| 1. |
- Ahlqvist, Emma, et al.
(författare)
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Novel subgroups of adult-onset diabetes and their association with outcomes : a data-driven cluster analysis of six variables
- 2018
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Ingår i: The Lancet Diabetes and Endocrinology. - 2213-8587 .- 2213-8595. ; 6:5, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDiabetes is presently classified into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous. A refined classification could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis.MethodsWe did data-driven cluster analysis (k-means and hierarchical clustering) in patients with newly diagnosed diabetes (n=8980) from the Swedish All New Diabetics in Scania cohort. Clusters were based on six variables (glutamate decarboxylase antibodies, age at diagnosis, BMI, HbA1c, and homoeostatic model assessment 2 estimates of β-cell function and insulin resistance), and were related to prospective data from patient records on development of complications and prescription of medication. Replication was done in three independent cohorts: the Scania Diabetes Registry (n=1466), All New Diabetics in Uppsala (n=844), and Diabetes Registry Vaasa (n=3485). Cox regression and logistic regression were used to compare time to medication, time to reaching the treatment goal, and risk of diabetic complications and genetic associations.FindingsWe identified five replicable clusters of patients with diabetes, which had significantly different patient characteristics and risk of diabetic complications. In particular, individuals in cluster 3 (most resistant to insulin) had significantly higher risk of diabetic kidney disease than individuals in clusters 4 and 5, but had been prescribed similar diabetes treatment. Cluster 2 (insulin deficient) had the highest risk of retinopathy. In support of the clustering, genetic associations in the clusters differed from those seen in traditional type 2 diabetes.InterpretationWe stratified patients into five subgroups with differing disease progression and risk of diabetic complications. This new substratification might eventually help to tailor and target early treatment to patients who would benefit most, thereby representing a first step towards precision medicine in diabetes.
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| 2. |
- Claesson, Rickard, et al.
(författare)
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HbA1c as a predictor of diabetes after gestational diabetes mellitus
- 2017
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Ingår i: Primary Care Diabetes. - : Elsevier BV. - 1751-9918. ; 11:1, s. 46-51
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Tidskriftsartikel (refereegranskat)abstract
- Aim We wanted to investigate third-trimester HbA1c as a predictor of diabetes after gestational diabetes mellitus (GDM). Methods Women with GDM were followed up prospectively for five years from pregnancy to detect the development of diabetes. The ability of HbA1c to predict diabetes was evaluated with receiver-operating characteristic (ROC) curves and logistic regression analysis. Results By five years, 73 of 196 women had been diagnosed with diabetes. An optimal cut-off point for HbA1c of 36 mmol/mol (5.4%) could predict diabetes with 45% sensitivity and 92% specificity. For HbA1c ≥39 mmol/mol (≥5.7%), sensitivity, specificity, and positive predictive value were 30%, 97%, and 91%, respectively. In logistic regression analysis, adjusting for the diagnostic glucose concentration during pregnancy, HbA1c levels in the upper quartile (≥36 mmol/mol) were associated with a 5.5-fold increased risk of diabetes. Conclusion Third-trimester HbA1c levels in the pre-diabetes range revealed women with post-partum diabetes with high specificity and high positive predictive value. HbA1c testing could be used as a strategy to select high-risk women for lifestyle interventions aimed at prevention of diabetes starting during pregnancy. The results should encourage further validation in other populations using new diagnostic criteria for GDM.
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| 3. |
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| 4. |
- Dhaher, Nadine Fadhel, et al.
