Efficacy and safety of PCSK9 inhibitors in patients with diabetes: A systematic review and meta-analysis

AimsIndividuals with diabetes have increased cardiovascular risk. Although PCSK9 inhibitors bring about a wide reduction in lipids, there is uncertainty about the effects for diabetic patients. We conducted a systematic review and meta-analysis to assess the efficacy and safety of PCSK9 inhibitors for diabetes.Data synthesisWe performed a meta-analysis comparing treatment with PCSK9 inhibitors versus controls up to July 2022. Primary efficacy endpoints were percentage changes in lipid profile parameters. We used random effects meta-analyses to combine data. Subgroups of diabetic patients (by diabetes type, baseline LDL-C, baseline HbA1c and follow-up time) were also compared. We included 12 RCTs comprising 14,702 patients. Mean reductions in LDL-C were 48.20% (95% CI: 35.23%, 61.17%) in patients with diabetes. Reductions observed with PCSK9 inhibitors were 45.23% (95% CI: 39.43%, 51.02%) for non-HDL-cholesterol, 30.39% (95% CI: 24.61%, 36.17%) for total cholesterol, 11.96% (95% CI: 6.73%, 17.19%) for triglycerides, 27.87% (95% CI: 22.500%, 33.17%) for lipoprotein(a), 42.43% (95% CI: 36.81%, 48.06%) for apolipoprotein B; increases in HDL-C of 5.97% (95% CI: 4.59%, 7.35%) were also observed. There was no significant difference in fasting plasma glucose (FPG) (WMD: 2.02 mg/mL; 95% CI: −1.83, 5.87) and HbA1c (WMD: 1.82%; 95% CI: −0.63, 4.27). Use of a PCSK9 inhibitor was not associated with increased risk of treatment-emergent adverse event (TEAE) (p = 0.542), serious adverse event (SAE) (p = 0.529) and discontinuations due to AEs (p = 0.897).ConclusionsPCSK9 inhibitor therapy should be considered for all diabetic individuals at high risk of atherosclerotic cardiovascular disease.Registration code in prosperoCRD42022339785.     

Dietary glycemic load and its association with glucose metabolism and lipid profile in young adults

Background and aimTo evaluate the association of Glycemic Load (GL) with glucose metabolism and blood lipids among young adults.Methods and resultsThis study included 1538 participants (51% females), evaluated at 21 years of age as part of the EPITeen cohort. The GL of each individual was obtained from the assessment of their dietary intake by using a 86-item semi-quantitative food frequency questionnaire. The evaluation included anthropometric measurements and a fasting blood sample was used to measure glucose, insulin, triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Insulin resistance was calculated based on the homeostasis model method (HOMA-IR). The association between the GL and the biochemical parameters was evaluated by linear regression models using β and 95% confidence intervals (95% CI), stratified by sex and adjusted for body mass index (BMI), energy and fiber intake, and self-perceived social class. No association was found between GL and the glucose metabolism parameters after adjustment. Regarding blood lipids, a positive association was found with LDL-C (β = 1.507, 95% CI 0.454; 2.561 for females; β = 0.216, 95% CI -0.587; 1.020 for males) and a negative association with HDL-C (β = ?0.647, 95% CI -1.112; ?0.181 for females; β = ?0.131, 95% CI -0.422; 0.160 for males).ConclusionsOur results suggest that, in healthy young subjects, a high GL diet may have a negative impact on lipid profile.     

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.     

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.     

Epidemiology of dyslipidemia and associated cardiovascular risk factors in northeast China: A cross-sectional study

