Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Current Diabetes Reports
Published in: Current Diabetes Reports 9/2020

Open Access 01-09-2020 | Type 1 Diabetes | Pathogenesis of Type 1 Diabetes (A Pugliese and SJ Richardson, Section Editors)

Lipidomic Abnormalities During the Pathogenesis of Type 1 Diabetes: a Quantitative Review

Author: Tommi Suvitaival

Published in: Current Diabetes Reports | Issue 9/2020

Login to get access

Abstract

Purpose of Review

The underlying factors triggering a cascade of autoimmune response that leads to the death of pancreatic beta cells and type 1 diabetes are to large extent unknown. Aberrations in the lipid balance have been suggested, either as factors directly contributing to autoimmunity or as a reflection of external factors, such as the diet or chemical exposure, which may increase the risk or even trigger the autoimmunity cascade.

Recent Findings

A small number of recent studies have investigated the blood lipidome before and after the onset of type 1 diabetes with a goal of identifying biomarkers of disease progression. Phosphatidylcholine levels in particular have been suggested to be reduced prior to the onset of type 1 diabetes.

Summary

In this review, we approach this question through a quantitative analysis of the reported lipids. We quantify the extent of consensus between these heterogeneous studies, describe the overall lipidomic pattern that has been reported, and call for more independent replication of the findings that we highlight in this review.
Appendix
Available only for authorised users
Literature
1.
Katsarou A, Gudbjornsdottir S, Rawshani A, Dabelea D, Bonifacio E, Anderson BJ, et al. Type 1 diabetes mellitus. Nat Rev Dis Primers. 2017;3:17016.CrossRef
2.
Han X. Lipidomics for studying metabolism. Nat Rev Endocrinol. 2016;12(11):668–79.CrossRef
3.
Rauschert S, Uhl O, Koletzko B, Kirchberg F, Mori TA, Huang RC, et al. Lipidomics reveals associations of phospholipids with obesity and insulin resistance in young adults. J Clin Endocrinol Metab. 2016;101(3):871–9.CrossRef
4.
Yin X, Willinger CM, Keefe J, Liu J, Fernandez-Ortiz A, Ibanez B, et al. Lipidomic profiling identifies signatures of metabolic risk. EBioMedicine. 2020;51:102520.CrossRef
5.
Markgraf DF, Al-Hasani H, Lehr S. Lipidomics-reshaping the analysis and perception of type 2 diabetes. Int J Mol Sci. 2016;17(11).
6.
Suvitaival T, Bondia-Pons I, Yetukuri L, Poho P, Nolan JJ, Hyotylainen T, et al. Lipidome as a predictive tool in progression to type 2 diabetes in Finnish men. Metabolism. 2018;78:1–12.CrossRef
7.
Suvitaival T, Legido-Quigley C. Understanding the Lipidome at the Systems Level with lipidomeR. bioRxiv. 2020.
8.
Epskamp S, Cramer AOJ, Waldorp LJ, Schmittmann VD, Borsboom D. qgraph: network visualizations of relationships in psychometric data. 2012. 2012;48(4):18.
9.
•• Lamichhane S, Ahonen L, Dyrlund TS, Kemppainen E, Siljander H, Hyoty H, et al. Dynamics of plasma lipidome in progression to islet autoimmunity and type 1 diabetes - type 1 diabetes prediction and prevention study (DIPP). Sci Rep. 2018;8(1):10635. This study reported the lipidome of 15-25 infants in age categories from 3 to 36 months of age, who were later in infancy diagnosed with T1D in Finland.
10.
•• La Torre D, Seppanen-Laakso T, Larsson HE, Hyotylainen T, Ivarsson SA, Lernmark A, et al. Decreased cord-blood phospholipids in young age-at-onset type 1 diabetes. Diabetes. 2013;62(11):3951–6. This study reported the cord-blood lipidome at birth in 76 babies, who were later in infancy diagnosed with T1D in Sweden.
11.
•• Lamichhane S, Ahonen L, Dyrlund TS, Dickens AM, Siljander H, Hyoty H, et al. Cord-blood lipidome in progression to islet autoimmunity and type 1 diabetes. Biomolecules. 2019;9(1). This study reported the cord-blood lipidome at birth in 30 babies, who were later in infancy diagnosed with T1D in Finland.
