| 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. |
- Albrechtsen, A., et al.
(författare)
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Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes
- 2013
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 56:2, s. 298-310
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Tidskriftsartikel (refereegranskat)abstract
- Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) > 1% with common metabolic phenotypes. The study comprised three stages. We performed medium-depth (8x) whole exome sequencing in 1,000 cases with type 2 diabetes, BMI > 27.5 kg/m(2) and hypertension and in 1,000 controls (stage 1). We selected 16,192 polymorphisms nominally associated (p < 0.05) with case-control status, from four selected annotation categories or from loci reported to associate with metabolic traits. These variants were genotyped in 15,989 Danes to search for association with 12 metabolic phenotypes (stage 2). In stage 3, polymorphisms showing potential associations were genotyped in a further 63,896 Europeans. Exome sequencing identified 70,182 polymorphisms with MAF > 1%. In stage 2 we identified 51 potential associations with one or more of eight metabolic phenotypes covered by 45 unique polymorphisms. In meta-analyses of stage 2 and stage 3 results, we demonstrated robust associations for coding polymorphisms in CD300LG (fasting HDL-cholesterol: MAF 3.5%, p = 8.5 x 10(-14)), COBLL1 (type 2 diabetes: MAF 12.5%, OR 0.88, p = 1.2 x 10(-11)) and MACF1 (type 2 diabetes: MAF 23.4%, OR 1.10, p = 8.2 x 10(-10)). We applied exome sequencing as a basis for finding genetic determinants of metabolic traits and show the existence of low-frequency and common coding polymorphisms with impact on common metabolic traits. Based on our study, coding polymorphisms with MAF above 1% do not seem to have particularly high effect sizes on the measured metabolic traits.
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| 3. |
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| 4. |
- Bogh, Morten, et al.
(författare)
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Narrowband ultraviolet B three times per week is more effective in treating vitamin D deficiency than 1600 IU oral vitamin D-3 per day: a randomized clinical trial
- 2012
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Ingår i: British Journal of Dermatology. - : Oxford University Press (OUP). - 1365-2133 .- 0007-0963. ; 167:3, s. 625-630
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Tidskriftsartikel (refereegranskat)abstract
- Background It is known that narrowband ultraviolet B (NB-UVB) radiation and oral vitamin D-3 supplementation can both improve serum levels of vitamin D, expressed as 25-hydroxyvitamin D-3 [25(OH)D-3]. However, surprisingly few studies have compared the effects of the two interventions in treating vitamin D deficiency. Objectives To compare the effect of NB-UVB exposure with oral vitamin D-3 supplementation on vitamin D levels in patients with vitamin D deficiency. Methods Seventy-three participants with vitamin D deficiency [25(OH)D-3 <= 25 nmol L-1] were consecutively enrolled from February 2010 to May 2011, avoiding the summer period (June to September). The participants were randomized into two groups, one receiving full body NB-UVB exposure three times per week, the other receiving 1600 IU (40 mu g) oral vitamin D-3 per day together with 1000 mg calcium. Thirty-two participants completed the 6-week study period, 16 in each group. In both groups blood samples were obtained at baseline and after 3 and 6 weeks. Results We found a significantly greater increase in 25(OH)D-3 levels (mean) in the NB-UVB treated group (from 19.2 to 75 nmol L-1) compared with the oral vitamin D-3 treated group (from 23.3 to 60.6 nmol L-1) after 6 weeks of treatment (P = 0.02), accompanied by a significant decrease in parathyroid hormone for the whole group (from 5.3 to 4.2 pmol L-1, P = 0.028). Conclusions Full body NB-UVB three times per week is more effective in treating vitamin D deficiency than prescription of a daily oral intake of 1600 IU (40 mu g) vitamin D-3.
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| 5. |
- Borgquist, Signe, et al.
