Umeå universitets logga

Objectives: To investigate the incidence, prevalence and mortality of anorexia nervosa (AN) among individuals with childhood-onset type 1 diabetes (T1D) compared with matched controls in Sweden.

Design: Retrospective nationwide cohort study using linked registry data.

Setting: Nationwide, Sweden; population-based registers (covering the period 1977–2019).

Participants: 12202 individuals diagnosed with T1D before age 15 years (5618 females; 6584 males) and 48484 age-matched, sex-matched and municipality-matched controls without diabetes (23618 females; 24866 males).

Primary and secondary outcome measures: AN diagnoses (International Classification of Diseases-10 codes F50.0 and F50.1) identified via the National Patient Register. Outcomes were period prevalence, point prevalence at ages 15 and 20 years, 10-year incidence rates and proportional mortality ratios (PMR), stratified by sex. ORs and incidence rate ratios (IRR) with 95% CIs were estimated using Mantel-Haenszel methods; Kaplan-Meier analysis compared time to AN diagnosis between groups.

Results: The period prevalence of AN among females with T1D was 1.9% compared with 1.1% in controls (OR 1.64, 95%CI 1.31 to 2.06; p<0.001). The 10-year incidence rate for females with T1D was 74.7 per 100000 person-years vs 45.2 per 100000 person-years in controls (IRR 1.77, 95%CI 1.35 to 2.32). Point prevalence at age 15 years was 0.87% (T1D) vs 0.53% (controls) (IRR 1.65, 95%CI 1.16 to 2.35), and at age 20 years was 1.73% (T1D) vs 1.11% (controls) (IRR 1.55, 95%CI 1.20 to 1.99). The PMR for females with both T1D and AN compared with controls without either condition was 20.4 (95% CI 6.6 to 47.6). Male cases were few (n=4 in the T1D group; n=12 in controls).

Conclusions: Females with childhood-onset T1D in Sweden have an elevated risk of AN and markedly higher mortality when both conditions are present. Despite the increased relative risk, the absolute risk of AN in females with T1D remained below 2%. These findings support routine screening for eating disorders in the T1D population, particularly among adolescent and young adult females.

Background: Adult-onset diabetes comprises subgroups differing in pathophysiology, clinical presentation, and risk of comorbidities. We investigated early phenotypic differences between individuals who later developed diabetes, stratified by subgroup at diabetes diagnosis.

Methods: We conducted a pooled analysis of nine prospective European cohorts with 3309 individuals developing incident diabetes and 13,963 age- and sex-matched controls without diabetes. Cases were assigned to previously defined cluster-based subgroups: severe autoimmune (SAID), insulin-deficient (SIDD), or insulin-resistant diabetes (SIRD), and moderate obesity- (MOD) or age-related diabetes (MARD). Clinical and metabolic characteristics were retroactively assessed for three time periods (>12, 6–12, 1–6 years) before diagnosis.

Findings: Despite similarly high body mass index (BMI) in MOD and SIRD at diagnosis, MOD differed from controls already >12 years before diagnosis (31% higher than controls), while BMI increased progressively in SIRD (from 14% to 25% higher than controls). Compared to controls in period 1–6 years, age-, sex-, and BMI-adjusted insulin-glucose ratio was higher in SIRD, MOD and MARD at fasting (88%, 45% and 14%, respectively) and 120 min (110%, 70%, 26%) during an oral glucose tolerance test (p < 0.0001 for all), and the first-phase insulin-glucose ratio was higher in SIRD (23% [6; 43] p = 0.0072) but lower in SIDD (−30% [−37; −22], p < 0.0001) and MARD (−29% [−34; −24], p < 0.0001). The autoimmune subgroup SAID also exhibited features of metabolic syndrome. Despite differences in HOMA2-B and HbA1c at diagnosis, insulin and glucose levels did not differ significantly between the SIDD and MARD subgroups 1–6 years earlier suggesting a rapid deterioration in glycemic control in SIDD around diagnosis.

Interpretation: Subgroups of diabetes display different trajectories of insulin resistance, insulin deficiency, and features of the metabolic syndrome before diagnosis. Funding: ERC, local governments, private foundations, University of Helsinki, and Research councils of Finland and Sweden.

Introduction: This study aimed to investigate if individuals with childhood-onset type 1 diabetes having a parent with the same condition (parental diabetes) had worse metabolic control and an increased risk of death and renal failure compared with those with parents without type 1 diabetes (sporadic diabetes).

