Association between insulin resistance and incidence of carotid atherosclerotic plaque: A cohort study

Background and aimsThere is limited evidence on the association between insulin resistance (IR) and carotid plaque was reported in prospective study. We aimed to exploit the relationship between IR and carotid plaque in a prospective cohort study.Methods and resultsThe study was performed in a functional community cohort in urban Beijing. In 2015, a total of 7061 individuals without intima-media thickness (IMT) thickening and carotid artery plaque were recruited and followed up until 2019. Restricted cubic spline was conducted to exploit the dose–response relationship between carotid plaque and baseline HOMA-IR or TyG index as continuous variables. Logistic regression was used to analyze the associations between carotid plaque and HOMA-IR or TyG index. During the average 4 years follow-up, 589 subjects developed carotid plaque. Both HOMA-IR and TyG index showed significant linear dose–response relationship on carotid plaque (p < 0.001). The RRs (95%CI) for subjects with baseline HOMA-IR in quartile 2, quartile 3 and quartile 4 were 1.52 (1.14–2.04), 1.86 (1.40–2.46), and 2.55 (1.94–3.35) compared to quartile 1, respectively. Compared to the first quartile of TyG, the RRs (95%CI) for subjects in quartile 2, quartile 3 and quartile 4 were 1.43 (1.08–1.90), 1.59 (1.20–2.12), and 1.69 (1.26–2.25), respectively. In total population, the predictive ability of HOMA-IR for carotid plaque was significantly better than that of TyG index (p = 0.025).ConclusionIR is an independent risk factor of carotid plaque. Both HOMA-IR and TyG has significant predictive ability for carotid plaque.     

Insulin resistance,but not insulin response,during oral glucose tolerance test (OGTT) is associated to worse histological outcome in obese NAFLD

Background and aimObese subjects are at high risk of nonalcoholic fatty liver disease (NAFLD) and diabetes (T2D) due to insulin resistance (IR). Since high glucose levels are as toxic as lipids for hepatic metabolism, we hypothesize that altered response to oral glucose tolerance test (OGTT) is associated to more severe NAFLD with significant/advanced liver damage.Methods and resultsWe studied 90 subjects with morbid obesity (73F/17M, BMI = 43.2 ± 5,9 kg/m²) undergoing bariatric surgery and intraoperative liver biopsy, and measured HbA1c, HOMA-IR (fasting Glucose x Insulin/22.5), OGTT glucose and insulin profile, and calculated OGIS (muscle insulin sensitivity), hepatic-IR (glucose [AUC_0-30] x insulin [AUC_0-30]) during OGTT, insulin response as (insulin [dAUC_0-120]/glucose [dAUC_0-120] or Insulinogenic Index (IGI = (I₃₀–I₀)/(G₃₀-G₀)). Patients were divided in 3 groups according to liver biopsy: A (no-NAFLD, 23%), B (simple steatosis (SS), 53%) and C (NASH, 24%) with similar age, gender and BMI. Diabetes was 0% in no-NAFLD, 13% in SS, 35% in NASH. During OGTT, OGIS decreased from A to C (422 vs 360 vs 338, p < 0.01). Increased insulin concentrations, HbA1c, HOMA-IR and OGIS, not Hep-IR, were strongly associated to hepatic steatosis (p = 0.03, p = 0.0001 and p = 0.01 respectively). Hepatic fibrosis stage was mild as most of the patients had fibrosis grade-1 (69% vs. 8% no fibrosis) and associated to fasting insulin, HbA1c and HOMA-IR. dAUC-I/dAUC-G was similar in the 3 groups, while only AUC-I was strongly associated to steatosis (r = 0.35, p = 0.005), but not to fibrosis.ConclusionsIn morbid obesity indexes of IR, and not of insulin response, are markers of histological severity of liver disease.     

