancy and at ages 1, 2.5 and 5 years. Cox models estimated adjusted HRs and 95% CIs for type 1 diabetes in relation to red meat, including beef, pork and sausage, analysed as high vs low intake frequency and per serving/week. Analyses were stratified by HLA risk genotype and family history of type 1 diabetes.ResultsFrequency of red meat intake during pregnancy or at age 1 was not associated with type 1 diabetes risk. The corresponding HRs per serving/week were 0.98 (95% CI 0.90, 1.07) and 0.98 (95% CI 0.88, 1.08), respectively. In type-specific analyses, higher frequency of beef intake at age 5 was associated with an increased risk of type 1 diabetes (HR 1.29 [95% CI 1.05, 1.58]), with a similar tendency for exposure at age 2.5 (HR 1.12 [95% CI 0.93, 1.36]). The association at age 5 was evident among children with high-risk HLA genotypes (HR 1.40 [95% CI 1.11, 1.78]) or a family history of type 1 diabetes (HR 1.56 [95% CI 1.08, 2.26]). In contrast, no statistically significant association was observed among children with low-risk HLA genotypes (HR 0.34 [95% CI 0.10, 1.19]) or without a family history of type 1 diabetes (HR 1.20 [95% CI 0.92, 1.56]). No associations were found for higher frequency of beef consumption during pregnancy or at age 1, nor for pork and sausage at any age.Conclusions/interpretationChildhood beef consumption may contribute to type 1 diabetes development in genetically at-risk individuals. Further research is needed to confirm this finding and clarify underlying mechanisms.

Background Diabetes is a heterogeneous disease and stratification into severe autoimmune (SAID), severe insulin-deficient (SIDD), severe insulin-resistant (SIRD), moderate obesity-related (MOD), and moderate age-related (MARD) diabetes reveals differing clinical courses. Identifying early predictors for these disease trajectories could enable more precise prevention. We studied the relationship between adolescent fitness and BMI, adult physical activity, genetic predisposition, and future subgroup-specific risk. Methods We analysed 4,417 men with diabetes (cases) from the ANDIS study with military conscription fitness and BMI data, compared with 235,953 controls. Adult physical activity was assessed using questionnaire data (2,616 cases and 2,753 controls). Finally, we performed polygenic score analyses (6,986 cases; 2,744 controls) and two-sample Mendelian randomisation (MR) analysis using published GWAS summary statistics. Findings Higher BMI at age 18 was associated with increased risk of MOD (OR 1·69 [95% CI 1·64–1·74]), SIRD (OR 1·31 [1·23–1·40]), and SIDD (OR 1·26 [1·19–1·33]), but not MARD (OR 0·85 [0·79–0·90]). In BMI-adjusted models, higher aerobic capacity at age 18 was most strongly associated with a lower SIRD risk (OR 0·69 [0·61–0·77]), but was also associated with SIDD and MOD risk. BMI-adjusted physical activity at age 30 was associated with lower SIRD, MOD, and SIDD risk. MR indicated a causal relationship, mediated by BMI, between sedentary lifestyle and SIRD. No evidence supported a causal link between BMI and MARD. Interpretation Adolescent fitness and BMI are divergent risk factors for diabetes subgroups. Low physical capacity is a specific risk factor for individuals following a SIRD-like trajectory, whereas the MOD phenotype is characterised by early obesity. In contrast, MARD exhibits preserved fitness and no causal link with BMI. These findings provide a pathophysiological rationale for stratified strategies, from prevention to clinical management, prioritising those with high cardio-renal-hepatic burden, such as individuals with a SIRD-like disease course.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes, which affect approximately 38

