Lipoprotein Insulin Resistance Index: A Lipoprotein Particle–Derived Measure of Insulin Resistance

Shalaurova, Irina; Connelly, Margery A.; Garvey, W. Timothy; Otvos, James D.

doi:10.1089/met.2014.0050

Cited by 138 publications

(188 citation statements)

References 36 publications

(53 reference statements)

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“…Objective indicators of HF history used for sensitivity analyses were generated during routine clinical care and extracted by automated search of medical records. Insulin resistance (IR) was measured for sensitivity analyses using the Lipoprotein Insulin Resistance Index (LP‐IR), a validated IR score having strong associations with glucose disposal rates and homeostasis model assessment of IR in the Multi‐Ethnic Study of Atherosclerosis (see Data S3 for additional details) 29. This research was approved by the Duke University Institutional Review Board.…”

Section: Methodsmentioning

confidence: 99%

“…Metabolite measurements were performed at the Sarah W. Stedman Nutrition Center and Metabolomics Core Laboratory at the Duke Molecular Physiology Institute. IR scores were derived from lipoprotein particle measurements, which were obtained using nuclear magnetic resonance spectroscopy at LipoScience Incorporated (Raleigh, NC) 29, 37. Team members were blinded to group status and samples were randomly distributed to mitigate biases.…”

Section: Methodsmentioning

confidence: 99%

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Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

Hunter

Kelly

McGarrah

et al. 2016

JAHA

186

128

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BackgroundMetabolic impairment is an important contributor to heart failure (HF) pathogenesis and progression. Dysregulated metabolic pathways remain poorly characterized in patients with HF and preserved ejection fraction (HFpEF). We sought to determine metabolic abnormalities in HFpEF and identify pathways differentially altered in HFpEF versus HF with reduced ejection fraction (HFrEF).Methods and ResultsWe identified HFpEF cases, HFrEF controls, and no‐HF controls from the CATHGEN study of sequential patients undergoing cardiac catheterization. HFpEF cases (N=282) were defined by left ventricular ejection fraction (LVEF) ≥45%, diastolic dysfunction grade ≥1, and history of HF; HFrEF controls (N=279) were defined similarly, except for having LVEF <45%. No‐HF controls (N=191) had LVEF ≥45%, normal diastolic function, and no HF diagnosis. Targeted mass spectrometry and enzymatic assays were used to quantify 63 metabolites in fasting plasma. Principal components analysis reduced the 63 metabolites to uncorrelated factors, which were compared across groups using ANCOVA. In basic and fully adjusted models, long‐chain acylcarnitine factor levels differed significantly across groups (P<0.0001) and were greater in HFrEF than HFpEF (P=0.0004), both of which were greater than no‐HF controls. We confirmed these findings in sensitivity analyses using stricter inclusion criteria, alternative LVEF thresholds, and adjustment for insulin resistance.ConclusionsWe identified novel circulating metabolites reflecting impaired or dysregulated fatty acid oxidation that are independently associated with HF and differentially elevated in HFpEF and HFrEF. These results elucidate a specific metabolic pathway in HF and suggest a shared metabolic mechanism in HF along the LVEF spectrum.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

Hunter

Kelly

McGarrah

et al. 2016

JAHA

186

128

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“…Since a ketogenic diet has shown to increase HDL and decrease LDL cholesterol in both obese and normal weight individuals, it has been proposed that ɛ4 carriers would benefit more from a ketogenic diet than non-carriers, particularly in regards to protection from AD (58–60). Furthermore, diets higher in saturated fats or diets rich in olive oil and high in monounsaturated fats both show more favorable outcomes in LDL-particle count in ɛ4 individuals than ɛ3 individuals (61–64); LDL-particle count is seen as a better measure of atherogenicity than LDL cholesterol itself (65, 66). …”

