uu.seUppsala University Publications
Change search
Link to record
Permanent link

Direct link
BETA
Publications (10 of 27) Show all publications
Ahlqvist, E., Storm, P., Käräjämäki, A., Martinell, M., Dorkhan, M., Carlsson, A., . . . Groop, L. (2018). Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. The Lancet Diabetes and Endocrinology, 6(5), 361-369
Open this publication in new window or tab >>Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables
Show others...
2018 (English)In: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 6, no 5, p. 361-369Article in journal (Refereed) Published
Abstract [en]

 Background

Diabetes 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.

Methods

We 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.

Findings

We 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.

Interpretation

We 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.

National Category
Endocrinology and Diabetes
Research subject
Endocrinology and Diabetology
Identifiers
urn:nbn:se:uu:diva-328355 (URN)10.1016/S2213-8587(18)30051-2 (DOI)000430631600013 ()
Projects
Diabetes Mellitus at the Time for Diagnosis, Studies on Prognostic Factors
Funder
EXODIAB - Excellence of Diabetes Research in Sweden, 2009-1039Swedish Research Council, 521-2010-3490Swedish Research Council, 2010-5983Linnaeus research environment CADICS, 349-2006-237
Note

Tredjeförfattarskapet delas av tredje och fjärde författaren.

Available from: 2017-08-22 Created: 2017-08-22 Last updated: 2018-07-20Bibliographically approved
Hjort, R., Ahlqvist, E., Carlsson, P.-O., Grill, V., Groop, L., Martinell, M., . . . Carlsson, S. (2018). Overweight, obesity and the risk of LADA: results from a Swedish case-control study and the Norwegian HUNT Study. Diabetologia, 61(6), 1333-1343
Open this publication in new window or tab >>Overweight, obesity and the risk of LADA: results from a Swedish case-control study and the Norwegian HUNT Study
Show others...
2018 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 61, no 6, p. 1333-1343Article in journal (Refereed) Published
Abstract [en]

Aims/hypothesis Excessive weight is a risk factor for type 2 diabetes, but its role in the promotion of autoimmune diabetes is not clear. We investigated the risk of latent autoimmune diabetes in adults (LADA) in relation to overweight/obesity in two large population-based studies. Methods Analyses were based on incident cases of LADA (n = 425) and type 2 diabetes (n = 1420), and 1704 randomly selected control participants from a Swedish case-control study and prospective data from the Norwegian HUNT Study including 147 people with LADA and 1,012,957 person-years of follow-up (1984-2008). We present adjusted ORs and HRs with 95% CI. Results In the Swedish data, obesity was associated with an increased risk of LADA (OR 2.93, 95% CI 2.17, 3.97), which was even stronger for type 2 diabetes (OR 18.88, 95% CI 14.29, 24.94). The association was stronger in LADA with low GAD antibody (GADA; <median) (OR 4.25; 95% CI 2.76, 6.52) but present also in LADA with high GADA (OR 2.14; 95% CI 1.42, 3.24). In the Swedish data, obese vs normal weight LADA patients had lower GADA levels, better beta cell function, and were more likely to have low-risk HLA-genotypes. The combination of overweight and family history of diabetes (FHD) conferred an OR of 4.57 (95% CI 3.27, 6.39) for LADA and 24.51 (95% CI 17.82, 33.71) for type 2 diabetes. Prospective data from HUNT indicated even stronger associations; HR for LADA was 6.07 (95% CI 3.76, 9.78) for obesity and 7.45 (95% CI 4.02, 13.82) for overweight and FHD. Conclusions/interpretation Overweight/obesity is associated with increased risk of LADA, particularly when in combination with FHD. These findings support the hypothesis that, even in the presence of autoimmunity, factors linked to insulin resistance, such as excessive weight, could promote onset of diabetes.