Background and aimsManagement of dyslipidemia remains the cornerstone for prevention of cardiovascular diseases. We aimed to evaluate the epidemiology of dyslipidemia in northeast China.Methods and resultsThis cross-sectional survey was administered on 18,796 participants aged ≥40 years from September 2017 to March 2019 through a multistage, stratified, and cluster random sampling method. Lipid profiles were proposed by National Cholesterol Education Program Adult Treatment Panel III. The crude prevalence of dyslipidemia was 35.8%, higher in urban and women than their counterparts (49.5% vs 30.2%, 37.6% vs 33.0%, p < 0.001). The age-standardized prevalence of dyslipidemia was 34.0% (urban 47.9%, and rural 28.9%; men 36.2%, and women 33.4%). The prevalence of high total cholesterol (TC), high triglyceride (TG), high low-density lipoprotein cholesterol (LDL-C) and low high-density lipoprotein cholesterol (HDL-C) were 14.2%, 17.7%, 5.7% and 11.4% respectively. Noticeably, the prevalence of high LDL-C and low HDL-C in urban areas showed a 2.2-fold and 6.3-fold increase over the rural areas (9.3% vs 4.2% and 28.4% vs 4.5%, respectively). Among participants with dyslipidemia, 14.7% were aware of their condition; 5.9% were taking lipid-regulating medications; and only 2.9% had their dyslipidemia controlled. Comorbidities including hypertension (63.6%), and diabetes (25.2%) were highly prevalent in patients with dyslipidemia, however, the control rates of those comorbidities were only 40.0% and 6.6%.ConclusionsPatients with dyslipidemia showed high cardiovascular burden with low control rates of dyslipidemia, high prevalence of coexisting risk factors. Therefore, region- and sex-specific strategies to manage dyslipidemia and related risk factors should be highlighted.     

The effectiveness of a structured group education programme for people with established type 2 diabetes in a multi-ethnic population in primary care: A cluster randomised trial

Background and aimsStructured self-management education has been shown to be effective in type 2 diabetes (T2DM) but more research is needed to look at culturally appropriate programmes in ethnic minority groups, where prevalence of T2DM is higher and diagnosis earlier. The study tested the effectiveness of a group education programme for people with established T2DM in a multi-ethnic primary care population.Methods and resultsCluster randomised trial conducted in two multi-ethnic UK sites. Practices were randomised (1:1) to a structured T2DM group education programme or to continue with routine care. A culturally-adapted version was offered to South Asians, who formed the majority of ethnic minority participants. Other ethnic minority groups were invited to attend the standard programme. Primary outcome was change in HbA1c at 12 months. All analyses accounted for clustering and baseline value.367 participants (64(SD 10.8) years, 36% women, 34% from minority ethnic groups) were recruited from 31 clusters. At 12 months, there was no difference in mean change in HbA1c between the two groups (?0.10%; (95% CI: ?0.37, 0.17). Subgroup analyses suggested the intervention was effective at lowering HbA1c in White European compared with ethnic minority groups. The intervention group lost more body weight than the control group (?0.82 kg at 6 months and ?1.06 kg at 12 months; both p = 0.03).ConclusionOverall, the programme did not result in HbA1c improvement but in subgroup analysis, a beneficial effect occurred in White Europeans. Findings emphasise a need to develop and evaluate culturally-relevant programmes for ethnic minority groups.     

Effects of nut consumption on blood lipid profile: A meta-analysis of randomized controlled trials

Background & aimsSeveral randomized controlled trials (RCTs) have assessed the effects of nut consumption on blood lipid profile. The aim of this study was to conduct a meta-analysis to quantitatively estimate the effects of nut consumption on blood lipid profile.Methods and resultsThe PubMed, EMBASE, Cochrane Library, and Google Scholar databases were systematically searched to identify RCTs examining the effects of nut intake on blood total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) from inception until March 2021. A random-effects model was used to pool standardized mean differences (SMDs) and 95% confidence intervals (CIs). Potential publication bias was assessed using Begg's test and Egger's test. Sensitivity analysis was performed to assess the impact of each individual study on the pooled results. The meta-analysis showed that nut consumption had no significant effect on the blood lipid profile. However, there was a significant reduction in TC (SMD: ?2.89, 95% CI: ?4.80, ?0.98, I² = 97.4) for pistachio consumption, and cashew consumption significantly increased HDL-C (SMD: 0.24, 95% CI: 0.04, 0.43, I² = 0.0) compared with that in controls. There was no significant publication bias in the meta-analysis. The sensitivity analysis showed that removing one study at a time did not change the significance of the results.ConclusionThere was no overall effect of nut consumption on lipid profile, and the results may vary depending on nut type. We found that pistachio consumption may reduce TC levels, while cashew consumption increases HDL-C.Registry numberPROSPERO CRD42021249147.     

