Circulating irisin in nonalcoholic fatty liver disease: an updated meta-analysis

Introduction: Exogenous administration of recombinant irisin may reverse hepatic steatosis and steatohepatitis. However, it remains controversial as to whether nonalcoholic fatty liver disease (NAFLD) shows reduced circulating (serum/plasma) irisin levels. A meta-analysis was conducted to address this issue. Material and methods: A literature search of databases was performed up to June 2021. Observational studies that reported circulating irisin in NAFLD ascertained by any methods (e.g. ultrasonography or magnetic resonance) and compared with any controls were eligible for inclusion. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were obtained using a random-effects meta-analysis model. Results: Eleven studies enrolling 1277 NAFLD cases and 944 non-NAFLD controls were included. The approaches used for NAFLD ascertainment included ultrasonography (4 studies), magnetic resonance (3 studies), and liver biopsy (5 studies). Meta-analysis showed that circulating irisin in NAFLD was comparable to any non-NAFLD controls (10 studies with 11 datasets; SMD –0.09, 95% CI: –0.48 to 0.29), including the body mass index (BMI)-matched and lean controls (both p ≥ 0.80). Restricting studies to NAFLD ascertained by magnetic resonance or liver biopsy rather than ultrasonography showed that serum irisin was reduced in NAFLD (5 studies, SMD –0.63, 95% CI: –1.14 to –0.13). Meta-analysis also suggested that circulating irisin did not differ between mild and moderate-to-severe NAFLD (7 studies; SMD 0.02, 95% CI: –0.25 to 0.30), and this association was not significantly moderated by study location (Europe versus Asia). Conclusions: Circulating irisin in NAFLD did not differ from any non-NAFLD controls and was unlikely to be affected by disease severity or racial-ethnic difference

Muscle strength and prediabetes progression and regression in middle‐aged and older adults: a prospective cohort study

Background: Prediabetes progression is associated with increased mortality while its regression decreases it. It is unclear whether muscle strength is related to prediabetes progression or regression. This study investigated the associations of muscle strength, assessed by grip strength and chair‐rising time, with prediabetes progression and regression based on the China Health and Retirement Longitudinal Study (CHARLS) enrolling middle‐aged and older adults. Methods: We included 2623 participants with prediabetes from CHARLS, who were followed up 4 years later with blood samples collected for measuring fasting plasma glucose and haemoglobin A1c. Grip strength (normalized by body weight) and chair‐rising time were assessed at baseline and categorized into tertiles (low, middle, and high groups). Prediabetes at baseline and follow‐up was defined primarily using the American Diabetes Association (ADA) criteria and secondarily using the World Health Organization (WHO) and International Expert Committee (IEC) criteria. Multinomial logistic regression analysis was applied to obtain the odds ratios (ORs) and 95% confidence intervals (CIs). Results: The mean age of included participants was 59.0 ± 8.6 years, and 46.6% of them were males. During follow‐up, 1646 participants remained as prediabetes, 379 progressed to diabetes, and 598 regressed to normoglycaemia based on ADA criteria. Participants who progressed to diabetes had lower normalized grip strength than those who remained as prediabetes (0.49 ± 0.15 vs. 0.53 ± 0.15, P < 0.001), but participants who regressed to normoglycaemia showed the opposite (0.55 ± 0.16 vs. 0.53 ± 0.15, P = 0.003). However, chair‐rising time was comparable across different groups (P overall = 0.17). Compared with participants in low normalized grip strength or high chair‐rising time group, those in high normalized grip strength or low chair‐rising time group had decreased odds of progression to diabetes (OR 0.62, 95% CI 0.44 to 0.87; and OR 0.69, 95% CI 0.51 to 0.93, respectively) after multivariable adjustment. However, both were unrelated to the odds of regression to normoglycaemia (OR 0.94, 95% CI 0.71 to 1.25; and OR 0.84, 95% CI 0.65 to 1.07, respectively). These outcomes remained generally comparable when prediabetes was defined by WHO or IEC criteria. Higher normalized grip strength but not lower chair‐rising time was prospectively associated with lower blood pressure, better glycaemic condition, and lower inflammation (all P ≤ 0.04). Conclusions: High muscle strength is associated with reduced odds of progression to diabetes but does not predict regression to normoglycaemia in prediabetes. Future studies are warranted to assess whether increases in muscle strength promote prediabetes regression

The effects of a whey protein and guar gum-containing preload on gastric emptying, glycaemia, small intestinal absorption and blood pressure in healthy older subjects

