Fasting Triglyceride Levels Research Articles

Comparative Determination of Mitochondrial Biomarkers and Their Relationship With Insulin Resistance in Type 2 Diabetic Patients: An Observational Cross-Sectional Study.

Data suggest malfunctioning mitochondria reduce oxidation and adenosine triphosphate (ATP) production, disrupting insulin signalling. Cytochrome c(CC), acylcarnitine (AC) and citrate synthase (CS) are essential components of the mitochondria machinery and can be used as reliable biomarkers of mitochondrial dysfunction. This study aimed to determine whether mitochondrial biomarkers (AC, CS and CC) are altered in individuals with type 2 diabetes mellitus (T2DM) and to examine the association between these biomarkers and insulin resistance. A cross-sectional observational study that recruited 170 participants (88 with T2DM and 82 without DM) was conducted. Blood samples were collected from the recruits and analysed for levels of fasting glucose (FBG), AC, CS, CC, insulin, total cholesterol, triglycerides (TG), glycated haemoglobin (HbA1c) and magnesium. Blood pressure (BP) and anthropometric characteristics of participants were also taken. Appropriate formulas were used to determine %body fat, body mass index (BMI), waist-to-hip ratio (WHR), the homeostatic model assessment for insulin resistance (HOMA-IR) and insulin sensitivity (HOMA-β). Patients with T2DM had higher levels of CC, %body fat, FBG, TG, HbA1c, BMI and HOMA-IR than controls (p < 0.05, respectively). Results showed a significant relationship between circulating CC levels versus HOMA-β (r = -0.40, p = 0.001), CS (r = -0.70, p = 0.001) and AC (r = -0.72, p = 0.001) levels in patients with T2DM. The adjusted odds increased in the T2DM patients for VLDL (OR = 6.66, p = 0.002), HbA1c (OR = 6.50, p = 0.001), FPG (OR = 3.17, p = 0.001), TG (OR = 2.36, p = 0.010), being female (OR = 2.09, p = 0.020) and CC (OR = 1.14, p = 0.016). Overall, alterations in mitochondrial biomarkers, measured by AC, CC and CS, were observed in people with T2DM and showed a direct relationship with insulin resistance. These findings are potentially significant in Africa, although additional confirmation from a larger cohort is necessary.

CLINICAL, DIETARY, AND REDOX PROFILE IN A SAMPLE OF INDIVIDUALS FROM SINOP/MT

Clinical and experimental evidence show that there is a relationship between obesity, dietary profile, and redox status. This study aimed to assess the clinical and dietary profile, and redox status of a sample of individuals from Sinop/MT. Thus, we designed a descriptive cross-sectional study involving a convenience sample of Brazilian adult participants of both genders. The study was conducted at a Basic Health Unit in the city of Sinop/MT. Participants were divided according to the body mass index (BMI) into eutrophic (n=5) and overweight (n=12) groups. Clinical parameters, metabolic and inflammatory indicators in the blood, redox status markers and food intake were analyzed. Seventy percent of participants were overweight and 82% presented an elevated waist circumference. Regarding metabolic data, there was a trend of increased fasting glucose and triglycerides levels and decreased HDL levels as body weight increases, with a positive correlation between these variables. It was not possible to demonstrate difference for redox status markers, and there was no significant linear correlation between BMI and these markers. The overweight group reported a lower industrialized beverages and sweets intake, but there was no difference to the other food variables. We conclude that most individuals were overweight, which was associated to comorbidities, regardless dietary intake, but age being an associated factor. Furthermore, overweight did not modulate redox status.

A mendelian randomization study revealing that metabolic syndrome is causally related to renal failure.

The onset and progression of chronic kidney disease (CKD) has been linked to metabolic syndrome (MetS), with the results of recent observational studies supporting a potential link between renal failure and MetS. The causal nature of this relationship, however, remains uncertain. This study thus leveraged a Mendelian Randomization (MR) approach to probe the causal link of MetS with renal failure. A genetic database was initially used to identify SNPs associated with MetS and components thereof, after which causality was evaluated through the inverse variance weighted (IVW), MR-Egger regression, and weighted media techniques. Results were subsequently validated through sensitivity analyses. IVW (OR = 1.48, 95% CI = 1.21-1.82, P =1.60E-04) and weighted median (OR = 1.58, 95% CI =1.15-2.17, P = 4.64E-03) analyses revealed that MetS was linked to an elevated risk of renal failure. When evaluating the specific components of MetS, waist circumference was found to be causally related to renal failure using the IVW (OR= 1.58, 95% CI = 1.39-1.81, P = 1.74e-11), MR-Egger (OR= 1.54, 95% CI = 1.03-2.29, P = 0.036), and weighted median (OR= 1.82, 95% CI = 1.48-2.24, P = 1.17e-8). The IVW method also revealed a causal association of hypertension with renal failure (OR= 1.95, 95% CI = 1.34-2.86, P = 5.42e-04), while renal failure was not causally related to fasting blood glucose, triglyceride levels, or HDL-C levels. These data offer further support for the existence of a causal association of MetS with kidney failure. It is thus vital that MetS be effectively managed in patients with CKD in clinical settings, particularly for patients with hypertension or a high waist circumference who are obese. Adequate interventions in these patient populations have the potential to prevent or delay the development of renal failure.

