Endurance-type exercise combined with acipimox administration provides superior benefits for glycemic control compared with endurance-type exercise alone in male patients with type 2 diabetes Dominique Hansen, PhD, FESC1,2 *, Kenneth Verboven, MSc1,3 *, Jan-Willem van Dijk, PhD4, Lennert Minten, BSc1, Kevin Smeets, BSc1, Luc van Loon, PhD3 Introduction ° Despite intake of blood glucose-lowering medication and healthy diets, glycemic variability remains highly prevalent throughout the day in type 2 diabetes mellitus (T2DM) patients. ° Adjuvant strategies to attenuate blood glucose excursions during the day and improve glycemic control is important to reduce the likelihood for developing cardiovascular disease or other diabetes-related complications. ° In this regard, a high turnover of intramuscular triglycerides (IMTG) is instrumental to lower skeletal muscle insulin resistance (see figure below). Methods ° 14 male T2DM patients (age 65±2 years, HbA1c 6.7±0.1%) participated in a double-blind placebo-controlled randomized cross-over study. ° Subjects performed a 60-min endurance-type exercise bout after being administered 250mg of nicotinic acid analog acipimox (ACP) or a placebo (PLA). In addition, a control experiment was included in which no exercise was performed and a placebo was taken (CON). ° Before, during and for 24 hours after cessation of exercise, blood samples were collected to assess systemic responses while consuming standardized meals in a laboratory setting. ° Subjects were subjected to an oral glucose tolerance test (OGTT) 24 hours after each treatment. Results ° Plasma FFA concentrations were substantially increased following PLA (+13%), whereas ACP resulted in a substantial suppression of plasma FFA concentrations (-22%) compared to CON (P<0.05, see figure below). ° After exercise PLA did not significantly lower circulating plasma glucose (+4%) and insulin (-3%) (P>0.10) concentrations. ° Significant reductions in plasma glucose (-7%) and insulin (-28%) excursions were observed after ACP intake compared to CON (P<0.05). ° Glycemic control was comparable between conditions during OGTT (P>0.10). Obesity and T2DM are associated with increased FFA influx in skeletal muscle, leading to higher levels of IMTG and fatty acids derivates such as DAG and ceramides. FFAs enter muscle cells and are converted to long chain Acyl-CoAs that are used for beta-oxidation or conversion into DAG or ceramides. DAG and ceramides cause hyperactivation of multiple PKC isoforms and JNK, which phosphorylate serine residues on IRS-1, leading to insulin resistance. Abbreviations: T2DM Type 2 diabetes mellitus, FFA free fatty acids, IMTG intramyocellular triglycerides, DAG diacylglycerol, PKC protein kinase C, JNK jun NH2-terminal kinase, IRS-1 insulin receptor substrate 1. ° Moderate-intensity endurance-type exercise, combined with adipose tissue lipolytic inhibition, has been shown to augment IMTG use and the increase in whole-body insulin sensitivity in type 2 diabetes mellitus (T2DM) patients. ° It may thus be anticipated that the stimulation of IMTG oxidation during exercise may lead to greater improvements in 24-hour glycemic control in T2DM patients. Aims The present study investigates the impact of adipose tissue lipolytic inhibition during endurance-type exercise on subsequent 24-hour glycemic control in male T2DM patients. Conclusion Inhibition of adipose tissue lipolysis during endurance-type exercise attenuates postprandial blood glucose and insulin excursions in male T2DM patients. 1 REVAL – Rehabilitation Research Center, BIOMED- Biomedical Research Center, Faculty of Medicine and Life Sciences, Hasselt University, Diepenbeek, Belgium 2 Jessa Hospital, Heart Centre Hasselt, Hasselt, Belgium 3 Department of Human Biology and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, the Netherlands 4 Institute of Sports and Exercise Studies, HAN University of Applied Sciences, Nijmegen, The Netherlands Conflict of interest: none to be declared. Contact: Dominique.hansen@uhasselt.be