No association between alcohol consumption and risk of atrial fibrillation: A two-sample Mendelian randomization study

Background and aimsAlthough many observational studies have suggested that alcohol intake was associated with incident atrial fibrillation (AF), controversy remains. This study aimed to examine the causal association of alcohol intake with the risk of AF.Methods and resultsTwo-sample Mendelian randomization (MR) analysis was performed to estimate the causal effects of alcohol consumption, alcohol dependence, or alcohol use disorder identification test (AUDIT) scores on AF. Summary data on single nucleotide polymorphisms (SNPs) associated with AF were obtained from a genome-wide association study (GWAS) with up to 1,030,836 participants. The fixed- and random-effect inverse-variance weighted (IVW) methods were used to calculate the overall causal effects. MR analysis revealed nonsignificant association of genetically predicted alcohol consumption with risk of AF using fixed- and random-effect IVW approaches (odds ratio (OR) [95% confidence interval (CI)] = 1.004 [0.796–1.266], P = 0.975; OR [95% CI] = 1.004 [0.766–1.315], P = 0.979). Genetically predicted alcohol dependence was also not causally associated with AF in the fixed- and random-effect IVW analyses (OR [95% CI] = 1.012 [0.978–1.048], P = 0.490; OR [95% CI] = 1.012 [0.991–1.034], P = 0.260). There was no significantly causal association between AUDIT and AF in the fixed- and random-effect IVW analyses (OR [95% CI] = 0.889 [0.433–1.822], P = 0.748; OR [95% CI] = 0.889 [0.309–2.555], P = 0.827). Sensitivity analyses indicated no evidence of pleiotropy and heterogeneity in statistical models.ConclusionsThis MR study did not find evidence of a causal association between alcohol intake and AF.     

Adherence to the Dietary Approaches to Stop Hypertension (DASH) diet is associated with low levels of insulin resistance among heart failure patients

Background and aimsHeart failure (HF) patients are at risk of developing type 2 diabetes. This study examined the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and insulin resistance among U.S. adults with HF.Methods and resultsUsing data from National Health and Nutrition Examination Survey 1999–2016 cycles, we included 348 individuals aged 20+ years with HF and no history of diabetes. DASH diet adherence index quartile 1 indicated the lowest and quartile 4 indicated the highest adherence. The highest level of insulin resistance was defined by the upper tertile of the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Associations between level of insulin resistance and DASH diet adherence and its linear trends were examined using logistic regressions. Trend analyses showed that participants in upper DASH diet adherence index quartiles were more likely older, female, non-Hispanic White, of normal weight, and had lower levels of fasting insulin than those in lower quartiles. Median values of HOMA-IR from lowest to highest DASH diet adherence index quartiles were 3.1 (interquartile range, 1.8–5.5), 2.9 (1.7–5.6), 2.1 (1.1–3.7), and 2.1 (1.3–3.5). Multivariable logistic analyses indicated that participants with the highest compared to the lowest DASH adherence showed 77.1% lower odds of having the highest level of insulin resistance (0.229, 95% confidence interval: 0.073–0.716; p = 0.017 for linear trend).ConclusionGood adherence to the DASH diet was associated with lower insulin resistance among community-dwelling HF patients. Heart healthy dietary patterns likely protect HF patients from developing type 2 diabetes.     

The role of insulin resistance in the relation of visceral,abdominal subcutaneous and total body fat to cardiovascular function

Background and aimsThe separate cardiovascular effects of type 2 diabetes and adiposity remain to be examined. This study aimed to investigate the role of insulin resistance in the relations of visceral (VAT), abdominal subcutaneous (aSAT) adipose tissue and total body fat (TBF) to cardiovascular remodeling.Methods and resultsIn this cross-sectional analysis of the population-based Netherlands Epidemiology of Obesity study, 914 middle-aged individuals (46% men) were included. Participants underwent magnetic resonance imaging. Standardized linear regression coefficients (95%CI) were calculated, adjusted for potential confounding factors. All fat depots and insulin resistance (HOMA-IR), separate from VAT and TBF, were associated with lower mitral early and late peak filling rate ratios (E/A): −0.04 (−0.09;0.01) per SD (54 cm²) VAT; −0.05 (−0.10;0.00) per SD (94 cm²) aSAT; −0.09 (−0.16;-0.02) per SD (8%) TBF; −0.11 (−0.17;-0.05) per 10-fold increase in HOMA-IR, whereas VAT and TBF were differently associated with left ventricular (LV) end-diastolic volume: −8.9 (−11.7;-6.1) mL per SD VAT; +5.4 (1.1;9.7) mL per SD TBF. After adding HOMA-IR to the model to evaluate the mediating role of insulin resistance, change in E/A was −0.02 (−0.07;0.04) per SD VAT; −0.03 (−0.08;0.02) per SD aSAT; −0.06 (−0.13;0.01) per SD TBF, and change in LV end-diastolic volume was −7.0 (−9.7;-4.3) mL per SD VAT. In women, adiposity but not HOMA-IR was related to higher aortic arch pulse wave velocity.ConclusionInsulin resistance was associated with reduced diastolic function, separately from VAT and TBF, and partly mediated the associations between adiposity depots and lower diastolic function.     