Place, publisher, year, edition, pages
SPRINGER, 2018
Keywords
ANDIS, ANDiU, Body mass index, Case-control study, ESTRID, HUNT Study, LADA, Latent autoimmune diabetes in adults, Prospective study, Type 2 diabetes
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-356380 (URN)10.1007/s00125-018-4596-0 (DOI)000431650800011 ()29589073 (PubMedID)
Funder
Forte, Swedish Research Council for Health, Working Life and WelfareEU, European Research Council, GA 269045Swedish Research Council
Available from: 2018-08-15 Created: 2018-08-15 Last updated: 2018-08-15Bibliographically approved
Carlbom, L., Espes, D., Lubberink, M., Martinell, M., Johansson, L., Ahlström, H., . . . Eriksson, O. (2017). [(11)C]5-Hydroxy-Tryptophan PET for Assessment of Islet Mass During Progression of Type 2 Diabetes. Diabetes, 66(5), 1286-1292
Open this publication in new window or tab >>[(11)C]5-Hydroxy-Tryptophan PET for Assessment of Islet Mass During Progression of Type 2 Diabetes
Show others...
2017 (English)In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 66, no 5, p. 1286-1292Article in journal (Refereed) Published
Abstract [en]

[(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP) PET of the pancreas has been shown to be a surrogate imaging biomarker of pancreatic islet mass. The change in islet mass in different stages of type 2 diabetes (T2D) as measured by non-invasive imaging is currently unknown. Here, we describe a cross-sectional study where subjects at different stages of T2D development with expected stratification of pancreatic islet mass were examined in relation to non-diabetic individuals. The primary outcome was the [(11)C]5-HTP uptake and retention in pancreas, as a surrogate marker for the endogenous islet mass.We found that metabolic testing indicated a progressive loss of beta cell function, but that this was not mirrored by a decrease in [(11)C]5-HTP tracer accumulation in the pancreas. This provides evidence of retained islet mass despite decreased beta cell function. The results herein indicates that beta cell dedifferentiation, and not necessarily endocrine cell loss, constitute a major cause of beta cell failure in T2D.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-316831 (URN)10.2337/db16-1449 (DOI)000399799800022 ()28246291 (PubMedID)
Funder
Swedish Society for Medical Research (SSMF), K2015-54X-12219-19-4 K2013-64X-08268-26-3 K2013-55X-15043 921-2014-7054Novo NordiskSwedish Child Diabetes Foundation
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2017-03-07 Created: 2017-03-07 Last updated: 2018-01-25Bibliographically approved
Ahlqvist, E., Karajamaki, A., Martinell, M., Storm, P., Dorkhan, M., Vikman, P., . . . Groop, L. (2017). Clustering of diabetes into novel subgroups provides improved prediction of outcome. Paper presented at 53rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 11-15, 2017, Lisbon, PORTUGAL. Diabetologia, 60, S117-S117
Open this publication in new window or tab >>Clustering of diabetes into novel subgroups provides improved prediction of outcome
Show others...
2017 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S117-S117Article in journal, Meeting abstract (Other academic) Published
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-346984 (URN)000408315001027 ()
Conference
53rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 11-15, 2017, Lisbon, PORTUGAL
Available from: 2018-03-23 Created: 2018-03-23 Last updated: 2018-03-23Bibliographically approved
Hjort, R., Alfredsson, L., Andersson, T., Carlsson, P.-O., Grill, V., Groop, L., . . . Carlsson, S. (2017). Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA). Diabetes & Metabolism, 43(6), 536-542
Open this publication in new window or tab >>Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA)
Show others...
2017 (English)In: Diabetes & Metabolism, ISSN 1262-3636, E-ISSN 1878-1780, Vol. 43, no 6, p. 536-542Article in journal (Refereed) Published
Abstract [en]

Background. - A family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives. Methods. - Data from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n = 378] and T2D (GADA-negative, n = 1199), and their matched controls (n = 1484). First-degree relatives with disease onset at age < 40 years and taking insulin treatment were classified as type 1 diabetes (T1D) or, if otherwise, as T2D. Odds ratios (ORs) were adjusted for age, gender, BMI, education and smoking. Cases were genotyped for high- and low-risk HLA genotypes. Results. - Both FHD-T1D (OR: 5.8; 95% CI: 3.2-10.3) and FHD-T2D (OR: 1.9; 95% CI: 1.5-2.5) were associated with an increased risk of LADA, whereas the risk of T2D was associated with FHD-T2D (OR: 2.7; 95% CI: 2.2-3.3), but not FHD-Tl D. In LADA patients, FHD-T1D vs FHD-T2D was associated with higher GADA but lower C-peptide levels, lower prevalence of low-risk HLA genotypes (5.0% vs 28.6%, respectively; P = 0.038) and a tendency for higher prevalence of high-risk genotypes (90.0% vs 69.1%, respectively; P = 0.0576). Conclusion. - The risk of LADA is substantially increased with FHD-Tl D but also, albeit significantly less so, with FHD-T2D. This supports the idea of LADA as a mix of both T1D and T2D, but suggests that the genes related to T1D have greater impact. LADA patients with FHD-Tl D had more T1D-like features, emphasizing the heterogeneity of LADA. (C) 2017 Elsevier Masson SAS. All rights reserved.

