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Background: The prevalence of diabetic dyslipidemia has gradually increased worldwide and individuals with hypertriglyceridemia often have a high polygenic burden of triglyceride (TG)-increasing variants. However, the contribution of genetic variants to dyslipidemia in patients with type 2 diabetes (T2D) remains limited. Therefore, in this study, we aimed to investigate the genetic characteristics of longitudinal changes in TG levels among patients with T2D and summarize the genetic effects of polygenic risk score (PRS) on TG trajectory and risk of diabetic complications., Methods: We conducted a case-control study. A total of 11,312 patients with T2D with longitudinal TG and genetic data were identified from a large hospital database in Taiwan. We then performed a genome-wide association study and calculated the relative PRS., Results: In total, 21 single-nucleotide polymorphisms (SNPs) related to TG trajectory were identified and yielded an area under the receiver operating characteristic curve (ROC) of 0.712 for high TG trajectory risk among Taiwanese patients with T2D. A cumulative genetic effect was observed for high TG trajectory, even when considering the adherence of a lipid-lowering agent in stratified analysis. An increased PRS increases high TG trajectory risk in a logistic regression model (odds ratio = 1.55; 95% confidence interval [CI] = 1.31-1.83 in the validation cohort). The TG-specific PRS was associated with the risk of diabetic microvascular complications, including diabetic retinopathy and nephropathy (with hazard ratios of 1.11 [95% CI = 1.01-1.21, P = 0.027] and 1.05 [95% CI = 1.01-1.1, P = 0.018], respectively)., Conclusions: This study may contribute to the identification of patients with T2D who are at risk of abnormal TG levels and diabetic microvascular complications using polygenic information., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

Abstract: Alcohol has both adverse and protective effects on the individual components of metabolic syndrome (MS). We hypothesize that alcohol consumption increases the risk of developing MS and that the consumption of different types of alcoholic beverages has different effects on the development of MS and its individual components. We enrolled 2358 men for this cross-sectional study. The data were collected from self-reported nutrition and lifestyle questionnaires. Individuals who drank at least once per week for 6 consecutive months were classified as current drinkers. Current drinkers were at a higher risk of developing MS, abdominal obesity, and high triglyceride levels, but they were at a lower risk of developing low levels of high-density lipoprotein cholesterol (HDL-C). The increased risk of developing MS, high triglyceride, and high fasting glucose levels was dose dependent, whereas low HDL-C levels demonstrated a reverse relationship. The dose needed to reduce the risk of having low HDL-C levels was ≧50 g/d. This dose, however, resulted in an increased risk of developing high fasting glucose and high triglyceride levels. Consuming mixed types of alcohol increased the risk of developing MS and abdominal obesity. Meanwhile, those who drank liquor or wine had a greater risk of developing high triglyceride or high fasting glucose levels, respectively. In conclusion, alcohol consumption dose-dependently increased the risk of developing MS and some of its individual components while dose-dependently decreasing the risk of developing low HDL-C levels. The type of alcoholic beverage had different effects on the development of the individual components of MS. [Copyright &y& Elsevier]

To evaluate the association of chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection with hypercholesterolemia and hypertriglyceridemia. We analyzed the computerized health datasets of 56 336 residents from a community-based comprehensive screening in Tainan County in southern Taiwan. The overall prevalence rates of HBV surface antigen (HBsAg) and anti-HCV were 10.9% and 10.2%, respectively. Anti-HCV, HBsAg, platelet counts, albumin/globulin ratio (A/G ratio), fasting glucose, triglyceride, cholesterol levels, and body mass index (BMI) were abstracted for analyses. Multivariate logistic analysis was used for identification of the independent factors of hypercholesterolemia and hypertriglyceridemia. The prevalence of hypercholesterolemia and hypertriglyceridemia were 48.9% and 28.0%, respectively. Hypercholesterolemia and hypertriglyceridemia were associated with each other. Older age, negativity for HBsAg and anti-HCV, normal platelet counts, A/G ratio ≥ 1, higher BMI, and being diagnosed as diabetic were common independently associated factors of both hypercholesterolemia and hypertriglyceridemia. Men had higher risk for hypertriglyceridemia, while women had higher risk for hypercholesterolemia. This large scale community-based study demonstrated that subjects with seropositivity for Hepatitis C not only had lower prevalence of hypercholesterolemia and hypertriglyceridemia but subjects with seropositivity for Hepatitis B had the same trend. [ABSTRACT FROM AUTHOR]

