Background: High-intensity interval training (HIIT) can improve several aspects of cardiometabolic health. Previous studies have suggested that adaptations to exercise training can be augmented with post-exercise milk or protein consumption, but whether this nutritional strategy can impact the cardiometabolic adaptations to HIIT in type 2 diabetes is unknown. Objective: To determine if the addition of a post-exercise milk or protein beverage to a high-intensity interval training (HIIT) intervention improves cardiometabolic health in individuals with type 2 diabetes. Design: In a proof-of-concept, double-blind clinical trial 53 adults with uncomplicated type 2 diabetes were randomized to one of three nutritional beverages (500 mL skim-milk, macronutrient control, or flavored water placebo) consumed after exercise (3 days/week) during a 12 week low-volume HIIT intervention. HIIT involved 10 X 1-min high-intensity intervals separated by 1-min low-intensity recovery periods.

Two sessions per week were cardio-based (at ~90% of heart rate max) and one session involved resistance-based exercises (at RPE of 5–6; CR-10 scale) in the same interval pattern. Continuous glucose monitoring (CGM), glycosylated hemoglobin (HbA 1c), body composition (dual-energy X-ray absorptiometry), cardiorespiratory fitness ( V ˙ O 2 peak), blood pressure, and endothelial function (%FMD) were measured before and after the intervention. Results: There were significant main effects of time (all p 0.71) for CGM 24-h mean glucose (−0.5 ± 1.1 mmol/L), HbA 1c (−0.2 ± 0.4%), percent body fat (−0.8 ± 1.6%), and lean mass (+1.1 ± 2.8 kg).

Similarly, V ˙ O 2 peak (+2.5 ± 1.6 mL/kg/min) and%FMD (+1.4 ± 1.9%) were increased, and mean arterial blood pressure reduced (−6 ± 7 mmHg), after 12 weeks of HIIT (all p 0.11). Conclusion: High-intensity interval training is a potent stimulus for improving several important metabolic and cardiovascular risk factors in type 2 diabetes. The benefits of HIIT are not augmented by the addition of post-exercise protein.

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Study design This double-blind, randomized clinical trial was conducted at The University of British Columbia Okanagan between January 2015 and December 2016 (clinicaltrials.gov #). Free Download Lagu Morrissey Everyday Is Like Sunday. The Clinical Research Ethics Board (CREB #H14-01636) approved the study and participants provided written informed consent. Randomization was by a third-party using variable permuted block sizes with computer-generated random numbers and sealed envelopes.

A researcher not involved in data analysis prepared the beverages so participants and study personnel were blinded to the beverage condition. Participants Men and women between 40 and 75 years with physician-diagnosed type 2 diabetes (>6 months) were recruited from the Kelowna Diabetes Program via mail-out advertisements and sign-up sheets. Exogenous insulin users, diagnosed cardiovascular disease and diabetes complications, or contraindications to exercise (Thompson et al., ) were excluded. After telephone/email interviews interested participants attended a screening visit, which included a medical history questionnaire, physical activity readiness questionnaire-plus (PARQ+), and informed consent. Eligible participants then completed a 12-lead stress test using a modified Bruce protocol and a cardiologist provided clearance for vigorous exercise. Experimental protocol overview Fifty-three participants were randomized to one of three beverages; (i) low-fat milk, (ii) macronutrient control, or (iii) placebo, consumed after exercise (details below).

Baseline and post-intervention outcomes were assessed over 5 days before and after the intervention (48–72 h after the last training session). Fasted blood and body composition measures were obtained on day 1 and CGM was performed across days 2–4 while participants followed a standardized diet. Blood pressure, endothelial function and fitness were assessed on day 5. Body weight, waist circumference, blood pressure, and endothelial function were also assessed at 6 weeks (Mid). Exercise training All groups performed supervised low-volume HIIT 3d/week for 12 weeks.

