A randomized controlled trial of pharmacist-led therapeutic carbohydrate and energy restriction in type 2 diabetes

Type 2 diabetes can be treated, and sometimes reversed, with dietary interventions; however, strategies to implement these interventions while addressing medication changes are lacking. We conducted a 12-week pragmatic, community-based parallel-group randomized controlled trial (ClinicalTrials.gov: NCT03181165) evaluating the effect of a low-carbohydrate (<50 g), energy-restricted diet (~850-1100 kcal/day; Pharm-TCR; n = 98) compared to treatment-as-usual (TAU; n = 90), delivered by community pharmacists, on glucose-lowering medication use, cardiometabolic health, and health-related quality of life. The Pharm-TCR intervention was effective in reducing the need for glucose-lowering medications through complete discontinuation of medications (35.7%; n = 35 vs. 0%; n = 0 in TAU; p < 0.0001) and reduced medication effect score compared to TAU. These reductions occurred concurrently with clinically meaningful improvements in hemoglobin A1C, anthropometrics, blood pressure, and triglycerides (all p < 0.0001). These data indicate community pharmacists are a viable and innovative option for implementing short-term nutritional interventions for people with type 2 diabetes, particularly when medication management is a safety concern

Glycemic and Metabolic Effects of Two Long Bouts of Moderate-Intensity Exercise in Men with Normal Glucose Tolerance or Type 2 Diabetes

BackgroundThe glycemic and insulinemic responses following 30–60 min of exercise have been extensively studied, and a dose–response has been proposed between exercise duration, or volume, and improvements in glucose tolerance or insulin sensitivity. However, few studies have examined the effects of longer bouts of exercise in type 2 diabetes (T2D). Longer bouts may have a greater potential to affect glucagon, interleukin-6 (IL-6) and incretin hormones [i.e., glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)].AimTo examine the effect of two bouts of long-duration, moderate-intensity exercise on incretins, glucagon, and IL-6 responses before and after exercise, as well as in response to an oral glucose tolerance test (OGTT) conducted the following day.MethodsTwelve men, six with and six without T2D, participated in two separate conditions (i.e., exercise vs. rest) according to a randomized crossover design. On day 1, participants either rested or performed two 90 min bouts of treadmill exercise (separated by 3.5 h) at 80% of their ventilatory threshold. All participants received standardized meals on day 1. On day 2 of each condition, glucose and hormonal responses were measured during a 4-h OGTT.ResultsOn day 1, exercise increased IL-6 at the end of the first bout of exercise (exercise by time interaction p = 0.03) and GIP overall (main effect of exercise p = 0.004). Glucose was reduced to a greater extent in T2D following exercise (exercise by T2D interaction p = 0.03). On day 2, GIP and active GLP-1 were increased in the fasting state (p = 0.05 and p = 0.03, respectively), while plasma insulin and glucagon concentrations were reduced during the OGTT (p = 0.01 and p = 0.02, respectively) in the exercise compared to the rest condition for both healthy controls and T2D. Postprandial glucose was elevated in T2D compared to healthy control (p &lt; 0.05) but was not affected by exercise.ConclusionLong-duration, moderate-intensity aerobic exercise can increase IL-6. On the day following exercise, fasting incretins remained increased but postprandial insulin and glucagon were decreased without affecting postprandial glucose. This long duration of exercise may not be appropriate for some people, and further research should investigate why next day glucose tolerance was unchanged

A low-carbohydrate, energy restricted diet implemented by community pharmacists for the treatment of type 2 diabetes

