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Characterization of Cellular Immunology in LADA Patients
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine. (Cardiovascular disease and diabetes)ORCID iD: 0000-0002-6060-6229
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.ORCID iD: 0000-0002-6771-7757
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.ORCID iD: 0000-0001-8843-7941
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Objective: Patients with latent autoimmune diabetes mellitus in adults (LADA) have antibodies against the insulin-producing b-cells but at disease onset they are not insulin-dependent. This study presents cellular immunological differences between LADA, type 1, type 2 diabetes and healthy controls.

Research Design and Methods: All patients and matched (by age, gender and body mass index) healthy controls were recruited from the County of Uppsala, Sweden. Peripheral blood mononuclear cells were isolated from freshly collected blood to determine proportions of innate, adaptive and regulatory immune cells by using flow cytometry.

Results: Included were 14 patients with LADA, 16 with type 1 diabetes, 16 with type 2 diabetes and 13 healthy controls. The proportion of CD11c+CD123- antigen presenting cells (APCs) was lower, whilst proportions of CD11c+CD123+ APCs and Interleukin (IL)-35+ tolerogenic APCs were higher in LADA patients compared to patients with type 1 diabetes. The proportion of CD3-CD56highCD16+ Natural Killer (NK) cells was higher in LADA patients than in both healthy controls and type 2 diabetes patients. IL-35+ Treg cell numbers were similar to those observed in both type 1 diabetes and type 2 diabetes patients, but a lower frequency of IL-35+ regulatory T (Treg) cells was observed in LADA patients than in healthy controls. The proportion of regulatory B (Breg) cells in LADA patients was higher than in healthy controls, type 1 and type 2 diabetes patients and IL-35+ Breg cell numbers were higher than in type 1 diabetes patients.

Conclusions: LADA patients present a mixed cellular immunological pattern compared to type 1 and type 2 diabetes patients. Numbers of APCs, IL-35+ tolerogenic APCs and IL-35+ Breg cells in LADA patients are similar to those observed in type 2 diabetes patients, whereas the changes in NK cells are similar to those observed in type 1 diabetes patients. 

Keywords [en]
Cellular immunology, latent autoimmun diabetes in adults, diabetes, type 1 diabetes, type 2 diabetes, interleukin 35
National Category
Immunology in the medical area
Research subject
Immunology
Identifiers
URN: urn:nbn:se:uu:diva-328352OAI: oai:DiVA.org:uu-328352DiVA, id: diva2:1135125
Projects
Diabetes Mellitus at the Time of Diagnosis - Studies on Prognostic Factors
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2017-08-22 Created: 2017-08-22 Last updated: 2018-01-13Bibliographically approved
In thesis
1. Diabetes Mellitus at the Time for Diagnosis: Studies on Prognostic Factors
Open this publication in new window or tab >>Diabetes Mellitus at the Time for Diagnosis: Studies on Prognostic Factors
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

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.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. p. 87
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1361
Keywords
New-onset Diabetes Mellitus, socioeconomic position, epidemiology, diabetes complications, diabetic retinopathy, cellular immunology, diabetes classification, type 2 diabetes, latent autoimmune diabetes in adults (LADA), type 1 diabetes
National Category
General Practice
Research subject
Family Medicine; Endocrinology and Diabetology
Identifiers
urn:nbn:se:uu:diva-328382 (URN)978-91-513-0047-4 (ISBN)
Public defence
2017-10-13, Auditorium Minus, Gustavianum, Akademigatan 3, Uppsala, 13:00 (Swedish)
Opponent
Supervisors
Funder
EXODIAB - Excellence of Diabetes Research in Sweden, 2009-1039
Available from: 2017-09-21 Created: 2017-08-22 Last updated: 2018-01-13

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Martinell, MatsSingh, KailashEspes, DanielStålhammar, JanSandler, StellanCarlsson, Per-Ola

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Immunology in the medical area

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