To be consistent with exercise recommendations by the American Diabetes Association and the American College of Sports Medicine (Colberg et al., ) both resistance and cardio-based exercises were included in the HIIT program. The first and last sessions per week were cardio-based (cycle ergometer, treadmill, or elliptical) involving 1-min bursts of exercise at 85–90% of the participants' maximum heart rate (HR max; obtained during baseline V ˙ O 2 peak test) with 1 min of easy recovery in between.

The middle session each week involved whole-body resistance exercises (using resistance bands or multi-gym). Similar to cardio-based HIIT, each resistance exercise was performed for 1 min (as many repetitions as possible) at an intensity eliciting an RPE of 5 “hard” on the CR-10 scale (Borg, ) followed by 1 min of recovery. A 3-min warm-up and cool-down was performed with all sessions. The number of 1-min intervals in each session progressed from four in week one to ten in week six of training. Thereafter, 10 X 1-min intervals eliciting ~90% of HR max (cardio-based) or RPE ~5 (resistance-based) were completed in each session.

Previous short-term training studies in individuals with, and at risk for, diabetes, have shown this low-volume HIIT protocol is effective for improving cardiometabolic health (Little et al.,; Francois et al., ). A heart rate monitor was worn to closely prescribe intensity, and capillary blood glucose and blood pressure measures were obtained before and after each exercise session.

Post-exercise nutrition supplementation After each session participants consumed 500 mL of either: (i) low-fat milk; (ii) milk protein macronutrient-matched control; or (iii) placebo (water), within 1 h. The beverages were designed to look and taste similar and distributed in opaque containers. To accomplish this, one-teaspoon of cocoa powder and ¼ teaspoon of stevia (Stevia In The Raw®, Cumberland Packing Corp; containing ~28 mg stevia) were added to each beverage.

Low-fat milk was prepared from skim-milk powder (MedallionMilk Co., Canada) providing 187 calories, 19 g protein, 26 g carbohydrate, and. Continuous glucose monitoring (CGM) A continuous glucose monitor (iPro 2, Medtronic Inc.) was used to continuously measure blood glucose across 3 days before and after the intervention.

CGM provides valuable insight (that a one-off fasting blood or HbA 1c sample cannot) into glycemic variability and the magnitude of postprandial excursions across several days under free-living conditions (Klonoff, ). The CGM continuously samples interstitial fluid from the abdomen, measuring glucose concentration every 5-min using the glucose oxidase reaction (Rossetti et al., ). Participants took capillary glucose samples (4X/d), which were used to retrospectively calculate retrospective blood glucose concentration via an algorithm within the online software program (CareLink Pro, Medtronic; Rossetti et al., ).

All food, drink, and medication were recorded (including time eaten, amount, brand) for pre-testing, and then replicated exactly for post-intervention. The primary outcome was 24-h average glucose (from 00:00 to 23:55), calculated as the mean of the 3 CGM days. Standard deviation of 24-h blood glucose and mean amplitude of glycemic excursions (MAGE; Molnar et al., ) were calculated from the same 24-h periods to assess glycemic variability. Download Prorat V1 9 Special Edition. Cardiorespiratory fitness ( V ˙ O 2 peak) V ˙ O 2 peak was assessed using a maximal incremental ramp test on a cycle ergometer (Lode Excalibur, Netherlands) with continuous sampling of expired gases (Parvomedics TrueOne2400, USA).

Beginning at 30 W, the test increased by 1 W every 4 s (15 W/min) until volitional exhaustion or contraindication (Fletcher et al., ). V ˙ O 2 peak and RER were calculated from the highest 30-s average, while HR max was recorded as the highest value obtained during the test. Biochemical analyses Fasting blood samples were collected by venipuncture into EDTA containing tubes, centrifuged for 15 min (1,550 g at 4°C) and the plasma stored at −80°C for subsequent batch analyses. Medications were withheld the morning of the fasting blood sample. Fasting glucose was measured by the hexokinase method, high-sensitivity C-reactive protein by latex particle enhanced immunoturbidimetric assay and triglycerides by the enzymatic glycerol kinase and glycerol phosphate oxidase method. Pre and post-intervention samples were analyzed concurrently in duplicate (average coefficient of variation 6.8%) on a clinical chemistry analyzer (Chemwell 2910, Awareness Technologies) using assays from Pointe Scientific (MI, USA).

