Search

The post-oral sensing of bitter compounds by a family of bitter taste receptors (TAS2Rs) is suggested to regulate postprandial glycemia in humans. However, reports are inconsistent. This systematic review used meta-analysis to synthesise the impact of bitter compound interventions on the postprandial glycaemic response in humans. Electronic databases (Medline, PubMed, and Web of Science) were systematically searched from inception to April 2024 to identify randomised controlled trials reporting the effect of interventions utilising post-oral bitter compounds vs. placebo on postprandial plasma glucose levels at t = 2 h (2 h-PPG), and area under the curve (AUC) of glucose, insulin, and c-peptide. The random-effect and subgroup analysis were performed to calculate pooled weighted mean differences (WMD), overall and by predefined criteria. Forty-six studies (within 34 articles) were identified; 29 and 17 studies described chronic and acute interventions, respectively. The chronic interventions reduced 2 h-PPG (n = 21, WMD = −0.35 mmol/L, 95%CIs = −0.58, −0.11) but not AUC for glucose or insulin. Subgroup analysis showed the former was particularly evident in individuals with impaired glycemia, interventions longer than three months, or quinine family administration. The acute interventions did not improve the postprandial glycemia response, but subgroup analysis revealed a decrease in AUC-glucose after quinine family administration (n = 4 WMD = −90.40 (nmol × time/L), 95%CIs = −132.70, −48.10). Chronic bitter compound interventions, particularly those from the quinine family, may have therapeutic potential in those with glycemia dysregulation. Acute intervention of the quinine family may also improve postprandial glucose. Given the very low quality of the evidence, further investigations with more rigorous methods are still required. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 15 (GDF15) increases with acute fast in animals, and high GDF15 reduces food intake in rodents. We explored whether GDF15 was altered following intermittent fasting (IF) versus caloric restriction (CR), and associations with energy intake. Females with obesity received all foods at 70% (IF70 and CR70) or 100% of energy requirements for 8 weeks. IF ate 2–9% less than provided on refeeding days, resulting in greater weight losses. GDF15 was increased 5% more in IF70 versus CR70, but not associated with energy intake. This rise in GDF15 is unlikely to explain restriction of energy intake during IF. [ABSTRACT FROM AUTHOR]

Introduction: We have previously shown that hyperbaric oxygen treatment (HBOT) increased insulin sensitivity in men who were obese or overweight, both with and without type 2 diabetes. The aim of this study was to test whether this insulinsensitising effect is seen in hyperbaric air (HA). Methods: Men with type 2 diabetes who were obese or overweight were randomised to two groups: HBOT (n = 13) or HA (n = 11). A hyperinsulinaemic euglycaemic glucose clamp (80 mU·m-2·min-1) was performed at baseline and during hyperbaric intervention. Both groups were compressed to 203 kPa (two atmospheres absolute) for 90 minutes followed by a linear 30-minute decompression. The HBOT group breathed oxygen via a hood while the HA group breathed chamber air. Insulin sensitivity was assessed from the glucose infusion rate (GIR) during the last 30 minutes in the hyperbaric chamber (SS1) and the first 30 minutes after exit (SS2). Data were analysed for within-group effect by paired student t-test and between-group effect by one-way ANOVA. Results: HBOT increased GIR by a mean 26% at SS1 (P = 0.04) and 23% at SS2 (P = 0.018). There was no significant change in GIR during or after HA. A between-group effect was evident for the change in GIR at SS1 in HBOT vs HA (P = 0.036). Conclusions: The pathway by which insulin sensitivity is increased in men with type 2 diabetes requires the high oxygen partial pressures of HBOT and should be further investigated. Insulin sensitivity was not changed in hyperbaric air. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies using a hyperinsulinaemic, euglycaemic glucose clamp have demonstrated an increase in peripheral insulin sensitivity in men with and without Type-2 diabetes mellitus on the third and thirtieth hyperbaric oxygen treatment (HBOT) session. In two studies using different techniques for assessment of insulin sensitivity, we investigated the onset and duration of this insulin-sensitising effect of HBOT. Methods: Men who were obese or overweight but without diabetes were recruited. One study performed a hyperinsulinaemic euglycaemic glucose clamp (80 mU.m-2.min-1) at baseline and during the first HBOT exposure (n = 9) at a pressure of 203 kPa. Data were analysed by paired t-test. The other study assessed insulin sensitivity by a frequently sampled intravenous glucose tolerance test (FSIGT) at three time points: baseline, during the third HBOT and 24-hours post-HBOT (n = 9). Results were analysed by repeated-measures ANOVA. Results: There was a significant 23% increase in insulin sensitivity by clamp measured during the first HBOT exposure. The FSIGT showed no significant changes in insulin sensitivity. Conclusions: The hyperinsulinaemic, euglycaemic glucose clamp demonstrated a significant increase in peripheral insulin sensitivity during a single, 2-hour HBOT session in a group of men who were obese or overweight but without diabetes. As an alternate technique for assessing insulin sensitivity during HBOT, the FSIGT failed to show any changes during the third HBOT and 24-hours later, however modification of the study protocol should be considered. [ABSTRACT FROM AUTHOR]