BACKGROUND:The major genetic high-risk of developing autoimmune diabetes are HLA-DR3DQ2 and HLA-DR4DQ8 haplotypes. Their importance in Latent Autoimmune Diabetes in Adults (LADA) has only been partly elucidated. Here we aimed to dissect their impact on autoimmunity, diabetic phenotype, and comorbidity. METHODS:Data from individuals with LADA were collected from two all-population based surveys, the Norwegian HUNT study (n = 231) and the Swedish ESTRID study (n = 519). RESULTS:The presence of DR3DQ2 and/or DR4DQ8 HLA-haplotypes augmented disease-associated parameters in LADA compared with the absence of risk haplotypes; this was seen in HUNT and ESTRID alike. Having both risk haplotypes vs. a single risk haplotype increased propensity for high levels of glutamic acid decarboxylase antibody (GADA) in HUNT, with a similar tendency in ESTRID. In HUNT, those with both risk haplotypes displayed higher propensity for treatment with insulin and higher prevalence of hypothyroidism. In ESTRID, the propensity for insulin treatment was more frequent for DR4DQ8 than for DR3DQ2. CONCLUSION:Presence of a DR3DQ2 or a DR4DQ8 diabetes risk-haplotype associate with different phenotypes of LADA with implications for the known heterogeneity of the disease. In HUNT, but not in ESTRID, the combination of the high-risk haplotypes DR3DQ2 and DR4DQ8 vs. separate high-risk haplotypes associate with enhanced effects on autoimmunity, signs of progression of disease, as well as on comorbidity. Lastly, exploratory findings are consistent with a stronger negative influence by DR4DQ8 than DR3DQ2 as shown in ESTRID. Measurements that include both DR3DQ2 and DR4DQ8 should be relevant when assessing disease progression in LADA patients.

Smoking increases the risk of type 2 diabetes, but its role in autoimmune diabetes remains unclear. We investigated whether smoking is associated with being GAD65 autoantibody (GAD65Ab) positive or the risk of progressing to diabetes. We also assessed its interaction with genetic susceptibility to type 1 diabetes. We used data from the EPIC-InterAct case–cohort study including 11,161 incident cases of adult-onset diabetes and 14,922 subcohort participants. Logistic regression was used to estimate odds ratios (ORs) for being GAD65Ab positive at baseline by smoking status. Hazard ratios (HRs) of diabetes by baseline smoking and GAD65Ab status were estimated using Prentice-weighted Cox regression. Two- and three-way interactions between smoking, GAD65Ab status and a type 1 diabetes genetic risk score (T1D-GRS) were assessed by attributable proportion due to interaction (AP). There was no evidence that smoking was associated with being GAD65Ab positive (OR 1.00, 95

Background:Effective glucose management is essential to prevent complications in type 1 diabetes. While nutrition therapy is crucial, the optimal diet remains uncertain. Our systematic review and meta-analysis synthesized evidence from randomized controlled trials (RCTs) on the impact of various diets on glucose management in type 1 diabetes. Methods:We systematically searched Medline, Embase, and Cochrane Library up to 11 November 2024 for RCTs on dietary patterns and glucose control outcomes in type 1 diabetes, including HbA1c, time in range (TIR), coefficient of variation (CV), hypoglycemia, insulin dose, and anthropometric characteristics. Two reviewers independently extracted data and assessed the risk of bias using the RoB-2 tool. We estimated summary mean differences (MD) with 95% CIs using random-effects models. The certainty of the evidence was evaluated using GRADE. The study protocol was registered in PROSPERO (CRD42023479252). Findings:Out of 5287 studies, 35 RCTs involving children, adolescents, and adults with type 1 diabetes were eligible. Higher-fiber diets (≥35 g/day, 5 RCTs) reduced HbA1c (MD -0.46%, 95% CI -0.93 to 0.00, I2 65%) and hypoglycemia (MD -0.81 episodes/month, 95% CI -1.34 to -0.28, I2 0%), with moderate and low certainty of evidence, respectively. Carbohydrate-restricted diets (≤45% energy, 20 RCTs) improved TIR (MD 3.84%, 95% CI 2.24-5.44, I2 0%), CV (MD -3.24%, 95% CI -5.51 to -0.97, I2 53%), and insulin needs (MD -5.63 U/day, 95% CI -9.51 to -1.74, I2 70%), but not HbA1c, with low to moderate certainty of evidence. Higher-protein, low-glycemic index, gluten-free, Mediterranean, vegan, and intermittent fasting diets showed no effects on glucose management (1-6 RCTs), although certainty of evidence was low. Interpretation:Maintaining a high-fiber diet while restricting other carbohydrates may improve glycemic control in individuals with type 1 diabetes. Further investigation is needed into long-term effects and other diets. Funding:Swedish Research Council, Swedish Diabetes Foundation, and the Strategic Research Programme in Diabetes at Karolinska Institutet.

