Nonfasting Triglyceride Levels Research Articles

Estimating Triglyceride Levels Using Total Cholesterol, Low-Density Lipoprotein Cholesterol, and High-Density Lipoprotein Cholesterol Levels: A Cross-Sectional Study.

Objective: Triglyceride (TG) levels are affected by food intake, and the cutoff values for nonfasting TG levels vary. This study aimed to calculate fasting TG levels based on total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels. Methods: Multiple regression analysis was performed to determine estimated triglyceride (eTG) levels using data from 39,971 participants divided into six groups based on non-high-density lipoprotein cholesterol (nHDL-C) levels (<100, <130, <160, <190, <220, and ≥220 mg/dL). Results: Provided that fasting TG and eTG levels ≥150 mg/dL were positive and those <150 mg/dL were negative, the three groups (nHDL-C levels <100, <130, and <160 mg/dL) consisting of 28,616 participants had a false-positive rate of <5%. The coefficient and constant terms in the formula for the eTG in groups with nHDL-C levels <100, <130, and <160 mg/dL were as follows: constant terms, 12.193, 0.741, and -7.157; coefficients of LDL-C, -3.999, -4.409, and -5.145; coefficients of HDL-C, -3.869, -4.555, and -5.215; and coefficients of TC, 3.984, 4.547, and 5.231, respectively. The adjusted coefficients of determination were 0.547, 0.593, and 0.678, respectively (P < 0.001, P < 0.001, and P < 0.001, respectively). Conclusion: Fasting TG levels can be calculated from TC, LDL-C, and HDL-C levels when nHDL-C levels are <160 mg/dL. Using nonfasting TG and eTG levels as indicators of hypertriglyceridemia might eliminate the need for venous sampling after overnight fasting.

Serum triglyceride levels and incidence of hypertension in a general Japanese population: ISSA-CKD study.

The aim of this study was to clarify the relationship between fasting and nonfasting serum triglyceride (TG) levels and the incidence of hypertension in a general Japanese population. We conducted a population-based retrospective cohort study using annual health check-up data of residents of Iki City, Nagasaki Prefecture, Japan. A total of 3202 participants without hypertension at baseline were included in the present analysis. TG levels were classified as quartile 1 (<0.82 mmol/L), quartile 2 (0.83-1.13 mmol/L), quartile 3 (1.14-1.70 mmol/L) and quartile 4 (≥1.71 mmol/L) for men, and as quartile 1 (<0.70 mmol/L), quartile 2 (0.71-0.96 mmol/L), quartile 3 (0.97-1.34 mmol/L) and quartile 4 (≥1.35 mmol/L) for women. The outcome was incident hypertension. During an average follow-up of 4.4 years, 983 participants developed hypertension, according to the Cox proportional hazards model. The annual incidence of hypertension increased with an elevation in TG levels for men (5.88% in quartile 1, 8.30% in quartile 2, 7.62% in quartile 3, and 9.82% in quartile 4). This association was significant, even after adjustment for other risk factors: hazard ratio 1.41 [95% CI 1.07-1.85] for quartile 2, 1.30 [0.99-1.71] for quartile 3, and 1.59 [1.22-2.08] for quartile 4 compared with quartile 1 (p = 0.041 for trend). In contrast, there was no clear association between serum TG levels and the incidence of hypertension after adjustment for confounding factors among women (p = 0.240 for trend). High levels of serum TG were associated with the future incidence of hypertension in a general population of Japanese men but were not associated with that in women. Casual serum triglyceride levels and incidence of hypertension in a general Japanese population: ISSA-CKD study.

Association of Apolipoprotein B and Triglyceride Levels with Coronary Artery Disease