(författare)
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Long-term exposure to insulin and volumetric mammographic density : Observational and genetic associations in the Karma study
- 2018
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Long-term insulin exposure has been implicated in breast cancer etiology, but epidemiological evidence remains inconclusive. The aims of this study were to investigate the association of insulin therapy with mammographic density (MD) as an intermediate phenotype for breast cancer and to assess associations with long-term elevated circulating insulin levels using a genetic score comprising 18 insulin-associated variants. Methods: We used data from the KARolinska MAmmography (Karma) project, a Swedish mammography screening cohort. Insulin-treated patients with type 1 (T1D, n = 122) and type 2 (T2D, n = 237) diabetes were identified through linkage with the Prescribed Drug Register and age-matched to 1771 women without diabetes. We assessed associations with treatment duration and insulin glargine use, and we further examined MD differences using non-insulin-treated T2D patients as an active comparator. MD was measured using a fully automated volumetric method, and analyses were adjusted for multiple potential confounders. Associations with the insulin genetic score were assessed in 9437 study participants without diabetes. Results: Compared with age-matched women without diabetes, insulin-treated T1D patients had greater percent dense (8.7% vs. 11.4%) and absolute dense volumes (59.7 vs. 64.7 cm3), and a smaller absolute nondense volume (615 vs. 491 cm3). Similar associations were observed for insulin-treated T2D, and estimates were not materially different in analyses comparing insulin-treated T2D patients with T2D patients receiving noninsulin glucose-lowering medication. In both T1D and T2D, the magnitude of the association with the absolute dense volume was highest for long-term insulin therapy (≥ 5 years) and the long-acting insulin analog glargine. No consistent evidence of differential associations by insulin treatment duration or type was found for percent dense and absolute nondense volumes. Genetically predicted insulin levels were positively associated with percent dense and absolute dense volumes, but not with the absolute nondense volume (percentage difference [95% CI] per 1-SD increase in insulin genetic score = 0.8 [0.0; 1.6], 0.9 [0.1; 1.8], and 0.1 [- 0.8; 0.9], respectively). Conclusions: The consistency in direction of association for insulin treatment and the insulin genetic score with the absolute dense volume suggest a causal influence of long-term increased insulin exposure on mammographic dense breast tissue.
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| 6. |
- Dencker, Magnus, et al.
(författare)
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Relationship between natriuretic peptides and echocardiography parameters in patients with poorly regulated type 2 diabetes.
- 2010
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Ingår i: Vascular Health and Risk Management. - 1178-2048. ; 6, s. 373-382
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Tidskriftsartikel (refereegranskat)abstract
- This study evaluated the relationship between natriuretic peptide levels and a wide range of echocardiography parameters in a population of thirty-three patients with poorly regulated type 2 diabetes, and no known heart failure. Natriuretic peptides brain natriuretic peptide (BNP) and N-terminal prohormone BNP (NT-proBNP) were measured. Transthoracic echocardiography was performed and cardiac volumes and ejection fraction were measured. Doppler and tissue Doppler were measured and diastolic function was stratified according to recent guidelines. Very few echocardiography parameters were correlated with BNP or NT-proBNP levels. However, left atrial end-systolic volume indexed for body surface area was correlated with natural logarithm (ln) BNP and ln NT-proBNP (r=0.62 and r=0.60; P<0.05). There were significant differences in ln BNP and ln NT-proBNP levels between those with normal and those with abnormal diastolic function (1.4 vs 3.1; P<0.001 and 3.4 vs 5.8; P<0.001). This study showed that very few echocardiography parameters were correlated with BNP or NT-proBNP levels in patients with poorly regulated type 2 diabetes, which in part contradicts previous studies in other diabetic populations. The exception was left atrial end-systolic volume that showed a moderate correlation with BNP or NT-proBNP levels. There were significant differences in BNP and NT-proBNP levels between the group with normal left ventricular diastolic function and the group with abnormal diastolic function.
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| 7. |
- Dorkhan, Mozhgan, et al.
(författare)
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A review of pioglitazone HCL and glimepiride in the treatment of type 2 diabetes.
