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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 -
Diabetes, Obesity & Metabolism Aug 2023To investigate the hypothesis that weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide alone would lead to a greater reduction in the... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of the glucagon-like peptide-1 receptor agonist liraglutide, compared to caloric restriction, on appetite, dietary intake, body fat distribution and cardiometabolic biomarkers: A randomized trial in adults with obesity and prediabetes.
AIMS
To investigate the hypothesis that weight loss with the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide alone would lead to a greater reduction in the proportion of fat to lean tissue mass when compared to caloric restriction (CR) alone, as well as when compared to treatment with sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, that also enhances GLP-1 activity - to determine the independent effects of each treatment.
METHODS
A total of 88 adults with obesity and prediabetes were randomized to 14 weeks of intervention with CR (-390 kcal/d), liraglutide (1.8 mg/d), or the dipeptidyl peptidase-4 inhibitor sitagliptin (100 mg/d) as a weight-neutral comparator. Changes between groups in appetite and hunger ratings measured via visual analogue scales, dietary intakes, body weight, body composition via dual energy x-ray absorptiometry, and resting energy expenditure via indirect calorimetry were assessed using the Kruskal-Wallis test or Pearson's chi-squared test.
RESULTS
Weight loss ≥5% of baseline body weight occurred in 44% of participants in the CR group, 22% of the liraglutide group and 5% of the sitagliptin group (p = 0.02). The ratio of fat to lean mass decreased by 6.5% in the CR group, 2.2% in the liraglutide group, and 0% in the sitagliptin group (p = 0.02). Visceral fat reduced by 9.5% in the CR group, 4.8% in the liraglutide group, and 0% in the sitagliptin group (p = 0.04). A spontaneous reduction in dietary simple carbohydrates in the CR group was associated with improved homeostatic model assessment of insulin resistance score (HOMA-IR).
CONCLUSIONS
Although both liraglutide and CR are valuable strategies for cardiometabolic risk reduction, CR was associated with greater weight loss and more favourable improvements in body composition than treatment with liraglutide alone. Differences in the response to each of these interventions enables patients to be stratified to the most optimal intervention for their personal risk factors.
Topics: Humans; Adult; Liraglutide; Glucagon-Like Peptide-1 Receptor; Prediabetic State; Caloric Restriction; Appetite; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Sitagliptin Phosphate; Obesity; Dipeptidyl-Peptidase IV Inhibitors; Body Weight; Eating; Body Fat Distribution; Weight Loss; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Cardiovascular Diseases
PubMed: 37188932
DOI: 10.1111/dom.15113 -
Cardiovascular Diabetology Oct 2023The association between the triglyceride-glucose (TyG) index and mortality in cardiovascular disease (CVD) patients with diabetes or pre-diabetes remains unclear. This...
BACKGROUND
The association between the triglyceride-glucose (TyG) index and mortality in cardiovascular disease (CVD) patients with diabetes or pre-diabetes remains unclear. This study aimed to investigate the relationship between baseline TyG index and all-cause and cardiovascular (CV) mortality in CVD patients with diabetes or pre-diabetes among American adults. .
METHODS
This study enrolled 1072 CVD patients with diabetes or pre-diabetes from the National Health and Nutrition Examination Survey (2001-2018). Mortality outcomes were determined by linking to National Death Index (NDI) records up to December 31, 2019. Multivariate Cox proportional hazards models were constructed to analyze explore the associations between baseline TyG index and mortality. Non-linear correlations were explored using restricted cubic splines, and a two-piecewise Cox proportional hazards model for both sides of the inflection point was constructed.
RESULTS
During 7541 person-years of follow-up, a total of 461 all-cause deaths and 154 CVD-related deaths were recorded. The restricted cubic splines revealed a U-shaped association between the baseline TyG index with all-cause and CVD mortality in CVD patients with diabetes or pre-diabetes. Specifically, baseline TyG index lower than the threshold values (TyG index < 9.05 in all-cause mortality and < 8.84 in CVD mortality) was negatively associated with mortality (HR 0.47, 95% CI = 0.27-0.81 for all-cause mortality and HR 0.25, 95% CI = 0.07-0.89 for CVD mortality). In contrast, baseline TyG index higher than the threshold values (TyG index > 9.05 in all-cause mortality and > 8.84 in CVD mortality) was positively associated with mortality (HR 1.42, 95% CI = 1.02-1.99 for all-cause mortality and HR 1.77, 95% CI = 1.08-2.91 for CVD mortality).
CONCLUSIONS
A U-shaped association was observed between the baseline TyG index with CVD and all-cause mortality in CVD patients with diabetes or pre-diabetes in a American population. The thresholds of 8.84 and 9.05 for CVD and all-cause mortality, respectively.
Topics: Adult; Humans; Prediabetic State; Cardiovascular Diseases; Nutrition Surveys; Diabetes Mellitus; Glucose; Triglycerides; Blood Glucose; Risk Factors; Biomarkers
PubMed: 37848879
DOI: 10.1186/s12933-023-02030-z -
Frontiers in Endocrinology 2023
Topics: Humans; Prediabetic State; Endocrine System
PubMed: 37664837
DOI: 10.3389/fendo.2023.1268552 -
Journal of Translational Medicine Jul 2023Diagnosis and intervention of prediabetes is an emerging method for preventing diabetic progression and complications. Periodontitis has been reported to strongly...