Evaluation of Insulin Resistance and Metabolic Syndrome Components in Patients with Seborrheic Dermatitis

Objective: Seborrheic dermatitis (SD) is a common inflammatory skin disorder. There is scarce data regarding SD and metabolic syndrome. We aimed to investigate the prevalence of metabolic syndrome in patients with seborrheic dermatitis. Methods: Sixty-six patients with seborrheic dermatitis and 52 healthy controls were enrolled. Subjects’ height, weight, waist circumference, smoking status, and comorbidities were recorded. Blood pressure, fasting blood glucose, triglyceride, HDL, total cholesterol, and insulin levels were measured. Seborrheic dermatitis area and severity index (SASI) score, body mass index (BMI), and Homeostatic Model Assessment-Insulin Resistance (HOMA-IR) were calculated. The presence of metabolic syndrome was evaluated. Results: BMI, waist circumference, glucose, HOMA-IR, and C-reactive protein (C-RP) were significantly higher in the SD group. The prevalence of hypertension and type II diabetes was significantly higher in the SD group than in the controls. There was no difference between the patient and control groups regarding metabolic syndrome. However, the duration of SD was significantly higher in SD with metabolic syndrome than those of SD without metabolic syndrome. There were no significant differences in age and SASI score between seborrheic dermatitis patients with and without metabolic syndrome. Conclusion: SD patients may have an increased risk of metabolic syndrome development and may have higher inflammation and insulin resistance status compared with controls.

Correlation analysis between the changes in plasma ghrelin level and weight loss after sleeve gastrectomy combined with fundoplication

BackgroundLaparoscopic sleeve gastrectomy combined with fundoplication (LSGFD) can significantly control body weight and achieve effective anti-reflux effects. The aim of this study is to investigate the correlation between the alteration in Ghrelin levels and weight loss following SGFD, and to compare Ghrelin levels, weight loss and metabolic improvements between SG and SGFD, with the objective of contributing to the existing body of knowledge on SGFD technique in the management of patients with obesity and gastroesophageal reflux disease (GERD).MethodsA retrospective analysis was conducted on the clinical data of 115 obese patients who underwent bariatric surgery between March 2023 and June 2023 at the Department of Minimally Invasivew Surgery, Hernia and Abdominal Wall Surgery, People’s Hospital of Xinjiang Uygur Autonomous Region. The subjects were divided into two groups based on surgical methods: sleeve gastrectomy group (SG group, 93 cases) and sleeve gastrectomy combined with fundoplication group (SGFD group, 22 cases). Clinical data, such as ghrelin levels before and after the operation, were compared between the two groups, and the correlation between changes in ghrelin levels and weight loss effectiveness after the operation was analyzed. Results: Three months after the operation, there was no significant difference in body mass, BMI, EWL%, fasting blood glucose, triglyceride, cholesterol, and uric acid levels between the SG and SGFD groups (P > 0.05). However, the SGFD group exhibited a significant decrease in body weight, BMI, and uric acid levels compared to preoperative levels (P < 0.05), while the decrease in ghrelin levels was not statistically significant (P > 0.05). Logistic regression analysis indicated that ghrelin levels three months after the operation were influential in postoperative weight loss.ConclusionThe reduction of plasma Ghrelin level in patients after SGFD is not as obvious as that in patients after SG, but it can make obese patients get the same good weight loss and metabolic improvement as patients after SG. Ghrelin level at the third month after operation is the influencing factor of postoperative weight loss.

