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.     

Association between non-alcoholic fatty liver disease and impaired cardiac sympathetic/parasympathetic balance in subjects with and without type 2 diabetes—The Cooperative Health Research in South Tyrol (CHRIS)-NAFLD sub-study

Background and aimsCardiovascular disease (CVD) is the leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD), both with and without type 2 diabetes mellitus (T2DM). Cardiac autonomic dysfunction is a risk factor for CVD morbidity and mortality. The aim of this pilot study was to assess whether there is an association between NAFLD and impaired cardiac autonomic function.Methods and resultsAmong the first 4979 participants from the Cooperative Health Research in South Tyrol (CHRIS) study, we randomly recruited 173 individuals with T2DM and 183 age- and sex-matched nondiabetic controls. Participants underwent ultrasonography and vibration-controlled transient elastography (Fibroscan®, Echosens) to assess hepatic steatosis and liver stiffness. The low-to-high-frequency (LF/HF) power ratio and other heart rate variability (HRV) measures were calculated from a 20-min resting electrocardiogram (ECG) to derive a measure of cardiac sympathetic/parasympathetic imbalance. Among the 356 individuals recruited for the study, 117 had NAFLD and T2DM, 56 had T2DM alone, 68 had NAFLD alone, and 115 subjects had neither condition. Individuals with T2DM and NAFLD (adjusted odds ratio [OR] 4.29, 95% confidence intervals [CI] 1.90–10.6) and individuals with NAFLD alone (adjusted OR 3.41, 95% CI 1.59–7.29), but not those with T2DM alone, had a substantially increased risk of having cardiac sympathetic/parasympathetic imbalance, compared with those without NAFLD and T2DM. Logistic regression models were adjusted for age, sex, body mass index (BMI), hypertension, dyslipidemia, insulin resistance, hemoglobin A1c (HbA1c), C-reactive protein (CRP), and Fibroscan®-measured liver stiffness.ConclusionsNAFLD was associated with cardiac sympathetic/parasympathetic imbalance, regardless of the presence or absence of T2DM, liver stiffness, and other potential confounding factors.     

Age at menopause,body mass index,and risk of type 2 diabetes mellitus in postmenopausal Chinese women: The Henan Rural Cohort study

Background and aimThe present study was conducted to explore the stratified and joint effects of age at menopause and body mass index (BMI) with the risk of type 2 diabetes mellitus (T2DM) in Chinese rural adults.Methods and resultsA total of 15,406 postmenopausal Chinese women were included in this study. Multivariable logistic regression analysis was used to quantify the stratified and joint effects of age at menopause and BMI on T2DM. Overall, the mean age at menopause and BMI was 48.8 ± 4.7 years and 25.1 ± 3.6 kg/m², respectively. In general, data suggest that: 1) women with BMI ≥ 24 had a higher risk of T2DM, irrespective of age at menopause; 2) in women with BMI < 24, later menopause had a higher risk of T2DM (OR, 1.52; 95% CI, 1.16–2.01); 3) the risk of T2DM was higher only in patients with early or normal age at menopause and BMI ≥ 24, with 0R (95% CI) of (1.58, 1.28–1.94) and (1.48, 1.31–1.67), respectively.ConclusionOur findings suggest that: 1) women with BMI ≥ 24 had a higher risk of T2DM, irrespective of age at menopause; 2) in women with BMI < 24, a higher risk of T2DM was found only in those with later menopause; 3) women with later menopause had a higher risk of T2DM, irrespective of BMI; 4) in patients with early or normal age at menopause, a higher risk of T2DM was found only in patients with BMI ≥ 24.The Chinese Clinical Trial RegistrationChiCTR–OOC–1500669(URL:http://www.chictr.org.cn/showproj.aspx?proj=11375)     

Associations between serum amino acids and incident type 2 diabetes in Chinese rural adults