(författare)
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Cancer, cardiovascular disease, and all-cause mortality in Iraqi- and Swedish-born individuals in Sweden : the MEDIM cohort study
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13:1, s. 13-13
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Tidskriftsartikel (refereegranskat)abstract
- Immigrants from the Middle East to Sweden have a twice as high prevalence of type 2 diabetes (T2D) and obesity as native-born Swedes. Both obesity and T2D have been linked to increased incidence of cancer, cardiovascular disease (CVD) and all-cause mortality (ACM); however, data on differences between ethnicities are scarce. In a population-based cohort we aimed to study the impact of Middle Eastern and European ethnicity on ACM, cancer- and CVD related mortality, incidence of cancer and CVD in an eight-year follow-up study. Methods: People born in Iraq or Sweden, who were 30-75 years of age, were invited from 2010 to 2012 to participate in the population based MEDIM study including a health exam, fasting blood sampling, assessment of insulin secretion and action (through oral glucose tolerance test) and questionnaires assessing history of CVD, cancer and T2D. Register data were retrieved from baseline until the 31st of December 2018 from the Swedish National Patient Register and Cause of Death register regarding CVD diagnosis, cancer diagnosis and cause of death. Information regarding diabetes diagnosis was retrieved from the National Diabetes Register. Individuals with a history of cancer or CVD at baseline were excluded. Cox regression analysis was assessed to study the adjusted hazard ratios (HR) for the relationships between ethnicity and ACM, cancer events, CVD events, death from cancer, and death from CVD, with adjustments for age, sex, anthropometrical measures, T2D and lifestyle. A total of 1398 Iraqi- and 757 Swedish-born residents participated in the study. ACM was considerably lower in Iraqi- compared to Swedish-born individuals HR 0.32 (95% CI 0.13-0.79) (p < 0.05). Furthermore, cancer related morbidity and mortality HR 0.39 (0.22-0.69) (p < 0.01) as well as CVD related morbidity and mortality HR 0.56 (0.33-0.95) (p < 0.05) were lower in the Iraqi-born group compared to the Swedish-born group for. The differences in mortality and cancer rates across ethnicities are not fully explained by anthropometric, environmental or metabolic measures but lie elsewhere. Further studies are needed to increase the understanding of contributing mechanisms.
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| 5. |
- Dhaher, Nadine Fadhel, et al.
(författare)
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Insulin secretion and action with increasing age - A comparison between Middle Eastern immigrants and native Swedes
- 2022
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Ingår i: Heliyon. - : Elsevier BV. - 2405-8440. ; 8:10
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Little is known how insulin secretion and action change over time in populations of different ethnicities. We studied changes in insulin secretion and action with increasing age in Iraqi-born immigrants and native Swedes, and investigated if the changes were modified by region of origin.Methods: Residents of Malmö, 30-75 years of age born in Iraq or Sweden, were invited to participate in this population-based, cross-sectional study. Health examination, medical history, lifestyle, sociodemographic data, and fasting blood samples were assessed. Oral glucose tolerance tests were performed and insulin secretion (disposition index, DIo) and insulin sensitivity index (ISI) calculated using the Matsuda indices.Results: In total 1881 people participated; 1193 Iraqi- and 688 Swedish born. DIo decreased with increasing age in the total study population (β for the effect of age on ln DIo: -0.018, 95% CI -0.023 to -0.013, P < 0.001), adjusted for origin, lifestyle and anthropometric measures. DIo was generally lower in Iraqis vs. Swedes (median: 12,712.9 vs. 14,659.2, P = 0.004), but the difference disappeared when adjusted for BMI.Further, ISI declined with increasing age in both Iraqis and Swedes. ISI was generally lower among Iraqis compared to Swedes, (median: 76.9 vs. 102.3, p < .001). The difference could not be fully explained by age, sex, lifestyle, and anthropometric measures. No significant interactions were observed.Conclusions: The levels of DIo and ISI were lower among Iraqis compared to Swedes and declined with increasing age, irrespective of origin.
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| 6. |
- Ekelund, Magnus, et al.