Association of systemic inflammatory indices with anthropometric measures, metabolic factors, and liver function in non-alcoholic fatty liver disease

The present cross-sectional study aimed to explore the relationship between systemic inflammatory indices (SIIs) and anthropometric measures, metabolic, and liver function biomarkers in patients with non-alcoholic fatty liver disease (NAFLD). This study was carried out on 238 NAFLD patients with overweight or obesity, aged 18–55 years. Anthropometric measurements were done and body mass index (BMI), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) were estimated. Metabolic factors including serum glucose, lipid profile, liver function biomarkers, and complete blood cell count were assessed after a 24-h fasting state. SIIs including the ratios of neutrophil to lymphocyte (NLR), monocytes to lymphocyte (MLR), platelet to lymphocyte (PLR), and monocytes to high-density lipoprotein cholesterol (MHR) were calculated. Results indicate that apart from PLR, all of the SIIs significantly changed by increasing steatosis severity (all p < 0.05). Moreover, changes in NLR showed a significant association with anthropometric indices including waist circumference (p = 0.032), BMI (p = 0.047), and WHtR (p = 0.002), as well as levels of fasting blood sugar (p = 0.045), triglycerides, (p = 0.025) and low-density lipoprotein cholesterol (p = 0.006). The findings also indicate the relations between lipid profile and all studied SIIs, notably MHR and MLR. All of the SIIs exhibited associations with some liver function indices as well. MHR was positively correlated with the metabolic risk factors of NAFLD while, oppositely, PLR was considered as a preventive marker of NAFLD.

Apple cider vinegar for weight management in Lebanese adolescents and young adults with overweight and obesity: a randomised, double-blind, placebo-controlled study

Background and aimsObesity and overweight have become significant health concerns worldwide, leading to an increased interest in finding natural remedies for weight reduction. One such remedy that has gained popularity...

Effects of antipsychotic medications in glucose and lipid metabolism at the fasted state in drug-naïve first episode patients with psychosis after six months and three years of treatment.

Diabetes and dyslipidemia are common in patients with psychosis and may be related to adverse effects of antipsychotic medications. Metabolic disturbances in first-episode patients with psychosis are common, even prior to any antipsychotic treatment, and antipsychotic medications are implicated in the development of metabolic syndrome, at least in the long run. We therefore aimed to follow a group of drug-naïve, first-episode patients with psychosis at different time points (baseline, six months, and 36 months after the initiation of antipsychotic treatment) in order to evaluate the progression of metabolic abnormalities after antipsychotic therapy and the time-course of their onset. We assessed glucose and lipid metabolism during the fasted state in 54 drug-naïve patients with first-episode psychosis (FEP) before the initiation of any antipsychotic treatment and compared them with matched controls. The same parameters were assessed in the patient group (n=54) after six months of antipsychotic treatment and in a subgroup of patients (n=39) after three years of continuous and stable treatment in comparison to baseline. Measurements were obtained for fasting serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL), glucose, insulin, connecting peptide (C-peptide), homeostatic model assessment index (HOMA-IR), glycated hemoglobin (HbA1c) and body mass index (BMI). Insulin, C-peptide, triglyceride levels, and HOMA-IR index were significantly higher compared to controls. Total cholesterol, triglyceride levels and BMI, increased significantly in the patient group after six months of antipsychotic treatment. After three years of continuous antipsychotic treatment, we found statistically significant increases in fasting glucose, insulin, total cholesterol, triglyceride levels, HbA1c, HOMA-IR index, and BMI compared to baseline. In conclusion, FEP patients developed significant increases in BMI and serum lipid levels as soon as six months after antipsychotic treatment. These metabolic abnormalities persisted following 36 months of treatment and in addition, increases in fasting glucose, insulin, HbA1c and HOMA-IR were observed compared to baseline.

Zodasiran, an RNAi Therapeutic Targeting ANGPTL3, for Mixed Hyperlipidemia

BackgroundAngiopoietin-like 3 (ANGPTL3) inhibits lipoprotein and endothelial lipases and hepatic uptake of triglyceride-rich lipoprotein remnants. ANGPTL3 loss-of-function carriers have lower levels of triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and non-HDL cholesterol and a lower risk of atherosclerotic cardiovascular disease than noncarriers. Zodasiran is an RNA interference (RNAi) therapy targeting expression of ANGPTL3 in the liver.MethodsWe conducted a double-blind, placebo-controlled, dose-ranging phase 2b trial to evaluate the safety and efficacy of zodasiran in adults with mixed hyperlipidemia (fasting triglyceride level of 150 to 499 mg per deciliter and either an LDL cholesterol level of ≥70 mg per deciliter or a non-HDL cholesterol level of ≥100 mg per deciliter). Eligible patients were randomly assigned in a 3:1 ratio to receive subcutaneous injections of zodasiran (50, 100, or 200 mg) or placebo on day 1 and week 12 and were followed through week 36. The primary end point was the percent change in the triglyceride level from baseline to week 24.ResultsA total of 204 patients underwent randomization. At week 24, substantial mean dose-dependent decreases from baseline in ANGPTL3 levels were observed with zodasiran (difference in change vs. placebo, −54 percentage points with 50 mg, −70 percentage points with 100 mg, and −74 percentage points with 200 mg), and significant dose-dependent decreases in triglyceride levels were observed (difference in change vs. placebo, −51 percentage points, −57 percentage points, and −63 percentage points, respectively) (P<0.001 for all comparisons). Other differences in change from baseline as compared with placebo included the following: for non-HDL cholesterol level, −29 percentage points with 50 mg, −29 percentage points with 100 mg, and −36 percentage points with 200 mg; for apolipoprotein B level, −19 percentage points, −15 percentage points, and −22 percentage points, respectively; and for LDL cholesterol level, −16 percentage points, −14 percentage points, and −20 percentage points, respectively. We observed a transient elevation in glycated hemoglobin levels in patients with preexisting diabetes who received the highest dose of zodasiran.ConclusionsIn patients with mixed hyperlipidemia, zodasiran was associated with significant decreases in triglyceride levels at 24 weeks. (Funded by Arrowhead Pharmaceuticals; ARCHES-2 ClinicalTrials.gov number, NCT04832971.)