Place, publisher, year, edition, pages
MASSON EDITEUR, 2017
Keywords
Autoimmune diabetes, Case-control study, Family history of diabetes, Heredity, Latent autoimmune diabetes in adults, Type 2 diabetes
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-340480 (URN)10.1016/j.diabet.2017.05.010 (DOI)000419260000006 ()
Available from: 2018-01-31 Created: 2018-01-31 Last updated: 2018-01-31Bibliographically approved
Hjort, R., Lofvenborg, J. E., Ahlqvist, E., Alfredsson, L., Andersson, T., Carlsson, P.-O., . . . Carlsson, S. (2017). Overweight, obesity, genetic susceptibility and the risk of LADA: Latent Autoimmune Diabetes in Adults. Paper presented at 53rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 11-15, 2017, Lisbon, PORTUGAL. Diabetologia, 60(S1), S118-S118, Article ID 252.
Open this publication in new window or tab >>Overweight, obesity, genetic susceptibility and the risk of LADA: Latent Autoimmune Diabetes in Adults
Show others...
2017 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, no S1, p. S118-S118, article id 252Article in journal, Meeting abstract (Other academic) Published
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-347285 (URN)000408315001030 ()
Conference
53rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 11-15, 2017, Lisbon, PORTUGAL
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-03Bibliographically approved
Rasouli, B., Andersson, T., Carlsson, P.-O., Hjort, R., Lofvenborg, J. E., Martinell, M., . . . Carlsson, S. (2017). Serious life events and the risk of latent autoimmune diabetes in adults (LADA) and Type 2 diabetes. Diabetic Medicine, 34(9), 1259-1263
Open this publication in new window or tab >>Serious life events and the risk of latent autoimmune diabetes in adults (LADA) and Type 2 diabetes
Show others...
2017 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 34, no 9, p. 1259-1263Article in journal (Refereed) Published
Abstract [en]

AimIt has been suggested that experiencing serious life events may promote Type1 diabetes in children. Studies in adults are lacking, as are studies on the interaction of life events with genetic factors. We aimed to investigate life events and the risk of latent autoimmune diabetes in adults (LADA) and Type 2 diabetes while taking into account HLA genotype. MethodsAnalysis was based on 425 incident cases of LADA, 1417 incident cases of Type 2 diabetes and 1702 population-based controls recruited in Sweden between 2010 and 2016. Self-reported information on life events including conflicts, divorce, illness/accidents, death and financial problems experienced during the 5years preceding diagnosis/index year was used. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated by logistic regression and adjusted for age, sex, BMI, family history of diabetes, smoking, physical activity and education. ResultsOverall there was no association between experience of any life event and either LADA (OR 0.86, 95% CI 0.68-1.08) or Type2 diabetes (OR 1.00, 95% CI 0.83-1.21). The results were similar for individual events as well as in separate analysis of men and women. Similar results were seen in more autoimmune LADA (glutamic acid decarboxylase antibodies >median) [OR (any life event) 0.88, 95% CI 0.64-1.21] and in LADA carriers of the high-risk HLADR4-DQ8 genotype (OR 0.89, 95% CI 0.61-1.29). ConclusionsOur findings indicate that experience of a serious life event, including the death of a family member, divorce or financial problems, is not associated with an increased risk of LADA, overall or in genetically susceptible individuals.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-333745 (URN)10.1111/dme.13410 (DOI)000407819200011 ()
Available from: 2017-11-16 Created: 2017-11-16 Last updated: 2017-11-16Bibliographically approved
Rasouli, B., Ahlqvist, E., Andersson, T., Carlsson, P.-O., Groop, L., Hjort, R., . . . Carlsson, S. (2017). Sodium intake and the risk of type 2 diabetes and Latent Autoimmune Diabetes in Adults (LADA). Paper presented at 53rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 11-15, 2017, Lisbon, PORTUGAL. Diabetologia, 60, S103-S103
Open this publication in new window or tab >>Sodium intake and the risk of type 2 diabetes and Latent Autoimmune Diabetes in Adults (LADA)
Show others...
2017 (English)In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 60, p. S103-S103Article in journal, Meeting abstract (Other academic) Published
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-347294 (URN)000408315000223 ()
Conference
53rd Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), SEP 11-15, 2017, Lisbon, PORTUGAL
Available from: 2018-04-03 Created: 2018-04-03 Last updated: 2018-04-03Bibliographically approved
Rasouli, B., Andersson, T., Carlsson, P.-O., Grill, V., Groop, L., Martinell, M., . . . Carlsson, S. (2017). Use of Swedish smokeless tobacco (snus) and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA). Diabetic Medicine, 34(4), 514-521
Open this publication in new window or tab >>Use of Swedish smokeless tobacco (snus) and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA)
Show others...
2017 (English)In: Diabetic Medicine, ISSN 0742-3071, E-ISSN 1464-5491, Vol. 34, no 4, p. 514-521Article in journal (Refereed) Published
Abstract [en]