Associations between food portion sizes,insulin resistance,VO2 max and metabolic syndrome in European adolescents: The HELENA study

Background and aimsThis study aims to examine the associations of food portion size (PS) with markers of insulin resistance (IR) and clustered of metabolic risk score in European adolescents.MethodsA total of 495 adolescents (53.5% females) from the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study were included. The association between PS from food groups and homeostasis model assessment of insulin resistance (HOMA-IR) index, VO2 max, and metabolic risk score was assessed by multilinear regression analysis adjusting for several confounders. Analysis of covariance (ANCOVA) was used to determine the mean differences of food PS from food groups by HOMA-IR cutoff categories by using maternal education as a covariable.ResultsLarger PS from vegetables in both gender and milk, yoghurt, and milk beverages in males were associated with higher VO2 max, while larger PS from margarines and vegetable oils were associated with lower VO2 max (p < 0.05). Males who consumed larger PS from fish and fish products; meat substitutes, nuts, and pulses; cakes, pies, and biscuits; and sugar, honey, jams, and chocolate have a higher metabolic risk score (p < 0.05). Males with lower HOMA-IR cutoff values consumed larger PS from vegetables, milk, yoghurt, and milk beverages (p < 0.05). Females with lower HOMA-IR cutoff values consumed larger PS from breakfast cereals, while those with higher HOMA-IR cutoff values consumed larger PS from butter and animal fats (p = 0.018).ConclusionThe results show that larger PS from dairy products, cereals, and high energy dense foods are a significant determinant of IR and VO2 max, and larger PS from food with higher content of sugar were associated with higher metabolic risk score.     

Changes in adiposity mediate the associations of diet quality with insulin sensitivity and beta-cell function

Background and aimsTo examine the mediating role of adiposity on the associations of diet quality with longitudinal changes in insulin sensitivity and beta-cell function.Methods and resultsAdults at-risk for type 2 diabetes (T2D) in the PROMISE cohort had 4 assessments over 9 years (n = 442). Alternate Healthy Eating Index (AHEI) scores were used to assess diet quality. Generalized Estimating Equations (GEE) evaluated the associations between the AHEI and longitudinal changes in insulin sensitivity (HOMA2-%S and ISI) and beta-cell function (IGI/HOMA-IR and ISSI-2). The proportion of the mediating effect of waist circumference changes was estimated using the difference method. In the primary longitudinal analysis, AHEI was positively associated with insulin sensitivity and beta-cell function over time (% difference per standard deviation increase of AHEI for HOMA2-%S (β = 11.0, 95%CI 5.43–17.0), ISI (β = 10.4, 95%CI 4.35–16.8), IGI/HOMA-IR (β = 7.12, 95%CI 0.98–13.6) and ISSI-2 (β = 4.38, 95%CI 1.05–7.80), all p < 0.05). There was no significant association between AHEI and dysglycemia incidence (OR = 0.95, 95%CI 0.77–1.17). Adjustments for longitudinal changes in waist circumference substantially attenuated all associations of AHEI with insulin sensitivity and beta-cell function. Mediation analysis indicated that waist circumference mediated 73%, 70%, 83% and 81% of the association between AHEI and HOMA2-%S, ISI, IGI/HOMA-IR, and ISSI-2, respectively (all p < 0.01).ConclusionIn a Canadian population at-risk for T2D, AHEI score was positively associated with changes in insulin sensitivity and beta-cell function. These associations were substantially mediated by waist circumference, suggesting that changes in adiposity may represent an important pathway linking diet quality with risk phenotypes for T2D.     