BACKGROUND
Diagnosis and intervention of prediabetes is an emerging method for preventing diabetic progression and complications. Periodontitis has been reported to strongly correlate with the dysregulation of glucose metabolism. Nonetheless, the relationship between periodontal status and the prevalence of prediabetes as well as its prognosis remains elusive. This study aimed to investigate the association of periodontitis with the prevalence of prediabetes and furtherly explore the all-cause mortality of different periodontal status among patients with prediabetes.
METHODS
The dateset from the National Health and Nutrition Examination Survey (NHANES) was utilized for our study. Participants were divided into two groups (with or without periodontitis) and further assigned into subgroups by different grades of periodontitis to analyze the association between periodontitis and prevalence of prediabetes. Then we analyzed the association between all-cause mortality and periodontitis among patients with prediabetes. Weighted multivariate logistic/Cox regression models were adopted in our study.
RESULTS
A total of 15390 participants were included and divided into a periodontitis group (n = 5033) and a nonperiodontitis group (n = 10357). The results showed that participants with periodontitis had a higher risk of prediabetes. After adjusting for covariables, more severe periodontitis was positively related to prediabetes (moderate vs. no periodontitis: OR = 1.46, 95% CI: 1.29-1.65; severe vs. no periodontitis: OR = 1.62, 95% CI 1.31-2.01). Furtherly, we explored the association between all-cause mortality and periodontal status among patients diagnosed with prediabetes (n = 4518) and found that severe (HR = 1.806, 95% CI 1.19-2.74) and moderate periodontitis (HR = 2.42, 95% CI 1.95-3.01) were associated with elevated all-cause mortality among patients with prediabetes.
CONCLUSIONS
In general, the results suggest that periodontitis is positively associated with the prevalence and mortality of prediabetes. These results suggest that good management of periodontal status could be a potential strategy to reduce the occurrence and development of prediabetes.
Topics: Humans; Prediabetic State; Nutrition Surveys; Prevalence; Periodontitis; Prognosis
PubMed: 37475034
DOI: 10.1186/s12967-023-04340-y -
Nature Communications Sep 2023Diabetes and associated comorbidities are a global health threat on the rise. We conducted a six-month dietary intervention in pre-diabetic individuals (NCT03222791), to... (Clinical Trial)
Clinical Trial
Diabetes and associated comorbidities are a global health threat on the rise. We conducted a six-month dietary intervention in pre-diabetic individuals (NCT03222791), to mitigate the hyperglycemia and enhance metabolic health. The current work explores early diabetes markers in the 200 individuals who completed the trial. We find 166 of 2,803 measured features, including oral and gut microbial species and pathways, serum metabolites and cytokines, show significant change in response to a personalized postprandial glucose-targeting diet or the standard of care Mediterranean diet. These changes include established markers of hyperglycemia as well as novel features that can now be investigated as potential therapeutic targets. Our results indicate the microbiome mediates the effect of diet on glycemic, metabolic and immune measurements, with gut microbiome compositional change explaining 12.25% of serum metabolites variance. Although the gut microbiome displays greater compositional changes compared to the oral microbiome, the oral microbiome demonstrates more changes at the genetic level, with trends dependent on environmental richness and species prevalence in the population. In conclusion, our study shows dietary interventions can affect the microbiome, cardiometabolic profile and immune response of the host, and that these factors are well associated with each other, and can be harnessed for new therapeutic modalities.
Topics: Humans; Cytokines; Gastrointestinal Microbiome; Hyperglycemia; Microbiota; Prediabetic State
PubMed: 37666816
DOI: 10.1038/s41467-023-41042-x -
Diabetes Therapy : Research, Treatment... Oct 2023In this commentary I will evaluate whether prediabetes should be treated pharmacologically. To consider this question, certain information concerning prediabetes is...
OBJECTIVE
In this commentary I will evaluate whether prediabetes should be treated pharmacologically. To consider this question, certain information concerning prediabetes is relevant.
BACKGROUND INFORMATION
(1) Prediabetes is not independently associated with cardiovascular disease; the other factors in the metabolic syndrome increase that risk; (2) various tests and criteria for diagnosing prediabetes are recommended, yielding prevalences varying from 6% to 38% depending on which are used; (3) one-third of patients with prediabetes revert to normal over time; (4) up to two-thirds of patients with prediabetes do not develop diabetes; (5) people with prediabetes have insulin resistance and impaired insulin secretion; (6) although pharmacological treatment of the dysglycemia temporarily lowers it, when the drugs are discontinued, incident diabetes develops similarly as that in those who received placebos; (7) when the drugs are discontinued, there are no changes in insulin resistance or impaired insulin secretion; (8) incident diabetes was similar at 10 years in people remaining on metformin in the Diabetes Prevention Program Outcome Study compared with those who did not receive the drug; (9) no current drugs will directly increase insulin secretion (except sulfonylureas and glinides which have not been used to treat prediabetes because of hypoglycemia concerns); (10) sufficient weight loss to lower insulin resistance by nutritional means is challenging and especially difficult to maintain.