AimsIt has been suggested that moist snuff (snus), a smokeless tobacco product that is high in nicotine and widespread in Scandinavia, increases the risk of Type 2 diabetes. Previous studies are however few, contradictory and, with regard to autoimmune diabetes, lacking. Our aim was to study the association between snus use and the risk of Type 2 diabetes and latent autoimmune diabetes of adulthood (LADA). MethodAnalyses were based on incident cases (Type 2 diabetes, n = 724; LADA, n = 200) and population-based controls (n = 699) from a Swedish case-control study. Additional analyses were performed on cross-sectional data from the Norwegian HUNT study (n = 21 473) with 829 prevalent cases of Type 2 diabetes. Odds ratios (OR) were estimated adjusted for age, BMI family history of diabetes and smoking. Only men were included. ResultsNo association between snus use and Type 2 diabetes or LADA was seen in the Swedish data. For Type 2 diabetes, the OR for > 10 box-years was 1.00 [95% confidence interval (CI), 0.47 to 2.11] and for LADA 1.01 (95% CI, 0.45 to 2.29). Similarly, in HUNT, the OR for Type 2 diabetes in ever-users was estimated at 0.91 (95% CI, 0.75 to 1.10) and in heavy users at 0.92 (95% CI, 0.46 to 1.83). ConclusionThe risk of Type 2 diabetes and LADA is unrelated to the use of snus, despite its high nicotine content. This opens the possibility of the increased risk of Type 2 diabetes seen in smokers may not be attributed to nicotine, but to other substances in tobacco smoke.

National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-321337 (URN)10.1111/dme.13179 (DOI)000397490900009 ()27353226 (PubMedID)
Funder
Swedish Diabetes AssociationSwedish Research Council
Available from: 2017-05-03 Created: 2017-05-03 Last updated: 2017-05-03
Martinell, M., Dorkhan, M., Stålhammar, J., Storm, P., Groop, L. & Gustavsson, C. (2016). 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). Journal of diabetes and its complications, 30(8), 1456-1461
Open this publication in new window or tab >>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)
Show others...
2016 (English)In: Journal of diabetes and its complications, ISSN 1056-8727, E-ISSN 1873-460X, Vol. 30, no 8, p. 1456-1461Article in journal (Refereed) Published
Abstract [en]

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.

Keywords
Diabetes, Diabetic macular edema, Diabetic retinopathy, Diabetic retinopathy at diagnosis (DRAD), Latent autoimmune diabetes in the adult (LADA), Type 2 diabetes (T2D)
National Category
Endocrinology and Diabetes
Research subject
Endocrinology and Diabetology
Identifiers
urn:nbn:se:uu:diva-319750 (URN)10.1016/j.jdiacomp.2016.08.009 (DOI)000399434900009 ()27593902 (PubMedID)
Available from: 2017-04-08 Created: 2017-04-08 Last updated: 2017-08-22Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-6060-6229

Search in DiVA

Show all publications