Metformin use linked to pigment epithelium-derived factor level in diabetes
MedWire News: Metformin treatment over 6 months is associated with a significant increase in serum pigment epithelium-derived factor (PEDF) in patients with diabetes, show study findings.
"The observed increase in PEDF levels potentially plays an important role in the prevention of late diabetic complications given the important effects of PEDF on oxidative stress, advanced glycation, and angiogenesis," write the researchers in Clinical Endocrinology.
In animal models, PEDF plays a role in obesity-induced insulin resistance, but the authors say that, to the best of their knowledge, no previous study has investigated the potential effects of metformin treatment on PEDF levels and the resultant decrease in insulin resistance in diabetes patients.
Led by Alper Gurlek (Hacettepe University, Ankara, Turkey), the team assessed anthropomorphic, glycemic, and insulin resistance parameters in 31 individuals with newly diagnosed diabetes. They also measured PEDF levels and assessed visceral fat distribution using dual X-ray absorbsiometry. Thirty-three age-matched, healthy individuals served as a control group for baseline comparisons.
The patients were given metformin 850 mg twice daily, as recommended by the recent American Diabetes Association consensus, for a period of 6 months, after which they underwent further assessment.
The researchers report that, compared with the control group, the diabetes patients had significantly higher postprandial plasma glucose (PPPG), glycated hemoglobin (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), weight, waist circumference (WC), and truncal fat mass.
The baseline PEDF levels were similar between the groups.
The authors found that treatment with 6-month metformin 850 mg resulted in significant decreases from baseline in weight, WC, fasting plasma glucose, PPPG, HOMA-IR, and total and truncal fat mass in the diabetes patients.
Moreover, the researchers observed a significant increase in mean PEDF level, from 4.11 to 5.01 mg/L.
The researchers say they did not observe a direct relationship between the incremental PEDF and HOMA-IR and decreased fat mass, and the change in PEDF level did not correlate with the change in HbA1c towards better glycemic control.
"However, it should be noted that the final HbA1c showed a significant inverse correlation with PEDF," remark Gurlek et al.
The most likely reason for increased PEDF in the context of weight and fat loss in this study could be the direct stimulatory effect of metformin on PEDF production and/or secretion from adipose tissue, they say.
This hypothesis warrants further testing by looking into the effect of metformin on PEDF gene and protein expression in vitro, suggests the team.
MedWire (www.medwire-news.md) is an independent clinical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2012
By Sally Robertson