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1.
Temporal Patterns of Glucagon and Its Relationships with Glucose and Insulin following Ingestion of Different Classes of Macronutrients.
Göbl, C, Morettini, M, Salvatori, B, Alsalim, W, Kahleova, H, Ahrén, B, Tura, A
Nutrients. 2022;(2)
Abstract
BACKGROUND glucagon secretion and inhibition should be mainly determined by glucose and insulin levels, but the relative relevance of each factor is not clarified, especially following ingestion of different macronutrients. We aimed to investigate the associations between plasma glucagon, glucose, and insulin after ingestion of single macronutrients or mixed-meal. METHODS thirty-six participants underwent four metabolic tests, based on administration of glucose, protein, fat, or mixed-meal. Glucagon, glucose, insulin, and C-peptide were measured at fasting and for 300 min following food ingestion. We analyzed relationships between time samples of glucagon, glucose, and insulin in each individual, as well as between suprabasal area-under-the-curve of the same variables (ΔAUCGLUCA, ΔAUCGLU, ΔAUCINS) over the whole participants' cohort. RESULTS in individuals, time samples of glucagon and glucose were related in only 26 cases (18 direct, 8 inverse relationships), whereas relationship with insulin was more frequent (60 and 5, p < 0.0001). The frequency of significant relationships was different among tests, especially for direct relationships (p ≤ 0.006). In the whole cohort, ΔAUCGLUCA was weakly related to ΔAUCGLU (p ≤ 0.02), but not to ΔAUCINS, though basal insulin secretion emerged as possible covariate. CONCLUSIONS glucose and insulin are not general and exclusive determinants of glucagon secretion/inhibition after mixed-meal or macronutrients ingestion.
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2.
The effect of bedtime snacks on fasting blood glucose levels in gestational diabetes mellitus.
Henze, M, Burbidge, H, Nathan, E, Graham, DF
Diabetic medicine : a journal of the British Diabetic Association. 2022;(3):e14718
Abstract
AIM: To investigate the effect of different bedtime snacks (higher carbohydrate versus lower carbohydrate versus no snack) on first morning fasting blood glucose levels (BGLs) in women with diet-controlled gestational diabetes mellitus (GDM) and borderline fasting glucose levels. METHODS This prospective randomised crossover trial enrolled women with diet controlled GDM between 24 and 34 weeks gestation who had two or more first morning fasting BGLs between 4.7 and 5.4 mmol/L in the week prior to recruitment. The women were randomly allocated to 6 different orders of 5 days each of a standardised higher carbohydrate bedtime snack, a lower carbohydrate bedtime snack and no bedtime snack. The primary outcome was fasting capillary BGL as measured with a home glucometer, and the secondary outcome was requirement for insulin as assessed by a physician. RESULTS A total of 68 women with GDM were enrolled in and completed the study at a median gestation of 30.8 weeks. Compared with no bedtime snack, the higher carbohydrate snack (4.96 vs 4.87 mmol/L, mean difference: 0.09 mmol/L, 95% CI 0.05-0.13, p < 0.001) and the lower carbohydrate snack (5.01 vs 4.87 mmol/L, mean difference: 0.14 mmol/L, 95% CI 0.09-0.18, p < 0.001) were both associated with a slightly higher fasting BGL the following morning. CONCLUSIONS Taking a bedtime snack was associated with slightly higher fasting BGLs in women with diet-controlled GDM compared with no bedtime snack (Clinical trial registration: ACTRN12617000659303).
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3.
Observational Study of Lipid Profile and C-Reactive Protein after a Seven-Day Fast.
Galetti, V, Brnic, M, Lotin, B, Frigeri, M
Nutrients. 2021;(1)
Abstract
Fasting is becoming an increasingly popular practice. Nevertheless, its clinical benefits and possible inconveniences remain limitedly evaluated. We observed the effects of a seven-day fast conducted in a non-medical center located in the Swiss Alps. Clinical parameters were measured on the first and last day of fasting (D1 and D7), and two months later (D60). Among the 40 participants, blood analyses were done on 25 persons with an increased metabolic risk, with the primary goal of assessing the lasting effect on low-density lipoprotein (LDL) cholesterol. By comparing D60 with D1, high-density lipoprotein cholesterol (HDL) (+0.15 mmol/L) and insulin-like growth factor-1 (IGF-1) (+2.05 mmol/L) increased (both p < 0.009), all other blood parameters (LDL, glucose, total cholesterol, triglycerides, C-reactive protein (CRP)) did not change; weight (-0.97 kg) and hearth rate (-7.31 min-1) decreased (both p < 0.006). By comparing D7 with D1, total cholesterol (+0.44 mmol/L), triglycerides (+0.37 mmol/L) and CRP (+3.37 mg/L) increased (all p < 0.02). The lack of LDL variation at D60 may be due to the low metabolic risk level of the participants. The increase of total cholesterol, triglycerides and CRP at D7 warrants studies to understand whether such fluctuations represent a stress reaction to the fasting state, which may vary in different fasting types.
