Latent Autoimmune Diabetes in Systemic Lupus Erythematosus

A case of latent autoimmune diabetes of adult with systemic lupus erythematosus

Subhashchandra Daga¹

The Primary Health Centre, Kamshet, 414003, India.

OPEN ACCESS

PUBLISHED: 31 December 2024

CITATION: DAGA, Subhashchandra. A case of latent autoimmune diabetes of adult with systemic lupus erythematosus. Medical Research Archives, [S.l.], v. 12, n. 12, dec. 2024.

COPYRIGHT: © 2025 European Society of Medicine. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

DOI: https://doi.org/10.18103/mra.v12i12.5947

ISSN 2375-1924

DOI: 10.18103/jl.1212.52

Abstract

Systemic lupus erythematosus and latent autoimmune diabetes of adults (LADA) are chronic systemic disorders that affect many parts of the body. Both have autoimmune origins. However, their coexistence is rare. A fifty-five-year-old woman of average build presented with skin rashes at Kamseth Primary Health Centre. Her blood test was positive for antinuclear antibodies, and she was treated with hydroxychloroquine. Her fasting blood sugar was 26.0 mg/dl; her HbA1c was 11.2%, and her C-peptide level was low (1.6 ng/ml). This case highlights the association between LADA and systemic lupus erythematosus.

Keywords

Latent autoimmune diabetes
Systemic lupus erythematosus
Autoimmunity

Introduction

Neither Latent autoimmune diabetes of adults (LADA) nor systemic lupus erythematosus (SLE) is uncommon; however, their coexistence is rare. LADA is an autoimmune disorder in which the autoantibodies damage the islet cells of the pancreas. The World Health Organization (WHO) considers LADA one of the hybrid forms of diabetes. The WHO renames it as the slowly evolving immune-mediated diabetes in adults but more often has features of the metabolic syndrome, a single GAD autoantibody, and retains greater β-cell function(1). LADA is believed to be a form of type 1 diabetes that develops much more slowly and presents in adulthood. It has features of both type 1 and type 2 diabetes; hence, it’s sometimes called type 1.5 diabetes. The syndrome is slowly progressive. Lean people diagnosed with type 2 diabetes who are physically active may have LADA.

SLE is a complex disease currently defined using a variety of case definitions. The gold standard case definition is diagnosed by expert clinical assessment, usually by a rheumatologist, which is impractical for a low-resource setting(2). Diverse clinical features and the disease’s relapsing and remitting course pose challenges in diagnosing SLE and conducting epidemiological studies(3,4). The global SLE prevalence was estimated to be 43.7 (15.87 to 108.92) per 100,000 persons. People in high-income regions were likelier to suffer from SLE than those in lower-income communities(5). Compounded by poor access to healthcare and limited understanding of SLE among primary care physicians, there is a paucity of SLE epidemiological studies in low-resource countries(6).

CASE REPORT

A fifty-five-year-old woman presented to the Primary Health Centre (PHC), Kamshet, with a non-itchy and linear lesion on the arm and abdomen for eight months (Figures 1 and 2). This rash was preceded by a fever that responded to a short course of treatment. The clinical examination also revealed a scaly lesion in the “butterfly area” over the face (Figure 3). She had no history of red urine. Her blood pressure was 126/84 mm Hg, and complete blood counts were normal. Blood urea, serum creatinine, liver function tests, and thyroid profile were within normal limits. The antinuclear antibody test was positive (1 in 100), and ESR and CRP were not raised. Systemic lupus erythematosus (SLE) was diagnosed and treated with hydroxychloroquine. Steroids were not administered.

On direct questioning, she admitted increased urination and blurred vision. There was no weight loss. Her BMI was 21.8. There is a strong family history of diabetes. Her two brothers have type II diabetes. Her fasting blood sugar level was 260 mg/dl, Hb A1c was 12.2 %, and the C-peptide level was low (1.67 ng/ml). The anti-insulin antibody test was negative (2.5 U/ml). IA2-Insulin (3.35U/ml) and GAD-65 Antibody Type I (1.3 IU/ml) were also negative. She did not respond to oral antidiabetic treatment, singly or in combination, despite adherence, but responded promptly to insulin therapy, 20 units twice a day. Her post-meal plasma glucose was 120 mg/dl. Metformin and pioglitazone were continued.

A fifty-five-year-old woman presented to the Primary Health Centre (PHC), Kamshet, with a non-healing ulcer on the arm and abdomen for eight months (Figures 1 and 2).

Her fasting blood sugar was 26.0 mg/dl; her HbA1c was 11.2%, and her C-peptide level was low (1.6 ng/ml). She was treated with hydroxychloroquine and insulin.