Objective: To find the association of Apolipoprotein B and triglycerides with coronary artery disease.&#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, in collaboration with HITEC Institute of Medical Sciences, Taxila Pakistan, from Mar 2019 to Mar 2020.&#x0D; Methodology: Four hundred and forty-four individuals of either gender and 18-70 years were included in the study. According to CT angiography, participants were differentiated into those with coronary artery disease and without coronary artery disease. In addition, serum triglycerides were analysed by glycerol phosphate enzymatic endpoint method on ADVIA 1800R Clinical Chemistry Auto analyzer, and apolipoprotein B was analysed on BT1500 Clinical Chemistry turbidimetric analyzer.&#x0D; Results: The sample population had 144(32.0%) females and 300(68.0%) males. 164(37.0%) patients had coronary artery disease. 120(27.0%) participants were between 35 and 45 years of age, and 96(22.0%) were between 56 and 65 years. 126(30.0%) patients had hypertension, 352(79.3%) had apolipoprotein B levels &gt;130 mg/dl. Positive Pearson’s correlation was found between apolipoprotein B and triglycerides with coronary artery disease.&#x0D; Conclusion: There is a strong association between apolipoprotein B and non-fasting triglyceride levels with coronary artery disease. The apolipoprotein B can be used as a routine biomarker for screening and treatment monitoring coronary artery disease along with other lipid profile parameters.

Non-Fasting Hypertriglyceridemia Burden as a Residual Risk of the Progression of Carotid Artery Stenosis.

The relationships between repeated non-fasting triglyceride (TG) measurements and carotid stenosis progression during follow-ups have never been investigated. In 111 consecutive carotid arteries of 88 patients with ≥50% atherosclerotic stenosis on at least one side, who had ≥3 blood samples taken during ≥one-year follow-ups, clinical variables were compared between carotid arteries with and without subsequent stenosis progression. To evaluate non-fasting TG burden, a new parameter area [TG ≥ 175] was calculated by integrating non-fasting TG values ≥ 175 mg/dL (i.e., TG values minus 175) with the measurement intervals (year). Carotid stenosis progression occurred in 22 arteries (19.8%) during the mean follow-up period of 1185 days. Younger age, symptomatic stenosis, higher mean values of TG during follow-ups, the area [TG ≥ 175], mean TG values ≥ 175 mg/dL and maximum TG values ≥175 mg/dL were significant factors related to the progression on univariate analyses. The cut-off value of the area [TG ≥ 175] to discriminate carotid stenosis progression was 6.35 year-mg/dL. Multivariate analyses demonstrated that symptomatic stenosis and the area [TG ≥ 175] ≥ 6.35 year-mg/dL were independently related to carotid stenosis progression. In conclusion, the area [TG ≥ 175] was an independent risk factor for carotid stenosis progression, and this study suggests the importance to continuously control non-fasting TG levels < 175 mg/dL during follow-ups to prevent carotid stenosis progression.

Relationship Between Non-fasting Triglycerides and Cardiovascular Disease Mortality in a 20-year Follow-up Study of a Japanese General Population: NIPPON DATA90.

BackgroundNon-fasting triglycerides (TG) are considered a better predictor of cardiovascular disease (CVD) than fasting TG. However, the effect of non-fasting TG on fatal CVD events remains unclear. In the present study, we aimed to explore the relationship between non-fasting TG and CVD mortality in a Japanese general population.MethodsA total of 6,831 participants without a history of CVD, in which those who had a blood sampling over 8 hours or more after a meal were excluded, were followed for 18.0 years. We divided participants into seven groups according to non-fasting TG levels: ≤59 mg/dL, 60–89 mg/dL, 90–119 mg/dL, 120–149 mg/dL, 150–179 mg/dL, 180–209 mg/dL, and ≥210 mg/dL, and estimated the multivariable-adjusted hazard ratios (HRs) of each TG group for CVD mortality after adjusting for potential confounders, including high density lipoprotein cholesterol. Additionally, we performed analysis stratified by age <65 and ≥65 years.ResultsDuring the follow-up period, 433 deaths due to CVD were detected. Compared with a non-fasting TG of 150–179 mg/dL, non-fasting TG ≥210 mg/dL was significantly associated with increased risk for CVD mortality (HR 1.56: 95% CI, 1.01–2.41). Additionally, lower levels of non-fasting TG were also significantly associated with increased risk for fatal CVD. In participants aged ≥65 years, lower levels of non-fasting TG had a stronger impact on increased risk for CVD mortality, while higher levels of non-fasting TG had a stronger impact in those aged <65 years.ConclusionIn a general Japanese population, we observed a U-shaped association between non-fasting TG and fatal CVD events.