(författare)
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Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus
- 2012
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 97:3, s. 394-398
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To examine whether genetic variants that predispose individuals to type 2 diabetes (T2D) could predict the development of diabetes after gestational diabetes mellitus (GDM). Methods: 13 SNPs (FTO rs8050136, CDKAL1 rs7754840 and rs7756992, CDKN2A/2B rs10811661, HHEX rs1111875, IGF2BP2 rs1470579 and rs4402960, SLC30A8 rs13266634, TCF7L2 rs7903146, PPARG rs1801282, GCK rs1799884, HNF1A rs1169288, and KCNJ11 rs5219) were genotyped in 793 women with GDM after a median follow-up of 57 months. Results: After adjustment for age and ethnicity, the TCF7L2 rs7903146 and the FTO rs8050136 variants significantly predicted postpartum diabetes; hazard ratio (95% confidence interval 1.29 (1.01-1.66) and 1.36 (1.06-1.74), respectively (additive model) versus 1.45 (1.01-2.08) and 1.56 (1.06-2.29) (dominant model)). Adjusting for BMI attenuated the effect of the FTO variant, suggesting that the effect was mediated through its effect on BMI. Combining all risk alleles to a weighted risk score was significantly associated with the risk of postpartum diabetes (hazard ratio 1.11, 95% confidence interval 1.05-1.18, p = 0.00016 after adjustment for age and ethnicity). Conclusions: The TCF7L2 rs7903146 and FTO rs8050136 polymorphisms, and particularly a weighted risk score of T2D risk alleles, predict diabetes after GDM. Further studies in other populations are needed to confirm our results. (C) 2012 Elsevier Ireland Ltd. All rights reserved.
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| 7. |
- Ekelund, M., et al.
(författare)
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Prediction of postpartum diabetes in women with gestational diabetes mellitus
- 2010
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 53:3, s. 452-457
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Tidskriftsartikel (refereegranskat)abstract
- We studied the incidence of postpartum diabetes after gestational diabetes mellitus and investigated biochemical and clinical predictors of postpartum diabetes. We monitored 174 women with gestational diabetes by performing oral glucose tolerance tests during pregnancy as well as 1, 2 and 5 years postpartum. Women who developed impaired fasting glucose, impaired glucose tolerance or diabetes were compared with women who remained normoglycaemic at 5 years. Insulinogenic index, disposition index and HOMA-beta cell index were used to assess beta cell function; insulin resistance was estimated by HOMA index of insulin resistance. At 5 years postpartum, 30% of the women had developed diabetes and 51% some form of abnormal glucose tolerance. Women who developed diabetes had higher fasting glucose and HbA(1c) during pregnancy than those who remained normoglycaemic. They also had lower HOMA-beta cell index, insulinogenic index and disposition index than the normoglycaemic women. HbA(1c) and fasting glucose during pregnancy as well as the number of previous pregnancies and family history of diabetes were independent predictors of postpartum diabetes. HbA(1c) a parts per thousand yen4.7% (Swedish Mono S) or a parts per thousand yen5.7% (National Glycohemoglobin Standardization Program) and fasting blood glucose a parts per thousand yen5.2 mmol/l were associated with a four- to sixfold increased risk. Among women with gestational diabetes mellitus, those at risk of future diabetes can be identified by HbA(1c) and fasting glucose values in the upper normal range during pregnancy. A family history of diabetes and previous pregnancies further increase this risk.
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| 8. |
- Ekholm, Ella, et al.
(författare)
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Can complement factors 5 and 8 and transthyretin be used as biomarkers for MODY 1 (HNF4A-MODY) and MODY 3 (HNF1A-MODY)?
- 2008
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Ingår i: Diabetic Medicine: A journal of the British Diabetic Association. - : Wiley. - 1464-5491. ; May 29, s. 788-791
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Tidskriftsartikel (refereegranskat)abstract
- Aims Genetic testing is needed for the formal diagnosis of maturity-onset diabetes of the young (MODY), but this is not widely available. If any MODY biomarkers were known, these could possibly be used as an alternative. Hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha regulate transcription of genes encoding complement 5 (C5), complement 8 (C8) and transthyretin (TTR), suggesting that these could be potential biomarkers for the disease. We therefore set out to determine whether serum concentrations of C5, C8 and TTR can be used as biomarkers for patients with HNF4A-MODY and HNF1A-MODY. Methods The serum concentrations of C5, C8 and TTR were analysed in patients with mutations in the HNF-1alpha (n = 29) and EtaNuF-4alpha (n = 13) genes. Type 2 diabetic (n = 14) and healthy subjects (n = 20), matched for body mass index (BMI), served as diabetic and non-diabetic control groups, respectively. Results Type 2 diabetic patients had markedly increased levels of C5 and C8 compared with healthy control subjects. Levels of C5 and C8 correlated with glycated haemoglobin (C5: r = 0.48, P = 0.019). After adjustment for BMI, glycated haemoglobin, age and gender, HNF4A-MODY and HNF1A patients had reduced levels of C5 and C8 compared with Type 2 diabetic patients (C5: P = 0.001; C8: P = 0.004). In addition, patients with HNF4A-MODY, but not those with HNF1A-MODY, had decreased TTR compared with diabetic patients (P = 0.038). Conclusions Serum concentrations of C5 and C8 seem to distinguish HNF4A and HNF1A-MODY from other forms of diabetes. However, hyperglycaemia per se increases the serum concentrations, thereby attenuating their potential role as biomarkers for MODY.
