Elevated α-Hydroxybutyrate and Branched-Chain Amino Acid Levels Predict Deterioration of Glycemic Control in Adolescents

Tricò, Domenico; Prinsen, Hetty; Giannini, Cosimo; Graaf, Robin de; Juchem, Christoph; Li, Fangyong; Caprio, Sonia; Santoro, Nicola; Herzog, Raimund I.

doi:10.1210/jc.2017-00475

Cited by 65 publications

(61 citation statements)

References 34 publications

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“…These findings may explain in part our previous finding that, among participants of PREDIMED who were initially free of diabetes, the MedDiet+EVOO intervention significantly reduced risk of type 2 diabetes [16]. Our results are consistent with the findings from our systematic review on metabolomics and type 2 diabetes [6], other recent findings [5, 7–12, 25] and our previous observation on the association between plasma levels of BCAA and incident cardiovascular disease [26]. …”

Section: Discussionsupporting

confidence: 92%

“…The pooled RR per SD of each amino acid ranged from 1.26 (95% CI 1.10, 1.44) to 1.36 (95% CI 1.24, 1.48) [6]. However, none of these studies or subsequent studies [7–13] used repeated measurements of these amino acids over time nor evaluated how dietary interventions can influence changes in the levels of these plasma amino acids and risk of type 2 diabetes. This more dynamic assessment is important because a decreased uptake and an increased release of amino acids from skeletal muscle can also be a consequence of increased protein catabolism with underlying insulin resistance [14].…”

Section: Introductionmentioning

confidence: 99%

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Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk of type 2 diabetes: case-cohort study within the PREDIMED Trial

et al. 2018

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk of type 2 diabetes: case-cohort study within the PREDIMED Trial

et al. 2018

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“…28 Also, as a screening tool, it may contribute to detecting glucose abnormalities at an earlier stage, which would be critical in implementing timely interventions to prevent rapid progression of the disease in this highrisk population. 6,[42][43][44] In fact, 1hPG above or equal to 7.4 mmol/L was associated with early alterations in whole-body insulin sensitivity and β-cell function that persisted at follow-up, in agreement with previous observations. 28,29 In our study, the 7.4 mmol/L-cut point, but not the 8.6 mmol/L-threshold, was associated with increased odds of developing prediabetes over time.…”

Section: Discussionsupporting

confidence: 91%

“…The lower cut point of 7.4 mmol/L may have some advantages in a population of obese youths because it provides a better combination of sensitivity and specificity than the 8.6 mmol/L cut point in our study and in previous cross‐sectional analyses . Also, as a screening tool, it may contribute to detecting glucose abnormalities at an earlier stage, which would be critical in implementing timely interventions to prevent rapid progression of the disease in this high‐risk population . In fact, 1hPG above or equal to 7.4 mmol/L was associated with early alterations in whole‐body insulin sensitivity and β‐cell function that persisted at follow‐up, in agreement with previous observations .…”

Section: Discussionmentioning

confidence: 65%

One‐hour post‐load plasma glucose predicts progression to prediabetes in a multi‐ethnic cohort of obese youths

Tricò

Galderisi

Mari

et al. 2019

Diabetes Obesity Metabolism

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AIMS One‐hour post‐load hyperglycaemia has been proposed as an independent predictor of type 2 diabetes in adults. We examined whether 1‐hour plasma glucose (1hPG) during an oral glucose tolerance test (OGTT) can predict changes in the glucose tolerance status of a multi‐ethnic cohort of youths with normal glucose tolerance (NGT). Materials and methods A total of 202 obese youths with NGT (33.7% Caucasian, 31.1% Hispanic, 32.2% African American) underwent a 3‐hour OGTT at baseline and after a 2‐year follow‐up period. Whole‐body insulin sensitivity, insulin secretion, β‐cell function and insulin clearance were estimated by modeling plasma glucose, insulin and C‐peptide levels. Results Obese youths with 1hPG ≥7.4 mmol/L (or 133 mg/dL; n = 83) exhibited higher body mass index (BMI), plasma triglycerides and fasting and post‐load glucose concentrations than individuals with 1hPG <7.4 mmol/L. Also, 1hPG ≥7.4 mmol/L was associated with a lower disposition index (DI) (P < 0.0001) and with alterations in whole‐body insulin sensitivity, β‐cell function and insulin clearance. Adolescents with 1hPG ≥7.4 mmol/L were approximately three times more likely to develop prediabetes (ie, impaired glucose tolerance and/or impaired fasting glucose) over time (OR, 2.92 [1.22‐6.98]; P = 0.02), independent of age, sex, race/ethnicity, BMI, insulin sensitivity, DI and plasma glucose concentrations. No differences emerged in the risk of prediabetes related to 1‐hour hyperglycaemia among different ethnic groups. Conclusions A plasma glucose concentration ≥ 7.4 mmol/L at 1 hour during an OGTT is associated with a worse clinical and metabolic phenotype and may be an independent predictor of progression to prediabetes in obese youths with NGT.