Section: Overview Of Apoementioning

confidence: 99%

Age, APOE and sex: Triad of risk of Alzheimer’s disease

Riedel

Thompson

Brinton

2016

The Journal of Steroid Biochemistry and Molecular Biology

455

373

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Age, apolipoprotein E ɛ4 (APOE) and chromosomal sex are well-established risk factors for late-onset Alzheimer’s disease (LOAD; AD). Over 60% of persons with AD harbor at least one APOE-ɛ4 allele. The sex-based prevalence of AD is well documented with over 60% of persons with AD being female. Evidence indicates that the APOE-ɛ4 risk for AD is greater in women than men, which is particularly evident in heterozygous women carrying one APOE-ɛ4 allele. Paradoxically, men homozygous for APOE-ɛ4 are reported to be at greater risk for mild cognitive impairment and AD. Herein, we discuss the complex interplay between the three greatest risk factors for Alzheimer’s disease, age, APOE-ɛ4 genotype and female sex. We propose that the convergence of these three risk factors, and specifically the bioenergetic aging perimenopause to menopause transition unique to the female, creates a risk profile for AD unique to the female. Further, we discuss the unique risk of the APOE4 positive male which appears to emerge early in the aging process. Evidence for impact of the triad of AD risk factors is most evident in the temporal trajectory of AD progression and burden of pathology in relation to APOE genotype, age and sex. Collectively, the data indicate complex interactions between age, APOE genotype and gender that belies a one size fits all approach and argues for a precision medicine approach that integrates across the three main risk factors for Alzheimer’s disease.

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“…Of note, based on HDL-C, total cholesterol, insulin, and free fatty acids, another lipid parameterbased index has been derived (10 ). Recently, Shalaurova et al introduced the lipoprotein resistance index, based on nuclear magnetic resonance (NMR)-derived lipoprotein information, to identify individuals with insulin resistance (11 ).…”

mentioning

confidence: 99%

Modification and Validation of the Triglyceride-to–HDL Cholesterol Ratio as a Surrogate of Insulin Sensitivity in White Juveniles and Adults without Diabetes Mellitus: The Single Point Insulin Sensitivity Estimator (SPISE)

et al. 2016

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BACKGROUND The triglyceride-to–HDL cholesterol (TG/HDL-C) ratio was introduced as a tool to estimate insulin resistance, because circulating lipid measurements are available in routine settings. Insulin, C-peptide, and free fatty acids are components of other insulin-sensitivity indices but their measurement is expensive. Easier and more affordable tools are of interest for both pediatric and adult patients. METHODS Study participants from the Relationship Between Insulin Sensitivity and Cardiovascular Disease [43.9 (8.3) years, n = 1260] as well as the Beta-Cell Function in Juvenile Diabetes and Obesity study cohorts [15 (1.9) years, n = 29] underwent oral-glucose-tolerance tests and euglycemic clamp tests for estimation of whole-body insulin sensitivity and calculation of insulin sensitivity indices. To refine the TG/HDL ratio, mathematical modeling was applied including body mass index (BMI), fasting TG, and HDL cholesterol and compared to the clamp-derived M-value as an estimate of insulin sensitivity. Each modeling result was scored by identifying insulin resistance and correlation coefficient. The Single Point Insulin Sensitivity Estimator (SPISE) was compared to traditional insulin sensitivity indices using area under the ROC curve (aROC) analysis and χ2 test. RESULTS The novel formula for SPISE was computed as follows: SPISE = 600 × HDL-C0.185/(TG0.2 × BMI1.338), with fasting HDL-C (mg/dL), fasting TG concentrations (mg/dL), and BMI (kg/m2). A cutoff value of 6.61 corresponds to an M-value smaller than 4.7 mg · kg−1 · min−1 (aROC, M:0.797). SPISE showed a significantly better aROC than the TG/HDL-C ratio. SPISE aROC was comparable to the Matsuda ISI (insulin sensitivity index) and equal to the QUICKI (quantitative insulin sensitivity check index) and HOMA-IR (homeostasis model assessment–insulin resistance) when calculated with M-values. CONCLUSIONS The SPISE seems well suited to surrogate whole-body insulin sensitivity from inexpensive fasting single-point blood draw and BMI in white adolescents and adults.

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Lipoprotein Insulin Resistance Index: A Lipoprotein Particle–Derived Measure of Insulin Resistance

Abstract: LP-IR scores had strong associations with multiple measures, HOMA-IR, and GDR, the former being more reflective of hepatic and the latter of peripheral insulin sensitivity, and may represent a simple means to identify individuals with IR.

Cited by 138 publications

References 36 publications

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

Metabolomic Profiling Identifies Novel Circulating Biomarkers of Mitochondrial Dysfunction Differentially Elevated in Heart Failure With Preserved Versus Reduced Ejection Fraction: Evidence for Shared Metabolic Impairments in Clinical Heart Failure

Age, APOE and sex: Triad of risk of Alzheimer’s disease

Modification and Validation of the Triglyceride-to–HDL Cholesterol Ratio as a Surrogate of Insulin Sensitivity in White Juveniles and Adults without Diabetes Mellitus: The Single Point Insulin Sensitivity Estimator (SPISE)

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