Lipid profiles and the risk of new-onset hypertension in a Chinese community-based cohort

Background and aimsDyslipidemia and hypertension, key risk factors for cardiovascular disease, may share similar pathophysiological processes. A longitudinal association was reported between dyslipidemia and new-onset hypertension, but few data were published in Asian. We aimed to investigate the association of lipid profiles with new-onset hypertension in a Chinese community-based non-hypertensive cohort without lipid-lowering treatment (n = 1802).Methods and resultsNew-onset hypertension was defined as any self-reported history of hypertension, systolic blood pressure ≥140 mmHg, or diastolic blood pressure ≥90 mmHg, or receiving antihypertensive medications at follow-up. Logistic regression models were used to evaluate the associations. Participants were aged 53.97 ± 7.49 years, 31.19% were men, and 64.54% with dyslipidemia. During a median of 2.30 years follow-up, the incidence of new-onset hypertension was 12.99%. Multivariate adjusted risks of new-onset hypertension increased with triglyceride increases (odds ratio [OR] = 1.14, 95% confidence interval [CI]: 1.03–1.27) and high-density lipoprotein cholesterol (HDL-C) decreases (OR = 0.47, 95% CI: 0.29–0.76) for one unit. However, threshold effects were observed for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-HDL-C. Compared with subjects with hyperlipidemia, in those with normal concentrations of TC, LDL-C, and non-HDL-C increased risks of new-onset hypertension were observed with OR (95% CI) of 1.65 (1.10–2.46), 1.58 (1.07–2.33), and 1.57 (1.15–2.15) for one unit increasement, respectively, after adjusting for all covariates.ConclusionHigher TG and lower HDL-C increased the risk of new-onset hypertension, but for TC, LDL-C and non-HDLC, the risk of new-onset hypertension was increased only at normal concentrations in a Chinese community-based cohort.     

Dietary intake and lipid levels in Norwegian and Spanish children with familial hypercholesterolemia

Background and aimsBoth the Nordic and Mediterranean diets claim to have a beneficial effect on lipid metabolism and cardiovascular prevention. The objective of this study was to compare diets consumed by children with FH at the time of diagnosis in Norway and Spain and to study their relationship with the lipid profile.Methods and resultsIn this cross-sectional study, we appraised the dietary intake in children (4–18 years old) with (n = 114) and without FH (n = 145) from Norway and Spain. We compared Nordic and Mediterranean diet composition differences and determined the association between food groups and lipid profiles.ResultsThe Spanish FH group had a higher intake of total fats (mainly monounsaturated fatty acids (MUFAs)), cholesterol and fibre, but a lower intake of polyunsaturated fatty acids (PUFAs) compared to the Norwegian FH group. The Norwegian children consumed more rapeseed oil, low-fat margarine and whole grains and less olive oil, eggs, fatty fish, meat, legumes and nuts. In the Norwegian FH group, fat and MUFAs were directly correlated with total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B and inversely correlated with high-density lipoprotein (HDL-C). In Spanish children with FH, the intake of fats (mainly MUFAs) was directly associated with HDL-C and apolipoprotein A1.ConclusionsDespite a similar lipid phenotype, diets consumed by children with FH in Norway and Spain have significant differences at time of diagnosis. Nutrition advice should be more adapted to local intake patterns than on specific nutrient composition.     

Triglyceride to high-density lipoprotein cholesterol ratio and cardiovascular events in the general population: A systematic review and meta-analysis of cohort studies

AimsThe ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) has been regarded as a novel surrogate indicator of insulin resistance and the atherogenic index of plasma. This meta-analysis aimed to evaluate the association between the TG/HDL-C ratio and the incidence of cardiovascular events in the general population.Data synthesisCohort studies reporting the association between the TG/HDL-C ratio and cardiovascular events in the general population were obtained by a systematic literature search of PubMed, Embase and Web of Science databases until April 11, 2021. 13 cohort studies with a total of 207,515 participants were included in this meta-analysis. In a random-effects model, compared with those with the lowest category of the TG/HDL-C ratio, participants with the highest category were independently associated with a higher risk of cardiovascular events (pooled HR: 1.43, 95%CI: 1.26–1.62, I² = 72.9%). For the presence of publication bias detected by the Egger's test (p = 0.011), correction for publication bias using the trim-and-fill method reduced the HR to 1.26 (95%CI: 1.11–1.44). This result was consistent with the finding of the TG/HDL-C ratio analyzed as a continuous variable (pooled HR per unit increment of the TG/HDL-C ratio: 1.08, 95%CI: 1.04–1.12, I² = 67.0%). Subgroup analyses indicated that population gender, geographical region, duration of follow-up, adjustment for other lipid parameters, adjustment for diabetes and categorical number did not significantly vary the relationship.ConclusionElevated TG/HDL-C ratio may be independently associated with an increased risk of cardiovascular events in the general population. More well-designed studies are needed to confirm the current findings.Registration number in PROSPEROCRD42021244583.     