HbA 1 c was analyzed from a separate EDTA tube by a medical laboratory that routinely performs this analysis according to the National Glycohemoglobin Standardization Program (NGSP). Flow-mediated dilation Brachial artery flow-mediated dilation (FMD) is an important prognostic indicator of endothelial function and incident cardiovascular disease (Yeboah et al., ). The ability of the vessel to dilate (%FMD) is measured in response to a physiological (shear stress) stimulus (Thijssen et al., ). In the current study, brachial artery FMD was assessed according to current guidelines (Thijssen et al., ).

Briefly, simultaneous measures of diameter and blood velocity were obtained with high-resolution ultrasound (Terason 3200), 2 cm from the antecubital fossa. Data were collected over a 1-min baseline, for the last 30 s of a 5 min period of forearm ischemia (pneumatic cuff inflated 60 mmHg above systolic blood pressure) and for 3 min thereafter. Brachial artery dilatory capacity The peak blood flow and diameter response to ischemic handgrip exercise provides an index of resistance artery size or remodeling and the maximal dilatory capacity (Naylor et al., ). This is important since changes in artery function (%FMD) with exercise training are thought to occur rapidly (i.e., first few weeks) after which are superseded by changes in structure, potentially concealing further changes in function (Tinken et al., ). After 15 min of rest, following the FMD procedure, baseline diameter and blood velocity were recorded for 1 min. This was followed by 5 min of forearm ischemia (as above), including 3 min of isotonic handgrip exercise (1 contraction every 2 s using a dynamometer) between 1-min periods of ischemia alone (Naylor et al., ). Again recording resumed 30 s before cuff deflation and continued for 3 min thereafter.

Absolute FMD (peak diameter – baseline diameter),%FMD (peak – baseline diameter/baseline diameter), and time to peak diameter were measured using custom designed edge-detection and wall-tracking software, which minimizes user bias (Woodman et al., ). This protocol is routinely performed in our lab using the methods outlined in Francois et al. (); coefficients of variation for diameter and%FMD are 2.1 and 7.3%, respectively. Diet and exercise standardization Participants maintained their usual diet, lifestyle, and medication habits throughout the testing and training sessions, verified by physical activity and diet records.

Baseline dairy consumption was assessed using a food frequency questionnaire, and dietary intake before and during the study was assessed using 3-day diet records analyzed using FoodWorks16 (The Nutrition Company, NJ, USA). Baseline activity was examined using both accelerometry (Actigraph GT3x, FL, USA) over a 7-day period to assess minutes of moderate-vigorous physical activity (MVPA, Freedson et al., cut-points) and a Godin leisure-time exercise questionnaire (Godin and Shephard,; Table ). Statistics Analyses were performed on all participants that completed the intervention. Characteristics of the intervention groups are shown in Table. Linear mixed models using SPSS 22.0 (SPSS, Chicago, Illinois) examined changes in trial outcomes (pre-post or pre-mid-post) between groups. Significant interactions were probed with pre-planned contrasts comparing the change within each group, whereas isolated significant main effects of time were examined by pairwise comparisons with groups collapsed using Least Significant Difference (LSD) test (Hopkins et al., ).

Results are reported as means and standard deviations with 95% confidence limits. Magnitude based inferences were used to identify clinically meaningful changes in major outcomes using techniques described by Batterham and Hopkins (). The threshold for clinically beneficial changes in 24-h glucose and HbA 1 c were reductions of 0.5 mmol/l and 0.7%, respectively, based on the reduced risk for diabetes complications (Mazzone, ). For cardiorespiratory fitness an increase of 1 metabolic equivalent (MET) was used for a 15% risk reduction in cardiovascular disease (Kodama et al., ).