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4.
Five Days Periodic Fasting Elevates Levels of Longevity Related Christensenella and Sirtuin Expression in Humans.
Lilja, S, Stoll, C, Krammer, U, Hippe, B, Duszka, K, Debebe, T, Höfinger, I, König, J, Pointner, A, Haslberger, A
International journal of molecular sciences. 2021;(5)
Abstract
Periodic fasting (PF) is an increasingly popular approach that assists in the management of metabolic and inflammatory diseases as well as in preventing mechanisms involved in aging. However, little is known about the effects of fasting on gut microbiota and its impact on the epigenetic regulation of metabolically relevant enzymes, especially sirtuins (SIRTs). We analyzed the effect of periodic fasting on the human gut microbiota, SIRTs expression, and mitochondrial content in 51 males and females. The participants fasted under supervision for five consecutive days following the Buchinger fasting guidelines. Ketogenesis, selected mRNAs, miRNAs, mitochondrial (mt) DNA, and gut composition were analyzed before and after PF. PF triggered a significant switch in metabolism, as indicated by the increase in ß-hydroxybutyrate (BHB) and pyruvate dehydrogenase kinase isoform 4 (PDK4) expression in the capillary blood. MtDNA, SIRT1, SIRT3, and miRlet7b-5p expression in blood cells were elevated, whereas SIRT6 and miR125b-5p were not affected. Following fasting, gut microbiota diversity increased, and a statistically significant correlation between SIRT1 gene expression and the abundance of Prevotella and Lactobacillus was detected. The abundance of longevity related Christensenella species increased after fasting and inversely correlated with age as well as body mass index (BMI). Thus, this represents the first study that showing that fasting not only changes the composition of the gut microbiota, making it more diverse, but also affects SIRT expression in humans.
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5.
Intermittent Fasting Improves Cardiometabolic Risk Factors and Alters Gut Microbiota in Metabolic Syndrome Patients.
Guo, Y, Luo, S, Ye, Y, Yin, S, Fan, J, Xia, M
The Journal of clinical endocrinology and metabolism. 2021;(1):64-79
Abstract
CONTEXT Intermittent fasting (IF) is an effective strategy to improve cardiometabolic health. OBJECTIVE The objective of this work is to examine the effects of IF on cardiometabolic risk factors and the gut microbiota in patients with metabolic syndrome (MS). DESIGN AND SETTING A randomized clinical trial was conducted at a community health service center. PATIENTS Participants included adults with MS, age 30 to 50 years. INTERVENTION Intervention consisted of 8 weeks of "2-day" modified IF. MAIN OUTCOME MEASURE Cardiometabolic risk factors including body composition, oxidative stress, inflammatory cytokines, and endothelial function were assessed at baseline and at 8 weeks. The diversity, composition, and functional pathways of the gut microbiota, as well as circulating gut-derived metabolites, were measured. RESULTS Thirty-nine patients with MS were included: 21 in the IF group and 18 in the control group. On fasting days, participants in the IF group reduced 69% of their calorie intake compared to nonfasting days. The 8-week IF significantly reduced fat mass, ameliorated oxidative stress, modulated inflammatory cytokines, and improved vasodilatory parameters. Furthermore, IF induced significant changes in gut microbiota communities, increased the production of short-chain fatty acids, and decreased the circulating levels of lipopolysaccharides. The gut microbiota alteration attributed to the IF was significantly associated with cardiovascular risk factors and resulted in distinct genetic shifts of carbohydrate metabolism in the gut community. CONCLUSION IF induces a significant alteration of the gut microbial community and functional pathways in a manner closely associated with the mitigation of cardiometabolic risk factors. The study provides potential mechanistic insights into the prevention of adverse outcomes associated with MS.
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6.
Innate immune remodeling by short-term intensive fasting.
