Auburn University AUBURN, ALABAMA

Auburn University at MontgomeryAcute Insulin Responses Following Exercise and Relationship to Lipid Changes

Scott J. Clark1, Joshua S. Wooten1, Sofiya Alhassan2, Eric P. Plaisance2, Victor Ben-Ezra1, Kyle Taylor3, Kyle D. Biggerstaff1, Peter W Grandjean2, FACSM. 1Texas Woman’s University, Denton, TX, 2Auburn University, Auburn, AL, and 3Auburn University-Montgomery AL. (Sponsor: Peter W. Grandjean, FACSM)

The metabolic syndrome is associated with elevated serum lipids, insulin, and glucose concentrations. Frequent exercise is often prescribed as a method of reducing risk of developing both diabetes and hyperlipidemia; however, relatively little data exists documenting the acute response of insulin with respect to serum lipids following exercise. PURPOSE: To determine the response of fasted insulin and glucose concentrations following four days of exercise and to determine if this response was related to variables associated with serum lipid concentrations. METHODS: Participants (N = 15 females, mean ± sd, age = 50 ± 2 y, BMI = 31.9 ± 1.2 kg/m2, % fat = 29 ± 1, total cholesterol = 253 ± 11 mg/dl, triglycerides = 266 ± 38 mg/dl, HDL-C = 32 ± 1 mg/dl) performed 350 kcal of treadmill exercise at ~70% VO2peak on four consecutive days. Fasting insulin (μU/ml) and glucose (mM) concentrations, adjusted for plasma volume changes, were measured prior to each of the four exercise sessions and 24 h and 72 h following the fourth exercise session. RESULTS: As revealed by one-way repeated measures ANOVA, fasting insulin concentration was significantly (p < 0.05) reduced by repeated days of exercise.

Table: Means ± sd. Same superscripts are not different (p > 0.05)The change in insulin concentration from baseline to 24 h following four days of exercise was significantly (p < 0.05) correlated with percent body fat (r = 0.64) and the previously reported (MSSE 33(5): No. 1211, p. S215, 2001) change (-30%) in triglyceride concentration (r = 0.31) and (MSSE 34(5): No. 113, p. S21, 2002) change (-5.1%) in hepatic lipase activity (r=0.49). CONCLUSION: These data suggest that four consecutive days of exercise decrease fasting insulin concentrations. Furthermore, a reduction in post-exercise fasting insulin is associated with markers of lipid metabolism.

Baseline Day 2 Day 3 Day 4 +24h +72h Ins 15.5±10.0a 11.5±6.6b 10.7±4.4b 13.0±8.3a 9.5±3.7b 12.5±7.7ab Glu 5.5±0.7a 5.3±0.5a 5.7±0.6a 5.6±0.8a 5.7±0.6a 5.8±0.7a

Physiological Assessments cont. Fasting post-heparin plasma samples were obtained

each day before exercise and 24 and 72 hr after the last exercise bout. Post-heparin plasma samples were assayed for total lipase (TLa), lipoprotein lipase (LPLa) and hepatic lipase (HLa) activities (mol FFA/mL/hr) (MSSE 34(5): No. 113, p. S21, 2002).

Plasma samples at each time point were measured for glucose in duplicate on an automated analyzer (YSI, Inc., Yellow Springs, Ohio), and the average value was used for subsequent data analysis. In addition, duplicate samples were obtained and analyzed for insulin using a double anti-body, competitive RIA technique1. The general schema for the experimental protocol is illustrated in Figure 1.

Figure 1. Experimental Protocol.

EX = days in which exercise was completed; POST = days after completing the last exercise bout.

Significant changes were determined using one-way repeated measures ANOVA. Post hoc tests to determine significant differences between single cells were used when necessary. Pearson product correlations were calculated to examine relationships between fasting insulin and glucose concentration change with lipid variables. The criterion reference for statistical significance was set at p < 0.05.

All data are reported as mean ± standard deviation.

ResultsTable 2. Physiological Variables and Exercise Data.

Means ± sd. Same superscripts are not different (p > 0.05). (MSSE 34(5): No. 113, p. S21, 2002)

Table 3. Lipase Activity.

Means ± sd. Same superscripts are not different (p > 0.05). (MSSE 34(5): No.

113, p. S21, 2002)

Baseline Day 2 Day 3 Day 4 +24h +72h

TLa 97±34a 101±31a 99±31a 101±34a 99±33a 101±30a

LPLa 18±9a 25±12a,b 22±9b 24±8b 23±10b 24±9b

HLa 79±33a 76±29a 77±27a 77±33a 75±3a 78±30a

Table 1. Descriptive Characteristics of Participants.

Physiological Assessments Peak oxygen consumption and work rate were

determined from a standardized graded exercise test performed on a treadmill (model Q-65, Quinton Instrument, Seattle, WA). Throughout the test, continuous HR and rhythm were monitored by a 12-lead ECG (model-4100, Quinton Instrument), blood pressure was determined manually, and ratings of perceived exertion were obtained during the last 30-s of every stage and at maximal exercise.

Respiratory gas exchange was determined on a breath-by-breath basis and averaged over 30-s intervals (CARDIO2 Exercise Stress Testing System, Medical Graphics, Minneapolis, MN). The test was considered a maximal effort if two of the following criteria were met: the achieved maximum HR was within 10 beats/min of participants age-predicated maximum, the respiratory exchange ratio (RER) was > 1.1, the rating of perceived exertion was 18, or a plateau for VO2 was achieved despite a further increase in workload4.

The experimental blood sampling and exercise were initiated after one week of stable dietary and nutrition intake. All participants provided a 3-day diet record to be analyzed by a licensed Nutritionist.

