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Lipidomic risk score independently and cost-effectively predicts risk of future type 2 diabetes: results from diverse cohorts
被引：43
作者：
Mamtani, Manju
[1
]
Kulkarni, Hemant
[1
]
Wong, Gerard
[2
]
Weir, Jacquelyn M.
[2
]
Barlow, Christopher K.
[2
]
Dyer, Thomas D.
[1
]
Almasy, Laura
[1
]
Mahaney, Michael C.
[1
]
Comuzzie, Anthony G.
[3
]
Glahn, David C.
[4
,5
]
Magliano, Dianna J.
[2
]
Zimmet, Paul
[2
]
Shaw, Jonathan
[2
]
Williams-Blangero, Sarah
[1
]
Duggirala, Ravindranath
[1
]
Blangero, John
[1
]
Meikle, Peter J.
[2
]
Curran, Joanne E.
[1
]
机构：
[1] Univ Texas Rio Grande Valley, Sch Med, South Texas Diabet & Obes Inst, Brownsville, TX 78520 USA
[2] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia
[3] Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA
[4] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA
[5] Hartford Hosp, Inst Living, Olin Neuropsychiat Res Ctr, 200 Retreat Ave, New Haven, CT USA
来源：
LIPIDS IN HEALTH AND DISEASE
|
2016年
/
15卷
基金：
美国国家卫生研究院;
英国医学研究理事会;
关键词：
Diabetes;
Endocrine disorders;
Lipidomics;
Diagnostic tools;
Genetics;
MEXICAN-AMERICAN FAMILIES;
DIAGNOSING INSULIN-RESISTANCE;
SATURATED FATTY-ACIDS;
CERAMIDE ACCUMULATION;
METABOLIC SYNDROME;
GLUCOSE-TOLERANCE;
HUMAN PLASMA;
LIFE-STYLE;
US ADULTS;
MELLITUS;
D O I：
10.1186/s12944-016-0234-3
中图分类号：
Q5 [生物化学];
Q7 [分子生物学];
学科分类号：
071010 ;
081704 ;
摘要：
Background: Detection of type 2 diabetes (T2D) is routinely based on the presence of dysglycemia. Although disturbed lipid metabolism is a hallmark of T2D, the potential of plasma lipidomics as a biomarker of future T2D is unknown. Our objective was to develop and validate a plasma lipidomic risk score (LRS) as a biomarker of future type 2 diabetes and to evaluate its cost-effectiveness for T2D screening. Methods: Plasma LRS, based on significantly associated lipid species from an array of 319 lipid species, was developed in a cohort of initially T2D-free individuals from the San Antonio Family Heart Study (SAFHS). The LRS derived from SAFHS as well as its recalibrated version were validated in an independent cohort from Australia - the AusDiab cohort. The participants were T2D-free at baseline and followed for 9197 person-years in the SAFHS cohort (n = 771) and 5930 person-years in the AusDiab cohort (n = 644). Statistically and clinically improved T2D prediction was evaluated with established statistical parameters in both cohorts. Modeling studies were conducted to determine whether the use of LRS would be cost-effective for T2D screening. The main outcome measures included accuracy and incremental value of the LRS over routinely used clinical predictors of T2D risk; validation of these results in an independent cohort and cost-effectiveness of including LRS in screening/intervention programs for T2D. Results: The LRS was based on plasma concentration of dihydroceramide 18: 0, lysoalkylphosphatidylcholine 22:1 and triacyglycerol 16:0/18:0/18:1. The score predicted future T2D independently of prediabetes with an accuracy of 76 %. Even in the subset of initially euglycemic individuals, the LRS improved T2D prediction. In the AusDiab cohort, the LRS continued to predict T2D significantly and independently. When combined with risk-stratification methods currently used in clinical practice, the LRS significantly improved the model fit (p < 0.001), information content (p < 0.001), discrimination (p < 0.001) and reclassification (p < 0.001) in both cohorts. Modeling studies demonstrated that LRS-based risk-stratification combined with metformin supplementation for high-risk individuals was the most cost-effective strategy for T2D prevention. Conclusions: Considering the novelty, incremental value and cost-effectiveness of LRS it should be used for risk-stratification of future T2D.
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页数：12
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