scholarly journals SGLT2 Inhibition Does Not Affect Myocardial Fatty Acid Oxidation or Uptake, But Reduces Myocardial Glucose Uptake and Blood Flow in Individuals With Type 2 Diabetes– a Randomized Double-Blind, Placebo-Controlled Crossover Trial

Diabetes ◽  
2020 ◽  
pp. db200921
Author(s):  
Katrine M. Lauritsen ◽  
Bent R.R. Nielsen ◽  
Lars P. Tolbod ◽  
Mogens Johannsen ◽  
Jakob Hansen ◽  
...  
2020 ◽  
Author(s):  
Katrine M. Lauritsen ◽  
Bent R.R. Nielsen ◽  
Lars P. Tolbod ◽  
Mogens Johannsen ◽  
Jakob Hansen ◽  
...  

Sodium-glucose cotransporter 2 (SGLT2) inhibition reduces cardiovascular morbidity and mortality in individuals with type 2 diabetes. Beneficial effects have been attributed to increased ketogenesis, reduced cardiac fatty acid oxidation and diminished cardiac oxygen consumption. We therefore studied whether SGLT2 inhibition altered cardiac oxidative substrate consumption, efficiency, and perfusion. <p>13 individuals with type 2 diabetes were studied after four weeks treatment with empagliflozin and placebo in a randomized, double-blind, placebo-controlled crossover study. Myocardial palmitate and glucose uptake were measured with <sup>11</sup>C-palmitate and <sup>18</sup>F-FDG PET/CT. Oxygen consumption and myocardial external efficiency (MEE) were measured with <sup>11</sup>C-acetate PET/CT. Resting and adenosine stress myocardial blood flow (MBF) and myocardial flow reserve (MFR) were measured using <sup>15</sup>O-H<sub>2</sub>O PET/CT. </p> <p>Empagliflozin did not affect myocardial FFA uptake but reduced myocardial glucose uptake by 57% (p<0.001). Empagliflozin did not change myocardial oxygen consumption or MEE. Empagliflozin reduced resting MBF by 13% (p<0.01), but did not significantly affect stress MBF or MFR.</p> <p>In conclusion, SGLT2 inhibition did not affect myocardial FFA uptake, but channeled myocardial substrate utilization from glucose towards other sources and reduced resting MBF. However, the observed metabolic and hemodynamic changes were modest and most likely contribute only partially to the cardioprotective effect of SGLT2 inhibition. </p>


2020 ◽  
Author(s):  
Katrine M. Lauritsen ◽  
Bent R.R. Nielsen ◽  
Lars P. Tolbod ◽  
Mogens Johannsen ◽  
Jakob Hansen ◽  
...  

Sodium-glucose cotransporter 2 (SGLT2) inhibition reduces cardiovascular morbidity and mortality in individuals with type 2 diabetes. Beneficial effects have been attributed to increased ketogenesis, reduced cardiac fatty acid oxidation and diminished cardiac oxygen consumption. We therefore studied whether SGLT2 inhibition altered cardiac oxidative substrate consumption, efficiency, and perfusion. <p>13 individuals with type 2 diabetes were studied after four weeks treatment with empagliflozin and placebo in a randomized, double-blind, placebo-controlled crossover study. Myocardial palmitate and glucose uptake were measured with <sup>11</sup>C-palmitate and <sup>18</sup>F-FDG PET/CT. Oxygen consumption and myocardial external efficiency (MEE) were measured with <sup>11</sup>C-acetate PET/CT. Resting and adenosine stress myocardial blood flow (MBF) and myocardial flow reserve (MFR) were measured using <sup>15</sup>O-H<sub>2</sub>O PET/CT. </p> <p>Empagliflozin did not affect myocardial FFA uptake but reduced myocardial glucose uptake by 57% (p<0.001). Empagliflozin did not change myocardial oxygen consumption or MEE. Empagliflozin reduced resting MBF by 13% (p<0.01), but did not significantly affect stress MBF or MFR.</p> <p>In conclusion, SGLT2 inhibition did not affect myocardial FFA uptake, but channeled myocardial substrate utilization from glucose towards other sources and reduced resting MBF. However, the observed metabolic and hemodynamic changes were modest and most likely contribute only partially to the cardioprotective effect of SGLT2 inhibition. </p>


2021 ◽  
Author(s):  
Katrine M. Lauritsen ◽  
Bent R.R. Nielsen ◽  
Lars P. Tolbod ◽  
Mogens Johannsen ◽  
Jakob Hansen ◽  
...  

