Alterations in the metabolism of phospholipids, bile acids and branched-chain amino acids predicts development of type 2 diabetes in black South African women: a prospective cohort study.
Metabolism
; 95: 57-64, 2019 06.
Article
in En
| MEDLINE
| ID: mdl-30954560
ABSTRACT
BACKGROUND:
South Africa (SA) has the highest global projected increase in diabetes risk. Factors typically associated with insulin resistance and type 2 diabetes risk in Caucasians are not significant correlates in black African populations. Therefore, we aimed to identify circulating metabolite patterns that predict type 2 diabetes development in this high-risk, yet understudied SA population.METHODS:
We conducted a prospective cohort study in black SA women with normal glucose tolerance (NGT). Participants were followed for 13â¯years and developed (i) type 2 diabetes (nâ¯=â¯20, NGT-T2D), (ii) impaired glucose tolerance (IGT) (nâ¯=â¯27, NGT-IGT), or (iii) remained NGT (nâ¯=â¯28, NGT-NGT). Mass-spectrometry based metabolomics and multivariate analyses were used to elucidate metabolite patterns at baseline and at follow-up that were associated with type 2 diabetes development.RESULTS:
Metabolites of phospholipid, bile acid and branched-chain amino acid (BCAA) metabolism, differed significantly between the NGT-T2D and NGT-NGT groups. At baseline the NGT-T2D group had i) a higher lysophosphatidylcholinelysophosphatidylethanolamine ratio containing linoleic acid (LPC(C182)LPE(C182)), ii) lower proliferation-related bile acids (ursodeoxycholic- and chenodeoxycholic acid), iii) higher levels of leucine and its catabolic intermediates (ketoleucine and C5-carnitine), compared to the NGT-NGT group. At follow-up the NGT-T2D group had i) lower LPC(C182) levels, ii) higher apoptosis-related bile acids (deoxycholic- and glycodeoxycholic acid), and iii) higher levels of all BCAAs and their catabolic intermediates.CONCLUSIONS:
Changes in lysophospholipid metabolism and the bile acid pool occur during the development of type 2 diabetes in black South African women. Further, impaired leucine catabolism precedes valine and isoleucine catabolism in the development of type 2 diabetes. These metabolite patterns can be useful to identify and monitor type 2 diabetes risk >10â¯years prior to disease onset and provide insight into the pathophysiology of type 2 diabetes in this high risk, but under-studied population.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phospholipids
/
Bile Acids and Salts
/
Diabetes Mellitus, Type 2
/
Amino Acids, Branched-Chain
Type of study:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
/
Middle aged
Country/Region as subject:
Africa
Language:
En
Journal:
Metabolism
Year:
2019
Document type:
Article
Affiliation country:
Sweden