Incidence of early-onset (< 40 years) type 2 diabetes (T2D) is increasing. While multiple risk factors have been identified, particularly obesity and low socioeconomic status, early-life factors are hypothesised to play a role via fetal programming. We investigated sociodemographic and early-life factors in relation to early-onset T2D using a family-based design that accounts for shared genetic and environmental factors. We included 1,814,062 individuals born in Sweden 1983 to 2002 with follow-up data until 2020, and identified early-onset (age 19–39) T2D cases (n = 3505) through National Diabetes, Patient and Prescribed Drug Registers. Perinatal and sociodemographic factors were retrieved from registers. We used a cohort and sibling design, with multivariable-adjusted Cox proportional hazards regression. Sociodemographic factors associated with early-onset T2D included low parental education, single parenthood, younger parental age and non-Swedish origin. The latter association did not remain after mutual adjustment. Regarding perinatal factors, a higher incidence was noted in relation to lower birth weight (hazard ratio 2.38 [95

The use of new tobacco and nicotine products, including e-cigarettes, heated tobacco products (HTPs) and tobacco-free snus (white snus), is rising, especially among adolescents and young adults. However, evidence on their long-term health effects is limited. This review assesses current knowledge on the health risks of these products, with a focus on asthma and allergic diseases, cancer, cardiovascular disease, diabetes, lung disease and pregnancy outcomes. E-cigarettes are associated with increased risks of asthma, respiratory symptoms, chronic bronchitis and chronic obstructive pulmonary disease (COPD). Associations with cardiovascular disease, type 2 diabetes, cancer and adverse pregnancy outcomes are supported by limited epidemiological and experimental data. Less evidence is available on health risks associated with HTPs, but a few epidemiological studies indicate increased risks of asthma and COPD, with supporting data from experimental studies. Evidence on white snus is notably lacking across the different health outcomes. Given its high nicotine content – similar to or higher than in brown snus – it is plausible that white snus increases risks of diabetes, pregnancy complications and other nicotine-related health effects. Methodological limitations of existing epidemiological studies include reliance on self-reported data, inadequate adjustment for cigarette smoking, cross-sectional design and/or short follow up. Future research should prioritize large-scale, longitudinal studies assessing dose, duration and product formulation, including second-hand and prenatal exposure, as well as mechanistic studies. There is an urgent need to elucidate the health impacts of the new nicotine and tobacco products, which are growing in popularity, to inform policy, regulation and public health strategies.

BACKGROUND AND AIMS:The prognosis of adult-onset type 1 diabetes (T1D) and prognostic factors are sparsely investigated. This study assessed mortality, major adverse cardiovascular events (MACE), and prognostic factors in adult-onset T1D, particularly focusing on those diagnosed at age ≥40. METHODS:Participants were people diagnosed with adult-onset T1D (n = 10 184) or type 2 diabetes (T2D, n = 375 523) in 2001-20 from the Swedish National Diabetes Register and 509 172 population controls from the Total Population Register, followed until 2022. Hazard ratios (HR) and population attributable risk fraction (PAR%) were estimated. RESULTS:People with T1D had higher incidence of MACE (HR 1.30 [95% confidence interval 1.17, 1.45]), all-cause mortality (1.71 [1.60, 1.84]), and mortality from cardiovascular or non-cardiovascular diseases, cancer, or infection than population controls. They had lower MACE incidence (0.67 [0.60, 0.75]) and higher mortality from diabetic coma or ketoacidosis (7.04 [4.54, 10.9]) than people with T2D. Smoking (PAR% 10.7%) and glycated haemoglobin (HbA1c) ≥ 53 mmol/mol (10.4%) accounted for most deaths while overweight/obesity (19.8%), smoking (8.4%), and high HbA1c (8.8%) accounted for most MACE events in T1D. Results were similar for T1D diagnosed at age ≥40, although they had lower insulin pump use and higher HbA1c than people diagnosed earlier. CONCLUSIONS:Adult-onset T1D carries excess risk of death and MACE compared with population controls but less MACE risk than T2D. Individuals diagnosed after age 40 had similar excess risk and poorer glycaemic control than those diagnosed earlier, underscoring the need for improved management. Key prognostic factors were smoking, poor glycaemic control, and overweight/obesity.

