RÉSUMÉ
BACKGROUND/OBJECTIVE: To identify predictors of incident type 2 diabetes using a mixed meal tolerance test (MMTT). METHODS: Adult Indigenous Americans without diabetes (n = 501) from a longitudinal cohort underwent at baseline a 4-h MMTT, measures of body composition, an oral glucose tolerance test, an intravenous glucose tolerance test for acute insulin response (AIR), and a hyperinsulinemic-euglycemic clamp for insulin action (M). Plasma glucose responses from the MMTT were quantified by the total and incremental area under the curve (AUC/iAUC). RESULTS: At follow-up (median time 9.6 [inter-quartile range: 5.6-13.5] years), 169 participants were diagnosed with diabetes. Unadjusted Cox proportional hazards models, glucose AUC180-min (HR: 1.98, 95% CI: 1.67, 2.34, p < 0.0001), AUC240-min (HR: 1.93, 95% CI: 1.62, 2.31, p < 0.0001), and iAUC180-min (HR: 1.43, 95% CI: 1.20, 1.71, p < 0.0001) were associated with an increased risk of diabetes. After adjustment for covariates (age, sex, body fat percentage, M, AIR, Indigenous American heritage) in three subsequent models, AUC180-min (HR: 1.44, 95% CI: 1.10, 1.88, p = 0.007) and AUC240-min (HR: 1.41, 95% CI: 1.09, 1.84, p < 0.01) remained associated with increased risk of diabetes. CONCLUSIONS: Glucose responses to a mixed meal predicted the development of type 2 diabetes. This indicates that a mixed nutritional challenge provides important information on disease risk. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov identifier : NCT00340132, NCT00339482.
Sujet(s)
Glycémie , Diabète de type 2 , Hyperglycémie provoquée , Repas , Humains , Diabète de type 2/épidémiologie , Diabète de type 2/sang , Diabète de type 2/diagnostic , Diabète de type 2/ethnologie , Mâle , Femelle , Adulte , Adulte d'âge moyen , Glycémie/analyse , Études longitudinales , Indiens d'Amérique Nord , Technique du clamp glycémique , Modèles des risques proportionnels , Insuline/sangRÉSUMÉ
AIM: Reduced renal insulin signalling is implicated in the pathogenesis of albuminuria. We sought to investigate whether insulin action and secretion, measured before diabetes onset, are associated with the development of albuminuria after diabetes onset. MATERIALS AND METHODS: Baseline body composition, insulin sensitivity by hyperinsulinaemic-euglycaemic clamp at submaximal and maximal insulin stimulation (240 and 2400 pmol/m2/min; M-low and M-high), and insulin secretion by intravenous glucose tolerance test [acute insulin response (AIR)] were measured in 170 Southwestern Indigenous American adults who subsequently developed diabetes. After diabetes onset and during the median follow-up of 13.6 years, 81 participants (48%) developed albuminuria (urine albumin-to-creatinine ratio ≥30 mg/g). Separate associations of M-low, M-high and AIR (per 1-SD change) with the risk of albuminuria were assessed by Cox regression models adjusted for age, sex and body fat (%). RESULTS: Participants who developed albuminuria were of similar age (26.4 ± 5.4 vs. 27.5 ± 6.1 years), sex (46% vs. 48% male), body fat (36.4 ± 7.5 vs. 35.7 ± 7.9%) and AIR [2.3 ± 0.3 vs. 2.3 ± 0.3, pmol/L (log)] as those who did not develop albuminuria but had lower insulin sensitivity [M-low: 0.33 ± 0.08 vs. 0.36 ± 0.12, p = .03; M-high: 0.87 ± 0.11 vs. 0.91 ± 0.12, p = .02; mg/kg-metabolic body size/min (log)]. In separate adjusted models, lower M-low and M-high were both associated with an increased risk for albuminuria [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.14, 2.00, p = .004; HR 1.31, 95% CI 1.06, 1.63, p = .01), whereas AIR was not (HR 1.15, 95% CI 0.87, 1.56, p = .3). CONCLUSIONS: Lower insulin sensitivity is associated with the development of albuminuria, suggesting a role for insulin signalling in the pathogenesis of proteinuria.