Trends in lipid profiles and control of LDL-C among adults with diabetes in the United States: An analysis of NHANES 2007–2018

Background and aimTo determine trends in lipid profiles and lipid control in US adults with diabetes and assess variation in these trends across sex and race/ethnicity from 2007 to 2018.Methods and resultsSerial cross-sectional analysis of data from diabetic adults participating in the National Health and Nutrition Examination Survey (NHANES; 2007–2008 to 2017–2018). Among the 6116 participants included (weighted mean age, 61.0 years; 50.7% men), age-adjusted TC (p for trend < 0.001), LDL-C (p for trend < 0.001), TG (p for trend = 0.006), TG/HDL-C (p for trend = 0.014) and VLDL-C (p for trend = 0.015) decreased significantly. Age-adjusted LDL-C levels were consistently higher in women than in men over the study period. Age-adjusted LDL-C improved significantly for diabetic whites and blacks but did not change significantly for the other races/ethnicity. Lipid parameters improved for non-coronary heart disease (CHD) diabetic adults, except for HDL-C, while no lipid parameter significantly changed for diabetic adults with concomitant CHD. Among diabetic adults receiving statin therapy, age-adjusted lipid control remained unchanged from 2007 to 2018, as did adults with concomitant CHD. However, age-adjusted lipid control improved significantly for men (p for trend < 0.01) and diabetic Mexican Americans (p for trend < 0.01). In 2015–2018, female diabetic participants receiving statins had lower odds of achieving lipid control (OR: 0.55; 95% CI: 0.35–0.84; P = 0.006) than men. Differences in lipid control across different races/ethnicities no longer existed.ConclusionsLipid profiles improved in the US adults with diabetes from 2007 to 2018. Although rates of lipid control did not improve nationally in adults receiving statins, these patterns varied by sex and race/ethnicity.     

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.     

Identification of genetic loci simultaneously associated with multiple cardiometabolic traits

Background and aimsCardiometabolic disorders (CMD) arise from a constellation of features such as increased adiposity, hyperlipidemia, hypertension and compromised glucose control. Many genetic loci have shown associations with individual CMD-related traits, but no investigations have focused on simultaneously identifying loci showing associations across all domains. We therefore sought to identify loci associated with risk across seven continuous CMD-related traits.Methods and resultsWe conducted separate genome-wide association studies (GWAS) for systolic and diastolic blood pressure (SBP/DBP), hemoglobin A1c (HbA1c), low- and high- density lipoprotein cholesterol (LDL-C/HDL-C), waist-to-hip-ratio (WHR), and triglycerides (TGs) in the UK Biobank (N = 356,574–456,823). Multiple loci reached genome-wide levels of significance (N = 145–333) for each trait, but only four loci (in/near VEGFA, GRB14-COBLL1, KLF14, and RGS19-OPRL1) were associated with risk across all seven traits (P < 5 × 10^?8). We sought replication of these four loci in an independent set of seven trait-specific GWAS meta-analyses. GRB14-COBLL1 showed the most consistent replication, revealing nominally significant associations (P < 0.05) with all traits except DBP.ConclusionsOur analyses suggest that very few loci are associated in the same direction of risk with traits representing the full spectrum of CMD features. We identified four such loci, and an understanding of the pathways between these loci and CMD risk may eventually identify factors that can be used to identify pathologic disturbances that represent broadly beneficial therapeutic targets.     

