[37] How does metformin reduce cancers?

[Akin,Clin Endocrinology, 12,Metformin, Pigment epithelium derived factor, insulin resistance]

Clin Endocrinol (Oxf). 2012 Dec;77(6):852-6. doi: 10.1111/j.1365-2265.2012.04341.x.

#mp111212

Pigment epithelium-derived factor increases in type 2 diabetes after treatment with metformin.

Akın S, Aksoy DY, Cınar N, Aydın K, Karaağaoğlu E, Arıyürek M, Gülçelik NE, Usman A, Gürlek A.

Source

Section of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Hacettepe University.

Abstract

OBJECTIVE:

Pigment epithelium-derived factor (PEDF) has anti-angiogenic, immunomodulatory and anti-inflammatory properties. In addition to the significant role it plays in reducing diabetic complications, PEDF is now used in the treatment of certain cancers. It possibly plays a role in insulin resistance cases, too. However, whether metformin treatment has any significant effects on PEDF levels is not known. In this study, we investigated the regulation of PEDF in type 2 diabetes in relation to fat mass and insulin resistance before and after the use of metformin for treatment.

DESIGN:

Prospective cohort study.

SUBJECTS:

Thirty-six patients with newly diagnosed type 2 diabetes and 33 healthy individuals.

MEASUREMENTS:

Baseline weight, waist circumference (WC), fasting (FPG) and postprandial (PPPG) glucose, insulin, HbA1c, HOMA, PEDF and total/truncal fat mass were determined both in the diabetic and control subjects. Procedures were repeated in the diabetic group after a 6-month metformin treatment.

RESULTS:

Baseline FPG, PPPG, HbA1c, HOMA, weight, WC and truncal fat mass were higher in patients with diabetes whereas PEDF levels were found to be comparable with the controls. We completed the study with 31 of the 36 patients with diabetes we had selected for the study. We observed a decrease in the weight, WC, FPG, PPPG, HOMA, total and truncal fat mass of the patients while there was a significant rise in the PEDF levels (P = 0·002) after the metformin treatment. On the other hand, no significant correlation was observed between the change in PEDF levels and the clinical and laboratory findings.

CONCLUSION:

Our study is the first to identify a metformin-related increase in PEDF levels in diabetes. The increase observed in PEDF levels after the metformin treatment does not seem to be related to the changes in insulin resistance, fat mass or glycemic control. Hence, our results suggest that further investigation is necessary to determine the direct effects of metformin on PEDF gene and protein expression in vitro.