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Published in final edited form as: Appl Physiol Nutr Metab. 2017 Feb 16;42(7):732–737. doi: 10.1139/apnm-2016-0382

Exercise timing and blood lactate concentrations in individuals with type 2 diabetes

Timothy D Heden 1,*, Ying Liu 1, Jill A Kanaley 1
PMCID: PMC9627643  NIHMSID: NIHMS1840708  PMID: 28208021

Abstract

The purpose of this study was to characterize how resistance exercise prior to or after a meal alters fasting and postprandial blood lactate concentrations in individuals with type 2 diabetes. Obese individuals with type 2 diabetes (N = 12) completed three 2-day trials, including (i) no exercise (NoEx), (ii) resistance exercise prior to dinner (Ex-M), and (iii) resistance exercise beginning at 45 min postdinner (M-Ex). During day 1 of each trial, fasting and postprandial blood lactate concentrations, perceived exertion, and substrate oxidation were measured, and subsequently on day 2 the following morning fasting blood lactate was measured. The premeal lactate incremental area under the curve (iAUC) during Ex-M (109 ± 66 mmol·L−1·1.6 h−1) was over 100-fold greater (P < 0.01) compared with NoEx (−15 ± 24 mmol·L−1·1.6 h−1) and M-Ex (−2 ± 18 mmol·L−1·1.6 h−1). The postprandial lactate iAUC during M-Ex (304 ± 116 mmol·L−1·4 h−1) was over 2-fold greater (P < 0.01) compared with NoEx (149 ± 74 mmol·L−1·4 h−1) and Ex-M (−140 ± 196 mmol·L−1·4 h−1). Average lactate during exercise was ~45% greater (P = 0.03) during M-Ex (3.2 ± 0.9 mmol/L) compared with Ex-M (2.2 ± 0.9 mmol/L), but the change in lactate during Ex-M (2.4 ± 1.6 mmol/L) or M-Ex (2.3 ± 1.3 mmol/L) was not different (P > 0.05). Perceived exertion, substrate oxidation, or fasting blood lactate concentrations the day after testing were not different between trials. Blood lactate concentrations during acute resistance exercise are greater when exercise is performed in the postprandial period. Acute resistance exercise performed the night prior does not alter fasting blood lactate concentrations the following morning.

Keywords: lactic acid, weight training, type 2 diabetes, exercise timing, meal timing

Mots-clés : acide lactique, entraînement avec des haltères, diabète de type 2, moment de l’exercice, moment du repas

Introduction

Lactate is an organic compound formed as a product of glucose metabolism. A large contributor to blood lactate concentrations is skeletal muscle (Juel and Halestrap 1999) and in situations where skeletal muscle glycolytic flux increases, such as exercise (Karagiorgos et al. 1979; MacRae et al. 1992; Bangsbo et al. 1993; Henderson et al. 2004; de Lima et al. 2015) or glucose ingestion (Lovejoy et al. 1990; Konrad et al. 1999; Heden et al. 2014a; Berhane et al. 2015), blood lactate concentrations rapidly rise. Emerging evidence has now linked elevated fasting blood lactate concentrations to obesity, type 2 diabetes, and longevity. In epidemiological studies, fasting blood lactate is strongly associated with type 2 diabetes risk (Crawford et al. 2010) and is independently associated with heart failure and all-cause mortality (Matsushita et al. 2013). Fasting blood lactate concentrations are positively related to insulin resistance (Lovejoy et al. 1990, 1992) and are elevated in obese individuals with (Chen et al. 1993) or without type 2 diabetes (Lovejoy et al. 1990; Berhane et al. 2015). Lactate infused in subjects with type 2 diabetes is more robustly converted to glucose via gluconeogenesis compared with subjects without diabetes (Consoli et al. 1990). Furthermore, lactate infusion has been shown to reduce glucose oxidation in healthy, nondiabetic subjects (Miller et al. 2002). In preclinical models, lactate infusion impairs skeletal muscle glucose uptake (Lombardi et al. 1999) and insulin signaling (Choi et al. 2002). On the other hand, inhibition of lactate dehydrogenase with oxamate reduces blood glucose concentrations and improves insulin sensitivity in db/db mice (Ye et al. 2016). Taken together, the available data suggest that fasting blood lactate concentrations are an important biomarker of health.