A whey protein/guar gum preload reduces postprandial glycaemia in type 2 diabetes through slowing gastric emptying. However, gastric emptying has previously been assessed using a stable isotope breath test technique, which cannot discriminate between slowing of gastric emptying and small intestinal absorption. This preload also may be useful in the management of postprandial hypotension. We evaluated the effects of a whey protein/guar preload on gastric emptying, glucose absorption, glycaemic/insulinaemic and blood pressure (BP) responses to an oral glucose load. Eighteen healthy older participants underwent measurements of gastric emptying (scintigraphy), plasma glucose and insulin, glucose absorption, superior mesenteric artery (SMA) flow, BP and heart rate (HR) after ingesting a 50 g glucose drink, with or without the preload. The preload reduced plasma glucose (p = 0.02) and serum 3-O-methylglucose (3-OMG) (p = 0.003), and increased plasma insulin (p = 0.03). There was no difference in gastric emptying or BP between the two days. The reduction in plasma glucose on the preload day was related to the reduction in glucose absorption (r = 0.71, p = 0.002). In conclusion, the glucose-lowering effect of the preload may relate to delayed small intestinal glucose absorption and insulin stimulation, rather than slowing of gastric emptying.publishedVersio

Prediabetes Progression and Regression on Objectively- Measured Physical Function: A Prospective Cohort Study

Prediabetes leads to declines in physical function in older adults, but the impact of prediabetes progression or regression on physical function is unknown. This study assessed this longitudinal association, with physical function objectivelymeasured by grip strength, walking speed, and standing balance, based on the Health and Retirement Study enrolling United States adults aged >50 years. Participants with prediabetes were followed-up for 4-year to ascertain prediabetes status alteration (maintained, regressed, or progressed), and another 4-year to assess their impacts on physical function. Weak grip strength was defined as <26 kg for men and <16 kg for women, slow walking speed was as <0.8 m/sec, and poor standing balance was as an uncompleted fulltandem standing testing. Logistic and linear regression analyses were performed. Of the included 1,511 participants with prediabetes, 700 maintained as prediabetes, 306 progressed to diabetes, and 505 regressed to normoglycemia over 4 years. Grip strength and walking speed were declined from baseline during the 4-year followup, regardless of prediabetes status alteration. Compared with prediabetes maintenance, prediabetes progression increased the odds of developing weak grip strength by 89% (95% confidence interval [CI], 0.04 to 2.44) and exhibited larger declines in grip strength by 0.85 kg (95% CI, -1.65 to -0.04). However, prediabetes progression was not related to impairments in walking speed or standing balance. Prediabetes regression also did not affect any measures of physical function. Prediabetes progression accelerates grip strength decline in aging population, while prediabetes regression may not prevent physical function decline due to aging

Gut Mechanisms Linking Intestinal Sweet Sensing to Glycemic Control

Copyright © 2018 Kreuch, Keating, Wu, Horowitz, Rayner and Young. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Sensing nutrients within the gastrointestinal tract engages the enteroendocrine cell system to signal within the mucosa, to intrinsic and extrinsic nerve pathways, and the circulation. This signaling provides powerful feedback from the intestine to slow the rate of gastric emptying, limit postprandial glycemic excursions, and induce satiation. This review focuses on the intestinal sensing of sweet stimuli (including low-calorie sweeteners), which engage similar G-protein-coupled receptors (GPCRs) to the sweet taste receptors (STRs) of the tongue. It explores the enteroendocrine cell signals deployed upon STR activation that act within and outside the gastrointestinal tract, with a focus on the role of this distinctive pathway in regulating glucose transport function via absorptive enterocytes, and the associated impact on postprandial glycemic responses in animals and humans. The emerging role of diet, including low-calorie sweeteners, in modulating the composition of the gut microbiome and how this may impact glycemic responses of the host, is also discussed, as is recent evidence of a causal role of diet-induced dysbiosis in influencing the gut-brain axis to alter gastric emptying and insulin release. Full knowledge of intestinal STR signaling in humans, and its capacity to engage host and/or microbiome mechanisms that modify glycemic control, holds the potential for improved prevention and management of type 2 diabetes

