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.     

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.     

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.     

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.     

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.     

Effects of individualized dietary advice compared with conventional dietary advice for adults with type 2 diabetes: A randomized controlled trial

Background and aimsTo investigate the superiority of individualized dietary advice based on dietary assessment for patients with type 2 diabetes.Methods and resultsA total of 136 Japanese adults with type 2 diabetes were randomized into either individualized or conventional dietary advice groups after dietary assessment using a self-administered brief-type diet history questionnaire. Both participants received three 30-min face-to-face dietary advice sessions by dietitians at 1, 3, and 5 months from study entry. The individualized group received dietary advice based on individual dietary intakes. The conventional group received dietary advice using generalized pamphlets. The primary outcome was the change in HbA1c over 6 months, and secondary outcomes were changes in weight, serum triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and dietary intakes. In total, 126 participants were included in the analysis. After adjustment for age, sex, and baseline measurements, HbA1c significantly decreased larger in the individualized group [?1.1%, (95% CI: ?1.3 to ?0.8)] than the conventional group [?0.7% (95% CI: ?1.0 to ?0.4)] (P = 0.0495). The individualized group significantly decreased weight, serum triglyceride, and LDL-C, and significantly increased HDL-C, without a significant difference to the conventional group. In dietary changes, the individualized group decreased intakes of energy, confectioneries, meats, oil and fats, and sugar-sweetened beverages. The conventional group decreased alcohol intake and increased total fat and saturated fatty acid intakes.ConclusionsIndividualized dietary advice among patients with type 2 diabetes was superior to conventional dietary advice in lowering HbA1c.Trial registrationUMIN000037268 (https://www.umin.ac.jp/ctr/index.htm) in July 4, 2019.     

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.     

Uric acid is independent and inversely associated to glomerular filtration rate in young adult Brazilian individuals

Background and aimsUric acid, the end-product of human purine metabolism, is associated with hypertension, diabetes and obesity. It has also been independently associated with the onset of chronic kidney disease in several populations. In this study, the association between serum uric acid (SUA) level and estimated glomerular filtration rate (eGFR) was investigated in healthy individuals belonging to two Brazilian birth cohorts.Methods and resultsData from 3541 to 3482 individuals, aged 30 and 22-years old, respectively, was included. eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on creatinine measurement. Regression analyses were sex-stratified due to interaction between SUA and sex (p < 0.001) and adjusted for perinatal, cardiometabolic and behavioral variables.We observed an inverse association between eGFR and SUA even after adjustment. In the highest tertile (3rd) of SUA, the eGFR coefficients at 30-years were-0.21 (95%CI -0.24;-0.18) for men and −0.20 (95%CI -0.23; −0.17) for women; at 22-years, were −0.09 (95%CI -0.12;-0.05) for men and −0.13 (95%CI -0.15; −0.10) for women. Higher differences among exponential means (95% CI) of eGFR between the 1st and the 3rd tertile of SUA were seen in older participants, being more pronounced in men. At 22-years, the highest difference was found in women.ConclusionsIn young healthy individuals from a low-middle income country, SUA level was inversely associated with eGFR. Gender-related differences in eGFR according tertiles of SUA were higher in men at 30-years and in women at 22-years.     

Fruit consumption and cardiometabolic risk in the PREDIMED-plus study: A cross-sectional analysis

Background and aimsTotal fruit consumption is important for cardiovascular disease prevention, but also the variety and form in which is consumed. The aim of the study was to assess the associations between total fruit, subgroups of fruits based on their color and fruit juices consumption with different cardiometabolic parameters.Methods and resultsA total of 6633 elderly participants (aged 55–75 years) with metabolic syndrome from the PREDIMED-Plus study were included in this analysis. Fruit and fruit juice consumption was assessed using a food frequency questionnaire. Linear regression models were fitted to evaluate the association between exposure variables (total fruit, subgroups based on the color, and fruit juices) and different cardiometabolic risk factors. Individuals in the highest category of total fruit consumption (≥3 servings/d) had lower waist circumference (WC) (β = ?1.04 cm; 95%CI:-1.81, ?0.26), fasting glucose levels (β = ?2.41 mg/dL; 95%CI(-4.19, ?0.63) and LDL-cholesterol (β = ?4.11 mg/dL; 95%CI:-6.93, ?1.36), but, unexpectedly, higher systolic blood pressure (BP) (β = 1.84 mmHg; 95%CI: 0.37, 3.30) and diastolic BP (β = 1.69 mmHg; 95%CI:0.83, 2.56) when compared to those in the lowest category of consumption (<1 servings/d). Participants consuming ≥1 serving/day of total fruit juice had lower WC (β = ?0.92 cm; 95%CI:-1.56, ?0.27) and glucose levels (β = ?1.59 mg/dL; 95%CI:-2.95, ?0.23) than those consuming <1 serving/month. The associations with cardiometabolic risk factors differed according to the color of fruits.ConclusionFruit consumption is associated with several cardiometabolic risk factors in Mediterranean elders with metabolic syndrome. The associations regarding BP levels could be attributed, at least partially, to reverse causality bias inherent to the cross-sectional design of the study.     