Long-term burden of higher body mass index from childhood on adult cardiometabolic biomarkers: A 30-year cohort study

Background and aimsData are limited regarding the association between long-term burden of higher body mass index (BMI) from childhood and cardiometabolic biomarkers.Methods and resultsA total of 1553 individuals aged 6–15 years, who were examined 4 or more times for BMI since childhood and followed for 30 years were included in our analysis. Total area under the curve (AUCt) and incremental AUC (AUCi) were calculated as the long-term burden and trends of BMI. Cardiometabolic biomarkers including serum uric acid (SUA), fasting blood-glucose (FBG), and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) were obtained from venous blood samples. The results showed a positive association of BMI AUCt and AUCi with cardiometabolic biomarkers. After adjusting for demographic variables, the AUCt and AUCi of BMI were significantly associated with a higher level of SUA (β = 3.71; 2.87), FBG (β = 0.09; 0.09), and TG/HDL-C (β = 0.14; 0.11). We performed further studies after dividing subjects into four groups according to AUCt and AUCi of BMI by quartiles. Compared with the lowest quartile group, the highest quartile group had significantly increased risk ratios of hyperuricemia (RR = 2.01; 1.74), type 2 diabetes mellitus (RR = 8.18; 3.96), and high-risk TG/HDL-C (RR = 4.05; 3.26).ConclusionOur study identifies all subjects’ BMI growth curve from childhood and indicates that the long-term burden of higher BMI significantly increases the cardiometabolic risk, and the impact of excessive body weight on cardiometabolic health originates in early life. We emphasize the importance of weight control from childhood for cardiometabolic health.     

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.     

Evaluation of protein and amino acid intake estimates from the EPIC dietary questionnaires and 24-h dietary recalls using different food composition databases

Background and aimsThis study aimed to expand the European Prospective Investigation into Cancer and Nutrition (EPIC) nutrient database (ENDB) by adding amino acid (AA) values, using the U.S. nutrient database (USNDB). Additionally, we aimed to evaluate these new protein and AA intake estimates from the EPIC dietary questionnaires (DQ) and 24-h dietary recalls (24-HDR) using different matching procedures.Methods and resultsDietary energy, protein and AA intakes were assessed via DQ and 24-HDR by matching with the USNDB food composition table. Energy and protein intakes calculated using USNDB matching were compared with those calculated using ENDB, that uses country specific food composition tables. Pearson correlations, Cohen's weighted kappa statistic and Bland–Altman plots were used to compare data resulting from USNDB matching with our reference from ENDB matching.Very high correlations were found when comparing daily energy (r = 0.99) and dietary protein intakes (r = 0.97) assessed via USNDB with those obtained via ENDB (matching for DQ and 24-HDR). Significant positive correlations were also found with energy and protein intakes acquired via 24-HDRs in the EPIC calibration sample.ConclusionVery high correlations between total energy and protein intake obtained via the USDA matching and those available in ENDB suggest accuracy in the food matching. Individual AA have been included in the extended EPIC Nutrient database that will allow important analyses on AA disease prospective associations in the EPIC study.     

The role of adiposity,diet and inflammation on the discordance between LDL-C and apolipoprotein B

Background and aimsWhile low-density lipoprotein cholesterol (LDL-C) is a good predictor of atherosclerotic cardiovascular disease, apolipoprotein B (ApoB) is superior when the two markers are discordant. We aimed to determine the impact of adiposity, diet and inflammation upon ApoB and LDL-C discordance.Methods and resultsMachine learning (ML) and structural equation models (SEMs) were applied to the National Health and Nutrition Examination Survey to investigate cardiometabolic and dietary factors when LDL-C and ApoB are concordant/discordant. Mendelian randomisation (MR) determined whether adiposity and inflammation exposures were causal of elevated/decreased LDL-C and/or ApoB. ML showed body mass index (BMI), dietary saturated fatty acids (SFA), dietary fibre, serum C-reactive protein (CRP) and uric acid were the most strongly associated variables (R² = 0.70) in those with low LDL-C and high ApoB. SEMs revealed that fibre (b = ?0.42, p = 0.001) and SFA (b = 0.28, p = 0.014) had a significant association with our outcome (joined effect of ApoB and LDL-C). BMI (b = 0.65, p = 0.001), fibre (b = ?0.24, p = 0.014) and SFA (b = 0.26, p = 0.032) had significant associations with CRP. MR analysis showed genetically higher body fat percentage had a significant causal effect on ApoB (Inverse variance weighted (IVW) = Beta: 0.172, p = 0.0001) but not LDL-C (IVW = Beta: 0.006, p = 0.845).ConclusionOur data show increased discordance between ApoB and LDL-C is associated with cardiometabolic, clinical and dietary abnormalities and that body fat percentage is causal of elevated ApoB.     

