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All-Cause Mortality, Cardiovascular and Microvascular Diseases in Latent Autoimmune Diabetes in Adults

39 Pages Posted: 1 Dec 2022

See all articles by Yuxia Wei

Yuxia Wei

Karolinska Institutet - Institute of Environmental Medicine

Katharina Herzog

Karolinska Institutet - Institute of Environmental Medicine

Emma Ahlqvist

Lund University - CRC - Clinical Research Center

Tomas Andersson

Karolinska Institutet - Institute of Environmental Medicine

Yiqiang Zhan

Karolinska Institutet - Institute of Environmental Medicine

Tiinamaija Tuomi

University of Helsinki - Institute for Molecular Medicine Finland (FIMM)

Sofia Carlsson

Karolinska Institutet - Institute of Environmental Medicine

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Abstract

Background: Latent autoimmune diabetes in adults (LADA) is a heterogenous, slowly progressing autoimmune diabetes. We investigated the prognosis of LADA with varying degrees of autoimmunity.

Methods: This population-based Swedish study followed newly diagnosed LADA (n=550, stratified into LADAlow and LADAhigh by autoimmunity levels), adult-onset type 2 (n=2001) and type 1 diabetes (n=1573), and matched controls (n=2355) in 2007-2019. We estimated hazard ratios (HRs) for mortality and vascular outcomes, and trajectories for clinical characteristics.

Findings: During the follow-up, 402 deaths, 323 cardiovascular diseases (CVD), 79 nephropathy, and 190 retinopathy events occurred. Compared to controls, both LADAlow (HR: 1·86; 95% confidence interval [CI]: 1·27, 2·73) and type 2 diabetes were associated with excess mortality. While CVD incidence was increased in LADAhigh (HR: 1·67 [1·04, 2·69]) and type 2 diabetes, it was not increased in LADAlow or type 1 diabetes. Compared to type 2 diabetes, higher incidence of retinopathy but not nephropathy was observed in LADAhigh (HR: 2·41 [1·62, 3·59]) and LADAlow (HR: 2·12 [1·43, 3·14]). More favorable blood pressure and lipid profiles and higher HbA1c levels were seen in LADA than type 2 diabetes, especially in LADAhigh, whose trajectories were similar with type 1 diabetes. A significant proportion of LADA did not use any glucose-lowering drug.

Interpretation: Despite having fewer metabolic risk factors than type 2 diabetes, LADA has an equal to higher risk of death or vascular diseases. Poorer glycemic control, particularly in LADAhigh, and the absence of glucose-lowering therapy in some patients highlight the need for improved LADA management.

Funding Information: The ESTRID study was supported by the Swedish Research Council (2018-03035), Research Council for Health, Working Life and Welfare (FORTE, 2018-00337) and Novo Nordisk Foundation (NNF19OC0057274). The ANDIS study was financed by Swedish governmental funding of clinical research (ALF), the Swedish Research Council project grant nos. 2020- 02191, 2015-2558, infrastructure grant nos. 2010-5983, 2012-5538, 2014-6395, Linnaeus grant no. 349-2006-237, and strategic research grant nos. 2009-1039 (EXODIAB) and IRC15- 0067 (LUDC-IRC)). YW received a scholarship from the China Scholarship Council (student number 202006010041).

Declaration of Interests: The authors declared no conflict of interest.

Ethics Approval Statement: ANDIS and ESTRID participants provided informed consent. The study was approved by the Ethical Review Board in Stockholm (2010/336-31/1, 2018/1036-32, and 2022-02549-02).

Keywords: LADA, mortality, cardiovascular, retinopathy, nephropathy, trajectory

Suggested Citation

Wei, Yuxia and Herzog, Katharina and Ahlqvist, Emma and Andersson, Tomas and Zhan, Yiqiang and Tuomi, Tiinamaija and Carlsson, Sofia, All-Cause Mortality, Cardiovascular and Microvascular Diseases in Latent Autoimmune Diabetes in Adults. Available at SSRN: https://ssrn.com/abstract=4287478 or http://dx.doi.org/10.2139/ssrn.4287478

Yuxia Wei (Contact Author)

Karolinska Institutet - Institute of Environmental Medicine ( email )

Katharina Herzog

Karolinska Institutet - Institute of Environmental Medicine ( email )

Emma Ahlqvist

Lund University - CRC - Clinical Research Center ( email )

Tomas Andersson

Karolinska Institutet - Institute of Environmental Medicine ( email )

Yiqiang Zhan

Karolinska Institutet - Institute of Environmental Medicine ( email )

Tiinamaija Tuomi

University of Helsinki - Institute for Molecular Medicine Finland (FIMM) ( email )

Sofia Carlsson

Karolinska Institutet - Institute of Environmental Medicine ( email )

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