Background and aimsSome amino acids (AAs) may be associated with type 2 diabetes (T2DM). This study aimed to determine the associations of individual AAs with the development of T2DM in rural Chinese adults.Methods and resultsA cohort study of 1199 individuals aged 18 years or older was conducted from 2006 to 2008 in a rural community of Deqing, China, a repeated survey was done in 2015 and data linkage with the electronic health records system was performed each year for identifying new T2DM cases. A high-performance liquid chromatography approach was used to measure the baseline serum concentrations of 15 AAs. Cox proportional hazards models were used to examine the associations between AAs and the risk of incident T2DM. A total of 98 new T2DM cases were identified during the follow-up of 12 years on average. Among 15 AAs, proline was associated with an increased risk of incident T2DM after adjusted for age, sex, body mass index, fasting plasma glucose, family history of T2DM, smoking status, alcohol use, and history of hypertension, the adjusted hazard ratio for 1-standard deviation increment was 1.20 (95% confidence interval: 1.00, 1.43). The association tended to be more marked in subjects younger than 60 years and overweight/obese subjects. Among participants without hypertension, proline and phenylalanine were associated with an increased risk of incident T2DM, while aspartic acid was associated with a decreased risk.ConclusionSerum proline was associated with the risk of incident T2DM in rural Chinese adults and might be a potential predictor.     

Association between lipids and apolipoproteins on type 2 diabetes risk; moderating effects of gender and polymorphisms; the ATTICA study

Background and aimsType 2 diabetes mellitus (T2DM) is a condition defined by hyperglycaemia, but also often presents with dyslipidaemia and suppressed HDL cholesterol. Mendelian randomization studies have suggested a causal link between low HDL cholesterol and T2DM. However, influences of gender, polymorphisms and lifestyle, all known to influence HDL cholesterol, have not been fully explored in a prospective cohort.Methods and resultsIn 2001–2002, a random sample of 1514 males (18–87 years old) and 1528 females (18–89 years old) were recruited in the ATTICA study. The 10-year follow-up (2011–2012) included 1485 participants. Lipids and lipoproteins levels, glucose and insulin levels were measured together with apolipoprotein A1 (apoA1) 75 G/A genotype, which is known to influence HDL-cholesterol. In total, 12.9% of the study sample developed T2DM within the 10-year follow-up period. In multivariable models, for each mg/dL increase in apoA1 levels in males, 10-year T2DM risk decreased 1.02%; while every unit increase in apoB/LDL-cholesterol ratio increased risk 4-fold. Finally, for every unit increase in triglycerides/apoA1 ratio, the risk increased 85%. HOMA-IR independently predicted T2DM 10-year incidence only for carriers of GG polymorphism (all, p < 0.05), but not in carriers of the GA polymorphism (all, p > 0.05).ConclusionApoA1 was associated with decreased T2DM risk and TG/ApoA1 and apoB/LDL were associated with increased risk of T2DM, only in males. ApoA1 polymorphism, which is associated with lower HDL cholesterol, influenced the predictive effects of HOMA-IR on T2DM incidence, which appeared to be moderated by physical activity, suggesting potential scope for more targeted preventative strategies.     

Heart failure is associated with non-adherence to pharmacotherapy in elderly with type 2 diabetes mellitus in public health system Brazilians

The rising prevalence of T2DM poses a serious threat to human health and the viability of many health care systems around the world. Non-adherence to therapeutic in the T2DM is high, and Brazilian studies of public heath for to identify new variables are scares. The present study explored cardiovascular consequences associated with compliance and non-adherence among T2DM in Brazilian patients seeking medical care in Brazilian basic health unit clinics.MethodsThis is a cross-sectional study carried out in a city the interior of Sao Paulo state, with patients with T2DM, being municipal PHS users. Data were collected from the computerized system of the municipality for a one single researcher and patient records, and analyzed using the IBM SPSS v.18 statistical package. The response variables was categorized in adherent MGT (>80) and non-adherent MGT (≤80).ResultsThe mean age of patients was 63.6 ± 9.5 with predominance for the sex male 66.4% and 42% of patients with T2DM do not adherence to treatment. We found an associated odds ratio (OR) = 2.3 (1.1–5.1) between heart failure and non-adherence in patients with T2DM.ConclusionHeart failure is a factor associated with non-adherence to treatment in patients with T2DM and in the practice clinical, the screening for heart failure and interventions may improve adherence to pharmacotherapy.     