Plozasiran, an RNA Interference Agent Targeting APOC3, for Mixed Hyperlipidemia

BackgroundPersons with mixed hyperlipidemia are at risk for atherosclerotic cardiovascular disease due to an elevated non–high-density lipoprotein (HDL) cholesterol level, which is driven by remnant cholesterol in triglyceride-rich lipoproteins. The metabolism and clearance of triglyceride-rich lipoproteins are down-regulated through apolipoprotein C3 (APOC3)–mediated inhibition of lipoprotein lipase.MethodsWe carried out a 48-week, phase 2b, double-blind, randomized, placebo-controlled trial evaluating the safety and efficacy of plozasiran, a hepatocyte-targeted APOC3 small interfering RNA, in patients with mixed hyperlipidemia (i.e., a triglyceride level of 150 to 499 mg per deciliter and either a low-density lipoprotein [LDL] cholesterol level of ≥70 mg per deciliter or a non-HDL cholesterol level of ≥100 mg per deciliter). The participants were assigned in a 3:1 ratio to receive plozasiran or placebo within each of four cohorts. In the first three cohorts, the participants received a subcutaneous injection of plozasiran (10 mg, 25 mg, or 50 mg) or placebo on day 1 and at week 12 (quarterly doses). In the fourth cohort, participants received 50 mg of plozasiran or placebo on day 1 and at week 24 (half-yearly dose). The data from the participants who received placebo were pooled. The primary end point was the percent change in fasting triglyceride level at week 24.ResultsA total of 353 participants underwent randomization. At week 24, significant reductions in the fasting triglyceride level were observed with plozasiran, with differences, as compared with placebo, in the least-squares mean percent change from baseline of −49.8 percentage points (95% confidence interval [CI], −59.0 to −40.6) with the 10-mg-quarterly dose, −56.0 percentage points (95% CI, −65.1 to −46.8) with the 25-mg-quarterly dose, −62.4 percentage points (95% CI, −71.5 to −53.2) with the 50-mg-quarterly dose, and −44.2 percentage points (95% CI, −53.4 to −35.0) with the 50-mg-half-yearly dose (P<0.001 for all comparisons). Worsening glycemic control was observed in 10% of the participants receiving placebo, 12% of those receiving the 10-mg-quarterly dose, 7% of those receiving the 25-mg-quarterly dose, 20% of those receiving the 50-mg-quarterly dose, and 21% of those receiving the 50-mg-half-yearly dose.ConclusionsIn this randomized, controlled trial involving participants with mixed hyperlipidemia, plozasiran, as compared with placebo, significantly reduced triglyceride levels at 24 weeks. A clinical outcomes trial is warranted. (Funded by Arrowhead Pharmaceuticals; MUIR ClinicalTrials.gov number NCT04998201.)

Triglyceride-Glucose Index Associated with Future Renal Function Decline in the General Population.