Comparison of triglyceride-glucose index and HOMA-IR for predicting prevalence and incidence of metabolic syndrome

Background and aimsInsulin resistance is related closely to metabolic syndrome (MetS). The homeostasis model assessment of insulin resistance (HOMA-IR) is the most commonly used insulin resistance index, but the triglyceride-glucose (TyG) index has been suggested as a reliable alternative insulin resistance index. This study aims to compare the predictive powers of TyG index and HOMA-IR for the prevalence and incidence of MetS in a large, community-based, prospective cohort over 12 years of follow-up.Methods and resultsData from 9730 adults with or without MetS at baseline, 6091 adults without MetS who were followed as part of the Korean Genome and Epidemiology Study were analyzed. Receiver-operating-characteristic (ROC) curves and time-dependent ROC curves were performed to compare the areas under the ROC curve (AUROC) of the TyG index and HOMA-IR for predicting the prevalence and incidence of MetS. The optimal cut-off points were calculated. Cox proportional hazard spline curves were used to verify dose-response relationship between TyG index/HOMA-IR and incident MetS. TyG index showed higher predictive power for prevalent MetS than HOMA-IR (0.837 vs. 0.680, p < 0.001). The AUROC for incident MetS of TyG index and HOMA-IR was 0.654 (0.644–0.664) and 0.556 (0.531–0.581), respectively (p < 0.001). Cut-off points of TyG index and HOMA-IR for predicting the prevalence of MetS were 8.718 and 1.8 and for predicting incident MetS were 8.518 and 1.5, respectively. Both TyG index and HOMA-IR had a linear relationship with incident MetS.ConclusionsTyG index is superior to HOMA-IR for predicting MetS.     

High triglyceride-glucose index is associated with adverse cardiovascular outcomes in patients with acute myocardial infarction

Background and aimsTriglyceride glucose (TyG) index is considered a new surrogate marker of insulin resistance that associated with the development of vascular disease. The aim of this study was to evaluate the prognostic value of TyG index in patients with acute myocardial infarction (AMI).Methods and resultsA total of 3181 patients with AMI were included in the analysis. Patients were stratified into 2 groups according to their TyG index levels: the TyG index <8.88 group and the TyG index ≥8.88 group. The incidence of major adverse cardiovascular events (MACEs) during a median of 33.3-month follow-up were recorded. Multivariable Cox regression models revealed that the TyG index was positively associated with all-cause death [HR (95% CI): 1.51 (1.10,2.06), p = 0.010], cardiac death [HR (95% CI): 1.68 (1.19,2.38), p = 0.004], revascularization [HR (95% CI): 1.50 (1.16,1.94), p = 0.002], cardiac rehospitalization [HR (95% CI): 1.25 (1.05,1.49), p = 0.012], and composite MACEs [HR (95% CI): 1.19 (1.01,1.41), p = 0.046] in patients with AMI. The independent predictive effect of TyG index on composite MACEs was mainly reflected in the subgroups of male gender and smoker. The area under the curve (AUC) of the TyG index predicting the occurrence of MACEs in AMI patients was 0.602 [95% CI 0.580,0.623; p < 0.001].ConclusionHigh TyG index levels appeared to be associated with an increased risk of MACEs in patients with AMI. The TyG index might be a valid predictor of cardiovascular outcomes of patients with AMI.Trial registrationRetrospectively registered.     

Uric acid and blood pressure in NHANES dated from 2009 to 2018: A cross-sectional research

Background and aimThis study aimed to explore the association between uric acid (UA) and blood pressure (BP), included systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP).Methods and resultsA cross-sectional study with 22,478 individuals aged from 12 to 80 years (11,443 males and 11,035 females) from the National Health and Nutrition Examination Survey (NHANES) was performed. Multiple linear regression analysis was applied to explore the relationship between UA and BP, Stratified analysis and interaction were performed based on gender, race, age, body mass index (BMI), and alcohol consumption. Significantly positively associations were presented in SBP(β, 0.84 [95% CI, 0.67, 1.00]), DBP(β, 0.23 [95% CI, 0.11, 0.36]), and MAP (β, 0.43 [95% CI, 0.31, 0.55]). The associations were much more stronger between UA and SBP in females (β, 1.04 [95% CI, 0.78, 1.30], p for interaction 0.0003), black group (β, 1.17 [95% CI, 0.77, 1.56], p for interaction 0.0296), age (≥45) group (β, 1.03 [95% CI, 0.68, 1.39], p for interaction <0.0001) and drinking group (β, 0.98 [95% CI, 0.75, 1.21], p for interaction <0.0001). The significant interactions were found between UA and DBP in gender and alcohol consumption (all p for interaction <0.05). In terms of MAP, the significant interactions were found in race, age, and alcohol consumption (all p for interaction <0.05).ConclusionsA significantly positively association was found between UA and BP, including SBP, DBP, and MAP.     