- 2007
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Ingår i: Vascular Health and Risk Management. - 1178-2048. ; 3:5, s. 721-731
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Forskningsöversikt (refereegranskat)abstract
- Type 2 diabetes (T2D) is a progressive disorder with a consistent and steady increase in glycosylated hemoglobin (HbA1c) over time associated with enhanced risk of micro- and macrovascular complications and a substantial reduction in life expectancy. There are three major pathophysiologic abnormalities associated with T2D: impaired insulin secretion, excessive hepatic glucose output, and insulin resistance in skeletal muscle, liver, and adipose tissue. These defects have been treated in clinical praxis by use of oral insulin secretagogues (sulfonylureas/ glinides) or insulin, biguanides, and thiazolidinediones (TZDs) respectively. Pioglitazone HCL is an insulin sensitizer in the TZD family and glimepiride is an insulin secretagogue in the SU family. This article reviews mechanisms of action and clinical data behind the use of these two commonly used oral hypoglycemic agents with documented efficacy and good safety profile of once-daily administration, alone or in combination with insulin or metformin, in the management of T2D in terms of glycemic and non-glycemic effects, tolerability and side effects, and impact on vascular health.
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| 8. |
- Dorkhan, Mozhgan
(författare)
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Assessment and Treatment of Impaired Insulin- Secretion and Action in Type 2 Diabetes
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Type 2 diabetes (T2D) is a disease characterised by varying degrees of defect in insulin secretion and insulin sensitivity and associated with increased morbidity and mortality. Optimal glycaemic control reduces the progression of diabetic complications. Over time, there is a steady deterioration of glycaemic control that raises the need for effective therapy targeted at the underlying defects in order to achieve treatment goals. The methods available for assessment of insulin secretion and insulin sensitivity have not been suitable for use in clinical practice. The introduction of thiazolidinediones (TZDs) targeting the insulin resistance component of T2D has been promising but accompanied with some adverse effects, mainly fluid retention and heart failure. In this thesis, a simple method for independent measurement of β-cell function and insulin sensitivity at the same time (combined glucagon-insulin tolerance test, GITT) has been developed (Paper I). We also evaluated the effect of a TZD (pioglitazone) and a long-acting insulin (glargine) as add-on in the treatment of patients with T2D, not achieving glycaemic goals when treated with classic anti-diabetic agents on glycaemic control, insulin sensitivity, β-cell function and markers of increased cardiovascular load (Papers II &IV). We also investigated the effect of pioglitazone on eye protrusion (Paper III). GITT showed good reproducibility and the index of insulin sensitivity derived from the GITT showed good correlation with the M-value from the euglycaemic clamp. The test also showed good discriminating capacity between individuals with varying degrees of glucose tolerance (Paper I). Both pioglitazone and insulin glargine were effective in reducing HbA1c levels in combination with other oral glucose lowering agents but pioglitazone caused fluid retention and increased levels of natriuretic peptides suggesting increased cardiac load (Papers II & IV). While pioglitazone improved insulin sensitivity and lipids, insulin glargine resulted in improved β-cell function (Paper IV). Pioglitazone also caused an increase in eye protrusion in a subgroup of patients, probably by causing an increase in retrobulbar adipogenesis (Paper III). Taken together, these results can hopefully help clinicians in the choice of novel add-on treatment and in monitoring of untoward side effects. GITT seems to be a promising tool for assessing insulin secretion and action in clinical practice.
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| 9. |
- Dorkhan, Mozhgan, et al.
(författare)
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Differences in effects of insulin glargine or pioglitazone added to oral anti-diabetic therapy in patients with type 2 diabetes What to add-Insulin glargine or pioglitazone?
- 2008
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Ingår i: Diabetes Research and Clinical Practice. - : Elsevier BV. - 1872-8227 .- 0168-8227. ; 82, s. 340-345
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: While metformin is the first line treatment in type 2 diabetes, the best way to escalate therapy is not always clear, particularly whether to add one or two oral agents or to introduce insulin. METHODS: Thirty-six patients inadequately controlled on metformin and sulfonylurea/meglitinide were randomized to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Insulin was up-titrated to achieve fasting plasma glucose <6mmol/l. Pioglitazone was increased to 45mg/day after 16 weeks if HbA1c>6.2%. beta-Cell function and insulin sensitivity were assessed by measuring insulin, proinsulin and adiponectin, and in a subgroup using a combined glucagon-stimulated C-peptide test and insulin tolerance test (GITT). Lipids and natriuretic peptides were measured at start and end of study. RESULTS: The reduction in HbA1c was slightly greater in the insulin glargine group and used as co-variate when analysing other variables. The effect on beta-cell function was more favourable with insulin glargine measured by proinsulin (42+/-48 to 19+/-16, p=0.01 vs. 36+/-26 to 27+/-16 p=0.04) while the improvement in insulin sensitivity measured by adiponectin (7.5+/-3.7 to 15+/-10, p<0.01 vs. 8.7+/-4 to 7.6+/-3, p=0.04) and HDL cholesterol (1.10+/-0.24 to 1.24+/-0.3, p<0.01 vs. 1.08+/-0.35 to 1.04+/-0.33, ns) (all p between groups <0.01) was more favourable in pioglitazone group. Pioglitazone caused significant increase in natriuretic peptides (BNP pmol/l 6.6+/-5.2 to 13.7+/-16.1, p=0.04 vs. 8.8+/-11.6 to 8.6+/-10.6, ns, p between groups 0.028). CONCLUSIONS: The results demonstrate characteristic differences in the effects of insulin glargine vs. pioglitazone on measures of beta-cell function and insulin sensitivity as well as cardiac load.
