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Mechanisms of Glucose Absorption in the Small Intestine in Health and Metabolic Diseases and Their Role in Appetite Regulation.
Gromova, LV, Fetissov, SO, Gruzdkov, AA
Nutrients. 2021;(7)
Abstract
The worldwide prevalence of metabolic diseases such as obesity, metabolic syndrome and type 2 diabetes shows an upward trend in recent decades. A characteristic feature of these diseases is hyperglycemia which can be associated with hyperphagia. Absorption of glucose in the small intestine physiologically contributes to the regulation of blood glucose levels, and hence, appears as a putative target for treatment of hyperglycemia. In fact, recent progress in understanding the molecular and cellular mechanisms of glucose absorption in the gut and its reabsorption in the kidney helped to develop a new strategy of diabetes treatment. Changes in blood glucose levels are also involved in regulation of appetite, suggesting that glucose absorption may be relevant to hyperphagia in metabolic diseases. In this review we discuss the mechanisms of glucose absorption in the small intestine in physiological conditions and their alterations in metabolic diseases as well as their relevance to the regulation of appetite. The key role of SGLT1 transporter in intestinal glucose absorption in both physiological conditions and in diabetes was clearly established. We conclude that although inhibition of small intestinal glucose absorption represents a valuable target for the treatment of hyperglycemia, it is not always suitable for the treatment of hyperphagia. In fact, independent regulation of glucose absorption and appetite requires a more complex approach for the treatment of metabolic diseases.
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Associations of Serum Magnesium With Insulin Resistance and Testosterone in Women With Polycystic Ovary Syndrome.
Luo, X, Cai, WY, Ma, HL, Cong, J, Chang, H, Gao, JS, Shen, WJ, Wang, Y, Yang, XM, Wu, XK
Frontiers in endocrinology. 2021;:683040
Abstract
OBJECTIVE This article aimed to investigate whether serum magnesium is associated with insulin resistance index and testosterone level in women with polycystic ovary syndrome (PCOS). MATERIALS AND METHODS Overall 1000 women with PCOS were enrolled in a randomized controlled trial and a cross-sectional analysis of the association of serum magnesium with glucose metabolism markers and testosterone was performed. Serum magnesium, glucose metabolism markers and testosterone were measured. Insulin resistance was evaluated by homeostatic model assessment of insulin resistance (HOMA-IR) and quantitative insulin-sensitivity check index (QUICKI). Multivariable linear regression and logistic regression models were used to estimate the association between serum magnesium, insulin resistance and testosterone. RESULTS In comparative analyses, women with higher quartile of serum magnesium had significantly lower fasting glucose, HOMA-IR and testosterone. Multiple linear regression showed serum magnesium was independently negatively associated with insulin, glucose, HOMA-IR, testosterone and positively associated with QUICKI (P for trend <0.05) after adjusting confounding covariates. Logistic regression showed serum magnesium in quartile 1 and 2 were independently associated with insulin resistance status (Quartile 1: OR: 2.15, 95%CI: 1.35-3.40, P = 0.001; Quartile 2: OR: 1.90, 95%CI: 1.20-3.02, P = 0.006), while quartile 1 was marginally associated with hyperandrogenemia status (Quartile 1: OR: 1.45, 95%CI: 0.99-2.11, P = 0.055) after adjusting confounding covariates. CONCLUSION The current findings suggest that lower serum magnesium was associated with aggravated insulin resistance and higher testosterone levels among women with PCOS.
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Beneficial effects of whole-body cryotherapy on glucose homeostasis and amino acid profile are associated with a reduced myostatin serum concentration.
Kozłowska, M, Kortas, J, Żychowska, M, Antosiewicz, J, Żuczek, K, Perego, S, Lombardi, G, Ziemann, E
Scientific reports. 2021;(1):7097
Abstract
The study investigated the effect of single and chronic (10 sessions) whole-body cryotherapy (WBC; 3-min, - 110 °C) on amino acid (AA) profile, myostatin, fibroblast growth factor 21 (FGF21), and concentrations of brain-derived neurotrophic factor (BDNF), irisin and adiponectin in relation to glucose homeostasis. Thirty-five, healthy men were randomly split into experimental (young: 28 ± 7 years and middle-aged: 51 ± 3 years) and control groups. Blood samples were taken before and 1 h after the first and last (10th) WBC session. Baseline myostatin correlated significantly with visceral fat area, glucose, insulin, HOMA-IR and irisin (all p < 0.05). The single session of WBC induced temporary changes in AA profile, whereas chronic exposure lowered valine and asparagine concentrations (p < 0.01 and p = 0.01, respectively) compared to the baseline. The chronic WBC reduced fasting glucose (p = 0.04), FGF21 (- 35.8%, p = 0.06) and myostatin (-18.2%, p = 0.06). Still, the effects were age-dependent. The decrease of myostatin was more pronounced in middle-aged participants (p < 0.01). Concentrations of irisin and adiponectin increased in response to chronic WBC, while BDNF level remained unchanged. By improving the adipo-myokine profile, chronic WBC may reduce effectively the risk of the metabolic syndrome associated with hyperinsulinemia, increased levels of valine and asparagine, and muscle atrophy.