Sujet(s)
Diabète de type 2 , Insulinorésistance , Adulte , Humains , Mâle , Femelle , Diabète de type 2/complications , Insulinorésistance/physiologie , Études prospectives , Albuminurie/épidémiologie , Albuminurie/étiologie , InsulineRÉSUMÉ
OBJECTIVE: The aim of this study was to assess the reproducibility and physiological determinants of mixed-meal tolerance tests (MMTTs) on glucose and insulin responses. METHODS: While inpatients on a weight-maintaining diet, 894 individuals (574 with normal and 267 with impaired glucose regulation and 53 with type 2 diabetes [T2D]) underwent 9-hour MMTTs (breakfast and lunch; 30% weight-maintaining diet each; 40% carbohydrate, 40% fat, and 20% protein). Total/incremental areas under the curve (AUC/iAUC) were calculated from MMTT plasma glucose/insulin concentrations. Acute insulin response (AIR) was quantified by intravenous glucose tolerance test and insulin action (M) via hyperinsulinemic-euglycemic clamp. A subset had repeat MMTTs (median follow-up = 1.4 years). RESULTS: In individuals without T2D, for breakfast-versus-lunch reproducibility of glucose, AUCs were moderate (intraclass correlation coefficients [ICCs]: 0.44-0.61), and iAUCs were poor (ICCs < 0.15). For repeated MMTTs, reproducibility of AUC/iAUCs was low (ICCs: 0.11-0.36). For insulin, AUC reproducibility was high (ICCs > 0.70), and iAUCs were moderate (ICCs: 0.64-0.71). For repeated MMTTs, ICC AUC/iAUCs were 0.34 to 0.54. In those with T2D, ICC glucose AUC/iAUCs were >0.80 and >0.50, respectively, and for insulin were <0.40. For repeated MMTTs, ICC glucose/insulin AUC/iAUCs were moderate. Glucose AUCs associated with M/AIR (partial Rs < -0.25), and insulin AUCs negatively/positively associated with M/AIR (partial Rs = -0.51/0.24). CONCLUSIONS: Reproducibility of glucose/insulin responses to MMTTs varied by subtraction of fasting values, glucose status, and time. Insulin secretion and action explained ~20% of MMTT responses. The substantial variability in MMTT response requires consideration in studies using MMTT outcomes.
Sujet(s)
Glycémie , Diabète de type 2 , Humains , Glycémie/métabolisme , Diabète de type 2/métabolisme , Reproductibilité des résultats , Insuline , Glucose , Période post-prandiale/physiologieRÉSUMÉ
BACKGROUND: Molecular stable isotope ratios are a novel type of dietary biomarker with high sensitivity and specificity for certain foods. Among these, fatty acid carbon isotope ratios (CIRs) have strong potential but have not been investigated as dietary biomarkers. OBJECTIVES: We evaluated whether fatty acid CIRs and mass proportions were associated with meat, fish, and sugar-sweetened beverage (SSB) intake. METHODS: Thirty-two men [aged 46.2 ± 10.5 y; BMI (kg/m2): 27.2 ± 4.0] underwent a 12-wk inpatient dietary intervention at the National Institute of Diabetes and Digestive and Kidney Diseases in Phoenix, Arizona. Men were randomly assigned to 1 of 8 dietary treatments varying the presence/absence of dietary meat, fish, and SSBs in all combinations. Fatty acid CIRs and mass proportions were measured in fasting blood samples and adipose tissue biopsies that were collected pre- and postintervention. Dietary effects were analyzed using multivariable regression and receiver operating characteristic AUCs were calculated using logistic regression. RESULTS: CIRs of the several abundant SFAs, MUFAs and arachidonic acid (20:4n-6) in plasma were strongly associated with meat, as were a subset of these fatty acids in RBCs. Effect sizes in plasma ranged from 1.01 to 1.93 and were similar but attenuated in RBCs. Mass proportions of those fatty acids were not associated with diet. CIRs of plasma dihomo-γ-linolenic acid (20:3n-6) and adipose palmitic acid (16:0) were weakly associated with SSBs. Mass proportions of plasma odd-chain fatty acids were associated with meat, and mass proportions of plasma EPA and DHA (20:5n-3 and 22:6n-3) were associated with fish. CONCLUSIONS: CIRs of plasma and RBC fatty acids show promise as sensitive and specific measures of dietary meat. These provide different information from that provided by fatty acid mass proportions, and are informative where mass proportion is not. This trial is registered at www.clinicaltrials.gov as NCT01237093.