Impact of triglyceride levels on plaque characteristics in patients with coronary artery disease

BackgroundHigh triglyceride (TG) levels have been demonstrated to be a risk factor for coronary artery disease. This study aimed to clarify the impact of TG levels on the characteristics of coronary plaques. MethodsA total of 850 consecutive patients who underwent optical coherence tomography (OCT) imaging of the culprit lesion were included. The morphologies of culprit plaques were compared between the higher TG group (nonfasting TG levels ≥150 mg/dL, n = 337) and the lower TG group (nonfasting TG <150 mg/dL, n = 513). ResultsThe prevalence of lipid-rich plaques (43% vs. 33%, p = 0.005), thin-cap fibroatheromas (TCFAs) (24% vs. 17%, p = 0.015) and macrophages (40% vs. 31%, p = 0.006) was significantly higher in the higher TG group than in the lower TG group. In addition to a high low-density lipoprotein cholesterol (LDL-C) level (≥140 mg/dL), high TGs (≥150 mg/dL) were identified as an independent factor for the presence of TCFAs (odds ratio 1.465, 95% confidence interval 1.004–2.137, p = 0.048). Among patients with lower LDL-C levels (<100 mg/dL), the prevalence of macrophages (38% vs. 26%, p = 0.007) and layered plaques (48% vs. 38%, p = 0.019) was significantly higher in the higher TG group than in the lower TG group. ConclusionsHigher TG levels were associated with a higher prevalence of TCFAs in culprit coronary lesions. The prevalence of macrophages and layered plaques was more frequently observed in patients with higher TGs than those with lower TGs among patients with LDL-C < 100 mg/dL.

Nonfasting Triglyceride as an Independent Predictor of Carotid Restenosis After Carotid Endarterectomy or Carotid Artery Stenting

Nonfasting serum triglyceride (TG) level is attracting more and more attention as an atherosclerosis-promoting factor. However, no study has investigated the relationships between nonfasting TG levels and carotid restenosis after carotid endarterectomy (CEA) or carotid artery stenting (CAS). This study was conducted to investigate if nonfasting TG levels can be used to assess a risk for carotid restenosis after CEA or CAS. This was a single-center retrospective study. We reviewed 201 consecutive primary carotid artery revascularization procedures (39 CEAs and 162 CASs), which were performed from 2008 to 2018 for 179 patients (163 men and 16 women) with atherosclerotic carotid stenosis, and were followed up for at least 1 year. Clinical variables including nonfasting lipid profiles and findings of magnetic resonance plaque imaging were compared between groups with and without postprocedural carotid restenosis (≥50% stenosis on ultrasonography). During a mean follow-up period of 1413 days, 24 of 201 carotid stenosis procedures (11.9%) suffered restenosis after successful revascularization procedures. Multivariate analyses demonstrated that nonfasting TG level was the only independent risk factor of postprocedural restenosis. The receiver operating characteristic curve analyses revealed that a cutoff value of nonfasting TG to discriminate postprocedural carotid restenosis was 127.5 mg/dL, which was much lower than the upper limit of normal. This study showed that nonfasting TG level may be a useful marker to predict carotid restenosis after CEA or CAS, and could be a new therapeutic target to prevent carotid restenosis after revascularization procedures.

Icosapent ethyl: safely reducing cardiovascular risk in adults with elevated triglycerides

ABSTRACT Introduction In patients at high cardiovascular risk, the rate of events remains elevated despite traditional, evidence-based lipid-lowering therapy. Residual hypertriglyceridemia is an important contributor to this risk. However, prior medications with triglyceride-lowering effects have not reduced adverse clinical outcomes in the statin era. Areas covered The present review summarizes evidence and recommendations related to triglyceride-lowering therapy in the primary and secondary preventive settings. We provide an overview of findings from recent meta-analyses, important observational studies, and a detailed description of landmark trials, including the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT). We further review recommendations from current guidelines. Expert opinion Icosapent ethyl is a stable, highly purified ethyl ester of eicosapentaenoic acid that safely and effectively reduces cardiovascular events in the contemporary setting. It is prescribed at a dose of 2 grams twice daily and is indicated in patients at high cardiovascular risk who have fasting or non-fasting triglyceride levels ≥150 mg/dl despite maximally tolerated statin treatment, or in individuals with triglyceride levels ≥500 mg/dl. Conversely, omega-3 fatty acid preparations containing a combination of eicosapentaenoic acid and docosahexaenoic acid are not indicated for reduction of cardiovascular risk and should be actively deprescribed.