It is well established that blood lactate concentrations increase transiently during the postprandial period and during acute exercise in nondiabetic and diabetic individuals (Karagiorgos et al. 1979; Brooks 1986; Bergman and Brooks 1999; Musi et al. 2001; Boschmann et al. 2009; Heden et al. 2014a; de Lima et al. 2015; Wilburn et al. 2015) and that greater increases occur with higher exercise intensities (Bergman and Brooks 1999). This transient increase in blood lactate concentrations dissipates quickly and unlike fasting blood lactate concentrations, there is no link between meal or exercise-induced increases in blood lactate concentrations and the risk of diabetes or heart disease. Nevertheless, the timing of a meal relative to eating could have an impact on exercise-induced blood lactate concentrations, which in turn may impact fasting blood lactate concentrations. Since eating increases carbohydrate oxidation and lactate production in multiple tissues and exercise increases lactate production in the exercising muscle, it seems logical that postprandial exercise would augment the postprandial rise in blood lactate concentration. Yet there is limited data characterizing how exercise timing impacts blood lactate concentrations and the available data are mixed. For instance, after a prolonged fast, blood lactate concentrations were higher during exercise compared with fed state exercise in some (Dohm et al. 1986) but not all studies (Bergman and Brooks 1999). Exercise under normoxic or hypoxic conditions performed prior to a meal does not alter postprandial blood lactate concentrations (Morishima et al. 2014). Given the link between fasting blood lactate concentrations, heart disease, and all-cause mortality, understanding how the timing of exercise impacts fasting blood lactate concentrations is important to establish exercise guidelines to prevent or treat fasting hyperlactatemia and lower the risk of heart disease in individuals with type 2 diabetes.

The main purpose of this study was to characterize the effects of resistance exercise performed prior to or after a dinner meal on fasting and postprandial blood lactate concentrations in individuals with type 2 diabetes. Additionally, a secondary aim was to characterize ratings of perceived exertion (RPE) and the respiratory exchange ratio (RER, substrate oxidation) during exercise in the fasted and fed states.

Materials and methods

Clinical and metabolic characteristics of the participants

Twelve participants (4 men/8 women) with type 2 diabetes completed this study. Inclusion criteria included participants that were obese with type 2 diabetes (body mass index > 30 kg/m2, fasting blood glucose > 126 mg/dL), not tobacco users, not prescribed or using insulin, no bariatric surgery, and weight stable. All participants were receiving standard medical care for diabetes and they took their medications at the usual dose, frequency, and time while participating in this study. The clinical and metabolic characteristics of the participants are listed in Table 1. This study was approved by the University of Missouri’s Institutional Review Board and all participants provided written informed consent.

Table 1.

Clinical and metabolic characteristics of participants.

Age (y) 49±12
Height (m) 1.65±0.09
Weight (kg) 99.0±17.8
Body mass index (kg/m2) 36.1±5.0
Body fat (%) 39.7±8.9
Fasting glucose (mmol/L) 8.3±2.4
Hemoglobin A1 C % (% [mmol/mol]) 7.3±1.1 [56.3]
Diagnosed with diabetes (y) 3.9±4.0
Medication usage (N)
 Metformin only 2
 Metformin, glyburide 1
 Metformin, fenofibrate 1
 Metformin, lipitor 1
 Metformin, januvia 2
 Metformin, pravastatin 1
 Metformin, lisinopril, pravastatin 1
 Glimepiride, pravastatin, lisinopril 2
 Glyburide, janumet, lisinopril, lyrica 1
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Note: Values are means ± SD and includes data from 4 males and 8 females.

Overall study design

This study was part of another study that has been published (Heden et al. 2014b). Due to missing data, 1 subject from the parent study (Heden et al. 2014b) was not included in this study. All participants completed baseline testing which included assessments of height, weight, body composition (measured with air displacement technology, i.e., the BOD POD (Cosmed USA Inc., Chicago, Ill., USA), and familiarization and strength testing (described later). Following baseline testing, the participants performed 3 different trials, all in a random order and at least 1 week apart. Each trial consisted of ~6 h of testing in the lab during the evening, which was followed by a fasting blood draw the following morning. During the 6-h testing day, the participants reported to the lab in the late afternoon and upon arrival a venous catheter was inserted into a forearm vein for frequent blood samples. The participants consumed a dinner meal in the lab with (i) no exercise (NoEx), (ii) predinner resistance exercise (Ex-M) ending at ~20–30 min before dinner, or (iii) postdinner resistance exercise beginning at ~45 min after dinner (M-Ex). After the 6 h of testing, the participants went home and the following morning the participants reported back to the lab after fasting overnight and provided a blood sample.

