Efficacy and Safety of Cannabidiol and Tetrahydrocannabivarin on Glycemic and Lipid Parameters in Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Pilot Study

OBJECTIVE Cannabidiol (CBD) and D9-tetrahydrocannabivarin (THCV) are nonpsychoactive phytocannabinoids affecting lipid and glucose metabolism in animal models. This study set out to examine the effects of these compounds in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized, double-blind, placebo-controlled study, 62 subjects with noninsulin-treated type 2 diabetes were randomized to five treatment arms: CBD (100 mg twice daily), THCV (5 mg twice daily), 1:1 ratio of CBD and THCV (5 mg/5 mg, twice daily), 20:1 ratio of CBD and THCV (100 mg/5 mg, twice daily), or matched placebo for 13 weeks. The primary end point was a change in HDL-cholesterol concentrations from baseline. Secondary/tertiary end points included changes in glycemic control, lipid profile, insulin sensitivity, body weight, liver triglyceride content, adipose tissue distribution, appetite, markers of inflammation, markers of vascular function, gut hormones, circulating endocannabinoids, and adipokine concentrations. Safety and tolerability end points were also evaluated. RESULTS Compared with placebo, THCV significantly decreased fasting plasma glucose (estimated treatment difference [ETD] = 21.2 mmol/L; P < 0.05) and improved pancreatic b-cell function (HOMA2 b-cell function [ETD = 244.51 points; P < 0.01]), adiponectin (ETD = 25.9 3 106 pg/mL; P < 0.01), and apolipoprotein A (ETD = 26.02 mmol/L; P < 0.05), although plasma HDL was unaffected. Compared with baseline (but not placebo), CBD decreased resistin (2898 pg/ml; P < 0.05) and increased glucose-dependent insulinotropic peptide (21.9 pg/ml; P < 0.05). None of the combination treatments had a significant impact on end points. CBD and THCV were well tolerated. CONCLUSIONS THCV could represent a newtherapeutic agent in glycemic control in subjects with type 2 diabetes.

Delay Assignment Optimization Strategies at Pre- Tactical and Tactical Levels

This paper compares different optimization strategies for the minimization of flight and passenger delays at two levels: pre-tactical, with on-ground delay at origin, and tactical, with airborne delay close to the destination airport. The optimization model is based on the ground holding problem and uses various cost functions. The scenario considered takes place in a busy European airport and includes realistic values of traffic. Uncertainty is introduced in the model for the passenger allocation, minimum time required for turnaround and tactical uncertainty. Performance of the various optimization processes is presented and compared to ratio by schedule results.

Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism

Aims/hypothesis - It is not known whether the beneficial effects of exercise training on insulin sensitivity are due to changes in hepatic and peripheral insulin sensitivity or whether the changes in insulin sensitivity can be explained by adaptive changes in fatty acid metabolism, changes in visceral fat or changes in liver and muscle triacylglycerol content. We investigated the effects of 6 weeks of supervised exercise in sedentary men on these variables. Subjects and methods - We randomised 17 sedentary overweight male subjects (age 50 ± 2.6 years, BMI 27.6 ± 0.5 kg/m2) to a 6-week exercise programme (n = 10) or control group (n = 7). The insulin sensitivity of palmitic acid production rate (Ra), glycerol Ra, endogenous glucose Ra (EGP), glucose uptake and glucose metabolic clearance rate were measured at 0 and 6 weeks with a two-step hyperinsulinaemic–euglycaemic clamp [step 1, 0.3 (low dose); step 2, 1.5 (high dose) mU kg−1 min−1]. In the exercise group subjects were studied >72 h after the last training session. Liver and skeletal muscle triacylglycerol content was measured by magnetic resonance spectroscopy and visceral adipose tissue by cross-sectional computer tomography scanning. Results - After 6 weeks, fasting glycerol, palmitic acid Ra (p = 0.003, p = 0.042) and NEFA concentration (p = 0.005) were decreased in the exercise group with no change in the control group. The effects of low-dose insulin on EGP and of high-dose insulin on glucose uptake and metabolic clearance rate were enhanced in the exercise group but not in the control group (p = 0.026; p = 0.007 and p = 0.04). There was no change in muscle triacylglycerol and liver fat in either group. Conclusions/interpretation - Decreased availability of circulating NEFA may contribute to the observed improvement in the insulin sensitivity of EGP and glucose uptake following 6 weeks of moderate exercise.