2/22/2016. Cardiometabolic Risk. Metabolic syndrome Prediabetes. Traditional/Framingham CVD risk factors

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1 Physical Activity for Managing CardiometabolicRisk Ralph LaForge, MSc Durham NC Speaker Disclosures I have no relevant commercial relationships to disclose Cardiometabolic Risk Diabetes Metabolic syndrome Prediabetes CVD Traditional/Framingham CVD risk factors 1

2 A single bout of exercise generates more realtime metabolic, arterial, and ANS changes than any single medical therapy A single bout of exercise generates more realtime metabolic, arterial, and ANS changes than any single medical therapy A large amount of evidence shows that exercise provides the best prevention and treatment for insulin resistance and type 2 diabetes Pandey 2015 Howard 2015 Butcher 2008 Goodpaster2003 Hawley 2004 Hooumard 2004 Helmrich 1991 Kraus 2004 Ross 2004 Laakosen2005 Schulze 2005 LaForge 2006 Short 2003 Thyfault2009 Slentz 2011 Chae 2012 Sluik 2012 Functional and metabolic benefits (glucose transport, AMPK, PPARδ, insulin sensitization) Measurable body fat alterations, weight loss, LDL-C, Weight loss maintenance kcal/week walking ~5 miles ~10 miles ~15 miles ~20 miles 25+miles Weekly Physical Activity and Cardiometabolic Benefit 2

3 ATP hydrolysis + Insulin signaling Muscle contraction AMPK activation GLUT4 glucose transport Insulin sensitization PPARδγ activation TG & adiposity reduction Glucose and fatty acid oxidation Overall Lipid/Lipoprotein Response to Aerobic Exercise Training of Sufficient Quantity LDL-C 4-7 % LDL-Pnmr % HDL-C 4-25% Jacobson 2015 Mestek 2008 LaForge2007 Fletcher 2005 Durstine2002 Kraus 2002 Leon 2001 TG 4-37% Non HDL 5-12% Cholesterol is not an exercise energy substrate CHOL FA 3

4 Diet vs Exercise for Weight Loss In randomized control trials, about 1 h of daily moderate aerobic exercise produces at least as much fat loss as equivalent caloric restriction, with resultant greater insulin action Ross 2000, 2004 ACSM/ADA 2011 Circulation. 2016;133: Prospective cohort analysis among 4207 US men and women of a mean age of 73 years. Walking (pace, blocks, combined walking score) was updated annually from baseline through Walking pace, distance, and overall walking score, leisure-time activity, and exercise intensity were each associated with lower risk. For example, in comparison with a walking pace <2 mph, those that habitually walked at a pace >3 mph had a 50% lower risk of CHD, CVD and 53% lower incidence of stroke Conclusions These data provide empirical evidence supporting PA recommendations, in particular, walking, to reduce the incidence of CVD among older adults. Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: the European Prospective Investigation into Cancer and Nutrition Study (EPIC) Ulf Ekelund, et.al. Am J Clin NutrJanuary 15, 2015 UK Cohort study in 334,161 European men and women. The authors estimate that doing exercise equivalent to just a 20-minute brisk walk each day burning between 90 and 110 kcal would take an individual from the inactive to moderately inactive group and thereby reduce the risk for premature death by this same amount (ie, between 16% and 30%). The impact was greatest among normal-weight individuals, but even those with higher BMI saw a benefit of physical activity. 4

5 Metabolic Effects of Exercise Training Among Fitness-Nonresponsive Patients With T2D: The HART-D Study AmbarishPandey, Church T et.al. Diabetes Care 2015;38:1494 UTSW 202 participants (mean age 57.1 years, 63% women) - Randomized to a control group or one of three supervised ET groups (AE,RT, Comb) for 9 months. ExRx: 9 months, 3 5 days/week at an intensity of 50 80% RESULTS: Both fitness responders and nonresponders (respectively) had significant improvements in hemoglobin A 1c and measures of adiposity ( HbA 1c,waist circumference, & body fat. No significant differences were observed in the degree of change of these metabolic parameters between fitness responders and nonresponders. ExTris associated with significant improvements in metabolic parameters irrespective of improvement in cardiorespiratory fitness, i.e., aerobic capacity Increasing physical activity can significantly reduce abdominal adipose tissue (including waist circumference) and improve insulin sensitivity without significant changes in body weight and/or BMI Pandey A. Diabetes Care 2015;38:1494 Ekelund Am J Clin Nutr 2011;93: Yates T et.al. Diabetes Care 2009;32:1404, Velthuis MJ et.al. Menopause 2009;16:777 van der Heijden et.al. J Clin Endo Met. 2009;94:4292 Carey AL et.al. Exercise Mimetics, Diabetologia, 9/09 Hansen D Diabetologia 2009; 52: Brown R Med Sci Sports Ex 2009;41:497 Ribeiro ICD Med.Sci Spts Ex 2008;40:779 Despres JP SYNERGIE Trial EAS 2008 Misra A et.al., Diabetes Care 2008;31: Bell LM et.al. J Clin Endo Met 2007;92:4230 Ekelund, U et.al. Diabetes Care 2007;30:2101 Dekker M Metabolism 2007;56:332 DiPietro L et. al. JAP 2006 Lee SJ & Ross JAP 2005;99:1220 Wong SL et.al. Med Sci Sports Ex 2004;36:286 Duncan GE Diabetes Care 2003;26:557 Ross R et.al. Obes Res. 2004;12: Ross R et.al. Relat Met Dis 2003;27:204 Mourier A et.al. Diabetes Care 1997;20:385 Ross R et.al. Ann Intern Med 2000;133:92 SEDENTARY TIME and Metabolic Syndrome Bankoski, A. Sedentary Activity Associated With Metabolic Syndrome Independent of Physical Activity Diabetes Care February 1, : NIH and GMUSe 5

