| 1. |
- Butwicka, Agnieszka, et al.
(author)
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Risks of psychiatric disorders and suicide attempts in children and adolescents with type 1 diabetes : a population-based cohort study
- 2015
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In: Diabetes Care. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0149-5992 .- 1935-5548.
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Journal article (peer-reviewed)abstract
- Objective: To assess the risk of psychiatric disorders and suicide attempts in children with type 1 diabetes and their healthy siblings. Research Design and Methods: We performed a population-based case cohort study of individuals born in Sweden between 1973 and 2009. Children with type 1 diabetes (n=17,122) and their healthy siblings (n=18,847) were identified and followed until their 18th birthday. Their risk of psychiatric disorders was compared with matched controls. Results: The risk of psychiatric morbidity in children with type 1 diabetes compared to the general population was tripled within 6 months after the onset of diabetes (hazard ratio, HR 3.0, 95% confidence interval, CI 2.7-3.4) and doubled within the total observation period (HR 2.1, CI 2.0-2.2). An increased risk was noted in suicide attempts (HR 1.7, CI 1.4-2.0) and in most categories of psychiatric disorders. The risk of psychiatric disorders in probands declined from HR 2.7 (CI 2.2-3.3) for those in the cohort born 1973-1986 to 1.9 (CI 1.8-2.0) in those born 1997-2009. The risk for any psychiatric disorders among siblings of patients with type 1 diabetes was estimated to be HR 1.1 (CI 1.0-1.1) and there was no increased risk in any of the specific category of disorders. Conclusions: Children with type 1 diabetes are at high risk of psychiatric disorders, which seems to be a consequence of the disease rather than due to a common familial etiology. The results support recommendations on comprehensive mental health surveillance in children with type 1 diabetes, especially in recently diagnosed children.
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| 2. |
- Khashan, Ali S, et al.
(author)
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Gestational age and birth weight and the risk of childhood type 1 diabetes : a population-based cohort and sibling design study
- 2015
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In: Diabetes Care. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0149-5992 .- 1935-5548.
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Journal article (peer-reviewed)abstract
- Objectives: We investigated the effects of gestational age, birthweight, small for gestational age (SGA) and large for gestational age (LGA) on childhood type 1 diabetes. Methods: We conducted a population-based cohort study of all singleton live births in Sweden between 1973-2009 and a sibling-control study. Perinatal data were extracted from the Swedish Medical Birth Register. Children with type 1 diabetes diagnosis were identified from the Swedish National Patient Register. Log-linear Poisson regression and conditional logistic regression were used for data analysis. Results: The study cohort consisted of 3,624,675 singleton live births (42,411,054 person-years). There were 13,944 type 1 diabetes cases during the study period. The sibling-control study consisted of 11,403 children with type 1 diabetes and 17,920 siblings. Gestational age between 33-36 weeks (RR=1.18; [95%CIs: 1.09, 1.28) and 37-38 weeks (RR=1.12; [95%CIs: 1.07, 1.17]) was associated with type 1 diabetes in the cohort study and remained significant in the sibling-control study. SGA (RR=0.83; [95%CIs: 0.75, 0.93]) and LGA (RR=1.14; [95%CIs: 1.04, 1.24]) were associated with type 1 diabetes in the cohort study. The SGA association remained unchanged in the sibling study while the LGA association disappeared. Very low birthweight was associated with a reduced risk of type 1 diabetes. Conclusions: The findings suggest a small association between gestational age and type 1 diabetes that is not likely due to familial confounding factors. Gestational age and type 1 diabetes may be related to insulin resistance due to early life growth restriction or altered gut microbiota in preterm babies.
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| 3. |
- Ahren, Bo, et al.