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)     

Effects of weight loss medications on mortality and cardiovascular events: A systematic review of randomized controlled trials in adults with overweight and obesity

AimsAdults affected by obesity are at higher risk of premature mortality. Medications can help to lose weight and to maintain weight loss. Aim of this meta-analysis was to assess whether anti-obesity medications affect all-cause mortality, mortality due to cardiovascular events, cardiovascular risk factors and body weight.Data synthesisA Medline search was performed to identify randomized controlled trials (RCTs) of anti-obesity medications in adults with overweight or obesity reporting data on all-cause mortality, cardiovascular mortality or non-fatal cardiovascular events, with a follow-up of at least 6 months. We identified 28 RCTs with 50,106 participants. The median follow-up was 52 weeks. Evidence did not show superiority of anti-obesity medications over placebo in reducing all-cause mortality (risk ratio 1.03, 95%Confidence Interval [CI] 0.87 to 1.21) or cardiovascular mortality (risk ratio 0.92, 95%CI 0.72 to 1.18). All-cause mortality rate was positively associated with weight loss (β = 0.0007; p = 0.045); hence, for each kg of body weight lost there was a 0.07% decrease of all-cause mortality. The pharmacological treatment reduced total-cholesterol (7.15 mg/dl; 95%CI 1.46–12.85), LDL-cholesterol (5.06 mg/dl; 95%CI 1.12–9.00), and triglycerides levels (9.88 mg/dl; 95%CI 5.02–14.75), while it increased HDL-cholesterol (1.37 mg/dl; 95%CI 0.17–2.57). Systolic blood pressure decreased (0.90 mmHg; 95%CI 0.15–1.64).ConclusionsAlthough we were unable to demonstrate a superiority of anti-obesity medications over placebo on mortality, metaregression showed that even a small weight reduction tends to reduce all-cause mortality in obesity. Our data support public health measures to reduce the obesity burden by including the use of anti-obesity medications.Registration number (PROSPERO)CRD42020210329.     

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.     

Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study

Background and aimPlasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association of baseline and 1-year levels of plasma CAC-related metabolites with CVD incidence (a composite of myocardial infarction, stroke or cardiovascular death), and their interaction with Mediterranean diet interventions.Methods and resultsCase-cohort study from the PREDIMED trial involving participants aged 55–80 years at high cardiovascular risk, allocated to MedDiets or control diet. A subcohort of 791 participants was selected at baseline, and a total of 231 cases were identified after a median follow-up of 4.8 years. Nine plasma CAC-related metabolites (pyruvate, lactate, citrate, aconitate, isocitrate, 2-hydroxyglutarate, fumarate, malate and succinate) were measured using liquid chromatography-tandem mass spectrometry. Weighted Cox multiple regression was used to calculate hazard ratios (HRs). Baseline fasting plasma levels of 3 metabolites were associated with higher CVD risk, with HRs (for each standard deviation, 1-SD) of 1.46 (95%CI:1.20–1.78) for 2-hydroxyglutarate, 1.33 (95%CI:1.12–1.58) for fumarate and 1.47 (95%CI:1.21–1.78) for malate (p of linear trend <0.001 for all). A higher risk of CVD was also found for a 1-SD increment of a combined score of these 3 metabolites (HR = 1.60; 95%CI: 1.32–1.94, p trend <0.001). This result was replicated using plasma measurements after one-year. No interactions were detected with the nutritional intervention.ConclusionPlasma 2-hydroxyglutarate, fumarate and malate levels were prospectively associated with increased cardiovascular risk.Clinical trial numberISRCTN35739639     

Mediating effect of metabolic diseases on the relationship between hyperuricemia and coronary heart disease

Background and aimsStudies have shown that elevated serum uric acid (SUA) may increase the risk of coronary heart disease (CHD). However, it is still disputable how mediate effects between metabolic diseases and hyperuricemia affect the incidence of CHD. This study aimed to explore whether metabolic diseases may mediate the connection from hyperuricemia at baseline to the elevated incidence risk of CHD during follow-ups.Methods and ResultsBased on the Jinchang cohort, 48 001 subjects were followed for 9 years between June 2011 and December 2019. Multivariate-adjusted Cox regression models were applied to estimate hazard ratios (HRs) of CHD with 95% confidence intervals (CIs). Significantly increased risks of CHD were observed in hyperuricemia (HR:1.46, 95%CI:1.28, 1.67) when compared with normouricemia population. The mediating effect model further demonstrated that metabolic diseases could mediate the association between hyperuricemia and CHD pathogenesis, partially for the combined metabolic diseases with mediation effects of 45.12%, 25.24% for hypertension, 28.58% for overweight or obese status, 29.05% for hypertriglyceridemia, 6.70% for hypercholesterolemia, 3.52% for low high density lipoprotein cholesterol (HDL-C), and 6.51% for high low density lipoprotein cholesterol (LDL-C), respectively.ConclusionsHyperuricemia significantly increased the risk of incident CHD, and this association was partly mediated by metabolic diseases.     

