PMID- 36539818
OWN - NLM
STAT- MEDLINE
DCOM- 20221222
LR  - 20230108
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 21
IP  - 1
DP  - 2022 Dec 20
TI  - Elevated circulating level of beta-aminoisobutyric acid (BAIBA) in heart failure 
      patients with type 2 diabetes receiving sodium-glucose cotransporter 2 
      inhibitors.
PG  - 285
LID - 10.1186/s12933-022-01727-x [doi]
LID - 285
AB  - AIMS: The mechanism by which a sodium-glucose cotransporter inhibitor (SGLT2i) 
      induces favorable effects on diabetes and cardiovascular diseases including heart 
      failure (HF) remains poorly understood. Metabolomics including amino acid 
      profiling enables detection of alterations in whole body metabolism. The aim of 
      this study was to determine whether plasma amino acid profiles are modulated by 
      SGLT2i use in HF patients with type 2 diabetes mellitus (T2DM). METHODS: We 
      retrospectively examined 81 HF patients with T2DM (68 +/- 11 years old; 78% male). 
      Plasma amino acid concentrations in a fasting state after stabilization of HF 
      were determined using ultraperformance liquid chromatography. To minimize 
      potential selection bias in the retrospective analyses, the differences in 
      baseline characteristics between patients receiving an SGLT2i and patients not 
      receiving an SGLT2i were controlled by using an inverse probability of treatment 
      weighting (IPTW)-adjusted analysis. RESULTS: Of amino acids measurable in the 
      present assay, plasma beta-aminoisobutyric acid (BAIBA), an exercise-induced 
      myokine-like molecule also known as 3-aminoisobutyric acid or 
      3-amino-2-methyproponic acid, was detected in 77% of all patients and the 
      proportion of patients in whom plasma BAIBA was detected was significantly higher 
      in patients receiving an SGLT2i than in patients not receiving an SGLT2i (93% vs. 
      67%, p = 0.01). Analyses in patients in whom plasma BAIBA was detected showed 
      that plasma BAIBA concentration was significantly higher in patients receiving an 
      SGLT2i than in patients not receiving an SGLT2i (6.76 +/- 4.72 vs. 4.56 +/- 2.93 
      nmol/ml, p = 0.03). In multivariate logistic regression analyses that were 
      adjusted for age and sex, SGLT2i use was independently associated with BAIBA 
      detection. The independent association between BAIBA and SGLT2i use remained 
      after inclusion of body mass index, HF with reduced ejection fraction, ischemic 
      etiology, renal function, NT-proBNP, albumin, hemoglobin, and HbA1c into the Cox 
      proportional hazards model. When the differences in baseline characteristics 
      between patients receiving an SGLT2i and patients not receiving an SGLT2i were 
      controlled by using an IPTW-adjusted analysis, least squares mean of plasma BAIBA 
      concentration was significantly higher in patients receiving an SGLT2i than in 
      patients not receiving an SGLT2i. CONCLUSION: SGLT2i use is closely associated 
      with increased circulating BAIBA concentration in HF patients with T2DM.
CI  - (c) 2022. The Author(s).
FAU - Katano, Satoshi
AU  - Katano S
AD  - Division of Rehabilitation, Sapporo Medical University Hospital, South-1, 
      West-16, Chuo-ku, Sapporo, 060-8543, Japan.
FAU - Yano, Toshiyuki
AU  - Yano T
AD  - Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical 
      University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, 
      Japan. tyano@sapmed.ac.jp.
FAU - Kouzu, Hidemichi
AU  - Kouzu H
AD  - Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical 
      University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, 
      Japan.
FAU - Nagaoka, Ryohei
AU  - Nagaoka R
AD  - Division of Rehabilitation, Sapporo Medical University Hospital, South-1, 
      West-16, Chuo-ku, Sapporo, 060-8543, Japan.
FAU - Numazawa, Ryo
AU  - Numazawa R
AD  - Graduate School of Medicine, Sapporo Medical University, South-1, West-16, 
      Chuo-ku, Sapporo, 060-8543, Japan.
FAU - Yamano, Kotaro
AU  - Yamano K
AD  - Division of Rehabilitation, Sapporo Medical University Hospital, South-1, 
      West-16, Chuo-ku, Sapporo, 060-8543, Japan.
FAU - Fujisawa, Yusuke
AU  - Fujisawa Y
AD  - Division of Rehabilitation, Sapporo Medical University Hospital, South-1, 
      West-16, Chuo-ku, Sapporo, 060-8543, Japan.
FAU - Ohori, Katsuhiko
AU  - Ohori K
AD  - Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical 
      University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, 
      Japan.
AD  - Department of Cardiology, Hokkaido Cardiovascular Hospital, Sapporo, Japan.
FAU - Nagano, Nobutaka
AU  - Nagano N
AD  - Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical 
      University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, 
      Japan.
FAU - Fujito, Takefumi
AU  - Fujito T
AD  - Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical 
      University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, 
      Japan.
FAU - Nishikawa, Ryo
AU  - Nishikawa R
AD  - Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical 
      University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, 
      Japan.
FAU - Ohwada, Wataru
AU  - Ohwada W
AD  - Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical 
      University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, 
      Japan.
FAU - Katayose, Masaki
AU  - Katayose M
AD  - Second Division of Physical Therapy, Sapporo Medical University School of Health 
      Science, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
FAU - Sato, Tatsuya
AU  - Sato T
AD  - Department of Cellular Physiology and Signal Transduction, Sapporo Medical 
      University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, 
      Japan.
FAU - Kuno, Atsushi
AU  - Kuno A
AD  - Department of Pharmacology, Sapporo Medical University School of Medicine, 
      South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan.
FAU - Furuhashi, Masato
AU  - Furuhashi M
AD  - Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical 
      University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221220
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - T68ALE2O9F (3-aminoisobutyric acid)
RN  - 0 (Aminoisobutyric Acids)
RN  - 0 (Sodium-Glucose Transporter 2 Inhibitors)
RN  - IY9XDZ35W2 (Glucose)
RN  - 9NEZ333N27 (Sodium)
SB  - IM
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Aged
MH  - Female
MH  - *Diabetes Mellitus, Type 2/diagnosis/drug therapy
MH  - Aminoisobutyric Acids
MH  - Retrospective Studies
MH  - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects
MH  - *Heart Failure/diagnosis/drug therapy/chemically induced
MH  - Glucose
MH  - Sodium
PMC - PMC9768967
OTO - NOTNLM
OT  - Amino acid
OT  - Diabetes mellitus
OT  - Heart failure
OT  - SGLT2
OT  - Sodium-glucose cotransporter 2 inhibitors
OT  - beta-aminoisobutyric acid
COIS- We declare that we have no competing interests.
EDAT- 2022/12/21 06:00
MHDA- 2022/12/23 06:00
PMCR- 2022/12/20
CRDT- 2022/12/20 23:56
PHST- 2022/11/16 00:00 [received]
PHST- 2022/12/14 00:00 [accepted]
PHST- 2022/12/20 23:56 [entrez]
PHST- 2022/12/21 06:00 [pubmed]
PHST- 2022/12/23 06:00 [medline]
PHST- 2022/12/20 00:00 [pmc-release]
AID - 10.1186/s12933-022-01727-x [pii]
AID - 1727 [pii]
AID - 10.1186/s12933-022-01727-x [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2022 Dec 20;21(1):285. doi: 10.1186/s12933-022-01727-x.