Sujet(s)
Acides gras , Patients hospitalisés , Animaux , Humains , Isotopes du carbone , Viande , Régime alimentaireRÉSUMÉ
OBJECTIVE: Food insecurity is known to be associated with obesity, but its association with physiological measures is unclear. Therefore, it was hypothesized that, compared with food-secure individuals, those with food insecurity would have higher 24-hour energy expenditure (EE [kilocalories per day]) and 24-hour respiratory quotient (RQ [ratio]). Subsequently, hormones involved in appetite regulation, substrate oxidation, and EE were explored. METHODS: A total of 113 healthy participants without diabetes (75 men; mean [SD], age 40 [12] years; BMI 30 [8] kg/m2 ) were included in this analysis. Participants completed the Food Security Short Form, underwent a dual-energy x-ray absorptiometry scan, and spent 24 hours in a human respiratory chamber following a weight-maintaining diet. RESULTS: Compared with individuals with food security, participants with food insecurity had no difference in 24-hour EE. However, they had higher carbohydrate oxidation rates (p = 0.03) and lower lipid oxidation rates (p = 0.02), resulting in higher 24-hour RQ (p < 0.01). They also had lower fasting glucagon-like peptide 1 (p = 0.03) concentrations. CONCLUSIONS: Food insecurity is associated with higher 24-hour RQ and lower fasting glucagon-like peptide 1 concentrations, metabolic and hormonal differences previously shown to drive greater calorie intake in the setting of unrestricted food availability. These findings therefore provide new insight into the paradoxical link between restricted food access and increased adiposity.
Sujet(s)
Métabolisme énergétique , Glucagon-like peptide 1 , Adulte , Ration calorique/physiologie , Métabolisme énergétique/physiologie , Insécurité alimentaire , Humains , Mâle , Obésité/métabolismeRÉSUMÉ
PURPOSE OF REVIEW: The present review focuses on the epidemiology of type 2 diabetes (T2D) in Indigenous communities in the continental United States (U.S.)-including disease prevention and management-and discusses special considerations in conducting research with Indigenous communities. RECENT FINDINGS: Previous studies have reported the disparately high prevalence of diabetes, especially T2D, among Indigenous peoples in the U.S. The high prevalence and incidence of early-onset T2D in Indigenous youth relative to that of all youth in the U.S. population pose challenges to the prevention of complications of diabetes. Behavioral, dietary, lifestyle, and genetic factors associated with T2D in Indigenous communities are often investigated. More limited is the discussion of the historical and ongoing consequences of colonization and displacement that impact the aforementioned risk factors. Future research is necessary to assess community-specific needs with respect to diabetes prevention and management across the diversity of Indigenous communities in the U.S.