Alcohol Abstinence Improves Prognosis Across All Stages of Portal Hypertension in Alcohol-Related Cirrhosis

Background and AimsAlcohol-related liver disease is a leading cause of liver-related mortality. The effect of alcohol abstinence on the natural history of alcohol-related cirrhosis across distinct stages of portal hypertension has not been thoroughly investigated. In this study, we assessed the clinical implications of abstinence in patients with alcohol-related cirrhosis and clinically significant portal hypertension.MethodsAlcohol abstinence, hepatic decompensation, and mortality were assessed in patients with alcohol-related cirrhosis who underwent a baseline hepatic venous pressure gradient (HVPG) measurement and were diagnosed with clinically significant portal hypertension (HVPG ≥10 mm Hg).ResultsA total of 320 patients with alcohol-related cirrhosis (median age: 57 [interquartile range (IQR), 49.7-63.1] years; 75.6% male; 87.5% decompensated) and a median HVPG of 20 (IQR, 17-23) mm Hg were followed up for a median of 36 (IQR, 14-80) months. Overall, 241 (75.3%) patients remained abstinent, while 79 (24.7%) patients had active alcohol consumption. Alcohol abstinence was linked to a significantly reduced risk of hepatic decompensation (adjusted hazard ratio [aHR], 0.391; P < .001), as well as liver-related (aHR, 0.428; P < .001) and all-cause (aHR, 0.453; P < .001) mortality, after adjusting for baseline HVPG, MELD, and previous decompensation. Importantly, alcohol abstinence significantly reduced the cumulative incidence of hepatic decompensation in both groups with HVPG 10–19 mm Hg (P < .001) and HVPG ≥20 mm Hg (P = .002). The 3-year decompensation probability was 32.4% vs 60.0% in HVPG 10–19 mm Hg and 57.5% vs 82.6% in HVPG ≥20 mm Hg for abstinent patients vs active drinkers, respectively.ConclusionsAlcohol abstinence improves prognosis across all stages of portal hypertension in alcohol-related cirrhosis, including in patients who have already progressed to high-risk portal hypertension. (ClinicalTrials.gov, Number: NCT03267615).     

Genetically Predicted Adiposity,Diabetes, and Lifestyle Factors in Relation to Diverticular Disease

Background & AimsAdiposity, type 2 diabetes, alcohol and coffee consumption, and smoking have been examined in relation to diverticular disease in observational studies. We conducted a Mendelian randomization study to assess the causality of these associations.MethodsIndependent genetic instruments associated with the studied exposures at genome-wide significance were obtained from published genome-wide association studies. Summary-level data for the exposure-associated single nucleotide polymorphisms with diverticular disease were available in the FinnGen consortium (10,978 cases and 149,001 noncases) and the UK Biobank study (12,662 cases and 348,532 noncases).ResultsHigher genetically predicted body mass index and genetic liability to type 2 diabetes and smoking initiation were associated with an increased risk of diverticular disease in meta-analyses of results from the two studies. The combined odds ratio of diverticular disease was 1.23 (95% confidence interval [CI], 1.14–1.33; P < .001) for a 1-standard deviation (~4.8 kg/m²) increase in body mass index, 1.04 (95% CI, 1.01–1.07; P = .007) for a 1-unit increase in log-transformed odds ratio of type 2 diabetes, and 1.21 (95% CI, 1.12–1.30; P < .001) for a 1-standard deviation increase in prevalence of smoking initiation. Coffee consumption was not associated with diverticular disease, whereas the association for alcohol consumption largely differed between the 2 studies.ConclusionsThis study strengthens the causal associations of higher body mass index, type 2 diabetes, and smoking with an increased risk of diverticular disease. Coffee consumption is not associated with diverticular disease. Whether alcohol consumption affects the risk of diverticular disease needs further investigation.     

