scholarly journals Exercise, Pharmaceutical Therapies and Type 2 Diabetes: Looking beyond Glycemic Control to Whole Body Health and Function

Author(s):  
Thomas Yates ◽  
Joseph Henson ◽  
Jack Sargeant ◽  
James A King ◽  
Ehtasham Ahmad ◽  
...  

Exercise, Pharmaceutical Therapies and Type 2 Diabetes: Looking beyond Glycemic Control to Whole Body Health and Function Thomas Yates()1,2, Joseph Henson1,2, Jack Sargeant1,2, James A King2,4, Ehtasham Ahmad1, Francesco Zaccardi1,3 and Melanie J Davies1,2  1Diabetes Research Center, University of Leicester, Leicester General Hospital, Leicester, LE5 4PW, UK 2NIHR Leicester Biomedical Research Center, University Hospitals of Leicester NHS Trust and University of Leicester, UK 3Leicester Real World Evidence Unit, Diabetes Research Center, University of Leicester, Leicester, UK 4National Center for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, UK © The Authors   Abstract Exercise is a powerful therapy for improving glycemic control and increasing cardiorespiratory fitness in adults with type 2 diabetes mellitus (T2DM). However, there is a dearth of evidence investigating interactions or synergies between exercise and most pharmaceutical therapies. This is important as exercise is rarely prescribed in isolation of other background medications used to manage T2DM. Therefore understanding which exercise and drug combinations optimize or blunt responses is crucial. This narrative review discusses advances in weight loss management in diabetes and highlights research opportunities and challenges for combining exercise therapies with newer generations of glucose-lowering therapies with weight loss effects, particularly glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is). We discuss the role of exercise in preserving lean mass and increasing physical function along with other potential areas of synergy. We conclude that until the evidence base investigating areas of interaction or synergy between exercise and other glucose-lowering or weight loss therapies is developed, exercise will remain a generic rather than a tailored therapy in the management of T2DM. 

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1014-P
Author(s):  
JULIO ROSENSTOCK ◽  
CRISTOBAL MORALES ◽  
ULRICH WENDISCH ◽  
GEORGE E. DAILEY ◽  
MICHAEL E. TRAUTMANN ◽  
...  

2004 ◽  
Vol 17 (3) ◽  
pp. 176-180 ◽  
Author(s):  
R. M. Tucker ◽  
C. May ◽  
R. Bennett ◽  
J. Hymer ◽  
B. McHaney

2018 ◽  
Vol 315 (5) ◽  
pp. G810-G823 ◽  
Author(s):  
Leslie R. Sedgeman ◽  
Carine Beysen ◽  
Ryan M. Allen ◽  
Marisol A. Ramirez Solano ◽  
Scott M. Turner ◽  
...  

Colesevelam is a bile acid sequestrant approved to treat both hyperlipidemia and type 2 diabetes, but the mechanism for its glucose-lowering effects is not fully understood. The aim of this study was to investigate the role of hepatic microRNAs (miRNAs) as regulators of metabolic disease and to investigate the link between the cholesterol and glucose-lowering effects of colesevelam. To quantify the impact of colesevelam treatment in rodent models of diabetes, metabolic studies were performed in Zucker diabetic fatty (ZDF) rats and db/db mice. Colesevelam treatments significantly decreased plasma glucose levels and increased glycolysis in the absence of changes to insulin levels in ZDF rats and db/db mice. High-throughput sequencing and real-time PCR were used to quantify hepatic miRNA and mRNA changes, and the cholesterol-sensitive miR-96/182/183 cluster was found to be significantly increased in livers from ZDF rats treated with colesevelam compared with vehicle controls. Inhibition of miR-182 in vivo attenuated colesevelam-mediated improvements to glycemic control in db/db mice. Hepatic expression of mediator complex subunit 1 (MED1), a nuclear receptor coactivator, was significantly decreased with colesevelam treatments in db/db mice, and MED1 was experimentally validated to be a direct target of miR-96/182/183 in humans and mice. In summary, these results support that colesevelam likely improves glycemic control through hepatic miR-182–5p, a mechanism that directly links cholesterol and glucose metabolism. NEW & NOTEWORTHY Colesevelam lowers systemic glucose levels in Zucker diabetic fatty rats and db/db mice and increases hepatic levels of the sterol response element binding protein 2-responsive microRNA cluster miR-96/182/183. Inhibition of miR-182 in vivo reverses the glucose-lowering effects of colesevelam in db/db mice. Mediator complex subunit 1 (MED1) is a novel, direct target of the miR-96/182/183 cluster in mice and humans.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Soohyun Nam ◽  
Soohyun Nam ◽  
Devon A Dobrosielski ◽  
Kerry J Stewart

Background: Though a high amount of visceral fat is associated with insulin resistance, which can lead to type 2 diabetes (T2D) and cardiovascular diseases (CVDs), less is known about whether lifestyle modification (weight loss diet and exercise) induced changes in visceral fat are associated with improvements in glycemia. Methods: We randomized 77 individuals aged 35-65 years with T2D or pre-diabetes to 6-months of weight loss diet (D); or D combined with supervised moderate-intensity exercise training (D+E). Study measures were total abdominal, visceral and subcutaneous fat volumes by magnetic resonance imaging, aerobic fitness expressed as VO 2 peak during treadmill testing, body mass index (BMI), and HbA1c levels from blood samples. Results: Of 77 subjects (mean age, 54.8±7.8 years; mean BMI, 34.5 ± 4.7 kg/m 2 , women, 77.9%; Whites-65%, Blacks-34%, Asians-1%), n=37 had T2D and n=40 had pre-diabetes. At 6 months, both D and D+E groups improved from baseline (p<0.05 for all) but did not differ in their changes for body weight (D: -6.04 ± 4.54 kg; D+E: -6.68 ± 4.48 kg, p= 0.61 for the group differences in change), abdominal total fat (D: -101.93 ± 68.67 cm 2 ; D+E:-104.16 ± 72.37 cm 2 , p= 0.92), visceral fat (D:-25.53 ± 39.44 cm 2 ; D+E:,-23.24 ± 35.62 cm 2 , p=0.85), HbA1c (D:0.04 ± 0.46%; D+E:0.03 ± 0.63%, p=0.96), and VO 2 peak (D: 2.26 ± 3.92 ml/kg/min ; D+E:3.71 ± 2.65 ml/kg/min, p=0.11). In a multivariate analysis, adjusting for baseline visceral fat, T2D status, body weight loss and increases in aerobic fitness, a reduction in HbA1c (β=-0.49, p =0.007) was associated with a reduction in visceral fat (R 2 =0.34, p=0.02). Conclusion: The key finding was that diet or diet plus exercise-mediated reductions in visceral fat was associated with reduced HbA1c among individuals with T2D or pre-diabetes. These data contribute to growing body of evidence of the benefits of reducing abdominal obesity, in this case, resulting in better glycemic control in T2D and pre-diabetes.


2012 ◽  
Vol 15 (7) ◽  
pp. A494
Author(s):  
C. Mcadam-marx ◽  
B.K. Bellows ◽  
G.D. Wygant ◽  
J. Mukherjee ◽  
S. Unni ◽  
...  

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