Incidence of type 1 diabetes is increasing globally, which is hypothesized to be due to environmental influences. We leverage Swedish nationwide registers linked to all children (n = 2,928,704) born in 1982-2010 to investigate if the heritability of childhood-onset type 1 diabetes has changed over time and how alterations in environmental factors have contributed to the rising type 1 diabetes incidence. The heritability is estimated at 0.83 (95% confidence interval: 0.79, 0.86) and stable over the observation period (0.80 [0.71, 0.86] in 1982, 0.83 [0.79, 0.86] in 2000, and 0·83 [0.79, 0.86] in 2010, respectively). Environmental factors including maternal smoking during pregnancy and childhood adiposity explain <10% of the increasing type 1 diabetes incidence. In this work, the heritability of childhood-onset type 1 diabetes has remained high and stable over the last 30 years. Our findings indicate that the available environmental factors are not the major contributors to the rise in type 1 diabetes in Sweden.

BACKGROUND AND OBJECTIVE:Information on absolute risks of sudden unexpected death in epilepsy (SUDEP) in individual patients with epilepsy is scarce. Our main objective was therefore to explore the range in incidence rates of SUDEP to provide a more solid basis for individualized counseling and to characterize patients with high and very high SUDEP incidence for future intervention studies aiming at prevention of SUDEP. METHODS:We used data on everyone in Sweden diagnosed with epilepsy from 1998 to 2005 (n = 60,952), followed until 2011 and identified SUDEP cases through adjudication of deceased patients who had epilepsy. We conducted a nested case-control study and retrieved detailed information on clinical characteristics for the SUDEP cases and matched living epilepsy controls (5:1). Estimates of the strengths of associations from the case-control study were used to estimate the incidence rate of SUDEP (per 100,000 person-years) in the full cohort by SUDEP risk factors. RESULTS:Two hundred fifty-five SUDEP cases (median age 48 years; 154 males) were identified. The lowest incidence, 8 (95% CI 3-17), was observed among patients without a history of tonic-clonic seizures (TCS), whereas patients with 1 or more TCS the preceding year had an incidence of 287 (95% CI 192-428). Incidence rates above 200 were also found among patients with a history of nocturnal TCS, substance abuse or alcohol dependence, and nonadherence with antiseizure medication (ASM) treatment. Considering combination of risk factors, the incidence rate was very low, 5 (95% CI 2-12), for patients who share bedroom and are free from TCS the preceding year as well as adherent with the prescribed ASM treatment. By contrast, patients living alone who are nonadherent have a history of nocturnal TCS and at least 1 TCS the preceding year have an incidence at 1808 (95% CI 594-5,504), more than 350 times higher than the low-risk patient. DISCUSSION:In this analysis of Swedish population-based SUDEP data, we have identified a 350-fold difference in the SUDEP incidence depending on individual circumstances and epilepsy characteristics. Although somewhat old, our data should be useful for patient counseling about individual SUDEP risks amenable to modification and for case stratifications for intervention studies aiming at prevention of SUDEP.

BACKGROUND & AIMS:Alcohol consumption has been inversely associated with type 2 diabetes (T2D), but its influence on autoimmune diabetes is unclear. We investigated the risk of latent autoimmune diabetes in adults (LADA) and T2D in relation to alcohol intake and assessed if potential associations were modified by genetic susceptibility to diabetes. METHODS:We used data from a case-control study with incident diabetes cases (n = 695 LADA and n = 2679 T2D) and matched controls (n = 2752), and a prospective cohort study with 59,710 participants and incident diabetes cases (n = 221 LADA and n = 3335 T2D). Pooled relative risks (RR) with 95 % confidence intervals (CI) were estimated in relation to self-reported alcohol consumption. Analyses were stratified according to human leukocyte antigen (HLA) genotypes and polygenic score (PGS) for T2D (T2D-PGS). RESULTS:Moderate alcohol consumption (10-14.9 g/day) compared to low consumption (0.1-4.9 g/day) was associated with a reduced risk of LADA (RR: 0.74, CI: 0.56, 0.98) and T2D (RR: 0.81, CI: 0.69, 0.94). No further risk reduction was observed for the highest intake category (≥15 g/day). Stratification by T2D-PGS revealed an inverse association with LADA in those with high T2D-PGS (≥10 g/day vs. 0.1-4.9 g/day; RR: 0.38, CI: 0.23, 0.64), but not low/intermediate T2D-PGS (RR: 0.89, CI: 0.54, 1.46). The corresponding RRs for high- and low/intermediate-risk HLA carriers were 0.64 (CI: 0.35, 1.17) and 0.48 (CI: 0.31, 0.74). For T2D, RRs were 0.70 (95 % CI: 0.53, 0.93) in individuals with low/intermediate T2D-PGS and 0.85 (95 % CI: 0.64, 1.14) in those with high T2D-PGS. CONCLUSION:Moderate alcohol intake was linked to reduced LADA risk, particularly in individuals with high T2D-PGS and low/intermediate-risk HLA genotypes, indicating that the association is primarily present for T2D-like LADA. The extent to which genetic predisposition influences the association between alcohol and T2D remains less clear.