CAC for Risk Stratification Among Individuals With Hypertriglyceridemia Free of Clinical Atherosclerotic Cardiovascular Disease

ObjectivesIn this study, we sought to evaluate whether the coronary artery calcium (CAC) score can enhance current paradigms for risk stratification among individuals with hypertriglyceridemia in primary prevention. The eligibility criteria for icosapent ethyl (IPE) were used as case example.BackgroundRecent trials of atherosclerotic cardiovascular disease (ASCVD) risk-reduction therapies for individuals with hypertriglyceridemia without clinical ASCVD restricted enrollment to participants with diabetes or various other risk factors. These criteria were mirrored in the Food and Drug Administration product label for IPE.MethodsWe pooled 2,345 participants with triglycerides 150 to <500 mg/dL (or >178-<500 mg/dL if not on a statin) and without clinical ASCVD from MESA, CARDIA, the Dallas Heart Study, and the Heinz Nixdorf Recall study. We evaluated the incidence of ASCVD events overall, by IPE eligibility (as defined in the product label), and further stratified by CAC scores (0, >0-100, >100). The number needed to treat for 5 years (NNT₅) to prevent 1 event was estimated among IPE-eligible participants, assuming a 21.8% relative risk reduction with IPE. In exploratory analyses, the NNT₅ was also estimated among noneligible participants.ResultsThere was marked heterogeneity in CAC burden overall (45% CAC 0; 24% CAC >100) and across IPE eligibility strata. Overall, 17% of participants were eligible for IPE and 11.9% had ASCVD events within 5 years. Among participants eligible for IPE, 38% had CAC >100, and their event rates were markedly higher (15.9% vs 7.2%) and the NNT₅ 2.2-fold lower (29 vs 64) than those of the 25% eligible participants with CAC 0. Among the 83% participants not eligible for IPE, 20% had CAC >100, and their 5-year incidence of ASCVD (13.9%) was higher than the overall incidence among IPE-eligible participants.ConclusionsCAC can improve current risk stratification and therapy allocation paradigms among individuals with hypertriglyceridemia without clinical ASCVD. Future trials of risk-reduction therapies in hypertriglyceridemia could use CAC >100 to enroll a high-risk study sample, with implications for a larger target population.     

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.     

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.     

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.     

Validation of the 2019 Expert Consensus Algorithm for the Management of Conduction Disturbances After TAVR

ObjectivesThe aim of this study was to validate the 2019 consensus algorithm in a large cohort of contemporary transcatheter aortic valve replacement (TAVR) patients.BackgroundThe optimal management of patients with atrioventricular conduction disturbances after TAVR is unknown. Guidance was consolidated in an expert consensus algorithm in 2019.MethodsIn a retrospective analysis of a prospective registry, patients were classified according to the 2019 consensus algorithm as eligible for early discharge (day 1 or 2 after TAVR), higher risk for high-degree atrioventricular block (HAVB) or complete heart block (CHB) or in need for a permanent pacemaker (PPM). The primary endpoint was the incidence of PPM implantation for HAVB or CHB within 30 days after TAVR. Patients with prior PPM or implantable cardioverter-defibrillator implantation, valve-in-valve procedures, or incomplete electrocardiographic data were excluded.ResultsAmong 1,439 patients undergoing TAVR between January 2014 and December 2019, the 2019 consensus algorithm classified 73% as eligible for early discharge, 21% as at higher risk for HAVB or CHB, and 6% as in need of PPM. PPM implantation for HAVB or CHB occurred in 234 patients (16%) within 30 days after TAVR. The incidence of PPM implantation was 2.7% in the early discharge group, 41% in the group with higher risk for HAVB or CHB, and 100% in the PPM group.ConclusionsThe 2019 consensus algorithm safely identifies patients with no need for PPM implantation. This strategy allows more uniform management of TAVR patients and facilitates early discharge of low-risk patients without prolonged monitoring in 3 of 4 patients. However, the algorithm is less precise in the identification of high-risk patients.     

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.     

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.     

Association between metabolic dysfunction-associated fatty liver disease and supraventricular and ventricular tachyarrhythmias in patients with type 2 diabetes

