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The effect of a short-term low-carbohydrate, high-fat diet with or without postmeal walks on glycemic control and inflammation in type 2 diabetes: a randomized trial.
Myette-Côté, É, Durrer, C, Neudorf, H, Bammert, TD, Botezelli, JD, Johnson, JD, DeSouza, CA, Little, JP
American journal of physiology. Regulatory, integrative and comparative physiology. 2018;315(6):R1210-R1219
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Inflammation is associated with the pathogenesis of insulin resistance, type 2 diabetes (T2D), and related complications. Lifestyle therapy is a frontline treatment for improving glucose control in people with T2D. The main aim of this study was to determine whether reducing hyperglycaemia with a low-carbohydrate high-fat (LC) diet could lower markers of innate immune cell activation and systemic inflammation in people with T2D. A secondary aim was to examine if the combination of an LCHF diet with strategically timed postmeal walking was superior to an LCHF diet alone. The study is a randomised cross over study which enrolled Individuals with physician-diagnosed T2D to complete three short-term controlled-intervention periods. Sixteen participants were enrolled (men = 8 and women = 8) who were aged between 48 and 72 years. Results indicate that while LC and LC together with exercise (LC+Ex) led to superior improvements in glucose control and fasting proinsulin (the pro-hormone precursor to insulin) levels as compared with low-fat low glycaemic index diet (GL), all three diets (GL, LC and LC+Ex), appeared to lower a particular marker of cellular inflammation over the short-term. Authors conclude that an LCHF diet with or without daily postmeal walks improved four-day glycaemic control and fasting proinsulin levels compared with a GL diet.
Abstract
Lowering carbohydrate consumption effectively lowers glucose, but impacts on inflammation are unclear. The objectives of this study were to: 1) determine whether reducing hyperglycemia by following a low-carbohydrate, high-fat (LC) diet could lower markers of innate immune cell activation in type 2 diabetes (T2D) and 2) examine if the combination of an LC diet with strategically timed postmeal walking was superior to an LC diet alone. Participants with T2D ( n = 11) completed a randomized crossover study involving three 4-day diet interventions: 1) low-fat low-glycemic index (GL), 2) and 3) LC with 15-min postmeal walks (LC+Ex). Four-day mean glucose was significantly lower in the LC+Ex group as compared with LC (-5%, P < 0.05), whereas both LC+Ex (-16%, P < 0.001) and LC (-12%, P < 0.001) conditions were lower than GL. A significant main effect of time was observed for peripheral blood mononuclear cells phosphorylated c-Jun N-terminal kinase ( P < 0.001), with decreases in all three conditions (GL: -32%, LC: -45%, and LC+Ex: -44%). A significant condition by time interaction was observed for monocyte microparticles ( P = 0.040) with a significant decrease in GL (-76%, P = 0.035) and a tendency for a reduction in LC (-70%, P = 0.064), whereas there was no significant change in LC+Ex (0.5%, P = 0.990). Both LC (-27%, P = 0.001) and LC+Ex (-35%, P = 0.005) also led to significant reductions in circulating proinsulin. An LC diet improved 4-day glycemic control and fasting proinsulin levels when compared with GL, with added glucose-lowering benefits when LC was combined with postmeal walking.
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A whole-grain diet reduces peripheral insulin resistance and improves glucose kinetics in obese adults: A randomized-controlled trial.
Malin, SK, Kullman, EL, Scelsi, AR, Haus, JM, Filion, J, Pagadala, MR, Godin, JP, Kochhar, S, Ross, AB, Kirwan, JP
Metabolism: clinical and experimental. 2018;82:111-117
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Literature shows that dietary whole-grain intake is associated with a lower incidence of type 2 diabetes. The aim of the study was to investigate the association between a whole-grain diet and insulin resistance and glucose use in individuals at risk for type 2 diabetes. The study was a randomized, double-blind, controlled crossover trial involving fourteen middle-aged, obese adults at risk for diabetes. Randomisation was carried out prior to metabolic testing. Results indicate that whole-grain intake as part of a mixed-meal diet significantly improved post-prandial (after a meal) glucose metabolism in middle-aged obese adults. Furthermore, both whole-grain and refined-grain interventions induced about 3–6% weight and fat loss. Authors conclude that whole-grain intake effectively promotes glycaemic control by improving insulin action.
