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

2021 ◽  
Author(s):  
Yvo J.M. Op den Kamp ◽  
Marlies de Ligt ◽  
Bas Dautzenberg ◽  
Esther Kornips ◽  
Russell Esterline ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Caloric Restriction ◽  
Sglt2 Inhibitor ◽  
Metabolic Effects ◽  
Night Time ◽  
Double Blind ◽  
Urinary Glucose

<b>Background:</b> 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 24h energy metabolism and insulin sensitivity in patients with type 2 diabetes mellitus. <p><b>Methods</b>: Twenty-six type 2 diabetes patients were randomized to a 5-week double-blind, cross-over study with 6-8-week wash-out. 24h energy metabolism and respiratory exchange ratio (RER) were measured by indirect calorimetry, 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 (LSM) (95% CI) between treatments.</p> <p><b>Results</b>: Evaluable patients (n=24) had a mean (SD) age of 64<b>.</b>2(4<b>.</b>6) years, BMI of 28<b>.</b>1(2<b>.</b>4) kg/m2, and HbA1c of 6.9 (0.7)% (51<b>.</b>7 (6<b>.</b>8) mmol/mol). Rate of glucose disappearance was unaffected by dapagliflozin, while fasting endogenous glucose production (EGP) increased by dapagliflozin (+2<b>.</b>27 (1<b>.</b>39, 3<b>.</b>14) μmol/kg/min, p<0<b>.</b>0001). Insulin-induced suppression of EGP (-1<b>.</b>71 (-2<b>.</b>75, -0<b>.</b>63) μmol/kg/min, p=0<b>.</b>0036) and plasma free fatty acids (-21<b>.</b>93 (-39<b>.</b>31, -4<b>.</b>54) %, p=0.016) was greater with dapagliflozin. 24h energy expenditure (-0.11 (-0.24, 0.03) MJ/day) remained unaffected by dapagliflozin, but dapagliflozin reduced RER during day- and night-time resulting in an increased day to night-time difference in RER (-0.010 (-0.017, -0.002), p=0.016). Dapagliflozin treatment resulted in a negative 24h energy and fat balance (-20.51 (-27.90, -13.12) g/day). </p> <p><b>Interpretation</b>: 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 24h energy metabolism.</p>

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

2021 ◽  
Author(s):  
Yvo J.M. Op den Kamp ◽  
Marlies de Ligt ◽  
Bas Dautzenberg ◽  
Esther Kornips ◽  
Russell Esterline ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Caloric Restriction ◽  
Sglt2 Inhibitor ◽  
Metabolic Effects ◽  
Night Time ◽  
Double Blind ◽  
Urinary Glucose

<b>Background:</b> 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 24h energy metabolism and insulin sensitivity in patients with type 2 diabetes mellitus. <p><b>Methods</b>: Twenty-six type 2 diabetes patients were randomized to a 5-week double-blind, cross-over study with 6-8-week wash-out. 24h energy metabolism and respiratory exchange ratio (RER) were measured by indirect calorimetry, 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 (LSM) (95% CI) between treatments.</p> <p><b>Results</b>: Evaluable patients (n=24) had a mean (SD) age of 64<b>.</b>2(4<b>.</b>6) years, BMI of 28<b>.</b>1(2<b>.</b>4) kg/m2, and HbA1c of 6.9 (0.7)% (51<b>.</b>7 (6<b>.</b>8) mmol/mol). Rate of glucose disappearance was unaffected by dapagliflozin, while fasting endogenous glucose production (EGP) increased by dapagliflozin (+2<b>.</b>27 (1<b>.</b>39, 3<b>.</b>14) μmol/kg/min, p<0<b>.</b>0001). Insulin-induced suppression of EGP (-1<b>.</b>71 (-2<b>.</b>75, -0<b>.</b>63) μmol/kg/min, p=0<b>.</b>0036) and plasma free fatty acids (-21<b>.</b>93 (-39<b>.</b>31, -4<b>.</b>54) %, p=0.016) was greater with dapagliflozin. 24h energy expenditure (-0.11 (-0.24, 0.03) MJ/day) remained unaffected by dapagliflozin, but dapagliflozin reduced RER during day- and night-time resulting in an increased day to night-time difference in RER (-0.010 (-0.017, -0.002), p=0.016). Dapagliflozin treatment resulted in a negative 24h energy and fat balance (-20.51 (-27.90, -13.12) g/day). </p> <p><b>Interpretation</b>: 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 24h energy metabolism.</p>

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

Diabetes Care ◽  
2021 ◽  
pp. dc202887
Author(s):  
Yvo J.M. Op den Kamp ◽  
Marlies de Ligt ◽  
Bas Dautzenberg ◽  
Esther Kornips ◽  
Russell Esterline ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Energy Metabolism ◽  
Crossover Trial ◽  
Sglt2 Inhibitor ◽  
Double Blind

Abstract 16844: Effect of Canagliflozin on Gene Expression and CD34+ Function on Type 2 Diabetes Subjects

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Hassan Awal ◽  
Seshagiri Rao Nandula ◽  
Nabanita KUNDU ◽  
Mona Fakhri ◽  
Beda Brichacek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Mixed Model ◽  
Cell Function ◽  
Sglt2 Inhibitor ◽  
P Value ◽  
Vegf Receptor ◽  
Double Blind ◽  
Endothelial Cell Function

