Increased Plasma Branched Short-Chain Fatty Acids and Improved Glucose Homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES).

Short-chain fatty acids (SCFAs) have been extensively studied for potential beneficial roles in glucose homeostasis and risk of diabetes; however, most of this research has focused on butyrate, acetate, and propionate. The effect on metabolism of branched SCFAs (BSCFAs; isobutyrate, isovalerate, and methylbutyrate) is largely unknown. In a cohort of 219 non-Hispanic White participants and 126 African American participants, we examined the association of BSCFA with dysglycemia (prediabetes and diabetes) and oral glucose tolerance test-based measures of glucose and insulin homeostasis, as well as with demographic, anthropometric, lifestyle, and lipid traits, and other SCFAs. We observed a bimodal distribution of BSCFAs, with 25 individuals having high levels (H-BSCFA group) and 320 individuals having lower levels (L-BSCFA group). The prevalence of dysglycemia was lower in the H-BSCFA group compared with the L-BSCFA group (16% vs. 49%; P = 0.0014). This association remained significant after adjustment for age, sex, race, BMI, and levels of other SCFAs. Consistent with the lower rate of dysglycemia, fasting and postprandial glucose levels were lower and the disposition index was higher in the H-BSCFA group. Additional findings in H-BSCFA versus L-BSCFA included lower fasting and postprandial C-peptide levels and lower insulin clearance without differences in insulin levels, insulin sensitivity, insulin secretion, or other variables examined, including diet and physical activity. As one of the first human studies associating higher BSCFA levels with lower odds of dysglycemia and improved glucose homeostasis, this study sets the stage for further investigation of BSCFA as a novel target for prevention or treatment of diabetes.

Associations between avocado intake and measures of glucose and insulin homeostasis in Hispanic individuals with and without type 2 diabetes: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

BACKGROUND AND AIMS: To investigate associations between avocado intake and glycemia in adults with Hispanic/Latino ancestry. METHODS AND RESULTS: The associations of avocado intake with measures of insulin and glucose homeostasis were evaluated in a cross-sectional analysis of up to 14,591 Hispanic/Latino adults, using measures of: average glucose levels (hemoglobin A1c; HbA1c), fasting glucose and insulin, glucose and insulin levels after an oral glucose tolerance test (OGTT), and calculated measures of insulin resistance (HOMA-IR, and HOMA-%ß), and insulinogenic index. Associations were assessed using multivariable linear regression models, which controlled for sociodemographic factors and health behaviors, and which were stratified by dysglycemia status. In those with normoglycemia, avocado intake was associated with a higher insulinogenic index (ß = 0.17 ± 0.07, P = 0.02). In those with T2D (treated and untreated), avocado intake was associated with lower hemoglobin A1c (HbA1c; ß = -0.36 ± 0.21, P = 0.02), and lower fasting glucose (ß = -0.27 ± 0.12, P = 0.02). In the those with untreated T2D, avocado intake was additionally associated with HOMA-%ß (ß = 0.39 ± 0.19, P = 0.04), higher insulin values 2-h after an oral glucose load (ß = 0.62 ± 0.23, P = 0.01), and a higher insulinogenic index (ß = 0.42 ± 0.18, P = 0.02). No associations were observed in participants with prediabetes. CONCLUSIONS: We observed an association of avocado intake with better glucose/insulin homeostasis, especially in those with T2D.

Accuracy and Glycemic Efficacy of Continuous Glucose Monitors in Critically Ill COVID-19 Patients: A Retrospective Study.

BACKGROUND: Continuous glucose monitoring (CGM) is approved for insulin dosing decisions in the ambulatory setting, but not currently for inpatients. CGM has the capacity to reduce patient-provider contact in inpatients with coronavirus disease 2019 (COVID-19), thus potentially reducing in hospital virus transmission. However, there are sparse data on the accuracy and efficacy of CGM to titrate insulin doses in inpatients. METHODS: Under an emergency use protocol, CGM (Dexcom G6) was used alongside standard point-of-care (POC) glucose measurements in patients critically ill from complications of COVID-19 requiring intravenous (IV) insulin. Glycemic control during IV insulin therapy was retrospectively assessed comparing periods with and without adjunctive CGM use. Accuracy metrics were computed and Clarke Error Grid analysis performed comparing CGM glucose values with POC measurements. RESULTS: Twenty-four critically ill patients who met criteria for emergency use of CGM resulted in 47 333 CGM and 5677 POC glucose values. During IV insulin therapy, individuals' glycemic control improved when CGM was used (mean difference -30.7 mg/dL). Among 2194 matched CGM: POC glucose pairs, a high degree of concordance was observed with a mean absolute relative difference of 14.8% and 99.5% of CGM: POC pairs falling in Zones A and B of the Clarke Error Grid. CONCLUSIONS: Continuous glucose monitoring use in critically ill COVID-19 patients improved glycemic control during IV insulin therapy. Continuous glucose monitoring glucose data were highly concordant with POC glucose during IV insulin therapy in critically ill patients suggesting that CGM could substitute for POC measurements in inpatients thus reducing patient-provider contact and mitigating infection transmission.

The Roles of Gut Microbiome and Plasma Metabolites in the Associations between ABO Blood Groups and Insulin Homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES).

Non-O blood groups are associated with decreased insulin sensitivity and risk of type 2 diabetes. A recent study pinpointed the associations between ABO blood groups and gut microbiome, which may serve as potential mediators for the observed increased disease risks. We aimed to characterize associations between ABO haplotypes and insulin-related traits as well as potential mediating pathways. We assessed insulin homeostasis in African Americans (AAs; n = 109) and non-Hispanic whites (n = 210) from the Microbiome and Insulin Longitudinal Evaluation Study. The ABO haplotype was determined by six SNPs located in the ABO gene. Based on prior knowledge, we included 21 gut bacteria and 13 plasma metabolites for mediation analysis. In the white study cohort (60 ± 9 years, 42% male), compared to the O1 haplotype, A1 was associated with a higher Matsuda insulin sensitivity index, while a lower relative abundance of Bacteroides massiliensis and lactate levels. Lactate was a likely mediator of this association but not Bacteroides massiliensis. In the AAs group (57 ± 8 years, 33% male), we found no association between any haplotype and insulin-related traits. In conclusion, the A1 haplotype may promote healthy insulin sensitivity in non-Hispanic whites and lactate likely play a role in this process but not selected gut bacteria.

Butyrate-Producing Bacteria and Insulin Homeostasis: The Microbiome and Insulin Longitudinal Evaluation Study (MILES).

Gut microbiome studies have documented depletion of butyrate-producing taxa in type 2 diabetes. We analyzed associations between butyrate-producing taxa and detailed measures of insulin homeostasis, whose dysfunction underlies diabetes in 224 non-Hispanic Whites and 129 African Americans, all of whom completed an oral glucose tolerance test. Stool microbiome was assessed by whole-metagenome shotgun sequencing with taxonomic profiling. We examined associations among 36 butyrate-producing taxa (n = 7 genera and 29 species) and insulin sensitivity, insulin secretion, disposition index, insulin clearance, and prevalence of dysglycemia (prediabetes plus diabetes, 46% of cohort), adjusting for age, sex, BMI, and race. The genus Coprococcus was associated with higher insulin sensitivity (ß = 0.14; P = 0.002) and disposition index (ß = 0.12; P = 0.012) and a lower rate of dysglycemia (odds ratio [OR] 0.91; 95% CI 0.85-0.97; P = 0.0025). In contrast, Flavonifractor was associated with lower insulin sensitivity (ß = -0.13; P = 0.004) and disposition index (ß = -0.11; P = 0.04) and higher prevalence of dysglycemia (OR 1.22; 95% CI 1.08-1.38; P = 0.0013). Species-level analyses found 10 bacteria associated with beneficial directions of effects and two bacteria with adverse associations on insulin homeostasis and dysglycemia. Although most butyrate producers analyzed appear to be metabolically beneficial, this is not the case for all such bacteria, suggesting that microbiome-directed therapeutic measures to prevent or treat diabetes should be targeted to specific butyrate-producing taxa rather than all butyrate producers.

Associations between adherence to the dietary approaches to stop hypertension (DASH) diet and six glucose homeostasis traits in the Microbiome and Insulin Longitudinal Evaluation Study (MILES).

BACKGROUND AND AIMS: The DASH diet conveys protection against type 2 diabetes mellitus (T2D) Via plant-based and non-plant-based recommendations. Research has not identified which glucose homeostasis pathways are improved. We examined associations between adherence to a DASH diet and six glucose homeostasis traits, probing whether associations could be attributed to the plant-based (DASH-P) and/or non-plant based (DASH-NP) components. METHODS AND RESULTS: We included data from 295 adults without T2D (age 59.3 ± 9.00 years; 63.46% non-Hispanic White and 36.54% African American, self-reported race ancestry) participating in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). An oral glucose tolerance test (OGTT) yielded fasting plasma glucose, insulin, C-peptide, and insulin secretion, sensitivity, and disposition index. Habitual dietary intake was assessed by food frequency questionnaire (FFQ). Associations between DASH components and glucose homeostasis traits were examined, controlling for demographics, body mass index (BMI), physical activity, and energy intake. For significant associations, the models were repeated with scores for DASH-P and DASH-NP as predictors in the same model. DASH and DASH-P scores were inversely associated with fasting plasma glucose (DASH:ß = -0.036 ± 0.012,P = 0.005; DASH-P: ß = -0.04 ± 0.017,P = 0.002), and positively associated with insulin sensitivity (DASH:ß = 0.022 ± 0.012,P = 0.042; DASH-P: = 0.036 ± 0.015,P = 0.014). The DASH score was also associated with disposition index (ß = 0.026 ± 0.013,P = 0.038), but this association did not reach significance with DASH-P (ß = 0.035 ± 0.018,P = 0.051). No associations were observed with DASH-NP score (all P > 0.05). CONCLUSIONS: DASH diet is associated with improvement in specific glucose homeostasis traits, likely arising from increased plant-based foods. Such research may help tailor future dietary advice to specific metabolic risk, and to food groups most effective at improving these.

Agricultural policy and societal factors influence patients' ability to follow a healthy diet.

•Cardiovascular and cardiometabolic diseases are largely preventable, and are propagated by a poor diet.•Poor diet may be due to a lack of supply and access to healthy foods, agricultural subsidies, and marketing.•Improving national dietary intake starts with enhancing dietary guidelines, enacting legislative changes to optimize agricultural subsidies and food advertising, and incentivizing a plant-forward diet.

Defining the Relative Role of Insulin Clearance in Early Dysglycemia in Relation to Insulin Sensitivity and Insulin Secretion: The Microbiome and Insulin Longitudinal Evaluation Study (MILES).

Insulin resistance and insufficient insulin secretion are well-recognized contributors to type 2 diabetes. A potential role of reduced insulin clearance has been suggested, but few studies have investigated the contribution of insulin clearance while simultaneously examining decreased insulin sensitivity and secretion. The goal of this study was to conduct such an investigation in a cohort of 353 non-Hispanic White and African American individuals recruited in the Microbiome and Insulin Longitudinal Evaluation Study (MILES). Participants underwent oral glucose tolerance tests from which insulin sensitivity, insulin secretion, insulin clearance, and disposition index were calculated. Regression models examined the individual and joint contributions of these traits to early dysglycemia (prediabetes or newly diagnosed diabetes). In separate models, reduced insulin sensitivity, reduced disposition index, and reduced insulin clearance were associated with dysglycemia. In a joint model, only insulin resistance and reduced insulin secretion were associated with dysglycemia. Models with insulin sensitivity, disposition index, or three insulin traits had the highest discriminative value for dysglycemia (area under the receiver operating characteristics curve of 0.82 to 0.89). These results suggest that in the race groups studied, insulin resistance and compromised insulin secretion are the main independent underlying defects leading to early dysglycemia.

