PED/PEA-15 Protein, PCOS, Obesity, Insulin Sensitivity Indexes, Metformin, Oral Contraceptives

Summary

Insulin-resistance plays an important role in polycystic ovary syndrome (PCOS) physiopathology. The phosphoprotein enriched in the diabetes (PED/PEA-15), a 15 kDa protein related to insulin sensitivity, is over-expressed in type 2 diabetic patients and in PCOS women, independently of obesity. The effectiveness of oral contraceptives pills (OCP) or metformin (MET) in PCOS management is still uncertain. Aim of this pilot clinical study was to compare the effects of OCPs or MET on the expression of PED/PEA-15 in association with insulin sensitivity in obese PCOS women. Outcome measures: PED/PEA-15, BMI, plasma glucose and insulin, 1/HOMA-IR, homeostasis model assessment of insulin resistance; QUICKI, quantitative insulin sensitivity check index; ISI: whole-body insulin sensitivity index. Study design: twenty obese PCOS women (age: 24.7±18 yr; BMI: 30±2.4 kg/m2) were randomized according to insulin sensitivity to receive 30 µg ethinylestradiol plus 30 mg drospirenone 21 day/month or MET 1250 mg three times daily for 6 months. Results: At baseline, age and BMI were not different in the two groups; PED/PEA-15 protein expression was higher in MET than in OCP group (p=0.011), along with higher 1/HOMA-IR (p=0.004), and lower QUICKI and ISI (p=0.003 and p\<0.001, respectively). After treatment, independently of body weight, only in MET group PED/PEA-15 decreased (p=0.004), along with insulin and 1/HOMA-IR (p\<0.001), and QUICKI and ISI increased (p\<0.001). Insulin sensitivity indexes improvement correlated significantly with PED/PEA-15 protein expression, but not with BMI. Conclusions: PED/PEA-15 protein over-expression in obese PCOS women with IR reduced after a six month treatment with MET, while remained unchanged in the OCP group. The reduction was independent of body weight, and correlated with insulin sensitivity indexes. This effect further supported MET as a more effective therapy than OCPs for obese PCOS women with IR, also when fertility is not required.

Timeline

Start

2006-12

Primary completion

2006-12

Completion

2009-01

Publications

• Savastano S, Di Somma C, Pizza G, De Rosa A, Nedi V, Rossi A, Orio F, Lombardi G, Colao A, Tarantino G. Liver-spleen axis, insulin-like growth factor-(IGF)-I axis and fat mass in overweight/obese females. J Transl Med. 2011 Aug 16;9:136. doi: 10.1186/1479-5876-9-136.
• Savastano S, Valentino R, Pizza G, De Rosa A, Orio F, Passaretti F, Formisano P, Lombardi G, Beguinot F, Colao A. Preliminary data on effects of metformin on PED/PEA-15 cellular levels in obese women with polycystic ovary syndrome. J Endocrinol Invest. 2010 Jul-Aug;33(7):446-50. doi: 10.1007/BF03346622.

Drugs

Indications