BackgroundCurrently, it remains uncertain whether metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with increased risk of supraventricular and ventricular tachyarrhythmias in people with type 2 diabetes mellitus (T2DM).MethodsWe retrospectively examined the data of 367 ambulatory patients with T2DM who underwent 24-hour Holter monitoring between 2015 and 2022 for clinical indications, and who did not have pre-existing permanent atrial fibrillation (AF), kidney failure or known liver diseases. Paroxysmal supraventricular tachycardia (PSVT), paroxysmal AF and episodes of ventricular tachyarrhythmias (i.e., presence of ventricular tachycardia, >30 premature ventricular complexes per hour, or both) were recorded. The presence and severity of MAFLD was diagnosed by ultrasonography and fibrosis-4 (FIB-4) index.ResultsPatients with T2DM who had MAFLD (n = 238) had a significantly greater prevalence of PSVT (51.7% vs. 38.8%), paroxysmal AF (6.3% vs. 1.3%) and combined ventricular tachyarrhythmias (31.9% vs. 20.2%) compared to their counterparts without MAFLD (n = 129). MAFLD was significantly associated with a greater than two-fold risk of having PSVT (adjusted-odds ratio [OR] 2.04, 95% confidence interval 1.04–4.00) or ventricular tachyarrhythmias (adjusted-OR 2.44, 95%CI 1.16–5.11), after adjusting for age, sex, smoking, alcohol intake, diabetes-related factors, comorbidities, medication use and left ventricular ejection fraction on echocardiography. The risk of supraventricular and ventricular tachyarrhythmias was even greater amongst patients with MAFLD and FIB-4 ≥ 1.3.ConclusionsIn ambulatory patients with T2DM, the presence and severity of MAFLD was strongly associated with an increased risk of supraventricular and ventricular arrhythmias on 24-hour Holter monitoring.     

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.     

Diet quality in association to lipidaemic profile in adults of families at high-risk for type 2 diabetes in Europe: The Feel4Diabetes study

Background and aimsThe role of diet in blood lipids is scarcely investigated in adults at risk of Type 2 Diabetes Mellitus (T2DM) and even less studied regarding their socioeconomic status (SES). This study aimed to investigate the associations of diet quality with blood lipids in adults from families at high-risk for developing T2DM from six European countries, considering their SES.Methods and resultsIn total 2049 adults (67% women) from relatively low-SES regions and high T2DM risk families were enrolled. Dietary habits, sedentary behaviour and sociodemographic characteristics were assessed using standardised questionnaires. The associations of tertiles of healthy diet score (HDS) with blood lipids were tested by univariate analysis of variance (UNIANOVA). HDL-Cholesterol (HDL-C) was positively (B 1.54 95%CI 0.08 to 2.99) and LDL-Cholesterol (LDL-C) (B ?4.15 95%CI ?7.82 to ?0.48), ratio of total cholesterol to HDL-C (B ?0.24 95%CI ?0.37 to ?0.10), ratio of LDL-C to HDL-C (B ?0.18 95%CI ?0.28 to ?0.08) and Atherogenic Index of Plasma (B ?0.03 95%CI ?0.06 to 0.00) inversely associated with the highest tertile of diet score compared to the lowest tertile independently of age, sex, Body Mass Index, total screen time and smoking. In sub-analysis of education (<14 and ≥ 14 years of education), these findings were only significant in the high-SES group.ConclusionWhile diet quality was poorer in the low-SES group, an association between diet quality and lipidemic profile was not found, as increased central obesity and smoking prevalence might have confounded this association. These findings indicate the need for tailor-made interventions, guided by the specific risk factors identified per population sub groups.     

Ticagrelor With or Without Aspirin in High-Risk Patients With Diabetes Mellitus Undergoing Percutaneous Coronary Intervention

BackgroundP2Y₁₂ inhibitor monotherapy with ticagrelor after a brief period of dual antiplatelet therapy can reduce bleeding without increasing ischemic harm after percutaneous coronary intervention (PCI). The impact of this approach among patients with diabetes mellitus (DM) remains unknown.ObjectivesThe purpose of this study was to examine the effect of ticagrelor monotherapy versus ticagrelor plus aspirin among patients with DM undergoing PCI.MethodsThis was a pre-specified analysis of the DM cohort in the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial. After 3 months of ticagrelor plus aspirin, patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. The primary endpoint was Bleeding Academic Research Consortium 2, 3, or 5 bleeding. The composite ischemic endpoint was all-cause death, myocardial infarction, or stroke.ResultsPatients with DM comprised 37% (n = 2,620) of the randomized cohort and were characterized by more frequent comorbidities and a higher prevalence of multivessel disease. The incidence of Bleeding Academic Research Consortium 2, 3, or 5 bleeding was 4.5% and 6.7% among patients with DM randomized to ticagrelor plus placebo versus ticagrelor plus aspirin (hazard ratio: 0.65; 95% confidence interval: 0.47 to 0.91; p = 0.012). Ticagrelor monotherapy was not associated with an increase in ischemic events compared with ticagrelor plus aspirin (4.6% vs. 5.9%; hazard ratio: 0.77; 95% confidence interval: 0.55 to 1.09; p = 0.14). In the overall trial population, there was no significant interaction between DM status and treatment group for the primary bleeding or ischemic endpoints.ConclusionsCompared with ticagrelor plus aspirin, the effect of ticagrelor monotherapy in reducing the risk of clinically relevant bleeding without any increase in ischemic events was consistent among patients with or without DM undergoing PCI. (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention [TWILIGHT]; NCT02270242)     

