Associations Between Triglyceride/High-Density Lipoprotein Cholesterol Ratio and Micro- and Macroangiopathies in Type 2 Diabetes Mellitus

Objective: The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been reported to be a marker of insulin resistance. The aim of this study was to investigate associations between the TG/HDL-C ratio and micro- and macroangiopathies in patients with type 2 diabetes mellitus (DM).Methods: A total of 1,981 (851 male and 1,130 female) patients with type 2 DM were enrolled from our outpatient clinic. These patients were stratified into 4 groups according to TG/HDL-C ratio quartiles.Results: There were significant trends for stepwise increases in albuminuria ≥30 mg/g (P<.001), coronary artery disease (CAD, P =.040), cerebrovascular disease (CVA, P =.002) and ankle-brachial index (ABI) <0.9 (P =.001) corresponding to TG/HDL-C ratio quartiles, but not diabetic retinopathy (P =.105). Furthermore, quartile 4 of the TG/HDL-C ratio was significantly associated with albuminuria, CAD, CVA, and ABI <0.9 after multivariate analysis compared to quartile 1.Conclusion: A high TG/HDL-C ratio was significantly associated with albuminuria, CAD, CVA, and peripheral artery occlusive disease (PAOD) in patients with DM, which translated into an increased risk of cardiovascular disease.Abbreviations: ABI = ankle-brachial index; ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blocker; BMI = body mass index; CAD = coronary artery disease; CI = confidence interval; CVA = cerebrovascular disease; DM = diabetes mellitus, DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; HbA1c = glycated hemoglobin A1c; HDL-C = high-density lipoprotein cholesterol; OR = odds ratio; PAOD = peripheral artery occlusive disease; TGs = triglycerides     

Eggs distinctly modulate plasma carotenoid and lipoprotein subclasses in adult men following a carbohydrate-restricted diet

We previously reported that carbohydrate restriction (CR) (10–15% en) during a weight loss intervention lowered plasma triglycerides (TG) by 45% in male subjects (P<.001). However, those subjects with a higher intake of cholesterol provided by eggs (640 mg additional cholesterol, EGG group) had higher concentrations of high-density lipoprotein (HDL) cholesterol (P<.0001) than the individuals consuming lower amounts (0 mg of additional cholesterol, SUB group). The objectives of the present study were to evaluate whether CR and egg intake (1) modulate circulating carotenoids and (2) affect the concentrations of plasma apolipoproteins (apo), lipoprotein size and subfraction distribution. CR decreased the number of large and medium very low-density lipoprotein cholesterol subclasses (P<.001), while small low-density lipoprotein (LDL) were reduced (P<.001). In agreement with these observations, a decrease in apo B (P<.01) was observed. In addition, CR resulted in a 133% increase in apo C-II and a 65% decrease in apo C-III (P<.0001). Although an increase of the larger LDL subclass was observed for all subjects, the EGG group had a greater increase (P<.05). The EGG group also presented a higher number of large HDL particles (P<.01) compared to the SUB group. Regarding carotenoids, CR resulted in no changes in dietary or plasma α- or β-carotene and β-cryptoxanthin, while there was a significant reduction in both dietary and plasma lycopene (P<.001). In contrast, dietary lutein and zeaxanthin were increased during the intervention (P<.05). However, only those subjects from the EGG group presented higher concentrations of these two carotenoids in plasma, which were correlated with the higher concentrations of large LDL observed in the EGG group. These results indicate that CR favorably alters VLDL metabolism and apolipoprotein concentrations, while the components of the egg yolk favor the formation of larger LDL and HDL leading to an increase in plasma lutein and zeaxanthin.     

Apolipoprotein A-V is a potential target for treating coronary artery disease: evidence from genetic and metabolomic analyses

