4 research outputs found
Beta-cell function, incretin effect and glucose kinetics in response to a mixed meal in patients with type 2 diabetes treated with dapagliflozin plus saxagliptin
Objective - To explore complementary effects of DPP-4 and SGLT2 inhibitors combination as add on to metformin on hormonal and metabolic responses to meal ingestion. Research Design and Methods - Forty-five patients (58±8 y, HbA1c: 58±6 mmol/mol, BMI: 30.7±3.2 Kg/m2) uncontrolled with metformin were evaluated at baseline, 3- and 28-days after saxagliptin 5 mg (SAXA), dapagliflozin 10 mg (DAPA), and saxagliptin 5 mg plus dapagliflozin 10 mg (SAXA+DAPA) with a mixed meal tolerance test (MMTT) spiked with dual-tracer glucose to assess glucose metabolism, insulin secretion and sensitivity. Results - At day 3, fasting and mean MMTT glucose were lower with SAXA+DAPA (-31.1± 1.6 mg/dl; -91.5± 12.4 mg/dl) than SAXA (-7.1± 2.1 and -53±10.5 mg/dl) and DAPA (-17.0±1.1; -42.6±10.0 mg/dl; p<0.001). Insulin secretion rate (SAXA+DAPA +75%; SAXA +11%; DAPA 3%) and insulin sensitivity (+2.2±1.7, +0.4±0.7, +0.4±0.4 mg kg-1 min-1; respectively) improved with SAXA+DAPA (p<0.007). Mean GLP-1 was higher in SAXA+DAPA than SAXA and DAPA. Fasting glucagon increased with DAPA and SAXA+DAPA but not with SAXA. Fasting EGP increased with SAXA+DAPA and DAPA. During MMTT EGP suppression was greater (48%) with SAXA+DAPA (SAXA 44%, p=0.02; DAPA 34%, p=0.2). Metabolic Clearance Rate of glucose (MCRglu) increased more with SAXA+DAPA. At week 4, insulin secretion rate, b cell glucose sensitivity, insulin sensitivity further increased in SAXA+DAPA (p=0.02) with no further changes in GLP-1, glucagon, fasting and MMTT EGP, and MCRglu. Conclusions SAXA+DAPA provided superior glycemic control compared with DAPA or SAXA due to improved β cell function, insulin sensitivity, GLP-1 availability and glucose clearance.</p
Comparison of the transcriptional response to T<sub>1</sub>AM with the known genomic effects of thyroid hormone, Insulin and Cortisol (up-regulated  = ↑, down-regulated  = ↓, not regulated or no data available  =  -).
<p>Comparison of the transcriptional response to T<sub>1</sub>AM with the known genomic effects of thyroid hormone, Insulin and Cortisol (up-regulated  = ↑, down-regulated  = ↓, not regulated or no data available  =  -).</p
Differentially expressed genes in the subcutaneous adipose tissue annotated by <i>Onto-Express</i>, <i>GeneCards</i> and <i>COREMINE</i>.
<p>Differentially expressed genes in the subcutaneous adipose tissue annotated by <i>Onto-Express</i>, <i>GeneCards</i> and <i>COREMINE</i>.</p
Changes in gene expression evidenced by microarrays were confirmed by RT-qPCR for four of the five genes tested in the subcutaneus adipose tissue (the differential expression of Cebpb was not statistically significant) and for all the seven genes tested in the liver.
<p>Data reported as: log2 fold-change ± SE; *: p≤0.05.</p