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Nature Sep 2023Insulin resistance is the primary pathophysiology underlying metabolic syndrome and type 2 diabetes. Previous metagenomic studies have described the characteristics of...
Insulin resistance is the primary pathophysiology underlying metabolic syndrome and type 2 diabetes. Previous metagenomic studies have described the characteristics of gut microbiota and their roles in metabolizing major nutrients in insulin resistance. In particular, carbohydrate metabolism of commensals has been proposed to contribute up to 10% of the host's overall energy extraction, thereby playing a role in the pathogenesis of obesity and prediabetes. Nevertheless, the underlying mechanism remains unclear. Here we investigate this relationship using a comprehensive multi-omics strategy in humans. We combine unbiased faecal metabolomics with metagenomics, host metabolomics and transcriptomics data to profile the involvement of the microbiome in insulin resistance. These data reveal that faecal carbohydrates, particularly host-accessible monosaccharides, are increased in individuals with insulin resistance and are associated with microbial carbohydrate metabolisms and host inflammatory cytokines. We identify gut bacteria associated with insulin resistance and insulin sensitivity that show a distinct pattern of carbohydrate metabolism, and demonstrate that insulin-sensitivity-associated bacteria ameliorate host phenotypes of insulin resistance in a mouse model. Our study, which provides a comprehensive view of the host-microorganism relationships in insulin resistance, reveals the impact of carbohydrate metabolism by microbiota, suggesting a potential therapeutic target for ameliorating insulin resistance.
Topics: Animals; Humans; Mice; Carbohydrate Metabolism; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Insulin Resistance; Monosaccharides; Insulin; Metabolic Syndrome; Feces; Metabolomics
PubMed: 37648852
DOI: 10.1038/s41586-023-06466-x -
Nutrients Jan 2024The low FODMAP (fermentable oligosaccharide, disaccharide, monosaccharide, and polyol) diet is a beneficial therapeutic approach for patients with irritable bowel... (Review)
Review
The low FODMAP (fermentable oligosaccharide, disaccharide, monosaccharide, and polyol) diet is a beneficial therapeutic approach for patients with irritable bowel syndrome (IBS). However, how the low FODMAP diet works is still not completely understood. These mechanisms encompass not only traditionally known factors such as luminal distension induced by gas and water but also recent evidence on the role of FOMAPs in the modulation of visceral hypersensitivity, increases in intestinal permeability, the induction of microbiota changes, and the production of short-chain fatty acids (SCFAs), as well as metabolomics and alterations in motility. Although most of the supporting evidence is of low quality, recent trials have confirmed its effectiveness, even though the majority of the evidence pertains only to the restriction phase and its effectiveness in relieving abdominal bloating and pain. This review examines potential pathophysiological mechanisms and provides an overview of the existing evidence on the effectiveness of the low FODMAP diet across various IBS subtypes. Key considerations for its use include the challenges and disadvantages associated with its practical implementation, including the need for professional guidance, variations in individual responses, concerns related to microbiota, nutritional deficiencies, the development of constipation, the necessity of excluding an eating disorder before commencing the diet, and the scarcity of long-term data. Despite its recognized efficacy in symptom management, acknowledging these limitations becomes imperative for a nuanced comprehension of the role of a low FODMAP diet in managing IBS. By investigating its potential mechanisms and evidence across IBS subtypes and addressing emerging modulations alongside limitations, this review aims to serve as a valuable resource for healthcare practitioners, researchers, and patients navigating the intricate landscape of IBS.
