Understanding the Heterogeneity in Exercise-Induced Changes in Glucose Metabolism to Help Optimize Treatment Outcomes

Editorial

27 May 2021

Editorial: Understanding the Heterogeneity in Exercise-Induced Changes in Glucose Metabolism to Help Optimize Treatment Outcomes

Thomas P. J. Solomon

John P. Thyfault

Jacob M. Haus

and

Kristian Karstoft

2,533 views

1 citations

Editors

Thomas P J Solomon

Blazon Scientific

Kristian Karstoft

Centre for Physical Activity Research, Rigshospitalet

Jacob Haus

University of Michigan

John P. Thyfault

University of Kansas Medical Center

Impact

Review

12 May 2021

Exercising for Insulin Sensitivity – Is There a Mechanistic Relationship With Quantitative Changes in Skeletal Muscle Mass?

Jasmine Paquin

, 2 more and

Isabelle J. Dionne

Skeletal muscle (SM) tissue has been repetitively shown to play a major role in whole-body glucose homeostasis and overall metabolic health. Hence, SM hypertrophy through resistance training (RT) has been suggested to be favorable to glucose homeostasis in different populations, from young healthy to type 2 diabetic (T2D) individuals. While RT has been shown to contribute to improved metabolic health, including insulin sensitivity surrogates, in multiple studies, a universal understanding of a mechanistic explanation is currently lacking. Furthermore, exercised-improved glucose homeostasis and quantitative changes of SM mass have been hypothesized to be concurrent but not necessarily causally associated. With a straightforward focus on exercise interventions, this narrative review aims to highlight the current level of evidence of the impact of SM hypertrophy on glucose homeostasis, as well various mechanisms that are likely to explain those effects. These mechanistic insights could provide a strengthened rationale for future research assessing alternative RT strategies to the current classical modalities, such as low-load, high repetition RT or high-volume circuit-style RT, in metabolically impaired populations.

Summary of studies that has investigated fat-free mass quantitative changes and glucose homeostasis in response to either resistance or mixed training intervention or a comparison.

16,040 views

27 citations

Mini Review

21 October 2020

Factors Influencing Insulin Absorption Around Exercise in Type 1 Diabetes

Jason P. Pitt

, 3 more and

Richard M. Bracken

Insulin is injected/released from formulation in the insulin pen/pump cartridge into the subcutaneous tissue. The insulin oligomers disassociate into monomer units before translocating across the capillary endothelium into blood circulation. Insulin circulates before binding to an insulin receptor to facilitate glucose uptake into the cell (e.g. into the myocyte). Factors at rest, acute exercise, and chronic exercise which affect each stage are listed along the row beside each illustrated stage of the pathway. Insulin diffusion in the subcutaneous layer is adapted with permission from digital images of insulin depot formation 15 to 30 s after bolus injection into porcine subcutaneous tissue; authored by Jockel et al. (1). Image is not to scale for illustration purposes. Created using Servier Medical Art (https://smart.servier.com/); Sevier Medical Art by Servier is licensed under a Creative Commons Attribution 3.0 Unported License.

International charities and health care organizations advocate regular physical activity for health benefit in people with type 1 diabetes. Clinical expert and international diabetes organizations’ position statements support the management of good glycemia during acute physical exercise by adjusting exogenous insulin and/or carbohydrate intake. Yet research has detailed, and patients frequently report, variable blood glucose responses following both the same physical exercise session and insulin to carbohydrate alteration. One important source of this variability is insulin delivery to the circulation. With modern insulin analogs, it is important to understand how different insulins, their delivery methods, and inherent physiological factors, influence the reproducibility of insulin absorption from the injection site into circulation. Furthermore, contrary to the adaptive pancreatic response to exercise in the person without diabetes, the physiological and metabolic shifts with exercise may increase circulating insulin concentrations that may contribute to exercise-related hyperinsulinemia and consequent hypoglycemia. Thus, a furthered understanding of factors underpinning insulin delivery may offer more confidence for healthcare professionals and patients when looking to improve management of glycemia around exercise.

14,583 views

24 citations

Shaded area indicates that diet records were kept from day 13 to 17 in the first treatment period, and subsequently this diet was mirrored from day 13 to 17 in the 2nd treatment period.

Brief Research Report

25 February 2021

The Effect of Metformin on Self-Selected Exercise Intensity in Healthy, Lean Males: A Randomized, Crossover, Counterbalanced Trial

Nanna Skytt Pilmark

, 5 more and

Kristian Karstoft

12,229 views

7 citations

Pre-trial monitoring involving physical activity () and CGM-derived glycemic control () began 24 h before each experimental trial. During experimental trials, participants were exposed to differing glycemic profiles followed by 45 min of rest () or exercise (). Post-trial glycemic control was assessed under strict dietary control () but otherwise free-living conditions. A full description is provided in the text.

