Objectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) modulate lipid metabolism and improve cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). The... Show moreObjectives: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) modulate lipid metabolism and improve cardiovascular morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). The exact cardioprotective mechanism of SGLT2i is unclear. We evaluated the effects of SGLT2i on postprandial lipids, lipoprotein concentrations, glucose and fatty acids. Design: A placebo-controlled randomized, proof-of-concept study. Methods: Fourteen male patients with T2DM on intensive insulin regimen were randomly and double-blind allocated to 12 weeks dapagliflozin (10 mg) or placebo. Postprandial effects were assessed with an 8-h standardized oral fat loading test. Results: Mean glycated A1c did not change by dapagliflozin, but the mean daily insulin dose was significantly reduced. Although dapagliflozin did not affect fasting or postprandial levels of glucose and insulin, it increased the postprandial levels of glucagon. While fasting levels of free fatty acids and beta-hydroxybutyrate (bHBA) were unchanged, dapagliflozin significantly increased the postprandial bHBA response. This was seen in the context of increased postprandial glucagon levels by dapagliflozin, without influencing postprandial insulin or glucose levels. Dapagliflozin did not affect fasting or postprandial plasma cholesterol and triglycerides nor postprandial inflammatory markers. Fasting apolipoprotein B48 was decreased without affecting the postprandial response. Markers of inflammation and vascular function did not change. Conclusion: Treatment with dapagliflozin of patients with T2DM led to a reduction of fasting chylomicron remnants and increased postprandial ketone bodies compared to placebo suggesting enhanced hepatic fatty acid oxidation. The latter may have been caused by decreasing the insulin-glucagon ratio. The beneficial clinical effects seen in the trials using dapagliflozin most likely are not due to effects on postprandial inflammation nor postprandial lipemia. Show less
Turk, Y.; Theel, W.; Huisstede, A. van; Geijn, G.J.M. van de; Birnie, E.; Hiemstra, P.S.; ... ; Braunstahl, G.J. 2020
Objective: To determine the short-term and long-term effects of a high intensity pulmonary rehabilitation programme on asthma control, body composition, lung function and exercise capacity in obese... Show moreObjective: To determine the short-term and long-term effects of a high intensity pulmonary rehabilitation programme on asthma control, body composition, lung function and exercise capacity in obese asthma patients.Methods: Patients with obesity (body mass index (BMI).30 kg.m(-2)) and suboptimal controlled asthma (Asthma Control Questionnaire (ACQ).0.75) were randomly assigned to a 3-month pulmonary rehabilitation programme (PR only), pulmonary rehabilitation programme with the use of an internet based self-management support programme (PR+SMS) or usual care. The pulmonary rehabilitation programme included high-intensity interval training, nutritional intervention and psychological group sessions. Patients in the usual care group were advised to lose weight and to exercise. The primary outcome was the difference of change of ACQ between PR only and PR+SMS after 3 months. Total followup was 12 months.Results: 34 patients were included in the study (14 PR only, nine PR+SMS, 11 control). Compared with patients in usual care, patients in the PR only group had a significant reduction in BMI and significant improvements in asthma control, exercise capacity and aerobic capacity after 3 months. These improvements persisted during 12 months of follow-up. No difference in ACQ between PR+SMS and PR only groups was observed. However, users of the SMS programme had a significantly lower BMI after 12 months compared with subjects in the PR only group.Conclusion: A high-intensity pulmonary rehabilitation programme provides sustained improvements in asthma control, body composition and exercise capacity in obese asthmatics that are not optimally controlled and, therefore, should be considered in the treatment of these patients. Show less
Aim Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD) linked to atherogenic dyslipidaemia and postprandial hyperlipidaemia. Alirocumab, a... Show moreAim Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD) linked to atherogenic dyslipidaemia and postprandial hyperlipidaemia. Alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, improves CVD risk by reducing the concentration of low-density lipoprotein-cholesterol (LDL-C). However, effects of PCK9 inhibitors on other aspects of diabetic dyslipidaemia, particularly in the postprandial situation, are less clear. Material and Methods Twelve male patients with T2DM on an intensive insulin regimen completed a 6-week randomized, double-blind, placebo-controlled, proof-of-concept study. Participants received three biweekly dosages of subcutaneous alirocumab (150 mg) or placebo. Before and after the intervention, fasting and postprandial triglyceride (TG) plasma levels, apolipoprotein (apo) B48, lipoprotein composition isolated by ultracentrifugation, vascular function and markers of inflammation were evaluated. Results Alirocumab treatment reduced fasting plasma TG levels (between group median change -24.7%; P = 0.018) and fasting apoB48 serum levels (-35.9%; P = 0.039) compared with placebo. Alirocumab reduced the plasma TG area under the curve (AUC) (-26.4%; P = 0.006) and apoB48 AUC (-55.7%; P = 0.046), as well as plasma TG incremental AUC (-21.4%; P = 0.04) and apoB48 incremental AUC (-26.8%; P = 0.02). In addition, alirocumab reduced fasting and postprandial TG levels in very low-density lipoprotein (VLDL) and LDL. Alirocumab improved fasting pulse wave velocity, but no changes in postprandial markers of inflammation were observed. Conclusions In addition to the well-known LDL-C-reducing effects, 6 weeks of alirocumab treatment lowered both fasting and postprandial plasma TG levels by reducing the TG levels in VLDL and LDL and the concentration of intestinal remnants. Show less
Klop, B.; Pol, P. van der; Bruggen, R. van; Wang, Y.A.; Vries, M.A. de; Santen, S. van; ... ; Cabezas, M.C. 2014