Validity of Random Triglyceride Levels in Infants Receiving Parenteral Nutrition.

Background: Intravenous lipid emulsions (IL) are an important part of parenteral nutrition (PN) to meet essential fatty acid (EFA) requirements and metabolic demands of neonates and preterm infants. Some critically-ill neonates may not metabolize IL effectively which can lead to hypertriglyceridemia. Risks associated with this include increased pulmonary vascular resistance, displaced bilirubins, and platelet or macrophage dysfunction. Serum triglyceride (TG) concentration is used as a marker for lipid tolerance and predictor of potential complications involved with IL administration, but the clinical significance of this is still debated. Management of TG levels with regard to timing of laboratory tests, the ideal goal range, and duration of infusion of IL varies across institutions and is not standardized.Methods: Single-center, retrospective study of newborn infants receiving parenteral nutrition (PN). Fasting and non-fasting TG levels were drawn during the same lipid infusion of 2–3g/kg/day. The primary outcome was the difference between fasting and non-fasting TG levels. Statistical assessment of continuous data was done with student t-test and nominal data was evaluated using X2-test and logistic regression.Results: Forty infants were included with mean gestational age at birth of 29.5 ± 3.4 weeks and mean birth weight of 1.3 ± 0.5 kg. Mean time between lab draws while on same IL dose was 11.6 ± 0.2 h with resulting mean fasting and non-fasting (random) TG levels 82 ± 40 mg/dL (95% CI 68.4, 97.6) and 101 ± 40 mg/dL (95% CI 88.5, 115.8), respectively. Mean difference between TG levels during lipid-free interval and during infusion was −18.6 ± 51.2 mg/dL (95% CI −35.0, −2.3; p = 0.03).Conclusion: We concluded there is no difference in the management of IL, when TG level was drawn randomly or as fasting sample. Obtaining TG level during routine lab draws is appropriate. We extrapolated that the administration of IL over 24 h will not interfere with TG level.

Impact of Pemafibrate in Patients with Hypertriglyceridemia and Metabolic Dysfunction-associated Fatty Liver Disease Pathologically Diagnosed with Non-alcoholic Steatohepatitis: A Retrospective, Single-arm Study.

Objective The therapeutic effect of pemafibrate on metabolic dysfunction-associated fatty liver disease (MAFLD) remains unknown. This retrospective, single-arm study investigated the efficacy and safety of pemafibrate in MAFLD patients with hypertriglyceridemia. Methods A total of 10 patients who received pemafibrate (oral, 0.1 mg, twice a day) at Gunma Saiseikai Maebashi Hospital between September 2018 and September 2019 were included. All patients underwent a liver biopsy, and the disease grade and stage were pathologically assessed based on the FLIP algorithm. Results The median age was 66.0 (53.8-74.8) years old, and 5 patients (50.0%) were men. All patients were diagnosed with non-alcoholic steatohepatitis (NASH). The fasting and non-fasting triglyceride (TG) levels were 175 (149-247) mg/dL and 228 (169-335) mg/dL, respectively. The AST and ALT values at 6 months were significantly lower than at baseline [AST: 28.0 (22.0-33.8) U/L vs. 43.5 (24.0-55.0) U/L, p=0.008, ALT: 23.0 (14.8-26.5) U/L vs. 51.5 (23.0-65.3) U/L, p=0.005, respectively], especially in NASH patients with significant activity and advanced fibrosis (p=0.040 and 0.014, respectively). Fasting TG levels were significantly lower and HDL-C levels significantly higher at 6 months than at baseline (p=0.005 and 0.032, respectively). At six months, FIB-4, the aspartate aminotransferase-to-platelet ratio index, and the macrophage galactose-specific lectin-2 binding protein glycosylation isomer level were significantly improved compared with baseline (p=0.041, 0.005 and 0.005, respectively). Treatment-related adverse events were not observed. Conclusion Pemafibrate treatment may be safe and effective for MAFLD patients with hypertriglyceridemia.

Higher Non-fasting Serum Triglyceride Preceding the Carotid Stenosis Progression.