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Association of Triglyceride-Glucose Index and Lung Health: A Population-Based Study.
Wu, TD, Fawzy, A, Brigham, E, McCormack, MC, Rosas, I, Villareal, DT, Hanania, NA
Chest. 2021;(3):1026-1034
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Abstract
BACKGROUND Metabolic syndrome and insulin resistance are associated with worsened outcomes of chronic lung disease. The triglyceride-glucose index (TyG), a measure of metabolic dysfunction, is associated with metabolic syndrome and insulin resistance, but its relationship to lung health is unknown. RESEARCH QUESTION What is the relationship of TyG to respiratory symptoms, chronic lung disease, and lung function? STUDY DESIGN AND METHODS This study analyzed data from the National Health and Nutrition Examination Survey from 1999 to 2012. Participants included fasting adults age ≥ 40 years (N = 6,893) with lung function measurements in a subset (n = 3,383). Associations of TyG with respiratory symptoms (cough, phlegm production, wheeze, and exertional dyspnea), chronic lung disease (diagnosed asthma, chronic bronchitis, and emphysema), and lung function (FEV1, FVC, and obstructive or restrictive spirometry pattern) were evaluated, adjusting for sociodemographic variables, comorbidities, and smoking. TyG was compared vs insulin resistance, represented by the homeostatic model assessment of insulin resistance (HOMA-IR), and vs the metabolic syndrome. RESULTS TyG was moderately correlated with HOMA-IR (Spearman ρ = 0.51) and had good discrimination for metabolic syndrome (area under the receiver-operating characteristic curve, 0.80). A one-unit increase in TyG was associated with higher odds of cough (adjusted OR [aOR], 1.28; 95% CI, 1.06-1.54), phlegm production (aOR, 1.20; 95% CI, 1.01-1.43), wheeze (aOR, 1.18; 95% CI, 1.03-1.35), exertional dyspnea (aOR, 1.21; 95% CI, 1.07-1.38), and a diagnosis of chronic bronchitis (aOR, 1.21; 95% CI, 1.02-1.43). TyG was associated with higher relative risk of a restrictive spirometry pattern (adjusted relative risk ratio, 1.45; 95% CI, 1.11-1.90). Many associations were maintained with additional adjustment for HOMA-IR or metabolic syndrome. INTERPRETATION TyG was associated with respiratory symptoms, chronic bronchitis, and a restrictive spirometry pattern. Associations were not fully explained by insulin resistance or metabolic syndrome. TyG is a satisfactory measure of metabolic dysfunction with relevance to pulmonary outcomes. Prospective study to define TyG as a biomarker for impaired lung health is warranted.
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Treatment with Anaerobutyricum soehngenii: a pilot study of safety and dose-response effects on glucose metabolism in human subjects with metabolic syndrome.
Gilijamse, PW, Hartstra, AV, Levin, E, Wortelboer, K, Serlie, MJ, Ackermans, MT, Herrema, H, Nederveen, AJ, Imangaliyev, S, Aalvink, S, et al
NPJ biofilms and microbiomes. 2020;(1):16
Abstract
Dysbiosis of the intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We performed a phase I/II dose-finding and safety study on the effect of oral intake of the anaerobic butyrogenic strain Anaerobutyricum soehngenii on glucose metabolism in 24 subjects with metabolic syndrome. We found that treatment with A. soehngenii was safe and observed a significant correlation between the measured fecal abundance of administered A. soehngenii and improvement in peripheral insulin sensitivity after 4 weeks of treatment. This was accompanied by an altered microbiota composition and a change in bile acid metabolism. Finally, we show that metabolic response upon administration of A. soehngenii (defined as improved insulin sensitivity 4 weeks after A. soehngenii intake) is dependent on microbiota composition at baseline. These data in humans are promising, but additional studies are needed to reproduce our findings and to investigate long-term effects, as well as other modes of delivery.