Triglyceride (TG)-lowering LPL variants in combination with genetic LDL-C-lowering variants are associated with reduced risk of coronary artery disease (CAD). Genetic variation in the APOA5 gene encoding apolipoprotein A-V also strongly affects TG levels, but the potential clinical impact and underlying mechanisms are yet to be resolved. Here, we aimed to study the effects of APOA5 genetic variation on CAD risk and plasma lipoproteins through factorial genetic association analyses. Using data from 309,780 European-ancestry participants from the UK Biobank, we evaluated the effects of lower TG levels as a result of genetic variation in APOA5 and/or LPL on CAD risk with or without a background of reduced LDL-C. Next, we compared lower TG levels via APOA5 and LPL variation with over 100 lipoprotein measurements in a combined sample from the Netherlands Epidemiology of Obesity study (N = 4,838) and the Oxford Biobank (N = 6,999). We found that lower TG levels due to combined APOA5 and LPL variation and genetically-influenced lower LDL-C levels afforded the largest reduction in CAD risk (odds ratio: 0.78 (0.73–0.82)). Compared to patients with genetically-influenced lower TG via LPL, genetically-influenced lower TG via APOA5 had similar and independent, but notably larger, effects on the lipoprotein profile. Our results suggest that lower TG levels as a result of APOA5 variation have strong beneficial effects on CAD risk and the lipoprotein profile, which suggest apo A-V may be a potential novel therapeutic target for CAD prevention.     

ACUTE PANCREATITIS IN PATIENTS WITH SEVERE HYPERTRIGLYCERIDEMIA IN A MULTI-ETHNIC MINORITY POPULATION

Objective: To investigate the prevalence and predictors of hypertriglyceridemic acute pancreatitis (HTG-AP) in a multi-ethnic minority population.Methods: A retrospective, cross-sectional study from 2003 to 2013 of 1,157 adults with a serum triglyceride (TG) level =1,000 mg/dL comparing baseline characteristics and risk factors between those with and without HTG-AP.Results: Mean study population age was 49.2 ± 11.5 years; 75.6% were male, 31.6% African American, 38.4% Hispanic, 22.7% Caucasian, 5.7% Asian, and 1.6% Pacific Islander. Prevalence of HTG-AP was 9.2%. Patients with HTG-AP were significantly younger (41.3 years vs. 50.0 years; P<.001) than those without HTG-AP. Excessive alcohol intake (odds ratio [OR], 3.9; 95% confidence interval [CI], 2.5 to 6.0; P<.001), gallstone disease (OR, 3.9; 95% CI, 1.4 to 10.8; P = .008), and TG >2,000 mg/dL (OR, 4.8; 95% CI, 3.1 to 7.4; P<.001) remained significant independent risk factors. TG levels for patients with HTG-AP were higher (median TG, 2,394 mg/dL; interquartile range [IQR], 1,152 to 4,339 mg/dL vs. median TG, 1,406 mg/dL; IQR, 1,180.7 to 1,876.5 mg/dL). TG levels >2,000 mg/dL were associated with higher incidence of AP (22% vs. 5%). Patients with TG levels <2,000 mg/dL and no risk factors had prevalence of 2% compared to 33.6% with one risk factor and TG >2,000 mg/dL. Patients with HTG-AP had higher incidence of diabetic ketoacidosis at admission (7.5% vs. 2.5%; P = .004).Conclusion: TG level =2,000 mg/dL is associated with higher HTG-AP prevalence in ethnic minorities. Presence of excessive alcohol intake and/or gallstones further accentuates risk.Abbreviations: AP = acute pancreatitis; CT = computed tomography; DM = diabetes mellitus; HbA1c = hemoglobin A1c; HIV = human immunodeficiency virus; HTG = hyper-triglyceridemia; HTG-AP = hypertriglyceridemic acute pancreatitis; ROC = receiver operating characteristic; TG = triglyceride     

Are Markers of Inflammation More Strongly Associated with Risk for Fatal Than for Nonfatal Vascular Events?

Background

Circulating inflammatory markers may more strongly relate to risk of fatal versus nonfatal cardiovascular disease (CVD) events, but robust prospective evidence is lacking. We tested whether interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen more strongly associate with fatal compared to nonfatal myocardial infarction (MI) and stroke.

Methods and Findings

In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), baseline inflammatory markers in up to 5,680 men and women aged 70–82 y were related to risk for endpoints; nonfatal CVD (i.e., nonfatal MI and nonfatal stroke [n = 672]), fatal CVD (n = 190), death from other CV causes (n = 38), and non-CVD mortality (n = 300), over 3.2-y follow-up. Elevations in baseline IL-6 levels were significantly (p = 0.0009; competing risks model analysis) more strongly associated with fatal CVD (hazard ratio [HR] for 1 log unit increase in IL-6 1.75, 95% confidence interval [CI] 1.44–2.12) than with risk of nonfatal CVD (1.17, 95% CI 1.04–1.31), in analyses adjusted for treatment allocation. The findings were consistent in a fully adjusted model. These broad trends were similar for CRP and, to a lesser extent, for fibrinogen. The results were also similar in placebo and statin recipients (i.e., no interaction). The C-statistic for fatal CVD using traditional risk factors was significantly (+0.017; p<0.0001) improved by inclusion of IL-6 but not so for nonfatal CVD events (p = 0.20).