Diet

Diet was controlled during the testing days and all participants were provided breakfast, lunch, and dinner as described previously (Heden et al. 2014b). The macronutrient composition of each meal was 50% carbohydrate, 35% fat, and 15% protein. The total caloric content supplied to each participant was equal to their estimated total daily energy expenditure, which was determined from 2 measurements. First, the resting energy expenditure of each participant was measured with indirect calorimetry (ParvoMedics TrueOne 2400; Parvo Medics, Sandy, Utah, USA). Second, the average physical activity energy expenditure during a typical day was measured with a BodyMedia armband (BodyMedia Inc., Pittsburgh, Penn., USA) over 2–3 days. These 2 measurements were combined and used as an estimate of total daily energy expenditure.

Resistance exercise

Each participant underwent familiarization and strength testing prior to completing the main testing visits. The participants underwent testing for their 10-repetition maximum for 7 out of the 8 exercises used in this study, including the leg press, seated calf raises, seated chest flyes, seated back flyes, back extensions, shoulder raises, and leg curls. For the eighth exercise that was performed, abdominal crunches, no additional weight was added and instead only body weight was used. Following strength testing, the participants performed a familiarization session in which they performed 3 sets (1–2 min rest between sets) of 10 repetitions for each exercise, with the first set being a warm-up set (50% of the participant’s 10-repetition maximum) and the following 2 sets being the participant’s previously determined 10-repetition maximum. The participants performed 3 sets of each exercise prior to moving onto the next exercise and the exercises performed were in the same order as stated previously (i.e., leg press, followed by seated calf raises, etc.). Following familiarization, the participants performed the 3 testing days, and the resistance exercise session during the study days was identical to the familiarization protocol described previously. RPE were measured immediately after each set using the Borg 6–20 RPE scale.

RER (substrate oxidation)

During each exercise trial, the ParvoMedics TrueOne 2400 metabolic cart was utilized to measure the respiratory exchange ratio (substrate oxidation). The cart was calibrated according to manufacturer guidelines. Indirect calorimetry measurements were collected during the entire resistance exercise session during each trial. Additionally, indirect calorimetry measurements were collected during the NoEx trial at the same time frames as when exercise was performed, and served as a control measurement for comparisons with the exercise trials.

Blood collection and lactate analysis

Blood samples were taken every 5–10 min during the first ~4 h of testing and every 30 min during the last 2 h. During each trial a total of ~160 mL of blood was drawn (~1.5–8 mL of blood per blood draw). The following morning, a single blood sample was taken from a forearm vein with a butterfly needle. Blood samples were transferred immediately into chilled EDTA tubes and whole-blood lactate was assessed in fresh blood using a YSI 2700 Select (YSI Inc., Yellow Springs, Ohio, USA). Additionally, hematocrit was measured after every blood draw and samples were corrected for plasma volume shifts during testing in the lab. Fasting hematocrit was not significantly different between trials the day after testing in the lab (data not shown), so fasting lactate values were not corrected for plasma volume shifts.

Calculations and statistics

During the testing period, the lactate time-course data prior to and after the dinner meal was used to calculate the premeal lactate incremental area under the curve (iAUC) and postprandial lactate iAUC, respectively. The formulas provided by Pruessner et al. (2003) were utilized to calculate the iAUC. Statistical analyses were performed using GraphPad Prism 6 (GraphPad Software Inc., La Jolla, Calif., USA). A 1-way repeated-measures ANOVA with follow-up Holm–Sidak post hoc tests were used to test for statistical significance between fasting lactate, premeal lactate iAUC, postprandial lactate iAUC, and average RPE values between each set, for each exercise. A paired-samples t test was used to compare the average lactate concentrations during exercise between pre- and postprandial exercise, and to compare the iAUC RPE values between each exercise trial. The change in blood lactate during exercise was calculated by subtracting the blood lactate concentration at the time point immediately prior to exercise from the peak blood lactate concentration during exercise. Statistical significance was set at an alpha level P ≤ 0.05. The data presented are means ± SD unless otherwise noted.