Sodium-glucose cotransporter 2 (SGLT2) inhibition reduces cardiovascular morbidity and mortality in individuals with type 2 diabetes. Beneficial effects have been attributed to increased ketogenesis, reduced cardiac fatty acid oxidation and diminished cardiac oxygen consumption. We therefore studied whether SGLT2 inhibition altered cardiac oxidative substrate consumption, efficiency, and perfusion. <p>13 individuals with type 2 diabetes were studied after four weeks treatment with empagliflozin and placebo in a randomized, double-blind, placebo-controlled crossover study. Myocardial palmitate and glucose uptake were measured with <sup>11</sup>C-palmitate and <sup>18</sup>F-FDG PET/CT. Oxygen consumption and myocardial external efficiency (MEE) were measured with <sup>11</sup>C-acetate PET/CT. Resting and adenosine stress myocardial blood flow (MBF) and myocardial flow reserve (MFR) were measured using <sup>15</sup>O-H<sub>2</sub>O PET/CT. </p> <p>Empagliflozin did not affect myocardial FFA uptake but reduced myocardial glucose uptake by 57% (p<0.001). Empagliflozin did not change myocardial oxygen consumption or MEE. Empagliflozin reduced resting MBF by 13% (p<0.01), but did not significantly affect stress MBF or MFR.</p> <p>In conclusion, SGLT2 inhibition did not affect myocardial FFA uptake, but channeled myocardial substrate utilization from glucose towards other sources and reduced resting MBF. However, the observed metabolic and hemodynamic changes were modest and most likely contribute only partially to the cardioprotective effect of SGLT2 inhibition. </p>


2019 ◽  
Vol 14 (12) ◽  
pp. 1934578X1989081
Author(s):  
Yoshio Suzuki ◽  
Keishoku Sakuraba ◽  
Takuya Wada ◽  
Naoya Watabane ◽  
Seijiro Wada ◽  
...  

Limited studies have demonstrated that chronic consumption of pinitol improved glucose tolerance, and single-dose ingestion (0.6 g) 60 minutes prior to meals suppressed postprandial glucose levels in patients with type 2 diabetes mellitus. However, higher doses (6 g) were required in healthy people who ingested pinitol with a meal. This randomized, double-blind, placebo-controlled, crossover trial was conducted to clarify the effect of 0.6 g of pinitol with a meal on postprandial blood glucose levels in healthy adults. Twenty volunteers aged 18 to 25 years participated in this study. Participants visited the laboratory after an overnight fast. After measuring fasting blood glucose levels (FBG), they consumed test food (0.6 g of pinitol or placebo) and then ate breakfast (577 kcal; protein 14.0 g; fat 5.6 g; and carbohydrate 117.7 g). Blood glucose levels were measured immediately after eating and at 30, 60, 90, and 120 minutes after breakfast. Participants’ mean FBG level was 102.6 ± 8.2 mg/dL. Participants were categorized by their FBG as normal ( n = 5; ≤99 mg/dL) or impaired glucose tolerance (IGT) ( n = 15; 100-125 mg/dL). The incremental area under the curve of blood glucose over 120 minutes after the meal was significantly suppressed by pinitol in the IGT group ( P < 0.05), but not in the normal group. Therefore, pinitol was considered to maintain postprandial blood glucose levels in healthy people with IGT, and may contribute to the prevention of type 2 diabetes.


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