(author)
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Efficacy and safety of liraglutide added to capped insulin treatment in subjects with type 1 diabetes : The adjunct two randomized trial
- 2016
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:10, s. 1693-1701
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Journal article (peer-reviewed)abstract
- OBJECTIVE To investigate the efficacy and safety of liraglutide added to capped insulin doses in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS A 26-week, placebo-controlled, double-blind, parallel-group trial enrolling 835 subjects randomized 3:1 receiving once-daily subcutaneous liraglutide (1.8, 1.2, and 0.6 mg) or placebo added to an individually capped total daily dose of insulin. RESULTS Mean baseline glycated hemoglobin (HbA1c ) (8.1% [65.0 mmol/mol]) was significantly decreased with liraglutide versus placebo at week 26 (1.8 mg: -0.33% [3.6mmol/mol]; 1.2mg: -0.22% [2.4mmol/mol]; 0.6 mg: -0.23% [2.5mmol/mol]; placebo: 0.01% [0.1 mmol/mol]). Liraglutide significantly reduced mean body weight (-5.1, -4.0, and -2.5 kg for 1.8, 1.2, and 0.6 mg, respectively) versus placebo (-0.2 kg). Significant reductions in daily insulin dose and increases in quality of life were seen with liraglutide versus placebo. There were higher rates of symptomatic hypoglycemia (21.3 vs. 16.6 events/patient/year; P = 0.03) with liraglutide 1.2mg vs. placebo and of hyperglycemia with ketosis >1.5mmol/L with liraglutide 1.8 mg vs. placebo (0.5 vs. 0.1 events/patient/year; P = 0.01). CONCLUSIONS In a broad population of subjects with long-standing type 1 diabetes, liraglutide added to capped insulin reduced HbA1c, body weight, and insulin requirements but with higher rates of hypoglycemia for liraglutide 1.2 mg and hyperglycemia with ketosis for liraglutide 1.8 mg.
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| 4. |
- Anderson, B. J., et al.
(author)
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Factors associated with diabetes-specific health-related quality of life in youth with type 1 diabetes: The global teens study
- 2017
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 40:8, s. 1002-1009
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Journal article (peer-reviewed)abstract
- OBJECTIVE Our objective was to characterize diabetes-specific health-related quality of life (D-HRQOL) in a global sample of youth and young adults with type 1 diabetes (T1D) and to identify the main factors associated with quality of life. RESEARCH DESIGN AND METHODS The TEENs study was an international, cross-sectional study of youth, 8-25 years of age, with T1D. Participants (N= 5,887)were seen in clinical sites in 20 countries across 5 continents enrolled for 3 predetermined age groups: 8-12, 13-18, and 19-25 years of age. To assess D-HRQOL, participants completed the PedsQL DiabetesModule 3.0 and were interviewed about family-related factors. Specifics about treatment regimen and self-management behaviors were collected from medical records. RESULTS Across all age groups, females reported significantly lower D-HRQOL than didmales. The 19-25-year age group reported the lowest D-HRQOL. Multivariate linear regression analyses revealed that D-HRQOL was significantly related to HbA1c; the lower the HbA1c, the better the D-HRQOL. Three diabetes-management behaviors were significantly related to better D-HRQOL: advanced methods used to measure food intake;more frequent daily blood glucose monitoring; and more days per week that youth had 30 min of physical activity. CONCLUSIONS In all three age groups, the lower the HbA1c, the better the D-HRQOL, underscoring the strong association between better D-HRQOL and optimal glycemic control in a global sample of youth and young adults. Three diabetes-management behaviors were also related to optimal glycemic control, which represent potentially modifiable factors for clinical interventions to improve D-HRQOL as well as glycemic control.
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| 5. |
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| 6. |
- Berhan, Yonas, et al.
(author)
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Impact of Parental Socioeconomic Status on Excess Mortality in a Population-Based Cohort of Subjects With Childhood-Onset Type 1 Diabetes
- 2015
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 38:5, s. 827-832
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Journal article (peer-reviewed)abstract
- 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.
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| 7. |
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| 8. |
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| 9. |
- Charalampopoulos, Dimitrios, et al.