Background and ObjectiveInformation on absolute risks of sudden unexpected death in epilepsy (SUDEP) in individual patients with epilepsy is scarce. Our main objective was therefore to explore the range in incidence rates of SUDEP to provide a more solid basis for individualized counseling and to characterize patients with high and very high SUDEP incidence for future intervention studies aiming at prevention of SUDEP.MethodsWe used data on everyone in Sweden diagnosed with epilepsy from 1998 to 2005 (n = 60,952), followed until 2011 and identified SUDEP cases through adjudication of deceased patients who had epilepsy. We conducted a nested case-control study and retrieved detailed information on clinical characteristics for the SUDEP cases and matched living epilepsy controls (5:1). Estimates of the strengths of associations from the case-control study were used to estimate the incidence rate of SUDEP (per 100,000 person-years) in the full cohort by SUDEP risk factors.ResultsTwo hundred fifty-five SUDEP cases (median age 48 years; 154 males) were identified. The lowest incidence, 8 (95% CI 3-17), was observed among patients without a history of tonic-clonic seizures (TCS), whereas patients with 1 or more TCS the preceding year had an incidence of 287 (95% CI 192-428). Incidence rates above 200 were also found among patients with a history of nocturnal TCS, substance abuse or alcohol dependence, and nonadherence with antiseizure medication (ASM) treatment. Considering combination of risk factors, the incidence rate was very low, 5 (95% CI 2-12), for patients who share bedroom and are free from TCS the preceding year as well as adherent with the prescribed ASM treatment. By contrast, patients living alone who are nonadherent have a history of nocturnal TCS and at least 1 TCS the preceding year have an incidence at 1808 (95% CI 594-5,504), more than 350 times higher than the low-risk patient.DiscussionIn this analysis of Swedish population-based SUDEP data, we have identified a 350-fold difference in the SUDEP incidence depending on individual circumstances and epilepsy characteristics. Although somewhat old, our data should be useful for patient counseling about individual SUDEP risks amenable to modification and for case stratifications for intervention studies aiming at prevention of SUDEP.

Abstract Background and aim The world-wide prevalence of diabetes distress varies, and studies are mainly undertaken in clinical settings. By using data from the Trøndelag Health (HUNT) study, we aimed to estimate diabetes distress prevalence, its determinants, and associations with anxiety and depression among adults with type 2 diabetes. Methods This population-based cross-sectional study consists of individuals ≥ 20 years with type 2 diabetes participating in the HUNT4 survey (2017–2019). Diabetes-distress prevalence with 95% confidence interval (CI) was calculated based on the five item Problem Areas in Diabetes (PAID-5) questionnaire. PAID-5 sum scores were rescaled to a 0-100 scale by multiplying the sum score by five. Linear and logistic regression models were used to examine associations of demographic, lifestyle- and clinical factors, with diabetes distress. Results In total, 1954 individuals completed the PAID-5 questionnaire, with a mean score of 15.2 (SD 18.3) and 11.9% (95% CI 10.6–13.4) reporting high diabetes distress (PAID-5 ≥ 40). Multivariable linear regression showed that diabetes distress was associated with a 0.2 (95% CI 0.2–0.3) lower score for each year older age, 7.6 (95% CI 5.4–9.7) higher score for current insulin use, and 9.3 (95% CI 5.3–13.2) higher score for a history of diabetes foot ulcers. High levels of anxiety and depression symptoms were associated with higher diabetes distress (Anxiety: B 16.0, 95% CI 13.6–18.4, Depression: B 13.3, 95% CI 10.7–16.0). Conclusions Diabetes distress is common and strongly associated with younger age at diabetes onset, insulin use, foot ulcer, and anxiety and depression symptoms. Identifying and addressing diabetes distress in diabetes follow-up may facilitate improving health outcomes and prevent more serious mental health issues in individuals with T2D. Nevertheless, the findings should be further examined in longitudinal studies.