Topics: Humans; Irritable Bowel Syndrome; FODMAP Diet; Fermentation; Disaccharides; Oligosaccharides; Diet; Monosaccharides; Diet, Carbohydrate-Restricted
PubMed: 38337655
DOI: 10.3390/nu16030370 -
The Journal of Family Practice Jul 2023After reading this review article, participants should be able to: Prepare the practice for continuous glucose monitoring (CGM). Understand options available to the... (Review)
Review
After reading this review article, participants should be able to: Prepare the practice for continuous glucose monitoring (CGM). Understand options available to the practice for professional (practice-owned) and personal (patient-owned) CGM. Locate and interpret CGM data, using the ambulatory glucose profile (AGP), to determine if the patient is achieving targets established by the International Consensus on Time in Range. Modify a patient's treatment plan based on CGM data to improve patient outcomes.
Topics: Humans; Blood Glucose; Blood Glucose Self-Monitoring; Glucose; Patient Care Planning; Diabetes Mellitus, Type 1
PubMed: 37549413
DOI: 10.12788/jfp.0568 -
Cardiovascular Diabetology Nov 2023The triglyceride glucose-body mass (TyG-BMI) index is acknowledged as both a reliable indicator of the risk of cardiovascular disease and an accurate surrogate biomarker...
BACKGROUND
The triglyceride glucose-body mass (TyG-BMI) index is acknowledged as both a reliable indicator of the risk of cardiovascular disease and an accurate surrogate biomarker for evaluating insulin resistance (IR). The importance of the TyG-BMI index among people with heart failure (HF), however, requires more investigation. The objective of this study was to inquire about the relationship between HF patients' TyG-BMI index and their risk of 360-day mortality.
METHODS
The Medical Information Mart for Intensive Care (MIMIC-IV) database provided the study's patient data, which were divided into quartiles according to their TyG-BMI index. The endpoint was mortality from all causes within 360 days. Kaplan-Meier analysis was used to compare this primary endpoint amongst the four groups indicated above. The association between the TyG-BMI index and the endpoint was investigated using restricted cubic splines and Cox proportional hazards analysis.
RESULTS
The study enrolled a total of 423 patients with HF (59.2% male), of whom 70 patients (16.9%) died within 360 days. Patients with higher TyG-BMI indexes had significantly lower mortality risks, according to the Kaplan-Meier analysis (log-rank P = 0.003). Furthermore, the restricted cubic spline analysis illustrated a decrease in the risk of all-cause mortality with an increasing TyG-BMI index. Additionally, multivariable Cox proportional hazards analyses showed that the risk of 360-day death from all causes was considerably higher in the lowest quartile of TyG-BMI. In comparison to the lowest TyG-BMI group, the fully adjusted Cox model yielded a hazard ratio (HR) of 0.24 (95% CI: 0.10, 0.59; p = 0.002) for 360-day mortality.
CONCLUSIONS
In patients diagnosed with HF, a lower TyG-BMI index is strongly related to a higher risk of 360-day mortality. This index can be employed to categorize the risk levels of patients with HF and predict their one-year all-cause mortality .
Topics: Humans; Male; Female; Retrospective Studies; Heart Failure; Cardiovascular Diseases; Glucose; Triglycerides; Blood Glucose; Risk Factors; Biomarkers
PubMed: 37940979
DOI: 10.1186/s12933-023-02047-4 -
Current Diabetes Reports Jul 2023Inpatient glucose data analysis, or glucometrics, has developed alongside the growing emphasis on glycemic control in the hospital. Shortcomings in the initial... (Review)
Review
PURPOSE OF REVIEW
Inpatient glucose data analysis, or glucometrics, has developed alongside the growing emphasis on glycemic control in the hospital. Shortcomings in the initial capabilities for glucometrics have pushed advancements in defining meaningful units of measurement and methods for capturing glucose data. This review addresses the growth in glucometrics and ends with its promising new state.
RECENT FINDINGS
Standardization, allowing for benchmarking and purposeful comparison, has been a goal of the field. The National Quality Foundation glycemic measures and recently enacted Center for Medicare and Medicaid Services (CMS) electronic quality measures for hypo- and hyperglycemia have allowed for improved integration and consistency. Prior systems have culminated in an upcoming measure from the Center for Disease Control and Prevention's National Healthcare Safety Network. It is poised to create a new gold standard for glucometrics by expanding and refining the CMS metrics, which should empower both local improvement and benchmarking as the program matures.