Conclusions

In PROSPER, inflammatory markers, in particular IL-6 and CRP, are more strongly associated with risk of fatal vascular events than nonfatal vascular events. These novel observations may have important implications for better understanding aetiology of CVD mortality, and have potential clinical relevance. Please see later in the article for Editors'' Summary     

Parathyroidectomy Is Associated With Reversed Nondipping Heart Rate That Impacts Mortality in Chronic Kidney Disease Patients

ObjectiveNondipping heart rate (HR), defined as a night/day HR ratio >0.90, has been associated with increased mortality in epidemiologic studies. However, its prognostic value in stage 5 chronic kidney disease (CKD5) patients and the effects of parathyroidectomy (PTX) on nondipping HR remain unknown.MethodsThis case-control study of 162 healthy controls and 502 CKD5 patients was performed between 2011 and 2018, in which CKD5 patients were further divided into non-PTX (n = 186) and severe secondary hyperparathyroidism (SHPT) with PTX (n = 316) subgroups. Each participant underwent 24-hour Holter monitoring for HR ratio. Mortality was followed up in CKD5 patients (median time: 46.0 months).ResultsThe HR ratio in CKD5 patients was higher than in controls (0.92 ± 0.08 vs 0.81 ± 0.08, P <.001), associated with a 44% increase in mortality risk per 0.1 increment (hazard ratio, 1.44; 95% CI: 1.02-2.03; P =.04), and was positively related to serum intact parathyroid hormone levels (P <.001). PTX reversed nondipping HR in SHPT patients (n = 50, median time: 6.3 months, P <.001). Survival probabilities for PTX (n = 294) were better than non-PTX (n = 47) (hazard ratio, 0.31; 95% CI: 0.14-0.67; P <.01) in SHPT patients (serum intact parathyroid hormone >500.0 pg/mL).ConclusionCKD5 patients displayed a nondipping HR pattern, which is a prognostic marker of all-cause mortality. PTX for SHPT patients was associated with a reversal in nondipping HR ratio, which may mediate a better outcome.     

Increased Serum Cholesteryl Ester Transfer Protein in Obese Children

Objective: To determine whether serum cholesteryl ester transfer protein (CETP), which is one of the physiologically active gene products secreted from adipose tissue, is increased and associated with atherogenic lipoprotein profile in obese children. Research Methods and Procedures: Subjects were 42 consecutive outpatient Japanese obese children, 29 boys and 13 girls, ranging in age from 5 to 14 years, and 25 age‐matched non‐obese children, 13 boys and 12 girls, as the control group for measuring CETP mass. Blood was drawn after an overnight fast and, at the same time, and anthropometric measurements including height, body weight, waist girth, hip girth, and triceps and subscapular skinfold thicknesses were taken. Paired samples were obtained from 15 obese children who underwent psychoeducational therapy. Serum CETP mass was assayed by an enzyme‐linked immunosorbent assay. Results: The serum levels of triglyceride, total cholesterol (TC), low‐density lipoprotein cholesterol, TC/high‐density lipoprotein cholesterol (HDLC), apolipoproteins (apo) B, apo B/apo A₁, and insulin in obese children were significantly higher than the respective reference values. Serum CETP level was ～2‐fold higher (98.7 ± 3.6 vs. 50.9 ± 4.0 nM, means ± SEM, p < 0.001) in the obese children than in the controls. In 15 obese children, whose percentage of overweight declined during therapy, CETP levels decreased significantly. CETP level was correlated with HDLC, TC/HDLC, and insulin, and with percentage of overweight when the data of the obese and non‐obese children were combined. Discussion: CETP is increased and associated with the atherogenic lipoprotein profile in obese children.     