Clinical Trial

15 October 2020

Exercise-Induced Improvements in Postprandial Glucose Response Are Blunted by Pre-Exercise Hyperglycemia: A Randomized Crossover Trial in Healthy Individuals

Steven Carter

and

Thomas P. J. Solomon

5,916 views

5 citations

Group differences [(A); mean C_IS and SD] and heterogeneity in individual response (B) for C_IS. *Significantly different from HED; #Significantly different from WL.

Original Research

10 September 2020

Individual Response Variation in the Effects of Weight Loss and Exercise on Insulin Sensitivity and Cardiometabolic Risk in Older Adults

Andrea M. Brennan

, 4 more and

Bret H. Goodpaster

6,051 views

21 citations

Glucose responses to a dinner meal in non-obese and obese individuals with and without type 2 diabetes (T2D) on a study day (A) with no post dinner exercise or a study day (C) with exercise (PMEX- 45 min, at 55%VO2 max). Individual glucose values at time point 120 and time point 165 in each group on the NOEX day (B) or PMEX day (D). Mean ± SE.

Brief Research Report

02 September 2020

Post Meal Exercise May Lead to Transient Hypoglycemia Irrespective of Glycemic Status in Humans

Jay W. Porter

, 7 more and

Jill A. Kanaley

11,058 views

5 citations

The regulation of fasting blood glucose homeostasis. Subtle changes in fasting glucose levels (FG) entering the pancreas regulate the release of the islet hormones insulin (INS) and glucagon (GGN). In turn, these hormones control the rate of hepatic glucose production (HGP), making HGP equal to the rate at which all other tissues of the body utilize glucose, thereby preserving fasting glucose levels at a steady state. CNS, central nervous system; WBC, white blood cells; RBC, red blood cells.

Review

28 August 2020

Exercise-Induced Improvements to Whole Body Glucose Metabolism in Type 2 Diabetes: The Essential Role of the Liver

Shana O. Warner

, 2 more and

Jason J. Winnick

Type 2 diabetes (T2D) is a metabolic disease characterized by obesity, insulin resistance, and the dysfunction of several key glucoregulatory organs. Among these organs, impaired liver function is recognized as one of the earliest contributors to impaired whole-body glucose homeostasis, with well-characterized hepatic insulin resistance resulting in elevated rates of hepatic glucose production (HGP) and fasting hyperglycemia. One portion of this review will provide an overview of how HGP is regulated during the fasted state in healthy humans and how this process becomes dysregulated in patients with T2D. Less well-appreciated is the liver's role in post-prandial glucose metabolism, where it takes up and metabolizes one-third of orally ingested glucose. An abundance of literature has shown that the process of hepatic glucose uptake is impaired in patients with T2D, thereby contributing to glucose intolerance. A second portion of this review will outline how hepatic glucose uptake is regulated during the post-prandial state, and how it becomes dysfunctional in patients with T2D. Finally, it is well-known that exercise training has an insulin-sensitizing effect on the liver, which contributes to improved whole-body glucose metabolism in patients with T2D, thereby making it a cornerstone in the management of the disease. To this end, the impact of exercise on hepatic glucose metabolism will be thoroughly discussed, referencing key findings in the literature. At the same time, sources of heterogeneity that contribute to inconsistent findings in the field will be pointed out, as will important topics for future investigation.

11,915 views

29 citations

Systematic Review

04 August 2020

Acute and Chronic Effects of Exercise on Continuous Glucose Monitoring Outcomes in Type 2 Diabetes: A Meta-Analysis

Matthew Munan

, 5 more and

Normand G. Boulé

Objective: To examine the acute and chronic effects of structured exercise on glucose outcomes assessed by continuous glucose monitors in adults with type 2 diabetes.

Methods: PubMed, Medline, EMBASE were searched up to January 2020 to identify studies prescribing structured exercise interventions with continuous glucose monitoring outcomes in adults with type 2 diabetes. Randomized controlled trials, crossover trials, and studies with pre- and post-designs were eligible. Short-term studies were defined as having exercise interventions lasting ≤2 weeks. Longer-term studies were defined as >2 weeks.