(author)
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Exploring Variation in Glycemic Control Across and Within Eight High-Income Countries: A Cross-sectional Analysis of 64,666 Children and Adolescents With Type 1 Diabetes
- 2018
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In: Diabetes Care. - : AMER DIABETES ASSOC. - 0149-5992 .- 1935-5548. ; 41:6, s. 1180-1187
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Journal article (peer-reviewed)abstract
- OBJECTIVE International studies on childhood type 1 diabetes (T1D) have focused on whole-country mean HbA(1c) levels, thereby concealing potential variations within countries. We aimed to explore the variations in HbA(1c) across and within eight high-income countries to best inform international benchmarking and policy recommendations. RESEARCH DESIGN AND METHODS Data were collected between 2013 and 2014 from 64,666 children with T1D who were amp;lt; 18 years of age across 528 centers in Germany, Austria, England, Wales, U.S., Sweden, Denmark, and Norway. We used fixed-and random-effects models adjusted for age, sex, diabetes duration, and minority status to describe differences between center means and to calculate the proportion of total variation in HbA(1c) levels that is attributable to between-center differences (intraclass correlation [ICC]). We also explored the association between within-center variation and childrens glycemic control. RESULTS Sweden had the lowest mean HbA(1c) (59mmol/mol [7.6%]) and together with Norway and Denmark showed the lowest between-center variations (ICC amp;lt;= 4%). Germany and Austria had the next lowest mean HbA(1c) (61-62 mmol/mol [7.7-7.8%]) but showed the largest center variations (ICC similar to 15%). Centers in England, Wales, and the U.S. showed low-to-moderate variation around high mean values. In pooled analysis, differences between counties remained significant after adjustment for children characteristics and center effects (P value amp;lt; 0.001). Across all countries, children attending centers with more variable glycemic results had higher HbA(1c) levels (5.6mmol/mol [0.5%] per 5mmol/mol [0.5%] increase in center SD of HbA(1c) values of all children attending a specific center). CONCLUSIONS A tsimilar average levels of HbA(1c), countries display different levels of center variation. The distribution of glycemic achievement within countries should be considered in developing informed policies that drive quality improvement.
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| 10. |
- Chatterjee, Saion, et al.
(author)
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Type 2 Diabetes as a Risk Factor for Dementia in Women Compared With Men: A Pooled Analysis of 2.3 Million People Comprising More Than 100,000 Cases of Dementia
- 2016
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:2, s. 300-307
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Journal article (peer-reviewed)abstract
- OBJECTIVE Type 2 diabetes confers a greater excess risk of cardiovascular disease in women than in men. Diabetes is also a risk factor for dementia, but whether the association is similar in women and men remains unknown. We performed a meta-analysis of unpublished data to estimate the sex-specific relationship between women and men with diabetes with incident dementia. RESEARCH DESIGN AND METHODS A systematic search identified studies published prior to November 2014 that had reported on the prospective association between diabetes and dementia. Study authors contributed unpublished sex-specific relative risks (RRs) and 95% CIs on the association between diabetes and all dementia and its subtypes. Sex-specific RRs and the women-to-men ratio of RRs (RRRs) were pooled using random-effects meta-analyses. RESULTS Study-level data from 14 studies, 2,310,330 individuals, and 102,174 dementia case patients were included. In multiple-adjusted analyses, diabetes was associated with a 60% increased risk of any dementia in both sexes (women: pooled RR 1.62 [95% CI 1.45–1.80]; men: pooled RR 1.58 [95% CI 1.38–1.81]). The diabetes-associated RRs for vascular dementia were 2.34 (95% CI 1.86–2.94) in women and 1.73 (95% CI 1.61–1.85) in men, and for nonvascular dementia the RRs were 1.53 (95% CI 1.35–1.73) in women and 1.49 (95% CI 1.31–1.69) in men. Overall, women with diabetes had a 19% greater risk for the development of vascular dementia than men (multiple-adjusted RRR 1.19 [95% CI 1.08–1.30]; P < 0.001). CONCLUSIONS Individuals with type 2 diabetes are at ∼60% greater risk for the development of dementia compared with those without diabetes. For vascular dementia, but not for nonvascular dementia, the additional risk is greater in women.
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| 11. |
- Cobb, Jeff, et al.