Abstract: Background: Apolipoprotein A5 gene (APOA5) has been shown to modulate plasma triglyceride concentrations. We investigated 2 distinct APOA1/C3/A5 haplotypes roles for hypertriglyceridemia. Methods: We recruited 308 cases of hypertriglyceridemia and 281 normal controls from a hospital. Twelve single nucleotide polymorphisms (SNPs) across the APOA1/C3/A5 gene region were genotyped. Results: One haplotype containing the minor alleles of the APOA5 (−1131T>C, c.553G>T) and APOA1 (−3013C>T,−75G>A) was more prevalent in cases than in controls (11.3% vs. 1.1%, respectively) and was statistically significantly associated with high triglycerides (adjusted odds ratio: 12.83, 95% confidence interval [CI]: 5.1–32.4, P <0.001). Another haplotype that was associated with hypertriglyceridemia (adjusted odds ratio 2.13, 95% CI, 1.37–3.29, P =0.001). Participants carrying both minor alleles of APOA5-1131CC and c.553TT had a 116% higher triglyceride concentration compared with those carrying common allele. Conclusions: The APOA1/C3/A5 haplotype represents an important locus for predicting risk of hypertriglyceridemia among Taiwanese. [Copyright &y& Elsevier]

Abstract: This study investigated the relationships between serum lipid profiles and schizophrenia and the effects of conventional or atypical antipsychotic drugs on serum lipid profiles. During a 1-year period, fasting blood samples for serum lipid profiles were collected from 126 schizophrenic patients and 59 healthy control subjects. The serum lipid profiles were detected by enzymatic determination. Patients were assessed for disease severity at baseline and endpoint at 3 weeks using the Positive and Negative Syndrome Scale. At baseline, patients with acute-phase schizophrenia had lower high-density lipoprotein (HDL) levels, higher low-density lipoprotein (LDL) levels, and higher ratios of total cholesterol/high-density lipoprotein (TC/HDL) and LDL/HDL than healthy control subjects. At endpoint, after a 3-week treatment with antipsychotics, the blood samples of the 97 schizophrenic patients were assessed again. Responders to antipsychotic treatment (n =68) but not nonresponders (n =29) had significantly increased TC, triglyceride (TG), and very low-density lipoprotein (VLDL) levels and decreased ratio of LDL/HDL. Experimental findings also showed significantly increased TC, TG, HDL, and VLDL levels and decreased ratio of LDL/HDL in responders taking atypical antipsychotic drugs (n =32), but not in patients treated with conventional antipsychotic drugs (n =36). In conclusion, this study identified strong associations between dyslipidemia and acute-phase schizophrenia and dyslipidemia and responders taking atypical antipsychotics; both associations would increase the risk of developing diabetes and coronary heart disease. [Copyright &y& Elsevier]

Hepatic lipase (encoded by LIPC ) is a glycoprotein in the triacylglycerol lipase family and mainly synthesized in and secreted from the liver. Previous studies demonstrated that hepatic lipase is crucial for reverse cholesterol transport and modulating metabolism and the plasma levels of several lipoproteins. This study was conducted to investigate the suppression effect of high-density lipoprotein cholesterol (HDL-C) levels in a genome-wide association study and explore the possible mechanisms linking triglyceride (TG) to LIPC variants and HDL-C. Genome-wide association data for TG and HDL-C were available for 4657 Taiwan-biobank participants. The prevalence of haplotypes in the LIPC promoter region and their effects were calculated. The cloned constructs of the haplotypes were expressed transiently in HepG2 cells and evaluated in a luciferase reporter assay. Genome-wide association analysis revealed that HDL-C was significantly associated with variations in LIPC after adjusting for TG. Three haplotypes (H1: TCG, H2: CTA and H3: CCA) in LIPC were identified. H2: CTA was significantly associated with HDL-C levels and H1: TCG suppressed HDL-C levels when a third factor, TG, was included in mediation analysis. The luciferase reporter assay further showed that the H2: CTA haplotype significantly inhibited luciferase activity compared with the H1: TCG haplotype. In conclusion, we identified a suppressive role for TG in the genome-wide association between LIPC and HDL-C. A functional haplotype of hepatic lipase may reduce HDL-C levels and is suppressed by TG.