The present study was conducted to investigate whether non-fasting serum triglyceride (TG) levels can be used to assess a risk for the progression of carotid artery stenosis. This was a single- center retrospective study. Consecutive 96 patients with ≥50% stenosis of at least unilateral cervical internal carotid artery and normal fasting serum low-density lipoprotein cholesterol (LDL-C) levels of ≤140 mg/dL were followed up for at least 1 year (mean, 3.1 years), and clinical variables were compared between patients with and without carotid stenosis progression (≥10% increases in the degree on ultrasonography). Carotid stenosis progression was shown in 21 patients, associated with less frequent treatment with calcium channel blockers (CCBs), higher non-fasting TG and glucose levels. In carotid artery-based analyses including <50% stenosis side, stenosis progression was shown in 23 of 121 arteries except for those with complete occlusion and less than 1-year follow-up period because of carotid artery stenting (CAS) or carotid endarterectomy (CEA). Stenosis progression was more frequently observed in symptomatic and/or radiation-induced lesions, and was also accompanied with less frequent treatment with CCBs, higher non-fasting TG and glucose levels in carotid artery-based analyses. The receiver operating characteristic (ROC) curve analyses revealed that a cutoff value of non-fasting TG to discriminate carotid stenosis progression was 169.5 mg/dL for carotid arteries with the baseline stenosis of <50%, and 154.5mg/dL for those of ≥50%. Non-fasting TG level was an independent risk factor of carotid stenosis progression, and more strict control of non-fasting TG may be necessary for higher degree of carotid artery stenosis.

Reduced Reverse Cholesterol Transport Efficacy in Healthy Men with Undesirable Postprandial Triglyceride Response.

Elevation of nonfasting triglyceride (TG) levels above 1.8 g/L (2 mmol/L) is associated with increased risk of cardiovascular diseases. Exacerbated postprandial hypertriglyceridemia (PP–HTG) and metabolic context both modulate the overall efficacy of the reverse cholesterol transport (RCT) pathway, but the specific contribution of exaggerated PP–HTG on RCT efficacy remains indeterminate. Healthy male volunteers (n = 78) exhibiting no clinical features of metabolic disorders underwent a postprandial exploration following consumption of a typical Western meal providing 1200 kcal. Subjects were stratified according to maximal nonfasting TG levels reached after ingestion of the test meal into subjects with a desirable PP–TG response (GLow, TG < 1.8 g/L, n = 47) and subjects with an undesirable PP–TG response (GHigh, TG > 1.8 g/L, n = 31). The impact of the degree of PP–TG response on major steps of RCT pathway, including cholesterol efflux from human macrophages, cholesteryl ester transfer protein (CETP) activity, and hepatic high-density lipoprotein (HDL)-cholesteryl ester (CE) selective uptake, was evaluated. Cholesterol efflux from human macrophages was not significantly affected by the degree of the PP–TG response. Postprandial increase in CETP-mediated CE transfer from HDL to triglyceride-rich lipoprotein particles, and more specifically to chylomicrons, was enhanced in GHigh vs. GLow. The hepatic HDL-CE delivery was reduced in subjects from GHigh in comparison with those from GLow. Undesirable PP–TG response induces an overall reduction in RCT efficacy that contributes to the onset elevation of both fasting and nonfasting TG levels and to the development of cardiometabolic diseases.

SUN-167 Quetiapine-Induced Hypertriglyceridemia and Hyperglycemia Presenting as Simultaneous Diabetic Ketoacidosis and Acute Pancreatitis