(author)
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α-Hydroxybutyric acid is a selective metabolite biomarker of impaired glucose tolerance
- 2016
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:6, s. 988-995
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Journal article (peer-reviewed)abstract
- OBJECTIVE Plasma metabolites that distinguish isolated impaired glucose tolerance (iIGT) from isolated impaired fasting glucose (iIFG) may be useful biomarkers to predict IGT, a high-risk state for the development of type 2 diabetes. RESEARCH DESIGN AND METHODS Targeted metabolomics with 23 metabolites previously associated with dysglycemia was performed with fasting plasma samples from subjects without diabetes at time 0 of an oral glucose tolerance test (OGTT) in two observational cohorts: RISC (Relationship Between Insulin Sensitivity and Cardiovascular Disease) and DMVhi (Diabetes Mellitus and Vascular Health Initiative). Odds ratios (ORs) for a one-SD change in the metabolite level were calculated using multiple logistic regression models controlling for age, sex, and BMI to test for associations with iIGT or iIFG versus normal. Selective biomarkers of iIGT were further validated in the Botnia study. RESULTS α-Hydroxybutyric acid (α-HB) was most strongly associated with iIGT in RISC (OR 2.54 [95% CI 1.86-3.48], P value 5E-9) and DMVhi (2.75 [1.81-4.19], 4E-5) while having no significant association with iIFG. In Botnia, a-HB was selectively associated with iIGT (2.03 [1.65-2.49], 3E-11) and had no significant association with iIFG. Linoleoyl-glycerophosphocholine (L-GPC) and oleic acid were also found to be selective biomarkers of iIGT. In multivariate IGT prediction models, addition of α-HB, L-GPC, and oleic acid to age, sex, BMI, and fasting glucose significantly improved area under the curve in all three cohorts. CONCLUSIONS α-HB, L-GPC, and oleic acid were shown to be selective biomarkers of iIGT, independent of age, sex, BMI, and fasting glucose, in 4,053 subjects without diabetes from three European cohorts. These biomarkers can be used in predictive models to identify subjects with IGT without performing an OGTT.
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| 12. |
- Cousminer, Diana L, et al.
(author)
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First Genome-Wide Association Study of Latent Autoimmune Diabetes in Adults Reveals Novel Insights Linking Immune and Metabolic Diabetes
- 2018
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 41:11, s. 2396-2403
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Latent autoimmune diabetes in adults (LADA) shares clinical features with both type 1 and type 2 diabetes; however, there is ongoing debate regarding the precise definition of LADA. Understanding its genetic basis is one potential strategy to gain insight into appropriate classification of this diabetes subtype.RESEARCH DESIGN AND METHODS: We performed the first genome-wide association study of LADA in case subjects of European ancestry versus population control subjects (n = 2,634 vs. 5,947) and compared against both case subjects with type 1 diabetes (n = 2,454 vs. 968) and type 2 diabetes (n = 2,779 vs. 10,396).RESULTS: The leading genetic signals were principally shared with type 1 diabetes, although we observed positive genetic correlations genome-wide with both type 1 and type 2 diabetes. Additionally, we observed a novel independent signal at the known type 1 diabetes locus harboring PFKFB3, encoding a regulator of glycolysis and insulin signaling in type 2 diabetes and inflammation and autophagy in autoimmune disease, as well as an attenuation of key type 1-associated HLA haplotype frequencies in LADA, suggesting that these are factors that distinguish childhood-onset type 1 diabetes from adult autoimmune diabetes.CONCLUSIONS: Our results support the need for further investigations of the genetic factors that distinguish forms of autoimmune diabetes as well as more precise classification strategies.
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| 13. |
- Cropano, Catrina, et al.
(author)
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The rs7903146 variant in the tcf7l2 gene increases the risk of prediabetes/type 2 diabetes in obese adolescents by impairing b-cell function and hepatic insulin sensitivity
- 2017
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 40:8, s. 1082-1089
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Journal article (peer-reviewed)abstract
- OBJECTIVE In this study, we aimed to explore the mechanism by which TCF7L2 rs7903146 risk allele confers susceptibility to impaired glucose tolerance (IGT) or type 2 diabetes (T2D) in obese adolescents. RESEARCH DESIGN AND METHODS The rs7903146 variant in the TCF7L2 gene was genotyped in a multiethnic cohort of 955 youths. All subjects underwent an oral glucose tolerance test with the use of the Oral Minimal Model to assess insulin secretion, and 33 subjects underwent a hyperinsulinemic-euglycemic clamp. In 307 subjects, a follow-up oral glucose tolerance test was repeated after 3.11 6 2.36 years. RESULTS The TCF7L2 rs7903146 risk allele was associated with higher 2-h glucose levels in Caucasians (P = 0.006) and African Americans (P = 0.009), and a trendwas seen also in Hispanics (P = 0.072). Also, the T allele was associated with decreased b-cell responsivity and IGT (P < 0.05). Suppression of endogenous hepatic glucose productionwas lower in subjects with the risk variant (P = 0.006). Finally, the odds of showing IGT/T2D at follow-up were higher in subjects carrying the minor allele (odds ratio 2.224; 95% CI 1.370-3.612; P = 0.0012). CONCLUSIONS The rs7903146 variant in the TCF7L2 gene increases the risk of IGT/T2D in obese adolescents by impairing b-cell function, and hepatic insulin sensitivity predicts the development of IGT/T2D over time.
