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

Autor: Cosimo Giannini, Nicola Santoro, Raimund I. Herzog, Fangyong Li, Hetty Prinsen, Robin A. de Graaf, Sonia Caprio, Domenico Tricò, Christoph Juchem
Rok vydání: 2017
Předmět:
Blood Glucose
Male
0301 basic medicine
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Hydroxybutyrates
Type 2 diabetes
Biochemistry
0302 clinical medicine
Endocrinology
Reference Values
Longitudinal Studies
Amino Acids
Adolescent
Amino Acids
Branched-Chain
Biomarkers
Child
Cross-Sectional Studies
Diabetes Mellitus
Type 2
Female
Glucose Tolerance Test
Humans
Insulin Resistance
Linear Models
Multivariate Analysis
Obesity
Predictive Value of Tests
Risk Assessment
Glycemic Index
Glucose tolerance test
medicine.diagnostic_test
Diabetes and Metabolism
Glycemic index
Type 2
medicine.medical_specialty
030209 endocrinology & metabolism
Context (language use)
03 medical and health sciences
Insulin resistance
Internal medicine
Diabetes Mellitus
medicine
Clinical Research Articles
Glycemic
business.industry
Biochemistry (medical)
Type 2 Diabetes Mellitus
Branched-Chain
medicine.disease
030104 developmental biology
business
Body mass index
Zdroj: The Journal of Clinical Endocrinology & Metabolism. 102:2473-2481
ISSN: 1945-7197
0021-972X
DOI: 10.1210/jc.2017-00475
Popis: Context Traditional risk factors for type 2 diabetes mellitus are weak predictors of changes in glucose tolerance and insulin sensitivity in youth. Objective To identify early metabolic features of insulin resistance (IR) in youth and whether they predict deterioration of glycemic control. Design and Setting A cross-sectional and longitudinal study was conducted at the Yale Pediatric Obesity Clinic. Patients and Intervention Concentrations of α-hydroxybutyrate, β-hydroxybutyrate, lactate, and branched-chain amino acids (BCAAs) were measured by nuclear magnetic resonance spectroscopy in 78 nondiabetic adolescents during an oral glucose tolerance test (OGTT). Associations between baseline metabolic alterations and longitudinal changes in glucose control were tested in 16 subjects after a mean follow-up of 2.3 years. Main Outcome Measures The relationship between metabolite levels, parameters of IR, and glycemic control, and their progression over time. Results Elevated fasting α-hydroxybutyrate levels were observed in adolescents with reduced insulin sensitivity after adjusting for age, sex, ethnicity, Tanner stage, and body mass index z-score (P = 0.014). Plasma α-hydroxybutyrate and BCAAs were increased throughout the course of the OGTT in this group (P < 0.03). Notably, borderline IR was associated with a progressive α-hydroxybutyrate decrease from elevated baseline concentrations to normal levels (P = 0.02). Increased baseline α-hydroxybutyrate concentrations were further associated with progressive worsening of glucose tolerance and disposition index. Conclusion 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.
Databáze: OpenAIRE
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