Introduction: Targeted nutritional approaches for treating type 2 diabetes (T2D) have garnered attention due to the increasing evidence base suggesting they can induce T2D reversal/remission. While physicians are typically at the centre of diabetes care, pharmacists are more accessible and patients with T2D make more visits to their pharmacist than primary care physician. Given their accessibility and expertise in medication management, community pharmacists may be ideally positioned to safely and effectively deliver nutrition interventions targeted at reducing diabetes medication use and promoting T2D remission. Aim and methods: The aim of the Pharmacist-led therapeutic carbohydrate restriction (Pharm-TCR) as a treatment strategy for T2D trial was to determine if a 12-week very-low carbohydrate, low-calorie diet - led by community pharmacists - could reduce the need for glucose-lowering medications and facilitate improvements in cardiometabolic health when compared to guideline-based treatment-as-usual (TAU). Second, we tested the hypothesis that fasting markers of beta-cell stress/function, liver adiposity, and liver function are improved following the Pharm-TCR intervention. Thus, a pragmatic community-based RCT following a parallel-group design was conducted through 12 community pharmacies throughout British Columbia, Canada (Paper 1: trial protocol). Results: Following the 12-week intervention, 35.7% of participants in the Pharm-TCR group were completely off all glucose-lowering medications compared to 0% in the TAU group (difference = 35.7%, [CI₉₅ 25.9 to 44.8%], p<0.0001). Among other cardiometabolic improvements, there were substantial improvements in A1c (-1.4% [CI₉₅ -1.8 to -1.0%]), body weight (-12.0 kg [CI₉₅ -13.6 to -10.4 kg]), and systolic blood pressure (-13 mmHg [CI₉₅ -17 to -8]) (Paper 2). We also observed improvements indices of liver adiposity, and liver function related to T2D (Paper 3; secondary/exploratory outcomes). Conclusions: The Pharm-TCR intervention led to a reduced need for glucose-lowering medications, improved glycemic control, weight loss, and reduced blood pressure compared to usual care. In addition, we observed improvements in markers of T2D pathophysiology, indicating that the Pharm-TCR intervention positively affected the underlying drivers of the disease. Overall, the Pharm-TCR intervention was effective in treating T2D and can be viewed as a pragmatic and viable strategy for implementing a nutritional intervention in the community for people with T2D.Health and Social Development, Faculty of (Okanagan)Health and Exercise Sciences, School of (Okanagan)Graduat

The effect of acute high-intensity interval exercise on toll-like receptor expression and monocyte subsets in type 2 diabetes

Type 2 diabetes (T2D) is characterized by a state of chronic low-grade inflammation that is implicated in driving the pathophysiology of the disease. Exercise has been shown to have anti-inflammatory effects but the impact of high-intensity interval training, an exercise strategy gaining popularity for the prevention and treatment of T2D, is not known. The research in this thesis examined the impact of a single session of high-intensity interval training (HIIT) on cellular, molecular, and circulating markers of inflammation in individuals with T2D and healthy age-matched controls. Participants completed an acute bout of high-intensity interval training (7 X 1-min @ ~85% maximal aerobic power output, separated by 1-min recovery) on a cycle ergometer with blood samples obtained before (Pre), immediately after (Post), and at one hour of recovery (1-h Post). Inflammatory markers on white blood cells were measured by flow cytometry, plasma cytokines assessed by multiplex assay, and innate immune activation measured in whole blood cultures stimulated with bacterial lipopolysaccharide (LPS). Results showed that a single session of HIIT had an overall anti-inflammatory effect, as evidenced by: i) significantly lower levels of toll-like receptor 2 (TLR2) surface protein expression on both classical and CD16+ monocytes assessed at both Post and 1-h Post compared with Pre (p<0.05 for all); ii) significantly lower levels of plasma tumour necrosis factor (TNF)-alpha at 1-h Post (p<0.05 vs. Pre); and iii) significantly lower LPS-stimulated TNF-alpha release in whole blood cultures at 1-h Post (p<0.05 vs. Pre). There were no differences between T2D and age-matched control participants in these responses to exercise (all main effects of time, p<0.05). In conclusion, the results of this study provide evidence that a single session of low-volume HIIT has direct immunomodulatory effects and supports the potential anti-inflammatory benefits of this type of exercise for people with, and without, T2D.Graduate Studies, College of (Okanagan)Graduat

Acute high-intensity interval exercise reduces human monocyte Toll-like receptor 2 expression in type 2 diabetes