The triglyceride-glucose index (TyG index), calculated as the logarithmic product of fasting triglyceride and glucose concentrations, is recognized as a simple marker of insulin resistance. However, the association between the TyG index and future decline of renal function remains unclear in the general population. To investigate whether the TyG index was associated with future decline of renal function in the general population who had not progressed to chronic kidney disease stage G2. Retrospective longitudinal observational cohort study. Individuals who received a population-based health checkup at JA Ehime Kouseiren Checkup Center from 2010 to 2019 (n = 134,007). Individuals without data of baseline fasting triglyceride or glucose levels, or baseline and follow-up data of estimated glomerular filtration rate (eGFR), or those with baseline eGFR < 60mL/min/1.73 m2 were excluded. Future renal function decline, defined as a ≥ 25% decrease in eGFR from baseline. Of 10,758 participants, 8,076 were classified into the low TyG index group (TyG index < 8.76, 1st to 3rd quartiles) and 2,682 into the high TyG index group (TyG index ≥ 8.76, 4th quartile). The mean follow-up period was 37.8 ± 23.6months. The incidence rates of renal function decline were 0.31 and 0.69 per 100 person-years in the low and high TyG index groups, respectively. In multivariate Cox proportional hazard models, high TyG index was significantly associated with future renal function decline (hazard ratio 2.25, 95% CI 1.40-3.60). This association was consistent across subgroups stratified by age, sex, body mass index, baseline eGFR, and diagnosed hypertension, diabetes, or dyslipidemia. In the general population, high TyG index was associated with future renal function decline. The TyG index may be useful in identifying individuals at high risk for future renal function decline in the setting of health checkups.

High body mass index and triglyceride levels at health checkups increase the risk of new-onset chronic kidney disease and worsening renal function: the TAMA MED Project-CKD

BackgroundHealth checkups are important in patients with chronic kidney disease (CKD), which is not easily accompanied by subjective symptoms. CKD can be caused or aggravated by factors that have not yet been identified.MethodsThis retrospective cohort study included 7 483 patients who underwent specific annual health checkups at a medical institution in Tama City, did not have CKD in 2012, and continued to undergo checkups (aged 40–74 years). We examined the risk factors for new-onset CKD and 1.5-fold increase in serum creatinine levels among laboratory values from 2012 to 2020.ResultsAge, body mass index (BMI), triglyceride levels, atrial fibrillation, and medication for hypertension (HT) and diabetes mellitus were independent risk factors for proteinuria, whereas current smoking, BMI, systolic blood pressure (SBP), and medication for HT were independent risk factors for estimated glomerular filtration rate < 60 mL/min/1.73 m2. SBP, triglyceride levels and medication for HT were risk factors for a 1.5-fold increase in serum creatinine levels during course of the study. The cut-off values of BMI for eGFR < 60 mL/min/1.73 m2 were 22.2 (men 24.7, women 22.1) kg/m2 and fasting triglyceride levels for a 1.5-fold increase in serum creatinine level were 171 (men 247, women 170) mg/dL, respectively.ConclusionsHealth checkups provide information to prevent new-onset CKD and worsening of renal function. It is necessary to increase the rate of health checkups and visits to medical institutions after health checkups as well as to use these results for health guidance.

Association between pathologic complete response and biochemical indicators after neoadjuvant therapy for HER2-positive breast cancer

PurposeThis study investigated the changes in the fasting blood glucose (FBG), fasting triglyceride (FTG), and fasting total cholesterol (FTC) levels during neoadjuvant therapy (NAT) for human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) and the association with pathologic complete response (pCR).MethodsRelevant data from Sichuan Cancer Hospital from June 2019 to June 2022 were collected and analyzed, and FBG, FTG, and FTC were divided into baseline, change, and process groups, which were grouped to analyze the changes after receiving NAT and the association with pCR.Results In the estrogen receptor (ER)-negative subgroup, patients with low levels of FTG in the process group were more likely to achieve pCR compared to high levels, and in the progesterone receptor (PR)-negative subgroup, patients with lower FTG compared to higher FTG after receiving NAT was more likely to achieve pCR.ConclusionsPatients with HER2-positive BC undergoing NAT develop varying degrees of abnormalities (elevated or decreased) in FBG, FTG, and FTC; moreover, the status of FTG levels during NAT may predict pCR in ER-negative or PR-negative HER2-positive BC.Early monitoring and timely intervention for FTG abnormalities may enable this subset of patients to increase the likelihood of obtaining a pCR along with management of abnormal markers.

The Effectiveness and Safety of Fenofibrate and Saroglitazar in the Treatment of Diabetic Dyslipidemia