• No significant differences across time were found in diet records for total calories and macronutrient composition.

Exercise was completed by expending approximately 350 kcal of energy while treadmill walking / jogging on four consecutive days at 70% VO2max.

All blood samples were obtained after an overnight fast and prior to exercise on days 1 through 4.

Post-exercise blood samples were obtained at the same time of day under the same conditions on days 5 and 7 (MSSE 34(5): No. 113, p. S21, 2002). All lipid, lipoprotein-cholesterol, insulin, and glucose concentrations were corrected for post-exercise plasma volume change. Hematocrit and hemoglobin values were used to determine the percentage of change in plasma volume according to the equations of Dill and Costill4.

Variable Mean±SD Range Age (yr) 50±8 37-67 Height (cm) 178±6 168-188 Weight (kg) 101±18 67-127 Body Fat (%) 29±4 19-34 VO2max (mL/kg/min) 28.9±4.3 22.1-36.5 VO2max (L/min) 2.9±0.4 2.1-3.7 Cholesterol (mg/dL) 253±44 194-333 LDL-C (mg/dL) 168±42 104-260 HDL-C (mg/dL) 32±5 25-44 TG (mg/dL) 267±145 45-494 Fasting Insulin (U/mL) 15.5±10.0 3.7-36.2 Fasting Glucose (mM) 5.5±0.07 4.5-7.3

Figure 2. Total Serum Triglyceride Concentrations.

Means ± sd. Same superscripts are not different (p > 0.05). (MSSE 33(5): No. 1211, p. S215, 2001)

Table 4. Post-Exercise Fasting Insulin and Glucose Responses.

Means ± sd. Same superscripts are not different (p > 0.05).

As revealed by one-way repeated measures ANOVA, fasting insulin concentration was significantly (p < 0.05) reduced by repeated days of exercise.

The change in insulin concentration from baseline to 24 h following four days of exercise was significantly (p < 0.05) correlated with percent body fat (r = 0.64).

There were no significant relationships between lipoprotein variables and changes in glucose concentrations across time.

There was a significant (p < 0.05) 30% reduction in TG concentrations from baseline to 24 hr post-exercise, which tends to remain depressed 72 hr post-exercise.

In addition, the change in insulin concentration from baseline to 24 hr following four consecutive days of exercise was significantly correlated (p < 0.05) with the previously reported (MSSE 33(5): No. 1211, p. S215, 2001) change (-30%) in triglyceride concentration (r = 0.31; see Figure 2) and (MSSE 34(5): No. 113, p. S21, 2002) change (-5.1%) in hepatic lipase activity (r = 0.49; see Table 3).

Conclusions Moderate intensity exercise performed on 4

successive days significantly lowers fasting plasma triglyceride and insulin concentrations 24 hr after the last bout of exercise.

Reduced post-exercise fasting insulin is associated with markers of lipid metabolism and may be directly linked to lipid enzymatic activity.

350 kcal of moderate intensity aerobic exercise may be enough caloric expenditure to elicit a concomitant reduction of fasting plasma triglyceride and insulin concentrations in dyslipidemic men.

Baseline Day 2 Day 3 Day 4 +24h +72h

Ins 15.5±10.0a 11.5±6.6b 10.7±4.4b 13.0±8.3a 9.5±3.7b 12.5±7.7ab

Glu 5.5±0.7a 5.3±0.5a 5.7±0.6a 5.6±0.8a 5.7±0.6a 5.8±0.7a

Introduction Elevated fasting insulin, a surrogate marker of insulin

resistance, has been associated with dyslipidemia. When clustered together, these present as hallmark descriptors of the Metabolic Syndrome3. Despres, et al3 has succinctly linked insulin resistance to the dyslipidemic profile associated with the Metabolic Syndrome (e.g., elevated triglycerides and low HDL). Currently, it has been accepted that the primary derangements common to the Metabolic Syndrome (i.e., insulin resistance and dyslipidemia) result from a reduced lipoprotein lipase (LPL) sensitivity to insulin which in turn creates a metabolic environment of elevated plasma free fatty acids (FFA). Chronic elevation of plasma FFA may lead to increased tissue triglyceride storage (i.e.,lipotoxicity), hepatic and skeletal muscle insulin resistance, increased hepatic glucose production, and a reduced pancreatic ß-cell secretion of insulin.

Aerobic exercise has been used to reduce the risks and complications associated with insulin resistance and dyslipidemia1,2,8,9,10,11. In fact, a variety of chronic and acute exercise protocols manipulating intensity and duration or both can improve insulin sensitivity, lower triglycerides, and elevate HDL cholesterol1,2,8,9,10,11. However, an appropriate dose of exercise to positively and concomitantly improve the primary variables associated with the Metabolic Syndrome (insulin and lipid-lipoproteins) has yet to be fully elucidated. In addition, controversy exists as to whether postexercise changes in lipid variables like triglycerides and insulin are even related5.

Purpose To determine the response of fasted insulin and

glucose concentrations following four consecutive days of exercise and to determine if this response was related to variables associated with serum lipid concentrations.

MethodsParticipants Fifteen middle-aged males with elevated plasma

cholesterol (> 200 mg/dL) and/or elevated triglyceride concentrations (> 200 mg/dL) and who did not engage in regular physical (< 3 d/wk and < 30 min/bout) were recruited from the Auburn-Opelika, Alabama area. All volunteers were screened for

Continued

Participants , continued.contraindications to exercise, cardiovascular and metabolic disease and drugs known to alter lipid metabolism prior to entry into the study. Subject baseline characteristics are provided in Table 1.