Background: Quetiapine-induced metabolic emergencies such as diabetic ketoacidosis (DKA) and acute pancreatitis (AP) are rare. We describe a case of new-onset hypertriglyceridemia (HTG) and diabetes mellitus (DM) following the initiation of quetiapine, presenting as concurrent new-onset DKA and AP. Clinical Case: A 34 year-old male with bipolar disorder and schizophrenia presented with three days of epigastric pain, nausea, and vomiting. He had no prior history of DM or dyslipidemia (DLD). He reported long-standing use of divalproex, benztropine, and haloperidol. He had started quetiapine three months prior, at which time glycosylated hemoglobin A1c (HgbA1c) was 5.7% and non-fasting triglyceride (TG) level was 266 (range 30-150 mg/dL). He was a smoker, but denied alcohol or drug use. On admission, he was hypertensive, tachycardic, and febrile with significant abdominal pain. His blood glucose was 522 (range 55-110 mg/dL) with an anion gap of 27 (range 5-17), venous pH of 7.18 (range 7.33-7.43), bicarbonate of 7 (range 23-31 mEq/L), and serum creatinine of 1.8 (0.6-1.4 mg/dL). He also had an elevated serum lipase of 317 (range 5-55 U/L), TG of 2436 (range 30-150 mg/dL), and computed tomography confirmed peri-pancreatic edema consistent with AP. Thyroid function tests were normal. Abdominal ultrasound was negative for cholelithiasis. He was treated with aggressive intravenous (IV) hydration and IV insulin, and later transitioned to subcutaneous (SQ) insulin after resolution of DKA. Quetiapine was stopped and he was discharged on haloperidol, benztropine, fenofibrate, and SQ insulin. Due to improving BG levels, insulin was gradually tapered over the next few weeks and subsequently discontinued. HgbA1c obtained three months later was 5.7% (off insulin) and fasting TG level was 212 mg/dL. Discussion: Second generation antipsychotics (SGAs), particularly olanzapine and clozapine, are known to cause metabolic abnormalities such as weight gain, hyperglycemia, and hyperlipidemia. Although quetiapine is described to have low risk for development of diabetes or lipid abnormalities, it can cause life-threatening complications like DKA and AP. While DKA has been reported in many case series, AP is exceedingly rare. There are fewer than ten reported cases with or without HTG following quetiapine use, usually within the first year of drug initiation. Since many of these patients do not have pre-existing DLD or DM, it is important for providers and patients to be aware of the risk of developing these life-threatening complications, even with a relatively safe SGA. Current guidelines recognize the importance of laboratory monitoring for early detection of metabolic disturbances in patients taking SGAs; however, recommendations regarding frequency of monitoring remain variable. Updated surveillance parameters are needed to facilitate the prevention of such metabolic emergencies.

Triglycerides and triglyceride-rich lipoproteins in the development and progression of atherosclerosis.

In this review, we intend to show the heterogenicity of the triglyceride group, including the triglyceride-rich lipoproteins and its subparticles, apolipoproteins, and its role in atherogenesis through epidemiological and genetic studies, observing the association of these various components and subclasses with subclinical atherosclerosis and cardiovascular events. Also, we reevaluated the moment of blood collection for the triglyceride measurement and its repercussion in atherosclerosis. Finally, we present the current scenario and new insights about the pharmacologic treatment of hypertriglyceridemia. Recent studies have been observed, a correlation between cardiovascular disease and triglyceride components (as apolipoproteins A-V, C-I, C-III) as well as proteins involved in the metabolism pathway, such as the angiopoietin-like proteins. Also, the triglyceride-rich lipoproteins, also known as remnants, were recently associated with atherogenesis. Another important topic addressed is about nonfasting triglyceride level, which has been postulated as a better predictor of cardiovascular events than fasting collection. Regarding hypertriglyceridemia treatment, the drug therapy was updated, as the omega-3 polyunsaturated fatty acids were tested in primary prevention as eicosapentaenoic acid and docosahexaenoic acid combination resulted in no benefit, whereas the administration of icosapent ethyl in secondary prevention and high-risk patients showed a robust decrease of the cardiovascular outcomes.

2-Acyl-3-carboxyl-tetrahydroisoquinoline Derivatives: Mixed-Type PTP1B Inhibitors without PPARγ Activation.

A novel series of 2-acyl-3-carboxyl-tetrahydroisoquinoline derivatives were synthesized and biologically evaluated. Among them, (S)-2-{(E)-3-furan-2-ylacryloyl}-7-[(2E,4E)-5-(2,4,6-trifluorophenyl)penta-2,4-dienyloxy]-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (compound 17u) was identified as a potent protein tyrosine phosphatase 1B (PTP1B) inhibitor without peroxisome proliferator-activated receptor (PPAR) γ activation: PTP1B inhibition IC50=0.19 µM and PPARγ ΕC50>10 µM. Compound 17u exhibited mixed-type inhibition for PTP1B, and this mode of inhibition was rationalized by computational ligand docking into the catalytic and allosteric sites of PTP1B. Compound 17u also showed high oral absorption at 10 mg/kg (per os (p.o.), Cmax=4.67 µM) in rats, significantly reduced non-fasting plasma glucose and triglyceride levels with no side effects at 30 mg/kg/d (p.o.) for 4 weeks, and attenuated elevations in plasma glucose levels in the oral glucose tolerance test performed 24 h after its final administration in db/db mice. In conclusion, the substituted 2-acyl-3-carboxyl-tetrahydroisoquinoline is a novel scaffold of mixed-type PTP1B inhibitors without PPARγ activation, and compound 17u has potential as an efficacious and safe anti-diabetic drug as well as a useful tool for investigations on the physiological and pathophysiological effects of mixed-type PTP1B inhibition.