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| 10. |
- Dorkhan, Mozhgan, et al.
(författare)
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Effect of pioglitazone versus insulin glargine on cardiac size, function, and measures of fluid retention in patients with type 2 diabetes
- 2009
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Both insulin and thiazolidinediones (TZDs) are effective in the treatment of hyperglycaemia and amelioration of insulin resistance in type 2 diabetes but have side effects including weight gain and fluid retention. The use of TZDs has been further hampered by the risk of adverse cardiovascular events including heart failure. The present study evaluated the effect of pioglitazone or insulin glargine on cardiac function and size as well as on surrogate markers of fluid retention such as weight, haemoglobin and natriuretic peptides. Methods: Thirty patients with inadequate glycaemic control on metformin and sulfonylurea were randomised to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Echocardiographic data and blood samples were collected from the two groups before the start of the treatment and after 26 weeks. Left ventricular end-diastolic and left atrial end-systolic volumes were quantified, weight measured and blood samples analyzed. Results: After 26 weeks of treatment, the changes in HbAlc, weight and haemoglobin were similar between the two groups. HDL increased significantly in the pioglitazone group. While there was an increase in natriuretic peptides in the pioglitazone group (NT-proBNP 11.4 +/- 19.6 to 22.8 +/- 44.0, p = 0.046), the difference between the treatment groups was not significant. Left ventricular end-diastolic volume increased by 11% and left atrial end-systolic volume by 17% in the pioglitazone group (Both, p < 0.05, between treatment groups). There was a borderline significant increase in ejection fraction in the pioglitazone group. Conclusion: This randomised pilot-study showed that six-month treatment with pioglitazone induced significant increases in natriuretic peptides and alterations of cardiac size. These changes were not observed with insulin glargine, which also is known to induce fluid retention. Larger randomised trials are warranted to confirm these findings.
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| 11. |
- Dorkhan, Mozhgan, et al.
(författare)
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Independent measures of insulin secretion and insulin sensitivity during the same test: the glucagon-insulin tolerance test.
- 2008
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 264, s. 62-71
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Tidskriftsartikel (refereegranskat)abstract
- Background. To validate a test for independent assessment of insulin secretion and insulin sensitivity during the same occasion for metabolic studies in clinical practice, i.e. combined glucagon-stimulated C-peptide test and insulin tolerance test (GITT). Subjects and methods. We measured C-peptide response to 0.5 mg of intravenous glucagon followed 30 min later by administration of 0.05 U kg(-1) insulin (insulin tolerance test, ITT). Ten subjects with normal glucose tolerance participated on different days in an ITT, glucagon-C-peptide test, ITT followed by glucagon-C-peptide test and glucagon-C-peptide test followed by ITT to establish whether and how the tests could be combined. The test was then repeated in nine patients with type 2 diabetes to investigate its reproducibility. In 20 subjects with varying degrees of glucose tolerance, the test was compared with the Botnia clamp (an intravenous glucose tolerance test combined with a euglycaemic hyperinsulinemic clamp). Results. When ITT preceded the glucagon test, C-peptide response was blunted. Therefore, we first administered glucagon and then insulin (GITT). The K(ITT) from the GITT was reproducible (CV = 13 %) and correlated strongly with the glucose disposal rate from the Botnia clamp (r = 0.87, r(2) = 0.75, P < 0.001). The C-peptide response to glucagon was reproducible (CV = 13 %). The disposition index, providing a measure of beta-cell function adjusted for insulin sensitivity, calculated from the GITT showed good discrimination between individuals with varying degrees of glucose tolerance. Conclusions. The GITT provides simple, reproducible and independent estimates of insulin sensitivity and secretion on the same occasion for metabolic studies in individuals with normal and abnormal glucose tolerance.