Elevated serum uric acid was associated with pre-inflammatory state and impacted the role of HDL-C on carotid atherosclerosis

Background and aimsUric acid (UA) and high-density lipoprotein cholesterol (HDL-C) are positively and negatively associated with atherosclerosis, respectively. UA and HDL-C are involved in the balance of proinflammatory and anti-inflammatory processes in atherosclerosis. However, it is still unclear whether UA affects the effect of HDL-C on atherosclerosis.Methods and resultsIn this retrospective study, we enrolled 1437 patients with multiple risk factors for atherosclerosis. Patients were categorized into two groups according to their baseline UA level. Multivariate logistic regression analysis and restricted cubic spline curves were used to assess the relationship between HDL-C and carotid atherosclerosis (abnormal carotid intima–media thickness [cIMT] and carotid artery plaque) at different UA levels. Compared to patients with normouricemia, patients with hyperuricemia were older and had a more extensive history of disease and unhealthy behavior. In the normouricemia group, multivariate-adjusted odds ratios (95% CIs) for HDL-C were 0.55 (0.33–0.92) for abnormal mean cIMT, 0.59 (0.35–1.00) for abnormal maximum cIMT, and 0.53 (0.29–0.94) for the occurrence of carotid artery plaque, while the correlation between each of these three indicators with HDL-C were not significant in those with hyperuricemia. Spline regression models yielded similar results. The effect of UA on the association between HDL-C and carotid atherosclerosis remained in the subset of patients with optimal low-density lipoprotein cholesterol.ConclusionElevated UA marks a pre-inflammatory state and impacts the role of HDL-C on carotid atherosclerosis.     

Diets high in glycemic index and glycemic load are associated with an increased risk of metabolic syndrome among Korean women

Background and aimsAccurate estimation of the glycemic index (GI) and glycemic load (GL) of diets is essential when assessing health implications of dietary GI and GL. The present study aimed to estimate dietary GI and GL utilizing the updated GI tables with a large number of new, reliable GI values and assess their associations with metabolic syndrome among Korean adults.Methods and resultsWe analyzed data from 3317 men and 6191 women for this cross-sectional study. Dietary intake was assessed with a validated food frequency questionnaire. Metabolic syndrome and its components were defined based on the harmonized criteria with Korean-specific cutoffs for waist circumference. Multivariate logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Compared with women in the lowest quintiles of energy-adjusted dietary GI and GL, women in the highest quintiles had significantly greater risks of metabolic syndrome (GI, OR = 1.56, 95% CI = 1.18–2.06; GL, OR = 1.80, 95% CI = 1.27–2.57), elevated blood pressure, reduced high-density lipoprotein cholesterol (HDL-C, both GI and GL), elevated triglycerides (GI only), elevated waist circumference, and elevated fasting glucose (GL only). Among men, no significant association was noted except for a higher risk of reduced HDL-C (OR = 1.59, 95% CI = 1.01–2.29) in the highest quintile of energy-adjusted dietary GI than in the lowest quintile.ConclusionOur findings suggest that dietary GI and GL are positively associated with metabolic syndrome risk among women, but not men, in Korea.     

Independent euglycaemic hyperinsulinaemic clamp studies validate clinically applicable formulae to estimate insulin sensitivity in people with type 1 diabetes

Background and aimLow insulin sensitivity (IS) increases Type 1 diabetes (T1D) complication risk and can be estimated by simple formulae developed from complex euglycemic hyperinsulinaemic clamp studies. We aimed to validate these formulae using independent clamp data.MethodsClamps were performed in 104 T1D adults. Measured glucose disposal rate (GDR) was correlated with eGDR and eLog10 M/I calculated by five IS formulae.ResultsCorrelations ranged between 0.23–0.40. Two IS formulae (by the authors), using age, sex, HDL-C, HbA1c, pulse pressure, BMI, and waist-hip-ratio had the highest correlation with measured GDR and the best performance in detecting low IS.