Intermittent fasting and changes in Galectin-3: A secondary analysis of a randomized controlled trial of disease-free subjects

Background and aimsIntermittent fasting reduces risk of interrelated cardiometabolic diseases, including type 2 diabetes and heart failure (HF). Previously, we reported that intermittent fasting reduced homeostasis model assessment of insulin resistance (HOMA-IR) and Metabolic Syndrome Score (MSS) in the WONDERFUL Trial. Galectin-3 may act to reduce insulin resistance. This post hoc evaluation assessed whether intermittent fasting increased galectin-3.Methods and resultsThe WONDERFUL Trial enrolled adults ages 21–70 years with ≥1 metabolic syndrome features or type 2 diabetes who were not taking anti-diabetic medication, were free of statins, and had elevated LDL-C. Subjects were randomized to water-only 24-h intermittent fasting conducted twice-per-week for 4 weeks and once-per-week for 22 weeks or to a parallel control arm with ad libitum energy intake. The study evaluated 26-week change scores of galectin-3 and other biomarkers. Overall, n = 67 subjects (intermittent fasting: n = 36; control: n = 31) completed the trial and had galectin-3 results. At 26-weeks, the galectin-3 change score was increased by intermittent fasting (median: 0.793 ng/mL, IQR: ?0.538, 2.245) versus control (median: ?0.332 ng/mL, IQR: ?0.992, 0.776; p = 0.021). Galectin-3 changes correlated inversely with 26-week change scores of HOMA-IR (r = ?0.288, p = 0.018) and MSS (r = ?0.238, p = 0.052). Other HF biomarkers were unchanged by fasting.ConclusionA 24-h water-only intermittent fasting regimen increased galectin-3. The fasting-triggered galectin-3 elevation was inversely correlated with declines in HOMA-IR and MSS. This may be an evolutionary adaptive survival response that protects human health by modifying disease risks, including by reducing inflammation and insulin resistance.Trial registrationClinicaltrials.gov, NCT02770313 (registered on May 12, 2016; first subject enrolled: November 30, 2016; final subject's 26-week study visit: February 19, 2020).     

SARS-CoV-2 and COVID-19 in diabetes mellitus. Population-based study on ascertained infections,hospital admissions and mortality in an Italian region with ∼5 million inhabitants and ∼250,000 diabetic people

Background and aimsDiabetes conveys an increased risk of infectious diseases and related mortality. We investigated risk of ascertained SARS-CoV-2 infection in diabetes subjects from the Veneto Region, Northeastern Italy, as well as the risk of being admitted to hospital or intensive care unit (ICU), or mortality for COVID-19.Methods and resultsDiabetic subjects were identified by linkage of multiple health archives. The rest of the population served as reference. Information on ascertained infection by SARS-CoV-2, admission to hospital, admission to ICU and mortality in the period from February 21 to July 31, 2020 were retrieved from the regional registry of COVID-19. Subjects with ascertained diabetes were 269,830 (55.2% men; median age 72 years). Reference subjects were 4,681,239 (men 48.6%, median age 46 years). Ratios of age- and gender-standardized rates (RR) [95% CI] for ascertained infection, admission to hospital, admission to ICU and disease-related death in diabetic subjects were 1.31 [1.19–1.45], 2.11 [1.83–2.44], 2.45 [1.96–3.07], 1.87 [1.68–2.09], all p < 0.001. The highest RR of ascertained infection was observed in diabetic men aged 20–39 years: 1.90 [1.04–3.21]. The highest RR of ICU admission and death were observed in diabetic men aged 40–59 years: 3.47 [2.00–5.70] and 5.54 [2.23–12.1], respectively.ConclusionsThese data, observed in a large population of ∼5 million people of whom ∼250,000 with diabetes, show that diabetes not only conveys a poorer outcome in COVID-19 but also confers an increased risk of ascertained infection from SARS-CoV-2. Men of young or mature age have the highest relative risks.     