Introduction: CD34 +ve Endothelial progenitor cells (EPCs) has been shown to be dysfunctional in subjects with type 2 diabetes mellitus (T2DM) leading to poor endothelial cell function (ECF). Hypothesis: Canagliflozin, an SGLT2 inhibitor when added to other oral antidiabetic medication such Metformin, Insulin, GLP1-agonists, DPP-IV inhibitor, or sulfonylureas, may improve the cardiovascular risk by improving CD34+ EPCs function such as migration, colony formation and maturation towards endothelium. Methods: 29 subjects were enrolled in this 16 weeks, double-blind, two-arm, randomized placebo matched trial, with 100 mg Canagliflozin (Cana, low dose) compared to placebo. T2DM (30-70 years old), HbA1c of 6.5-10%, and all stages of CKD were included. Peripheral blood derived CD34+ cell number, migratory function, mRNA gene expression along with cardiometabolic parameters such as arterial stiffness, biochemistry, resting energy expenditure, and body composition were measured. Data were collected at weeks 0, 8, and 16. A mixed model regression analysis was done with a p-value <0.05 considered significant. Results: We found a statistically significant reduction in systolic (p=0.008) and diastolic (p=0.038) blood pressure. There was a reduction in blood glucose level (p=0.0047) and HbA1c (p=0.03). There was a statistically significant increase in adiponectin (p=0.0062) and trend level reduction in IL6 (p=0.16), indicating an anti-inflammatory effect of canagliflozin. There is also an increase in mRNA expression of genes associated with endothelial function in CD34+ cells such as VEGFA (p=0.049), VEGF receptor KDR (p=0.13), PECAM-1, a mature endothelial marker was also upregulated (p=0.002) and NOS3 (or eNOS) was also upregulated. There were no significant changes in CD34+ numbers by direct counting and parameters tested. We also tested for serum ketones bodies and found no difference at the dose tested. Data on urine podocyte specific exosome is pending Conclusions: Our study indicates that Canagliflozin improves several components of ECF by improving adiponectin, reducing inflammatory cytokines, and by increasing expression of endothelium specific genes.

scholarly journals Resting Whole Body Energy Metabolism in Class 3 Obesity; from Preserved Insulin Sensitivity to Overt Type 2 Diabetes

2020 ◽  
Vol Volume 13 ◽  
pp. 489-497 ◽  
Author(s):  
Giuseppina Manzoni ◽  
Alice Oltolini ◽  
Silvia Perra ◽  
Emanuele Muraca ◽  
Stefano Ciardullo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Whole Body ◽  
Body Energy

scholarly journals Metabolic Effects of Replacing Sucrose by Isomaltulose in Subjects With Type 2 Diabetes: A randomized double-blind trial

Diabetes Care ◽  
2012 ◽  
Vol 35 (6) ◽  
pp. 1249-1251 ◽  
Author(s):  
S. Brunner ◽  
I. Holub ◽  
S. Theis ◽  
A. Gostner ◽  
R. Melcher ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Effects ◽  
Double Blind Trial ◽  
Double Blind ◽  
Blind Trial

scholarly journals Metabolic Effects of Testosterone Replacement Therapy in Patients with Type 2 Diabetes Mellitus or Metabolic Syndrome: A Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Shu-ying Li ◽  
Ya-ling Zhao ◽  
Yu-fan Yang ◽  
Xi Wang ◽  
Min Nie ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Type 2 Diabetes Mellitus ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Meta Analysis ◽  
Metabolic Effects ◽  
Testosterone Replacement Therapy

Background. Testosterone replacement therapy (TRT) is commonly used for the treatment of hypogonadism in men, which is often associated with type 2 diabetes mellitus (T2DM) and metabolic syndrome (Mets). Recent compiling evidence shows that TRT has beneficial metabolic effects on these patients. Objective. A meta-analysis has been conducted to evaluate the effects of TRT on cardiovascular metabolic factors. Methods. We conducted a systemic search on PubMed, Embase, Cochrane Library, Wanfang, and CNKI and selected randomized controlled trials (RCTs) to include. The efficacy of TRT on glycemia, insulin sensitivity, lipid profile, and body weight was meta-analyzed by Review Manager. Results. A total of 18 RCTs, containing 1415 patients (767 in TRT and 648 in control), were enrolled for the meta-analysis. The results showed that TRT could reduce HbA1c (MD = −0.67, 95% CI −1.35, −0.19, and P = 0.006 ) and improve HOMA-IR (homeostatic model assessment of insulin resistance) (SMD = −1.94, 95% CI −2.65, −1.23, and P < 0.0001 ). TRT could also decrease low-density lipoprotein (SMD = −0.50, 95% CI −0.82, −0.90, and P = 0.002 ) and triglycerides (MD = −0.64, 95% CI −0.91, −0.36, and P < 0.0001 ). In addition, TRT could reduce body weight by 3.91 kg (MD = −3.91, 95% CI −4.14, −3.69, and P < 0.00001 ) and waist circumference by 2.8 cm (MD −2.80, 95% CI −4.38, −1.21 and P = 0.0005 ). Erectile dysfunction (measured by IIEF-5) did not improve, while aging-related symptoms (measured by AMS scores) significantly improved. Conclusions. TRT improves glycemic control, insulin sensitivity, and lipid parameters in hypogonadism patients with T2DM and MetS, partially through reducing central obesity.

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