Intermittent fasting (IF) is proposed as a viable alternative to moderate calorie restriction (CR) for weight loss and metabolic health, but few long term randomized trials have been conducted. This protocol paper describes the rationale and detailed protocol for DIRECT study (D aily versus I ntermittent R estriction of E nergy: C ontrolled T rial to Reduce Diabetes Risk), comparing long term effectiveness of IF versus CR on metabolic health in individuals who are at increased risk of developing type 2 diabetes. Anticipated 260 non-diabetic men and women aged 35–75 years, BMI 25−50 kg/m2 with score ≥12 on the Australian Diabetes Risk (AUSDRISK) calculator will be recruited into this open-label, multi-arm, parallel group sequential randomized controlled trial. Participants will be randomized to one of three groups for 18 months: IF (30% of energy needs on fast days), CR (70% of energy needs daily), or standard care (SC) group. All participants will visit the clinic fortnightly for weight assessments during active intervention phase (6 months), followed by a 12-month follow-up phase. IF and CR groups will receive further diet counselling by dietitian. Two primary outcomes are the changes in glycated haemoglobin (HbA1c) and postprandial glucose area under the curve (AUC) at week 24 post-randomization. Secondary outcomes include changes in weight, body composition via dual-energy X-ray absorptiometry, gastro-intestinal hormones, cardiovascular risk factors, and dietary record by a smartphone-based application. This study will provide substantial evidence as to whether IF is an effective nutrition intervention for glycaemic control in a population at risk of developing type 2 diabetes. [ABSTRACT FROM AUTHOR]

This Perspective for Progress provides a synopsis for the potential of time-restricted eating (TRE) to rescue some of the deleterious effects on circadian biology induced by our modern-day lifestyle. We provide novel insights into the comparative and potential complementary effects of TRE and exercise training on metabolic health. [ABSTRACT FROM AUTHOR]

• Energy restricted intermittent fasting reduces greater body weight and fat mass. • Daily calorie restriction does not alter systemic, fat and muscle inflammation. • Intermittent fasting transiently increases systemic, fat and muscle inflammation. • Adipose tissue macrophages are linked with lipolysis in response to a 24-h fast. This study compared the effects of daily calorie restriction (DR) versus intermittent fasting (IF) on markers of inflammation and extracellular matrix deposition in adipose tissue and skeletal muscle in a controlled feeding trial in women with overweight or obesity. Women (N = 76) were randomised to one of three diets and provided with all foods at 100% (IF100) or 70% (IF70 and DR70) of calculated energy requirements for 8 weeks. IF groups ate breakfast prior to fasting for 24-h on 3 non-consecutive days/week. Weight, body composition, serum non-esterified fatty acids (NEFA), tumour necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-10 (IL-10), M1- and M2-macrophage markers by qPCR and immunohistochemistry in adipose tissue and skeletal muscle were measured following a 12-h overnight fast (fed day, all groups) and a 24-h fast (IF groups only). IF70 resulted in greater weight and fat losses and reductions in serum NEFA versus DR70 and IF100 (P < 0.05) after fed days. Markers of inflammation in serum (TNFα, IL6 and IL10), subcutaneous adipose tissue and skeletal muscle (CD68, CD40 and CD163) were unchanged by DR or IF after fed days. After fasting, NEFA, M1-macrophages (CD40+) in adipose tissue, and M2-macrophages (CD163+) in muscle were increased in IF70 and IF100 (all P < 0.05) and the changes in NEFA and mRNA of pan-macrophage marker CD68 in adipose tissue were positively correlated (r = 0.56, P = 0.002). Unlike caloric restriction, IF transiently elevated markers of macrophage infiltration in adipose tissue and skeletal muscle, possibly in response to marked increases in adipose tissue lipolysis. [ABSTRACT FROM AUTHOR]