12.
•• Oresic M, Simell S, Sysi-Aho M, Nanto-Salonen K, Seppanen-Laakso T, Parikka V, et al. Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes. J Exp Med. 2008;205(13):2975–84. This study reported the lipidome in age categories from birth to 10 years of age in 5-46 children, who were later diagnosed with T1D Finland.
13.
•• Pflueger M, Seppanen-Laakso T, Suortti T, Hyotylainen T, Achenbach P, Bonifacio E, et al. Age- and islet autoimmunity-associated differences in amino acid and lipid metabolites in children at risk for type 1 diabetes. Diabetes. 2011;60(11):2740–7. This study reported the lipidome in auto-antibody positive and auto-antibody negative participants in two age categories (26 infants younger than 2 years and 44 children older than eight years), who later progressed to T1D in Germany.
14.
•• Sen P, Dickens AM, Lopez-Bascon MA, Lindeman T, Kemppainen E, Lamichhane S, et al. Metabolic alterations in immune cells associate with progression to type 1 diabetes. Diabetologia. 2020;63:1017–31. This study reported the lipidome of peripheral blood mononuclear cells in 34 children in age categories from one to three years, who were later diagnosed with T1D in Finland.
15.
•• Overgaard AJ, Weir JM, Jayawardana K, Mortensen HB, Pociot F, Meikle PJ. Plasma lipid species at type 1 diabetes onset predict residual beta-cell function after 6 months. Metabolomics. 2018;14(12):158. This study reported lipidomic associations with the decrease in insulin secretion one and six months after the onset of T1D in 111-123 individuals under 17 years of age in Denmark.
16.
•• Sorensen CM, Ding J, Zhang Q, Alquier T, Zhao R, Mueller PW, et al. Perturbations in the lipid profile of individuals with newly diagnosed type 1 diabetes mellitus: lipidomics analysis of a diabetes antibody standardization program sample subset. Clin Biochem. 2010;43(12):948–56. This study reported the lipidome in 10 individuals between 10 and 29 years of age with newly-onset T1D in USA.
17.
Johnson RK, Vanderlinden L, DeFelice BC, Kechris K, Uusitalo U, Fiehn O, et al. Metabolite-related dietary patterns and the development of islet autoimmunity. Sci Rep. 2019;9(1):14819.CrossRef
18.
McGlinchey A, Sinioja T, Lamichhane S, Bodin J, Siljander H, Dickens AM, et al. Prenatal exposure to perfluoroalkyl substances modulates neonatal serum phospholipids, increasing risk of type 1 diabetes. bioRxiv. 2019.
19.
Tofte N, Suvitaival T, Ahonen L, Winther SA, Theilade S, Frimodt-Moller M, et al. Lipidomic analysis reveals sphingomyelin and phosphatidylcholine species associated with renal impairment and all-cause mortality in type 1 diabetes. Sci Rep. 2019;9(1):16398.CrossRef
20.
Treede I, Braun A, Sparla R, Kuhnel M, Giese T, Turner JR, et al. Anti-inflammatory effects of phosphatidylcholine. J Biol Chem. 2007;282(37):27155–64.CrossRef
21.
Huynh K, Pernes G, Mellett NA, Meikle PJ, Murphy AJ, Lancaster GI. Lipidomic profiling of murine macrophages treated with fatty acids of varying chain length and saturation status. Metabolites. 2018;8(2).
22.
Tan AH, Chong WP, Ng SW, Basri N, Xu S, Lam KP. Aberrant presentation of self-lipids by autoimmune B cells depletes peripheral iNKT cells. Cell Rep. 2014;9(1):24–31.CrossRef
23.
Xu X, Yu Y, Wang Z, Zhu T, Wang Y, Zhu J, et al. Mass spectrometry based phospholipidomics of mammalian thymus and leukemia patients: implication for function of iNKT cells. Anal Bioanal Chem. 2013;405(15):5267–78.CrossRef
24.
Li Y, Thapa P, Hawke D, Kondo Y, Furukawa K, Furukawa K, et al. Immunologic glycosphingolipidomics and NKT cell development in mouse thymus. J Proteome Res. 2009;8(6):2740–51.CrossRef
25.