External Validation of a Predictive Model for Acute Pancreatitis Risk in Patients with Severe Hypertriglyceridemia

Objective: We previously developed a predictive model to assess the risk of developing acute pancreatitis (AP) in patients with severe hypertriglyceridemia (HTG). In this study, we aimed to externally validate this model.Methods: The validation cohort included cross-sectional data between 2013 and 2017. Adult patients (≥18 years old) with triglyceride levels ≥1,000 mg/dL were identified. Based on our previous 4-factor predictive model (age, triglyceride &lsqb;TG], excessive alcohol use, and gallstone disease), we estimated the probability of developing AP. Model performance was assessed using area under receiver operating characteristic curve (AUROC).Results: In comparison to the original cohort, patients in the validation cohort had more prevalent acute pancreatitis (16.2% versus 9.2%; P<.001) and gallstone disease (7.5% versus 2.1%; P<.001). Other characteristics were comparable and not statistically significant. The AUROCs were almost identical: 0.8337 versus 0.8336 in the validation and the original cohorts, respectively. In univariable analyses, the highest increase in odds of AP was associated with HTG, followed by gallstones, excessive alcohol use, and younger age.Conclusion: This study externally validates the 4-factor predictive model to estimate the risk of AP in adult patients with severe HTG (TG ≥1,000 mg/dL). Younger age was confirmed to place patients at high risk of AP. The clinical risk categories suggested in this study may be useful to guide treatment options.Abbreviations: AP = acute pancreatitis; ASCVD = atherosclerotic cardiovascular disease; AUROC = area under the receiver operating characteristic curve; FRAX = fracture risk assessment tool; HTG = hypertriglyceridemia; OR = odds ratio; TG = triglyceride level     

How do Different Indices of Obesity Correlate with Cardiometabolic Disease Risk Factors in Multiethnic Youths?

ObjectiveTo investigate the relationship between cardiometabolic disease risk factors (CDRFs) among ethnic minorities and anthropometric factors including body mass index z score, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHTR) in Hispanic and non-Hispanic black youths originating primarily from Central America, South America, and the Caribbean.MethodsClinical data of 167 young persons 2 to 19 years of age encountered in an outpatient pediatric endocrinology clinic were analyzed. The CDRFs included fasting insulin and glucose, homeostasis model assessment of insulin resistance (HOMA-IR), systolic blood pressure (SBP) and diastolic blood pressure (DBP), high-density lipoprotein cholesterol, triglycerides, cardiac C-reactive protein (CRP), and apolipoproteins.ResultsFor both the non-Hispanic black and the Hispanic youths, WC was significantly correlated with SBP (r = 0.63; P < .001 and r = 0.50; P < .001, respectively), DBP (r = 0.61; P < .001 and r = 0.47; P < .001, respectively), and cardiac CRP (r = 0.76; P < .001 and r = 0.26; P = .026, respectively). Similarly, WHTR was significantly correlated with SBP, DBP, and cardiac CRP for the non-Hispanic black study subjects, whereas SBP (r = 0.22; P = .01), DBP ( r = 0.34; P < .001), fasting insulin ( r = 0.43; P < .001), HOMA-IR (r = 0.38; P < .001), apolipoprotein A-I (r = 0.30; P = .01), and CRP (r = 0.44; P < .001) were significantly correlated for the Hispanic group. For both groups, body mass index z score was not consistently correlated with CDRFs, and waist-to-hip ratio was not significantly correlated with any CDRFs, except for apolipoprotein B in non-Hispanic black youths.ConclusionOur study shows that WC and WHTR may be useful anthropometric factors for better identification of ethnic minority youths at risk for adult-onset cardiometabolic disease. (Endocr Pract. 2009;15:403-409)     

Improvements in body fat distribution and circulating adiponectin by alternate-day fasting versus calorie restriction

Calorie restriction (CR) and alternate-day fasting (ADF) beneficially affect several aspects of adipose tissue physiology, but direct comparisons between regimens have yet to be performed. The present study evaluated the effects of ADF versus CR on body fat distribution and circulating adiponectin levels and examined the kinetic mechanisms that underlie changes in fat distribution. Thirty female C57BL/6J mice were randomized to one of five groups for 4 weeks: (a) CR-25% (25% energy restriction daily), (b) ADF-75% (75% restriction on fast day), (c) ADF-85% (85% restriction on fast day), (d) ADF-100% (100% restriction on fast day) and (e) control (ad libitum fed). Body weights of the CR mice were lower than that of the ADF and control groups posttreatment. After 4 weeks of diet, the proportion of visceral fat decreased (P<.001) and the proportion of subcutaneous fat increased (P<.001) similarly in ADF and CR animals. Adiponectin increased (P<.05) by 62–86% in the ADF groups and by 69% in the CR group. Triglyceride (TG) synthesis and de novo lipogenesis were augmented (P<.05) in the subcutaneous fat pad of ADF and CR animals, relative to control. No differences in net lipolysis were observed, resulting in greater TG accumulation in the subcutaneous fat pad, with a shift in the ratio of TG between depots. These findings indicate that ADF (both modified and true) produces similar beneficial modulations in body fat distribution and adiponectin levels as daily CR.     

