Changements dans la captation du glucose suite à une perte de poids induite par une restriction calorique chez des femmes ménopausées obèses : caractéristiques des répondants positifs et négatifs

Pour les besoins du présent mémoire, nous avons étudié quarante-deux femmes obèses ménopausées (pourcentage de masse grasse initiale: 45 +/- 4%) âgées de 57 +/- 4 ans qui ont suivi une diète hypocalorique sur une période de six mois. À l'aide de la méthode par absorptiométrie biphotonique à rayons X (dual energy X-ray absorptiometry "DXA") et celle de la tomodensitométrie axiale (CT-scan), plusieurs variables telles l'indice de masse corporelle (IMC), la masse maigre (MM), l'indice de MM (IMM), la masse grasse (MG), la graisse viscérale (GV) et la graisse abdominale sous-cutanée (GAS) ont été évaluées. De plus, des prélèvements sanguins nous ont permis d'obtenir un bilan lipidique sanguin complet, les niveaux de hsCRP ainsi que le glucose et l'insuline à jeun. La captation du glucose (mg/kg MM/min et mg/kg/min) quant à elle a été analysée à l'aide d'un clamp hyperinsulinémique-euglycémique. Les participantes ont ensuite été divisées en deux groupes selon leur changement de captation du glucose en réponse à la perte de poids [répondants négatifs : 1,0 mg/kg MM/min (n= 23)]. Avant le début de l'intervention, nous avons observé une différence significative entre nos deux groupes pour l'IMM (17,5 +/- 2,6 vs 15,9 +/- 1,5 kg/m² ; P < 0,05) et les niveaux de hsCRP (5,04 +/- 3,67 vs 2,36 +/- 1,75 mg/L; P < 0,01); lesquels étaient plus élevés chez les répondants positifs. De plus, la disposition relative du glucose était moins importante chez les répondants positifs (P < 0,001). L'ANOVA à mesure répétée a révélé une diminution significative de l'IMC (-7,4%), du %MG (-6,1%), de la MG (-12,2%), de la GV (-15,7%), de la GAS (-11,4%) et de l'insuline à jeun (-13,6%) pour l'ensemble des sujets (p [plus petit ou égal à] 0.005 pour tous les changements). De plus, une interaction (temps x groupe) a révélé que nos deux groupes répondaient différemment au traitement au niveau du poids corporel (P < 0,01), de la protéine C-réactive (P < 0,005) et des mesures de masse maigre (P < 0,001). En effet, les répondants positifs ont vu des diminutions plus importantes que le groupe de répondants négatifs. Au niveau du profil lipidique, malgré une forte tendance au niveau des triglycérides plasmatiques, aucun changement ne fut enregistré. Finalement, les répondants positifs ont significativement augmenté leur captation du glucose suite à la perte de poids, tandis que les répondants négatifs ont plutôt vu cette dernière se détériorer significativement (P < 0,001 dans les deux cas); la différence de changements entre les deux groupes étant significative (P < 0,005). En conclusion, notre étude démontre qu'il existe d'importantes variabilités interindividuelles en ce qui a trait aux changements de la sensibilité à l'insuline en réponse à une perte de poids chez les femmes ménopausées. Les femmes ménopausées obèses présentant des valeurs élevées d' IMM et de hsCRP élevés, ainsi qu'une faible captation du glucose seront celles qui bénéficieraient davantage d'une perte de poids. Il est d'une grande importance d'être en mesure de développer des programmes d'interventions personnalisées au profil métabolique et physiologique de chaque individu

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

The effects of short-term low-carbohydrate and ketogenic interventions on cardiometabolic health

Type 2 diabetes (T2D) is currently one of the most common chronic diseases worldwide and is characterized by impaired insulin secretion and action, elevated blood glucose and chronic inflammation. Lifestyle interventions including exercise and nutritional manipulations are considered first-line non-pharmacological treatments for this metabolic disease. While most health care providers agree that diet is of extreme importance for the prevention and management of T2D, the type of diet that should be consumed is highly debated. One dietary intervention, the low-carbohydrate high-fat (LCHF) diet, has been shown to be particularly effective at improving diabetes symptoms by reducing glucose excursions and lowering hyperinsulinemia. The first study of this thesis was to determine if changes in insulin levels in saliva were reflective of those observed in plasma following high and low-carbohydrate meals in 20 individuals (10 normal weight; BMI 20.0–24.9 kg/m2 and 10 with overweight/obesity; BMI > 28.0 kg/m2). The findings of this study indicate that saliva could potentially be used to delineate between low and high insulin levels following mixed meals, providing a potential avenue for personalizing dietary choices based on non-invasive saliva insulin measurement. In a second study, the effect of three 4-day diet interventions: i) Low-fat low-glycemic index (GL); ii) LCHF, and iii) LCHF with 15-min post-meal walks (LC+Ex) on the inflammatory and glycemic profiles of 11 individuals with T2D were compared. The main findings were that: a) LCHF and LCHF+EX improved glycemic control and proinsulin levels to a greater extent than GL and b) all diets improved some markers of inflammation. For the third and fourth study, we investigated the isolated effect of a new exogenous ketone monoester (KM) drink taken before a 2-hour oral glucose tolerance test in 20 healthy young individuals (BMI < 25 kg/m2) and 15 adults with overweight/obesity (BMI ≥ 28 kg/m2). The main findings are that the KM improved glucose control and decreased non-esterified fatty acids levels without a concomitant increase in circulating insulin. Overall, low-carbohydrate diets and ketone supplements seem to be effective at controlling glucose levels and could be considered as preventive and management therapies for metabolic diseases.Health and Social Development, Faculty of (Okanagan)Health and Exercise Sciences, School of (Okanagan)Graduat

