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  • 1.
    Berhan, Yonas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Epidemiological studies of childhood diabetes and important health complications to the disease2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background and aims: The overall aim of this thesis was to increase knowledge regarding the occurrence of childhood onset T1D and T2D in Sweden and in relation to that describe and elucidate important aspects on two grave complications to diabetes; end-stage renal disease (ESRD) and mortality. The two first studies included in this thesis aimed to describe and analyze the cumulative incidence of childhood onset T1D in Sweden and to assess the occurrence of undetected T2D in Swedish children. The aim with the third study was to describe the cumulative incidence of ESRD, and to analyze how ESRD risk differs with age at-onset and sex. The aim of the fourth study was to show how parental socioeconomic status (SES) affects all cause mortality in Swedish patients with childhood onset T1D.

    Study populations: The foundation for the studies on T1D was data from the Swedish Childhood Diabetes Registry (SCDR). When studying ESRD we also included adult onset T1D cases from the Diabetes Incidence Study in Sweden (DISS). The study on T2D was a population-based screening study where BMI was measured in 5528 school-children and hemoglobin A1c was measured in children with overweight according to international age and sex specific BMI cut-offs. To study ESRD and mortality, we linked the SCDR to various nationwide registers containing individual information on SES, mortality and ESRD.

    Results: The incidence rates of childhood onset T1D has continued to increase in Sweden 1977–2007. Age- and sex-specific incidence rates varied from 21.6 (95% CI 19.4–23.9) during 1978–1980 to 43.9 (95% CI 40.7– 47.3) during 2005–2007. Cumulative incidence by birth-cohorts has shifted to a younger age at-onset over the first 22 years of incidence registration. From the year 2000 there was a significant reverse in this trend (p<0.01). In contrast to the increase of T1D, we found no evidence of undetected T2D among Swedish school children. Despite a relatively high incidence in T1D in Sweden there is low cumulative incidence of ESRD, 3.3% at maximum 30 years of duration. We found difference between the sexes regarding long-term risk of developing ESRD that was dependent on the age at onset of T1D. When analyzing how socioeconomic status affects mortality in different age at death groups, we found that having parents that received income support increased mortality up to three times in those who died after 18 years of age.

    Conclusion: The incidence of childhood onset T1D continued to increase in Sweden 1978-2007. Between the years 1978-1999 there was a shift to a younger age at-onset, but from the year 2000 there is a change in this shift indicating a possible trend break. The prevalence of T2D among Swedish children up to 12 years of age is probably very low. There is still a low cumulative incidence of T1D associated ESRD in Sweden. The risk of developing ESRD depends on age at-onset of T1D, and there is a clear difference in risk between men and woman. Excess mortality among subjects with childhood onset T1D still exists, and low parental socioeconomic status additionally increased mortality in this group.

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  • 2.
    Berhan, Yonas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Waernbaum, Ingeborg
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Impact of Parental Socioeconomic Status on Excess Mortality in a Population-Based Cohort of Subjects With Childhood-Onset Type 1 Diabetes2015In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 38, no 5, p. 827-832Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The aim of this study was to analyze the possible impact of parental and individual socioeconomic status (SES) on all-cause mortality in a population-based cohort of patients with childhood-onset type 1 diabetes.

    RESEARCH DESIGN AND METHODS: Subjects recorded in the Swedish Childhood Diabetes Registry (SCDR) from 1 January 1978 to 31 December 2008 were included (n =14,647). The SCDR was linked to the Swedish Cause of Death Registry (CDR) and the Longitudinal Integration Database for Health Insurance and Labour Market Studies (LISA).

    RESULTS: At a mean follow-up of 23.9 years (maximum 46.5 years), 238 deaths occurred in a total of 349,762 person-years at risk. In crude analyses, low maternal education predicted mortality for male patients only (P = 0.046), whereas parental income support predicted mortality in both sexes (P < 0.001 for both). In Cox models stratified by age-at-death group and adjusted for age at onset and sex, parental income support predicted mortality among young adults (≥18 years of age) but not for children. Including the adult patient’s own SES in a Cox model showed that individual income support to the patient predicted mortality occurring at ≥24 years of age when adjusting for age at onset, sex, and parental SES.

    CONCLUSIONS: Exposure to low SES, mirrored by the need for income support, increases mortality risk in patients with childhood-onset type 1 diabetes who died after the age of 18 years.

  • 3.
    Berhan, Yonas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Eliasson, Mats
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Waernbaum, Ingeborg
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Impact of parental socioeconomic status on excess mortality in subjects with childhood onset type-1 diabetesManuscript (preprint) (Other academic)
    Abstract [en]

    Aims/Hypothesis: The aim of this study was to analyze the possible impact of parental and individual socioeconomic status (SES) on all cause mortality in a population based cohort of childhood onset T1D.