Urinary Iodine Concentration is Inversely Associated with Thyroglobulin Antibodies

Objective: Epidemiologic studies on the relationship between iodine and thyroid antibodies are inconsistent. Iodine nutrition, genetic, and environmental factors have been shown to modify the effects of iodine on thyroid autoimmunity. We investigated the relationship between urinary iodine concentration (UIC) and thyroglobulin antibodies (TgAbs) in individuals living in iodine-sufficient areas in this cross-sectional study.Methods: A total of 15,008 participants were recruited according to the age range of the population of China in our study. An oral questionnaire was administered to collect basic demographic information. Serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAbs), TgAbs, and UIC were measured, and thyroid ultrasonography was performed in all subjects. Participants were further divided according to the level of UIC and the status of TgAb, and logistic regression was applied to determine the relationship between UIC and TgAbs.Results: The median UIC of the study population was 205.23 (95% confidence interval &lsqb;CI], 65.7 to 537.67) μg/L. A total of 17.6% of participants had UIC <100 μg/L. With the increase in UIC, the prevalence of positive TgAbs decreased gradually. UIC level was lowest in subjects with high TgAb titer (median, 182.36 μg/L; 95% CI, 52.88 μg/L to 506.71 μg/L) and highest in the TgAb-negative group (median, 207.16 μg/L; 95% CI, 66.94 μg/L to 538.72 μg/L). Multilinear correlation analysis showed that gender (β = 37.632; P<.001), age (β = 0.467; P = .038), TSH (β = 13.107; P<.001), TPOAb (β = 1.150; P<.001), thyroid volume (β = 2.883; P<.001), and UIC (β = -0.047; P = .032) were independent predictors of TgAb variations. Low UIC (<100 μg/L) was associated with increased risk of positive TgAbs (adjusted odds ratio = 1.255 &lsqb;1.004 to 1.568]).Conclusion: Low UIC is an independent risk factor for positive TgAb in individuals living in iodine-sufficient areas.Abbreviations: CI = confidence interval; CV = coefficient of variation; FT3 = free triiodothyronine; FT4 = free thyroxine; OR = odds ratio; TgAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyrotropin; UIC = urinary iodine concentration; USI = universal salt iodization     

ApoE and ApoC-I polymorphisms: association of genotype with cardiovascular disease phenotype in African Americans

Apolipoproteins (apo) E and C-I are components of triglyceride (TG)-rich lipoproteins and impact their metabolism. Functional polymorphisms have been established in apoE but not in apoC-I. We studied the relationship between apoE and apoC-I gene polymorphisms and plasma lipoproteins and coronary artery disease (CAD) in 211 African Americans and 306 Caucasians. In African Americans but not in Caucasians, apoC-I H2-carriers had significantly lower total and LDL cholesterol and apoB levels, and higher glucose, insulin, and HOMA-IR levels compared with H1 homozygotes. Differences across CAD phenotypes were seen for the apoC-I polymorphism. African-American H2-carriers without CAD had significantly lower total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), and apoB (P < 0.001) levels compared with H1 homozygotes, whereas no differences were found across apoC-I genotypes for African Americans with CAD. Among African-American apoC-I H1 homozygotes, subjects with CAD had a profile similar to the metabolic syndrome (i.e., higher triglyceride, glucose, and insulin) compared with subjects without CAD. For African-American H2-carriers, subjects with CAD had a pro-atherogenic lipid pattern (i.e., higher LDL cholesterol and apoB levels), compared with subjects without CAD. ApoC-I genotypes showed an ethnically distinct phenotype relationship with regard to CAD and CAD risk factors.     