Topics: Aged; United States; Humans; Blood Glucose; Medicare; Hyperglycemia; Hospitals; Glucose
PubMed: 37052789
DOI: 10.1007/s11892-023-01507-1 -
Journal of Diabetes Science and... Sep 2023A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM...
BACKGROUND
A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data.
METHODS
We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation.
RESULTS
The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals.
CONCLUSION
The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.
Topics: Adult; Humans; Blood Glucose; Blood Glucose Self-Monitoring; Hypoglycemia; Hyperglycemia; Glucose
PubMed: 35348391
DOI: 10.1177/19322968221085273 -
Cardiovascular Diabetology Nov 2023The Triglyceride-glucose (TyG) index, a novel indicator of insulin resistance, has been associated with mortality from coronary artery diseases, ischemic stroke, and...
OBJECTIVE
The Triglyceride-glucose (TyG) index, a novel indicator of insulin resistance, has been associated with mortality from coronary artery diseases, ischemic stroke, and heart failure. In recent years, much emphasis has been placed on the relationship between the TyG index and mortality in the general population. However, the impact of age on the association between TyG and all-cause and cardiovascular mortality remains controversial. This study investigated the link between the TyG index and all-cause and cardiovascular mortality, emphasizing differences between older and non-older populations.
METHODS
Data from the National Health and Nutrition Examination Survey (2009-2018), encompassing 20,194 participants, were analyzed. The baseline TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Multivariate Cox proportional hazards regression models with restricted cubic splines and trend tests were employed to explore the association between the TyG index and all-cause and cardiovascular mortality, with emphasis on age-specific analysis. Subgroup analysis was conducted to examine whether the TyG index's association with mortality varied across different subgroups. Additionally, receiver operating characteristic curves were used to compare the predictive ability of the TyG index with the homeostasis model assessment of insulin resistance (HOMA-IR) for all-cause and cardiovascular mortality.
RESULTS
Over a median follow-up period of 105 months, all-cause mortality accounted for 13.345% of cases, and cardiovascular mortality accounted for 3.387%. Kaplan-Meier curves showed a significant increase in all-cause and cardiovascular mortality with higher TyG index values (both P for log-rank test < 0.001). However, during Cox proportional hazards regression analysis, no linear trend was observed between the TyG index and all-cause or cardiovascular mortality after adjusting for confounding factors (all-cause mortality: P for trend = 0.424; cardiovascular mortality: P for trend = 0.481). Restricted cubic splines revealed a non-linear association between the baseline TyG index and all-cause and cardiovascular mortality in the overall population (all-cause mortality: Non-linear P = 0.003; cardiovascular mortality: Non-linear P = 0.034). The effect of the TyG index was consistent across most subgroups in terms of all-cause and cardiovascular mortality, with no significant interaction with randomized factors (all-cause mortality: P for interaction = 0.077-0.940, cardiovascular mortality: P for interaction = 0.173-0.987), except for the age subgroup (all-cause mortality: P for interaction < 0.001, cardiovascular mortality: P for interaction < 0.001). Further age-specific analysis revealed that the association between the TyG index and all-cause and cardiovascular mortality remained significant in patients aged < 65 but not in those aged ≥ 65. Interestingly, a non-linear association was observed between the TyG index and all-cause mortality in individuals aged < 65 (Non-linear P = 0.011), while a linear relationship was observed with cardiovascular mortality, showing an upward trend (Non-linear P = 0.742, P for trend = 0.010). Further stratification according to age yielded similar results only in patients aged 45-64 (all-cause mortality: Non-linear P = 0.001 and cardiovascular mortality: Non-linear P = 0.902, P for trend = 0.015). Compared to HOMA-IR, the TyG index demonstrated superior predictive performance for all-cause and cardiovascular mortality (all-cause mortality: 0.620 vs. 0.524, P < 0.001; cardiovascular mortality: 0.623 vs. 0.537, P < 0.001).
