Longitudinal Plasma Lipidome and Risk of Type 2 Diabetes in a Large Sample of American Indians With Normal Fasting Glucose: The Strong Heart Family Study

Miao, Guanhong; Zhang, Ying; Huo, Zhiguang; Zhang, Wenjie; Zhu, Jianhui; Umans, Jason G.; Wohlgemuth, Gert; Pedrosa, Diego França; DeFelice, Brian C.; Cole, Shelley A.; Fretts, Amanda M.; Lee, Elisa T.; Howard, Barbara V.; Fiehn, Oliver; Zhao, Jinying

doi:10.2337/dc21-0451

Cited by 17 publications

(15 citation statements)

References 47 publications

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“…These results seem to be consistent with a previous study demonstrating that very-long-chain ceramides (e.g., 18:1/20:0 and 18:1/24:0) were negatively correlated with insulin resistance or glucose levels in rats with pre-diabetes [59]. The observed positive associations of very-long-chain unsaturated SMs with LTL corroborate findings from our own group in the same study population showing that some specific SMs (e.g., d40:3) were associated with decreased risk of diabetes [30] and chronic kidney disease [60].…”

Section: Discussionsupporting

confidence: 86%

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Lipidomics profiling of biological aging in American Indians: the Strong Heart Family Study

Subedi

Palma-Gudiel²,

Fiehn³

et al. 2022

GeroScience

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of biological aging assessed by LTL. Briefly, LTL was quantified by qPCR. Fasting plasma lipids were quantified by untargeted liquid chromatography-mass spectrometry. Lipids associated with LTL were identified by elastic net modeling. Of 1542 molecular lipids identified (518 known, 1024 unknown), 174 lipids (36 knowns) were significantly associated with LTL, independent of chronological age, sex, BMI, hypertension, diabetes status, smoking status, bulk HDL-C, and LDL-C. These findings suggest that altered lipid metabolism is associated with biological aging and provide novel insights that may enhance our understanding of the relationship between dyslipidemia, biological aging, and age-related diseases in American Indians.

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Section: Discussionsupporting

confidence: 86%

“…Detailed methods for plasma sample collection, lipidomic data generation, pre-processing, and quality control in the SHFS have been reported elsewhere [30]. Briefly, a modified liquid-liquid extraction method (cold methanol/MTBE/water) [31,32] was used to extract fasting plasma samples.…”

Section: Lipidomics Data Acquisition By Liquid Chromatography-mass Sp...mentioning

confidence: 99%

Lipidomics profiling of biological aging in American Indians: the Strong Heart Family Study

Subedi

Palma-Gudiel²,

Fiehn³

et al. 2022

GeroScience

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“…Although the specific lipid species may vary between studies (due to using different mass spectrometry platforms), our findings appeared to be consistent with previous reports showing that some species of glycerophospholipids, for example, PC(32:1), PC(34:1), PC(36:5), PC(38:4), PC(p-36:2)/PC(o-36:3), PE(38:4), were associated with hypertension in other racial/ethnic groups. 9,13,[36][37][38] In addition, many of the identified glycerophospholipids (eg, PC(32:1), PC(34:1), PE(16:0/16:1), PE(36:4), LPC(18:2)) were also associated with risk of chronic kidney disease in American Indians 21 and CVD in Europeans. 25 Plasminogen, a subclass of membrane glycerophospholipids, is primarily present as PCs or PEs and exhibits diverse biological functions.…”

Section: Discussionmentioning

confidence: 99%

“…In the SHFS, methods for lipidomic data acquisition, processing, and normalization have been described previously. 21 Briefly, relative abundance of molecular lipid species in fasting plasma samples at 2 time points (~5.5 years apart) was quantified by untargeted liquid chromatography-mass spectrometry. After preprocessing and quality control, we obtained 1542 lipids (518 known) in 3925 samples (1970 at baseline, 1955 at follow-up).…”