Type 2 diabetes mellitus in metabolic-associated fatty liver disease vs. type 2 diabetes mellitus non-alcoholic fatty liver disease: a longitudinal cohort analysis

Introduction and ObjectivesType 2 Diabetes Mellitus (T2DM) is comorbidity commonly presenting with fatty liver. A recently proposed definition of "metabolic associated fatty liver disease" (MAFLD) is thought to replace non-alcoholic fatty liver disease (NAFLD). Yet, despite the significant prevalence of T2DM among fatty liver, there remains limited evidence on the impact of the change in the definition of T2DM.Materials and MethodsThe current study uses data from the United States National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. Survival analysis was conducted with a cox regression and sub-distribution hazard ratio for competing risk events.Results6727 patients had a diagnosis of T2DM. 4982 individuals with T2DM had MAFLD and 2032 were MAFLD(+)/NAFLD(-), while 2950 patients were MAFLD(+)/NAFLD(+). The new definition increased fatty liver diagnosis by 68.89%. Patients who were classified as MAFLD(+)/NAFLD(-) were at a higher risk of major adverse cardiovascular events, advanced fibrosis, all-cause and cardiovascular-related mortality compared to MAFLD(+)/NAFLD(+). In MAFLD(+)/NAFLD(-), viral hepatitis significantly increases the odds of advanced fibrosis (OR: 6.77, CI: 3.92 to 11.7, p < 0.001) and all-cause mortality (HR: 1.75, CI: 1.29 to 2.40, p < 0.001).ConclusionsThe identification and treatment of NAFLD in patients with T2DM is a major concern and the premature change to MAFLD results in an over-diagnosis of fatty liver, exaggerated mortality, and morbidity in patients with T2DM. The definition of MAFLD causes further heterogeneity in fatty liver disease/NAFLD.     

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.     

Moderate and heavy alcohol consumption are prospectively associated with decreased left ventricular ejection fraction: The Hoorn Study

Background and aimsData on the prospective relationship of alcohol consumption at more moderate levels with systolic and diastolic function are scarce. We aimed to examine the prospective association of alcohol consumption with echocardiographic measures of cardiac structure and function, in individuals with and without type 2 diabetes (T2DM).Methods and resultsWe included 778 participants from the Hoorn Study (aged 68.4 ± 7.2 years, 49% women), a population-based prospective cohort study, oversampled for people with impaired glucose metabolism or T2DM. Self-reported alcohol consumption was collected at baseline with a validated food-frequency questionnaire and categorized into: none (0/week), light (>0-≤30 g/week), light-to-moderate (>30-≤70 g/week), moderate (>70-≤140 g/week), and heavy drinkers (>140 g/week). Echocardiography was performed at baseline (N = 778) and after 8 years follow-up (N = 404). Multiple linear regression was used to study the association between alcohol consumption and echocardiographic measures (left ventricular ejection fraction (LVEF), left atrial volume index (LAVI) and left ventricular mass index (LVMI)), adjusted for confounders. Moderate and heavy alcohol consumption were associated with a decreased LVEF of −3.91% (CI: −7.13;-0.69) for moderate and −4.77% (−8.18;-1.36) for heavy drinkers compared to light drinkers. No associations were found between alcohol consumption, LVMI and LAVI. Modified Poisson regression showed a trend that higher alcohol consumption amounts were associated with a higher risk of incident systolic dysfunction (LVEF≤50%) (P-for-trend 0.058).ConclusionThe findings provide longitudinal evidence that moderate and heavy alcohol consumption are associated with decreased LVEF and trend towards a higher risk of incident LV systolic dysfunction, compared to light drinkers.