Results: A total of 28 studies were included. Of these, 23 studies were short-term exercise interventions. For all short-term studies, the same participants completed a control condition as well as at least one exercise condition. Compared to the control condition, exercise decreased the primary outcome of mean 24-h glucose concentrations in short-term studies (−0.5 mmol/L, [−0.7, −0.3]; p < 0.001). In longer-term studies, mean 24-h glucose was not significantly reduced compared to control (−0.9 mmol/L [−2.2, 0.3], p = 0.14) but was reduced compared to pre-exercise values (−0.5 mmol/L, [−0.7 to −0.2] p < 0.001). The amount of time spent in hyperglycemia and indices of glycemic variability, but not fasting glucose, also improved following short-term exercise. Among the shorter-term studies, subgroup, and regression analyses suggested that the timing of exercise and sex of participants explained some of the heterogeneity among trials.

Conclusion: Both acute and chronic exercise can improve 24-h glucose profiles in adults with type 2 diabetes. The timing of exercise and sex of participants are among the factors that may explain part of the heterogeneity in acute glycemic improvements following exercise.

12,126 views

50 citations

Summary of exercise and/or metformin interactions. Exercise lowers blood glucose mainly through increases in AMPK production in most organs excluding the brain, where production is decreased; and the vasculature, where adaptations are largely driven by nitric oxide (NO) (A). Metformin alone also improves glycemic control through similar mechanisms, primarily by decreasing hepatic glucose production. Metformin also decreases reactive oxygen species (ROS) production which is suspected to improve tissue glycemic control as well as memory and cognitive function in the brain (B). The combination of metformin with exercise has blunted effects on skeletal muscle glucose uptake and visceral adiposity. The effects of metformin with exercise on the liver, vasculature, and brain are still largely unknown (C). We hypothesize that the combination of metformin and exercise are not necessarily additive in terms of glycemic control. Metformin blunts the beneficial adaptations that are typically seen with aerobic and/or resistance training in skeletal muscle tissue. VO2max, maximal oxygen consumption; FFM, fat-free mass; AMPK, adenosine monophosphate kinase; IHTG, intrahepatic triglycerides; FFA, free fatty acids; NO, nitic oxide.

Review

11 August 2020

Metformin May Contribute to Inter-individual Variability for Glycemic Responses to Exercise

Steven K. Malin

and

Nathan R. Stewart

8,892 views

23 citations

Systematic Review

03 April 2020

Comparative Effectiveness of High-Intensity Interval Training and Moderate-Intensity Continuous Training for Cardiometabolic Risk Factors and Cardiorespiratory Fitness in Childhood Obesity: A Meta-Analysis of Randomized Controlled Trials

Jingxin Liu

, 1 more and

Yu Su

Purpose: The main objective of this meta-analysis was to compare the effectiveness of high-intensity interval training (HIIT) and of moderate-intensity continuous training (MICT) on cardiometabolic health in childhood obesity and determine whether HIIT is a superior form of training in managing obese children's metabolic health.

Methods: Relevant studies published in PubMed, Web of Science, Embase, the Cochrane Library, EBSCO, and CNKI were searched, restricted to those published from inception to 1 October 2019. Only randomized controlled trials (RCTs) depicting the effect of HIIT on childhood obesity were included.

Results: Nine RCTs involving 309 participants were included in the meta-analysis. Among the 309 participants, 158 subjects were randomized for HIIT, while the others were randomized for MICT. Significant differences were observed in the body weight (mean difference [MD] = −5.45 kg, p = 0.001), body mass index (BMI; MD = −1.661 kg/m², p = 0.0001), systolic blood pressure (SBP; MD = −3.994 mmHg, p = 0.003), and diastolic blood pressure (DBP; MD = −3.087 mmHg, p = 0.0001) in the HIIT group relative to the baseline values. Similar effects were found in the MICT group, as depicted by the significantly decreased values for body weight (MD = −4.604 kg, p = 0.0001), BMI (MD = −2.366 kg/m², p = 0.0001), SBP (MD = −3.089 mmHg, p = 0.019), and DBP (MD = −3.087 mmHg, p = 0.0001). However, no significant differences were observed in the changes in body weight, BMI, SBP, or DBP between the HIIT and MICT groups. Furthermore, our studies showed that both HIIT and MICT could significantly improve VO_2peak (HIIT, MD = 4.17 ml/kg/min, 95% CI: 3.191 to 5.163, p = 0.0001; MICT, MD = 1.704 ml/kg/min, 95% CI: 0.279 to 3.130, p = 0.019). HIIT also showed more positive effects on VO_2peak (SMD = 0.468, 95% CI: 0.040 to 0.897, p = 0.006) than MICT.

Conclusion: HIIT positively affects the cardiometabolic risk factors in childhood obesity. Similar positive effects on body composition and blood pressure were established. Moreover, HIIT can improve cardiorespiratory fitness more significantly than MICT. These findings indicate that HIIT may be an alternative and effective training method for managing childhood obesity.

PROSPERO Registration Number: CRD42018111308.

17,928 views

40 citations

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