Qian, J, Fang, Y, Yuan, N, Gao, X, Lv, Y, Zhao, C, Zhang, S, Li, Q, Li, L, Xu, L, et al
Aging cell. 2021;(11):e13507
Abstract
Previous studies have shown that long-term light or moderate fasting such as intermittent fasting can improve health and prolong lifespan. However, in humans short-term intensive fasting, a complete water-only fasting has little been studied. Here, we used multi-omics tools to evaluate the impact of short-term intensive fasting on immune function by comparison of the CD45+ leukocytes from the fasting subjects before and after 72-h fasting. Transcriptomic and proteomic profiling of CD45+ leukocytes revealed extensive expression changes, marked by higher gene upregulation than downregulation after fasting. Functional enrichment of differentially expressed genes and proteins exposed several pathways critical to metabolic and immune cell functions. Specifically, short-term intensive fasting enhanced autophagy levels through upregulation of key members involved in the upstream signals and within the autophagy machinery, whereas apoptosis was reduced by down-turning of apoptotic gene expression, thereby increasing the leukocyte viability. When focusing on specific leukocyte populations, peripheral neutrophils are noticeably increased by short-term intensive fasting. Finally, proteomic analysis of leukocytes showed that short-term intensive fasting not only increased neutrophil degranulation, but also increased cytokine secretion. Our results suggest that short-term intensive fasting boost immune function, in particular innate immune function, at least in part by remodeling leukocytes expression profile.
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7.
A Low-Calorie Diet with or without Exercise Reduces Postprandial Aortic Waveform in Females with Obesity.
Heiston, EM, Gilbertson, NM, Eichner, NZM, Malin, SK
Medicine and science in sports and exercise. 2021;(4):796-803
Abstract
PURPOSE Arterial stiffness is considered a predictor of cardiovascular disease. Females have higher values of arterial stiffness than males, suggesting a greater risk of heart-related complications. Although a low-calorie diet (LCD) reduces fasting arterial stiffness, in part through weight loss, it is unknown if interval exercise (INT) adds to the benefit of LCD on fasting and postprandial arterial stiffness in females with obesity. METHODS Twenty-five females (47 ± 2.6 yr, 37.6 ± 1.3 kg·m-2) were randomized to 13 d of LCD (n = 12; mixed meals of ~1200 kcal·d-1) or LCD + INT (n = 13; 60 min·d-1 of supervised 3-min intervals at 90% HRpeak and 50% HRpeak). Arterial stiffness (augmentation index [AIx] and carotid-femoral pulse wave velocity [cfPWV]) and blood biochemistries were measured during a 75-g oral glucose tolerance test before and after the intervention to determine fasting and postprandial arterial stiffness as well as insulin sensitivity (simple index of insulin sensitivity [SIIS]) and inflammation (C-reactive protein, interleukin 8, and tumor necrosis factor alpha). RESULTS Although LCD + INT increased V˙O2peak and HDL compared with LCD (P = 0.04 and P < 0.01, respectively), both interventions decreased body fat, LDL, total cholesterol, and triglycerides (all P < 0.01) and increased SIIS (P = 0.03). Despite no effect on fasting AIx (P = 0.27), LCD and LCD + INT decreased AIx60min (-7.4% ± 4.3% vs -7.0% ± 5.0%, P = 0.04) and tAUC120min (-663 ± 263 vs -457 ± 406, P = 0.03). There were no changes in fasting cfPWV (P = 0.91) or cfPWV120min (P = 0.62). Increased SIIS and decreased interleukin 8 were associated with reduced fasting AIx (r = -0.44, P = 0.03, and r = 0.40, P = 0.055), whereas decreased C-reactive protein correlated with reduced postprandial AIx60min (r = 0.43, P = 0.04). CONCLUSION Independent of exercise, 13 d of LCD reduces postprandial AIx in females with obesity. Insulin sensitivity and inflammation correlated with improved arterial stiffness, suggesting unique mechanisms regulate fasted versus postprandial arterial stiffness.
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8.
Fasting alters the gut microbiome reducing blood pressure and body weight in metabolic syndrome patients.
Maifeld, A, Bartolomaeus, H, Löber, U, Avery, EG, Steckhan, N, Markó, L, Wilck, N, Hamad, I, Šušnjar, U, Mähler, A, et al
Nature communications. 2021;(1):1970
Abstract
Periods of fasting and refeeding may reduce cardiometabolic risk elevated by Western diet. Here we show in the substudy of NCT02099968, investigating the clinical parameters, the immunome and gut microbiome exploratory endpoints, that in hypertensive metabolic syndrome patients, a 5-day fast followed by a modified Dietary Approach to Stop Hypertension diet reduces systolic blood pressure, need for antihypertensive medications, body-mass index at three months post intervention compared to a modified Dietary Approach to Stop Hypertension diet alone. Fasting alters the gut microbiome, impacting bacterial taxa and gene modules associated with short-chain fatty acid production. Cross-system analyses reveal a positive correlation of circulating mucosa-associated invariant T cells, non-classical monocytes and CD4+ effector T cells with systolic blood pressure. Furthermore, regulatory T cells positively correlate with body-mass index and weight. Machine learning analysis of baseline immunome or microbiome data predicts sustained systolic blood pressure response within the fasting group, identifying CD8+ effector T cells, Th17 cells and regulatory T cells or Desulfovibrionaceae, Hydrogenoanaerobacterium, Akkermansia, and Ruminococcaceae as important contributors to the model. Here we report that the high-resolution multi-omics data highlight fasting as a promising non-pharmacological intervention for the treatment of high blood pressure in metabolic syndrome patients.
