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The amino acid response to a mixed meal in patients with type 2 diabetes: effect of sitagliptin treatment.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Muscelli, E. Frascerra, S. Casolaro, A. Baldi, S. Mari, A. Gall, W. Cobb, J. Ferrannini, E.
Description	Country affiliation: Italy Author Affiliation: Muscelli E ( Department of Clinical & Experimental Medicine, University of Pisa, Pisa, Italy.)
Abstract	AIMS: Amino acid (AA) metabolism is altered in type 2 diabetes (T2D), and fasting levels of -hydroxybutyrate ( -HB), a biomarker for insulin resistance, have been suggested to track AA metabolism. We investigated the changes in AA and -HB induced by a mixed-meal tolerance test (MTT) and the effects of sitagliptin treatment. METHODS: Forty-seven T2D patients [56 ± 7 years, body mass index (BMI) 29.9 ± 4.2 kg/m(2) ] were randomized to sitagliptin (100 mg/day, 6 weeks) or placebo. Seven age- and BMI-matched non-diabetic subjects served as control (CT). RESULTS: During a 5-h MTT, branched-chain AA (BCAA) peaked earlier in T2D than CT [75(25) vs. 62(3) mmol/l · h over 2 h, median(interquartile range), p = 0.05], and rose higher [5-h increment: 31(23) vs. 19(24) mmol/l · h, p = 0.05]. Fasting -HB was higher [7.5(2.7) vs. 5.9(1.3) µg/ml, p = 0.04 T2D vs. CT], and its meal-induced increments were larger [24(99) vs. -41(86) µg/ml · h, p = 0.006]. Plasma non-esterified fatty acids (NEFA) declined during MTT, but their increments were greater in patients (53 ± 16 vs. 35 ± 10 mEq/l · h, p = 0.005). Compared to placebo, both BCAA [-6.4(21.1) vs. 0.0(48.0) mmol/l · h, p = 0.01] and -HB increments [-114(250) vs. 114(428) µg/ml · h, p = 0.002] decreased with sitagliptin, and meal-induced NEFA suppression was improved. Changes in BCAA and -HB were reciprocally related to changes in insulin sensitivity (ρ = -0.37 and -0.43, p ≤ 0.01). CONCLUSIONS: T2D is associated with a hyperaminoacidaemic response to MTT, which circulating -HB levels track. Sitagliptin-induced glycaemic improvement was associated with reductions in BCAA and -HB excursions and better NEFA suppression, in parallel with improved insulin sensitivity, confirming that -HB is a readout of metabolic overload.
File Format	HTM / HTML
ISSN	14628902
Issue Number	11
Volume Number	16
e-ISSN	14631326
Journal	Diabetes, Obesity and Metabolism
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2014-11-01
Publisher Place	Great Britain (UK)
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Metabolism Discipline Endocrinology Discipline Pharmacology Discipline Diabetology Amino Acids Drug Effects Blood Glucose Diabetes Mellitus, Type 2 Drug Therapy Dipeptidyl-peptidase Iv Inhibitors Administration & Dosage Hydroxybutyrates Metabolism Pyrazines Triazoles Adult Aged Biological Markers Body Mass Index Blood Fasting Female Humans Insulin Insulin Resistance Male Meals Middle Aged Sitagliptin Phosphate Journal Article Randomized Controlled Trial Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Endocrinology, Diabetes and Metabolism Internal Medicine Endocrinology

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