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| 14. |
- Dagenais, G. R., et al.
(author)
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Variations in Diabetes Prevalence in Low-, Middle-, and High-Income Countries: Results From the Prospective Urban and Rural Epidemiological Study
- 2016
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:5, s. 780-787
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Journal article (peer-reviewed)abstract
- OBJECTIVE The goal of this study was to assess whether diabetes prevalence varies by countries at different economic levels and whether this can be explained by known risk factors. The prevalence of diabetes, defined as self-reported or fasting glycemia >= 7 mmol/L, was documented in 119,666 adults from three high-income (HIC), seven upper-middle-income (UMIC), four lower-middle-income (LMIC), and four low-income (LIC) countries. Relationships between diabetes and its risk factors within these country groupings were assessed using multivariable analyses. Age- and sex-adjusted diabetes prevalences were highest in the poorer countries and lowest in the wealthiest countries (LIC 12.3%, UMIC 11.1%, LMIC 8.7%, and HIC 6.6%; P < 0.0001). In the overall population, diabetes risk was higher with a 5-year increase in age (odds ratio 1.29 [95% CI 1.28-1.31]), male sex (1.19 [1.13-1.25]), urban residency (1.24 [1.11-1.38]), low versus high education level (1.10 [1.02-1.19]), low versus high physical activity (1.28 [1.20-1.38]), family history of diabetes (3.15 [3.00-3.31]), higherwaist-to-hip ratio (highest vs. lowest quartile; 3.63 [3.33-3.96]), and BMI (>= 35 vs. < 25 kg/m(2); 2.76 [2.52-3.03]). The relationship between diabetes prevalence and both BMI and family history of diabetes differed in higher-versus lower-income country groups (P for interaction < 0.0001). After adjustment for all risk factors and ethnicity, diabetes prevalences continued to show a gradient (LIC 14.0%, LMIC 10.1%, UMIC 10.9%, and HIC 5.6%). Conventional risk factors do not fully account for the higher prevalence of diabetes in LIC countries. These findings suggest that other factors are responsible for the higher prevalence of diabetes in LIC countries.
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| 15. |
- Dawed, Adem Y., et al.
(author)
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Variation in the plasma membrane monoamine transporter (PMAT) (encoded by SLC29A4) and organic cation transporter 1 (OCT1) (encoded by SLC22A1) and gastrointestinal intolerance to metformin in type 2 diabetes : An IMI direct study
- 2019
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 42:6, s. 1027-1033
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Journal article (peer-reviewed)abstract
- OBJECTIVE Gastrointestinal adverse effects occur in 20–30% of patients with metformin-treated type 2 diabetes, leading to premature discontinuation in 5–10% of the cases. Gastrointestinal intolerance may reflect localized high concentrations of metformin in the gut. We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects. RESEARCH DESIGN AND METHODS The study included 286 severe metformin-intolerant and 1,128 metformin-tolerant individuals from the IMI DIRECT (Innovative Medicines Initiative: DIabetes REsearCh on patient straTification) consortium. We assessed the association of patient characteristics, concomitant medication, and the burden of mutations in the SLC29A4 and SLC22A1 genes on odds of intolerance. RESULTS Women (P < 0.001) and older people (P < 0.001) were more likely to develop metformin intolerance. Concomitant use of transporter-inhibiting drugs increased the odds of intolerance (odds ratio [OR] 1.72, P < 0.001). In an adjusted logistic regression model, the G allele at rs3889348 (SLC29A4) was associated with gastrointestinal intolerance (OR 1.34, P = 0.005). rs3889348 is the top cis-expression quantitative trait locus for SLC29A4 in gut tissue where carriers of the G allele had reduced expression. Homozygous carriers of the G allele treated with transporter-inhibiting drugs had more than three times higher odds of intolerance compared with carriers of no G allele and not treated with inhibiting drugs (OR 3.23, P < 0.001). Use of a genetic risk score derived from rs3889348 and SLC22A1 variants found that the odds of intolerance were more than twice as high in individuals who carry three or more risk alleles compared with those carrying none (OR 2.15, P = 0.01). CONCLUSIONS These results suggest that intestinal metformin transporters and concomitant medications play an important role in the gastrointestinal adverse effects of metformin.
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| 16. |
- Du, YT, et al.
