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3 results on '"Yvo J.M. op den Kamp"'

1. Effects of SGLT2 inhibitor dapagliflozin in patients with type 2 diabetes on skeletal muscle cellular metabolism

Author

Yvo J.M. op den Kamp, Anne Gemmink, Marlies de Ligt, Bas Dautzenberg, Esther Kornips, Johanna A. Jorgensen, Gert Schaart, Russell Esterline, Diego A. Pava, Joris Hoeks, Vera B. Schrauwen-Hinderling, Sander Kersten, Bas Havekes, Timothy R. Koves, Deborah M. Muoio, Matthijs K.C. Hesselink, Jan Oscarsson, Esther Phielix, and Patrick Schrauwen

Subjects
Acylcarnitines, Dapagliflozin, Myocellular lipid metabolism, Mitochondrial function, SGLT2i, TCA cycle Intermediates, Internal medicine, RC31-1245
Abstract

Objective: SGLT2 inhibitors increase urinary glucose excretion and have beneficial effects on cardiovascular and renal outcomes; the underlying mechanism may be metabolic adaptations due to urinary glucose loss. Here, we investigated the cellular and molecular effects of 5 weeks of dapagliflozin treatment on skeletal muscle metabolism in type 2 diabetes patients. Methods: Twenty-six type 2 diabetes mellitus patients were randomized to a 5-week double-blind, cross-over study with 6-8-week wash-out. Skeletal muscle acetylcarnitine levels, intramyocellular lipid (IMCL) content and phosphocreatine (PCr) recovery rate were measured by magnetic resonance spectroscopy (MRS). Ex vivo mitochondrial respiration was measured in skeletal muscle fibers using high resolution respirometry. Intramyocellular lipid droplet and mitochondrial network dynamics were investigated using confocal microscopy. Skeletal muscle levels of acylcarnitines, amino acids and TCA cycle intermediates were measured. Expression of genes involved in fatty acid metabolism were investigated. Results: Mitochondrial function, mitochondrial network integrity and citrate synthase and carnitine acetyltransferase activities in skeletal muscle were unaltered after dapagliflozin treatment. Dapagliflozin treatment increased intramyocellular lipid content (0.060 (0.011, 0.110) %, p = 0.019). Myocellular lipid droplets increased in size (0.03 μm2 (0.01–0.06), p

Published
2022
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2. Erratum. Effects of the SGLT2 Inhibitor Dapagliflozin on Energy Metabolism in Patients With Type 2 Diabetes: A Randomized, Double-Blind Crossover Trial. Diabetes Care 2021;44:1334–1343

Author

Yvo J.M. Op den Kamp, Marlies de Ligt, Bas Dautzenberg, Esther Kornips, Russell Esterline, Matthijs K.C. Hesselink, Joris Hoeks, Vera B. Schrauwen-Hinderling, Bas Havekes, Jan Oscarsson, Esther Phielix, and Patrick Schrauwen

Subjects
Advanced and Specialized Nursing, Blood Glucose, Glycated Hemoglobin, Cross-Over Studies, Endocrinology, Diabetes and Metabolism, Middle Aged, Diabetes Mellitus, Type 2, Double-Blind Method, Glucosides, Internal Medicine, Humans, Hypoglycemic Agents, Erratum, Benzhydryl Compounds, Energy Metabolism, Sodium-Glucose Transporter 2 Inhibitors
Abstract

SGTL2 inhibitors increase urinary glucose excretion and have beneficial effects on cardiovascular and renal outcomes. The underlying mechanism may involve caloric restriction-like metabolic effects due to urinary glucose loss. We investigated the effects of dapagliflozin on 24-h energy metabolism and insulin sensitivity in patients with type 2 diabetes.There were 26 patients with type 2 diabetes randomized to a 5-week double-blind, crossover study with a 6- to 8-week washout. Indirect calorimetry was used to measure 24-h energy metabolism and the respiratory exchange ratio (RER), both by whole-room calorimetry and by ventilated hood during a two-step euglycemic-hyperinsulinemic clamp. Results are presented as the differences in least squares mean (95% CI) between treatments.Evaluable patients (Dapagliflozin treatment for 5 weeks resulted in major adjustments of metabolism mimicking caloric restriction, increased fat oxidation, improved hepatic and adipose insulin sensitivity, and improved 24-h energy metabolism.

Published
2022

3. Effects of the SGLT2 Inhibitor Dapagliflozin on Energy Metabolism in Patients With Type 2 Diabetes: A Randomized, Double-Blind Crossover Trial

Author

Esther Kornips, Matthijs K. C. Hesselink, Jan Oscarsson, Yvo J.M. Op den Kamp, Vera B. Schrauwen-Hinderling, Marlies de Ligt, Esther Phielix, Joris Hoeks, Russell Esterline, Patrick Schrauwen, Bas Dautzenberg, Bas Havekes, Nutrition and Movement Sciences, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, MUMC+: DA BV Research (9), Interne Geneeskunde, and MUMC+: MA Endocrinologie (9)

Subjects
medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Urinary system, 030209 endocrinology & metabolism, Type 2 diabetes, Excretion, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, 030212 general & internal medicine, Dapagliflozin, Respiratory exchange ratio, Advanced and Specialized Nursing, Emerging Therapies: Drugs and Regimens, business.industry, INSULIN SENSITIVITY, MEN, medicine.disease, Crossover study, Endocrinology, chemistry, SECRETION, SGLT2 Inhibitor, business, RESPIRATION CHAMBER
Abstract

OBJECTIVE SGTL2 inhibitors increase urinary glucose excretion and have beneficial effects on cardiovascular and renal outcomes. The underlying mechanism may involve caloric restriction-like metabolic effects due to urinary glucose loss. We investigated the effects of dapagliflozin on 24-h energy metabolism and insulin sensitivity in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS There were 26 patients with type 2 diabetes randomized to a 5-week double-blind, crossover study with a 6- to 8-week washout. Indirect calorimetry was used to measure 24-h energy metabolism and the respiratory exchange ratio (RER), both by whole-room calorimetry and by ventilated hood during a two-step euglycemic-hyperinsulinemic clamp. Results are presented as the differences in least squares mean (95% CI) between treatments. RESULTS Evaluable patients (n = 24) had a mean (SD) age of 64.2 (4.6) years, BMI of 28.1 (2.4) kg/m2, and HbA1c of 6.9% (0.7) (51.7 [6.8] mmol/mol). Rate of glucose disappearance was unaffected by dapagliflozin, whereas fasting endogenous glucose production (EGP) increased by dapagliflozin (+2.27 [1.39, 3.14] μmol/kg/min, P CONCLUSIONS Dapagliflozin treatment for 5 weeks resulted in major adjustments of metabolism mimicking caloric restriction, increased fat oxidation, improved hepatic and adipose insulin sensitivity, and improved 24-h energy metabolism.

Published
2021
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