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Impact of flash glucose monitoring on glycaemic control and quality of life in patients with type 1 diabetes: A 18-month follow-up in real life.
Rouhard, S, Buysschaert, M, Alexopoulou, O, Preumont, V
Diabetes & metabolic syndrome. 2020;(2):65-69
Abstract
We conducted a prospective observational study to evaluate the medium-term impact of the flash glucose monitoring system (FGM) in a type 1 diabetic population. We included 248 patients, switched from conventional blood glucose monitoring (BGM) to FGM. We evaluated glycaemic control at 2-4 (T1) and 5-11 (T2) months after initiation and at the last available visit (T3, 18 ± 4 months). We asked patients to fill in, at T0 and T2, two questionnaires based on the Diabetes Treatment Satisfaction Questionnaire; and on the Hypoglycaemia Fear Survey. Glycaemic control improved, from 8.1 ± 1.3% at T0 to 7.8 ± 1.2% at T1 (p < 0.001) and remained unchanged after. Average number of controls increased from 3.2 ± 1.2 BGM to 7.7 ± 3.9 at T1 (p < 0.001). We observed a modest decrease in daily insulin doses. We evidenced an increase in mild hypoglycaemic events, especially in well-controlled subjects, but no increase of severe events. Satisfaction score improved from 30.5 ± 7.7 points to 38.3 ± 5.1 points (p = 0.018), was correlated with the reduction in and was higher in less controlled patients at inclusion. "Behaviour" score regarding hypoglycaemias decrease from 5.7 ± 4.1 to 4.4 ± 3.6 points (p < 0.001). In conclusion, this 18-months study trial indicates that using the FGM technology in patients with T1D may improve glycaemic control, in real-life conditions, especially in less controlled patients. FGM was associated with an increase of patients' satisfaction regarding treatment. Hypoglycaemic events, however, were not reduced in frequency. Therefore, the need for an educational team and a structure program in the management of this new technology remains mandatory.
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Glucose metabolism in Cushing's syndrome.
Sharma, A, Vella, A
Current opinion in endocrinology, diabetes, and obesity. 2020;(3):140-145
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Abstract
PURPOSE OF REVIEW Impairment of glucose metabolism is commonly encountered in Cushing's syndrome. It is the source of significant morbidity and mortality even after successful treatment of Cushing's. This review is to understand the recent advances in understanding the pathophysiology of diabetes mellitus from excess cortisol. RECENT FINDINGS In-vitro studies have led to significant advancement in understanding the molecular effects of cortisol on glucose metabolism. Some of these findings have been translated with human data. There is marked reduction in insulin action and glucose disposal with a concomitant, insufficient increase in insulin secretion. Cortisol has a varied effect on adipose tissue, with increased lipolysis in subcutaneous adipose tissue in the extremities, and increased lipogenesis in visceral and subcutaneous truncal adipose tissue. SUMMARY Cushing's syndrome results in marked impairment in insulin action and glucose disposal resulting in hyperglycemia. Further studies are required to understand the effect on incretin secretion and action, gastric emptying, and its varied effect on adipose tissue.
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Fructose vs glucose decreased liking/wanting and subsequent intake of high-energy foods in young women.
Ao, H, Li, J, Li, O, Su, M, Gao, X
Nutrition research (New York, N.Y.). 2020;:60-71
Abstract
Recent research on the health impacts of added sugar has prompted the comparison of the effects of its 2 major components: glucose and fructose. Fructose was identified as a risk factor for obesity and metabolic syndrome. However, because of the differences in metabolic responses and responsivity of reward circuitry to palatable food, it is unknown if glucose and fructose induce similar appetite-related responses in humans with varying weights. This study compared the behavioral responses to food in young women of a healthy weight (n = 31) and with excess weight (n = 28). We hypothesized that (1) the inhibitory effect of glucose (vs fructose) on food-related responses would be greater in subjects of a healthy weight than in those with overweight/obesity and (2) subjects with overweight/obesity would exhibit a stronger preference for food than subjects with a healthy weight. After an overnight fast, the subjects ingested a glucose or equienergetic fructose beverage on 2 separate days, respectively. Then, they completed liking and wanting ratings and 2 decision-making tasks followed by ad libitum food intake. The results revealed that fructose reduced both liking and wanting for food in subjects with overweight/obesity and also decreased energy intake in all subjects. Relative to the healthy-weight group, subjects with overweight/obesity preferred the immediate reward. Moreover, only in the healthy-weight group were liking and wanting scores for food positively associated with actual food consumption. Overall, fructose (vs glucose) showed an acute inhibitory effect on appetite-related responses in subjects with excess weight.
