Jephcott symposium - Runsweet

Jephcott symposium - Runsweet

Diabetes and exercise Ian Gallen What do we need to know Effect of exercise on blood glucose Differences between types of exercise Timing, type and quantity of carbohydrate What to do with insulin dose Nocturnal hypoglycaemia How to use insulin pump treatment Glucose metabolism during exercise Production Use m mol/kg/min 60 Glucose mmol/l 6 4.9

5 4.5 4.6 4.55 4.3 3.9 40 4 20 3 0 2

0 50 100 150 0 20 40 60 80 100 Exercise time (min) McConell et al. 1994

120 What is different about exercise in diabetes? Food storage Athletes require high energy intake of high glycaemic index foods. Usually excessive background insulin levels Endocrinology of exercise Abnormal glucagon response Abnormal portal insulin regulation of gluconeogenesis and ketogenesis Impaired catecholamine response Diabetic complications Autonomic neuropathy/microvascular disease What Happens to Blood Glucose in Exercise in Type 1 Diabetes? 22.2 22.2 15/01/2006

16. 7 06/10/2005 (Thu) Glucose - mmmol/L mmmol/L 16.7 11.1 Exercise 5.6 11.1 10.0 Exercise

5.6 3.9 0.0 0.0 03:00 06:00 09:00 22.2 12:00 15:00 18:00 21:00

03:00 00:00 06:00 09:00 24/11/2005 12:00 15:00 18:00 Aerobics mmmol/L 16.7 Cycling

11.1 5.6 Data from Buckinghamshire Hospitals Diabetes Sports clinic 0.0 03:00 06:00 09:00 12:00 15:00 18:00

21:00 00:00 21:00 00:00 Trends in Glucose Production and Use in T1DM During Prolonged Aerobic Exercise Glucose use Glucose production Blood glucose Counter-regulatory hormone response Meal

60 min training run Trends in Glucose Production and Use in T1DM During Short Intense Exercise Blood glucose Glucose production Counter-regulatory hormone response Meal 30 min exercise Ian Gallen Glucose use Rest Effect of high or low intensity exercise on blood glucose in T1DM Blood glucose and metabolite response

during exercise in T1DM Glucose levels during and following different forms of exercise Aerobic first Resistance first Aerobic first Resistance first Hypoglycaemia is frequent following aerobic and resistance training Effects of exercise on blood glucose Aerobic exercise causes blood glucose to fall rapidly Anaerobic exercise cause blood glucose to rise Aerobic exercise increases risk of nocturnal hypoglycaemia Intermittent high intensity exercise protects against hypoglycaemia during exercise, but is

more likely to cause nocturnal hypoglycaemia Team sports have variable effect on glucose depending on position and intensity of play Carbohydrate support Why not just start with a high glucose? Some mathematics Available free glucose space is 20% lean person total weight 1mm/l measured glucose is 0.18g free glucose or total 2.5g in 70 kg person Thus raising bg to 15mmol/l, will only provide 25g readily available glucose. At 60%VO max glucose oxidation typically 130 mol/kg/min.mol/kg/min. Thus approximately 2g/min or 12 minutes! 2 Capillary Blood Glucose Concentration (mg/dL) Effect of Carbohydrate Ingestion on the Glycaemic Response of Type 1 Diabetic Adolescents During Exercise

350 CHO 8% CHO 10% 300 66.5 g 250 200 Strategy 2 Taking extra glucose whilst exercising Using the mouth to do the livers job 150 100 55.3 g 50

* * 0 -15 0 15 30 Time (min) Exercise Data are means SD; *p<0.05. Perrone C, Laitano O, Meyer F. Diabetes Care. 2005;28:25372538. 45 60 (0)

(30) Recovery (60) 75g Isomaltulose or dextrose before exercise in T1DM West et al, 2011 Strategies for Glucose Replacement During Exercise Glucose 20 g 20 g 20 g Glucose Concentration (mM) 10 mM 5 mM Glucose 60 g 10 mM 5 mM 90 minutes aerobic exercise

Insulin dose adjustment 5 4 3 2 1 0 -1 -3 -4 -5 Exercise at 25% VO2 max for 60 min 5 4 3 2 1 0 % Dose

reduction -1 % Dose * reduction Baseline plasma glucose (mmol/L) LP 100% = 8.8 0.55 LP 50% = 6.1 1.3 -2 -3 -4 Exercise intensity 30 minmeal of 60 min of Reducing pre-exercise insulin

Time (minutes) Time (minutes) exercise exercise (% VO2max) -5 0 B Change from baseline in plasma glucose (mmol.L) * Baseline plasma glucose (mmol/L) LP 100% = 10.7 0.7 LP 50% = 9.4 0.8 -2 A

Change from baseline in plasma glucose (mmol.L) Exercise at 50% VO2 max for 30 min 30 60 90 120 150 180 0 Exercise at 75% VO2 max for 30 min 25

5 50 4 3 2 0 -1 * Baseline plasma glucose (mmol/L) LP 100% = 8.5 1.3 LP 25% = 6.8 1.1 -2 -3 -4 60

90 120 150 25 210 50 5 75 4 3 2 75

- 1 0 -1 180 Exercise at 50% VO2 max for 60 min 50 75 1 30 B Change from baseline in plasma glucose (mmol.L)

Change from baseline in plasma glucose (mmol.L) A * Baseline plasma glucose (mmol/L) LP 50% = 8.7 1.0 LP 25% = 6.0 1.4 -2 -3 -4 -5 -5 0 30