Changements dans la captation du glucose suite à une perte de poids induite par une restriction calorique chez des femmes ménopausées obèses : caractéristiques des répondants positifs et négatifs

Pour les besoins du présent mémoire, nous avons étudié quarante-deux femmes obèses ménopausées (pourcentage de masse grasse initiale: 45 +/- 4%) âgées de 57 +/- 4 ans qui ont suivi une diète hypocalorique sur une période de six mois. À l'aide de la méthode par absorptiométrie biphotonique à rayons X (dual energy X-ray absorptiometry "DXA") et celle de la tomodensitométrie axiale (CT-scan), plusieurs variables telles l'indice de masse corporelle (IMC), la masse maigre (MM), l'indice de MM (IMM), la masse grasse (MG), la graisse viscérale (GV) et la graisse abdominale sous-cutanée (GAS) ont été évaluées. De plus, des prélèvements sanguins nous ont permis d'obtenir un bilan lipidique sanguin complet, les niveaux de hsCRP ainsi que le glucose et l'insuline à jeun. La captation du glucose (mg/kg MM/min et mg/kg/min) quant à elle a été analysée à l'aide d'un clamp hyperinsulinémique-euglycémique. Les participantes ont ensuite été divisées en deux groupes selon leur changement de captation du glucose en réponse à la perte de poids [répondants négatifs : 1,0 mg/kg MM/min (n= 23)]. Avant le début de l'intervention, nous avons observé une différence significative entre nos deux groupes pour l'IMM (17,5 +/- 2,6 vs 15,9 +/- 1,5 kg/m² ; P < 0,05) et les niveaux de hsCRP (5,04 +/- 3,67 vs 2,36 +/- 1,75 mg/L; P < 0,01); lesquels étaient plus élevés chez les répondants positifs. De plus, la disposition relative du glucose était moins importante chez les répondants positifs (P < 0,001). L'ANOVA à mesure répétée a révélé une diminution significative de l'IMC (-7,4%), du %MG (-6,1%), de la MG (-12,2%), de la GV (-15,7%), de la GAS (-11,4%) et de l'insuline à jeun (-13,6%) pour l'ensemble des sujets (p [plus petit ou égal à] 0.005 pour tous les changements). De plus, une interaction (temps x groupe) a révélé que nos deux groupes répondaient différemment au traitement au niveau du poids corporel (P < 0,01), de la protéine C-réactive (P < 0,005) et des mesures de masse maigre (P < 0,001). En effet, les répondants positifs ont vu des diminutions plus importantes que le groupe de répondants négatifs. Au niveau du profil lipidique, malgré une forte tendance au niveau des triglycérides plasmatiques, aucun changement ne fut enregistré. Finalement, les répondants positifs ont significativement augmenté leur captation du glucose suite à la perte de poids, tandis que les répondants négatifs ont plutôt vu cette dernière se détériorer significativement (P < 0,001 dans les deux cas); la différence de changements entre les deux groupes étant significative (P < 0,005). En conclusion, notre étude démontre qu'il existe d'importantes variabilités interindividuelles en ce qui a trait aux changements de la sensibilité à l'insuline en réponse à une perte de poids chez les femmes ménopausées. Les femmes ménopausées obèses présentant des valeurs élevées d' IMM et de hsCRP élevés, ainsi qu'une faible captation du glucose seront celles qui bénéficieraient davantage d'une perte de poids. Il est d'une grande importance d'être en mesure de développer des programmes d'interventions personnalisées au profil métabolique et physiologique de chaque individu

The Impact of Acute Ingestion of a Ketone Monoester Drink on LPS-Stimulated NLRP3 Activation in Humans with Obesity