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| 12. |
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| 13. |
- Dorkhan, Mozhgan, et al.
(författare)
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Treatment with pioglitazone induced significant, reversible mitral regurgitation
- 2008
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 7:12
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Tidskriftsartikel (refereegranskat)abstract
- There has in recent years been great concern about possible cardiac side effects of thiazolidinediones ( TZDs). We present a case-report of a 60 year-old male who developed significant mitral regurgitation during six months treatment with pioglitazone in parallel with laboratory indications of fluid retention. Echocardiography six months after discontinuation of medication showed regression of mitral regurgitation and the laboratory parameters were also normalized. It is noteworthy that six months treatment with pioglitazone could induce significant valve dysfunction, which was reversible, and this underlines the importance of carefully monitoring patients when placing them on treatment with TZDs.
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| 14. |
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| 15. |
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| 16. |
- Gaulton, Kyle J, et al.
(författare)
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Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
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Tidskriftsartikel (refereegranskat)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
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| 17. |
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| 18. |
- Löfvenborg, J E, et al.
(författare)
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Fatty fish consumption and risk of latent autoimmune diabetes in adults
- 2014
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Ingår i: Nutrition & Diabetes. - : Springer Science and Business Media LLC. - 2044-4052. ; 4, s. e139-
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: It has been suggested that intake of fatty fish may protect against both type 1 and type 2 diabetes. Hypotheses rest on the high marine omega-3 fatty acid eicosapentaenoic acid+docosahexaenoic acid (EPA+DHA) and vitamin D contents, with possible beneficial effects on immune function and glucose metabolism. Our aim was to investigate, for the first time, fatty fish consumption in relation to the risk of latent autoimmune diabetes in adults (LADA).METHODS: Analyses were based on data from a Swedish case-control study with incident cases of LADA (n=89) and type 2 diabetes (n=462) and randomly selected diabetes-free controls (n=1007). Diabetes classification was based on the onset of age (⩾35), glutamic acid decarboxylase autoantibodies, and C-peptide. A validated food frequency questionnaire was used to derive information on previous intake of fish, polyunsaturated long-chain omega-3 fatty acids (n-3 PUFA) and supplementation of fish oil and vitamin D. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression, adjusted for age, gender, body mass index (BMI), family history of diabetes, physical activity, smoking, education, and consumption of alcohol, fruit, vegetables and red meat.RESULTS: Weekly fatty fish consumption (⩾1 vs <1 serving per week), was associated with a reduced risk of LADA but not type 2 diabetes (OR 0.51, 95% CI 0.30-0.87, and 1.01, 95% CI 0.74-1.39, respectively). Similar associations were seen for estimated intake of n-3 PUFA (⩾0.3 g per day; LADA: OR 0.60, 95% CI 0.35-1.03, type 2 diabetes: OR 1.14, 95% CI 0.79-1.58) and fish oil supplementation (LADA: OR 0.47, 95% CI 0.19-1.12, type 2 diabetes: OR 1.58, 95% CI 1.08-2.31).CONCLUSIONS: Our findings suggest that fatty fish consumption may reduce the risk of LADA, possibly through effects of marine-originated omega-3 fatty acids.
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| 19. |
- Löfvenborg, Josefin E., et al.