Sugar- and artificially-sweetened soda consumption and subclinical atherosclerosis among Mexican women

Background and aimsSugar-sweetened soda consumption is associated with most cardiometabolic risk factors. The role of artificially-sweetened beverages in cardiovascular disease (CVD) is inconclusive, but their consumption correlates with health impairment. Little is known about the contribution of soda consumption in subclinical stages of atherosclerosis. Therefore, we evaluated the relation between sugar- and artificially-sweetened soda consumption and carotid intima-media thickness (IMT) among Mexican women.Methods and resultsWe cross-sectionally evaluated 1093 women enrolled in the Mexican Teachers’ Cohort who were free of CVD, diabetes or cancer. Sugar- and artificially-sweetened soda consumption was estimated from a validated 140-item food frequency questionnaire in 2008 and all women underwent a carotid ultrasound assessment three years later. Participants were categorized into tertiles of soda consumption in servings/week. Subclinical atherosclerosis was defined as a mean left and/or right IMT ≥0.8 mm or the presence of plaque on either common carotid artery. In multivariable regression models, women in the highest tertile of sugar-sweetened soda consumption had 2.6% (95%CI: 0.8, 4.5) mean increased IMT, and had 2-fold the risk of carotid atherosclerosis (PR: 2.0, 95%CI: 1.3, 3.2) compared to those in the lowest tertile. In stratified analyses, older and postmenopausal women who consumed sugar-sweetened soda had an increased IMT and atherosclerosis risk. Artificially-sweetened soda consumption was not associated with IMT or carotid atherosclerosis.ConclusionsSugar-sweetened soda consumption was associated with subclinical atherosclerosis among disease-free Mexican women. Public health strategies to decrease CVD should consider the impact of sugar-sweetened soda consumption, particularly in older women.     

Long-Term Changes in Gut Microbial Metabolite Trimethylamine N-Oxide and Coronary Heart Disease Risk

BackgroundA gut-microbial metabolite, trimethylamine N-oxide (TMAO), has been associated with coronary atherosclerotic burden. No previous prospective study has addressed associations of long-term changes in TMAO with coronary heart disease (CHD) incidence.ObjectivesThe purpose of this study was to investigate whether 10-year changes in plasma TMAO levels were significantly associated with CHD incidence.MethodsThis prospective nested case-control study included 760 healthy women at baseline. Plasma TMAO levels were measured both at the first (1989 to 1990) and the second (2000 to 2002) blood collections; 10-year changes (Δ) in TMAO were calculated. Incident cases of CHD (n = 380) were identified after the second blood collection through 2016 and were matched to controls (n = 380).ResultsRegardless of the initial TMAO levels, 10-year increases in TMAO from the first to second blood collection were significantly associated with an increased risk of CHD (relative risk [RR] in the top tertile: 1.58 [95% confidence interval (CI): 1.05 to 2.38]; RR per 1-SD increment: 1.33 [95% CI: 1.06 to 1.67]). Participants with elevated TMAO levels (the top tertile) at both time points showed the highest RR of 1.79 (95% CI: 1.08 to 2.96) for CHD as compared with those with consistently low TMAO levels. Further, we found that the ΔTMAO-CHD relationship was strengthened by unhealthy dietary patterns (assessed by the Alternate Healthy Eating Index) and was attenuated by healthy dietary patterns (p interaction = 0.008).ConclusionsLong-term increases in TMAO were associated with higher CHD risk, and repeated assessment of TMAO over 10 years improved the identification of people with a higher risk of CHD. Diet may modify the associations of ΔTMAO with CHD risk.     

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.     

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.     

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.     

New onset diabetes predicts progression of low risk pancreatic mucinous cysts

BackgroundPatients with low-risk lesions require ongoing surveillance since the rate of progression to pancreatic cancer (PC), while small, is much greater than in the general population. Our objective was to study the relationship between new onset diabetes (NODM) and progression in patients with low risk mucinous cysts.MethodsWe evaluated a prospectively maintained cohort of 442 patients with a suspected mucinous cyst without worrisome features (WF) or high-risk stigmata (HRS). Multivariable Cox models were developed for progression to WF and HRS, with diabetes status formulated as both time independent and dependent covariates. The adjusted cumulative risk of progression was calculated using the corrected group prognosis method.ResultsThe 5-year cumulative progression rates to WFs and HRS were 12.8 and 3.6%, respectively. After controlling for other risk factors, the development of NODM was strongly associated with progression to HRS (HR = 11.6; 95%CI, 3.5–57.7%), but not WF. Among patients with the smallest cysts (<10 mm) at baseline, those who developed NODM had a 5-year adjusted cumulative risk of progression to HRS of 8.6% (95%CI, 0.0%–20.2%), compared to only 0.8% (95%CI, 0.0%–2.3%) for patients without NODM. Among patients with the largest cysts (20–29 mm), those who developed NODM during surveillance had a 5-year adjusted cumulative risk of progression of 53.5% (95%CI, 19.6%–89.9%) compared to only 7.5% (95%CI, 1.6%–15.2%) for patients without NODM.ConclusionNew onset diabetes may predict progression in patients with low risk mucinous cysts. Pending validation with large-scale studies, these findings support regular diabetes screening among patients surveilled for suspected IPMNs or MCNs.