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Record W4413451970 · doi:10.14814/phy2.70465

Metabolic shifts in plasma amino acids and related metabolites in response to <scp>SGLT2</scp> inhibition and hyperglycemia in type 1 diabetes

2025· article· en· W4413451970 on OpenAlexaff
Luxcia Kugathasan, Nagarjunachary Ragi, Subrata Debnath, Vikas S. Sridhar, Soumya Maity, Tianqing Feng, E.F. Martinez Trevino, Bruce A. Perkins, David Z.I. Cherney, Kumar Sharma

Bibliographic record

VenuePhysiological Reports · 2025
Typearticle
Languageen
FieldMedicine
TopicPancreatic function and diabetes
Canadian institutionsSinai Health SystemLunenfeld-Tanenbaum Research InstituteUniversity of TorontoUniversity of British ColumbiaUniversity Health Network
FundersEli Lilly and CompanyBoehringer Ingelheim
KeywordsType 2 diabetesPlasma glucoseDiabetes mellitusMedicineAmino acidEndocrinologyChemistryPharmacologyInternal medicineBiochemistry

Abstract

fetched live from OpenAlex

Regulated kidney function is dependent on maintaining efficient energy utilization. Our aim in this study was to determine the effects of acute, ambient hyperglycemia and sodium-glucose cotransporter-2 (SGLT2) inhibition on plasma amino acid metabolism in patients with type 1 diabetes (T1D). The ATIRMA trial, a single-arm study, evaluated the effects of 8 weeks of oral empagliflozin (25 mg/day) in 40 young adults with T1D. The study involved consecutive two-day assessments of clamped euglycemia and hyperglycemia at both baseline and post-treatment. MetaboAnalyst 6.0 categorized 35 metabolites into significant pathways, which were statistically compared using principal component analysis. Acute hyperglycemia induced changes to 10 metabolic pathways, including but not limited to increases in cysteine and methionine metabolism (0.52 ± 0.12, p < 0.0001), valine, leucine, and isoleucine biosynthesis (0.31 ± 0.10, p = 0.002); and nitrogen metabolism (0.11 ± 0.03, p = 0.003). Introduction of empagliflozin was associated with a decrease in adenine, and an increase in cysteine and methionine metabolism (0.31 ± 0.13, p = 0.02) when maintained under euglycemia and a decrease in nitrogen metabolism under hyperglycemia (-0.07 ± 0.04, p = 0.04). Our findings show that SGLT2 inhibition counteracts the hyperglycemia-induced changes in plasma amino acid metabolism, potentially improving energy efficiency and metabolic health, though more research is needed to confirm these metabolic effects.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.014
GPT teacher head0.261
Teacher spread0.247 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2025
Admission routes1
Has abstractyes

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