AIMS:To examine associations between sleep impairments and diabetes distress in men and women with type 2 diabetes (T2D) by using cross-sectional data from the Trøndelag Health Study (HUNT). METHODS:This population-based cross-sectional study consists of individuals ≥20 years with T2D participating in the HUNT4 survey (2017-2019; n = 1954). Sleep impairments (snoring, sleep apnoea, troubles falling asleep, wake up during the night, early wakening, difficulties coping during the daytime due to sleep problems and restless legs) were measured by the sleeping HUNT-Questionnaire, along with a separate question on the number of hours of sleep at night. Diabetes distress was measured using the Problem Areas in Diabetes (PAID-5) questionnaire. Diabetes distress prevalence, grouped by sleep impairment, was estimated with 95% confidence intervals. Multivariable linear regression models with distress as outcome and adjusted for demographic, clinical and mental health factors were used to examine associations with sleep. RESULTS:Overall, sleep impairment was associated with increased diabetes distress. Regression coefficients B (95% CI) for higher distress score were 0.6 (95% CI 0.2, 0.9) for ≤7 h of sleep, 0.6 (95% CI 0.1-1.1) for snoring, 1.4 (95% CI 0.8-2.2) for troubles falling asleep, 1.1 (95% CI 0.6-1.6) for waking up during the night, 1.2 (95% CI 0.7-1.8) for early wakening, 2.6 (95% CI 1.7-3.6) for troubles coping during daytime due to sleep problems and 0.8 (95% CI 0.2-1.3) for restless legs. CONCLUSION:Multiple components of sleep impairment were significantly associated with high diabetes distress in individuals with T2D.

The incidence of cardiovascular disease (CVD) in young individuals is increasing. This alarming trend underscores the need to identify at-risk groups for preventive measures. Emerging evidence suggests that maternal diabetes increases the risk for metabolic diseases and early-onset CVDs in their offspring. However, the evidence is largely observational, limited by confounding factors, and lacks crucial mechanistic insight. Here, we combine experimental, epidemiological, and clinical approaches to disentangle the effects of maternal diabetes on offspring metabolism and endothelial function. In mice, we find that maternal hyperglycemia induces early-onset endothelial dysfunction specifically in male offspring, independent of metabolic disease. In humans, a case-control study and an epidemiological study confirm elevated risk of early-onset endothelial dysfunction and related CVDs in metabolically healthy sons of mothers with type 1 diabetes. Our findings identify an underrecognized risk group for early-onset CVDs and emphasize the importance of maternal conditions in shaping the cardiovascular health of future generations.

Our aim was to provide new data on the incidence, prevalence, and secular trend of type 2 diabetes (T2D) in Sweden, specifically early-onset T2D. We followed the Swedish population 2006 to 2021 and calculated age-standardized incidence (per 100 000) and prevalence (%) of T2D (overall) and early-onset T2D (age 23-39 years) stratified by sex, region of birth, and educational level. We projected the future prevalence of early-onset T2D by combining observed trends with population projections. From 2006 to 2021, the prevalence of T2D rose from 4.87% to 7.50%, and incidence from 477 [95% confidence interval (CI) 471-482] to 574 (CI 568-579). Early-onset T2D incidence increased from 54 to 107 (4.7% annual rise; CI 3.7%-5.7%) during this period. Incidence of early-onset T2D was higher in individuals born outside Europe (211, CI 195-226 vs 89, CI 84-93 in 2021) or low education (204, CI 185-223 vs 71, CI 65-77 in 2021), but a rise in incidence was seen irrespective of educational level, region of origin, and sex. If the incidence of early-onset T2D continues to increase at the same pace, its prevalence is projected to increase from 0.64% in 2021 to 3.2% in 2050. While T2D incidence rose marginally in Sweden 2006 to 2021, there was a significant rise in early-onset T2D, seen across different socioeconomic characteristics, with prevalence more than doubling and incidence nearly doubling. This development calls for targeted preventive efforts.