Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men

Tai, E. Shyong; Tan, Mark; Stevens, Robert; Low, Yen-Ling; Muehlbauer, Michael J.; Goh, Denise; Ilkayeva, Olga; Wenner, Brett R.; Bain, James R.; Lee, J. J. M.; Lim, Su Chi; Khoo, Chin Meng; Shah, Svati H.; Newgard, Christopher B.

doi:10.1007/s00125-009-1637-8

Cited by 412 publications

(387 citation statements)

References 48 publications

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“…Increased levels of branched-chain (18)(19)(20) and aromatic (16)(17)(18)(19) amino acids in plasma and sera have been identified as markers and predictors of type 2 diabetes, whereas decreased levels of glycine were found to be correlated with diabetes (19,21). Our results from discovery metabonomic profiling showed no significant differences in the levels of these amino acids between DR cases and control subjects with diabetes (Supplementary Table 8).…”

Section: Metabolite Markers Of Dr Are Distinct From Diabetesmentioning

confidence: 59%

“…The study of metabolic phenotypes (metabotypes) in association with disease states may reveal new knowledge in disease mechanism and pathophysiology (12). Recent metabonomic studies have uncovered plasma and sera metabolic signatures associated with, or predictive of, impaired glucose tolerance and diabetes (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Furthermore, DR is a complex disease where findings from genomewide association studies have not been conclusive (23).…”

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confidence: 99%

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Plasma Metabonomic Profiling of Diabetic Retinopathy

et al. 2016

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Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of visual impairment in working-age adults. Patients with diabetes often develop DR despite appropriate control of systemic risk factors, suggesting the involvement of other pathogenic factors. We hypothesize that the plasma metabolic signature of DR is distinct and resolvable from that of diabetes alone. A nested populationbased case-control metabonomic study was first performed on 40 DR cases and 40 control subjects with diabetes using gas chromatography-mass spectrometry. Eleven metabolites were found to be correlated with DR, and the majority were robust when adjusted for metabolic risk factors and confounding kidney disease. The metabolite markers 2-deoxyribonic acid; 3,4-dihydroxybutyric acid; erythritol; gluconic acid; and ribose were validated in an independent sample set with 40 DR cases, 40 control subjects with diabetes, and 40 individuals without diabetes. DR cases and control subjects with diabetes were matched by HbA 1c in the validation set. Activation of the pentose phosphate pathway was identified from the list of DR metabolite markers. The identification of novel metabolite markers for DR provides insights into potential new pathogenic pathways for this microvascular complication and holds translational value in DR risk stratification and the development of new therapeutic measures.Diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of visual impairment in working-age adults worldwide (1,2). The global prevalence of diabetes is rising and the number of people with diabetes is projected to increase by 54% in 2030, compared with 2010 (3). The public health burden of diabetes and DR would thus increase correspondingly. The major risk factors of DR are poor glycemic control and hypertension, as well as the duration of diabetes (4,5), but their relative importance varies between studies (2,6). Although the risks of DR progression and vision loss are reduced with intensive control of risk factors (7,8), many patients with diabetes continue to develop complications despite tight glycemic and blood pressure control. There is increasing evidence to suggest that "metabolic memory" is responsible for this observation. The term metabolic memory refers to the persistent epigenetic modifications caused by early exposure to hyperglycemia that, in turn, predispose individuals to the development of diabetes complications even after good glycemic control

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Section: Metabolite Markers Of Dr Are Distinct From Diabetesmentioning

confidence: 59%

mentioning

confidence: 99%

Plasma Metabonomic Profiling of Diabetic Retinopathy

et al. 2016

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“…Briefly, 1 μl of cDNA was added to 12 μl of master mix containing specific primers for genes of interest. We designed primer pairs for all genes ( Gapdh , Htr1a , Htr2c , Slc6a4 , Drd1 , and Drd2 ; see Table 1) as previously described (Tai et al., 2010). Designed primers were obtained from Integrated DNA Technologies, Inc. (Coralville, IA, USA).…”