Smoking and alcohol consumption influence the risk of cardiovascular diseases in Korean adults with elevated blood pressure

Background and aimsCardiovascular disease (CVD) and hypertension are the main causes of global death. We aimed to investigate the independent and combined effects of smoking and alcohol consumption on CVD risk among Koreans with elevated blood pressure (BP).Methods and resultsAdults aged 20–65 years with elevated BP and without pre-existing CVDs were selected from the National Health Insurance Service-National Sample Cohort version 2.0. We followed up 59,391 men and 35,253 women between 2009 and 2015. The association of CVD incidence with smoking pack-years and alcohol consumption was investigated using the multivariate Cox proportional hazard model. Among women, smokers (10.1–20.0 pack-years) and alcohol drinkers (≥30.0 g/day) had higher CVD risks (hazard ratio [HR] = 1.15, 95% confidence intervals [CI] 1.06–1.25, HR = 1.06, 95% CI 1.00–1.12, respectively) compared to each referent group. However, men who smoked exhibited an increased CVD risk only with pack-years >20.0 (HR = 1.09, 1.03–1.14 and HR = 1.18, 1.11–1.26 for smokers with 20.1–30.0 and ≥ 30.1 pack-years, respectively) compared to nonsmokers. In the combined groups of those smoking and consuming alcohol, only nonsmoking men consuming alcohol 1.0–29.9 g/day had a lower CVD risk than did nonsmoking, nondrinking men (HR = 0.90, 0.83–0.97). Women smoking 1.0-10.0 pack-years and consuming alcohol ≥30.0 g/day had a higher CVD risk (HR = 1.25, 1.11–1.41) than nonsmoking and nondrinking women.ConclusionSmoking and alcohol consumption, independently and jointly, were associated with CVD risk in men and women. Women had a greater CVD risk than did men among Korean adults with elevated BP.     

Glycemic control metrics using flash glucose monitoring and hospital complications in patients with COVID-19

Background and aimsFew studies have reported on the use of continuous glucose monitoring (CGM) during the Covid-19 pandemic. We aimed to examine glycemic control metrics using flash glucose monitoring during insulin treatment and the clinical outcome in hospitalized patients with COVID-19.MethodsProspective, single-center cohort of adult patients diagnosed with type 2 diabetes or hyperglycemia and COVID-19 infection treated with basal bolus insulin regimen. Glycemic control was assessed with the use of intermittent Freestyle Libre flash glucose monitoring during the hospital stay. Outcome of interest were time in range [TIR], time above [TAR] and below [TBR] range, glycemic variability [coefficient of variation [% CV]), and differences in a composite of complications including ICU admission, acute respiratory distress syndrome (ARDS) and acute kidney injury.ResultsA total of 60 patients were included (44 known diabetes and 16 new onset hyperglycemia). In total 190,080 data points of CGM were available, of which 72.5% of values were within the target area [TIR (70–180 mg/dL)], 22% TAR (>180 mg/dL), and 3% were TBR (<70 mg/dL). During treatment, the coefficient of variation (% CV) was 30%. There were no association with TIR, but patients with TAR >180 mg/dl had higher rates of a composite of complications (22.5% vs 16%, p = 0.04).ConclusionsBasal bolus insulin regimen was safe and effective in achieving inpatient glycemic control in most patients with COVID-19. The association between TAR and complications indicates the need for improved inpatient glycemic control in hospitalized patients with COVID-19.     

Effect of extra virgin olive oil consumption on glycemic control: A systematic review and meta-analysis

AimsSeveral health benefits are contributed to extra virgin olive oil (EVOO). The polyphenol fraction of EVOO may be responsible for its cardioprotective impacts. This systematic review and meta-analysis aimed to investigate the effect of EVOO intake on glycemic parameters. Electronic literature searched through 1 September 2020 across MEDLINE/PubMed, Web of Science, and SCOPUS databases to find all clinical trials that reported the effect of EVOO intake on glycemic parameters [FBS(fasting blood glucose), insulin, HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) and HbA1c (glycated hemoglobin A1c)] vs. control.Data synthesisWe pooled standardized mean differences (SMD) and 95% confidence intervals (CIs) from randomized clinical trials (RCTs) using random-effects models. Heterogeneity was assessed by Cochran Q-statistic and quantified (I²). We found 13 related trials comprising a total of 633 subjects. In pooled analysis, EVOO intake had no effect on FBS (SMD: ?0.07; 95% CI: ?0.20, 0.07; I² = 0.0%), insulin (SMD: ?0.32; 95% CI: ?0.70, 0.06; I² = 38.0%), and HOMA-IR (SMD: ?0.32; 95% CI: ?0.75, 0.10; I² = 51.0%). However, a decreasing trend was observed in these effects. Subgroup analysis based on age, health status, dose, and EVOO intake duration also did not significantly change results.ConclusionAlthough EVOO seems a promising hypoglycemic effects, we did not find any significant evidence that EVOO consumption impacts glucose homeostasis. Furthermore, well-designed RCTs with longer durations are still needed to evaluate the EVOO's efficacy on glycemic parameters.     