CONCLUSIONS
Pharmacological treatment of the dysglycemia of prediabetes is not warranted. On the other hand, the ability of high doses of glucagon-like peptide (GLP)-1 receptor agonists and the combination of a GLP-1 receptor agonist and the glucose-dependent insulinotropic polypeptide (GIP) to lower weight by 15% and 20%, respectively, deserves consideration for the treatment of prediabetes. This amount of weight loss should decrease insulin resistance, allowing endogenous insulin secretion to be more effective and lower the risk for developing diabetes.
PubMed: 37490238
DOI: 10.1007/s13300-023-01449-7 -
Frontiers in Endocrinology 2023The purpose of this study is to investigate the independent influencing factors of the transition from normal population to prediabetes, and from prediabetes to...
OBJECTIVE
The purpose of this study is to investigate the independent influencing factors of the transition from normal population to prediabetes, and from prediabetes to diabetes, and to further construct clinical prediction models to provide a basis for the prevention and management of prediabetes and diabetes.
MATERIALS AND METHODS
The data for this study were based on clinical information of participants from the Health Management Center of Peking University Shenzhen Hospital. Participants were classified into normal group, prediabetes group, and diabetes group according to their functional status of glucose metabolism. Spearman's correlation coefficients were calculated for the variables, and a matrix diagram was plotted. Further, univariate and multivariate logistic regression analysis were conducted to explore the independent influencing factors. The independent influencing factors were used as predictors to construct the full-variable prediction model (Full.model) and simplified prediction model (Simplified.model).
RESULTS
This study included a total of 5310 subjects and 22 variables, among which there were 1593(30%) in the normal group, 3150(59.3%) in the prediabetes group, and 567(10.7%) in the diabetes group. The results of the multivariable logistic regression analysis showed that there were significant differences in 9 variables between the normal group and the prediabetes group, including age(Age), body mass index(BMI), systolic blood pressure(SBP), urinary glucose(U.GLU), urinary protein(PRO), total protein(TP), globulin(GLB), alanine aminotransferase(ALT), and high-density lipoprotein cholesterol(HDL-C). There were significant differences in 7 variables between the prediabetes group and the diabetes group, including Age, BMI, SBP, U.GLU, PRO, triglycerides(TG), and HDL.C. The Full.model and Simplified.model constructed based on the above influencing factors had moderate discriminative power in both the training set and the test set.
CONCLUSION
Age, BMI, SBP, U.GLU, PRO, TP, and ALT are independent risk factors, while GLB and HDL.C are independent protective factors for the development of prediabetes in the normal population. Age, BMI, SBP, U.GLU, PRO, and TG are independent risk factors, while HDL.C is an independent protective factor for the progression from prediabetes to diabetes. The Full.model and Simplified.model developed based on these influencing factors have moderate discriminative power.
Topics: Humans; Prediabetic State; Blood Glucose; Diabetes Mellitus; Triglycerides; Risk Factors
PubMed: 37964953
DOI: 10.3389/fendo.2023.1225696 -
Journal of Diabetes Investigation Oct 2023There has been conflicting evidence regarding the role of prediabetes as a risk factor of lung cancer. A systemic review and meta-analysis was conducted to determine the... (Meta-Analysis)
Meta-Analysis
AIMS/INTRODUCTION
There has been conflicting evidence regarding the role of prediabetes as a risk factor of lung cancer. A systemic review and meta-analysis was conducted to determine the relationship between prediabetes and lung cancer incidence and mortality in general adult populations.
MATERIALS AND METHODS
Observational studies relevant to the objective were found in Medline, Embase, Cochrane Library, and Web of Science. By incorporating potential heterogeneity into the model, a randomized-effects model was selected.
RESULTS
Ten cohort studies were included. People with prediabetes were associated with a mildly increased risk of lung cancer incidence compared with controls with normoglycemia (risk ratio [RR]: 1.09, 95% confidence interval [CI]: 1.01-1.18, P = 0.03; I = 79%), which was mainly observed in men rather than in women (RR: 1.07 vs 0.99, P for subgroup difference < 0.001). Prediabetes was related to a higher risk of lung cancer mortality (RR: 1.19, 95% CI: 1.02-1.39, P = 0.03; I = 52%), and the results were consistent in both men and women (P for subgroup difference = 0.67). The association between prediabetes and lung cancer incidence or mortality did not appear to be significantly affected by different definitions of prediabetes (P for subgroup difference = 0.27 and 0.37).
CONCLUSIONS
Prediabetes might be associated with a mildly increased risk of lung cancer incidence in men, but not in women. In addition, prediabetes may be related to a higher risk of lung cancer mortality in the adult population.
Topics: Male; Adult; Humans; Female; Incidence; Prediabetic State; Lung Neoplasms; Risk Factors
PubMed: 37517054
DOI: 10.1111/jdi.14057