    Methods: Subjects recorded in the Swedish Childhood Diabetes Registry (SCDR) January 1 1978 to December 31 2008 were included (n=14 409). The SCDR was linked to the Swedish Cause of Death Register (CDR) and the Longitudinal Integration Database for Health Insurance and Labour Market Studies (LISA). SES measures (education and income support) wtypeere retrieved from the LISA for the years 1990-2010. Mortality data were retrieved from the CDR as of December 31, 2010.

    Results: At a mean follow-up of 24.4 years (maximum 47.5), 238 deaths occurred in a total of 357 048 person-years at risk. In crude analyses, low maternal education predicted mortality for male cases only (p=0.046), while parental income support predicted mortality in both sexes (p<0.001 for both). In Cox models stratified by age at death groups and adjusted for age at onset and sex, parental income support predicted mortality among young adults ( ≥18 years of age) but not for children. Including the adult patient´s own SES in a Cox model showed that individual income support to the patient predicted mortality occurring at ≥ 24 years of age when adjusting for age at onset, sex and parental SES.

    Conclusions/Interpretation: Low parental SES, mirrored by the need of income support, increases mortality risk in childhood onset type-1 diabetics who died after the age of 18 years.

  • 4.
    Berhan, Yonas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Carlsson, Annelie
    Lund Univ, Dept Clin Sci, Lund, Sweden.
    Högberg, Lotta
    Linköping Univ, Dept Clin & Expt Med, Div Pediat, Linköping, Sweden.
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Five-region study finds no evidence of undiagnosed type 2 diabetes in Swedish 11- to 13-year-olds2014In: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 103, no 10, p. 1078-1082Article in journal (Refereed)
    Abstract [en]

    AIM: Childhood obesity is now an established public health problem in most developed countries, and there is concern about a parallel increase of type 2 diabetes. The aim of this study was to estimate the prevalence of undiagnosed type 2 diabetes in overweight Swedish school children from 11 to 13 years of age.

    METHODS: Body mass index (BMI) was measured in 5528 schoolchildren in the 6th grade, from 11 to 13 years of age, in five different regions in Sweden. Overweight was defined by international age- and sex-specific BMI cut-offs, corresponding to adult BMI cut-offs of 25 kg/m(2) at 18 years of age (ISO-BMI ≥25, n = 1275). Haemoglobin A1c (HbA1c) was measured in 1126 children with ISO-BMI ≥25. Children with a Diabetes Control and Complications Trial aligned HbA1c ≥6.1% on two occasions underwent an oral glucose tolerance test (OGTT) to establish the diabetes diagnosis.

    RESULTS: Of 1126 children with ISO-BMI ≥25, 24 (2.1%) had at least one HbA1c value ≥6.1%. Three of them had HbA1c ≥6.1% on two occasions, and all of them had a normal OGTT.

    CONCLUSION: In this cross-sectional, population-based screening study of a high-risk group of 11- to 13-year-old Swedish school children, we found no indication of undiagnosed diabetes or impaired glucose tolerance.

  • 5.
    Berhan, Yonas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Carlsson, Annelie
    Högberg, Lotta
    Ivarsson, Anneli
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Screening for undiagnosed type-2 diabetes in Swedish 6th grade school childrenManuscript (preprint) (Other academic)
    Abstract [en]

    Aims: To estimate the prevalence of undiagnosed type-2 diabetes in overweight Swedish school children 11-13 years old.

    Methods: BMI was measured in 5 528 school-children (11-13 years of age) attending the 6th grade, in five different regions in Sweden. Overweight was defined by international age-sex specific BMI cut-offs, corresponding to adult BMI cut-offs of 25 kg/m² at 18 years of age (ISO-BMI ≥25, n=1 275). Haemoglobin A1c (HbA1c) was measured in 1 126 children with ISO-BMI ≥25. Children with a DCCT-aligned HbA1c ≥ 6.1% on two occasions underwent an oral glucose-tolerance test (OGTT) to establish diabetes diagnosis.

    Results: Twenty four children (2.1%) had at least one HbA1c-value ≥6.1%. Three of them had HbA1c ≥6.1% on two occasions and all of them had a normal OGTT.

    Conclusion: In this cross-sectional population-based screening study of a high risk group of 11-13 years old Swedish school children we found no indication of undiagnosed diabetes or impaired glucose tolerance.Key

  • 6.
    Berhan, Yonas
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Waernbaum, Ingeborg
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Lind, Torbjörn
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Möllsten, Anna
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Dahlqvist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Thirty years of prospective nationwide incidence of childhood type 1 diabetes: the accelerating increase by time tends to level off in Sweden.2011In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 60, no 2, p. 577-81Article in journal (Refereed)
    Abstract [en]

    Childhood T1D increased dramatically and shifted to a younger age at onset the first 22 years of the study period. We report a reversed trend, starting in 2000, indicating a change in nongenetic risk factors affecting specifically young children.

