Plasma Amino Acids vs Conventional Predictors of Insulin Resistance Measured by the Hyperinsulinemic Clamp

Labonte, Cherise C; Farsijani, Samaneh; Marliss, Errol B.; Gougeon, Réjeanne; Morais, José A.; Pereira, Sandra; Bassil, Maya; Winter, Aaron; Murphy, Jessica; Combs, Terry P.; Chevalier, Stéphanie

doi:10.1210/js.2016-1108

Cited by 11 publications

(11 citation statements)

References 40 publications

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“…The physiological significance and underlying mechanisms responsible are unclear. Nonetheless, these findings support the suggestion of sex-specific regulation of amino acid metabolism [47].…”

Section: Discussionsupporting

confidence: 88%

Mechanisms of hyperinsulinaemia in apparently healthy non-obese young adults: role of insulin secretion, clearance and action and associations with plasma amino acids

et al. 2019

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Aims/hypothesisThis study aimed to examine the metabolic health of young apparently healthy non-obese adults to better understand mechanisms of hyperinsulinaemia.MethodsNon-obese (BMI < 30 kg/m2) adults aged 18–35 years (N = 254) underwent a stable isotope-labelled OGTT. Insulin sensitivity, glucose effectiveness and beta cell function were determined using oral minimal models. Individuals were stratified into quartiles based on their insulin response during the OGTT, with quartile 1 having the lowest and quartile 4 the highest responses.ResultsThirteen per cent of individuals had impaired fasting glucose (IFG; n = 14) or impaired glucose tolerance (IGT; n = 19), allowing comparisons across the continuum of insulin responses within the spectrum of normoglycaemia and prediabetes. BMI (~24 kg/m2) was similar across insulin quartiles and in those with IFG and IGT. Despite similar glycaemic excursions, fasting insulin, triacylglycerols and cholesterol were elevated in quartile 4. Insulin sensitivity was lowest in quartile 4, and accompanied by increased insulin secretion and reduced insulin clearance. Individuals with IFG had similar insulin sensitivity and beta cell function to those in quartiles 2 and 3, but were more insulin sensitive than individuals in quartile 4. While individuals with IGT had a similar degree of insulin resistance to quartile 4, they exhibited a more severe defect in beta cell function. Plasma branched-chain amino acids were not elevated in quartile 4, IFG or IGT.Conclusions/interpretationHyperinsulinaemia within normoglycaemic young, non-obese adults manifests due to increased insulin secretion and reduced insulin clearance. Individual phenotypic characterisation revealed that the most hyperinsulinaemic were more similar to individuals with IGT than IFG, suggesting that hyperinsulinaemic individuals may be on the continuum toward IGT. Furthermore, plasma branched-chain amino acids may not be an effective biomarker in identifying hyperinsulinaemia and insulin resistance in young non-obese adults.

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Section: Discussionsupporting

confidence: 88%

Mechanisms of hyperinsulinaemia in apparently healthy non-obese young adults: role of insulin secretion, clearance and action and associations with plasma amino acids

et al. 2019

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“…Importantly, among all plasmatic amino acids analyzed individually, glycine had the highest association with alteration in insulin sensitivity, measured using a hyperinsulinemic-euglycemic clamp in 399 non-diabetic subjects presenting a broad range of insulin sensitivity [15]. The same positive association was also found in a smaller study, which used a similar approach [20]. In a consistent fashion, plasma glycine concentration was found to be lower in the lean offspring of T2DM parents compared to healthy children of control subjects [73].…”

Section: Plasma Concentrations Of Glycine Are Decreased In Obesitymentioning

confidence: 78%

Glycine Metabolism and Its Alterations in Obesity and Metabolic Diseases

et al. 2019

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Glycine is the proteinogenic amino-acid of lowest molecular weight, harboring a hydrogen atom as a side-chain. In addition to being a building-block for proteins, glycine is also required for multiple metabolic pathways, such as glutathione synthesis and regulation of one-carbon metabolism. Although generally viewed as a non-essential amino-acid, because it can be endogenously synthesized to a certain extent, glycine has also been suggested as a conditionally essential amino acid. In metabolic disorders associated with obesity, type 2 diabetes (T2DM), and non-alcoholic fatty liver disease (NAFLDs), lower circulating glycine levels have been consistently observed, and clinical studies suggest the existence of beneficial effects induced by glycine supplementation. The present review aims at synthesizing the recent advances in glycine metabolism, pinpointing its main metabolic pathways, identifying the causes leading to glycine deficiency—especially in obesity and associated metabolic disorders—and evaluating the potential benefits of increasing glycine availability to curb the progression of obesity and obesity-related metabolic disturbances. This study focuses on the importance of diet, gut microbiota, and liver metabolism in determining glycine availability in obesity and associated metabolic disorders.

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“…Branched-chain amino acids (BCAA) are comprised of leucine, isoleucine and valine [1]. Their plasma levels have been positively associated with features of the metabolic syndrome (MS), such as insulin resistance (IR) and pre-diabetes [2,3], and thus with an increased risk of type 2 diabetes (T2D) and cardiovascular diseases (CVD) [4,5,6,7,8]. Controversies still remain on whether an increase in plasma BCAA levels is a cause or a consequence of IR.…”

Section: Introductionmentioning

confidence: 99%

Associations Between Dietary Protein Sources, Plasma BCAA and Short-Chain Acylcarnitine Levels in Adults

et al. 2019

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Elevated plasma branched-chain amino acids (BCAA) and C3 and C5 acylcarnitines (AC) levels observed in individuals with insulin resistance (IR) might be influenced by dietary protein intakes. This study explores the associations between dietary protein sources, plasma BCAA levels and C3 and C5 ACs in normal weight (NW) or overweight (OW) individuals with or without metabolic syndrome (MS). Data from 199 men and women aged 18–55 years with complete metabolite profile were analyzed. Associations between metabolic parameters, protein sources, plasma BCAA and AC levels were tested. OW/MS+ consumed significantly more animal protein (p = 0.0388) and had higher plasma BCAA levels (p < 0.0001) than OW/MS− or NW/MS− individuals. Plasma BCAA levels were not associated with BCAA intakes in the whole cohort, while there was a trend for an association between plasma BCAA levels and red meat or with animal protein in OW/MS+. These associations were of weak magnitude. In NW/MS− individuals, the protein sources associated with BCAA levels varied greatly with adjustment for confounders. Plasma C3 and C5 ACs were associated with plasma BCAA levels in the whole cohort (p < 0.0001) and in subgroups based on OW and MS status. These results suggest a modest association of meat or animal protein intakes and an association of C3 and C5 ACs with plasma BCAA levels, obesity and MS.

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Plasma Amino Acids vs Conventional Predictors of Insulin Resistance Measured by the Hyperinsulinemic Clamp

Cited by 11 publications

References 40 publications

Mechanisms of hyperinsulinaemia in apparently healthy non-obese young adults: role of insulin secretion, clearance and action and associations with plasma amino acids

Mechanisms of hyperinsulinaemia in apparently healthy non-obese young adults: role of insulin secretion, clearance and action and associations with plasma amino acids

Glycine Metabolism and Its Alterations in Obesity and Metabolic Diseases

Associations Between Dietary Protein Sources, Plasma BCAA and Short-Chain Acylcarnitine Levels in Adults

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