Discussion

Observational studies suggest a relationship between type-1 diabetes mellitus (T1DM) and systemic lupus erythematosus (SLE). Type 1 diabetes mellitus (T1DM) is an organ-specific autoimmune disorder, and SLE is an autoimmune disorder involving multiple systems. The pathogenesis of the B-cell-mediated autoimmune response in T1DM and the T-cell-mediated cytotoxic response in SLE is similar(7). Autoantibodies detected in T1DM have also been found in presymptomatic SLE(8). Mendelian Randomization analysis suggested a causal relationship between T1DM, 25-OHD levels, and SLE. T1DM and 25-OHD levels are associated with SLE and have causal associations with the risk of SLE. 25-OHD levels could mediate the causality of T1DM and SLE(9). However, the studies on association between SLE and diabetes have yielded conflicting results. There was no increased risk of DM in patients with SLE compared with controls(10). Patients with newly diagnosed SLE had a 22% increased risk of developing type 2 diabetes during the 3-year follow-up period compared with matched controls(11). Hemminki used data from three Swedish health databases to estimate the risk of subsequent type 2 diabetes in patients with autoimmune diseases. The study included 12,206 patients with SLE and found that patients with SLE had a higher risk of type 2 diabetes(12). As against this, a nationwide population-based study that used data from the UK, which included 1605 patients with SLE, found no increased risk of developing diabetes(13). The gene PTPN 1858T variant is a common link to type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus (SLE), and other autoimmune disorders, supporting the hypothesis that several autoimmune diseases may share specific genes or susceptibility pathways(14). An association between type B insulin resistance syndrome (TBIRS) and SLE has been described. Almost all these patients with TBIRS had antibodies against insulin receptors, and they required insulin in high doses ranging from 450 to 25,000U daily(15). As against TBIRS cases, our patient did not have antibodies against insulin and responded to a small insulin dose.
In summary, our patient with a normal BMI presented later than type 1 diabetes commonly presents. Her C-peptide levels were low, and she did not respond to oral antidiabetic drugs. She did not have islet cell antibodies but was diagnosed with SLE and promptly responded to small doses of insulin.

Funding Statement:

None.

Acknowledgements:

The author thanks Dr. Mohan Swaminathan for his help.

Corresponding author

Subhashchandra Daga
The Primary Health Centre, Kamshet, 410405 (India).
Mobile no. 0091-9960522259.
Email: [email protected]
ORCID: 0000 0001 5840 3804

Conflicts of Interest

The author declares no conflicts of interest.

References

1. Classification of diabetes mellitus. World Health Organization 2019. ISBN 978-92-4-15170-2.

2. Lim SS, Bayakly AR, Helmick CG, Gordon C, Easley KA, Drenkard C. The incidence and prevalence of systemic lupus erythematosus, 2002-2004: The Georgia Lupus Registry. Arthritis Rheumatol. 2014 Feb;66(2):357-68.

3. Carter EE, Barr SG, Clarke AE. The global burden of SLE: prevalence, health disparities, and socioeconomic impact. Nat Rev Rheumatol 2016; 12:605-20.

4. Barber MRW, Drenkard C, Falasinnu T, et al. Global epidemiology of systemic lupus erythematosus. Nat Rev Rheumatol 2021; 17: 515-32.

5. Tian J, Zhang D, Yao X, et al. Global epidemiology of systemic lupus erythematosus: a comprehensive systematic analysis and modelling study. Annals of the Rheumatic Diseases 2023;82:351-356.

6. Malaviya AN, Singh RR, Singh YN, Kapoor SK, Kumar A. Prevalence of Systemic Lupus Erythematosus in India. Lupus. 1993;2(2):115-118.

7. Katsarou A, Gudbjörnsdottir S, Rawshani A, et al. Type 1 diabetes mellitus. Nat Rev Dis Primers. 2017;3:17016.

8. Cortes S, Chambers S, Jerónimo A, Isenberg D. Diabetes mellitus complicating systemic lupus erythematosus—analysis of the UCL lupus cohort and literature review. Lupus. 2008;17(11):977–980.

9. Su K, Jia Z, Wu Y, Sun Y, Gao Q, Jiang Z, Jiang J. A network causal relationship between type-1 diabetes mellitus, 25-hydroxyvitamin D level, and systemic lupus erythematosus: Mendelian randomization study. PLoS One. 2023 May 17;18(5).

10. Etchegaray-Morales I, Mendoza-Pinto C, Munguía-Realpozo P, Solis-Poblano JC, Méndez-Martínez S, Ayón-Aguilar J, Abud-Mendoza C, García-Carrasco M, Cervera R. Risk of diabetes mellitus in systemic lupus erythematosus: systematic review and meta-analysis. Rheumatology (Oxford). 2024 Aug 1;63(8):2047-2055.

11. Lin YJ, Chien CC, Ho CH, Chen HA, Chen CY. Increased risk of type 2 diabetes in patients with systemic lupus erythematosus: A nationwide cohort study in Taiwan. Medicine (Baltimore). 2022 Dec 23;101(51).

12. Hemminki K, Liu X, Försti A, et al. Subsequent type 2 diabetes in patients with autoimmune disease. Sci Rep. 2015; 5:13871.

13. Kuo CF, Chou IJ, Rees F, et al. Temporal relationships between systemic lupus erythematosus and comorbidities. Rheumatology (Oxford). 2019; 58:840–8.

14. Tizaoui K, Terrazzino S, Cargnin S, et al. Seminars in arthritis and rheumatism. 2021; 51:513-22.

15. Alvarez-Payares JC, Ribero D, Rodríguez L, Builes CE, Prieto C, Arango C, Gamboa JG, Alvarez-Payares C. Late Systemic Lupus Erythematosus-Associated Insulin Resistance Syndrome: A Rare Cause of De Novo Diabetes Mellitus. Case Rep Med. 2022 Oct 14; 2022:4655804.