  • 7.
    Lind, Torbjörn
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Waernbaum, Ingeborg
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.
    Berhan, Yonas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Socioeconomic factors, rather than diabetes mellitus per se, contribute to an excessive use of antidepressants among young adults with childhood onset type 1 diabetes mellitus: a register-based study2012In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 55, no 3, p. 617-624Article in journal (Refereed)
    Abstract [en]

    AIMS/HYPOTHESIS: Mood disorders, including depression, are suggested to be prevalent in persons with type 1 diabetes and may negatively affect self-management and glycaemic control and increase the risk of diabetic complications. The aim of this study was to analyse the prevalence of antidepressant (AD) use in adults with childhood onset type 1 diabetes and to compare risk determinants for AD prescription among diabetic patients and a group of matched controls. METHODS: Young adults ≥18 years on 1 January 2006 with type 1 diabetes (n = 7,411) were retrieved from the population-based Swedish Childhood Diabetes Registry (SCDR) and compared with 30,043 age- and community-matched controls. Individual level data were collected from the Swedish National Drug Register (NDR), the Hospital Discharge Register (HDR) and the Labor Market Research database (LMR). RESULTS: ADs were prescribed to 9.5% and 6.8% of the type 1 diabetes and control subjects, respectively. Female sex, having received economic or other social support, or having a disability pension were the factors with the strongest association with AD prescription in both groups. Type 1 diabetes was associated with a 44% (OR 1.44, 95% CI 1.32, 1.58) higher risk of being prescribed ADs in crude analysis. When adjusting for potential confounders including sex, age and various socioeconomic risk factors, this risk increase was statistically non-significant (OR 1.11, 95% CI 0.99, 1.21). CONCLUSIONS/INTERPRETATION: The risk factor patterns for AD use are similar among type 1 diabetic patients and controls, and socioeconomic risk factors, rather than the diabetes per se, contribute to the increased risk of AD use in young adults with type 1 diabetes.

  • 8.
    Mollsten, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Svensson, M
    Berhan, Yonas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Age at onset and sex influence the risk of developing end-stage renal disease in young patients with type 1 diabetes2009In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 52, p. S25-S26Article in journal (Refereed)
  • 9.
    Möllsten, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Svensson, Maria
    Department of Nephrology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Waernbaum, Ingeborg
    Umeå University, Faculty of Social Sciences, Department of Statistics.
    Berhan, Yonas
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Schön, Staffan
    Department of Internal Medicine, Ryhov County Hospital, Jönköping, Sweden.
    Nyström, Lennarth
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Arnqvist, Hans J.
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Dahlquist, Gisela
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Cumulative risk, age at onset, and sex-specific differences for developing end-stage renal disease in young patients with type 1 diabetes: A nationwide population-based cohort study2010In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 59, no 7, p. 1803-1808Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE—This study aimed to estimate the current cumulativerisk of end-stage renal disease (ESRD) due to diabeticnephropathy in a large, nationwide, population-based prospectivetype 1 diabetes cohort and specifically study the effects ofsex and age at onset.RESEARCH DESIGN AND METHODS—In Sweden, all incidentcases of type 1 diabetes aged 0–14 years and 15–34 years arerecorded in validated research registers since 1977 and 1983,respectively. These registers were linked to the Swedish RenalRegistry, which, since 1991, collects data on patients who receiveactive uremia treatment. Patients with 13 years duration of type1 diabetes were included (n 11,681).RESULTS—During a median time of follow-up of 20 years, 127patients had developed ESRD due to diabetic nephropathy. Thecumulative incidence at 30 years of type 1 diabetes duration waslow, with a male predominance (4.1% [95% CI 3.1–5.3] vs. 2.5%[1.7–3.5]). In both male and female subjects, onset of type 1diabetes before 10 years of age was associated with the lowestrisk of developing ESRD. The highest risk of ESRD was found inmale subjects diagnosed at age 20–34 years (hazard ratio 3.0 [95%CI 1.5–5.7]). In female subjects with onset at age 20–34 years, therisk was similar to patients’ diagnosed before age 10 years.CONCLUSIONS—The cumulative incidence of ESRD is exceptionallylow in young type 1 diabetic patients in Sweden. There isa striking difference in risk for male compared with femalepatients. The different patterns of risk by age at onset and sexsuggest a role for puberty and sex hormones.

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