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| 9. |
- Ekholm, Ella, et al.
(författare)
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Characterization of beta cell and incretin function in patients with MODY1 (HNF4A MODY) and MODY3 (HNF1A MODY) in a Swedish patient collection.
- 2011
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 1432-5233 .- 0940-5429.
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to evaluate the beta cell and incretin function in patients with HNF4A and HNF1A MODY during a test meal. Clinical characteristics and biochemical data (glucose, proinsulin, insulin, C-peptide, GLP-1 and GIP) during a test meal were compared between MODY patients from eight different families. BMI-matched T2D and healthy subjects were used as two separate control groups. The early phase of insulin secretion was attenuated in HNF4A, HNF1A MODY and T2D (AUC0-30 controls: 558.2 ± 101.2, HNF4A MODY: 93.8 ± 57.0, HNF1A MODY: 170.2 ± 64.5, T2D: 211.2 ± 65.3, P < 0.01). Markedly reduced levels of proinsulin were found in HNF4A MODY compared to T2D and that tended to be so also in HNF1A MODY (HNF4A MODY: 3.7 ± 1.2, HNF1A MODY: 8.3 ± 3.8 vs. T2D: 26.6 ± 14.3). Patients with HNF4A MODY had similar total GLP-1 and GIP responses as controls (GLP-1 AUC: (control: 823.9 ± 703.8, T2D: 556.4 ± 698.2, HNF4A MODY: 1,257.0 ± 999.3, HNF1A MODY: 697.1 ± 818.4) but with a different secretion pattern. The AUC insulin during the test meal was strongly correlated with the GIP secretion (Correlation coefficient 1.0, P < 0.001). No such correlation was seen for insulin and GLP-1. Patients with HNF4A and HNF1A MODY showed an attenuated early phase of insulin secretion similar to T2Ds. AUC insulin during the test meal was strongly correlated with GIP secretion, whereas no such correlation was seen for insulin and GLP-1. Thus, GIP may be a more important factor for insulin secretion than GLP-1 in MODY patients.
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| 10. |
- Enattah, Nabil Sabri, et al.
(författare)
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Evidence of still-ongoing convergence evolution of the lactase persistence T-13910 alleles in humans
- 2007
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 81:3, s. 615-625
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Tidskriftsartikel (refereegranskat)abstract
- A single-nucleotide variant, C/T-13910, located 14 kb upstream of the lactase gene (LCT), has been shown to be completely correlated with lactase persistence (LP) in northern Europeans. Here, we analyzed the background of the alleles carrying the critical variant in 1,611 DNA samples from 37 populations. Our data show that the T-13910 variant is found on two different, highly divergent haplotype backgrounds in the global populations. The first is the most common LP haplotype (LP H98) present in all populations analyzed, whereas the others (LP H8-H12), which originate from the same ancestral allelic haplotype, are found in geographically restricted populations living west of the Urals and north of the Caucasus. The global distribution pattern of LP T-13910 H98 supports the Caucasian origin of this allele. Age estimates based on different mathematical models show that the common LP T-13910 H98 allele (similar to 5,000-12,000 years old) is relatively older than the other geographically restricted LP alleles (similar to 1,400-3,000 years old). Our data about global allelic haplotypes of the lactose-tolerance variant imply that the T-13910 allele has been independently introduced more than once and that there is a still-ongoing process of convergent evolution of the LP alleles in humans.
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