Ceramides and diabetes mellitus: an update on the potential molecular relationships

Yaribeygi, Habib; Bo, Simona; Ruscica, Massimiliano; Sahebkar, Amirhossein

doi:10.1111/dme.13943

Cited by 43 publications

(32 citation statements)

References 95 publications

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“…36 37 Several mechanisms, including β-cell apoptosis and pancreatic inflammation, were proposed to be involved in the risk posed by high levels of ceramides. 38 However, in contrast to studies suggesting associations between deoxysphingolipids and T2D, we did not find a significant association between Cer m18:0 (also referred to as deoxydihydroceramide). 39 This may be related to differences in analytical techniques.…”

Section: Sphingolipidscontrasting

confidence: 99%

Contributions of amino acid, acylcarnitine and sphingolipid profiles to type 2 diabetes risk among South-Asian Surinamese and Dutch adults

Muilwijk

Goorden

Celis-Morales

et al. 2020

BMJ Open Diab Res Care

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IntroductionPeople of South Asian origin are at high risk of type 2 diabetes (T2D), but the underpinning mechanisms are not fully understood. We determined ethnic differences in acylcarnitine, amino acid and sphingolipid concentrations and determined the associations with T2D.Research design and methodsAssociations between these metabolites and incident T2D among Dutch and South-Asian Surinamese were determined in participants from the Healthy Life in an Urban Setting (HELIUS) study (Amsterdam, the Netherlands) using Prentice-weighted Cox regression. The HELIUS study includes 95 incident T2D cases and a representative subcohort of 700 people from a cohort of 5977 participants with a mean follow-up of 4 years.ResultsConcentrations of acylcarnitines were comparable between both ethnic groups. Amino acid and lactosylceramide concentrations were higher among South-Asian Surinamese than Dutch (eg, isoleucine 65.7 (SD 16.3) vs 60.7 (SD 15.6) µmol/L). Ceramide concentrations were lower among South-Asian Surinamese than Dutch (eg, Cer d18:1 8.48 (SD 2.04) vs 9.08 (SD 2.29) µmol/L). Metabolic dysregulation preceded T2D without evidence for a multiplicative interaction by ethnicity. Most amino acids and (dihydro)ceramides were associated with increased risk (eg, Cer d18:1 HR 2.38, 95% CI 1.81 to 3.12) while acylcarnitines, glycine, glutamine and lactosylceramides were associated with decreased risk for T2D (eg, LacCer d18:2 HR 0.56, 95% CI 0.42 to 0.77).ConclusionsOverall, these data suggest that the disturbances underlying amino acid and sphingolipid metabolism may be predictive of T2D risk in populations of both South Asian and European background. These observations may be used as starting point to unravel the underlying metabolic disturbances.

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Section: Sphingolipidscontrasting

confidence: 99%

Contributions of amino acid, acylcarnitine and sphingolipid profiles to type 2 diabetes risk among South-Asian Surinamese and Dutch adults

Muilwijk

Goorden

Celis-Morales

et al. 2020

BMJ Open Diab Res Care

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“…The mechanistic role of ceramides in insulin resistance has been reviewed recently ( 8 , 27 ). Ceramide precursor molecules, dihydroceramides, are elevated years before the onset of type 2 diabetes mellitus (DM2) ( 28 ).…”

Section: Ceramides In Cardiovascular Diseasesmentioning

confidence: 99%

Ceramides and Ceramide Scores: Clinical Applications for Cardiometabolic Risk Stratification

et al. 2020

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Ceramides are bioactive lipids that have an important role in many cellular functions such as apoptosis and inflammation. During the past decade emerging clinical data have shown that ceramides are not only of great biochemical interest but may also have diagnostic utility. Ceramides have shown independent predictive value for negative cardiovascular outcomes as well as for the onset of type 2 diabetes. Based on abundant published data, risk score using the concentrations of circulating ceramides have been developed and adapted for routine clinical practice. Currently serum ceramides are used clinically as efficient risk stratifiers for primary and secondary prevention of atherosclerotic cardiovascular disease (CVD). A direct cause-effect relationship between CVD and ceramide has not been established to date. As ceramide-specific medications are being developed, conventional strategies such as lipid lowering agents and lifestyle interventions can be used to reduce overall risk. Ceramides can identify a very high-risk coronary heart disease category of patients in need for more intense medical attention, specifically those patients at higher risk as highlighted in the 2019 European Society of Cardiology guidelines for stable chronic coronary syndrome patients. In addition, the ceramide risk score may be used as a decision-making tool in primary prevention patients with moderate CVD risk. Finally, the ceramide risk score may have a unique utility as a motivational tool to increase patient's adherence to medical therapy and lifestyle changes.

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“…Also, the knockout of ceramide-generating enzymes in animals has increased insulin sensitivity [ 122 , 123 ]. Therefore, ceramide is now widely accepted as a potent insulin antagonist involved in the pathophysiology of insulin resistance and DM, especially in overweight and obese people [ 116 ].…”

Section: Pathophysiologic Links Between Physical Inactivity and Insulin Resistancementioning

confidence: 99%

Pathophysiology of Physical Inactivity-Dependent Insulin Resistance: A Theoretical Mechanistic Review Emphasizing Clinical Evidence

Yaribeygi

Maleki

Sathyapalan

et al. 2021

Journal of Diabetes Research

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The modern lifestyle has a negative impact on health. It is usually accompanied by increased stress levels and lower physical activity, which interferes with body homeostasis. Diabetes mellitus is a relatively common metabolic disorder with increasing prevalence globally, associated with various risk factors, including lower physical activity and a sedentary lifestyle. It has been shown that sedentary behavior increases the risk of insulin resistance, but the intermediate molecular mechanisms are not fully understood. In this mechanistic review, we explore the possible interactions between physical inactivity and insulin resistance to help better understand the pathophysiology of physical inactivity-dependent insulin resistance and finding novel interventions against these deleterious pathways.

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Ceramides and diabetes mellitus: an update on the potential molecular relationships

Cited by 43 publications

References 95 publications

Contributions of amino acid, acylcarnitine and sphingolipid profiles to type 2 diabetes risk among South-Asian Surinamese and Dutch adults

Contributions of amino acid, acylcarnitine and sphingolipid profiles to type 2 diabetes risk among South-Asian Surinamese and Dutch adults

Ceramides and Ceramide Scores: Clinical Applications for Cardiometabolic Risk Stratification

Pathophysiology of Physical Inactivity-Dependent Insulin Resistance: A Theoretical Mechanistic Review Emphasizing Clinical Evidence

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