Sex Differences in Renal Responses to Hyperglycemia, <scp>l</scp>-Arginine, and <scp>l</scp>-NMMA in Humans With Uncomplicated Type 1 Diabetes
Bibliographic record
Abstract
OBJECTIVE: Women exhibit exaggerated renal hemodynamic responses to hyperglycemia, which may promote kidney disease progression. Our aim was to determine if increased nitric oxide generation by l-arginine infusion would reverse this deleterious response to clamped hyperglycemia in women with type 1 diabetes mellitus. RESEARCH DESIGN AND METHODS: Renal function, blood pressure, and plasma cyclic guanosine monophosphate (cGMP) were measured in 20 men and 15 women with type 1 diabetes mellitus during clamped euglycemia and clamped hyperglycemia. Renal function, blood pressure, and plasma cGMP responses to graded infusions of intravenous l-arginine and N(G)-monomethyl-l-arginine (l-NMMA) were measured during clamped hyperglycemia. RESULTS: Subjects were young, normotensive, normoalbuminuric men and women who adhered to a high-sodium, moderate-protein diet. Plasma cGMP levels during euglycemia were generally lower in men compared with women, and systolic blood pressure (SBP) was higher in men. In response to hyperglycemia, cGMP levels did not change in men but did decline in women (Δ-1.10 ± 0.20 vs. Δ+0.05 ± 0.20 pmol/L, between-group effect of hyperglycemia on cGMP; P = 0.012). Hyperglycemia also was associated with an increase in SBP, glomerular filtration rate (GFR) (124 ± 6 to 143 ± 7 mL/min/1.73 m(2); P = 0.003) and filtration fraction (FF) in women, but these parameters did not change in men. In response to l-arginine during hyperglycemia, the increase in cGMP was exaggerated in women versus men and GFR and FF decreased in women only, back toward baseline values observed during clamped euglycemia. l-NMMA infusion did not exaggerate changes in hemodynamic function in response to hyperglycemia. CONCLUSIONS: l-Arginine reversed the renal hemodynamic effects of hyperglycemia in women, suggesting that nitric oxide is an important regulator of sex-dependent vascular responses to hyperglycemia in humans.
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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 | 0.000 | 0.000 |
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".