Sujet(s)
Diabète de type 2 , Adolescent , Prestations des soins de santé , Diabète de type 2/épidémiologie , Humains , Mode de vie , Prévalence , Facteurs de risque , États-Unis/épidémiologieRÉSUMÉ
Prediabetes affects 84.1 million adults, and many will progress to type 2 diabetes (T2D). The objective of this proof-of-concept trial was to determine the efficacy of inulin supplementation to improve glucose metabolism and reduce T2D risk. Adults (n = 24; BMI: 31.3 ± 2.9 kg/m2; age: 54.4 ± 8.3 years) at risk for T2D were enrolled in this controlled feeding trial and consumed either inulin (10 g/day) or placebo (maltodextrin, 10 g/day) for six weeks. Assessments included peripheral insulin sensitivity, fasting glucose, and insulin, HOMA-IR, in vivo skeletal muscle substrate preference, Bifidobacteria copy number, intestinal permeability, and endotoxin concentrations. Participant retention was 92%. There were no baseline group differences except for fasting insulin (p = 0.003). The magnitude of reduction in fasting insulin concentrations with inulin (p = 0.003, inulin = Δ-2.9, placebo = Δ2.3) was attenuated after adjustment for baseline concentrations (p = 0.04). After adjusting for baseline values, reduction in HOMA-IR with inulin (inulin = Δ-0.40, placebo=Δ0.27; p = 0.004) remained significant. Bifidobacteria 16s increased (p = 0.04; inulin = Δ3.1e9, placebo = Δ-8.9e8) with inulin supplementation. Despite increases in gut Bifidobacteria, inulin supplementation did not improve peripheral insulin sensitivity. These findings question the need for larger investigations of inulin and insulin sensitivity in this population.
Sujet(s)
Diabète de type 2/prévention et contrôle , Compléments alimentaires , Inuline/administration et posologie , Inuline/pharmacologie , Prébiotiques , Femelle , Humains , Insuline/sang , Insulinorésistance , Mâle , Adulte d'âge moyen , Projets pilotesRÉSUMÉ
OBJECTIVE: This study aimed to evaluate whether a 12-week, weight-maintaining, macronutrient-stable dietary intervention that varies only by meat, fish, or soda consumption alters 24-hour energy expenditure (24hrEE) and substrate oxidation. METHODS: Healthy males were recruited to participate in a 12-week inpatient study and were randomized to a weight-maintaining dietary intervention that contained varying combinations of meat (0% or 19%), fish (0% or 6%), or soda (0% or 14%) in a factorial design. Macronutrient composition across dietary intervention groups was as follows: 50% of energy from carbohydrates, 30% of energy from fat, and 20% of energy from protein. Whole-room indirect calorimetry at baseline and week 12 were used to measure 24hrEE and substrate oxidation. RESULTS: Twenty-six males (mean [SEM], age: 46.6 [10.4] years; BMI: 26.9 [4.1] kg/m2 ) completed all measurements. Fish consumption resulted in higher 24hrEE by 126 (55) kcal/d compared with no fish consumption (P = 0.03), whereas 24hrEE for soda consumption was 132 (56) kcal/d (P = 0.03) lower. Approximately 80% of the decrease in 24hrEE with soda consumption was due to lower awake-inactive energy expenditure (EE; P = 0.001). No specific EE component accounted for the differences observed with fish consumption. CONCLUSIONS: The data indicate that dietary sources of protein and carbohydrates appear to influence 24hrEE and inactive EE.
Sujet(s)
Boissons gazeuses , Régime alimentaire , Consommation alimentaire , Métabolisme énergétique , Viande , Adulte , Humains , Mâle , Adulte d'âge moyen , Composition corporelle/physiologie , Poids/physiologie , Calorimétrie indirecte , Boissons gazeuses/effets indésirables , Matières grasses alimentaires/métabolisme , Consommation alimentaire/physiologie , Ration calorique , Métabolisme énergétique/physiologie , Patients hospitalisés , Oxydoréduction , Projets pilotesRÉSUMÉ
An elevated circulating level of trimethylamine N-oxide (TMAO) has been identified as a risk factor for numerous diseases, including cardiovascular disease (CVD) and colon cancer. TMAO is formed from trimethylamine (TMA)-precursors such as choline via the combined action of the gut microbiota and liver. We conducted a Mediterranean diet intervention that increased intakes of fiber and changed intakes of many other foods containing fat to increase the relative amount of mono-unsaturated fats in the diet. The Mediterranean diet is associated with reduced risks of chronic diseases and might counteract the pro-inflammatory effects of increased TMAO formation. Therefore, the purpose of this study was to determine if the Mediterranean diet would reduce TMAO concentrations. Fasting TMAO concentrations were measured before and after six-months of dietary intervention in 115 healthy people at increased risk for colon cancer. No significant changes in plasma TMAO or in the ratios of TMAO to precursor compounds were found in either the Mediterranean group or the comparison group that followed a Healthy Eating diet. TMAO concentrations exhibited positive correlations with age and markers of metabolic health. TMAO concentrations were not associated with circulating cytokines, but the relative abundance of Akkermansia mucinophilia in colon biopsies was modestly and inversely correlated with baseline TMAO, choline, and betaine serum concentrations. These results suggest that broad dietary pattern intervention over six months may not be sufficient for reducing TMAO concentrations in an otherwise healthy population. Disruption of the conversion of dietary TMA to TMAO should be the focus of future studies.