Abstract
BACKGROUND Whole-grain intake is associated with lower risk of type 2 diabetes but the mechanisms are unclear. PURPOSE We tested the hypothesis that a WG diet reduces insulin resistance and improves glucose use in individuals at risk for type 2 diabetes compared with an isocaloric-matched refined-grain diet. METHODS A double-blind, randomized, controlled, crossover trial of 14 moderately obese adults (Age, 38 ± 2 y; BMI, 34.0 ± 1.1 kg/m2). Insulin resistance and glucose metabolism was assessed using an oral glucose tolerance test combined with isotopic tracers of [6,6-2H2]-glucose and [U-13C]-glucose, and indirect calorimetry. Peripheral and hepatic insulin resistance was assessed as 1/(rate of disposal/insulin), and endogenous glucose rates of appearance (Ra) iAUC60-240 × insulin iAUC60-240, respectively. Both diets met ADA nutritional guidelines and contained either whole-grain (50 g per 1000 kcal) or equivalent refined-grain. All food was provided for 8 wk. with an 8-10 wk. washout period between diets. RESULTS Post-prandial glucose tolerance, peripheral insulin sensitivity, and metabolic flexibility (insulin-stimulated - fasting carbohydrate oxidation) improvements were greater after whole-grain compared to the refined-grain diet (P < 0.05). Compared to baseline, body fat (~2 kg) and hepatic Ra insulin resistance was reduced by both diets, while fasting glucose and exogenous glucose-meal were unchanged after both interventions. Changes in peripheral insulin resistance and metabolic flexibility correlated with improved glucose tolerance (P < 0.05). CONCLUSION Whole-grains reduced diabetes risk and the mechanisms appear to work through reduced post-prandial blood glucose and peripheral insulin resistance that were statistically linked to enhanced metabolic flexibility.
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Hyperinsulinemia leads to uncoupled insulin regulation of the GLUT4 glucose transporter and the FoxO1 transcription factor.
Gonzalez, E, Flier, E, Molle, D, Accili, D, McGraw, TE
Proceedings of the National Academy of Sciences of the United States of America. 2011;108(25):10162-7
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Insulin resistance develops following extended periods of high insulin production, making cells unresponsive to its actions, however not all insulin functions are equally affected. Patients with Type 2 diabetes have impaired insulin regulation of glucose with increased fat storage in the liver. This results in a combination of raised insulin, glucose and triglycerides in the blood (hyperinsulinemia, hyperglycaemia, and hypertriglyceridemia), which affect health outcomes. Studies have shown that 'selective insulin resistance' occurs in the liver, however the molecular mechanisms by which this occurs are not known. It is also not known whether this is liver-specific or occurs in other insulin responsive tissues in the body. This in-vitro (cell culture) study found that high levels of insulin disturbs the PI3-kinase/Akt signalling pathway resulting in selective insulin resistance in fat cells (adipocytes), whilst expression of FoxO1 transcription factor (which controls lipid metabolism) is maintained. These changes are the result of inherent differences in insulin sensitivity of GLUT4 translocation and FoxO1 nuclear exclusion. The authors conclude that in a model of chronic hyperinsulinemia, fat cells develop a state of selective insulin resistance. Uncoupled insulin action, a phenomenon first described in the insulin-resistant liver, might be a general feature of insulin-resistant tissues consequent to deregulation of PI3-kinase/Akt signalling.
Abstract
Insulin resistance is a component of the metabolic syndrome and Type 2 diabetes. It has been recently shown that in liver insulin resistance is not complete. This so-called selective insulin resistance is characterized by defective insulin inhibition of hepatic glucose output while insulin-induced lipogenesis is maintained. How this occurs and whether uncoupled insulin action develops in other tissues is unknown. Here we show in a model of chronic hyperinsulinemia that adipocytes develop selective insulin resistance in which translocation of the GLUT4 glucose transporter to the cell surface is blunted yet nuclear exclusion of the FoxO1 transcription factor is preserved, rendering uncoupled insulin-controlled carbohydrate and lipid metabolisms. We found that in adipocytes FoxO1 nuclear exclusion has a lower half-maximal insulin dose than GLUT4 translocation, and it is because of this inherent greater sensitivity that control of FoxO1 by physiological insulin concentrations is maintained in adipocytes with compromised insulin signaling. Pharmacological and genetic interventions revealed that insulin regulates GLUT4 and FoxO1 through the PI3-kinase isoform p110α, although FoxO1 showed higher sensitivity to p110α activity than GLUT4. Transient down-regulation and overexpression of Akt isoforms in adipocytes demonstrated that insulin-activated PI3-kinase signals to GLUT4 primarily through Akt2 kinase, whereas Akt1 and Akt2 signal to FoxO1. We propose that the lower threshold of insulin activity for FoxO1's nuclear exclusion is in part due to its regulation by both Akt isoforms. Identification of uncoupled insulin action in adipocytes suggests this condition might be a general phenomenon of insulin target tissues contributing to insulin resistance's pathophysiology.