CONCLUSIONS
This study established a significant association between the TyG index and all-cause and cardiovascular mortality in the general population, particularly among individuals aged < 65. Notably, a non-linear association with all-cause mortality was observed in those aged < 65, while a linear relationship with cardiovascular mortality was found.
Topics: Humans; Insulin Resistance; Nutrition Surveys; Heart Failure; Glucose; Triglycerides; Blood Glucose; Biomarkers; Risk Factors
PubMed: 37993902
DOI: 10.1186/s12933-023-02054-5 -
The Lancet. Gastroenterology &... Jun 2024Dietary advice and medical treatments are recommended to patients with irritable bowel syndrome (IBS). Studies have not yet compared the efficacy of dietary treatment... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
A low FODMAP diet plus traditional dietary advice versus a low-carbohydrate diet versus pharmacological treatment in irritable bowel syndrome (CARIBS): a single-centre, single-blind, randomised controlled trial.
BACKGROUND
Dietary advice and medical treatments are recommended to patients with irritable bowel syndrome (IBS). Studies have not yet compared the efficacy of dietary treatment with pharmacological treatment targeting the predominant IBS symptom. We therefore aimed to compare the effects of two restrictive dietary treatment options versus optimised medical treatment in people with IBS.
METHODS
This single-centre, single-blind, randomised controlled trial was conducted in a specialised outpatient clinic at the Sahlgrenska University Hospital, Gothenburg, Sweden. Participants (aged ≥18 years) with moderate-to-severe IBS (Rome IV; IBS Severity Scoring System [IBS-SSS] ≥175) and no other serious diseases or food allergies were randomly assigned (1:1:1) by web-based randomisation to receive a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) plus traditional IBS dietary advice recommended by the UK National Institute for Health and Care Excellence (hereafter the LFTD diet), a fibre-optimised diet low in total carbohydrates and high in protein and fat (hereafter the low-carbohydrate diet), or optimised medical treatment based on predominant IBS symptom. Participants were masked to the names of the diets, but the pharmacological treatment was open-label. The intervention lasted 4 weeks, after which time participants in the dietary interventions were unmasked to their diets and encouraged to continue during 6 months' follow-up, participants in the LFTD group were instructed on how to reintroduce FODMAPs, and participants receiving pharmacological treatment were offered diet counselling and to continue with their medication. The primary endpoint was the proportion of participants who responded to the 4-week intervention, defined as a reduction of 50 or more in IBS-SSS relative to baseline, and was analysed per modified intention-to-treat (ie, all participants who started the intervention). Safety was analysed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02970591, and is complete.
FINDINGS
Between Jan 24, 2017, and Sept 2, 2021, 1104 participants were assessed for eligibility and 304 were randomly assigned. Ten participants did not receive their intervention after randomisation and thus 294 participants were included in the modified intention-to-treat population (96 assigned to the LFTD diet, 97 to the low-carbohydrate diet, and 101 to optimised medical treatment). 241 (82%) of 294 participants were women and 53 (18%) were men and the mean age was 38 (SD 13). After 4 weeks, 73 (76%) of 96 participants in the LFTD diet group, 69 (71%) of 97 participants in the low-carbohydrate diet group, and 59 (58%) of 101 participants in the optimised medical treatment group had a reduction of 50 or more in IBS-SSS compared with baseline, with a significant difference between the groups (p=0·023). 91 (95%) of 96 participants completed 4 weeks in the LFTD group, 92 (95%) of 97 completed 4 weeks in the low-carbohydrate group, and 91 (90%) of 101 completed 4 weeks in the optimised medical treatment group. Two individuals in each of the intervention groups stated that adverse events were the reason for discontinuing the 4-week intervention. Five (5%) of 91 participants in the optimised medical treatment group stopped treatment prematurely due to side-effects. No serious adverse events or treatment-related deaths occurred.
