Dipeptidyl Peptidase 4 Inhibition Stimulates Distal Tubular Natriuresis and Increases in Circulating SDF-1α1-67 in Patients With Type 2 Diabetes
Bibliographic record
Abstract
OBJECTIVE Antihyperglycemic agents, such as empagliflozin, stimulate proximal tubular natriuresis and improve cardiovascular and renal outcomes in patients with type 2 diabetes. Because dipeptidyl peptidase 4 (DPP-4) inhibitors are used in combination with sodium–glucose cotransporter 2 (SGLT2) inhibitors, we examined whether and how sitagliptin modulates fractional sodium excretion and renal and systemic hemodynamic function. RESEARCH DESIGN AND METHODS We studied 32 patients with type 2 diabetes in a prospective, double-blind, randomized, placebo-controlled trial. Measurements of renal tubular function and renal and systemic hemodynamics were obtained at baseline, then hourly after one dose of sitagliptin or placebo, and repeated at 1 month. Fractional excretion of sodium and lithium and renal hemodynamic function were measured during clamped euglycemia. Systemic hemodynamics were measured using noninvasive cardiac output monitoring, and plasma levels of intact versus cleaved stromal cell–derived factor (SDF)-1α were quantified using immunoaffinity and tandem mass spectrometry. RESULTS Sitagliptin did not change fractional lithium excretion but significantly increased total fractional sodium excretion (1.32 ± 0.5 to 1.80 ± 0.01% vs. 2.15 ± 0.6 vs. 2.02 ± 1.0%, P = 0.012) compared with placebo after 1 month of treatment. Moreover, sitagliptin robustly increased intact plasma SDF-1α1-67 and decreased truncated plasma SDF-1α3-67. Renal hemodynamic function, systemic blood pressure, cardiac output, stroke volume, and total peripheral resistance were not adversely affected by sitagliptin. CONCLUSIONS DPP-4 inhibition promotes a distal tubular natriuresis in conjunction with increased levels of intact SDF-1α1-67. Because of the distal location of the natriuretic effect, DPP-4 inhibition does not affect tubuloglomerular feedback or impair renal hemodynamic function, findings relevant to using DPP-4 inhibitors for treating type 2 diabetes.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 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".