Gut Mechanisms Linking Intestinal Sweet Sensing to Glycemic Control

Sensing nutrients within the gastrointestinal tract engages the enteroendocrine cell system to signal within the mucosa, to intrinsic and extrinsic nerve pathways, and the circulation. This signaling provides powerful feedback from the intestine to slow the rate of gastric emptying, limit postprandial glycemic excursions, and induce satiation. This review focuses on the intestinal sensing of sweet stimuli (including low-calorie sweeteners), which engage similar G-protein-coupled receptors (GPCRs) to the sweet taste receptors (STRs) of the tongue. It explores the enteroendocrine cell signals deployed upon STR activation that act within and outside the gastrointestinal tract, with a focus on the role of this distinctive pathway in regulating glucose transport function via absorptive enterocytes, and the associated impact on postprandial glycemic responses in animals and humans. The emerging role of diet, including low-calorie sweeteners, in modulating the composition of the gut microbiome and how this may impact glycemic responses of the host, is also discussed, as is recent evidence of a causal role of diet-induced dysbiosis in influencing the gut-brain axis to alter gastric emptying and insulin release. Full knowledge of intestinal STR signaling in humans, and its capacity to engage host and/or microbiome mechanisms that modify glycemic control, holds the potential for improved prevention and management of type 2 diabetes

A Protein Preload Enhances the Glucose-Lowering Efficacy of Vildagliptin in Type 2 Diabetes

Ranking and judging political misbehaviours: the benefits of focus group approach and of quantitative method for analysing qualitative dataQualitative researches based on focus group offer valuable insights in analyzing moral conflicts. This article suggests they also prove very useful to explore citizens’ perceptions of political misbehaviours. Moral expectations regarding politicians’ behaviours are ambiguous judgements because of the various criteria that underpin their perceptions of politics. This article is based on the analysis of eight different, socio-culturally homogeneous focus groups. Collected arguments are analysed through a quantitative method examining discursive contents. The existence of a common grid for ranking political misbehaviours is emphasized. The moderating effects of collective discussion on judgements are also outlined. The article emphasizes variations in judgments, differentiating groups according to their social and occupational experiences. At last, different “repertoires of arguments” are identified relying on different principles.Les enjeux de probité publique se prêtent bien aux recherches qualitatives menées par focus group, habituellement utilisées dans l’exploration des conflits moraux et normatifs. La démarche est ici mobilisée pour explorer l’ambiguïté des jugements portés par les citoyens sur les pratiques et transgressions des élus. Elle repose sur huit groupes socio-culturellement différenciés et sur une exploitation originale à partir d’une méthode de quantification du contenu des discours recueillis. L’article montre l’existence d’une échelle homogène de qualification et de classification des pratiques politiques qui graduent les jugements de réprobation. La discussion collective favorise l’expression de formes de modération dans les jugements. L’exploitation pointe des différences liées aux caractéristiques sociales des groupes. Elle identifie des « répertoires argumentatifs », mobilisant des principes de jugement divergents

Efficacy of Co-administration of Liuwei Dihuang Pills and Ginkgo Biloba Tablets on Albuminuria in Type 2 Diabetes: A 24-Month, Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial

Purpose: We investigated the effects of Traditional Chinese Medicine (TCM) on the occurrence and progression of albuminuria in patients with type 2 diabetes.Methods: In this randomized, double-blind, multicenter, controlled trial, we enrolled 600 type 2 diabetes without diabetic nephropathy (DN) or with early-stage DN. Patients were randomly assigned (1:1) to receive Liuwei Dihuang Pills (LWDH) (1.5 g daily) and Ginkgo biloba Tablets (24 mg daily) orally or matching placebos for 24 months. The primary endpoint was the change in urinary albumin/creatinine ratio (UACR) from baseline to 24 months.Results: There were 431 patients having UACR data at baseline and 24 months following-up in both groups. Changes of UACR from baseline to follow-up were not affected in both groups: −1.61(−10.24, 7.17) mg/g in the TCM group and −0.73(−7.47, 6.75) mg/g in the control group. For patients with UACR ≥30 mg/g at baseline, LWDH and Ginkgo biloba significantly reduced the UACR value at 24 months [46.21(34.96, 58.96) vs. 20.78(9.62, 38.85), P &lt; 0.05]. Moreover, the change of UACR from baseline to follow-up in the TCM group was significant higher than that in the control group [−25.50(−42.30, −9.56] vs. −20.61(−36.79, 4.31), P &lt; 0.05].Conclusion: LWDH and Ginkgo biloba may attenuate deterioration of albuminuria in type 2 diabetes patients. These results suggest that TCM is a promising option of renoprotective agents for early stage of DN.Trial registration: The study was registered in the Chinese Clinical Trial Registry. (no. ChiCTR-TRC-07000037, chictr.org

Gastrointestinal motor and sensory function, and hormone secretion: implications for postprandial blood glucose regulation in type 2 diabetes mellitus.