Fasting versus Non-fasting Lipid profile in the clinical practice

There are pros and cons doing fasting and random non-fasting lipid profile test. However, when we consider cardio vascular risk, non-fasting lipid test more reliable than fasting test. In current practice, using fasting lipid profile was challenged in 2007 by two studies that showed that random non-fasting triglyceride (TG) could be superior than fasting TG in predicting risk of cardiovascular risk. Postprandial concentrations of triglyceride were higher than fasting. However, levels of non-fasting triglycerides are better at predicting future cardiovascular events than levels of fasting triglycerides. Random non-fasting lipid test is not a new phenomenon, it already practicing in Denmark since 2009. Moreover, NICE guidelines have recommended non-fasting test in the primary prevention setting since 2014. As the major shift in newer guidelines reflects the changing focus of risk assessment from LDL to non-HDL cholesterol (apolipoprotein B) as a better predictor of cardiovascular risk, indirectly tell us non-fasting lipid level superior than fasting lipid. The aim of the review is to compare both fasting and non-fasting measurements in our clinical practice.

The Effect of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors on Nonfasting Remnant Cholesterol in a Real World Population.

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have demonstrated significant effects on low-density lipoprotein (LDL) cholesterol and nonhigh density lipoprotein (HDL) cholesterol. To date, there have been limited reports on the effect of PCSK9 inhibitors on remnant cholesterol. Objectives Assess the effect of PCSK9 inhibitors on nonfasting remnant cholesterol in a real world population. Identify whether pretreatment triglyceride levels are associated with PCSK9 inhibition success as indicated by changes in remnant cholesterol levels. Methods Patients in our adult lipid clinic (n = 109) receiving PCSK9 inhibition for atherosclerotic cardiovascular disease or familial hypercholesterolemia who had available pre- and post-PCSK9 inhibition standard nonfasting lipid data were, retrospectively, selected for data analysis. Remnant cholesterol was the difference between non-HDL and LDL cholesterol. LDL cholesterol was measured directly and calculated from Friedewald and Martin/Hopkins methods. Data were analyzed using repeated measures ANOVA and multivariable linear regression for differential effects on remnant and LDL cholesterol based upon pretreatment nonfasting triglyceride levels. Results Remnant cholesterol as well as total, LDL, non-HDL cholesterol, and triglycerides decreased significantly (P<0.001) after PCSK9 inhibition. Patients with higher pretreatment triglyceride levels showed greater decrease in remnant cholesterol after PCSK9 inhibition (P<0.001) than those with lower pretreatment triglycerides. Conclusions In patients receiving PCSK9 inhibitors, remnant cholesterol as determined from nonfasting blood was reduced in proportion to pretreatment triglycerides.

Mild hyperbaric oxygen inhibits the growth-related decline in skeletal muscle oxidative capacity and prevents hyperglycemia in rats with type 2 diabetes mellitus.

Humans and animals with type 2 diabetes mellitus (T2DM) exhibit low skeletal muscle oxidative capacity and impaired glucose metabolism. The aim of the present study was to investigate the effects of exposure to mild hyperbaric oxygen on these changes in obese rats with T2DM. Five-week-old non-diabetic Long-Evans Tokushima Otsuka (LETO) and diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats were divided into normobaric (LETO-NB and OLETF-NB) and mild hyperbaric oxygen (LETO-MHO and OLETF-MHO) groups. The LETO-MHO and OLETF-MHO groups received 1266 hPa with 36% oxygen for 3 h daily for 22 weeks. Fasting and non-fasting blood glucose, HbA1c, and triglyceride levels were lower in the OLETF-MHO group than in the OLETF-NB group (P < 0.05). In the soleus muscle, peroxisome proliferator-activated receptor δ/β (Pparδ/β), Pparγ, and PPARγ coactivator-1α (Pgc-1α) mRNA levels were lower in the OLETF-NB group than in all other groups (P < 0.05), whereas myogenin (Myog) and myogenic factor 5 (Myf5) mRNA levels were higher in the OLETF-MHO group than in the LETO-NB and OLETF-NB groups (P < 0.05). The soleus muscles in the OLETF-NB group contained only low-oxidative Type I fibers, whereas those in all other groups contained high-oxidative Type IIA and Type IIC fibers in addition to Type I fibers. Exposure to mild hyperbaric oxygen inhibits the decline in skeletal muscle oxidative capacity and prevents the hyperglycemia associated with T2DM. Pgc-1α, Myog, and Myf5 mRNA levels appear to be closely associated with skeletal muscle oxidative capacity in rats with T2DM.

