Barrett EJ, Wang H, Upchurch CT, Liu Z Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculature. Am J Physiol Endocrinol Metab. 2011 Aug;301(2):E252-63. doi: 10.1152/ajpendo.00186.2011. Epub 2011 May 24.
Bateman LA, Slentz CA, Willis LH, Shields AT, Piner LW, Bales CW, Houmard JA, Kraus WE Comparison of aerobic versus resistance exercise training effects on metabolic syndrome (from the Studies of a Targeted Risk Reduction Intervention Through Defined Exercise - STRRIDE-AT/RT). Am J Cardiol. 2011 Sep 15;108(6):838-44. doi: 10.1016/j.amjcard.2011.04.037. Epub 2011 Jul 7.
Cruickshank K, Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG Aortic pulse-wave velocity and its relationship to mortality in diabetes and glucose intolerance: an integrated index of vascular function? Circulation. 2002 Oct 15;106(16):2085-90. doi: 10.1161/01.cir.0000033824.02722.f7.
DeFronzo RA, Abdul-Ghani M Assessment and treatment of cardiovascular risk in prediabetes: impaired glucose tolerance and impaired fasting glucose. Am J Cardiol. 2011 Aug 2;108(3 Suppl):3B-24B. doi: 10.1016/j.amjcard.2011.03.013.
Liu J, Jahn LA, Fowler DE, Barrett EJ, Cao W, Liu Z Free fatty acids induce insulin resistance in both cardiac and skeletal muscle microvasculature in humans. J Clin Endocrinol Metab. 2011 Feb;96(2):438-46. doi: 10.1210/jc.2010-1174. Epub 2010 Nov 3.
Liu Z, Liu J, Jahn LA, Fowler DE, Barrett EJ Infusing lipid raises plasma free fatty acids and induces insulin resistance in muscle microvasculature. J Clin Endocrinol Metab. 2009 Sep;94(9):3543-9. doi: 10.1210/jc.2009-0027. Epub 2009 Jun 30.
Malin SK, Braun B Impact of Metformin on Exercise-Induced Metabolic Adaptations to Lower Type 2 Diabetes Risk. Exerc Sport Sci Rev. 2016 Jan;44(1):4-11. doi: 10.1249/JES.0000000000000070.
Malin SK, Gerber R, Chipkin SR, Braun B Independent and combined effects of exercise training and metformin on insulin sensitivity in individuals with prediabetes. Diabetes Care. 2012 Jan;35(1):131-6. doi: 10.2337/dc11-0925. Epub 2011 Oct 31.
Malin SK, Nightingale J, Choi SE, Chipkin SR, Braun B Metformin modifies the exercise training effects on risk factors for cardiovascular disease in impaired glucose tolerant adults. Obesity (Silver Spring). 2013 Jan;21(1):93-100. doi: 10.1002/oby.20235.
Mather KJ, Verma S, Anderson TJ Improved endothelial function with metformin in type 2 diabetes mellitus. J Am Coll Cardiol. 2001 Apr;37(5):1344-50. doi: 10.1016/s0735-1097(01)01129-9.
Phillips SA, Mahmoud AM, Brown MD, Haus JM Exercise interventions and peripheral arterial function: implications for cardio-metabolic disease. Prog Cardiovasc Dis. 2015 Mar-Apr;57(5):521-34. doi: 10.1016/j.pcad.2014.12.005. Epub 2014 Dec 18.
Potteiger JA, Claytor RP, Hulver MW, Hughes MR, Carper MJ, Richmond S, Thyfault JP Resistance exercise and aerobic exercise when paired with dietary energy restriction both reduce the clinical components of metabolic syndrome in previously physically inactive males. Eur J Appl Physiol. 2012 Jun;112(6):2035-44. doi: 10.1007/s00421-011-2174-y. Epub 2011 Sep 23.
Vlachopoulos C, Aznaouridis K, Stefanadis C Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. J Am Coll Cardiol. 2010 Mar 30;55(13):1318-27. doi: 10.1016/j.jacc.2009.10.061.
Exercise Dose and Metformin for Vascular Health in Adults With Metabolic Syndrome
Interventional studies are often prospective and are specifically tailored to evaluate direct impacts of treatment or preventive measures on disease.
Observational studies are often retrospective and are used to assess potential causation in exposure-outcome relationships and therefore influence preventive methods.
Expanded access is a means by which manufacturers make investigational new drugs available, under certain circumstances, to treat a patient(s) with a serious disease or condition who cannot participate in a controlled clinical trial.
Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.
Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.