Objective: This study aimed to evaluate the efficacy and safety of saroglitazar and fenofibrate in treatingdiabetic dyslipidemia.Study Design: Comparative cross-sectional study.Place and Duration of Study: The study was conducted at the Department of Biochemistry, Nishtar MedicalUniversity and Hospital Multan, Pakistan over 12 months from January 2021 to January 2022.Methods: Following a 4-week run-in phase, sixty newly diagnosed patients with a previous diagnosis ofdiabetes and dyslipidemia were included. Eligible participants were aged 18-65 years, with fasting triglyceride(TG) levels &gt;200–400 mg/dL and documented type 2 diabetes mellitus (T2DM). Following baselineassessments, participants were randomised into two treatment groups: Saroglitazar 4 mg with 10 mg ofAtorvastatin and Fenofibrate 200 mg with 10 mg of Atorvastatin. Lipid profiles, fasting blood glucose (FBG), andHbA1c were evaluated at baseline and after 12 weeks. Statistical analysis was conducted using appropriatetests with p&lt; 0.05, which is considered significant.Results: The study enrolled 60 participants, with comparable baseline characteristics between groups. Whileboth treatments showed similar effects on lipid profiles, Saroglitazar showed exceptional effectiveness inlowering HbA1c and FBG levels compared to Fenofibrate. No significant differences in adverse effects wereobserved.Conclusion: Saroglitazar may offer advantages in managing diabetic dyslipidemia and improving glycemiccontrol compared to Fenofibrate in a larger sample size. More investigation is necessary to confirm thesefindings and evaluate long-term safety and efficacy. How to cite this: Farooq B, Cheema RR, Qureshi ZH, Yasmeen N, Sahu EH. The Effectiveness and Safety of Fenofibrate and Saroglitazar in The Treatment of Diabetic Dyslipidemia. Life and Science. 2024; 5(2): 266-272. doi: http://doi.org/10.37185/LnS.1.1.632

Metabolic syndrome reduces cerebral blood flow more in women than men

One in three adults in the United States suffers from metabolic syndrome (MetSyn), a state of insulin resistance associated with reduced cerebral blood flow (CBF) and increased risk of stroke and neurologic diseases. Notably, females are at greater risk for cardiovascular and metabolic complications derived from insulin resistance. Still, it remains unclear whether the reduction in CBF seen in MetSyn is sex-specific or uniform between various brain regions. Additionally, fasting triglyceride (TG) levels are stronger predictors of cognitive disease in females than in males. However, little data exist examining the relationship between TG and CBF in females with MetSyn. Therefore, we aimed to examine the interaction between sex and MetSyn on global and regional CBF in young adults and to explore the relationship between fasting TG levels and CBF. We predict that males and females with MetSyn will have lower global and regional CBF compared to healthy controls of the same sex, but to a greater extent in females with MetSyn. Additionally, we predict fasting TG levels will have stronger relationships with CBF in females than in males with MetSyn. Twenty-five healthy controls (CON; 7 females; 24 ± 4 y) and 13 individuals with MetSyn (5 females; 27 ± 8 y) completed this study. Subjects were unmedicated, and females were studied on days 1-5 of their menstrual cycle. A metabolic panel, blood pressure, and waist circumference were collected in a fasted state. Magnetic resonance imaging (MRI, 3 Tesla) with arterial spin labeling was used to quantify global and regional CBF. Two-way (Group x Sex) linear models with Shaffer’s correction and Tukey adjusted post hocs were used to determine differences in CBF. In the MetSyn groups, Pearson correlation coeffcients were assessed between fasting TG levels and each global and regional CBF value. Global CBF was greater in female CON compared to all groups (p ≤ 0.01), and male CON had greater CBF than male MetSyn (p = 0.03), whereas there was no difference between male and female MetSyn (p = 0.43). Regional analyses resulted in the same pattern of between-group differences in the parietal lobe (p = 0.03), the precuneus (p = 0.01), and the frontal lobe (p = 0.01), outside of a nonsignificant difference between male CON and male MetSyn in the frontal lobe (p = 0.12). No interactions existed for the temporal lobe, occipital lobe, or thalamus (p ≥ 0.06). In females with MetSyn, fasting TG levels were moderately negatively correlated with CBF (r = -0.65), whereas a moderate positive relationship existed in males with MetSyn (r = 0.71). These data suggest that MetSyn reduces CBF to a greater extent in females than males, abolishing sex-dependent differences in CBF present in healthy young adults. While female sex is protective against cardiovascular disease in healthy young adults, this is not the case in individuals with MetSyn. Additionally, males and females with MetSyn had opposing relationships between fasting TG levels and CBF. These findings may help explain the greater cardiovascular risk in females with insulin resistance. American Diabetes Association (ADA1-16-ICTS-099 and ADA 1-12-IN-39); Clinical and Translational Science Award program (UL1TR002373); Wisconsin National Primate Research Center (P51OD011106). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Interaction of Apo E genotype on fasting and postprandial triglyceride levels in apparently healthy adult

Interaction of Apo E genotype on fasting and postprandial triglyceride levels in apparently healthy adult

Exercise promotes irisin expression to ameliorate renal injury in type 2 diabetic rats