Section: Methodsmentioning

confidence: 99%

Perinatal western‐type diet and associated gestational weight gain alter postpartum maternal mood

et al. 2017

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IntroductionThe role of perinatal diet in postpartum maternal mood disorders, including depression and anxiety, remains unclear. We investigated whether perinatal consumption of a Western‐type diet (high in fat and branched‐chain amino acids [BCAA]) and associated gestational weight gain (GWG) cause serotonin dysregulation in the central nervous system (CNS), resulting in postpartum depression and anxiety (PPD/A).MethodsMouse dams were fed one of four diets (high‐fat/high BCAA, low‐fat/high BCAA, high‐fat, and low‐fat) prior to mating and throughout gestation and lactation. Postpartum behavioral assessments were conducted, and plasma and brain tissues assayed. To evaluate potential clinical utility, we conducted preliminary human studies using data from an extant sample of 17 primiparous women with high GWG, comparing across self‐reported postpartum mood symptoms using the Edinburgh Postnatal Depression Scale (EPDS) for percent GWG and plasma amino acid levels.ResultsMouse dams fed the high‐fat/high BCAA diet gained more weight per kcal consumed, and BCAA‐supplemented dams lost weight more slowly postpartum. Dams on BCAA‐supplemented diets exhibited increased PPD/A‐like behavior, decreased dopaminergic function, and decreased plasma tyrosine and histidine levels when assessed on postnatal day (P)8. Preliminary human data showed that GWG accounted for 29% of the variance in EPDS scores. Histidine was also lower in women with higher EPDS scores.ConclusionsThese findings highlight the role of perinatal diet and excess GWG in the development of postpartum mood disorders.

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“…Also, it is previously proven that elevated branched chain and aromatic amino acids levels are associated with insulin resistance and type 2 diabetes [15].…”

Section: Anti-diabeticsmentioning

confidence: 99%

Metabolomics: A Tool Ahead for Understanding Molecular Mechanisms of Drugs and Diseases

2014

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To refer to metabolomics as a new field is injustice to ancient doctors who used ants to diagnose the patients of diabetes having glycosuria. Measuring the levels of molecules in biological fluids believing them to be the representatives of biochemical pathways of carbohydrates, fats, proteins, nucleic acids or xenobiotic metabolism and deciphering meaningful data from it is what can be called as metabolomics, just as high glucose in urine suggests diabetes mellitus. Genomics, epigenetics, proteomics, transcriptomics finally converge to metabolomics, which are the signatures of mechanisms of bodily processes which is why understanding this science can have many applications. Just as a heap of stones does not make a house, having data of metabolite levels does not make it a science. Analyzing this data would help us in constructing biochemical pathways and their interactions. Analyzing the changes caused by a drug in the metabolite levels would help us in deriving the mechanisms by which the drug acts. Comparing metabolite levels in diseased with non-diseased, good-responders with poor-responders to a particular drug can help in identifying new markers of a disease or response to a drug respectively. Also, metabolite levels of an endogenous substrate can tell us the status of a person's metabolizing enzymes and help in drug dose titration. Generating hypothesis by identifying the new molecular markers and testing their utility in clinics seems to be the most promising approach in future. This review narrates the modes of quantifying and identifying metabolome, its proposed applications in diagnosis, monitoring and understanding the diseases and drug responses. We also intend to identify hindrances in using metabolomics in clinical studies or experiments.

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Insulin resistance is associated with a metabolic profile of altered protein metabolism in Chinese and Asian-Indian men

Cited by 412 publications

References 48 publications

Plasma Metabonomic Profiling of Diabetic Retinopathy

Plasma Metabonomic Profiling of Diabetic Retinopathy

Perinatal western‐type diet and associated gestational weight gain alter postpartum maternal mood

Metabolomics: A Tool Ahead for Understanding Molecular Mechanisms of Drugs and Diseases

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