(author)
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Gastrointestinal Symptoms in Diabetes: Prevalence, Assessment, Pathogenesis, and Management
- 2018
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In: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 41:3, s. 627-637
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Journal article (peer-reviewed)abstract
- If you haven’t measured something, you really don’t know much about it. —Karl Pearson (attributed)Gastrointestinal (GI) symptoms represent an important and often unappreciated cause of morbidity in diabetes, although the significance of this burden across the spectrum of patients and the underlying pathophysiology, including the relationship of symptoms with glycemic control, remain poorly defined. The relevance of GI symptoms and the necessity for their accurate assessment have increased with the greater focus on the gut as a therapeutic target for glucose lowering. This review addresses the prevalence, assessment, pathogenesis, and management of GI symptoms in diabetes, beginning with broad principles and then focusing on specific segments of the GI tract. We initially performed a literature search of PubMed by using synonyms and combinations of the following search terms: “gastrointestinal symptoms”, “diabetes”, “prevalence”, “pathogenesis”, “diagnosis”, and “management”. We restricted the search results to English only. Review papers and meta-analyses are presented as the highest level of evidence where possible followed by randomized controlled trials, uncontrolled trials, retrospective and observational data, and expert opinion.
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| 17. |
- Edqvist, Jon, 1988, et al.
(author)
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BMI and Mortality in Patients With New-Onset Type 2 Diabetes: A Comparison With Age- and Sex-Matched Control Subjects From the General Population
- 2018
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 41:3, s. 485-493
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Type 2 diabetes is strongly associated with obesity, but the mortality risk related to elevated body weight in people with type 2 diabetes compared with people without diabetes has not been established. RESEARCH DESIGN AND METHODS: We prospectively assessed short- and long-term mortality in people with type 2 diabetes with a recorded diabetes duration /=40 kg/m(2) compared with control subjects after multiple adjustments. Long-term, all weight categories showed increased mortality, with a nadir at BMI 25 to <30 kg/m(2) and a stepwise increase up to HR 2.00 (95% CI 1.58-2.54) among patients with BMI >/=40 kg/m(2), that was more pronounced in patients <65 years old. CONCLUSIONS: Our findings suggest that the apparent paradoxical findings in other studies in this area may have been affected by reverse causality. Long-term, overweight (BMI 25 to <30 kg/m(2)) patients with type 2 diabetes had low excess mortality risk compared with control subjects, whereas risk in those with BMI >/=40 kg/m(2) was substantially increased.
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| 18. |
- Edqvist, Jon, 1988, et al.
(author)
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BMI, Mortality, and Cardiovascular Outcomes in Type 1 Diabetes: Findings Against an Obesity Paradox
- 2019
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 42:7, s. 1297-1304
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Journal article (peer-reviewed)abstract
- OBJECTIVE Low weight has been associated with increased mortality risks in type 1 diabetes. We aimed to investigate the importance of weight and weight gain/loss in the Swedish population diagnosed with type 1 diabetes. RESEARCH DESIGN AND METHODS Patients with type 1 diabetes (n = 26,125; mean age 33.3 years; 45% women) registered in the Swedish National Diabetes Registry from 1998 to 2012 were followed from the first day of study entry. Cox regression was used to calculate risk of death from cardiovascular disease (CVD), major CVD events, hospitalizations for heart failure (HF), and total deaths. RESULTS Population mean BMI in patients with type 1 diabetes increased from 24.7 to 25.7 kg/m(2) from 1998 to 2012. Over a median follow-up of 10.9 years, there were 1,031 deaths (33.2% from CVD), 1,460 major CVD events, and 580 hospitalizations for HF. After exclusion of smokers, patients with poor metabolic control, and patients with a short follow-up time, there was no increased risk for mortality in those with BMI <25 kg/m(2), while BMI >25 kg/m(2) was associated with a minor increase in risk of mortality, major CVD, and HF. In women, associations with BMI were largely absent. Weight gain implied an increased risk of mortality and HF, while weight loss was not associated with higher risk. CONCLUSIONS Risk of major CVD, HF, CVD death, and mortality increased with increasing BMI, with associations more apparent in men than in women. After exclusion of factors associated with reverse causality, there was no evidence of an obesity paradox.
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| 19. |
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| 20. |
- Espes, Daniel, 1985-, et al.