Activation of the NOD-like receptor pyrin-domain containing 3 (NLRP3) inflammasome is associated with chronic low-grade inflammation in metabolic diseases such as obesity. Mechanistic studies have shown that β-hydroxybutyrate (OHB) attenuates activation of NLRP3, but human data are limited. In a randomized, double-blind, placebo-controlled crossover trial (n = 11) we tested the hypothesis that acutely raising β-OHB by ingestion of exogenous ketones would attenuate NLRP3 activation in humans with obesity. Blood was sampled before and 30 min post-ingestion of a ketone monoester drink ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate, 482 mg/kg body mass) or placebo. A 75 g oral glucose load was then ingested, and a third blood sample was obtained 60 min following glucose ingestion. NLRP3 activation was quantified by assessing monocyte caspase-1 activation and interleukin (IL)-1β secretion in ex vivo lipopolysaccharide (LPS)-stimulated whole-blood cultures. LPS-stimulated caspase-1 activation increased following glucose ingestion (main effect of time; p = 0.032), with no differences between conditions. IL-1β secretion did not differ between conditions but was lower 60 min post-glucose ingestion compared to the fasting baseline (main effect of time, p = 0.014). Plasma IL-1β was detectable in ~80% of samples and showed a decrease from fasting baseline to 60 min in the ketone condition only (condition × time interaction, p = 0.01). In individuals with obesity, an excursion into hyperglycemia following ingestion of a glucose load augments LPS-induced activation of caspase-1 in monocytes with no apparent impact of raising circulating β-OHB concentration via ingestion of exogenous ketones. Exogenous ketone supplementation may impact plasma IL-1β, but these findings require confirmation in studies with larger sample sizes.Health and Social Development, Faculty of (Okanagan)Health and Exercise Sciences, School of (Okanagan)ReviewedFacult

Detection of Salivary Insulin Following Low versus High Carbohydrate Meals in Humans

Developing non-invasive alternatives to monitor insulin levels in humans holds potential practical value for identifying individuals with, or at risk of developing, insulin resistance. The aims of this study were: (1) to determine if saliva insulin can be used to delineate between low and high postprandial insulin levels following the ingestion of mixed breakfast meals; and (2) to determine if expected differences in postprandial hyperinsulinemia between young lean and young overweight/obese participants could be detected in saliva. Sixteen individuals (n = 8 classified as normal weight (NW); BMI 20.0–24.9 kg/m², and n = 8 classified as overweight/obese (OO); BMI ≥ 28.0 kg/m²) completed two isocaloric mixed-meal tolerance tests following an overnight fast, consisting of a low-carbohydrate (LC) breakfast or a high-carbohydrate (HC) breakfast. Blood and saliva samples were collected at regular intervals for two hours postprandially. In both groups, plasma and saliva insulin total area under the curve (AUC) and incremental AUC (iAUC) were significantly higher after the HC as compared to the LC meal (all p ≤ 0.005). Insulin AUC and iAUC in both plasma and saliva were higher in OO than in NW after the HC meal (all p ≤ 0.02) but only plasma and saliva total AUC were higher in OO after the LC meal (both p ≤ 0.01). Plasma insulin AUC was significantly correlated with salivary insulin AUC in LC (r = 0.821; p < 0.001) and HC (r = 0.882; p < 0.001). These findings indicate that saliva could potentially be used to delineate between low and high insulin levels following mixed breakfast meals.Health and Social Development, Faculty of (Okanagan)Medicine, Faculty ofHealth and Exercise Sciences, School of (Okanagan)Southern Medical Program (Okanagan)ReviewedFacult

Prevalence of nocturnal hypoglycemia in free-living conditions in adults with type 1 diabetes: What is the impact of daily physical activity?

International audienceStudies investigating strategies to limit the risk of nocturnal hypoglycemia associated with physical activity (PA) are scarce and have been conducted in standardized, controlled conditions in people with type 1 diabetes (T1D). This study sought to investigate the effect of daily PA level on nocturnal glucose management in free-living conditions while taking into consideration reported mitigation strategies to limit the risk of nocturnal hyoglycemia in people with T1D. Data from 25 adults (10 males, 15 females, HbA: 7.6 ± 0.8%), 20-60 years old, living with T1D, were collected. One week of continuous glucose monitoring and PA (assessed using an accelerometer) were collected in free-living conditions. Nocturnal glucose values (midnight-6:00 am) following an active day "ACT" and a less active day "L-ACT" were analyzed to assess the time spent within the different glycemic target zones (10.0 mmol/L) between conditions. Self-reported data about mitigation strategies applied to reduce the risk of nocturnal hypoglycemia was also analyzed. Only 44% of participants reported applying a carbohydrate- or insulin-based strategy to limit the risk of nocturnal hypoglycemia on ACT day. Nocturnal hypoglycemia occurrences were comparable on ACT night versus on L-ACT night. Additional post-meal carbohydrate intake was higher on evenings following ACT (27.7 ± 15.6 g, ACT vs. 19.5 ± 11.0 g, L-ACT; P=0.045), but was frequently associated with an insulin bolus (70% of participants). Nocturnal hypoglycemia the night following ACT occurred mostly in people who administrated an additional insulin bolus before midnight (3 out of 5 participants with nocturnal hypoglycemia). Although people with T1D seem to be aware of the increased risk of nocturnal hypoglycemia associated with PA, the risk associated with additional insulin boluses may not be as clear. Most participants did not report using compensation strategies to reduce the risk of PA related late-onset hypoglycemia which may be because they did not consider habitual PA as something requiring treatment adjustments