SGLT2-Mediated Changes in Urinary Handling of Ketones in Type 1 Diabetes
Bibliographic record
Abstract
Background: Adjunctive therapy with sodium glucose co-transporter 2 (SGLT2) inhibitors have demonstrated clinically meaningful metabolic benefits in type 1 diabetes (T1D), but also represent a component cause of diabetic ketoacidosis. In this post-hoc analysis we examined SGLT2-mediated changes in ketone concentrations during clamped euglycemia and hyperglycemia in people with T1D. Methods: T1D participants enrolled in the ATIRMA trial (NCT01392560) underwent measurement of plasma and urine beta-hydroxybutrate (BHB) and acetoacetate (AA) at baseline and after 8 weeks of empagliflozin 25 mg QD using a novel ZipChip Method developed at the CRPM, during both clamped euglycemia (4-6 mmol/L) and hyperglycemia (9-11 mmol/L). Results: Forty participants (50% female), aged 24±5 years, HbA1c 8.0±0.9% with diabetes duration of 17.5±7 years, were enrolled. Median [IQR] plasma BHB at baseline was 0.05 [0.02-0.16] mmol/L during euglycemia and 0.06 [0.02-0.17] mmol/L during hyperglycemia. Plasma BHB significantly increased after treatment during both euglycemia (0.20 [0.09-0.40] mmol/L) and hyperglycemia (0.21[0.05-0.40] mmol/L), p<0.05 for both comparisons. Urine BHB at baseline was 1.9 [1.2-4.3] μmol/mmol creatinine during euglycemia and was 3.7 [1.7-10.0] μmol/mmol creatinine during hyperglycemia. Urine BHB significantly increased after treatment during euglycemia (4.1 [1.8-9.7] umol/mmol creatinine), p<0.01. Results were similar for AA. Conclusions: In people with T1D, ketones were detectable in plasma and urine at baseline during clamped euglycemia and hyperglycemia and ketone concentrations significantly increased after 8 weeks of SGLT2 inhibition under the same study conditions. Further work is needed to establish factors associated with SGLT2-mediated changes in urinary handling of ketones and ketogenesis in people with T1D, which may assist in ketoacidosis prevention strategies. Funding: Commercial Support - Boehringer Ingelheim
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".