For%FMD +1% was used, based on the 13% risk reduction in cardiovascular events (Inaba et al., ). In line with previous studies, a 2 mmHg reduction in MAP was considered to be the smallest clinical threshold change for BP (Cook et al., ). The clinically meaningful difference in QOL was determined as a change >3 points (Warkentin et al., ). Consolidated Standards of Reporting Trials (CONSORT) flow diagram. Of the 53 participants randomized, 51 successfully completed 36 sessions of HIIT in 12 ± 1 wk. One participant suffered a non-fatal myocardial infarction in week eight (after 23 HIIT sessions) and one dropped out for personal reasons.

There were no reports of hypoglycemia after exercise or at home throughout the intervention. Exercise sessions were rescheduled on 10 occasions ( n = 6 due to sickness and n = 4 due to systolic blood pressure >144 mmHg prior to exercise). No musculoskeletal injuries were reported as a result of the training. V ˙ O 2 peak testing was truncated in three participants because systolic pressure exceeded 250 mmHg during the test (Fletcher et al., ).

For CGM analyses three participants were excluded due to sensor failure ( n = 1) and medication changes ( n = 2; required reduced medication). All other analyses are reported for n = 51 unless otherwise stated. Overall the exercise intensity achieved was 88 ± 7% of HR max during cardio-based intervals, and an average RPE of 5 ± 1 and 4 ± 1, for cardio- and resistance-based intervals, respectively. Glycemic control There was a significant reduction in mean 24-h glucose following 12 weeks of HIIT (by −0.5 ± 1.1 mmol/L, Figure ) with no difference between groups (Table ). The probability that the change in glucose was clinically beneficial was 54% (95% CI: −0.8, 0.1 mmol/L). Glycemic variability assessed by both SD (by −0.33 ± 0.78 mmol/L) and MAGE (by −0.98 ± 2.27 mmol/L) was significantly reduced, with no differences between groups (Table ).

HbA 1c was significantly reduced after 12 weeks of HIIT (by −0.22 ± 0.39%, Figure ) with no differences between groups (Table ). The probability that the change in HbA 1c was clinically beneficial was 0% (95% CI: −0.33, 0.16%), with the change being most likely trivial.

Fasting glucose was not significantly different after HIIT in all groups (Table ). Body composition Body mass was significantly lower after 12 weeks of HIIT (by −0.9 ± 3.9 kg, Table ), with no difference between groups.

There was a significant reduction in waist circumference after 12 weeks of HIIT (by −2.9 ± 3.5 cm, main effect of time: p 0.83, Figure ). Cardiorespiratory fitness ( V ˙ O 2 peak) and blood pressure V ˙ O 2 peak significantly increased 9.8% after 12 weeks of HIIT (main effect of time: p. Flow-mediated dilation%FMD significantly increased after 12 weeks of HIIT (by +1.4 ± 1.9%, main effect of time: p. Quality of life PCS scores significantly increased after 12 weeks of HIIT ( n = 49, by 8.1 ± 12.1, main effect of time: p. Dietary intake records Analysis of the 3-day diet records collected before and during the last week of the intervention showed no difference in the total daily energy intake between groups and/or across time (Table ).

Macronutrient composition of the diet was not different between groups ( p = 0.32), or across time: for% carbohydrate (Pre: 48.0 ± 12.5% vs. Post: 48.4 ± 13.0% of total energy, p = 0.47),% protein (Pre: 20.4 ± 4.9% vs.

Post: 19.9 ± 4.9% of total energy, p = 0.15) and% fat (Pre: 30.3 ± 12.5% vs. Post: 30.7 ± 13.3% of total energy, p = 0.49).