(författare)
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Genotypes of HLA, TCF7L2, and FTO as potential modifiers of the association between sweetened beverage consumption and risk of LADA and type 2 diabetes
- 2020
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 59:1, s. 127-135
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Sweetened beverage consumption is associated with type 2 diabetes (T2D) and LADA. We investigated to what extent this association is mediated by BMI and whether it is modified by genotypes of HLA, TCF7L2 rs7903146, or FTO rs9939609. Methods: Swedish case–control data including incident cases of LADA (n = 386) and T2D (n = 1253) with matched population-based controls (n = 1545) was used. We estimated adjusted ORs of diabetes (95% CI) in relation to sweetened beverage intake (per daily 200 mL serving) and genotypes. The impact of BMI was estimated using causal mediation methodology. Associations with HOMA-IR and HOMA-B were explored through linear regression. Results: Sweetened beverage intake was associated with increased risk of LADA (OR 1.15, 95% CI 1.03–1.29) and T2D (OR 1.21, 1.11–1.32). BMI was estimated to mediate 17% (LADA) and 56% (T2D) of the total risk. LADA was associated with risk variants of HLA (3.44, 2.63–4.50) and TCF7L2 (1.27, 1.00–1.61) but not FTO. Only among non-carriers of high-risk HLA genotypes was sweetened beverage intake associated with risk of LADA (OR 1.32, 1.06–1.56) and HOMA-IR (beta = 0.162, p = 0.0047). T2D was associated with TCF7L2 and FTO but not HLA, and the risk conferred by sweetened beverages appeared modified by FTO (OR 1.45, 95% CI 1.21–1.73 in non-carriers). Conclusions: Our findings suggest that sweetened beverages are associated with LADA and T2D partly through mediation by excess weight, but possibly also through other mechanisms including adverse effects on insulin sensitivity. These effects seem more pronounced in individuals without genetic susceptibility.
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| 20. |
- Löfvenborg, Josefin E., et al.
(författare)
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Sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes
- 2016
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 175:6, s. 605-614
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Sweetened beverage intake is associated with increased risk of type 2 diabetes, but its association with autoimmune diabetes is unclear. We aimed to investigate sweetened beverage intake and risk of latent autoimmune diabetes in adults (LADA); autoimmune diabetes with features of type 2 diabetes. Design/methods: Data from a Swedish population-based study was used, including incident cases of LADA (n = 357) and type 2 diabetes (n = 1136) and randomly selected controls (n = 1371). Diabetes classification was based on onset age (≥35), glutamic acid decarboxylase autoantibodies (GADA) and C-peptide. Sweetened beverage intake information was derived from a validated food frequency questionnaire. ORs adjusted for age, sex, family history of diabetes, education, lifestyle, diet, energy intake and BMI were estimated using logistic regression. Results: Daily intake of >2 servings of sweetened beverages (consumed by 6% of participants) was associated with increased risk of LADA (OR: 1.99, 95% CI: 1.11-3.56), and for each 200 mL daily serving, OR was 1.15 (95% CI: 1.02-1.29). Findings were similar for sugar-sweetened (OR: 1.18, 95% CI: 1.00-1.39) and artificially sweetened beverages (OR: 1.12, 95% CI: 0.95-1.32). Similarly, each daily serving increment in total sweetened beverage conferred 20% higher type 2 diabetes risk (95% CI: 1.07-1.34). In type 2 diabetes patients, high consumers displayed higher HOMA-IR levels (4.5 vs 3.5, P = 0.0002), but lower HOMA-B levels (55 vs 70, P = 0.0378) than non-consumers. Similar tendencies were seen in LADA. Conclusions: High intake of sweetened beverages was associated with increased risk of LADA. The observed relationship resembled that with type 2 diabetes, suggesting common pathways possibly involving insulin resistance.
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| 21. |
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| 22. |
- Martinell, Mats, 1971-
(författare)
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Diabetes Mellitus at the Time for Diagnosis : Studies on Prognostic Factors
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The aim for this thesis was to identify prognostic factors for chronic diabetes complications that exist at the time of diabetes diagnosis.Low level of education (<12 years) and low income (<60% of median) was found to increase the risk to have high (>70 mmol/mol) HbA1c at the time of diagnosis with 34 % and 35 %, respectively.Prevalence of diabetic retinopathy (DR) was 12% in a cohort of patients newly diagnosed with diabetes. Diabetic macular edema was present in 11% of patients with type 2 diabetes (T2D) and 13% of those with Latent Autoimmune Diabetes in Adults (LADA). Low beta cell function and low level of education increased the risk for DR with 110% and 43%, respectively. For every unit of increase in body mass index, the risk for DR was reduced by 3%.The cellular immunology of LADA patients was a mixture of that observed in both type 1 (T1D) and T2D patients. Compared to patients with T1D, LADA patients had more B-regulatory lymphocytes and antigen presenting cells capable of producing interleukine-35. This indicates a higher anti-inflammatory capacity in LADA patients compared to type T1D patients.By imputing age, body mass index, HbA1c at diagnosis, beta cell function and insulin resistance in a cluster analysis, five distinct diabetes clusters were identified. The four clusters representing T2D patients differed in incidence of DR, nephropathy and non-alcoholic fatty liver disease. This was replicated with similar results in three geographically separate populations.By studying socioeconomic background and factors present at the time of diagnosis we can better predict prognosis for chronic diabetes complications. These findings may facilitate better-targeted diabetes screening programs and more individually tailored treatment regimes.