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ABCA1 and metabolic syndrome; a review of the ABCA1 role in HDL-VLDL production, insulin-glucose homeostasis, inflammation and obesity.
Babashamsi, MM, Koukhaloo, SZ, Halalkhor, S, Salimi, A, Babashamsi, M
Diabetes & metabolic syndrome. 2019;(2):1529-1534
Abstract
ATP-binding cassette transporter A1 (ABCA1) is an integral cell-membrane protein that mediates the rate-limiting step of high density lipoprotein (HDL) biogenesis and suppression of inflammation by triggering a number of signaling pathways via interacting with an apolipoprotein acceptor. The hepatic ABCA1 is involved in regulation of very low density lipoprotein (VLDL) production by affecting the apolipoprotein B trafficking and lipidation of VLDL particles. This protein is involved in protecting the function of pancreatic β-cells and insulin secretion by cholesterol homeostasis. Adipose tissue lipolysis is associated with ABCA1 activity. This transporter is involved in controlling obesity and insulin sensitivity by regulating triglyceride (TG) lipolysis and influencing on adiponectin, visfatin, leptin, and GLUT4 genes expression. The ABCA1 of skeletal muscle cells play a role in increasing the glucose uptake by enhancing the Akt phosphorylation and transferring GLUT4 to the plasma membrane. Abnormal status of ABCA1-regulated phenotypes is observed in metabolic syndrome. This syndrome is associated with the occurrence of many diseases. This review is a summary of the role of ABCA1 in HDL and VLDL production, homeostasis of insulin and glucose, suppression of inflammation and obesity controlling to provide a better insight into the association of this protein with metabolic syndrome.
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Effects of oligosaccharide-sialic acid (OS) compound on maternal-newborn gut microbiome, glucose metabolism and systematic immunity in pregnancy: protocol for a randomised controlled study.
Wang, S, Peng, R, Qin, S, Liu, Y, Yang, H, Ma, J
BMJ open. 2019;(9):e026583
Abstract
INTRODUCTION The gut microbiota participates in multiple human biological processes, including metabolism and immune responses. During pregnancy, the dynamics of gut microbiota is involved in physiological adaptation. The disturbed profile of microbiome is associated with maternal complications, such as gestational diabetes mellitus (GDM), which further transfers to the offspring and influence their metabolic and immunological functions in the long term. Prebiotics targeting the gut microbiota and modulating metabolic and immune functions have been shown to be effective in non-pregnant populations with metabolic syndrome. Hence, we propose the use of a prebiotic supplement, oligosaccharide-sialic acid (OS) from the first trimester until delivery in pregnant women, can benefit maternal/new-born gut microbiome, glucose metabolism and innate immunity. METHODS AND ANALYSIS In this prospective double-blinded randomised clinical trial, recruited singleton pregnancies will be stratified by body mass index (BMI) and randomly assigned to consume the OS preparation or placebo daily from the first trimester. At seven later time points (before and after recruitment in the first trimester, in the middle and third trimesters, before delivery, at birth and 42 days postpartum), compliance will be evaluated and/or biological samples will be collected. Along with maternal clinical information, questionnaires on lifestyle and infant development will be recorded. The primary outcomes are the effect of OS on the maternal-offspring gut microbiome and GDM incidence. The secondary outcomes are maternal glycolipid biochemical parameters, cytokine profiles, weight gain during pregnancy and infant morbidities, growth and development. The study aims to validate the effects of OS on reducing maternal morbidity within different BMI groups. The multiple dimensional dataset generated from the study includes clinical and lifestyle-related information, various biological markers and associated protective or risk factors for morbidity and prognosis. An extended follow-up through 42 days after birth could further explore the intrauterine influence on the long-term health of offspring. ETHICS AND DISSEMINATION This protocol has been approved by Peking University First Hospital, National Unit of Clinical Trial Ethics Committee (reference number: 164). The results are expected to be published in scientific manuscripts by 2021. TRIAL REGISTRATION NUMBER ChiCTR1800017192.