Results

Lactate responses

Both exercise and food ingestion increased lactate concentrations (Fig. 1A). During the period prior to the dinner meal, the premeal lactate iAUC during the Ex-M trial (109 ± 66 mmol·L−1·1.6 h−1) was over 100-fold greater (P < 0.01) compared with the NoEx (−15 ± 24 mmol·L−1·1.6 h−1) and M-Ex trials (−2 ± 18 mmol·L−1·1.6 h−1) (Fig. 1B). During the postprandial period the iAUC during the M-Ex trial (304 ± 116 mmol·L−1·4 h−1) was over 2-fold greater (P < 0.01) compared with the NoEx (149 ± 74 mmol·L−1·4 h−1) and Ex-M (−140 ± 196 mmol·L−1·4 h−1) trials (Fig. 1C). Additionally, the postprandial lactate iAUC was significantly greater (P < 0.01) during the NoEx trial compared with the Ex-M trial. The average lactate concentration during exercise for the M-Ex trial (3.2 ± 0.9 mmol/L) was ~45% greater (P = 0.03) compared with exercise during the Ex-M trial (2.2 ± 0.9 mmol/L). The higher blood lactate concentrations during postprandial exercise was not due to increased lactate production because the change in blood lactate during exercise was not significantly different between Ex-M (2.4 ± 1.6 mmol/L) or M-Ex (2.3 ± 1.3 mmol/L) (P > 0.05). Fasting lactate concentrations the day after testing in the lab were not significantly different between trials (NoEx: 1.18 ± 0.36 mmol/L; Ex-M: 1.19 ± 0.64 mmol/L; M-Ex: 1.12 ± 0.42 mmol/L, P > 0.05).

Fig. 1.

Fig. 1.

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Blood lactate concentrations during each trial. (A) Blood lactate time course during the no exercise (NoEx; black line with circles), premeal exercise (Ex-M; grey line with squares), and postprandial exercise (M-Ex; dotted line with open triangles) trials. (B) Premeal blood lactate incremental area under the curve (iAUC) values during each trial. (C) Postprandial blood lactate incremental area under the curve values during each trial.

RER (substrate oxidation) data

Exercise in both the fasting and postprandial state increased RER (Figs. 2A–2B). The RER iAUC was significantly higher (P < 0.01) during exercise in the fasted state (8.1 ± 2.5 RER iAUC) compared with the same time frame during the NoEx trial (1.9 ± 1.8 RER iAUC) (Fig. 2C). Likewise, the RER iAUC was also significantly higher (P ≤ 0.02) during exercise in the postprandial state (7.1 ± 2.6 RER iAUC) compared with the same time frame during the NoEx trial (1.7 ± 3.9 RER iAUC) (Fig. 2C). Together, these data show that resistance exercise increases carbohydrate oxidation. There was no statistically significant difference (P > 0.05) in RER iAUC between exercise trials or between RER iAUC during the fasting state and postprandial time frames during the NoEx trial (Fig. 2C).

Fig. 2.

Fig. 2.

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Respiratory exchange ratio (whole-body substrate oxidation) during each trial. (A) The respiratory exchange ratio (RER) prior to the meal during the no exercise (NoEx) and premeal exercise (Ex-M) trials. (B) The RER during the postprandial period during the no exercise (NoEx) and postprandial exercise (M-Ex) trials. (C) The incremental area under the curve (iAUC) values during each trial.

RPE

The average RPE reported during set 2 and set 3 of all exercises, except abdominal crunches, was significantly greater compared with set 1 (Fig. 3A). There were no statistically significant differences in the iAUC RPE responses to each exercise between trials (Fig. 3B).

Fig. 3.

Fig. 3.

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Ratings of perceived exertion (RPE) during each exercise trial. (A) The RPE (taken immediately after each set for all exercises) during the premeal (Ex-M) and postprandial (M-Ex) exercise trials. (B) The RPE incremental area under the curve (iAUC) for each exercise, during both trials. *, The RPE value during set 2 or set 3 for each exercise was significantly greater (P < 0.05) compared with set 1, during the same trial.

Discussion

Blood lactate concentrations are an important biomarker of health (Lovejoy et al. 1990, 1992; Crawford et al. 2010; Matsushita et al. 2013). To our knowledge, this is the first study to test how resistance exercise timing impacts fasting and postprandial blood lactate concentrations in individuals with type 2 diabetes. Knowledge of the most optimal time to exercise to lower fasting blood lactate concentrations will help healthcare practitioners design more optimal exercise interventions to improve fasting blood lactate concentrations. The main finding of this study is that postprandial resistance exercise augments the rise in postprandial blood lactate concentrations, but this effect is transient as blood lactate concentrations at 4 h after a high-carbohydrate dinner meal or fasting blood lactate concentrations the following morning are not altered by premeal or postprandial resistance exercise. Thus, it is likely that reductions in fasting blood lactate concentrations, an important biomarker of health, in individuals with type 2 diabetes requires a longer term resistance training regimen.