Research design and methods: We conducted a population-based cohort study using data from the Swedish Childhood Diabetes Register, including cases with onset of type 1 diabetes before the age of 15 and recorded between 1977 and 2010. The cohort was linked to national registers to compare mortality, renal failure, and glycated hemoglobin (HBA1c) levels.

Results: We identified 16 572 incident cases of childhood-onset type 1 diabetes. Of these, 15 701 had data on parental diabetes status, with 1390 (8.9%) having at least one parent with this condition. HbA1c data were available in 9105 individuals at 20-30 years of age, with the parental group showing higher levels compared with the sporadic diabetes group (8.4% (68 mmol/mol) vs 8.2% (66 mmol/mol), p=0.004). The Cox proportional HR for death in parental diabetes was 1.33 (95% CI 1.00 to 1.75), and the competing risk HR for renal failure was 1.27 (95% CI 1.08 to 1.50). Women in the parental diabetes group had a higher risk of early death (HR 1.79, 95% CI 1.17 to 2.72) compared with the sporadic diabetes group.

Conclusions: Individuals with parental diabetes had slightly higher HbA1c and elevated risks of renal failure and death compared with those with sporadic diabetes, especially pronounced in women. Although the exact mechanisms behind these differences are unclear, we suggest that individualized care may benefit individuals with parental type 1 diabetes.

Aims/hypothesis: During the 1980s and 1990s, the incidence of childhood-onset type 1 diabetes more than doubled in Sweden, followed by a plateau. In the present 40 year follow-up, we investigated if the incidence remained stable and whether this could be explained by increased migration from countries reporting lower incidences.

Methods: We used 23,143 incident cases of childhood-onset type 1 diabetes reported between 1978 and 2019 to the nationwide, population-based Swedish Childhood Diabetes Registry and population data from Statistics Sweden. Generalised additive models and ANOVA were applied to analyse the effects of onset age, sex, time trends and parental country of birth and interaction effects between these factors.

Results: The flattening of the incidence increase seems to remain over the period 2005–2019. When comparing the incidence of type 1 diabetes for all children in Sweden with that for children with both parents born in Sweden, the trends were parallel but at a higher level for the latter. A comparison of the incidence trends between individuals with Swedish backgrounds (high diabetes trait) and Asian backgrounds (low diabetes trait) showed that the Asian subpopulation had a stable increase in incidence over time.

Conclusions/interpretation: In Sweden, the increase in incidence of childhood-onset type 1 diabetes in the late 20th century has been approaching a more stable albeit high level over the last two decades. Increased immigration from countries with lower incidences of childhood-onset type 1 diabetes does not provide a complete explanation for the observed levelling off. Graphical abstract: [Figure not available: see fulltext.]

Aims/hypothesis: In persons with type 1 diabetes, the risk of cancer remains controversial. We wanted to examine the excess risk of cancer in a large population-based cohort diagnosed with type 1 diabetes before 15 years of age.

Study population and methods: From 1 July 1977 to 31 December 2013, we prospectively and on a national scale included 18,724 persons (53% men) with childhood-onset type 1 diabetes. For each person with type 1 diabetes, we selected four referents, matched for the date at birth and municipality of living at the time when the case developed diabetes. Cases and referents were linked to national registers of cancer and of the cause of death.

Results: A total of 125 persons (61% women) with diabetes had 135 different cancers, all diagnosed after the diabetes diagnosis. The median duration from diabetes diagnosis to first cancer diagnosis was 19 years (interquartile range 10-26). The median age at cancer diagnosis in the diabetes group was 28 years (interquartile range 20-35). The overall standardized incidence ratio (95%), using the Swedish general population as referents for women with diabetes was 1.28 (1.02, 1.58) and when comparing women with diabetes with matched referents, we found a hazard ratio of 1.42 (1.10, 1.85). No elevated risk was seen for men. Cancers of the breast and testis were the most common types in women and men respectively.

Conclusions: Women with childhood-onset type 1 diabetes had a small but significantly elevated risk of cancer. No such tendency was seen for men. The reason behind this is unclear.

Objective: Diabetic nephropathy is a serious complication of type 1 diabetes. Recent studies indicate that end-stage renal disease (ESRD) incidence has decreased or that the onset of ESRD has been postponed; therefore, we wanted to analyze the incidence and time trends of ESRD in Sweden.