Acute highintensity interval exercise reduces human monocyte Toll-like receptor 2 expression in type 2 diabetes. Am J Physiol Regul Integr Comp Physiol 312: R529 -R538, 2017. First published January 25, 2017; doi:10.1152/ajpregu.00348.2016.-Type 2 diabetes (T2D) is characterized by chronic low-grade inflammation that contributes to disease pathophysiology. Exercise has anti-inflammatory effects, but the impact of high-intensity interval training (HIIT) is not known. The purpose of this study was to determine the impact of a single session of HIIT on cellular, molecular, and circulating markers of inflammation in individuals with T2D. Participants with T2D (n 10) and healthy age-matched controls (HC; n 9) completed an acute bout of HIIT (7 1 min at ~85% maximal aerobic power output, separated by 1 min of recovery) on a cycle ergometer with blood samples obtained before (Pre), immediately after (Post), and at 1 h of recovery (1-h Post). Inflammatory markers on leukocytes were measured by flow cytometry, and TNF- was assessed in both LPS-stimulated whole blood cultures and plasma. A single session of HIIT had an overall anti-inflammatory effect, as evidenced by 1) significantly lower levels of Toll-like receptor (TLR) 2 surface protein expression on both classical and CD16 monocytes assessed at Post and 1-h Post compared with Pre (P 0.05 for all); 2) significantly lower LPSstimulated TNF- release in whole blood cultures at 1-h Post (P 0.05 vs. Pre); and 3) significantly lower levels of plasma TNF- at 1-h Post (P 0.05 vs. Pre). There were no differences between T2D and HC, except for a larger decrease in plasma TNF- in HC vs. T2D (group time interaction, P 0.05). One session of low-volume HIIT has immunomodulatory effects and provides potential antiinflammatory benefits to people with, and without, T2D

Resistance-based interval exercise acutely improves endothelial function in type 2 diabetes

Different modes of exercise, disease, and training status can modify endothelial shear stress and result in distinct effects on endothelial function. To date, no study has examined the influence of type 2 diabetes (T2D) and training status on the acute endothelial response to different modes of interval exercise (INT). We examined the effect of a single session of resistance- and cardio-based INT compared with a time-matched control on endothelial function in 12 age-matched T2D participants, 12 untrained, and 11 trained adults (aged 56 ± 7 yr). Flow-mediated dilation (%FMD) of the brachial artery was assessed at baseline and immediately, 1, and 2 h after an acute bout of cardio interval (C-INT), resistance interval (R-INT), and seated control (CTL); these interventions were randomized and separated by ˃2 days. C-INT involved seven 1-min cycling intervals at 85% of peak power with 1-min recovery between. R-INT involved the same pattern of seven 1-min intervals using leg resistance exercises. Endothelial function (%FMD) was improved after R-INT in all groups (Condition x Time interaction, P ˂ 0.01), an effect that was most robust in T2D where %FMD was higher immediately (+4.0 ± 2.8%), 1 h (+2.5 ± 2.5%), and 2 h (+1.9 ± 1.9%) after R-INT compared with CTL (P ˂ 0.01 for all). C-INT improved %FMD in T2D at 1-h postexercise (+1.6 ± 2.2%, P = 0.03) compared with CTL. In conclusion, R-INT acutely improves endothelial function throughout the 2-h postexercise period in T2D patients. The long-term impact of resistance exercise performed in an interval pattern is warranted

Combined interval training and post-exercise nutrition in type 2 diabetes: A randomized control trial

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 (HbA1c), body composition (dual-energy X-ray absorptiometry), cardiorespiratory fitness (V.O2peak), blood pressure, and endothelial function (%FMD) were measured before and after the intervention. Results: There were significant main effects of time (all p \u3c 0.05) but no difference between groups (Interaction: all p \u3e 0.71) for CGM 24-h mean glucose (-0.5 ± 1.1 mmol/L), HbA1c(-0.2 ± 0.4%), percent body fat (-0.8 ± 1.6%), and lean mass (+1.1 ± 2.8 kg). Similarly, V.O2peak (+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 \u3c 0.01) with no difference between beverage groups (Interaction: all p \u3e 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

Nutritional ketone salts increase fat oxidation but impair high-intensity exercise performance in healthy adult males