Herz J, Pardo J, Kashkar H, Schramm M, Kuzmenkina E, Bos E, et al. Acid sphingomyelinase is a key regulator of cytotoxic granule secretion by primary T lymphocytes. Nat Immunol. 2009;10(7):761–8.CrossRef
26.
Kirschnek S, Paris F, Weller M, Grassme H, Ferlinz K, Riehle A, et al. CD95-mediated apoptosis in vivo involves acid sphingomyelinase. J Biol Chem. 2000;275(35):27316–23.PubMed
27.
Zhou Y, Salker MS, Walker B, Munzer P, Borst O, Gawaz M, et al. Acid sphingomyelinase (ASM) is a negative regulator of regulatory T cell (Treg) development. Cell Physiol Biochem. 2016;39(3):985–95.CrossRef
28.
Hollmann C, Wiese T, Dennstadt F, Fink J, Schneider-Schaulies J, Beyersdorf N. Translational approaches targeting ceramide generation from sphingomyelin in T cells to modulate immunity in humans. Front Immunol. 2019;10:2363.CrossRef
29.
Fox TE, Bewley MC, Unrath KA, Pedersen MM, Anderson RE, Jung DY, et al. Circulating sphingolipid biomarkers in models of type 1 diabetes. J Lipid Res. 2011;52(3):509–17.CrossRef
30.
Haus JM, Kashyap SR, Kasumov T, Zhang R, Kelly KR, Defronzo RA, et al. Plasma ceramides are elevated in obese subjects with type 2 diabetes and correlate with the severity of insulin resistance. Diabetes. 2009;58(2):337–43.CrossRef
31.
Koves TR, Ussher JR, Noland RC, Slentz D, Mosedale M, Ilkayeva O, et al. Mitochondrial overload and incomplete fatty acid oxidation contribute to skeletal muscle insulin resistance. Cell Metab. 2008;7(1):45–56.CrossRef
32.
Chaurasia B, Summers SA. Ceramides - lipotoxic inducers of metabolic disorders. Trends Endocrinol Metab. 2015;26(10):538–50.CrossRef
33.
Schmitz-Peiffer C. Targeting ceramide synthesis to reverse insulin resistance. Diabetes. 2010;59(10):2351–3.CrossRef
34.
Kurek K, Wiesiolek-Kurek P, Piotrowska DM, Lukaszuk B, Chabowski A, Zendzianendzian-Piotrowska M. Inhibition of ceramide de novo synthesis with myriocin affects lipid metabolism in the liver of rats with streptozotocin-induced type 1 diabetes. Biomed Res Int. 2014;2014:980815.CrossRef
35.
Makinen VP, Tynkkynen T, Soininen P, Forsblom C, Peltola T, Kangas AJ, et al. Sphingomyelin is associated with kidney disease in type 1 diabetes (the FinnDiane study). Metabolomics. 2012;8(3):369–75.CrossRef
36.
Hammad SM, Baker NL, El Abiad JM, Spassieva SD, Pierce JS, Rembiesa B, et al. Increased plasma levels of select deoxy-ceramide and ceramide species are associated with increased odds of diabetic neuropathy in type 1 diabetes: a pilot study. NeuroMolecular Med. 2017;19(1):46–56.CrossRef
Metadata
Title
Lipidomic Abnormalities During the Pathogenesis of Type 1 Diabetes: a Quantitative Review
Author
Tommi Suvitaival
Publication date
01-09-2020
Publisher
Springer US
Published in
Current Diabetes Reports / Issue 9/2020
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-020-01326-8

Other articles of this Issue 9/2020

Current Diabetes Reports 9/2020 Go to the issue

Obesity (KM Gadde and P Singh, Section Editors)

Endocrine Mechanisms Connecting Exercise to Brown Adipose Tissue Metabolism: a Human Perspective

Pathogenesis of Type 1 Diabetes (A Pugliese and S Richardson, Section Editors)

miRNA Regulation of T Cells in Islet Autoimmunity and Type 1 Diabetes

Other Forms of Diabetes and Its Complications (JJ Nolan and H Thabit, Section Editors)

Early Onset of Autoimmune Diabetes in Children with Down Syndrome—Two Separate Aetiologies or an Immune System Pre-Programmed for Autoimmunity?

Pathogenesis of Type 2 Diabetes and Insulin Resistance (ME Patti, Section Editor)

Type 2 Diabetes in Youth: the Role of Early Life Exposures

Pathogenesis of Type 2 Diabetes and Insulin Resistance (ME Patti, Section Editor)

The Physiological Importance of Bile Acid Structure and Composition on Glucose Homeostasis

Genetics (AP Morris, Section Editor)

New Insights into the Genetics of Latent Autoimmune Diabetes in Adults
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits