Compositional and functional alterations of gut microbiota in patients with stroke

Background and aimsThere is accumulating evidence that gut microbiota plays a key role in cardiovascular diseases. Gut bacteria can transform dietary choline, l-carnitine, and trimethylamine N-oxide (TMAO) into trimethylamine, which can be oxidized into TMAO again in the liver. However, the alterations of the gut microbiota in large artery atherosclerotic (LAA) stroke and cardioembolic (CE) stroke have been less studied.Methods and resultsWe performed a case–control study in patients with LAA and CE types of strokes. We profiled the gut microbiome using Illumina sequencing of the 16S ribosomal RNA gene (V4–V5 regions), and TMAO was determined via liquid chromatography–tandem mass spectrometry. Our results showed that the TMAO levels in the plasma of patients with LAA and CE strokes were significantly higher than those in controls (LAA stroke, 2931 ± 456.4 ng/mL; CE stroke, 4220 ± 577.6 ng/mL; healthy control, 1663 ± 117.8 ng/mL; adjusted p < 0.05). The TMAO level in the plasma of patients with LAA stroke was positively correlated with the carotid plaque area (rho = 0.333, 95% CI = 0.08–0.55, p = 0.0093). Notably, the composition and the function of gut microbiota in the LAA stroke group were significantly different from those in the control group (FDR-adjusted p-value < 0.05). There was no significant association between gut microbiota and CE stroke in our study.ConclusionThis study provides evidence for significant compositional and functional alterations of the gut microbiome in patients with LAA stroke. Gut microbiota might serve as a potential biomarker for patients with LAA stroke.     

Soy food intake associates with changes in the metabolome and reduced blood pressure in a gut microbiota dependent manner

Background and aimsConsumption of soy foods has been associated with protection against cardiometabolic disease, but the mechanisms are incompletely understood.We hypothesized that habitual soy food consumption associates with gut microbiome composition, metabolite production, and the interaction between diet, microbiota and metabolites.Methods and resultsWe analyzed dietary soy intake, plasma and stool metabolites, and gut microbiome data from two independent cross-sectional samples of healthy US individuals (N = 75 lean or overweight, and N = 29 obese).Habitual soy intake associated with several circulating metabolites. There was a significant interaction between soy intake and gut microbiome composition, as defined by gut enterotype, on metabolites in plasma and stool. Soy consumption associated with reduced systolic blood pressure, but only in a subset of individuals defined by their gut microbiome enterotype, suggesting that responsiveness to soy may be dependent on microbiome composition. Soy intake was associated with differences in specific microbial taxa, including two taxa mapping to genus Dialister and Prevotella which appeared to be suppressed by high soy intake We identified context-dependent effects of these taxa, where presence of Prevotella was associated with higher blood pressure and a worse cardiometabolic profile, but only in the absence of Dialister.ConclusionsThe gut microbiome is an important intermediate in the interplay between dietary soy intake and systemic metabolism. Consumption of soy foods may shape the microbiome by suppressing specific taxa, and may protect against hypertension only in individuals with soy-responsive microbiota.Clinical trials registryNCT02010359 at clinicaltrials.gov.     

Comparative effectiveness of glucagon-like peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors on noninvasive indices of hepatic steatosis and fibrosis in patients with type 2 diabetes mellitus

Background and aimsNonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM). There is currently no approved treatment for NAFLD. The main aim was the evaluation of the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) vs. dipeptidyl peptidase-4 inhibitor (DPP-4i) treatment on noninvasive indices of hepatic steatosis and fibrosis in patients with T2DM.MethodsIn this retrospective study, three noninvasive indices of hepatic steatosis [HSI, NAFLD ridge score, and triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio] and five of fibrosis (APRI, FIB-4, NAFLD fibrosis score, BAAT and BARD) were calculated before and after (6–18 months) the addition of a DPP-4i (n = 152) or a GLP-1 RA (n = 37) in patients with T2DM.ResultsRegarding steatosis indices, NAFLD ridge score was significantly decreased in the GLP-1 RA group (baseline: 0.90 ± 0.34, follow-up: 0.67 ± 0.24; p = 0.001), but not in the DPP-4i group (p = 0.25); the difference for group1time interaction was significant (p = 0.02). HSI showed a trend between groups, being significantly different at baseline and follow-up (p < 0.001) with no significant difference in group1time interaction. Indices of fibrosis were not essentially changed within or between groups.ConclusionsNAFLD ridge score was significantly decreased after the addition of GLP-1 RA in patients with T2DM. This study warrants further prospective clinical trials.     

The ankle-brachial index for assessing the prevalence of peripheral artery disease and cardiovascular risk in patients with type 2 diabetes mellitus

Background and aimsType 2 diabetes mellitus (T2DM) is an important risk factor for peripheral artery disease (PAD). Ankle-Brachial Index (ABI) was found associated with a higher cardiovascular (CV) risk and mortality. The main goals of this study were to establish the prevalence of PAD in a T2DM population, and assess the relationship between PAD and the CV risk calculated with the CUORE Project score (CPS) (https://www.cuore.iss.it/). The association between the ABI, the main risk factors for PAD and T2DM complications was also investigated.Methods and resultsTwo hundred patients were consecutively enrolled. The prevalence of PAD in this population was 17%. The CV risk tended to be higher (p = 0.0712) in the group with a pathological ABI than in the group with a normal ABI. Glycated hemoglobin (r = ?0.1591; p = 0.0244), total cholesterol (r = ?0.1958; p = 0.0054), LDL cholesterol (r = ?0.1708; p = 0.0156) and systolic blood pressure (r = ?0.1523; p = 0.0313) correlated significantly and inversely with the left ABI. The frequency of diabetic retinopathy was significantly higher in the group with a pathological ABI (p = 0.0316).ConclusionsThe data reveal a high prevalence of PAD in patients with T2DM. The CPS confirmed that patients with a pathological ABI have tendency to a higher CV risk. The results point to the importance of an accurate CV assessment – also measuring individuals’ ABI and calculating their CPS - to better pinpoint those at high risk of PAD, especially among patients with T2DM.     

A causal relationship between alcohol intake and type 2 diabetes mellitus: A two-sample Mendelian randomization study

Background and aimsWe investigated whether alcohol intake has a causal relationship with type 2 diabetes mellitus (T2DM) risk in adults of the Korean Genomic Epidemiology Study using two-sample Mendelian randomization (MR) analysis.Methods and resultsDaily alcohol intake was calculated based on the type, average amount, and frequency of alcohol consumption for six months before the interview. The participants were divided into low- and high-alcohol intake of 20 g/day. After adjusting for the covariates related to T2DM, the independent genetic variants (instrumental variables) related to alcohol intake were explored by GWAS analysis in a city hospital-based cohort (n = 58,701). SNPs with a significant level of p-value <5 × 10^?8 and linkage disequilibrium of r² < 0.001 were retrieved. MR methods were used to analyze the causality between alcohol intake and the T2DM risk, and the heterogeneity and leave-one-out sensitivity analyses were conducted in Ansan/Ansung plus rural cohorts (n = 13,598). High alcohol intake increased T2DM risk when the inverse-variance weighted (P = 0.012) and weighted median (P = 0.034) methods were used, but not when the MR-Egger method was used. No significant heterogeneity and horizontal pleiotropy between alcohol intake and T2DM were detected. A single genetic variant did not affect the causal association in a leave-one-out sensitivity analysis.ConclusionThis study supports that heavy alcohol intake appears to be causally associated with T2DM risk.     

The relationship of family history and risk of type 2 diabetes differs by ancestry

AimType 2 diabetes (T2DM) in a first-degree relative is a risk factor for incident diabetes. Americans of African ancestry (AA) have higher rates of T2DM than Americans of European ancestry (EA). Thus, we aimed to determine whether the presence, number and kinship of affected relatives are associated with race-specific T2DM incidence in a prospective study of participants from the Genetic Study of Atherosclerosis Risk (GeneSTAR), who underwent baseline screening including a detailed family history.MethodsNondiabetic healthy siblings (n = 1405) of patients with early-onset coronary artery disease (18–59 years) were enrolled (861 EA and 544 AA) and followed for incident T2DM (mean 14 ± 6 years).ResultsBaseline age was 46.2 ± 7.3 years and 56% were female. T2DM occurred in 12.3% of EA and 19.1% of AA. Among EA, 32.6% had ≥ 1 affected first-degree relatives versus 53.1% in AA, P < 0.0001. In fully adjusted Cox proportional hazard analyses, any family history was related to incident T2DM in EA (HR = 2.53, 95% CI: 1.58–4.06) but not in AA (HR = 1.01, 0.67–1.53). The number of affected relatives conferred incremental risk of T2DM in EA with HR = 1.82 (1.08–3.06), 4.83 (2.15–10.85) and 8.46 (3.09–23.91) for 1, 2, and ≥ 3 affected, respectively. In AA only ≥ 3 affected increased risk (HR = 2.45, 1.44–4.19). Specific kinship patterns were associated with incident T2DM in EA but not in AA.ConclusionsThe presence of any first-degree relative with T2DM does not discriminate risk in AA given the high race-specific prevalence of diabetes. Accounting for the number of affected relatives may more appropriately estimate risk for incident diabetes in both races.     

Evolution of Myocardial Dysfunction in Asymptomatic Patients at Risk of Heart Failure

ObjectivesThe determinants of changes in systolic and diastolic parameters in patients age >65 years, at risk of heart failure (HF), and with and without asymptomatic type 2 diabetes mellitus (T2DM) was assessed by echocardiography. The association between metformin and myocardial function was also assessed.BackgroundThe increasing prevalence of T2DM will likely further fuel the epidemic of HF. Understanding the development or progression of left ventricular (LV) dysfunction may inform effective measures for HF prevention.MethodsA total of 982 patients with at least one HF risk factor (hypertension, obesity, or T2DM) were recruited from 2 community-based populations and divided into 2 groups: T2DM (n = 431, age 71 ± 4 years) and non-T2DM (n = 551, age 71 ± 5 years). Associations of metformin therapy were evaluated in the T2DM group. All underwent a comprehensive echocardiogram, including global longitudinal strain (GLS) and diastolic function (transmitral flow [E], annular velocity [e’]) at baseline and follow-up (median 19 months [interquartile range: 17 to 26 months]). Comparisons were facilitated by propensity matching.ResultsA reduction in GLS was observed in the T2DM group (baseline ?17.8 ± 2.6% vs. follow-up ?17.4 ± 2.8%; p = 0.003), but not in the non-T2DM group (?18.7 ± 2.7% vs. ?18.6 ± 3.0%; p = 0.41). Estimated LV filling pressures increased in both the T2DM group (p = 0.001) and the non-T2DM group (p = 0.04). Metformin-treated patients with T2DM did not increase estimated LV filling pressure (E/e’ baseline 8.9 ± 2.7 vs. follow-up 9.1 ± 2.7; p = 0.485) or change e’ (7.6 ± 1.5 cm/s vs. 7.6 ± 1.8 cm/s; p = 0.88). After propensity matching, metformin was associated with a smaller change in e’ (β = 0.58 [95% CI: 0.13 to 1.03]; p = 0.013) and E/e’ (β = ?0.96 [95% CI: ?1.66 to ?0.26]; p = 0.007) but was not associated with a change in GLS (p = 0.46).ConclusionsOver 2 years, there is a worsening of GLS and LV filling pressures in asymptomatic diabetic patients with HF risk factors. Metformin use is associated with less deterioration of LV filling pressures and myocardial relaxation but had no association with systolic function.     

Postprandial endothelial dysfunction and CIMT after oral fat challenge in patients with type 2 diabetes mellitus with and without macrovascular disease - A preliminary study

BackgroundVery few studies have reported on association of postprandial lipids and endothelial dysfunction among patients with diabetes. Whether endothelial dysfunction particularly postprandial FMD is worse in patients with T2DM with macrovascular disease compared to those without and whether this difference is related to postprandial hypertriglyceridemia (PPHTg) is unclear. Therefore, present study was aimed to assess the relationship between PPHTg and endothelial function in patients with T2DM with and without macrovascular disease.MethodEndothelial dysfunction by FMD and CIMT were compared in patients with T2DM with and without macrovascular disease (n = 13 each group) and 13 age, sex and BMI matched healthy individuals after an oral fat challenge.ResultsThere was significant postprandial deterioration of FMD 4-hr after fat challenge in patients with diabetes (P < 0.001) as well as healthy individuals (P = 0.004). Patients with diabetes with macrovascular disease had significantly lower fasting (5.7 ± 6.1% vs. 22.7 ± 10.0% and vs. 24.7 ± 5.3%) as well as postprandial (4-hr) (3.1 ± 5.0% vs. 15.3 ± 8.1% and vs. 15.4 ± 5.7%) FMD compared to other two groups. Fasting, postprandial as well as change in FMD and CIMT in patients with diabetes correlated significantly with fasting as well as postprandial triglycerides with stronger correlation in those with macrovascular disease.ConclusionStudy found significant endothelial dysfunction by FMD that shows substantial further deterioration postprandially following high fat meal in patients with diabetes with macrovascular disease compared to patients with diabetes without macrovascular disease and healthy individuals. Study also indicates that PPHTg is a contributor to endothelial dysfunction. However, more studies are required to corroborate these findings.     

Effects of TM6SF2 rs58542926 polymorphism on hepatocellular lipids and insulin resistance in early type 2 diabetes

Background and aimsIncreased hepatocellular lipid content (HCL) is linked to insulin resistance, risk of type 2 diabetes and related complications. Conversely, a single-nucleotide polymorphism (TM6SF2^EK; rs58542926) in the transmembrane 6 superfamily member 2-gene has been associated with nonalcoholic fatty liver disease (NAFLD), but lower cardiovascular risk. This case-control study tested the role of this polymorphism for tissue-specific insulin sensitivity during early course of diabetes.Methods and resultsMales with recent-onset type 2 diabetes with (TM6SF2^EK: n = 16) or without (TM6SF2^EE: n = 16) the heterozygous TM6SF2-polymorphism of similar age and body mass index, underwent Botnia-clamps with [6,6-²H₂]glucose to measure whole-body-, hepatic- and adipose tissue-insulin sensitivity. HCL was assessed with ¹H-magnetic-resonance-spectroscopy. A subset of both groups (n = 24) was re-evaluated after 5 years. Despite doubled HCL, TM6SF2^EK had similar hepatic- and adipose tissue-insulin sensitivity and 27% higher whole-body-insulin sensitivity than TM6SF2^EE. After 5 years, whole-body-insulin sensitivity, HCL were similar between groups, while adipose tissue-insulin sensitivity decreased by 87% and 55% within both groups and circulating triacylglycerol increased in TM6SF2^EE only.ConclusionsThe TM6SF2-polymorphism rs58542926 dissociates HCL from insulin resistance in recent-onset type 2 diabetes, which is attenuated by disease duration. This suggests that diabetes-related metabolic alterations dominate over effects of the TM6SF2-polymorphism during early course of diabetes and NAFLD.     

Differences in Demographics and Outcomes Between Men and Women With Spontaneous Coronary Artery Dissection

BackgroundSpontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of myocardial infarction (MI) that most frequently affects women. The characteristics of men with SCAD are less well described.ObjectivesThe aim of this study was to describe the characteristics of men with SCAD.MethodsWe compared baseline demographics, clinical presentation, angiographic findings and cardiovascular outcomes of men and women in the Canadian SCAD Study. Major adverse cardiovascular events (MACE) were composite of death, MI, stroke or transient ischemic attack, heart failure hospitalization, and revascularization.ResultsOf 1,173 patients with SCAD, 123 (10.5%) were men. Men with SCAD were younger than women (mean age 49.4 ± 9.6 years vs 52.0 ± 10.6 years; P = 0.01). Men had lower rate of prior MI than women (0.8% vs 7.0%; P = 0.005). Men were less likely to have fibromuscular dysplasia (FMD) (27.8% vs 52.7%; P = 0.001), depression (9.8% vs 20.2%; P = 0.005), emotional stress (35.0% vs 59.3%; P < 0.001), or high score on the Perceived Stress Scale (3.5% vs 11.0%; P = 0.025) but were more likely to report isometric physical stress (40.2% vs 24.0%; P = 0.007). There was no difference in angiographic types of SCAD, but men had more circumflex artery (44.4% vs 30.9%; P = 0.001) and fewer right coronary artery (11.8% vs 21.7%; P = 0.0054) dissections. At median follow-up of 3.0 (IQR: 2.0-3.8) years, men had fewer hospital presentations with chest pain (10.6% vs 24.8%; P < 0.001). There were no differences in in-hospital events or follow-up MACE (7.3% vs 12.7%; P = 0.106).ConclusionsTen percent of SCAD patients were men. Men were younger and more likely to have a physical trigger but were less likely to have FMD, depression, or an emotional trigger. Men had less recurrent chest pain but no significant difference in MACE.     

Association between KLF6 rs3750861 polymorphism and plasma ceramide concentrations in post-menopausal women with type 2 diabetes

Background and aimBased on the emerging role of Kruppel-like factor 6 (KLF6) in lipid metabolism, we examined whether there is a relationship between the KLF6 rs3750861 genetic variant and plasma ceramide levels in people with type 2 diabetes mellitus (T2DM).Methods and resultWe measured six previously identified plasma ceramides, which have been associated with increased cardiovascular risk [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] amongst 101 Caucasian post-menopausal women with T2DM, who consecutively attended our diabetes outpatient service during a 3-month period. Plasma ceramides were measured by targeted liquid chromatography-tandem mass spectrometry assay. Genotyping of the KLF6 rs3750861 polymorphism was performed by TaqMan-Based RT-PCR system.Overall, 87 (86.1%) patients had KLF6 rs3750861 C/C genotype and 14 (13.9%) had C/T or T/T genotypes. After adjustment for age, diabetes-related variables, use of lipid-lowering drugs and other potential confounders, patients with C/T or T/T genotypes had higher plasma Cer(d18:1/18:0) (0.159 ± 0.05 vs. 0.120 ± 0.04 μmol/L, p = 0.012), Cer(d18:1/20:0) (0.129 ± 0.04 vs. 0.098 ± 0.03 μmol/L, p = 0.008), and Cer(d18:1/24:1) (1.236 ± 0.38 vs. 0.978 ± 0.36 μmol/L, p = 0.032) compared with those with C/C genotype.ConclusionsThe C/T or T/T genotypes of rs3750861 in the KLF6 gene were closely associated with higher levels of specific plasma ceramides in post-menopausal women with T2DM.     

Correlation between basal metabolic rate,visceral fat and insulin resistance among type 2 diabetes mellitus with peripheral neuropathy

BackgroundBasal Metabolic Rate (BMR) means the amount of energy utilized by body in physical and psychological resting rate, after a night sleep, awake without any previous physical activity post meal (10 h after last meal) & neutral environment. In people with type 2 diabetes mellitus (T2DM) there is an increase in BMR which is said to be associated with the level of glycaemic control. So, the objective of the study was to find out the correlation between BMR, Insulin resistance and Visceral fat in T2DM with peripheral neuropathy.Materials & methodsA total of 50 participants with T2DM with peripheral neuropathy were included. Age group of 30–75 years were selected for the study. Participants with a known history of neurological disease, locomotor disability, and pregnancy were excluded from the study. Demographic details of the participants like duration of diabetes mellitus, age, Fasting Blood Glucose, Fasting Insulin, HOMA-IR, Glycated Haemoglobin (HBA1c), Neuropathy and Blood pressure values were noted. We measured Basal Metabolic Rate (BMR) by using Mifflin-St Jeor predictive equation in T2DM with peripheral neuropathy.ResultsThe mean age of the participants is 60.16 ± 10.62. The mean duration of T2DM 13.44 ± 11.92. In the present study we found a statistical significant correlation between BMR and HOMA IR (r = 0.913*; p = 0.000), BMR & Fasting blood sugar (FBS) (r = 0.281*; p = 0.048), BMR and Visceral fat (VF) (r = 0.332*; p = 0.018).ConclusionBasal metabolic rate is correlated to Homa-IR, visceral fat, fasting blood sugar and musculoskeletal mass among T2DM with peripheral neuropathy.     

Effect of dietary sodium restriction on blood pressure in type 2 diabetes: A meta-analysis of randomized controlled trials

AimsAlthough current guidelines recommend reduction of salt intake in patients with diabetes, the benefits of reducing salt intake in people with type 2 diabetes mellitus (T2DM) lack clear evidence. Therefore, we performed a meta-analysis of available randomized controlled trials (RCTs) of sodium restriction and blood pressure (BP) in patients with T2DM.Data synthesisWe performed a systematic search of the online databases that evaluated the effect of dietary sodium restriction on BP in patients with T2DM. Sodium intake was expressed by 24 h urinary sodium excretion (UNaV). Q statistics and I² were used to explore between-study heterogeneity. A random-effects model was used in the presence of significant heterogeneity; otherwise, a fixed-effects model was applied. Eight RCTs with 10 trials (7 cross-over and 3 parallel designs) were included in the meta-analysis. Compared with ordinary sodium intake, dietary sodium restriction significantly decreased UNaV (weighted mean difference, WMD: ?38.430 mmol/24 h; 95% CI: ?41.665 mmol/24 h to ?35.194 mmol/24 h). Sodium restriction significantly lowered systolic BP (WMD: ?5.574 mm Hg; 95% CI: ?8.314 to ?2.834 mm Hg; I² = 0.0%) and diastolic BP (WMD: ?1.675 mm Hg; 95% CI: ?3.199 to ?0.150 mm Hg; I² = 0.0%) with low heterogeneity among the studies. No publication bias was found from Begg's and Egger's tests.ConclusionsSodium restriction significantly reduces SBP and DBP in patients with T2DM.     

The association between a novel inflammatory biomarker,systemic inflammatory response index and the risk of diabetic cardiovascular complications

Background and aimSystemic inflammatory response index (SIRI) is a novel inflammatory biomarker. The relationship between SIRI and the risk of diabetic cardiovascular complications is still unclear. The purpose of our study was to address the correlation between SIRI and the risk of cardiovascular diseases (CVD) in diabetes mellitus (DM) patients.Methods and resultsA total of 8759 individuals were selected from the National Health and Nutrition Examination Survey (NHANES) (2015–2020) in our study. Comparing with control (n = 6446) and pre-DM (n = 350) individuals, the DM patients (n = 1963) show the higher SIRI level (all P < 0.001) and prevalence of CVD (all P < 0.001). Furthermore, in a fully adjusted model, we observed the increase of tertiles of SIRI was a risk factor for CVD in DM patients (the middle tertile: 1.80, 95% CI: 1.13–3.13; the highest tertile: 1.91, 95% CI: 1.03–3.22; all P < 0.05), while the relationship between hypersensitive CRP (hs-CRP) and the risk of diabetic cardiovascular complications was not observed (all P > 0.05). Furthermore, the SIRI tertiles–CVD association was significant strongly in patients with high body mass index (BMI; >24 kg/m²) than in those with a low BMI (≤24 kg/m², P for interaction = 0.045). Using restricted cubic splines, we observed a dose–response relation between lg SIRI and the risk of CVD in DM patients.ConclusionsThe elevated SIRI was independently associated with the increased risk of CVD in the DM population with a high BMI (>24 kg/m²), and its clinical value is greater than hs-CRP.     

Associations of disordered eating with the intestinal microbiota and short-chain fatty acids among young adults with type 1 diabetes

Background and aimsDisordered eating (DE) in type 1 diabetes (T1D) includes insulin restriction for weight loss with serious complications. Gut microbiota-derived short chain fatty acids (SCFA) may benefit host metabolism but are reduced in T1D. We evaluated the hypothesis that DE and insulin restriction were associated with reduced SCFA-producing gut microbes, SCFA, and intestinal microbial diversity in adults with T1D.Methods and resultsWe collected stool samples at four timepoints in a hypothesis-generating gut microbiome pilot study ancillary to a weight management pilot in young adults with T1D. 16S ribosomal RNA gene sequencing measured the normalized abundance of SCFA-producing intestinal microbes. Gas-chromatography mass-spectrometry measured SCFA (total, acetate, butyrate, and propionate). The Diabetes Eating Problem Survey—Revised (DEPS-R) assessed DE and insulin restriction. Covariate-adjusted and Bonferroni-corrected generalized estimating equations modeled the associations. COVID-19 interrupted data collection, so models were repeated restricted to pre-COVID-19 data.Data were available for 45 participants at 109 visits, which included 42 participants at 65 visits pre-COVID-19. Participants reported restricting insulin “At least sometimes” at 53.3% of visits. Pre-COVID-19, each 5-point DEPS-R increase was associated with a ?0.34 (95% CI -0.56, ?0.13, p = 0.07) lower normalized abundance of genus Anaerostipes; and the normalized abundance of Lachnospira genus was ?0.94 (95% CI -1.5, ?0.42), p = 0.02 lower when insulin restriction was reported “At least sometimes” compared to “Rarely or Never”.ConclusionDE and insulin restriction were associated with a reduced abundance of SCFA-producing gut microbes pre-COVID-19. Additional studies are needed to confirm these associations to inform microbiota-based therapies in T1D.     

Sex differences in cardiovascular risk factors of children and adolescents with type 1 diabetes mellitus: A role for diet?

Background and aimsCardiovascular disease is the leading cause of morbidity and mortality in individuals with type 1 diabetes mellitus (T1DM). Cardiovascular risk is higher in women with diabetes than in men. With this study, we wanted to determine whether female children and adolescents with T1DM are more prone to cardiovascular risk factors (CVRFs) and an atherogenic diet than boys.Methods and resultsFor this cross-sectional study, anthropometric, clinical, biochemical, and dietary intake data of 314 children with diabetes (3–18 years; 178 boys) were analysed according to age and sex. Linear and binary logistic regression was performed to test independent associations between sex, dietary intake, and CVRFs.Low-density lipoprotein -cholesterol (LDL-c), triglyceride (TG), fibre, monounsaturated fatty acid levels (all p < 0.01), and lipid (p = 0.022) intake were higher in the girls than in the boys. Multiple regression analysis showed that LDL was associated with sex, glycated haemoglobin (HbA1c), and lipid intake percentage (R (Kannel, 1979) [2] = 0.130; p = 0.0004) independent of age, pubertal stage, body mass index (BMI), duration of diabetes, energy, and fibre intake. Logistic regression analysis showed that high LDL-c levels were present more often in girls [odds ratio, OR; confidence interval, CI = 2.569 (1.178–5.604); p = 0.018] who had a higher dietary lipid intake percentage [OR (CI) = 1.089 (1.011–1.173); p = 0.025].ConclusionsGirls with diabetes have higher LDL-c levels associated with higher dietary lipid intake. Our findings suggest that young people with diabetes, especially girls, may benefit from early dietary interventions to reduce their cardiovascular risk.     

Clopidogrel Monotherapy After 1-Month Dual Antiplatelet Therapy in Patients With Diabetes Undergoing Percutaneous Coronary Intervention

BackgroundDiabetes was reported to be associated with an impaired response to clopidogrel.ObjectivesThe aim of this study was to evaluate the safety and efficacy of clopidogrel monotherapy after very short dual antiplatelet therapy (DAPT) in patients with diabetes undergoing percutaneous coronary intervention (PCI).MethodsA subgroup analysis was conducted on the basis of diabetes in the STOPDAPT-2 (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2) Total Cohort (N = 5,997) (STOPDAPT-2, n = 3,009; STOPDAPT-2 ACS [Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS], n = 2,988), which randomly compared 1-month DAPT followed by clopidogrel monotherapy with 12-month DAPT with aspirin and clopidogrel after cobalt-chromium everolimus-eluting stent implantation. The primary endpoint was a composite of cardiovascular (cardiovascular death, myocardial infarction, definite stent thrombosis, or stroke) or bleeding (TIMI [Thrombolysis In Myocardial Infarction] major or minor) endpoints at 1 year.ResultsThere were 2,030 patients with diabetes (33.8%) and 3967 patients without diabetes (66.2%). Regardless of diabetes, the risk of 1-month DAPT relative to 12-month DAPT was not significant for the primary endpoint (diabetes, 3.58% vs 4.12% [HR: 0.87; 95% CI: 0.56-1.37; P = 0.55]; nondiabetes, 2.46% vs 2.49% [HR: 0.99; 95% CI: 0.67-1.48; P = 0.97]; P_interaction = 0.67) and for the cardiovascular endpoint (diabetes, 3.28% vs 3.05% [HR: 1.10; 95% CI: 0.67-1.81; P = 0.70]; nondiabetes, 1.95% vs 1.43% [HR: 1.38; 95% CI: 0.85-2.25; P = 0.20]; P_interaction = 0.52), while it was lower for the bleeding endpoint (diabetes, 0.30% vs 1.50% [HR: 0.20; 95% CI: 0.06-0.68; P = 0.01]; nondiabetes, 0.61% vs 1.21% [HR: 0.51; 95% CI: 0.25-1.01; P = 0.054]; P_interaction = 0.19).ConclusionsClopidogrel monotherapy after 1-month DAPT compared with 12-month DAPT reduced major bleeding events without an increase in cardiovascular events regardless of diabetes, although the findings should be considered as hypothesis generating, especially in patients with acute coronary syndrome, because of the inconclusive result in the STOPDAPT-2 ACS trial. (Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 [STOPDAPT-2], NCT02619760; Short and Optimal Duration of Dual Antiplatelet Therapy After Everolimus-Eluting Cobalt-Chromium Stent–2 for the Patients With ACS [STOPDAPT-2 ACS], NCT03462498)     

Carbohydrate quality,glycemic index,glycemic load and cardiometabolic risks in the US,Europe and Asia: A dose–response meta-analysis

Background and aimsDespite the proven evidence of high glycemic index (GI) and glycemic load (GL) diets to increase cardiometabolic risks, knowledge about the meta-evidence for carbohydrate quality within world geographic regions is limited. We conducted a meta-analysis to synthesize the evidence of GI/GL studies and carbohydrate quality, gathering additional exposures for carbohydrate, high glycemic carbohydrate, total dietary fiber, and cereal fiber and risks for type 2 diabetes (T2DM), coronary heart disease (CHD), stroke, and mortality, grouped into the US, Europe, and Asia. Secondary aims examined cardiometabolic risks in overweight/obese individuals, by sex, and dose–response dietary variable trends.Methods and results40-prospective observational studies from 4-Medline bibliographical databases (Ovid, PubMed, EBSCOhost, CINAHL) were search up to November 2019. Random-effects hazard ratios (HR) and 95% confidence intervals (CI) for highest vs. lowest categories and continuous form combined were reported. Heterogeneity (I²>50%) was frequent in US GI/GL studies due to differing study characteristics. Increased risks ((HR_GI,T2DM,US=1.14;CI:1.06,1.21), HR_GL,T2DM,US=1.02 (1.01, 1.03)), HR_GI,T2DM,Asia=1.25;1.02,1.53), and HR_GL,T2DM,Asia=1.37 (1.17, 1.60)) were associated with cardiometabolic diseases. GI/GL in overweight/obese females had the strongest magnitude of risks in US-and Asian studies. Total dietary fiber (HRT2DM,US = 0.92;0.88,0.96) and cereal fiber (HR_T2DM,US = 0.83;0.77,0.90) decreased risk of developing T2DM. Among females, we found protective dose–response risks for total dietary fiber (HR_{5g-total-dietary-fiber,T2DM,US} = 0.94;0.92,0.97)_, but cereal fiber showed better ability to lower T2DM risk (HR_{5g-cereal-fiber},_T2DM,US = 0.67;0.60,0.74). Total dietary-and cereal fibers' dose–response effects were nullified by GL, but not so for cereal fiber with GI.ConclusionsOverweight/obese females could shift their carbohydrate intake for higher cereal fiber to decrease T2DM risk, but higher GL may cancel-out this effect.     

Differences in taste and smell perception between type 2 diabetes mellitus patients and healthy controls

Background and aimsThe senses of taste and smell are essential determinants of food choice, which in turn may contribute to the development of chronic diseases, including diabetes. Although past studies have evaluated the relationship between type 2 diabetes mellitus (DM2) and senses disorders, this relationship remains controversial.In this study, we evaluated taste and smell perception in DM2 patients and healthy controls (HC). Moreover, we analyzed the association of chemosensory impairments with anthropometric and clinical outcomes (e.g. Body Mass Index (BMI), Fasting blood glucose (FBG), drugs, cardiovascular diseases (CVD), and hypertension) in DM2 patients.Methods and resultsThe study included 94 DM2 patients and 244 HC. Taste recognition for 6-n-propylthiouracil (PROP), quinine, citric acid, sucrose, and sodium chloride (NaCl) compounds was assessed using a filter paper method, while smell recognition of 12 odorants was performed using a Sniffin’ sticks test.We found that a higher percentage of DM2 patients showed identification impairment in salt taste (22% vs. 5%, p-value<0.0009) and smell recognition (55% vs. 27%, p-value = 0.03) compared to HC. We also observed that 65% of hypertensive DM2 subjects presented smell identification impairment compared to 18% of non-hypertensive patients (p-value = 0.019). Finally, patients with impairments in both taste and smell showed elevated FBG compared to patients without impairment (149.6 vs.124.3 mg/dL, p-value = 0.04).ConclusionThe prevalence of taste and smell identification impairments was higher in DM2 patients compared to HC, and a possible relationship with glycemic levels emerged.     

Clinical Characteristics and Prognosis of MINOCA Caused by Atherosclerotic and Nonatherosclerotic Mechanisms Assessed by OCT

BackgroundMyocardial infarction with nonobstructive coronary artery (MINOCA) is a heterogeneous syndrome caused by different pathophysiologic mechanisms. There is limited evidence regarding prognosis of patients with MINOCA caused by different mechanisms.ObjectivesThe present study aimed to assess the underlying mechanisms of MINOCA by optical coherence tomography (OCT) and to correlate with clinical outcomes.MethodsPatients with MINOCA were divided into 2 groups based on OCT findings: atherosclerotic MINOCA (Ath-MINOCA) and nonatherosclerotic MINOCA (non-Ath-MINOCA). Major adverse cardiac events (MACE) were defined as cardiac death, nonfatal MI, target lesion revascularization, stroke, and rehospitalization for unstable or progressive angina.ResultsAmong 7,423 patients with a clinical diagnosis of MI who underwent angiography, 190 of 294 MINOCA were studied using OCT. The causes of Ath-MINOCA (n = 99, 52.1%) were plaque erosion (n = 64, 33.7%), plaque rupture (n = 33, 17.4%), and calcified nodule (n = 2, 1.1%) whereas the causes of non-Ath-MINOCA (n = 91, 47.9%) were spontaneous coronary artery dissection (n = 8, 4.2%), coronary spasm (n = 9, 4.7%), and unclassified cause (n = 74, 38.9%). The 1-year MACE was 15.3% for Ath-MINOCA vs 4.5% for non-Ath-MINOCA (P = 0.015). An atherosclerotic cause was an independent predictor of MACE (HR: 5.36 [95% CI: 1.08-26.55]; P = 0.040), mainly driven by target lesion revascularization and rehospitalization, despite the composite endpoint including cardiac death and MI showing no difference.ConclusionsOCT identified a cause in 61.1% of MINOCA, in which Ath-MINOCA represents an important and distinct MINOCA subset. Ath-MINOCA were more common and associated with worse outcomes. (Incidence Rate of Heart Failure After Acute Myocardial Infarction With Optimal Treatment; NCT03297164; Paradigm Shift in the Treatment of Patients With ACS; NCT02041650)