CGMS and Glycemic Variability, Relevance in Clinical Research to Evaluate Interventions in T2D, a Literature Review

International audienceGlycemic variability (GV) appears today as an integral component of glucose homeostasis for the management of type 2 diabetes (T2D). This review aims at investigating the use and relevance of GV parameters in interventional and observational studies for glucose control management in T2D. It will first focus on the relationships between GV parameters measured by continuous glucose monitoring system (CGMS) and glycemic control and T2D-associated complications markers. The second part will be dedicated to the analysis of GV parameters from CGMS as outcomes in interventional studies (pharmacological, nutritional, physical activity) aimed at improving glycemic control in patients with T2D. From 243 articles first identified, 63 articles were included (27 for the first part and 38 for the second part). For both analyses, the majority of the identified studies were pharmacological. Lifestyle studies (including nutritional and physical activity-based studies, N-AP) were poorly represented. Concerning the relationships of GV parameters with those for glycemic control and T2D related-complications, the standard deviation (SD), the coefficient of variation (CV), the mean blood glucose (MBG), and the mean amplitude of the glycemic excursions (MAGEs) were the most studied, showing strong relationships, in particular with HbA1c. Regarding the use and relevance of GV as an outcome in interventional studies, in pharmacological ones, SD, MAGE, MBG, and time in range (TIR) were the GV parameters used as main criteria in most studies, showing significant improvement after intervention, in parallel or not with glycemic control parameters’ (HbA1c, FBG, and PPBG) improvement. In N-AP studies, the same results were observed for SD, MAGE, and TIR. Despite the small number of N-AP studies addressing both GV and glycemic control parameters compared to pharmacological ones, N-AP studies have shown promising results on GV parameters and would require more in-depth work. Evaluating CGMS-GV parameters as outcomes in interventional studies may provide a more integrative dimension of glucose control than the standard postprandial follow-up. GV appears to be a key component of T2D dysglycemia, and some parameters such as MAGE, SD, or TIR could be used routinely in addition to classical markers of glycemic control such as HbA1c, fasting, or postprandial glycemia

Caractérisation des mécanismes impliqués dans les altérations métaboliques liées à la prise de poids au cours d’un protocole de surnutrition chez l’homme

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Modulation of starch digestibility in breakfast cereals consumed by subjects with metabolic risk: impact on markers of oxidative stress and inflammation during fasting and the postprandial period

Scope: Decreasing postprandial glycaemic excursions may have a beneficial effect on inflammatory and oxidative stress profiles. In this study, we investigated the impact of carbohydrate digestibility modulation per se, as a means of reducing the glycaemic response, on metabolic and inflammatory responses in subjects with metabolic risk factors. Methods and results: Twenty healthy subjects with metabolic risk consumed a cereal product either high in Slowly Digestible Starch (HSDS) or low in SDS (LSDS) at breakfast daily for 3 weeks, in a cross-over design. Following each 3-week session, postprandial glycaemia, insulinaemia, the lipid profile, inflammation and oxidative stress markers were assessed and compared to those induced by ingestion of a glucose solution (as a reference). The 2-h glycaemic and insulinaemic responses were significantly lower following the HSDS breakfast compared with the LSDS breakfast or glucose. No significant differences between the products were observed in terms of the lipid profile, C-reactive protein, IL-6 and tumour necrosis factor alpha. We observed a slight increase in fasting lipid peroxidation markers, including an increase in plasma malondialdehyde (MDA) and a decrease in whole blood glutathione (GSH), without significant alteration of urinary F2-isoprostanes or plasma glutathione peroxidase (GPx) activity. Conclusion: Consumption of HSDS products for 3 weeks significantly altered both postprandial glycaemia and insulinaemia, but was not sufficient to modify the inflammatory profile. Consumption of both cereal products was associated with a slightly higher fasting oxidative stress profile

Influence of fat emulsification on postprandial lipemia and lipid oxidation in lean and obese subjects

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13C tracer recovery in human stools after digestion of a fat-rich meal labelled with [1,1,1-13C3]tripalmitin and [1,1,1-13C3]triolein

International audienceLipid metabolism studies focus mainly on oxidation and storage but rarely on faecal elimination, which is needed to assess total lipid distribution during the postprandial period. The purpose of the present work was to set up and validate the analysis of lipid tracers in stools, with an aim of later using this methodology in studies of postprandial lipid tracer metabolism. Eight subjects received a mixture of [1,1,1-(13)C3]tripalmitin and [1,1,1-(13)C3]triolein with a fat-rich meal. The nature and amounts of (13)C lipids excreted in stools during 3 days post-dose were determined by gas chromatography/mass spectrometry (GC/MS) and gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) analysis of fatty acid methyl esters (FAMEs) from total fatty acid (TFA), free fatty acid (FFA) and triacylglycerol (TAG) fractions. The results were expressed as the Cumulative Tracer Recovery of the administered dose (CTR%). The quantities and labelling of FAMEs were higher in FFA than in TAG, indicating that label loss was not due to a lack of digestive lipase activity. The labelling was higher for C16:0 than for C18:1. The CTRs were 7.03 ± 0.77% and 6.87 ± 0.91%, respectively, in TFA and FFA for [1-(13)C] C16:0, while they were 0.60 ± 0.15% and 0.51 ± 0.11% for [1-(13)C] C18:1 (mean ± sem). By studying the kinetics of lipid excretion from subjects, two groups emerged. The first one showed rapid excretion in stool #1, whereas the second showed slower excretion in stools #2-#3. A significant difference was found in the FFA in stool #1 for C16:0 (p < 0.01) and C18:1 (p < 0.05). Individual excretion kinetics showed marked variability. Nevertheless, the CTR over the 3-day study period was substantial and homogenous for all subjects. These results confirm that the assessment of faecal elimination is of great importance when establishing total lipid distribution during the postprandial period and validate the analysis of cumulative tracer loss during 72 h post-tracer ingestion