This study investigated the impact of raising plasma beta-hydroxybutyrate (β-OHB) through ingestion of ketone salts on substrate oxidation and performance during cycling exercise. Ten healthy adult males (23 ± 3 years, BMI 25 ± 3 kg/m2, VO2peak 45 ± 10 ml/kg/min) were recruited to complete two experimental trials. Before enrollment in the experimental conditions, baseline anthropometrics and cardiorespiratory fitness (VO2peak) were assessed and familiarization to the study protocol was provided. On experimental days, participants reported to the laboratory in the fasted state and consumed either 0.3 g/kg β-OHB ketone salts or a flavor-matched placebo 30 minutes prior to engaging in cycling exercise. Subjects completed steady-state exercise at 30%, 60%, and 90% ventilatory threshold (VT) followed by a 150 kJ cycling time trial. Respiratory exchange ratio (RER) and total substrate oxidation were derived from indirect calorimetry. Plasma glucose, lactate, and ketones were measured at baseline, 30 minutes post-supplement, post-steady-state exercise, and immediately following the time trial. Plasma β-OHB was elevated from baseline and throughout the entire protocol in the ketone condition (pThe accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

Carbohydrate restriction with postmeal walking effectively mitigates postprandial hyperglycemia and improves endothelial function in type 2 diabetes

Postprandial hyperglycemia has deleterious effects on endothelial function. Restricting carbohydrate intake and postmeal walking have each been shown to reduce postprandial hyperglycemia, but their combination and subsequent effects on endothelial function have not been investigated. Here, we sought to examine the effect of blunting postprandial hyperglycemia by following a low-carbohydrate diet, with or without postmeal walking exercise, on markers of vascular health in type 2 diabetes (T2D). In a randomized crossover design, individuals with T2D (n \u3c 11) completed three 4-day controlled diet interventions consisting of 1) low-carbohydrate diet alone (LC), 2) low-carbohydrate diet with 15-min postmeal walks (LC \u3e Ex), and 3) low-fat control diet (CON). Fasting blood samples and brachial artery flow-mediated dilation (%FMD) were measured before and after each intervention. Total circulating microparticles (MPs), endothelial MPs, platelet MPs, monocyte-platelet aggregates, and adhesion molecules were assessed as biomarkers of vascular health. There was a significant condition = time interaction for %FMD (P \u3c 0.01), with post hoc tests revealing improved %FMD after LC \u3e Ex (\u3e0.8 ± 1.0%, P \u3c 0.02), with no change after LC or CON. Endothelial MPs were significantly reduced with the LC diet by ~45% (from 99 ± 60 to 44 ± 31 MPs/μl, P \u3c 0.02), with no change after LC \u3e Ex or CON (interaction: P \u3c 0.04). Total MPs were lower (main effect time: P \u3c 0.02), whereas monocyte-platelet aggregates were higher (main effect time: P = 0.01) after all interventions. Plasma adhesion molecules and C-reactive protein were unaltered. Attenuating postprandial hyperglycemic excursions using a low-carbohydrate diet combined with postmeal walking appears to be an effective strategy to improve endothelial function in individuals with T2D. NEW & NOTEWORTHY Carbohydrate restriction and postmeal walking lower postprandial hyperglycemia in individuals with type 2 diabetes. Here, we show that the combination significantly improved endothelial function and that carbohydrate restriction alone reduced circulating endothelial microparticles in individuals with type 2 diabetes. Listen to this article\u27s corresponding podcast at http://ajpheart.pod-bean.com/e/low-carb-diet-and-exercise-improve-endothelial-health/

Combined Interval Training and Post-exercise Nutrition in Type 2 Diabetes: A Randomized Control Trial

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 (HbA1c), body composition (dual-energy X-ray absorptiometry), cardiorespiratory fitness (V˙O2peak), blood pressure, and endothelial function (%FMD) were measured before and after the intervention.Results: There were significant main effects of time (all p &lt; 0.05) but no difference between groups (Interaction: all p &gt; 0.71) for CGM 24-h mean glucose (−0.5 ± 1.1 mmol/L), HbA1c (−0.2 ± 0.4%), percent body fat (−0.8 ± 1.6%), and lean mass (+1.1 ± 2.8 kg). Similarly, V˙O2peak (+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 &lt; 0.01) with no difference between beverage groups (Interaction: all p &gt; 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