A low-carbohydrate protein-rich bedtime snack to control fasting and nocturnal glucose in type 2 diabetes: A randomized trial.

In type 2 diabetes, liver insulin resistance and excess hepatic glucose production results in elevated fasting glucose. A bedtime snack has been recommended to improve fasting glucose, yet there is little evidence supporting this recommendation. Moreover, the optimal composition of a bedtime snack is unknown. PURPOSE: To determine whether a low-carbohydrate protein-rich bedtime snack (Egg) could reduce fasting plasma glucose levels in people with type 2 diabetes when compared to a high-carbohydrate protein-rich bedtime snack (Yogurt) or a No Bedtime Snack condition. Secondary outcomes included glucose control assessed by continuous glucose monitoring (CGM) and fasting insulin sensitivity markers. METHODS: Using a randomized crossover design, participants with type 2 diabetes (N = 15) completed three separate isocaloric conditions: i) Egg, ii) Yogurt, and iii) No Bedtime Snack, each lasting three days. CGM was collected throughout and duplicate fasting blood samples were obtained on the morning of day 4 in each condition. RESULTS: Fasting plasma glucose (P = 0.04, d = 0.68), insulin (P = 0.04, d = 0.45), and nocturnal glucose (P = 0.02, d = 0.94) were significantly lower, and quantitative insulin sensitivity check index (QUICKI; P = 0.003) was improved, in the Egg compared to the Yogurt bedtime snack. There were no significant differences between either bedtime snack and No Bedtime Snack. CONCLUSION: In the short-term, a low-carbohydrate bedtime snack (Egg) lowered fasting glucose and improved markers of insulin sensitivity when compared to a high-carbohydrate protein-matched bedtime snack (Yogurt). However, consuming a low- or high-carbohydrate bedtime snack did not appear to lower fasting glucose compared to consuming an isocaloric diet with no bedtime snack. CLINICAL TRIAL REGISTRY: clinicaltrials.gov (NCT03207269).

Brief Exercise Counseling and High-Intensity Interval Training on Physical Activity Adherence and Cardiometabolic Health in Individuals at Risk of Type 2 Diabetes: Protocol for a Randomized Controlled Trial.

BACKGROUND: Worldwide incidence of type 2 diabetes (T2D) is rapidly increasing. Given the numerous negative health consequences associated with T2D, prevention of this disease has become a priority. Lifestyle changes, including regular exercise, can reduce the onset of T2D in those at elevated risk. However, long-term adherence to exercise is often poor in this population. Existing lifestyle interventions targeting exercise are labor intensive and costly for staff and participants. Evidence-informed counseling delivered in a manner that reduces dependence on staff and facilitates self-regulatory skills could alleviate time and financial barriers while promoting independent exercise. OBJECTIVE: This protocol outlines the design, recruitment, and proposed analysis of a brief, 2-week evidence-informed exercise counseling intervention combined with either high-intensity interval training (HIIT) or traditional moderate-intensity continuous training (MICT). METHODS: Small Steps for Big Changes is a 2-arm randomized controlled trial that will examine the effectiveness of combining brief exercise counseling with HIIT or MICT on adherence to moderate and vigorous exercise over 1 year. Cardiorespiratory fitness will be assessed at baseline, post intervention (2 weeks), and at 6- and 12-month follow-up. Physical activity behavior will be examined at baseline, post intervention, and 3-, 6-, 9-, and 12-month follow-up. The impact of the intervention on psychosocial outcomes pertinent to exercise adherence will be examined. RESULTS: Data collection was complete in March 2017. Data analysis is currently underway, and the first results are expected to be submitted for publication in 2019. CONCLUSIONS: The results of this brief intervention have the potential to inform future public health efforts designed to increase exercise in individuals at risk of T2D. TRIAL REGISTRATION: ClinicalTrials.gov NCT02164474; https://clinicaltrials.gov/ct2/show/NCT02164474 (Archived by WebCite at http://www.webcitation.org/74Hx1ipj6). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11226.

Short-term exercise training reduces glycaemic variability and lowers circulating endothelial microparticles in overweight and obese women at elevated risk of type 2 diabetes.

