(04-03-16) Impact of long-term poor and good glycemic control on metabolomics alterations in Type 1 diabetic people.

Dutta T1, Kudva YC2, Persson XT1, Schenck LA3, Ford GC1, Singh RJ4, Carter R3, Nair KS2,1.
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Abstract
1.
CONTEXT:
Poor glycemic control in individuals with type 1 diabetes (T1D) is associated with both micro and macrovascular complications but good glycemic control does not fully prevent the risk of these complications. 2.
OBJECTIVE:
To determine whether T1D with good glycemic control have persistent abnormalities of metabolites and pathways that exist in T1D with poor glycemic control 3.
DESIGN:
We compared plasma metabolites in T1D with poor (HbA1c ≥8.5%, T1D(-) and good (HbA1c of < 6.5%, T1D(+) glycemic control to non-diabetic controls (ND). 4.
SETTING:
Clinical Research Unit. 5.
PATIENTS OR OTHER PARTICIPANTS:
T1D with poor (n=14), T1D(-) and good, T1D(+) (n=15) glycemic control and matched (for age, sex, and BMI) ND participants. 6.
INTERVENTION(S):
No intervention. 7.
MAIN OUTCOME MEASURE(S):
Comparison of qualitative and quantitative profiling of metabolome was performed. 8.
RESULTS:
In T1D(-), 347 known metabolites belonging to 38 metabolic pathways involved in cholesterol, Vitamin-D, tRNA, amino acids (AA), bile acids, urea, TCA cycle, immune response and eicosanoids were different from ND. In T1D(+),154 known metabolites belonging to 26 pathways including glycolysis, gluconeogenesis, bile acids, tRNA biosynthesis, AA, BCAA, retinol and Vitamin-D metabolism remained altered from ND. Targeted measurements of amino acid metabolites, TCA and free fatty acids showed directional changes similar to the untargeted metabolomics approach. 9.
CONCLUSIONS:
Comprehensive metabolomic profiling identified extensive metabolomic abnormalities in T1D with poor glycemic control. Chronic good glycemic control failed to normalize many of these perturbations suggesting a potential role for these persistent abnormalities in many complications in T1D.

Source: J Clin Endocrinol Metab. 2016 Jan 21:jc20152640. [Epub ahead of print]

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