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| 23. |
- Martinell, Mats, 1971-, et al.
(författare)
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Education immigration and income as risk factors for hemoglobin a1c >70 mmol/mol when diagnosed with type 2 diabetes or latent autoimmune diabetes in adult : A population-based cohort study
- 2017
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Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of this research is to study education, income and immigration as risk factors for high hemoglobin A1c (HbA1c >70 mmol/mol (8.6%)) when diagnosed with type 2 diabetes (T2D) or latent autoimmune diabetes in the adult (LADA). Research design and methods Patients were included from the All New Diabetics in Scania study (2008-2013). Level of education, disposable income and immigration year were retrieved from the longitudinal integrated database for labour market research (LISA) register compiled by Statistics Sweden. Logistic regression models were used to estimate ORs for HbA1c >70 mmol/mol (8.6%) at diagnosis. Results A total of 3794 patients with incident T2D (n=3 525) or LADA (n=269) were included. Patients with T2D with a low (≤9 years) or medium (10-12 years) levels of education were more likely to have high HbA1c at diagnosis compared with patients with T2D with a high (>12 years) level of education (OR 1.34, 95% CI 1.08 to1.66, OR 1.26, 95% CI 1.03 to 1.54). Low-income patients with T2D (<60% of median) were more likely to have high HbA1c at diagnosis compared with high-income patients withT2D (>150% of median) (OR 1.35, 95% CI 1.02 to 1.79). Conclusions Patients with lower levels of education or low income and are more likely to have HbA1c is >70 mmol/ mol (8.6%) when diagnosed with T2D. An understanding of how socioeconomic position influences the clinical presentation at diagnosis may facilitate screening programs designed to target populations at risk for delayed diagnosis.
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| 24. |
- Martinell, Mats, 1971-, et al.
(författare)
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Prevalence and risk factors for diabetic retinopathy at diagnosis (DRAD) in patients recently diagnosed with type 2 diabetes (T2D) or latent autoimmune diabetes in the adult (LADA)
- 2016
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Ingår i: Journal of diabetes and its complications. - : Elsevier BV. - 1056-8727 .- 1873-460X. ; 30:8, s. 1456-1461
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To study prevalence of diabetic retinopathy (DR) at diagnosis (DRAD) and to estimate contributing risk by sociodemographic, cardiovascular and metabolic characteristics present in patients recently diagnosed with type 2 diabetes (T2D) or latent autoimmune diabetes in the adult (LADA).METHODS: Patients (n=2174) recently diagnosed T2D (93%) or LADA (7%) were included upon arrival for their baseline DR screening. Fundus photographs of 4902 eyes were graded by a senior ophthalmologist according to the International Diabetic Retinopathy Disease Severity Scale. Official registers held by Statistics Sweden provided sociodemographic variables. The National Patient Register and Swedish Prescribed Drug Register were used to assess cardiovascular risk. Beta cell function (HOMA2%b) and insulin sensitivity (HOMA2%s) were estimated from fasting (f) C-Peptide using the homeostasis model assessment (HOMA) 2 calculator. Odds ratios (OR) for DRAD were estimated using generalized estimating equation models.RESULTS: The prevalence of DRAD was 12% (7% mild and 5% moderate) and of diabetic macular edema it was 11% (all within vascular arch). The prevalence did not significantly differ between T2D and LADA. Due to sample size, the regression analysis of LADA patients did not yield any significant estimates. In T2D low educational level (≤9years) increased risk for DRAD by 44% (OR 1.44; 95% CI 1.07-1.93) and <50% beta-cell function adjusted for HbA1c and insulin sensitivity at diagnosis increased the risk by 77% (OR 1.77; 95% CI 1.28-2.44). For every unit increase in BMI, risk for DRAD decreased by 3% (OR 0.97; 95% CI 0.95-0.99).CONCLUSIONS: DRAD prevalence in patients recently diagnosed with T2D or is 12%. Low educational level and low beta cell function at diagnosis are risk factors for DRAD. Estimation of beta cell function from (f)C-Peptide and (f)P-Glucose may be a valuable tool in identifying patients at risk for DRAD.