(author)
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Increased Interleukin-35 Levels in Patients With Type 1 Diabetes With Remaining C-Peptide
- 2017
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 40:8, s. 1090-1095
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Journal article (peer-reviewed)abstract
- OBJECTIVE Many patients with long-standing type 1 diabetes have remaining functional β-cells. This study investigated immunological differences between patients with or without measurable remaining endogenous insulin production after ≥10 years duration of disease.RESEARCH DESIGN AND METHODS Patients (n = 113; ≥18 years of age) with type 1 diabetes and with disease duration of ≥10 years were recruited at Uppsala University Hospital. Residual β-cell function was determined with an ultrasensitive C-peptide ELISA. Circulating cytokines, including interleukin-35 (IL-35), were determined in plasma. Additional blood samples were collected from 14 of the identified C-peptide–positive patients and 12 of the C-peptide–negative patients, as well as from 15 healthy control subjects, and were used for immediate investigation of peripheral blood mononuclear cells.RESULTS The blood concentration of the cytokine IL-35 was markedly lower in C-peptide–negative patients, and this was associated with a simultaneous decrease in the proportion of IL-35+ regulatory T cells (Tregs), IL-35+ regulatory B cells, and IL-35–producing CD8+Foxp3+ cells. IL-35 has previously been shown to maintain the phenotype of Tregs, block the differentiation of T-helper 17 cells, and thereby dampen immune assaults to β-cells. We found that the proportions of IL-17a+ cells among the Tregs, CD4+ T cells, and CD8+ T cells were lower in the C-peptide–positive patients.CONCLUSIONS Patients with remaining endogenous β-cell function after >10 years duration of type 1 diabetes differ immunologically from other patients with long-standing type 1 diabetes. In particular, they have a much higher IL-35 production.
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| 21. |
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| 22. |
- Grip, Emilie Toresson, et al.
(author)
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Real-World Costs of Continuous Insulin Pump Therapy and Multiple Daily Injections for Type 1 Diabetes: A Population-Based and Propensity-Matched Cohort From the Swedish National Diabetes Register
- 2019
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 42:4, s. 545-552
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Journal article (peer-reviewed)abstract
- OBJECTIVE To investigate real-world costs of continuous insulin pump therapy compared with multiple daily injection (MDI) therapy for type 1 diabetes. RESEARCH DESIGN AND METHODS Individuals with type 1 diabetes and pump therapy in the Swedish National Diabetes Register (NDR) since 2002 were eligible. Control subjects on MDI were matched 2:1 using time-varying propensity scores. Longitudinal data on health care resource use, antidiabetes treatment, sickness absence, and early retirement were taken from national registers for 2005-2013. Mean annual costs were analyzed using univariate analysis. Regression analyses explored the role of sociodemographic factors. Subgroup and sensitivity analyses were performed. RESULTS A total of 14,238 individuals with type 1 diabetes entered in the NDR between 2005 and 2013 (insulin pump n = 4,991, MDI n = 9,247, with switches allowed during the study) were included. Mean age at baseline was 34 years, with 21 years of diabetes duration and a mean HbA(1c) of 8.1% (65 mmol/mol). We had 73,920 person-years of observation with a mean follow-up of 5 years per participant. Mean annual costs were higher for pump therapy than for MDI therapy ($12,928 vs. $9,005, respectively; P < 0.001; mean difference $3,923 [95% CI $3,703-$4,143]). Health care costs, including medications and disposables, accounted for 73% of the costs for pump therapy and 63% of the costs for MDI therapy. Regression analyses showed higher costs for low education, low disposable income, women, and older age. CONCLUSIONS Nine years of real-world data on all measurable diabetes-related resource use show robust results for additional costs of insulin pump therapy in adults by subgroup and alternative propensity score specifications. Identification of tangible and intangible benefits of pump therapy over time remain important to support resource allocation decisions.
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| 23. |
- Hagg-Holmberg, S., et al.