Impact of Early Urine Specimen Collection on Emergency Department Time to Disposition: A Randomized Controlled Trial.

Background Diagnostic testing in the ED increases the length of stay (LOS). Urinalysis testing is highlighted specifically as a source of delays. We aim to determine whether a triage-initiated urine specimen collection process decreases ED time to disposition (TTD) in ambulatory patients with abdominal pain. Methods This prospective, randomized controlled study was implemented at a Suburban Level One trauma ED with greater than 120,000 annual visits. A convenience sample of patients was recruited. Adult, non-ambulance patients presenting with abdominal pain were eligible. Participants were randomized into experimental and control groups. Patients in the control group provided a urine sample after physician evaluation, if ordered by the provider. Patients in the experimental group were prompted to provide a urine sample in the triage restrooms immediately after screening at the greeter desk. The UA sample was transported to the treatment area and sent to the laboratory after physician evaluation. Results A total of 125 control patients and 124 experimental patients were enrolled. Forty-two patients were excluded because they were unable to provide a urine sample. Patients who had a urinalysis ordered were included in statistical analysis. Final data set included 65 patients in the experimental group and 96 patients in the control group. No significant difference (p=0.5072) in disposition time between subjects in the experimental group (n=65, mean=5:17 [hours:min]) and subjects in the control group (n=96, mean=5:30) was found. Conclusions The triage protocol for urine specimen collection did not significantly reduce ED TTD. Further research in overcrowded EDs with long patient waiting room times may benefit from implementing a triage protocol for urine specimen collection.

Pediatric Integrative Medicine in Academia: Stanford Children's Experience.

Pediatric integrative medicine is an emerging field which, to date, has not been described in detail in academic medical centers in the United States. Early research of pediatric integrative medicine modalities shows promise for the treatment of common pediatric conditions such as irritable bowel syndrome, acute and chronic pain, headache, and allergy, among others. In light of the growing prevalence of pediatric illnesses and patient complexity, it is crucial to emphasize the patient's overall well-being. As academic centers around the world start to develop pediatric integrative medicine programs, the aim of this manuscript is to briefly highlight evidence of effective integrative treatments in pediatric subspecialties, to describe the establishment of our integrative medicine program, to summarize its early efforts, and to discuss potential barriers and keys to success.

Left ventricular dysfunction is associated with cerebral grey matter injury: an in-vivo brain MRI segmentation study.

BACKGROUND AND PURPOSE: Patients with heart failure often experience cognitive deficits. The relationship between systolic function and cerebral gray matter injury is unclear. METHODS: An automated program SIENAX (v2.2) was used to extract brain volume and for segmentation of grey and white matter in subjects with low left ventricular ejection fraction (< 50%) and normal ejection fraction (≥ 50%). T1-weighted spin-echo axial sequences were used for analysis. RESULTS: 14 cases with low left ventricular ejection fraction and 14 age-matched controls were evaluated. A modest correlation between grey matter volume and low left ventricular ejection fraction was demonstrated (r=0.51, p=0.06), not seen with white matter volumes. The mean grey matter volume was 507.4±166.3 ml in the low left ventricular ejection fraction group and 541.3±167.2 ml in the control group (p=0.57). CONCLUSION: Low left ventricular ejection fraction may lead to cerebral grey matter injury. Larger studies including multi-modal MRI and neuropsychological assessments are warranted to explore potential mechanisms.