The Effect of Metformin on Adipose Tissue Metabolism and Peripheral Blood Flow in Subjects With NIDDM

Abstract

To examine the effect of metformin on net lactate and glycerol release in NIDDM subjects, we used abdominal subcutaneous microdialysis combined with 133Xe clearance. Skeletal muscle blood flow (MBF) was assessed simultaneously both before and after metformin treatment. Nine male patients with NIDDM (age 53 +/- 2 years [mean +/- SE]; BMI 30.2 +/- 1.4 kg/m2; body fat 23.0 +/- 2.6 kg; diabetes duration 4.6 +/- 1.5 years; six of nine receiving sulfonylurea treatment) were recruited into an open study. They were studied after an overnight fast, both before and after 1 week of additional treatment with 500 mg metformin three times daily. Nine weight- and age-matched nondiabetic subjects served as a control group. Postabsorptive net subcutaneous lactate release increased (149 +/- 50 vs. 475 +/- 127 nmol.100 g-1.min-1, P < 0.05) whereas plasma lactate was unchanged after metformin treatment in the NIDDM patients. The net decrease of glycerol release 90 min after an oral glucose tolerance test was more pronounced (110 +/- 30 vs. 199 +/- 20 nmol.100 g-1.min-1, P < 0.05) after metformin treatment. Both adipose tissue blood flow (ATBF) (1.5 +/- 0.1 vs. 2.3 +/- 0.2 ml.100 g-1.min-1, P < 0.01) and MBF (3.2 +/- 0.4 vs. 4.2 +/- 0.5 ml.100 ml-1.min-1, P < 0.05) increased after metformin treatment. In this open study, postabsorptive net lactate release in abdominal subcutaneous adipose tissue was clearly increased in NIDDM patients after metformin treatment. Basal ATBF as well as MBF was improved after metformin treatment. Whether this reflects enhanced metabolic control or is a drug-specific effect remains to be established.