Sujet(s)
Tumeurs du côlon/diétothérapie , Régime méditerranéen , Méthylamines/sang , Adulte , Sujet âgé , Bactéries/classification , Bactéries/génétique , Bactéries/isolement et purification , Bactéries/métabolisme , Bétaïne/sang , Choline/sang , Tumeurs du côlon/sang , Tumeurs du côlon/métabolisme , Tumeurs du côlon/microbiologie , Jeûne , Femelle , Microbiome gastro-intestinal , Humains , Mâle , Adulte d'âge moyenRÉSUMÉ
PURPOSE: The objective of this systematic review of literature was to evaluate and summarize published research that has investigated the association between exercise and gut microbial composition in mammals. METHODS: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The databases searched for this review included: PubMed; PubMed Central; Medline; Cumulative Index of Nursing and Allied Health Literature; Web of Science; Commonwealth Agricultural Bureaux Direct; Health Source: Nursing Academic Edition; Clinicaltrials.gov; International Prospective Register of Systematic Reviews (PROSPERO); and the Cochrane Library. RESULTS: Twenty-five articles met the inclusion criteria: 17 rodent, one canine, two equine, and five human studies. All studies in rodents and equines included control groups; whereas only one study in humans included a control group. The remaining were cross-sectional or cohort studies. All studies in rodents controlled for dietary intake and one study in humans implemented a 3-d dietary control. Eleven studies assessed voluntary exercise and 13 studies used forced exercise. Diversification within the Firmicutes phylum was consistently observed in exercise groups across studies. There were no consistent trends within Bacteroidetes, Actinobacteria, or Proteobacteria phyla. In general, the potential interactions between exercise and diet composition and their respective influences on the intestinal microbiome were not well characterized. CONCLUSIONS: Exercise was associated with changes in gut microbial composition, an increase in butyrate producing bacteria and an increase in fecal butyrate concentrations independent of diet in rodents and humans. The overall quality of evidence in the studies in humans was low and the risk of bias was unclear. Future studies with standardized reporting and rigorous dietary control in larger samples are needed to further determine the influence of exercise on gut microbial composition.
Sujet(s)
Exercice physique/physiologie , Microbiome gastro-intestinal/physiologie , Animaux , Bactéries/métabolisme , Butyrates/analyse , Butyrates/métabolisme , Régime alimentaire , Fèces/composition chimique , HumainsRÉSUMÉ
Trimethylamine N-oxide (TMAO) is associated with type 2 diabetes (T2DM) and increased risk of adverse cardiovascular events. Prebiotic supplementation has been purported to reduce TMAO production, but whether prebiotics reduce fasting or postprandial TMAO levels is unclear. Sedentary, overweight/obese adults at risk for T2DM (n = 18) were randomized to consume a standardized diet (55% carbohydrate, 30% fat) with 10 g/day of either an inulin supplement or maltodextrin placebo for 6 weeks. Blood samples were obtained in the fasting state and hourly during a 4-h high-fat challenge meal (820 kcal; 25% carbohydrate, 63% fat; 317.4 mg choline, 62.5 mg betaine, 8.1 mg l-carnitine) before and after the diet. Plasma TMAO and trimethylamine (TMA) moieties (choline, l-carnitine, betaine, and γ-butyrobetaine) were measured using isocratic ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). There were no differences in fasting or postprandial TMAO or TMA moieties between the inulin and placebo groups at baseline (all p > 0.05). There were no significant changes in fasting or postprandial plasma TMAO or TMA moiety concentrations following inulin or placebo. These findings suggest that inulin supplementation for 6 weeks did not reduce fasting or postprandial TMAO in individuals at risk for T2DM. Future studies are needed to identify efficacious interventions that reduce plasma TMAO concentrations.