Risk Factors for Central Lymph Node Metastases in Patients with Papillary Thyroid Microcarcinoma

Objectives: Papillary thyroid carcinoma with a maximum tumor diameter no more than 10 mm is defined as papillary thyroid microcarcinoma (PTMC). The proportion of newly diagnosed PTMCs has increased significantly in recent years. Different guidelines have different comments about optimal management of PTMC, especially on prophylactic central lymph node (CLN) dissection. The aim of the present study was to analyze the risk factors for CLN metastases in patients with PTMC.Methods: A total of 4,389 patients underwent thyroid surgery at our center from January 2017 to March 2018, and 2,129 patients with PTMC were selected and assessed retrospectively. The relationship between CLN metastases and clinicopathologic features of PTMC were analyzed by both univariate and multivariate analyses.Results: Of the 2,129 patients with PTMC, CLN metastases were confirmed by pathology in 923 patients. Univariate and multivariate analyses found several independent factors associated with CLN metastases. They were male gender (odds ratio [OR], 1.694; 95% confidence interval [CI], 1.386 to 2.071; P<.001), younger age (<45 years) (OR, 2.687; 95% CI, 2.196 to 3.288; P<.001), larger tumor size (>5 mm) (OR, 2.168; 95% CI, 1.782 to 2.636; P<.001), positive CLN metastases via ultrasound (OR, 4.939; 95% CI, 3.534 to 6.902; P<.001), and multifocality (OR, 1.424; 95% CI, 1.176 to 1.724; P<.001).Conclusion: CLN metastases are common in PTMC patients. Male gender, younger age (<45 years), larger tumor size (>5 mm), positive CLN metastases via ultrasound, and multifocality are independent risk factors for CLN metastases. Our data should be considered in the decision-making process related to performing CLN dissection.Abbreviations: CLN = central lymph node; PTC = papillary thyroid carcinoma; PTMC = papillary thyroid microcarcinoma     

The Association Between Tumor Tissue Calcification,Obesity, and Thyroid Cancer Invasiveness In A Cohort Study

Objective: We examined the relationships between tumor tissue calcifications of papillary thyroid cancer (PTC), body mass index (BMI), and tumor invasiveness.Methods: This was a retrospective analysis of 13,995 patients with PTC. Comparisons were made between the clinical and pathologic features of the tumor tissue calcifications group and non–tumor tissue calcifications group. Odds ratios (ORs) of tumor tissue calcifications, BMI, and tumor invasiveness features were calculated using a binary logistic regression model. We analyzed the relationship between tumor tissue calcifications and certain characteristics of thyroid cancer based on the pathologic findings.Results: BMI was positively correlated with tumor tissue calcifications in patients with PTC (OR, 1.015; P = .011), and obesity increased the risk of tumor tissue calcifications (OR, 1.374; P = .038). Calcifications were positively correlated with T-size (OR, 1.899; P<.001), multifocality (OR, 1.217; P<.001), extrathyroidal extension (ETE) (OR, 1.287; P<.001), high T-stage (OR, 1.765; P<.001), N+ (OR, 1.763; P<.001), and a higher number of lymph node metastases (OR, 1.985; P<.001). Compared with normal-weight patients with tumor tissue calcifications, obese patients with tumor tissue calcifications had an increased risk of ETE (OR_obesity, 1.765 vs. OR_normal, 1.300) and N+ (OR_obesity, 1.992 vs. OR_normal, 1.784).Conclusion: Tumor tissue calcifications are positively correlated with the invasiveness of PTC. Obesity further promotes the risk of tumor invasiveness in PTC combined with tumor tissue calcifications. These findings suggest that more comprehensive evaluations by trained pathologists may help physicians identify the optimal therapeutic regimens in the postoperative period.Abbreviations: BMI = body mass index; CI = confidence interval; ETE = extrathyroidal extension; FT3 = free triiodothyronine; OR = odds ratio; PTC = papillary thyroid carcinoma; RET = rearranged during transfection; TTC = tumor tissue calcification; US = ultrasonography; USC = ultrasonography calcification; WHO = World Health Organization     

The Association Between First-Degree Family History of Diabetes and Metabolic Syndrome