Exercise is recognized as a frontline therapy for the prevention and treatment of type 2 diabetes (T2D) but the optimal type of exercise is not yet determined. We compared the effects of high-intensity interval training (HIIT) with moderate-intensity continuous training (MICT) for improvement of continuous glucose monitoring (CGM)-derived markers of glycaemic variability, and biomarkers of endothelial cell damage (CD31+ and CD62+ endothelial microparticles (EMPs)) within a population at elevated risk of developing T2D. Fifteen inactive overweight or obese women were randomized to 2 weeks (10-sessions) of progressive HIIT (n = 8, 4-10X 1-min @ ∼90% peak heart rate, 1-min rest periods) or MICT (n = 7, 20-50 min of continuous activity at ∼65% peak heart rate). Prior and three days post-training, fasting blood samples were collected. Both HIIT and MICT improved glycaemic variability as measured by CGM standard deviation (HIIT: 0.82 ± 0.39 vs. 0.72 ± 0.33 mmol/L; MICT: 0.82 ± 0.19 vs. 0.62 ± 0.16 mmol/L, pre vs. post) and mean amplitude of glycaemic excursions (MAGE; HIIT: 1.98 ± 0.81 vs. 1.41 ± 0.90; MICT; 1.98 ± 0.43 vs. 1.65 ± 0.48, pre vs. post) with no difference between groups. CD62+ EMPs were lower following HIIT (187.7 ± 65 vs. 174.9 ± 55, pre vs. post) and MICT (170 ± 60 vs. 160.3 ± 59, pre vs. post) with no difference between groups. There was no change in 24-h mean glucose or CD31+ EMPs. Two weeks of both HIIT or MICT similarly decreased glycaemic variability and CD62+ EMPs in overweight/obese women at elevated risk of T2D.

Impact of a single bout of high-intensity interval exercise and short-term interval training on interleukin-6, FNDC5, and METRNL mRNA expression in human skeletal muscle.

BACKGROUND: Exercise promotes numerous phenotypic adaptations in skeletal muscle that contribute to improved function and metabolic capacity. An emerging body of evidence suggests that skeletal muscle also releases a myriad of factors during exercise, termed "myokines". The purpose of this study was to examine the effects of high-intensity interval training (HIIT) on the acute regulation of the mRNA expression of several myokines, including the prototypical myokine interleukin-6 (IL-6), and recently identified myokines fibronectin type III domain-containing protein 5 (FNDC5) (irisin) and meteorin-like protein (METRNL). METHODS: Both before and after a 20-day period of twice-daily high-volume HIIT, 9 healthy males (20.5 ± 1.5 years performed a standardized bout of high-intensity interval exercise (HIIE; 5 × 4 min at ~80% pretraining peak power output) with skeletal muscle biopsy samples (vastus lateralis) obtained at rest, immediately following exercise, and at 3 h recovery. RESULTS: Before training, a single bout of HIIE increased IL-6 (p < 0.05) and METRNL (p < 0.05) mRNA expression measured at 3 h recovery when compared to rest. Following 20 days of HIIT, IL-6 and FNDC5 mRNA were increased at 3 h recovery from the standardized HIIE bout when compared to rest (both p < 0.05). Resting METRNL and FNDC5 mRNA expression were higher following training (p < 0.05), and there was an overall increase in FNDC5 mRNA post-training (main effect of training, p < 0.05). CONCLUSION: In human skeletal muscle (1) an acute bout of HIIE can induce upregulation of skeletal muscle IL-6 mRNA both before and after a period of intensified HIIT; (2) Resting and overall FNDC5 mRNA expression is increased by 20 days of HIIT; and (3) METRNL mRNA expression is responsive to both acute HIIE and short-term intense HIIT. Future studies are needed to confirm these findings at the protein and secretion level in humans.

Short-term exercise training reduces anti-inflammatory action of interleukin-10 in adults with obesity.

A key pathological component of obesity is chronic low-grade inflammation, which is propagated by infiltration of immune cells into tissues and overproduction of pro-inflammatory cytokines. Cytokines that possess anti-inflammatory properties, such as interleukin (IL)-10 and IL6, may also play an important role. This study was designed to determine the impact of short-term exercise on the anti-inflammatory action of IL10 and IL6. Thirty-three inactive obese adults were randomized to two weeks of high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT). Fasting blood samples were collected before and after training. Lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α production was measured in whole blood cultures in the presence or absence of IL10 or IL6. IL10 and IL6 receptor expression were measured on circulating monocytes, neutrophils, and T cells. HIIT and MICT reduced the ability of IL10 to inhibit LPS-induced TNFα production, with a greater effect with HIIT (Group × Time and IL10 × Time interactions, p's < 0.05). This reduction in IL10 function was not explained by altered IL10R1 expression, which was unchanged after training (p > 0.05). HIIT and MICT differentially affected IL6 function (Group × Time and IL6 × Time interactions, p's < 0.05) with evidence of reductions in the anti-inflammatory ability of IL6 with HIIT. Neither HIIT nor MICT altered levels of circulating IL10, IL6, or TNFα. The impact of short-term HIIT and MICT resulted in differential effects on anti-inflammatory cytokine function. The clinical implications remain to be determined but these novel findings indicate that measuring anti-inflammatory cytokine action could reveal important immunomodulatory effects of exercise.

High-Intensity Interval or Continuous Moderate Exercise: A 24-Week Pilot Trial.

