THE METABOLIC EFFECT OF DODECANEDIOIC ACID INFUSION IN NON-INSULIN-DEPENDENT DIABETIC-PATIENTS

Dodecanedioic acid (C12) is an even-numbered dicarboxylic acid (DA). D icarboxylic acids are water-soluble substances with a metabolic pathwa y intermediate to those of lipids and carbohydrates. Previous studies showed that contrary to other DAs, very low amounts of C12 are lost wi th urine. The effects of 46.6 mmol of C12 intravenous infusion for 195 min on blood glucose levels were investigated in five patients with n on-insulin-dependent diabetes mellitus (NIDDM), with a good metabolic compensation, and in five healthy volunteers matched for gender, age, and body mass index. Blood samples were taken every 15 min for a perio d of 360 min to measure glucose, insulin, C-peptide, ketone bodies, an d free fatty acid (FFA) levels, and 24-h urine samples were collected to measure C12 and urea excretion. Plasma and urinary C12 concentratio ns were determined by high-pressure liquid chromatography (HPLC). Indi rect calorimetry was continuously performed both basally and during th e study period. The average 24-h urinary excretion of C12 was 6.5% ver sus 6.7% of the administered dose, respectively, in NIDDM patients and in healthy controls. The area under the curve (AUC) values of plasma C12 were 279.9 +/- 42.7 mu mol in NIDDM patients and 219.7 +/- 14.0 mu mol in controls (P = ns). Plasma glucose levels significantly decreas ed in NIDDM patients during C12 infusion (from 7.8 +/- 0.6 to 5.4 +/- 0.8 mM at the end of the study period, P < 0.05). Lactate plasma conce ntration decreased in NIDDM patients from 3.5 +/- 0.2 to 1.5 +/- 0.1 m M (P < 0.001), whereas blood pyruvate increased at the end of the expe rimental session from 26.0 +/- 11.6 to 99.5 +/- 14.9 mu M (P < 0.01). Free fatty acids decreased in diabetic patients from the beginning unt il the end of C12 infusion, although this difference did not reach sta tistical significance. No significant increase was found between basal and final values in VO2 consumption and in the values of nonprotein r espiratory quotient in both groups of subjects examined. The experimen tal data indicate that C12 infusion decreases plasma glucose levels in NIDDM patients to normal range without influencing plasma insulin lev els. The balance between pyruvate and lactate was affected by C12 infu sion only in diabetics patients. C12 might represent a fuel substrate immediately available for tissue energy requirements, especially in co nditions such as diabetes mellitus in which glucose metabolism is impa ired. (C) Elsevier Science Inc. 1998.