To investigate the role of irisin in exercise-induced improvement of renal function in type 2 diabetic rats. Forty male SD rats aged 4-6 weeks were randomized into normal control group, type 2 diabetes mellitus model group, diabetic exercise (DE) group and diabetic irisin (DI) group (n=8). The rats in DE group were trained with treadmill running for 8 weeks, and those in DI group were given scheduled irisin injections for 8 weeks. After the treatments, blood biochemical parameters of the rats were examined, and renal histopathology was observed with HE, Masson and PAS staining. Western blotting was used to detect the protein expression levels in the rats'kidneys. The diabetic rats showed significantly increased levels of fasting insulin, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen with lowered serum irisin level (all P < 0.05). Compared with those in DM group, total cholesterol, triglyceride, serum creatinine and blood urea nitrogen levels were decreased and serum irisin levels were increased in both DE and DI groups (all P < 0.05). The rats in DM group showed obvious structural disorders and collagen fiber deposition in the kidneys, which were significantly improved in DE group and DI group. Both regular exercises and irisin injections significantly ameliorated the reduction of FNDC5, LC3-II/I, Atg7, Beclin-1, p-AMPK, AMPK and SIRT1 protein expressions and lowered of p62 protein expression in the kidneys of the diabetic rats (all P < 0.05). Both exercise and exogenous irisin treatment improve nephropathy in type 2 diabetic rats possibly due to irisin-mediated activation of the AMPK/SIRT1 pathway in the kidneys to promote renal autophagy.

Insulin resistance impairs biologic agent response in moderate-to-severe plaque psoriasis: insights from a prospective cohort study in China.

Psoriasis and insulin resistance (IR) are closely related, but it remains unclear whether IR affects the treatment of patients with psoriasis. To investigate whether IR impairs the treatment response to biologic agents in patients with moderate-to-severe plaque psoriasis. This project was based on a prospective cohort study design. Data were collected from the Shanghai Psoriasis Effectiveness Evaluation CoHort (SPEECH), which is a prospective cohort exploring treatment strategies for psoriasis in China. IR was assessed using triglyceride glucose-body mass index (TyG-BMI). Psoriasis severity was assessed using Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Multiple logistic regression was used to explore the differences between patients with high and low levels of IR. Subgroup and sensitivity analyses were performed to examine the robustness of the study results. A total of 290 patients were included in the analysis. Based on median TyG-BMI, the patients were divided into two groups: high and low IR. The high IR group exhibited a higher prevalence of diabetes, a higher BMI, and higher fasting blood glucose and triglyceride levels than the low IR group. Further analysis of treatment efficacy revealed that patients in the high IR group had lower PASI 75 [≥ 75% improvement in Psoriasis Area and Severity Index (PASI)], PASI 90 (≥ 90% improvement in PASI) and PGA 0/1 ('clear' or 'almost clear') response rates after 12 weeks of treatment. In the low IR group, 81.9% of patients achieved PASI 75, 58.3% achieved PASI 90 and 75.7% achieved PGA 0/1. However, the proportion of responses at each endpoint was significantly lower in the high IR group compared with the low IR group. The reduced PGA 0/1 response rate was more significant in the high IR group, indicated by lower odd ratios. Subsequent subgroup and sensitivity analyses produced consistent results. IR is associated with lower effectiveness of biologics in patients with psoriasis.

Olezarsen, Acute Pancreatitis, and Familial Chylomicronemia Syndrome

BackgroundFamilial chylomicronemia syndrome is a genetic disorder associated with severe hypertriglyceridemia and severe acute pancreatitis. Olezarsen reduces the plasma triglyceride level by reducing hepatic synthesis of apolipoprotein C-III.MethodsIn a phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with genetically identified familial chylomicronemia syndrome to receive olezarsen at a dose of 80 mg or 50 mg or placebo subcutaneously every 4 weeks for 49 weeks. There were two primary end points: the difference between the 80-mg olezarsen group and the placebo group in the percent change in the fasting triglyceride level from baseline to 6 months, and (to be assessed if the first was significant) the difference between the 50-mg olezarsen group and the placebo group. Secondary end points included the mean percent change from baseline in the apolipoprotein C-III level and an independently adjudicated episode of acute pancreatitis.ResultsA total of 66 patients underwent randomization; 22 were assigned to the 80-mg olezarsen group, 21 to the 50-mg olezarsen group, and 23 to the placebo group. At baseline, the mean (±SD) triglyceride level among the patients was 2630±1315 mg per deciliter, and 71% had a history of acute pancreatitis within the previous 10 years. Triglyceride levels at 6 months were significantly reduced with the 80-mg dose of olezarsen as compared with placebo (−43.5 percentage points; 95% confidence interval [CI], −69.1 to −17.9; P<0.001) but not with the 50-mg dose (−22.4 percentage points; 95% CI, −47.2 to 2.5; P=0.08). The difference in the mean percent change in the apolipoprotein C-III level from baseline to 6 months in the 80-mg group as compared with the placebo group was −73.7 percentage points (95% CI, −94.6 to −52.8) and between the 50-mg group as compared with the placebo group was −65.5 percentage points (95% CI, −82.6 to −48.3). By 53 weeks, 11 episodes of acute pancreatitis had occurred in the placebo group, and 1 episode had occurred in each olezarsen group (rate ratio [pooled olezarsen groups vs. placebo], 0.12; 95% CI, 0.02 to 0.66). Adverse events of moderate severity that were considered by a trial investigator at the site to be related to the trial drug or placebo occurred in 4 patients in the 80-mg olezarsen group.ConclusionsIn patients with familial chylomicronemia syndrome, olezarsen may represent a new therapy to reduce plasma triglyceride levels. (Funded by Ionis Pharmaceuticals; Balance ClinicalTrials.gov number, NCT04568434.)