Research design and methods: In this study, patients with duration of type 1 diabetes >14 years and age at onset of diabetes 0–34 years were included. Three national diabetes registers were used: the Swedish Childhood Diabetes Register, the Diabetes Incidence Study in Sweden, and the National Diabetes Register. The Swedish Renal Registry, a national register on renal replacement therapy, was used to identify patients who developed ESRD.

Results: We found that the cumulative incidence of ESRD in Sweden was low after up to 38 years of diabetes duration (5.6%). The incidence of ESRD was lower in patients with type 1 diabetes onset in 1991–2001 compared to onset in 1977–1984 and 1985–1990, independently of diabetes duration.

Conclusion: The risk of developing ESRD in Sweden in this population is still low and also seems to decrease with time.

Background: Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown.

Methods: To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function.

Results: Our GWAS meta-analysis included association results for up to 19,406 individuals of European descent with type 1 diabetes. We identified 16 genome-wide significant risk loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain (COL4A3) gene, which encodes a major structural component of the glomerular basement membrane (GBM). Mutations in COL4A3 are implicated in heritable nephropathies, including the progressive inherited nephropathy Alport syndrome. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of diabetic kidney disease, including albuminuria and ESKD, and demonstrated a significant association with GBM width; protective allele carriers had thinner GBM before any signs of kidney disease, and its effect was dependent on glycemia. Three other loci are in or near genes with known or suggestive involvement in this condition (BMP7) or renal biology (COLEC11 and DDR1).

Conclusions: The 16 diabetic kidney disease–associated loci may provide novel insights into the pathogenesis of this condition and help identify potential biologic targets for prevention and treatment.

Purpose: Diabetic nephropathy is a severe complication of type 1 diabetes (T1D) that may lead to renal failure and end-stage renal disease (ESRD) demanding dialysis and transplantation. The aetiology of diabetic nephropathy is multifactorial and both genes and environmental and life style related factors are involved. In this study we investigate the effect of the socioeconomic exposures unemployment and receiving income support on the development of ESRD in T1D patients, using a marginal structural model in comparison with standard logistic regression models.

Methods: The study is based on the Swedish Childhood Diabetes Register which in 1977 started to register patients developing T1D before 15 years of age. In the analyses we include patients born between 1965 and 1979, developing diabetes between 1977 and 1994, followed until 2013 (n=4034). A marginal structural model (MSM) was fitted to adjust for both baseline and time-varying confounders.

Results: The main results of the analysis indicate that being unemployed for more than one year and receiving income support are risk factors for the development of ESRD. Multiple exposure over time to these risk factors increases the risk associated with the disease.

Conclusions: Using a MSM is an advanced method well suited to investigate the effect of exposures on the risk of complications of a chronic disease with longitudinal data. The results show that socioeconomic disadvantage increases the risk of developing ESRD in patients with type 1 diabetes.

Aims: The development of end-stage renal disease (ESRD) in Type 1 diabetes is multifactorial. Familial socio-economic factors may influence adherence to and understanding of diabetes treatment, and also general health behaviour. We investigate how parental and personal education level and exposure to low economic status, indicated by the need for income support, influence the development of ERSD caused by Type 1 diabetes.

Methods: Participants were retrieved from the nationwide Swedish Childhood Diabetes Registry, which was linked to the Swedish Renal Registry, to find people with ESRD caused by Type 1 diabetes, and to Statistic Sweden to retrieve longitudinal socio-economic data on participants and their parents. Data were analysed using Cox regression modelling.

Results: Of 9287 people with diabetes of duration longer than 14 years, 154 had developed ESRD due to diabetes. Median diabetes duration (range) for all participants was 24.2 years (14.0-36.7 years). Low maternal education ( 12 years) more than doubled the risk of developing ESRD, hazard ration (HR) = 2.9 [95% confidence interval (95% CI): 1.7-4.8]. For people with a low personal level of education HR was 5.7 (3.4-9.5). In an adjusted model, the person's own education level had the highest impact on the risk of ESRD. If at least one of the parents had ever received income support the HR was 2.6 (1.9-3.6).

Conclusions: Socio-economic factors, both for the parents and the person with diabetes, have a strong influence on the development of ESRD in Type 1 diabetes. It is important for caregivers to give enough support to more vulnerable people and their families.