Non-fasting triglyceride levels in the Korean population with and without ischemic heart disease and cerebrovascular disease.

Background/AimsAssociations between non-fasting triglyceride (TG) levels and a risk of ischemic heart disease (IHD) and cerebrovascular accident (CVA) have been suggested in Caucasians. We aimed to investigate whether non-fasting TG levels reflect the risk of IHD/CVA in Koreans.MethodsWe conducted an analysis of patients aged ≥ 30 years from the nationwide survey database. Fasting TG was defined as a measurement taken ≥ 12 hours since the last meal. Non-fasting TG was categorized by fasting duration of 0 to 3, 4 to 7, and 8 to 11 hours.ResultsIn subjects without history of IHD/CVA, diabetes, or lipid-lowering medication, the TG level was significantly elevated for 7 hours in men compared to fasting TG levels (p = 0.011); the mean TG levels were 154.9 mg/dL (standard error [SE], 13.0), 177.0 mg/dL (SE, 12.1), 148.8 mg/dL (SE, 2.8), and 141.5 mg/dL (SE, 1.4) for 0 to 3, 4 to 7, 8 to 11, and ≥12 hours’ fasting, respectively. In women, there was no difference in TG level according to fasting duration after adjustment for confounders. In men without diabetes, the TG level from 4 to 7 hours’ fasting showed a significant difference between subjects with or without IHD/CVA even after adjustments for age, body mass index, lipid medication, exercise, and dietary factors (215.1 mg/dL vs. 177.3 mg/dL, p < 0.001).ConclusionsIn men, non-fasting TG levels from 4 to 7 hours’ fasting were significantly associated with IHD/CVA, and were superior to fasting TG levels level in the significant association with the history of IHD or CVA.

Mild Hyperbaric Oxygen Inhibits Growth-related Decrease in Muscle Oxidative Capacity of Rats with Metabolic Syndrome.

Aim: We examined the effects of mild hyperbaric oxygen on the properties of the soleus muscle in rats with metabolic syndrome.Methods: Five-week-old metabolic syndrome (SHR/NDmcr-cp, cp/cp) rats were divided into normobaric (CP) and mild hyperbaric oxygen (CP-H) groups (n = 5/group). In addition, 5-week-old Wistar rats were assigned as the normobaric control (WR) group (n = 5). The CP-H group was exposed to 1.25 atmospheres absolute with 36% oxygen for 3 h daily for 16 weeks. Succinate dehydrogenase (SDH) activity and mRNA levels of peroxisome proliferator-activated receptor γ coactivator-1α (Pgc-1α) in the soleus muscle were examined. The fiber type composition, cross-sectional areas, and SDH staining intensity in the soleus muscle were also examined.Results: The CP-H group showed lower fasting and nonfasting blood glucose, glycated hemoglobin, total cholesterol, triglyceride, insulin, and systolic blood pressure levels; higher adiponectin levels; and higher SDH activity and mRNA levels of Pgc-1α in the muscle than the CP group. Compared with the CP group, the CP-H group had a lower percentage of type I fibers and observed type IIA fibers in the muscle. The CP-H group also had higher SDH staining intensity of type I and type IIC fibers in the muscle than the CP group. No differences in these values were observed in the muscles of the WR and CP-H groups.Conclusion: Mild hyperbaric oxygen inhibited growth-related increase in blood glucose levels and decrease in muscle oxidative capacity of rats with metabolic syndrome because of improved oxidative metabolism.