Objective: Because they share genetic and environmental factors with patients with diabetes, the first-degree relatives (FDRs) of patients with diabetes exhibit early signs of metabolic abnormalities. The present study aimed to investigate the correlation between family history of diabetes in FDRs and metabolic syndrome (MS), as well as changes in related risk factors.Methods: The present study population was a part of the baseline survey from the REACTION study. FDRs were defined as individuals having one or more FDRs with diabetes. MS and its components were defined according to the 2007 Joint Committee for Developing Chinese Guidelines.Results: A total of 2,692 individuals with an average age of 57.24 ± 8.35 years were enrolled in the present study. The prevalence of MS in FDRs (36.44%) was significantly higher than that in non-FDRs (25.28%; P<.001). FDRs accounted for 13.37%, 14.32%, 16.67%, 22.47%, 23.53%, and 25.58% of subjects with 0 to 5 MS components, showing an increasing trend (P for trend <.001). After adjusting for gender and age, partial correlation analyses showed significant associations of first-degree family history of diabetes with MS-related indexes (all P<.05). After adjusting for gender, age, lifestyle habits, and total metabolic traits, the first-degree family history of diabetes remained an independent factor that was positively associated with MS (odds ratio, 1.765; P<.001).Conclusion: A first-degree family history of diabetes predisposes individuals to developing MS and stands out as an independent risk factor for MS even without considering the subsequent effects of hyperglycemia.Abbreviations: BMI = body mass index; DBP = diastolic blood pressure; FDR = first-degree relative; FPG = fasting plasma glucose; HbA1c = glycated hemoglobin A1c; HDL-c = high-density-lipoprotein cholesterol; LDL-c = low-density-lipoprotein cholesterol; MAP = mean arterial pressure; MS = metabolic syndrome; OR = odds ratio; SBP = systolic blood pressure; TC = total cholesterol; TG = triglyceride; WC = waist circumference; WHR = waist-to-hip ratio; 2hPG = 2-hour plasma glucose     

Dalcetrapib and anacetrapib increase apolipoprotein E-containing HDL in rabbits and humans

The large HDL particles generated by administration of cholesteryl ester transfer protein inhibitors (CETPi) remain poorly characterized, despite their potential importance in the routing of cholesterol to the liver for excretion, which is the last step of the reverse cholesterol transport. Thus, the effects of the CETPi dalcetrapib and anacetrapib on HDL particle composition were studied in rabbits and humans. The association of rabbit HDL to the LDL receptor (LDLr) in vitro was also evaluated. New Zealand White rabbits receiving atorvastatin were treated with dalcetrapib or anacetrapib. A subset of patients from the dal-PLAQUE-2 study treated with dalcetrapib or placebo were also studied. In rabbits, dalcetrapib and anacetrapib increased HDL-C by more than 58% (P < 0.01) and in turn raised large apo E-containing HDL by 66% (P < 0.001) and 59% (P < 0.01), respectively. Additionally, HDL from CETPi-treated rabbits competed with human LDL for binding to the LDLr on HepG2 cells more than control HDL (P < 0.01). In humans, dalcetrapib increased concentrations of large HDL particles (+69%, P < 0.001) and apo B-depleted plasma apo E (+24%, P < 0.001), leading to the formation of apo E-containing HDL (+47%, P < 0.001) devoid of apo A-I. Overall, in rabbits and humans, CETPi increased large apo E-containing HDL particle concentration, which can interact with hepatic LDLr. The catabolism of these particles may depend on an adequate level of LDLr to contribute to reverse cholesterol transport.     

Layer-specific strain analysis in patients with suspected stable angina pectoris and apparently normal left ventricular wall motion

Background

Non-invasive imaging tests are widely used in the evaluation of stable angina pectoris (SAP). Despite these tests, non-significant coronary lesions are not a rare finding in patients undergoing elective coronary angiography (CAG). Two-dimensional (2D) speckle tracking global longitudinal strain (GLS) imaging is a more sensitive and accurate technique for measuring LV function than conventional 2D methods. Layer-specific strain analysis is a relatively new method that provides endocardial and epicardial myocardial layer assessment. The aim of the present study was to evaluate longitudinal layer-specific strain (LSS) imaging in patients with suspected SAP.

Methods

Patients who underwent CAG for SAP were retrospectively screened. A total of 79 patients with no history of heart disease and wall motion abnormalities were included in the study. Forty-three patients with coronary lesions >?70% constituted the coronary artery disease (CAD) group and 36 patients without significant CAD constituted the control group. Layer-specific GLS transmural, endocardium, and epicardium values (GLS-trans, GLS-endo, and GLS-epi, respectively) were compared between the groups.

Results

Patients in the CAD group had significantly lower GLS values in all layers (GLS-trans: -18.2 + 2.4% vs -22.2 + 2.2% p?<?.001; GLS-endo: -20.8 + 2.8% vs -25.3 + 2.6%, p?<?.001; GLS-epi: 15.9 + 2.4% vs -19.5 + 1.9%, p?<?.001). Multivariate adjustment demonstrated GLS-trans as the only independent predictor of CAD [OR:0.472, CI (0.326–0.684), p?<?.001]. Additionally, the GLS values were all lower in myocardial perfusion scintigraphy (MPS) true-positive patients compared with MPS false-positive patients (GLS-trans: -17.7?±?2.4 vs. -21.9?±?2.4%, p?<?.001; GLS-endo: -20.2?±?2.9% vs -24.9?±?2.9%, P?<?.001; GLS-epi: 15.4?±?2.6% vs. -19.2?±?1.8%, P?<?.001).