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“…Subjects were phenotyped with respect to their glucose tolerance by a standard OGTT (Supporting Methods) and to HFF and abdominal fat distribution by using fast MRI. (19)(20)(21) From OGTT data, insulin sensitivity and early-phase insulin secretion were assessed by the whole-body insulin sensitivity index (WBISI) and the insulinogenic index (IGI), respectively. The disposition index (DI) was calculated as the product of the WBISI and the IGI (Supporting Methods).…”

Section: The Yale Pediatric Nafld Cohortmentioning

confidence: 99%

Metabolic Features of Nonalcoholic Fatty Liver (NAFL) in Obese Adolescents: Findings From a Multiethnic Cohort

Tricò¹,

Caprio²,

Umano³

et al. 2018

Hepatology

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We conducted a prospective study in a large, multiethnic cohort of obese adolescents to characterize clinical and genetic features associated with pediatric nonalcoholic fatty liver (NAFL), the most common cause of chronic liver disease in youth. A total of 503 obese adolescents were enrolled, including 191 (38.0%) whites, 134 (26.6%) blacks, and 178 (35.4%) Hispanics. Participants underwent abdominal magnetic resonance imaging (MRI) to quantify hepatic fat fraction (HFF), an oral glucose tolerance test (OGTT) to assess glucose tolerance and insulin sensitivity, and the genotyping of three single‐nucleotide polymorphisms (SNPs) associated with nonalcoholic fatty liver disease (NAFLD) (patatin‐like phospholipase domain‐containing protein 3 [PNPLA3] rs738409, glucokinase regulatory protein [GCKR] rs1260326, and transmembrane 6 superfamily member 2 [TM6SF2] rs58542926). Assessments were repeated in 133 subjects after a 2‐year follow‐up. Prevalence of nonalcoholic fatty liver (NAFL) was 41.6% (209 patients) and ranged widely among ethnicities, being 42.9% in whites, 15.7% in blacks, and 59.6% in Hispanics (P < 0.0001). Among adolescents with NAFL, blacks showed the highest prevalence of altered glucose homeostasis (66%; P = 0.0003). Risk factors for NAFL incidence were white or Hispanic ethnicity (P = 0.021), high fasting C‐peptide levels (P = 0.0006), and weight gain (P = 0.0006), whereas baseline HFF (P = 0.004) and weight loss (P = 0.032) predicted resolution of NAFL at follow‐up. Adding either gene variant to these variables improved significantly the model predictive performance. Conclusion: Black obese adolescents are relatively protected from liver steatosis, but are more susceptible to the deleterious effects of NAFL on glucose metabolism. The combination of ethnicity/race with markers of insulin resistance and genetic factors might help identify obese youth at risk for developing NAFL.

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Elevated α-Hydroxybutyrate and Branched-Chain Amino Acid Levels Predict Deterioration of Glycemic Control in Adolescents

Abstract: α-Hydroxybutyrate and BCAA concentrations during an OGTT characterize insulin-resistant youth and predict worsening of glycemic control. These findings provide potential biomarkers for risk assessment of type 2 diabetes and new insights into IR pathogenesis.

Cited by 65 publications

References 34 publications

Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk of type 2 diabetes: case-cohort study within the PREDIMED Trial

Plasma branched chain/aromatic amino acids, enriched Mediterranean diet and risk of type 2 diabetes: case-cohort study within the PREDIMED Trial

One‐hour post‐load plasma glucose predicts progression to prediabetes in a multi‐ethnic cohort of obese youths

Metabolic Features of Nonalcoholic Fatty Liver (NAFL) in Obese Adolescents: Findings From a Multiethnic Cohort

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