INTERPRETATION
Two 4-week dietary interventions and optimised medical treatment reduced the severity of IBS symptoms, with a larger effect size in the diet groups. Dietary interventions might be considered as an initial treatment for patients with IBS. Research is needed to enable personalised treatment strategies.
FUNDING
The Healthcare Board Region Västra Götaland, the Swedish Research Council, the Swedish Research Council for Health, Working Life and Welfare, AFA Insurance, grants from the Swedish state, the Wilhelm and Martina Lundgren Science Foundation, Skandia, the Dietary Science Foundation, and the Nanna Swartz Foundation.
Topics: Humans; Irritable Bowel Syndrome; Female; Male; Diet, Carbohydrate-Restricted; Single-Blind Method; Adult; Middle Aged; Oligosaccharides; Disaccharides; Monosaccharides; Treatment Outcome; Dietary Fiber; Polymers; Fermentation; Sweden; Severity of Illness Index; FODMAP Diet
PubMed: 38643782
DOI: 10.1016/S2468-1253(24)00045-1 -
Neuron Mar 2024Glucose homeostasis is controlled by brain-gut communications. Yet our understanding of the neuron-gut interface in the glucoregulatory system remains incomplete. Here,...
Glucose homeostasis is controlled by brain-gut communications. Yet our understanding of the neuron-gut interface in the glucoregulatory system remains incomplete. Here, we find that sympathetic nerves elevate postprandial blood glucose but restrict brain glucose utilization by repressing the release of glucagon-like peptide-1 (GLP-1) from enteroendocrine L cells. Sympathetic nerves are in close apposition with the L cells. Importantly, sympathetic denervation or intestinal deletion of the adrenergic receptor α2 (Adra2a) augments postprandial GLP-1 secretion, leading to reduced blood glucose levels and increased brain glucose uptake. Conversely, sympathetic activation shows the opposite effects. At the cellular level, adrenergic signaling suppresses calcium flux to limit GLP-1 secretion upon sugar ingestion. Consequently, abrogation of adrenergic signal results in a significant improvement in learning and memory ability. Together, our results reveal a sympathetic nerve-enteroendocrine unit in constraining GLP-1 secretion, thus providing a therapeutic nexus of mobilizing endogenous GLP-1 for glucose management and cognitive improvement.
Topics: Glucose; Glucagon-Like Peptide 1; Blood Glucose; Cell Communication; Brain; Cognition; Adrenergic Agents
PubMed: 38242116
DOI: 10.1016/j.neuron.2023.12.012 -
Biochimica Et Biophysica Acta. Reviews... Nov 2023Studies examining the regulatory roles and clinical applications of monosaccharides other than glucose in cancer have been neglected. Mannose, a common type of... (Review)
Review
Studies examining the regulatory roles and clinical applications of monosaccharides other than glucose in cancer have been neglected. Mannose, a common type of monosaccharide found in human body fluids and tissues, primarily functions in protein glycosylation rather than carbohydrate metabolism. Recent research has demonstrated direct anticancer effects of mannose in vitro and in vivo. Simply supplementing cell culture medium or drinking water with mannose achieved these effects. Moreover, mannose enhances the effectiveness of current cancer treatments including chemotherapy, radiotherapy, targeted therapy, and immune therapy. Besides the advancements in basic research on the anticancer effects of mannose, recent studies have reported its application as a biomarker for cancer or in the delivery of anticancer drugs using mannose-modified drug delivery systems. This review discusses the progress made in understanding the regulatory roles of mannose in cancer progression, the mechanisms underlying its anticancer effects, and its current application in cancer diagnosis and treatment.
Topics: Humans; Mannose; Neoplasms; Antineoplastic Agents; Glucose; Drug Delivery Systems
PubMed: 37657682
DOI: 10.1016/j.bbcan.2023.188970