Conclusion

Resting layer-specific strain as assessed by 2D speckle tracking analysis demonstrated that GLS values were reduced in all layers of myocardium with SAP and with no wall motion abnormalities. LSS analysis can improve the identification of patients with significant CAD but further prospective larger scale studies are needed to put forth the incremental value of LSS analysis over transmural GLS.

     

Serum miR‐92a‐1 is a novel diagnostic biomarker for colorectal cancer

Colorectal cancer (CRC) is one of the most common cancers worldwide, with high mortality. Abnormally expressed microRNAs (miRNAs) are considered novel biomarkers in cancer diagnosis. The aim of this study was to investigate the diagnostic value of miR‐92a‐1 in patients with CRC. Serum samples were collected from 148 patients pathologically diagnosed with CRC and 68 gender‐ and age‐matched healthy volunteers. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to measure serum miR‐92a‐1 level. Relationship between miR‐92a‐1 and clinicopathological features of CRC cases was analysed via chi‐square test. Receiver operating characteristic (ROC) curve was plotted to estimate the diagnostic value of miR‐92a‐1 in CRC. Serum miR‐92a‐1 was significantly up‐regulated in CRC patients compared with healthy individuals (P < .001). Moreover, miR‐92a‐1 expression was correlated with TNM stage (P = .02), histological stage (P = .003), lymph node metastasis (P = .003) and distant metastasis (P < .001). ROC analysis showed that the area under the ROC curve (AUC) was 0.914, suggesting high diagnostic accuracy of miR‐92a‐1 in ROC. The optimal cut‐off value was 1.485, with a sensitivity of 81.8% and a specificity of 95.6%. MiR‐92a‐1 is increased in CRC patients and correlated with aggressive clinical characteristics. Serum miR‐92a‐1 may be a potential diagnostic biomarker for CRC.     

Adipocytokines,C-Reactive Protein,and Cardiovascular Disease: A Population-Based Prospective Study

Background

Being overweight or obese is associated with a greater risk of coronary heart disease and stroke compared with normal weight. The role of the specific adipose tissue-derived substances, called adipocytokines, in overweight- and obesity-related cardiovascular disease (CVD) is still unclear.

Objective

To investigate the associations of three adipose tissue-derived substances: adiponectin, leptin, and interleukin-6 with incident CVD in a longitudinal population-based study, including extensive adjustments for traditional and metabolic risk factors closely associated with overweight and obesity. C-reactive protein (CRP) was used as a proxy for interleukin-6.

Methods

Prospective population-based study of 6.502 participants, 51.9% women, aged 30–60 years, free of CVD at baseline, with a mean follow-up time of 11.4 years, equivalent to 74,123 person-years of follow-up. As outcome, we defined a composite outcome comprising of the first event of fatal and nonfatal coronary heart disease and fatal and nonfatal stroke.

Results

During the follow-up period, 453 composite CV outcomes occurred among participants with complete datasets. In models, including gender, age, smoking status, systolic blood pressure, treatment for hypertension, diabetes, body mass index (BMI), total cholesterol, high-density-lipoprotein cholesterol, homeostasis model assessment of insulin resistance, estimated glomerular filtration rate, adiponectin, leptin, and CRP, neither adiponectin (hazard ratio [HR] with 95% confidence interval [CI]: 0.97 [0.87–1.08] per SD increase, P = 0.60) nor leptin (0.97 [0.85–1.12] per SD increase, P = 0.70) predicted the composite outcome, whereas CRP was significantly associated with the composite outcome (1.19 [1.07–1.35] per SD increase, P = 0.002). Furthermore, in mediation analysis, adjusted for age and sex, CRP decreased the BMI-associated CV risk by 43% (95%CI 29–72).

Conclusions

In this study, neither adiponectin nor leptin were independently associated with CVD, raising questions over their role in CVD. The finding that CRP was significantly associated with an increased risk of CVD and decreased the BMI-associated CVD risk substantially, could imply that interleukin-6-related pathways may play a role in mediating overweight- and obesity-related CVD.