This thesis focuses on the role of gastrointestinal motor and sensory function, and gut hormone secretion, in postprandial blood glucose regulation in health and type 2 diabetes. The key themes relate to: 1) evaluation of the effects of potential dietary and/or pharmacological strategies on gastric emptying, secretion of ‘incretin’ hormones (i.e. glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)), and postprandial glycaemia, 2) effects of intraluminal bile acids on GLP-1 secretion and blood glucose homeostasis, and 3) the role of the sweet taste sensing pathway in gastrointestinal motor, secretory, and absorptive function in health and type 2 diabetes. Macronutrient ‘preloads’ taken before a meal can stimulate endogenous GIP from the proximal gut, and GLP-1 from the distal gut, slow gastric emptying, and reduce postprandial glycaemic excursions, but entail additional energy intake. The study reported in Chapter 4 evaluates the effects of 1) 3-Omethylglucose (a non-metabolised substrate of sodium glucose co-transporter-1) and 2) a mixture of poorly absorbed tagatose and isomalt, when given as preloads in healthy humans. Since the incretin hormones are rapidly degraded by the enzyme, dipeptidyl peptidase 4 (DPP-4), the study in Chapter 5 evaluates whether the effects of a D-xylose preload (a poorly absorbed, low-energy pentose) could be further optimised by concurrent DPP-4 inhibition with sitagliptin, in patients with type 2 diabetes. It was recently established that a small dose of lauric acid, delivered to a long segment of distal gut via enteric-coated pellets, can stimulate GLP-1 and attenuate postprandial glycaemia in well controlled type 2 patients. The study reported in Chapter 6 evaluates the glucose-lowering effect of these pellets in less well-controlled type 2 patients, when given concurrently with sitagliptin. The effects of DPP-4 inhibition on the incretin hormone, glycaemic, and gastrointestinal motor responses to intraluminal glucose have not been well characterised in obesity and type 2 diabetes. It has been suggested that metformin has the capacity to augment plasma GLP-1 concentrations, and may synergise with DPP-4 inhibitors to improve glycaemia in type 2 diabetes. The study described in Chapter 7 examines the effects of sitagliptin on glycaemia and antropyloroduodenal motility in response to intraduodenal glucose infusion in health, obesity, and type 2 diabetes treated with or without metformin. It is emerging that bile acids function as important signalling molecules, and are essential in blood glucose regulation. In animal models, intraluminal bile acids have been shown to stimulate GLP-1 and peptide YY (PYY) via activation of theTGR5 receptor. The study reported in Chapter 8 evaluates the effects of rectally administered taurocholic acid (TCA) on the release of GLP-1 and PYY in healthy humans. In Chapter 9, the effects of intrajejunal TCA on blood glucose, GLP-1 and insulin responses to intrajejunal glucose infusion are evaluated. The mechanisms underlying nutrient detection in the small intestine and consequent stimulation of incretin hormone release are poorly understood. Emerging data support the involvement of intestinal sweet taste receptors (STR) in carbohydrate sensing. In rodents, intestinal STR transcript and protein levels are rapidly down-regulated upon acute luminal exposure to glucose or artificial sweeteners. In Chapter 10, the capacity for the non-caloric artificial sweeteners, sucralose and acesulfame potassium, to stimulate GLP-1 release, slow gastric emptying, and modify postprandial glycaemia when given with oral glucose is evaluated. In Chapter 11, the modulation of duodenal STR expression in response to acute changes in luminal and systemic glucose exposure in healthy humans is assessed, and comparison is made to patients with type 2 diabetes. Furthermore, relationships between STR expression, glucose absorption and gut hormone secretion are examined in both groups.Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 201

Enteroendocrine Hormone Secretion and Metabolic Control: Importance of the Region of the Gut Stimulation

It is now widely appreciated that gastrointestinal function is central to the regulation of metabolic homeostasis. Following meal ingestion, the delivery of nutrients from the stomach into the small intestine (i.e., gastric emptying) is tightly controlled to optimise their subsequent digestion and absorption. The complex interaction of intraluminal nutrients (and other bioactive compounds, such as bile acids) with the small and large intestine induces the release of an array of gastrointestinal hormones from specialised enteroendocrine cells (EECs) distributed in various regions of the gut, which in turn to regulate gastric emptying, appetite and postprandial glucose metabolism. Stimulation of gastrointestinal hormone secretion, therefore, represents a promising strategy for the management of metabolic disorders, particularly obesity and type 2 diabetes mellitus (T2DM). That EECs are distributed distinctively between the proximal and distal gut suggests that the region of the gut exposed to intraluminal stimuli is of major relevance to the secretion profile of gastrointestinal hormones and associated metabolic responses. This review discusses the process of intestinal digestion and absorption and their impacts on the release of gastrointestinal hormones and the regulation of postprandial metabolism, with an emphasis on the differences between the proximal and distal gut, and implications for the management of obesity and T2DM