60 90 120 Time (minutes) 150 0 180 Ian Gallen Data are means SEM; *p<0.05 by repeated measures using ANOVA; LP: lispro. Rabasa-Lhoret R et al. Diabetes Care. 2001;24:625630. 30 60

90 120 Time (minutes) 150 180 210 Hypoglycaemia seems to be more common with Glargine than either NPH or Detemir Nocturnal hypoglycaemia Biphasic response in glucose requirement with exercise Increased glucose up take during exercise, but also late after exercise Responses of glucose infusion rate (mg/kg{middle dot}min) (A), difference in glucose infusion rate (GIR) between

exercise and rest studies (mg/kg{middle dot}min) (B), rate of carbohydrate oxidation (mg/kg{middle dot}min) (C), and rate of lipid oxidation (D) to exercise (solid lines) and rest (dashed lines) studies McMahon, S. K. et al. J Clin Endocrinol Metab 2007;92:963-968 Skeletal muscle GLUT-4 gene expression before (0), immediately after (Post), and 3 h after (3 hrs) exercise at ~40% (Lo) or ~80% (Hi) peak pulmonary oxygen consumption Kraniou, G. N. et al. J Appl Physiol 101: 934-937 2006; doi:10.1152/japplphysiol.01489.2005 Copyright 2006 American Physiological Society Delayed hypoglycaemia CGMS following exercise in T1DM The complex interaction between hypoglycaemia and exercise Exercise markedly increases muscle insulin sensitivity by increasing GLUT4 transporters1 Effect from 6-12 hours post exercise lasting 48 hours. Prior hypoglycaemia impairs counter-regulatory response to exercise, and this is proportional to the level of hypoglycaemia2.

Prior exercise impairs the counter-regulatory response to hypoglycaemia2. The counter-regulatory response to exercise is relatively preserved in women following hypoglycaemia3. 1 Thorell A, Hirshman MF, Nygren J et al. Exercise and insulin cause GLUT-4 translocation in human skeletal muscle. Am J Physiol Endocrinol Metab 1999;277:E733-41. 2 Galassetti P, Tate D, Neill RA et al. Effect of antecedent hypoglycaemia on counterregulatory responses to subsequent euglycaemic exercise in type 1 diabetes. Diabetes 2003;52:1761-9. 3 Galassetti,P.; Tate,D.; Neill,R.A.; Morrey,S.; Wasserman,D.H.; Davis,S.N. Effect of sex on counterregulatory responses to exercise after antecedent hypoglycemia in type 1 diabetesAmerican Journal of Physiology Endocrinology & Metabolism.2004, 287(1):E16-24, AN10-551A Insulin infusion pumps Enables normal basal insulin to be markedly reduced or suspended whist performing exercise. with rapid post exercise increase in insulin to deal with post exercise glycogenic peak.

and lower post exercise nocturnal basal rate with intermittent exercise patterns. The gold standard for serious athletes where practical. Prevention of Hypoglycemia During Exercise in Children With Type 1 Diabetes by Suspending Basal Insulin Glucose Concentration (mg/dL) 200 150 100 50 Basal insulin continued Basal insulin stopped 0 Baseline

Rest #1 Rest #2 Rest #3 Ian Gallen End Post 15 Black dots denote mean values; Boxes denote median, and 25th and 75th percentiles. The Diabetes Research in Children Network. Diabetes Care 2006;29:22002204 Post 30 Post 45 Blood glucose with 1 hour of exercise at 50% VO2 MAX

Progress towards an artificial Pancreas? Combination CSII/CGMS Automatic low glucose infusion suspend during exercise Automatic low glucose infusion suspend during exercise Are there any other strategies? Sympathomimetics Endogenous sympathetic stimulation The 10-s Maximal Sprint: Bussau, et al Diabetes Care. 2006. 29, 601. Caffeine (5mg/kg) and Blood Glucose During Prolonged Exercise Glucose 20g given in 2 subjects 20 * 18

Placebo Glucose (mmol/L) 16 * 14 Caffeine * 12 n=5 10 8 6

4 2 Exercise 50% 0 -30 0 70% VO2 max 10 20 30 Time (min)

Ian Gallen Gallen IW, et al. Diabetes Care. 2010;Abstract 1184P 40 70 Summary of Clinical Strategies to Maintain Glycaemic Control With Exercise Strategy Advantages Disadvantages Reducing preexercise bolus insulin Reduces hypoglycaemia during and following exercise; reduces CHO requirement Needs preplanning; not helpful for

spontaneous exercise or for late postprandial exercise Reducing preexercise basal insulin As above As above, causes pre- and late postexercise hyperglycaemia Taking extra CHO with exercise Useful for unplanned or prolonged exercise May not be possible with some exercises; not helpful where weight control important; easy to overreplace causing hyperglycaemia Pre- or postsprint

exercise burst Reduces hypoglycaemia during and following sports Effect limited to shorter and less intense exercise Insulin pump therapy Offers flexibility and rapid change in insulin infusion rates postexercise Expensive; may not be practical for contact sports (eg, rugby/ football/ judo) Reducing basal insulin postexercise Reduces nocturnal hypoglycaemia May cause morning hyperglycaemia

Lumb A., Gallen I.W. Curr. Opin. Endo. Diab and Obesity. 2009 16 www.runsweet.com Ian Gallen

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