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| 25. |
- Rasouli, Bahareh, et al.
(författare)
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Alcohol and the risk for LADA: results based on the Swedish ESTRID study.
- 2014
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Ingår i: European Journal of Endocrinology. - 1479-683X. ; 171:5, s. 535-543
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Tidskriftsartikel (refereegranskat)abstract
- Objective Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes. Our aim was to investigate whether alcohol consumption is associated with risk of latent autoimmune diabetes in adults (LADA), an autoimmune form of diabetes with features of type 2 diabetes. Design Population-based case-control study Methods We used data from ESTRID case-control study carried out between 2010 and 2013, including 250 incident cases of LADA (glutamic acid decarboxylase antibodies [GADA] positive) and 764 cases of type 2 diabetes (GADA negative), and 1012 randomly selected controls aged ≥35. Logistic regression was used to estimate the odds ratios (OR) of diabetes in relation to alcohol intake, adjusted for age, sex, BMI, family history of diabetes, smoking, and education. Results Alcohol consumption was inversely associated with the risk of type 2 diabetes (OR 0.95, 95% confidence interval (CI); 0.92-0.99 for every 5-g increment in daily intake). Similar results were seen for LADA, but stratification by median GADA levels revealed that the results only pertained to LADA with low GADA (OR 0.85; 95% 0.76-0.94 per 5g alcohol/day), whereas no association was seen with LADA high GADA (OR 1.00, 95% CI; 0.94-1.06 per 5g/day). Every 5-g increment of daily alcohol intake was associated with a 10% increase in GADA levels (p=0.0312), and a10% reduction in HOMA-IR (p=0.0418). Conclusions Our findings indicate that alcohol intake may reduce risk of type 2 diabetes and type 2-like LADA, but has no beneficial effects on diabetes-related autoimmunity.
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| 26. |
- Rasouli, Bahareh, et al.
(författare)
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Alcohol and the risk for latent autoimmune diabetes in adults : results based on Swedish ESTRID study
- 2014
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Ingår i: European Journal of Endocrinology. - 0804-4643 .- 1479-683X. ; 171:5, s. 535-543
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes. Our aim was to investigate whether alcohol consumption is associated with the risk of latent autoimmune diabetes in adults (LADA), an autoimmune form of diabetes with features of type 2 diabetes. Design: A population-based case-control study was carried out to investigate the association of alcohol consumption and the risk of LADA. Methods: We used data from the ESTRID case-control study carried out between 2010 and 2013, including 250 incident cases of LADA (glutamic acid decarboxylase antibodies (GADAs) positive) and 764 cases of type 2 diabetes (GADA negative), and 1012 randomly selected controls aged >= 35. Logistic regression was used to estimate the odds ratios (ORs) of diabetes in relation to alcohol intake, adjusted for age, sex, BMI, family history of diabetes, smoking, and education. Results: Alcohol consumption was inversely associated with the risk of type 2 diabetes (OR 0.95, 95% CI 0.92-0.99 for every 5-g increment in daily intake). Similar results were observed for LADA, but stratification by median GADA levels revealed that the results only pertained to LADA with low GADA levels (OR 0.85, 95% CI 0.76-0.94/5 g alcohol per day), whereas no association was observed with LADA having high GADA levels (OR 1.00, 95% CI 0.94-1.06/5 g per day). Every 5-g increment of daily alcohol intake was associated with a 10% increase in GADA levels (P=0.0312), and a 10% reduction in homeostasis model assessment of insulin resistance (P=0.0418). Conclusions: Our findings indicate that alcohol intake may reduce the risk of type 2 diabetes and type 2-like LADA, but has no beneficial effects on diabetes-related autoimmunity.
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