Context: The association between circulating triglyceride (TG) and glycated hemoglobin A1c (HbA1c), a biomarker for type 2 diabetes, has been widely addressed, but the causal direction of the relationship is still ambiguous., Objective: To confirm the causal relationship between TG and HbA1c by using bidirectional and 2-step Mendelian randomization (MR) approaches., Methods: We carried out a bidirectional MR approach using the summarized results from the public database to examine any potential causal effects between serum TG and HbA1c in 16 000 individuals of the Taiwan Biobank cohort. We used the MR estimate and the MR inverse variance-weighted method to reveal that relationship between TG and HbA1c. To further determine whether the DNA methylation at specific sequences mediate the causal pathway between TG and HbA1c, using the 2-step MR approach., Results: We identified that a single-unit increase in TG measured via log transformation of mg/dL data was associated with a significant increase of 10 units of HbA1c (95% CI = 1.05-18.95, P = 0.029). In contrast, the genetic determinants of HbA1c do not contribute to the amount of circulating TG (beta = 1.75, 95% CI = -11.50 to 14.90). Sensitivity analyses, included the weighted-median approach and MR-Egger regression, were performed to confirm no pleiotropic effect among these instrumental variables. Furthermore, we identified the genetic variant, rs1823200, is associated with both methylation of the CpG site adjacent to CADPS gene and HbA1c level., Conclusion: Our study suggests that higher circulating TG can have an affect on genomic methylation status, ultimately causing elevated level of circulating HbA1c., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Both hepatitis B (HB) and nonalcoholic fatty liver disease (NAFLD) are related to metabolic syndrome (MetS); however, this relationship remains controversial. In this study, we determined the effects of NAFLD and HB infection on the risk of MetS among elderly individuals. Methods: In total, 24,500 individuals aged >65 years were enrolled; they were classified into four groups: normal individuals (N), patients with only HB infection without abnormal echogenicity (HB-alone), patients with only abnormal echogenicity or fatty liver alone (FL-alone), and patients with both HB infection and abnormal echogenicity (HB-FL). Results: After adjustment for age, compared with group N, men and women with NAFLD (FL-alone and HB-FL) had a significantly higher risk of MetS, whereas no significant difference was observed in the incidence of MetS between groups HB-alone and N. However, group HB-FL had a lower risk of MetS than did group FL-alone. HB infection (HB-alone and HB-FL) was associated with a lower risk of high triglycerides (TGs) and fasting plasma glucose (FPG) than HB infection absence (groups N and FL-alone) in men and women. Lower risk of TG derangement was observed in group HB-alone than in group N. In addition, both men and women in group HB-FL had a lower risk of TG and FPG abnormalities than in group FL-alone, whereas a decrease in incidence of high waist circumference and blood pressure was observed only in men. Conclusion: HB infection protects against MetS development, only in patients with HB infection and NAFLD, but not in normal individuals. Additional studies are warranted to clarify the pathogenesis.

Objective Serum lipid levels may be associated with the affective severity of bipolar disorder, but data on lipid profiles in Asian patients with bipolar disorder and the lipid alterations in different states of opposite polarities are scant. We investigated the lipid profiles of patients in the acute affective, partial, and full remission state in bipolar mania and depression. Methods The physically healthy patients aged between 18 and 45 years with bipolar I disorder, as well as age-matched healthy normal controls were enrolled. We compared the fasting blood levels of glucose, cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein of manic or depressed patients in the acute phase and subsequent partial and full remission with those of their normal controls. Results A total of 32 bipolar manic patients (12 women and 20 men), 32 bipolar depressed participants (18 women and 14 men), and 64 healthy control participants took part in this study. The mean cholesterol level in acute mania was significantly lower than that in acute depression (p < 0.025). The lowest rate of dyslipidemia (hypertriglyceridemia or low high-density lipoprotein cholesterol) was observed in acute bipolar mania. Conclusion Circulating lipid profiles may be easily affected by affective states. The acute manic state may be accompanied by state-dependent lower cholesterol and triglyceride levels relative to that in other mood states.

Chromosome 12q23-q24 has been linked to triglyceride (TG) levels by previous linkage studies, and it contains the Insulin-like growth factor 1 ( IGF1 ) gene. We investigated the association between IGF1 and TG levels using two independent samples collected in Taiwan. First, based on 954 siblings in 397 families from the Stanford Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe), we found that rs978458 was associated with TG levels ( β = -0.049, p = 0.0043) under a recessive genetic model. Specifically, subjects carrying the homozygous genotype of the minor allele had lower TG levels, compared with other subjects. Then, a series of stratification analyses in a large sample of 13,193 unrelated subjects from the Taiwan biobank (TWB) project showed that this association appeared in subjects with a family history (FH) of hypertension ( β = -0.045, p = 0.0000034), but not in subjects without such an FH. A re-examination of the SAPPHIRe sample confirmed that this association appeared in subjects with an FH of hypertension ( β = -0.068, p = 0.0025), but not in subjects without an FH. The successful replication in two independent samples indicated that IGF1 is associated with TG levels in subjects with an FH of hypertension in Taiwan., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.