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.     

Efficacy and safety of imeglimin in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized clinical trials

Background and aimImeglimin is a novel tetrahydrotriazine-containing drug suggested as a safe drug for glycemic management in patients with type 2 diabetes mellitus (T2DM). We aimed to 1) evaluate the efficacy of imeglimin on glycemic control and insulin resistance improvement measured by homeostatic model assessment of insulin resistance (HOMA-IR). 2) assess whether the novel drug improves lipid parameters in diabetic patients. 3) compare between different doses regarding safety.MethodsWe searched PubMed, Cochrane Library, Scopus, Web of Science, Google Scholar, and Wiley through April 25, 2021, for relevant randomized controlled trials comparing different doses of imeglimin supplied as a monotherapy or as add-on therapy versus placebo for adult patients with type 2 diabetes mellitus. Data on glycemic and lipid parameters and adverse events were extracted and pooled in random-effect models using Review Manager version 5.3.ResultsEight studies comprising 1555 patients with T2DM were included in this study. The overall effect estimate of the meta-analysis showed that the imeglimin group was superior to the control group concerning glycated hemoglobin and fasting plasma glucose (P < 0.00001). However, it did not affect HOMA-IR or lipid parameters, including triglyceride, LDL-C, and HDL-C (all p > 0.05). Regarding safety profile, imeglimin was safe and tolerable with no treatment-emergent or serious adverse events.ConclusionsImeglimin safely improved glycemic control by reducing HbA1c and FPG. However, no beneficial effects regarding insulin resistance measured by HOMA-IR or lipid parameters were observed. Further high-quality RCTs with high dose imeglimin are encouraged to ensure HOMA-IR and lipid parameters results.     

Increased visceral fat accumulation modifies the effect of insulin resistance on arterial stiffness and hypertension risk

Background and aimsBoth insulin resistance (IR) and visceral adipose tissue (VAT) are related cardiometabolic risk factors; nevertheless, their joint effect on endothelial functionality is controversial. This study aims to evaluate the joint effect of IR and VAT on endothelial functionality using the pulse-waveform analysis and explore the mediating role of VAT on the effect of IR on arterial pressure, arterial stiffness and incident arterial hypertension.Methods and resultsWe measured VAT (n = 586) using two methods (dual-energy X-ray absorptiometry and a clinical surrogate), arterial stiffness (with pulse-waveform velocity), and IR (using three methods: HOMA2-IR (n = 586), a frequently sampled intravenous glucose tolerance test (n = 131) and euglycemic hyperinsulinemic clamping (n = 97)) to confirm the mediator effect of IR on VAT. The incidence of arterial hypertension attributable to the mediating effect of IR related to VAT was evaluated using a prospective cohort (n = 6850). Adjusted linear regression models, causal mediation analysis, and Cox-proportional hazard risk regression models were performed to test our objective. IR and VAT led to increased arterial stiffness and increased blood pressure; the combination of both further worsened vascular parameters. Nearly, 57% (Δ_E→MY 95% CI: 31.7–100.0) of the effect of IR on altered pulse-wave velocity (PWV) analysis was mediated through VAT. Moreover, VAT acts as a mediator of the effect of IR on increased mean arterial pressure (Δ_E→MY 35.7%, 95% CI: 23.8–59) and increased hypertension risk (Δ_E→MY 69.1%, 95% CI: 46.1–78.8).ConclusionVAT acts as a mediator of IR in promoting arterial stiffness and arterial hypertension. Both phenomena should be targeted to ameliorate the cardiometabolic risk.