{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:20:47Z","timestamp":1791080447371,"version":"4.1.0"},"reference-count":43,"publisher":"American Diabetes Association","issue":"8","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,8,1]]},"abstract":"<jats:p>OBJECTIVE\u2014Diabetes, the leading cause of end-stage renal disease in the U.S., is believed to involve activation of the renin angiotensin system (RAS) as a risk factor for nephropathy. RAS activation occurs in healthy women using oral contraceptives (OCs), but the effects of OC use on the diabetic kidney are unclear.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHODS\u2014Renal plasma flow (RPF) response to captopril, as an index of RAS activity, was investigated in 92 women (41 nondiabetic OC nonusers, 10 nondiabetic OC users, 29 diabetic OC nonusers, and 12 diabetic OC users). Based on the hemodynamic findings, we examined the impact of OC use on the development of nephropathy as a post hoc analysis in an inception cohort of 114 female patients with newly diagnosed type 1 diabetes followed for a median of 20.7 years (range 1\u201324).<\/jats:p>\n               <jats:p>RESULTS\u2014Nondiabetic OC nonusers showed minimal RPF vasodilator response to captopril (9 \u00b1 10 ml \u00b7 min\u22121 \u00b7 1.73 m\u22122, P = 0.6). In comparison, nondiabetic OC users showed a significant increase (69 \u00b1 35 ml \u00b7 min\u22121 \u00b7 1.73 m\u22122, P = 0.02) (P = 0.04 vs. nondiabetic OC nonusers). Diabetic OC nonusers demonstrated the anticipated vasodilator response (58 \u00b1 12 ml \u00b7 min\u22121 \u00b7 1.73 m\u22122, P &amp;lt; 0.0001). Diabetic OC users showed the largest responses (84 \u00b1 12 ml \u00b7 min\u22121 \u00b7 1.73 m\u22122, P = 0.002) (P = 0.04 vs. diabetic OC nonusers). Plasma renin activity did not vary with OC use (P = 0.3). The RPF responses to captopril and angiotensin receptor blocker were highly correlated (r = 0.72, P &amp;lt; 0.001), suggesting clear involvement of the RAS. In the observational study, 18% (6\/33 [95% CI 4.3\u201332.1]) of OC users developed macroalbuminuria compared with 2% (2\/81 [0\u20135.9]) of OC nonusers (P = 0.003, univariate analysis). After adjustment for known risk factors with a Cox regression model, OC use remained a predictor for the development of macroalbuminuria (relative risk 8.90 [95%CI 1.79\u201344.36], P = 0.008).<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014The strong association of OC use with angiotensin-dependent control of the renal circulation and the development of macroalbuminuria suggest that OC use may be a risk factor for diabetic nephropathy. Large prospective studies are required to further investigate this relationship.<\/jats:p>","DOI":"10.2337\/diacare.28.8.1988","type":"journal-article","created":{"date-parts":[[2007,3,5]],"date-time":"2007-03-05T22:51:27Z","timestamp":1173135087000},"page":"1988-1994","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":75,"title":["Oral Contraceptives, Angiotensin-Dependent Renal Vasoconstriction, and Risk of Diabetic Nephropathy"],"prefix":"10.2337","volume":"28","author":[{"given":"Sofia B.","family":"Ahmed","sequence":"first","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Hovind","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center, Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Henrik","family":"Parving","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center, Gentofte, Denmark"},{"name":"Faculty of Health Science, University of Aarhus, Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Rossing","sequence":"additional","affiliation":[{"name":"Steno Diabetes Center, Gentofte, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah A.","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori M.","family":"Laffel","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Boston, Massachusetts"},{"name":"Joslin Diabetes Center, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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