Lactate is generated when the enzyme lactate dehydrogenase converts pyruvate and nicotinamide adenine dinucleotide (reduced form) to lactate and nicotinamide adenine dinucleotide (oxidized form) (Spriet et al. 2000). We found that eating a high-carbohydrate meal increased blood lactate concentrations, and this effect has been reported previously (Lovejoy et al. 1990; Konrad et al. 1999; Heden et al. 2014a; Berhane et al. 2015). In the current study, postprandial blood lactate concentrations were elevated above baseline for the entire 4-h postprandial period, and peaked at ~45 min after the meal. When exercise was performed prior to the meal, the rise in postprandial blood lactate was blunted (i.e., reduced iAUC) but the drop in blood lactate back to baseline was prolonged as lactate remained elevated during the entire postprandial period. The mechanism by which eating increases blood lactate is not entirely understood, but our data provides some clues. Lactate can either be shuttled into mitochondria through mitochondrial monocarboxylate transporters to be oxidized or transported out of the cell into the blood stream (Hashimoto and Brooks 2008), and blood lactate concentrations are ultimately the product of both lactate production and transport into the blood and blood lactate clearance (Donovan and Brooks 1983; Messonnier et al. 2013). In our parent study (Heden et al. 2014b), we reported that the average RER during the postprandial period was greater compared with the fasted state prior to the meal, which indicates eating increases carbohydrate oxidation. Thus, the increase in blood lactate was likely due to increased glycolytic flux with increased lactate production and release in both skeletal muscle and adipose tissue (Jansson et al. 1988). Additionally, given that eating caused a rise in insulin concentrations (reported previously (Heden et al. 2014b)), it is plausible the increase in blood lactate concentrations after eating was a result of reduced lactate clearance in the liver, because of the inhibitory effect of insulin on hepatic gluconeogenesis, which lactate can serve as a substrate for (Hostetler et al. 1969).

In addition to eating, in the current study resistance exercise both before and after the meal increased blood lactate concentrations temporally. Blood lactate concentrations steadily rose during resistance exercise and peaked toward the end of the exercise session, and once exercise stopped blood lactate concentrations rapidly decreased. Similarly, previous research has shown that resistance exercise increases blood lactate concentrations in nondiabetic and diabetic individuals (Lagally et al. 2002; Moreira et al. 2008; Wirtz et al. 2014), and our study adds to these data and demonstrates for the first time that lactate responses to resistance exercise performed in the postprandial period are greater compared with lactate responses during exercise in the fasted state prior to an evening meal. The augmented postprandial blood lactate concentrations does not seem to be due to increased lactate production with postprandial exercise, as we did not observe any difference in the change in blood lactate during exercise or whole-body carbohydrate oxidation (RER) during pre- or postprandial exercise. Nevertheless, the higher starting point of blood lactate immediately prior to exercise most likely is the reason why average blood lactate concentrations were higher during postprandial exercise. These data suggest that eating does not impact the effect of resistance exercise on skeletal muscle lactate production in individuals with type 2 diabetes. This notion is in agreement with previous research showing that aerobic exercise performed after a 12-h overnight fast or 3 h after a meal does not result in differential blood lactate responses in trained or untrained nondiabetic individuals (Bergman and Brooks 1999).

Fasting blood lactate is an important biomarker of health and longevity, with higher fasting blood lactate concentrations being negatively associated with health outcomes (Crawford et al. 2010; Matsushita et al. 2013). In the current study, there was no benefit of resistance exercise, either prior to or after the evening meal, on reducing fasting blood lactate concentrations the following morning. Prior research has shown that 9 months of exercise training reduces fasting blood lactate concentrations in overweight individuals with the metabolic syndrome (Hittel et al. 2005). Thus, a longer term exercise training intervention may be required to achieve improvements in fasting blood lactate concentrations.

In nondiabetic individuals greater RPE corresponded with greater blood lactate during resistance exercise (Lagally et al. 2002). On the contrary, despite greater average blood lactate concentrations with postprandial exercise, RPE was nearly identical during pre- and postprandial exercise in the current investigation. We did observe that RPE was greater during set 2 and set 3 of each exercise (except abdominal crunches) compared with set 1. This response was due to the heavier weight lifted during sets 2 and 3, as set 1 was a warm-up set with the workload at 50% of the participant’s 10-repetition maximum, whereas the workload for sets 2 and 3 was at 100% of the 10-repetition maximum.

In summary, exercising in the postprandial period augments the rise in postprandial blood lactate concentrations. The morning after premeal or postprandial exercise, fasting blood lactate concentrations are not altered. These data suggest that exercise training may be required to reduce fasting blood lactate concentrations in individuals with type 2 diabetes.

Acknowledgements

We would like to thank Nathan Winn for his assistance with some of the data collection. T.D.H. was supported by a National Institute of Health T32 Training Grant AR048523/AR/NIAMS NIH HHS/United States.

Footnotes

Conflict of interest statement

We have no conflict of interest to report.

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