PURPOSE: High-intensity interval training (HIIT) may lead to superior cardiometabolic improvements when compared with moderate-intensity continuous training (MICT). However, adherence to HIIT requires examination. The purpose of this pilot study was to examine moderate-to-vigorous physical activity (MVPA) adherence 24 wk after a brief counseling intervention combined with either HIIT or MICT. METHODS: Individuals at high risk of type 2 diabetes (T2D) were randomized to HIIT (n = 15) or MICT (n = 17) and completed 10 exercise sessions accompanied by a brief 10-min counseling intervention over a 2-wk period. Objectively measured purposeful MVPA (accelerometry) and cardiorespiratory fitness (V˙O2peak) were assessed at baseline and 24 wk postintervention. Self-regulatory efficacy and task self-efficacy were examined at baseline, postintervention, and 24 wk postintervention. Using an intention-to-treat analysis, change scores were calculated for HIIT and MICT and compared between groups. RESULTS: Individuals assigned to HIIT increased their MVPA by 53 min (Cohen's d = 1.52) at 24 wk compared with 19 min in MICT. Both HIIT and MICT increased relative V˙O2peak by 2 and 1 mL·kg·min, respectively. Participants in both groups increased in their self-regulatory and task self-efficacy postintervention, but both groups demonstrated similar decline at 24 wk. CONCLUSION: This pilot intervention was successful in increasing, and maintaining, free-living MVPA over a 24-wk period in individuals at high risk of T2D. Speculation that HIIT is inappropriate or unattainable for overweight individuals at high risk of T2D may be unfounded.

Short-Term Exercise Training Alters Leukocyte Chemokine Receptors in Obese Adults.

Obesity is characterized by chronic low-grade inflammation driven by activation and tissue infiltration of circulating leukocytes. Although exercise has anti-inflammatory effects, the impact of exercise on mediators of leukocyte migration is unclear. PURPOSE: To determine the impact of high-intensity interval training (HIIT) versus moderate-intensity continuous training (MICT), in the absence of weight/fat loss, on circulating chemokines and leukocyte chemokine receptors. METHODS: Thirty-seven inactive obese adults were randomized to 2 wk (10 sessions) of HIIT or MICT with fasting blood samples collected before and after training. Plasma concentration of C-C motif chemokine ligand 2 (CCL2; also known as monocyte chemoattractant protein-1), CCL3 (also known as macrophage inflammatory protein-1alpha), and C-X-C motif ligand 8 (CXCL8; also known as interleukin-8) were determined and the chemokine receptors CCR2, CCR5, and CXCR2 were measured on monocytes, neutrophils, and T cells. RESULTS: MICT reduced the percentage of monocytes positive for CCR2 and reduced surface protein expression of CXCR2 on monocytes (both P < 0.05), whereas HIIT increased CCR5 surface protein expression and percentage CCR5 positive monocytes and neutrophils (all P < 0.05) along with increasing the percentage of T cells that were positive for CCR5 (P < 0.05). There were no significant changes in circulating chemokines, percent body fat or visceral adipose tissue. CONCLUSIONS: Exercise, in the absence of weight/fat loss and without changes in circulating chemokines, has direct effects on leukocytes in obese adults with HIIT and MICT resulting in different responses. MICT may reduce monocyte migration potential through downregulation of CCR2 and CXCR2, whereas HIIT may increase potential for CCR5-mediated monocyte, neutrophil, and T-cell infiltration. The impact of different exercise protocols on leukocyte trafficking to tissues in obesity warrants further research.

Hyporesponsiveness to the anti-inflammatory action of interleukin-10 in type 2 diabetes.

Chronic low-grade inflammation contributes to the pathology and complications of type 2 diabetes (T2D). Interleukin-10 (IL10), an anti-inflammatory cytokine, is suggested to play a protective role in T2D. However, the impact of T2D on IL10 function has not been previously assessed. We examined the ability of IL10 to inhibit inflammation in human T2D immune cells and explored underlying mechanisms using macrophage models. IL10 was less effective at inhibiting tumour necrosis factor (TNF)-α secretion in T2D whole blood cultures, which was not explained by altered IL10 receptor surface expression. These findings were observed in macrophages exposed to high glucose, which demonstrated similar IL10 resistance or hyporesponsiveness. These findings were also not explained by changes in IL10 receptor protein or other downstream signaling proteins. High glucose was also shown to impair the ability of IL10 to activate STAT3, a downstream signaling protein of IL10. Treatment with the SHIP1 agonist, AQX-MN100, reversed IL10 hyporesponsiveness in macrophages cultured in high glucose and showed equal effectiveness at different glucose conditions. This data supports the idea that IL10 hyporesponsiveness may contribute to chronic inflammation in T2D. These novel findings suggest that strategies aimed to overcome IL10 hyporesponsiveness may hold therapeutic potential for reducing inflammation in T2D.