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9.
The nuclear magnetic resonance metabolic profile: Impact of fasting status.
Smy, L, De Biase, I, Genzen, JR, Yuzyuk, T
Clinical biochemistry. 2021;:85-92
Abstract
INTRODUCTION Measurement of lipoprotein subclass concentration (-c), particle number (-p), and size (-s) by nuclear magnetic resonance (NMR) has gained traction in the clinical laboratory due to associations between smaller lipid particle sizes and atherogenic risk, especially for LDL-p. The standard protocols for lipoprotein measurements by NMR require fasting blood samples; however, patients may not fast properly before sample collection. The study objective was to evaluate the impact of fasting status on the NMR-based lipid profile and to identify key parameters differentiating between fasting and post-meal specimens. METHODS Forty-eight self-reported healthy male and female participants were recruited. Blood was collected after a 12 h fast and 4 h after a high fat meal. Samples were analyzed using the AXINON LipoFIT by NMR assay. The measurements included triglyceride, total cholesterol, IDL-c, and LDL, HDL, VLDL concentration, particle number, and size, as well as glucose, and four amino acids (alanine, valine, leucine and isoleucine). RESULTS As expected, triglycerides increased after the meal (58%, p < 0.0001). Significant changes were also observed for VLDL, LDL, and HDL parameters, and the branched chain amino acids. The ratio of Valine*VLDL-c/LDL-c or Isoleucine*VLDL-c/LDL-c provided equally effective differentiation of fasting and post-meal samples. The ratio cutoffs (79.1 and 23.6 when calculated using valine and isoleucine, respectively) had sensitivities of 86% and specificities of 93-95%. CONCLUSIONS The clinical impact on NMR results from post-meal samples warrants further evaluation. Algorithms to differentiate fasting and post-meal specimens may be useful in identifying suboptimal specimens.
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10.
Impact of prolonged fasting on insulin secretion, insulin action, and hepatic versus whole body insulin secretion disposition indices in healthy young males.
Jørgensen, SW, Hjort, L, Gillberg, L, Justesen, L, Madsbad, S, Brøns, C, Vaag, AA
American journal of physiology. Endocrinology and metabolism. 2021;(2):E281-E290
Abstract
The extent to which reduced insulin secretion during prolonged fasting reflects failure to compensate for whole body insulin resistance or a normal adjustment to potentially increased hepatic insulin action is unknown. We examined the effects of 36- versus 12-h fasting on insulin secretion and whole body versus hepatic insulin action in 13 healthy young males. Hepatic glucose production and insulin action were studied using stable isotopes, whereas whole body insulin action and insulin secretion were studied using an intravenous glucose tolerance test (IVGTT) and minimal modeling. Insulin, glucose, and lipid profiles were subsequently measured during a refeeding meal test. Prolonged fasting caused a minor reduction of first-phase insulin secretion in a context of improved hepatic insulin action, contrasting an increase in whole body insulin resistance. Accordingly, prolonged fasting was associated with opposite-directed effects on hepatic versus whole body insulin secretion disposition indices. Thirty-six-hour fasting compared with 12-h fasting was associated with increased serum insulin levels during the refeeding meal test. In conclusion, reduced insulin secretion during prolonged fasting may represent a healthy response to improved hepatic insulin action. Use of insulin secretion disposition indices without taking organ-specific insulin action into account may lead to erroneous conclusions.NEW & NOTEWORTHY Thirty-six-hour prolonged, compared with 12-h overnight fasting, is associated with slightly reduced first-phase insulin secretion in the face of opposite-directed changes in hepatic versus whole body insulin action in healthy young males. The paradoxical finding of increased hepatic versus decreased whole body insulin secretion disposition indices during prolonged fasting challenges the physiological understanding and validity of insulin secretion disposition indices not taking organ-specific insulin action into account.