Metabolic and fibrinolytic response to changed insulin sensitivity in users of oral contraceptives.
The fundamental role of insulin resistance for metabolic changes linked to cardiovascular disease and type 2 diabetes is increasingly recognized. Oral contraceptives (OC) may affect insulin sensitivity, and a detailed characterization hereof, as well as the secondary effects on related metabolic systems, are relevant in the evaluation of the risk of developing vascular disorders or diabetes in OC users. We studied insulin sensitivity index (S(I)), glucose effectiveness (S(g)), and insulin response in young, healthy women by frequently sampled intravenous glucose tolerance tests before and after randomization to 6 months of treatment with ethinyl estradiol in triphasic combination with norgestimate (n = 17) or gestodene (n = 20). Measurements of fasting triglycerides and antigen concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were also included. Both compounds increased fasting plasma insulin and reduced S(i) but did not affect S(g). The relationships between S(i) and insulin response were unchanged. No consistent correlation between insulin sensitivity and triglycerides, t-PA, or PAI-1 were demonstrated before or during treatment. We conclude that the treatments were followed by a compensated decrease in insulin sensitivity that was unrelated to changes in triglycerides, t-PA, or PAI-1 antigen.
Petersen
K R
KR
Diabetes Center, Department of Gynecology and Obstetrics, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. kresternrp@dadinet.dk
Christiansen
E
E
Madsbad
S
S
Skouby
S O
SO
Andersen
L F
LF
Jespersen
J
J
D000328:Adult; D000911:Antibodies, Monoclonal; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D002318:Cardiovascular Diseases / Q000209:etiology*; D003280:Contraceptives, Oral, Synthetic / Q000009:adverse effects / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D004797:Enzyme-Linked Immunosorbent Assay; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000032:analysis; D007333:Insulin Resistance / Q000502:physiology*; D009644:Norgestrel / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011446:Prospective Studies; D010959:Tissue Plasminogen Activator / Q000097:blood; D014280:Triglycerides / Q000097:blood
D000911:Antibodies, Monoclonal; D001786:Blood Glucose; D002096:C-Peptide; D003280:Contraceptives, Oral, Synthetic; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D009644:Norgestrel; D004997:Ethinyl Estradiol; C017576:norgestimate; D010959:Tissue Plasminogen Activator