Summary Selenoprotein P (SeP) is secreted primarily by the liver and postulated to cause insulin resistance. The aim of this study was to measure plasma SeP in individuals who are lean ( N = 29) or overweight/obese ( N = 34), and examine relationships between circulating SeP, SEPP1 (SeP, plasma 1) expression in subcutaneous adipose tissue, and markers of insulin resistance. SeP was higher in individuals who were overweight/obese ( P < 0.001), and associated with insulin resistance by HOMA-IR and by clamp, but not independently of BMI. SEPP1 mRNA was correlated negatively with BMI, suggesting there may be tissue specific regulation. This study suggests that obesity, rather than insulin resistance, is central to the increase in SeP. [ABSTRACT FROM AUTHOR]

Background Skeletal muscle extracellular matrix (ECM) remodeling has been proposed as a feature of the pathogenic milieu associated with obesity and metabolic dysfunction. The aim of the current study was to examine the timeline of this response and determine whether 3 and 28 days of overfeeding alters markers of ECM turnover. Methods Forty healthy individuals were overfed by 1250 kcal/day for 28 days. Hyperinsulinemic–euglycemic clamps and abdominal fat distribution were performed at baseline and day 28 of overfeeding and skeletal muscle biopsies taken at baseline, day 3 and day 28. mRNA expression (COL1a1, COL3a1, MMP2, MMP9, TIMP1, CD68, Integrin) was performed in 19 subjects that consented to having all biopsies performed and microarray analysis was performed in 8 participants at baseline and day 28. Results In the whole cohort, body weight increased by 0.6 ± 0.1 and 2.7 ± 0.3 kg at days 3 and 28 (both P < 0.001), respectively. Glucose infusion rate during the hyperinsulinemic–euglycemic clamp decreased from 54.8 ± 2.8 at baseline to 50.3 ± 2.5 μmol/min/kg FFM at day 28 of overfeeding (P = 0.03). Muscle COL1 and COL3 and MMP2 mRNA levels were significantly higher 28 days after overfeeding (all P < 0.05), with no significant changes in MMP9, TIMP1, CD68 and integrin expression. Microarray based gene set tests revealed that pathways related to ECM receptor interaction, focal adhesion and adherens junction were differentially altered. Conclusions Skeletal muscle ECM remodeling occurs early in response to over-nutrition with as little as 3% body weight gain. Our findings contribute to the growing evidence linking muscle ECM remodeling and accumulation as another sequela of obesity-related insulin resistance. [ABSTRACT FROM AUTHOR]