Plozasiran (ARO-APOC3) for Severe Hypertriglyceridemia

Severe hypertriglyceridemia (sHTG) confers increased risk of atherosclerotic cardiovascular disease (ASCVD), nonalcoholic steatohepatitis, and acute pancreatitis. Despite available treatments, persistent ASCVD and acute pancreatitis-associated morbidity from sHTG remains. To determine the tolerability, efficacy, and dose of plozasiran, an APOC3-targeted small interfering-RNA (siRNA) drug, for lowering triglyceride and apolipoprotein C3 (APOC3, regulator of triglyceride metabolism) levels and evaluate its effects on other lipid parameters in patients with sHTG. The Study to Evaluate ARO-APOC3 in Adults With Severe Hypertriglyceridemia (SHASTA-2) was a placebo-controlled, double-blind, dose-ranging, phase 2b randomized clinical trial enrolling adults with sHTG at 74 centers across the US, Europe, New Zealand, Australia, and Canada from May 31, 2021, to August 31, 2023. Eligible patients had fasting triglyceride levels in the range of 500 to 4000 mg/dL (to convert to millimoles per liter, multiply by 0.0113) while receiving stable lipid-lowering treatment. Participants received 2 subcutaneous doses of plozasiran (10, 25, or 50 mg) or matched placebo on day 1 and at week 12 and were followed up through week 48. The primary end point evaluated the placebo-subtracted difference in means of percentage triglyceride change at week 24. Mixed-model repeated measures were used for statistical modeling. Of 229 patients, 226 (mean [SD] age, 55 [11] years; 176 male [78%]) were included in the primary analysis. Baseline mean (SD) triglyceride level was 897 (625) mg/dL and plasma APOC3 level was 32 (16) mg/dL. Plozasiran induced significant dose-dependent placebo-adjusted least squares (LS)-mean reductions in triglyceride levels (primary end point) of -57% (95% CI, -71.9% to -42.1%; P < .001), driven by placebo-adjusted reductions in APOC3 of -77% (95% CI, -89.1% to -65.8%; P < .001) at week 24 with the highest dose. Among plozasiran-treated patients, 144 of 159 (90.6%) achieved a triglyceride level of less than 500 mg/dL. Plozasiran was associated with dose-dependent increases in low-density lipoprotein cholesterol (LDL-C) level, which was significant in patients receiving the highest dose (placebo-adjusted LS-mean increase 60% (95% CI, 31%-89%; P < .001). However, apolipoprotein B (ApoB) levels did not increase, and non-high-density lipoprotein cholesterol (HDL-C) levels decreased significantly at all doses, with a placebo-adjusted change of -20% at the highest dose. There were also significant durable reductions in remnant cholesterol and ApoB48 as well as increases in HDL-C level through week 48. Adverse event rates were similar in plozasiran-treated patients vs placebo. Serious adverse events were mild to moderate, not considered treatment related, and none led to discontinuation or death. In this randomized clinical trial of patients with sHTG, plozasiran decreased triglyceride levels, which fell below the 500 mg/dL threshold of acute pancreatitis risk in most participants. Other triglyceride-related lipoprotein parameters improved. An increase in LDL-C level was observed but with no change in ApoB level and a decrease in non-HDL-C level. The safety profile was generally favorable at all doses. Additional studies will be required to determine whether plozasiran favorably modulates the risk of sHTG-associated complications. ClinicalTrials.gov Identifier: NCT04720534.