6 Med. Sci. Sports Exerc., Vol. 47, No. 9, pp , ,614 older adults (59 82 yr) in the National Institutes of Health-AARP Diet and Health Study Among less active adults, replacement of 1 hridayof sitting with an equal amount of either exercise or nonexerciseactivity was associated with lower (30-40%) total mortality. Older adults free of major medical conditions, greater overall sitting was associated with a graded increase in risk of 30% 40% for death from all causes aand 40% 55% greater risk f or cardiovascular mortality Prolonged sitting/sedentary time is associated with increased mortality and increased incidence of insulin resistance and type 2 diabetes Matthews et.al. 2015; Pavey 2015;Armstrong KatrienWijndaeleDiabetologia(2014) 57: ; Carr2013; Cooper 2012; Genevieve Healy, Diabetes Care, Feb. 2011;Wilmot EG et.al., et.al. Diabetologia Apr;56(4):942-3.;Gibbs, et.al. Diabetes Care, July 8, 2015; Sardinha et.al. Diabetes Care 31: , 2008 Replacing sitting time with standing or stepping: associations with cardio-metabolic risk biomarkers Genevieve Healy et.al. Eur. Heart J. July 2015 Methods: A subsample of participants from the 2011/12 Australian Diabetes, Obesity, and Lifestyle Studywore the posture-based activpal3 monitor [36 80 years (58y); 57% women;n= 698 with data]. Sitting-to-standing reallocations were only significantly (P< 0.05) associated with approximately 2% lower fasting plasma glucose, 11% lower triglycerides, 6% lower total/hdl-cholesterol ratio, and 0.06 mmol/l higher HDLcholesterol per 2 h/day. Sitting-to-stepping reallocations were only significantly associated with approximately 11% lower BMI, 7.5 cm lower waist circumference, 11% lower 2-h plasma glucose, 14% lower triglycerides, and higher HDL-cholesterol per 2 h/ day, while Sitting-reduction strategies targeting increased standing, stepping, or both, may benefit cardio-metabolic health. Standing is a simple alternative to sitting, and requires further examination in prospective and intervention studies. 6

7 The Physiology of Inactivity i.e., Prolonged Sitting Increased platelet stickiness Decreased lipoprotein lipase activity Workplace EE 5 min/hr X 7 hrs kcal/min steps kcal (insulin sensitization e.g., mg metformin) The modern world makes it very easy to out-eat exercise, and nearly impossible to out-exercise excessive eating David Katz Yale University Prevention Research Center 7

8 Men and women with pre-diabetes had a dramatic improvement in blood sugar control after only 6 days of exercise training, but only if the energy expended during exercise was not added back to their diet. Implication: Starting an exercise program can generate big improvements very quickly, well before any substantial weight loss. Braun B et.al. J ApplPhysiol99: , U Mass 1 scone = calories 5-10 minutes = mile walk minutes Department/Laboratory: Walking Behavior Catrine Tudor-Locke,PhD 8

9 2/22/2016 Pharmacology of Pedometry Metformin (Glucophage) Each step 9

10 Daily Rx: 6, yrs 10,000 Adults 12, yrs "Every step you take I'll be watching you. - Sting Colley R Med Sci Spts Ex 2012;44977 Diverse types of moderate exercise is also associated with lower incidence of diabetes and CVD mortality. This includes such utilitarian activities as walking, gardening, climbing, and household/yard chores. Those who expend kcal per week in such utilitarian activities may require very little additional exercise to lower diabetes and CVD risk. Lakka TA. Et.al. NEJM 1994;330:1549 Thompson P et.al. Circ. 2003;107:3101 Fransson E. et.al. Scan J Pub Health 2003;31:324 Meisinger C et.al. Diabetologia 2005;48:27 Marcus B et.al. Circ. 2006;114: 2739 Holme I et.al. BMC Public Health 2007, 7:154 Diverse types of daily physical activity 10

11 Name Date Rx: Household-Community Circuit Rx minutes 2-minute rest/water break between stations Always start and end session with warm-up/cool down exercise as prescribed Do not continue exercise or go the next station if you experience chest discomfort, palpitations, dizziness or unusual fatigue The Gym Inside Your Door Utilitarian household and yard chore circuit "workouts" that can be systematically and creatively organized into one productive workout expending kcal. Prediabetes and diabetes-centric focus. Conclusion Just move and move often! 11