Section: Methodsmentioning

confidence: 99%

Longitudinal Lipidomic Profile of Hypertension in American Indians: Findings From the Strong Heart Family Study

et al. 2023

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BACKGROUND: Dyslipidemia is an important risk factor for hypertension and cardiovascular disease. Standard lipid panel cannot reflect the complexity of blood lipidome. The associations of individual lipid species with hypertension remain to be determined in large-scale epidemiological studies, especially in a longitudinal setting. METHODS: Using liquid chromatography-mass spectrometry, we repeatedly measured 1542 lipid species in 3699 fasting plasma samples at 2 visits (1905 at baseline, 1794 at follow-up, ~5.5 years apart) from 1905 unique American Indians in the Strong Heart Family Study. We first identified baseline lipids associated with prevalent and incident hypertension, followed by replication of top hits in Europeans. We then conducted repeated measurement analysis to examine the associations of changes in lipid species with changes in systolic blood pressure, diastolic blood pressure, and mean arterial pressure. Network analysis was performed to identify lipid networks associated with the risk of hypertension. RESULTS: Baseline levels of multiple lipid species, for example, glycerophospholipids, cholesterol esters, sphingomyelins, glycerolipids, and fatty acids, were significantly associated with both prevalent and incident hypertension in American Indians. Some lipids were confirmed in Europeans. Longitudinal changes in multiple lipid species, for example, acylcarnitines, phosphatidylcholines, fatty acids, and triacylglycerols, were significantly associated with changes in blood pressure measurements. Network analysis identified distinct lipidomic patterns associated with the risk of hypertension. CONCLUSIONS: Baseline plasma lipid species and their longitudinal changes are significantly associated with hypertension development in American Indians. Our findings shed light on the role of dyslipidemia in hypertension and may offer potential opportunities for risk stratification and early prediction of hypertension.

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“…In the SHFS, relative abundance of molecular lipid species in fasting plasma samples at 2 time points (≈5.5 years apart) was quantified by untargeted liquid chromatography mass spectrometry. 19 Detailed methods for lipidomic data acquisition and preprocessing have been described elsewhere. 19 After preprocessing and quality control, we obtained 1542 lipids (518 known) in 3977 samples (1983 at baseline, 1994 at follow‐up).…”

Section: Methodsmentioning

confidence: 99%

Longitudinal Lipidomic Signature of Coronary Heart Disease in American Indian People

Miao,

Pechlaner,

Fiehn

et al. 2024

JAHA

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Background Dyslipidemia is an independent risk factor for coronary heart disease (CHD). Standard lipid panel cannot capture the complexity of the blood lipidome (ie, all molecular lipids in the blood). To date, very few large‐scale epidemiological studies have assessed the full spectrum of the blood lipidome on risk of CHD, especially in a longitudinal setting. Methods and Results Using an untargeted liquid chromatography–mass spectrometry, we repeatedly measured 1542 lipid species from 1835 unique American Indian participants who attended 2 clinical visits (≈5.5 years apart) and followed up to 17.8 years in the Strong Heart Family Study (SHFS). We first identified baseline lipid species associated with risk of CHD, followed by replication in a European population. The model adjusted for age, sex, body mass index, smoking, hypertension, diabetes, low‐density lipoprotein cholesterol, estimated glomerular filtration rate, education, and physical activity at baseline. We then examined the longitudinal association between changes in lipid species and changes in cardiovascular risk factors during follow‐up. Multiple testing was controlled by the false discovery rate. We found that baseline levels of multiple lipid species (eg, phosphatidylcholines, phosphatidylethanolamines, and ceramides) were associated with the risk of CHD and improved the prediction accuracy over conventional risk factors in American Indian people. Some identified lipids in American Indian people were replicated in European people. Longitudinal changes in multiple lipid species (eg, acylcarnitines, phosphatidylcholines, and triacylglycerols) were associated with changes in cardiovascular risk factors. Conclusions Baseline plasma lipids and their longitudinal changes over time are associated with risk of CHD. These findings provide novel insights into the role of dyslipidemia in CHD.

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Longitudinal Plasma Lipidome and Risk of Type 2 Diabetes in a Large Sample of American Indians With Normal Fasting Glucose: The Strong Heart Family Study

Cited by 17 publications

References 47 publications

Lipidomics profiling of biological aging in American Indians: the Strong Heart Family Study

Lipidomics profiling of biological aging in American Indians: the Strong Heart Family Study

Longitudinal Lipidomic Profile of Hypertension in American Indians: Findings From the Strong Heart Family Study

Longitudinal Lipidomic Signature of Coronary Heart Disease in American Indian People

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