Summary Background & aim Western diets rich in animal protein and poor in fruit and vegetables increase the body acid load, a predictor of type 2 diabetes risk. The relationships between dietary acid load, mild metabolic acidosis and insulin resistance remain unclear. The objective of this study was to assess the association between dietary acid load, body acid/base markers and peripheral insulin resistance at baseline and following a short-term overfeeding intervention in healthy individuals. Methods In a cross-sectional study of 104 men and women, insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp. Plasma lactate, a marker of metabolic acidosis, was assessed and acid load scores (potential renal acid load, PRAL and net endogenous acid production, NEAP) derived from diet diaries. The cohort was grouped into lean and overweight/obese and the latter further classified as insulin-sensitive (Ob sen ) and insulin-resistant (Ob res ) based on hyperinsulinemic-euglycemic clamp glucose infusion rate (GIR, top tertile vs. bottom 2 tertiles). A subset of 40 individuals participated in an overfeeding intervention (+1250 kcal/day) for 28 days and studies repeated. Results Ob sen and Ob res were matched for adiposity (BMI and fat mass, both P = 1). Fasting plasma lactate was higher in Ob res (0.78 [0.63–1.14] mmol/L) compared with both lean (0.71 [0.44–0.90] mmol/L, P = 0.02) and Ob sen (0.67 [0.56–0.79] mmol/L, P = 0.04) and not different between lean and Ob sen (P = 0.9). Overfeeding was characterized by an increase in dietary acid load scores PRAL (P = 0.003) and NEAP (P = 0.05), a reduction in GIR necessary to maintain euglycemia (P = 0.03) and an increase in fasting plasma lactate (P = 0.02). The change in lactate was inversely associated with the change in GIR (r = −0.36, P = 0.03). Conclusions Mild metabolic acidosis, measured by plasma lactate, aligns with insulin resistance independent of obesity and is induced by short-term increases in energy and dietary acid load in healthy humans. Further studies are required to determine whether buffering mild metabolic acidosis improves insulin resistance and reduces diabetes risk. [ABSTRACT FROM AUTHOR]

Summary: Context: Anorexia nervosa (AN) is an eating disorder characterized by self-induced energy deficit and low body weight with major consequences for most organ systems and a tendency towards self-perpetuation. Objectives: To compare metabolic responses to glucose and exercise in women hospitalized with AN (n =10) before and after 6-weeks weight gain program and in lean healthy weight women (BMI<22kg/m2) (n =7). Main outcomes: Weight, body composition, indirect calorimetry, and response of serum insulin, glucose, adiponectin and leptin to oral glucose (75g) and to 30-min of cycling at 50rpm. Results: Patients with AN had similar lean mass to controls, but had significantly less body fat. Adiponectin was 43% higher (p <0.01) and leptin 47% lower in AN subjects versus controls (p =0.04). In response to moderate exercise, fasting glucose increased in AN (p <0.05), but was unchanged in controls. After glucose ingestion, a trend towards a greater increase in diet-induced thermogenesis was also observed in patients with AN (p =0.07). Despite a further 6 weeks as in patients, weight was not significantly changed in AN. Similarly, glucose, insulin, leptin or adiponectin were not altered. Conclusions: AN patients appear metabolically healthy under resting conditions, but their responses to physiological stressors differed from those of controls. Potential impediments to weight gain should be further investigated to define mechanisms with a view to improving the effectiveness of nutritional management. [Copyright &y& Elsevier]

Purpose Of Review: The focus of this review is on current research involving long-term calorie restriction and the resulting changes observed in possible biomarkers of aging. Special emphasis will be given to the basic and clinical science studies which are currently investigating the effects of controlled, high-quality energy-restricted diets on both biomarkers of longevity and on the development of chronic diseases related to age and obesity in humans.Recent Findings: Prolonged calorie restriction has been shown to extend both the median and maximal lifespan in a variety of lower species such as yeast, worms, fish, rats, and mice. Mechanisms of this lifespan extension via calorie restriction are not fully elucidated, but possibly involve significant alterations in energy metabolism, oxidative damage, insulin sensitivity, and functional changes in both the neuroendocrine and sympathetic nervous systems. Ongoing studies of prolonged energy restriction in humans are now making it possible to analyze changes in these aging biomarkers to unravel some of the mechanisms of its antiaging phenomenon.Summary: With the incremental expansion of research endeavors in the area of energy or calorie restriction, data on the effects of calorie restriction in animal models and humans are becoming more accessible. Detailed analyses from controlled human trials involving long-term calorie restriction will allow investigators to link observed alterations in body composition down to changes in molecular pathways and gene expression, with their possible effects on the biomarkers of aging. [ABSTRACT FROM AUTHOR]