(author)
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Prognosis and Its Predictors After Incident Stroke in Patients With Type 1 Diabetes
- 2017
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 40:10, s. 1394-1400
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Journal article (peer-reviewed)abstract
- OBJECTIVE Although patients with type 1 diabetes have a poor prognosis after a stroke, predictors of survival after an incident stroke in these patients are poorly studied. In this observational study, a total of 144 patients of 4,083 with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study suffered an incident stroke in 1997-2010, and were followed for a mean 3.4 6 +/- 3.1 years after the stroke. Information was recorded on hard cardiovascular events and death as a result of cardiovascular or diabetes-related cause, collectively referred to as vascular composite end point. Information was collected from medical records, death certificates, and the National Care Register of Health Care. Predictors at the time of the incident stroke were studied for the end points. During follow-up, 104 (72%) patients suffered a vascular composite end point. Of these, 33 (32%) had a recurrent stroke, 33 (32%) a hard cardiovascular event, and 76 (53%) died of cardiovascular or diabetes-related causes, with an overall 1-year survival of 76% and 5-year survival of 58%. The predictors of a vascular composite end point were hemorrhagic stroke subtype (hazard ratio 2.03 [95% CI 1.29-3.19]), as well as chronic kidney disease stage 2 (2.48 [1.17-5.24]), stage 3 (3.04 [1.54-6.04]), stage 4 (3.95 [1.72-9.04]), and stage 5 (6.71 [3.14-14.34]). All-cause mortality increased with deteriorating kidney function. Patients with type 1 diabetes with an incident stroke have a poor cardiovascular prognosis and a high risk of all-cause mortality. In particular, hemorrhagic stroke subtype and progression of diabetic kidney disease conveys worse outcome.
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| 24. |
- Hallström, Sara, et al.
(author)
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Risk Factors for Atrial Fibrillation in People With Type 1 Diabetes: An Observational Cohort Study of 36,258 Patients From the Swedish National Diabetes Registry
- 2019
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 42:8, s. 1530-1538
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Journal article (peer-reviewed)abstract
- OBJECTIVE This study identified variables associated with increased risk of atrial fibrillation in people with type 1 diabetes. RESEARCH DESIGN AND METHODS We performed a cohort study of people with type 1 diabetes from the Swedish National Diabetes Registry followed up between 1 January 2001 and 31 December 2013. Median follow-up was 9.7 years (interquartile range 5.2-13.0). The association between potential risk factors and incident atrial fibrillation was investigated using adjusted Cox regression. To compare the impact of each risk factor, the gradient of risk per 1 SD was estimated. RESULTS In this cohort of 36,258 patients with type 1 diabetes, 749 developed atrial fibrillation during follow-up. Older age, male sex, renal complications, increased BMI and HbA(1c), coronary artery disease, heart failure, and heart valve disease increased the risk of atrial fibrillation. Age, signs of renal dysfunction with macroalbuminuria, and decreasing estimated glomerular filtration rate were associated with the highest gradient of risk for atrial fibrillation. High blood pressure, severe obesity (BMI >35 kg/m(2)), and elevated levels of HbA(1c) (>9.6%) were associated with increased risk, but no associations were found with hyperlipidemia or smoking. CONCLUSIONS The most prominent risk factors for atrial fibrillation in people with type 1 diabetes were older age, cardiovascular comorbidities, and renal complications, while obesity, hypertension, and hyperglycemia had more modest affects.
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| 25. |
- Hartstra, A. V., et al.
(author)
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Insights Into the Role of the Microbiome in Obesity and Type 2 Diabetes
- 2015
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In: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 38:1, s. 159-165
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Journal article (peer-reviewed)abstract
- The worldwide prevalence of obesity and type 2 diabetes mellitus (T2DM) continues to rise at an alarming pace. Recently the potential role of the gut microbiome in these metabolic disorders has been identified. Obesity is associated with changes in the composition of the intestinal microbiota, and the obese microbiome seems to be more efficient in harvesting energy from the diet. Lean male donor fecal microbiota transplantation (FMT) in males with metabolic syndrome resulted in a significant improvement in insulin sensitivity in conjunction with an increased intestinal microbial diversity, including a distinct increase in butyrate-producing bacterial strains. Such differences in gut microbiota composition might function as early diagnostic markers for the development of T2DM in high-risk patients. Products of intestinal microbes such as butyrate may induce beneficial metabolic effects through enhancement of mitochondrial activity, prevention of metabolic endotoxemia, and activation of intestinal gluconeogenesis via different routes of gene expression and hormone regulation. Future research should focus on whether bacterial products (like butyrate) have the same effects as the intestinal bacteria that produce it, in order to ultimately pave the way for more successful interventions for obesity and T2DM. The rapid development of the currently available techniques, including use of fecal transplantations, has already shown promising results, so there is hope for novel therapies based on the microbiota in the future.
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