Sujet(s)
Diabète de type 2 , Compléments alimentaires , Inuline/pharmacologie , Méthylamines/sang , Adulte , Sujet âgé , Méthode en double aveugle , Comportement alimentaire , Femelle , Humains , Inuline/administration et posologie , Mâle , Adulte d'âge moyen , Facteurs de risqueRÉSUMÉ
BACKGROUND: Three-fourths of adults older than 55 years in the United States are overweight or obese. Prebiotics including inulin-type fructans may benefit with weight management. AIM: We aimed to investigate the acute effects of pre-meal inulin consumption on energy intake (EI) and appetite in older adults. METHODS: Sedentary, overweight or obese middle-aged and older adults ( n = 7, 60.9 ± 4.4 years, BMI 32.9 ± 4.3 kg/m2) ingested inulin (10 g) or a water preload before each test period in a randomly assigned order. EI, appetite and gastrointestinal symptoms were monitored during the following 24 h. RESULTS: No differences in EI were noted between conditions (inulin: 14744 ± 5552 kJ, control: 13924 ± 4904 kJ, p > 0.05). Rumbling was increased with inulin consumption ( p < 0.05). CONCLUSION: Pre-meal inulin consumption does not acutely decrease EI or suppress appetite in older adults. Further research should address individual differences among diets, eating behaviors, and microbiota profiles.
Sujet(s)
Ration calorique , Inuline/administration et posologie , Obésité/traitement médicamenteux , Surpoids/traitement médicamenteux , Sujet âgé , Appétit , Indice de masse corporelle , Études croisées , Méthode en double aveugle , Exercice physique , Femelle , Humains , Mâle , Repas , Adulte d'âge moyen , Projets pilotesRÉSUMÉ
Prediabetes is associated with low-grade chronic inflammation that increases the risk for developing type 2 diabetes (T2D) and cardiovascular disease (CVD). An elevated lipopolysaccharide concentration, associated with dysbiosis of the intestinal microbiota, has been implicated in the development of both T2D and CVD. Selective modulation of the intestinal microbiota with prebiotics reduces intestinal permeability and endotoxin concentrations, inflammation, and metabolic dysfunction in rodents. The effect of prebiotic supplementation on cardio-metabolic function in humans at risk for T2D is not known. The primary aim of this trial is to determine the influence of prebiotic supplementation with inulin on insulin sensitivity and skeletal muscle metabolic flexibility in adults at risk for T2D. We hypothesize that prebiotic supplementation with inulin will improve insulin sensitivity and skeletal muscle metabolic flexibility. We will randomize 48 adults (40-75 yrs) with prediabetes or a score ≥ 5 on the American Diabetes Association (ADA) risk screener to 6 weeks of prebiotic supplementation with inulin (10 g/day) or placebo. Subjects will be provided with all food for the duration of the study, to avoid potential confounding through differences in dietary intake between individuals. Intestinal permeability, serum endotoxin concentrations, insulin sensitivity, skeletal muscle metabolic flexibility, endothelial function, arterial stiffness, and fecal bacterial composition will be measured at baseline and following treatment. The identification of prebiotic supplementation with inulin as an efficacious strategy for reducing cardio-metabolic risk in individuals at risk of T2D could impact clinical practice by informing dietary recommendations and increasing acceptance of prebiotics by the scientific and medical community.