Characterization of the early molecular events of adipose tissue development during overfeeding in humans

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Health benefits of cream cheese enriched with milk polar lipids: focus on lipid metabolism, shingolipidome and associated cardiovascular risk markers

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Impact of milk polar lipid supplementation on postprandial bile acid composition

International audienceBile acids (BA) are the end products of cholesterol catabolism and may act as signalling molecules and metabolic regulators of energy homeostasis. Disorders in BA metabolism can lead to liver and cardiovascular diseases. In a 4-week double-blind RCT, we demonstrated that the daily consumption of a cream cheese enriched with 3 or 5g of milk polar lipids (PL) improved lipid metabolism by reducing hypercholesterolemia in overweight postmenopausal women. Postprandial (pp) metabolic explorations (0-480 min) were performed before and after the intervention, including a standardized high fat-high sucrose breakfast at fasting and a standardized lunch containing the test cream cheese at 240min. We aimed to determine the effect of milk PL on circulating BA in the fasting and pp state. Before intervention, serum concentration of total fasting BA in the 3 groups was within physiological concentrations (<8µM). The milk PL intervention slightly increased total fasting BA concentrations (After-Before) (PPL=0.03), with no significant effect on BA species profile (% of total BA). Total BA concentration was not impacted during the pp period, but the primary/secondary BA ratio was significantly decreased in both milk PL groups versus control (Pgroup<0.001, PPL<0.001). Milk PL decreased the relative abundance of primary BA (PPL=0.02), increased Tauro-conjugated BA (Pgroup=0.02) and highly decreased Glyco-conjugated BA (Pgroup<0.001). Proportions of GCA (glycocholic acid), GCDCA (glycochenodeoxycholic acid) and GLCA (glycolithocholic acid) were also decreased during the pp period. The latter is derived from the LCA (litocholic acid) whose accumulation is toxic. In conclusion, the 4-week milk PL supplementation did not alter the overall circulating levels of BA in neither the fasting nor the pp state, but impacted the BA profile by decreasing some of deleterious species. Such results provide new insights in the knowledge of BA metabolism, and a potential link with the cholesterol-lowering effects of milk PL deserves to be investigated

Impact of milk polar lipid supplementation on postprandial bile acid composition

International audienceBile acids (BA) are the end products of cholesterol catabolism and may act as signalling molecules and metabolic regulators of energy homeostasis. Disorders in BA metabolism can lead to liver and cardiovascular diseases. In a 4-week double-blind RCT, we demonstrated that the daily consumption of a cream cheese enriched with 3 or 5g of milk polar lipids (PL) improved lipid metabolism by reducing hypercholesterolemia in overweight postmenopausal women. Postprandial (pp) metabolic explorations (0-480 min) were performed before and after the intervention, including a standardized high fat-high sucrose breakfast at fasting and a standardized lunch containing the test cream cheese at 240min. We aimed to determine the effect of milk PL on circulating BA in the fasting and pp state. Before intervention, serum concentration of total fasting BA in the 3 groups was within physiological concentrations (<8µM). The milk PL intervention slightly increased total fasting BA concentrations (After-Before) (PPL=0.03), with no significant effect on BA species profile (% of total BA). Total BA concentration was not impacted during the pp period, but the primary/secondary BA ratio was significantly decreased in both milk PL groups versus control (Pgroup<0.001, PPL<0.001). Milk PL decreased the relative abundance of primary BA (PPL=0.02), increased Tauro-conjugated BA (Pgroup=0.02) and highly decreased Glyco-conjugated BA (Pgroup<0.001). Proportions of GCA (glycocholic acid), GCDCA (glycochenodeoxycholic acid) and GLCA (glycolithocholic acid) were also decreased during the pp period. The latter is derived from the LCA (litocholic acid) whose accumulation is toxic. In conclusion, the 4-week milk PL supplementation did not alter the overall circulating levels of BA in neither the fasting nor the pp state, but impacted the BA profile by decreasing some of deleterious species. Such results provide new insights in the knowledge of BA metabolism, and a potential link with the cholesterol-lowering effects of milk PL deserves to be investigated

Impact of milk polar lipid supplementation on postprandial bile acid composition

Hybrid congress, online oral presentation.International audienc