Potential Research Questions
Which diabetes related complication will a patient suffer?
Which drug or lifestyle intervention is best for a patient?
Is modulating the microbiome a viable way to prevent diabetes or diabetes complications?
What are the commonalities and differences between diabetes and other chronic systemic diseases?
Status Quo and Medical Need
Although methods to predict and diagnose diabetes are available, there is still room for improvement. For example, glucose tolerance tests are inconvenient for the patient and time consuming for doctors. Further, not every diabetes patient or person at risk is the same. The lifestyle intervention or medication of choice may be different in spite of a similar clinical phenotype, and the prognosis of diabetes patients may differ dramatically.
Targeted metabolomics has helped to sub-classify people at risk, elucidate the function of diabetes risk genes, and assess the molecular effects of medication. Metabolic markers will also play a role in tailoring interventions, and in understanding the pathways that define long term outcome.
Relevant Metabolite Classes
Amino acids and biogenic amines:
- Role of branched chain amino acids (BCAA) in diabetes is well accepted.
- Glycine has been described as marker for pre-diabetes (independent of other known risk factors).
- Alpha-aminoadipic acid (alpha-AAA) has been implied in the pathogenesis of diabetes.
- All steroid hormones have influence on insulin sensitivity.
- Steroid hormone metabolism may be a major factor in gender differences of T1D incidence. These may also be playing a role in the suspected autoimmune component to T2D.
- Lifestyle associated changes in the gut microbiome seem to contribute to diabetes.
- Bile acids, via effects on FXR and other receptors, have an influence on insulin resistance, gluconeogenesis, and incretin hormones.
Phospho- and sphingolipids:
- Lipids are involved in multiple inflammation related processes. Vast changes in lipid metabolism have been implied in the pathogenesis of diabetes and obesity related inflammation. Ceramides are playing an important role in this context.
- Selected lipids may predict type 2 diabetes after gestational diabetes.
- Boon et al.: LysoPC-acyl C16:0 is associated with brown adipose tissue activity in men; Metabolomics 2017
- Sung et al.: Improved glucose homeostasis in obese mice treated with resveratrol is associated with alterations in the gut microbiome; Diabetes 2016
- Allalou et al.: A Predictive Metabolic Signature for the Transition from Gestational Diabetes to Type 2 Diabetes; Diabetes 2016
- Franko et al.: Bezafibrate improves insulin sensitivity and metabolic flexibility in STZ-treated diabetic mice; Diabetes 2016
- Geurts et al.: Adipose tissue NAPE-PLD controls fat mass development by altering the browning process and gut microbiota; Nature Communications 2015
- Xu et al.: Effects of Metformin on Metabolite Profiles and LDL Cholesterol in Patients With Type 2 Diabetes; Diabetes Care 2015
- Floegel et al.: Identification of Serum Metabolites Associated With Risk of Type 2 Diabetes Using a Targeted Metabolomic Approach; Diabetes 2012
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For Research Use Only. Not for use in diagnostic procedures.