Incretin hormone secretion in women with polycystic ovary syndrome: roles of obesity, insulin sensitivity, and treatment with metformin.
In normal subjects, the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are responsible for 70% of the insulin response during a meal; but in diabetic subjects and other insulin-resistant conditions, the incretin effect is impaired. Polycystic ovary syndrome (PCOS) is associated with insulin resistance, and the pathophysiologic mechanisms behind PCOS resemble those of type 2 diabetes mellitus; therefore, women with PCOS may have alterations in the incretin hormone response. Metformin is widely used in the treatment of both type 2 diabetes mellitus and PCOS. Metformin may exert some of its effect on glucose metabolism by increasing GLP-1 biosynthesis and secretion and thereby increasing the incretin effect. The objective of the study was to measure incretin hormone secretion in women with PCOS and to evaluate the effect of metformin treatment. Cross-sectional comparison of 40 women with PCOS (19 lean and 21 obese) and 26 healthy control women (9 lean and 17 obese) and longitudinal evaluation of the effects of 8 months of metformin 1000 mg twice daily in women with PCOS were performed. Plasma concentrations of GIP and GLP-1 were determined frequently during a 75-g glucose tolerance test, and insulin sensitivity was evaluated by the euglycemic hyperinsulinemic clamp. The incretin hormone response did not differ between subjects with and without PCOS. Subgroup analysis showed lower GIP (area under the curve [AUC]) levels in obese women with PCOS compared with obese control women (P < .05) and compared with lean women with PCOS (P < .05). Metformin increased GIP (AUC) and GLP-1 (AUC) in lean women with PCOS (P < .05), and a similar trend was seen in the obese women (P = .07). The GIP secretion is attenuated in obese women with PCOS, whereas treatment with metformin increases the levels of both GIP and GLP-1 in women with PCOS.
Department of Obstetrics and Gynaecology, Hvidovre Hospital, Hvidovre, 2650 Hvidovre, Denmark. pernille.svendsen@hvh.regionh.dk
Pernille Fog
PF
Svendsen
Lisbeth
L
Nilas
Sten
S
Madsbad
Jens Juul
JJ
Holst
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000378:metabolism*; D005947:Glucose / Q000008:administration & dosage; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008137:Longitudinal Studies; D008687:Metformin / Q000008:administration & dosage*; D009765:Obesity / Q000503:physiopathology; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D008687:Metformin; D005947:Glucose