Absence Of Hypertriglyceridemia Research Articles

In-Hospital Outcomes in Patients With Hyperosmolar Hyperglycemic State With and Without Hypertriglyceridemia: Analysis of National Inpatient Sample

Background: In patients hospitalized with Hyperosmolar hyperglycemic state (HHS) the presence of comorbid conditions including hypertension, heart disease, stroke, and dementia have been variably reported to be associated with higher mortality. HTG is increasingly prevalent in patients with DM, especially those with poor glycemic control who are more likely to suffer from HHS. Elevated triglyceride levels have independently been associated with higher mortality in certain conditions like coronary artery disease and acute pancreatitis. However, data on the effect of Hypertriglyceridemia (HTG) on mortality and morbidity in hospitalized patients with HHS is sparse. Objective: We wanted to compare the outcomes for HHS hospitalizations for patients with and without HTG. Methods: A retrospective cohort study was conducted using the Nationwide Inpatient Sample from 2016 and 2017. About 42 740 hospitalizations who had HHS as primary diagnosis were enrolled and further stratified based on the presence or absence of HTG as secondary diagnosis using ICD-10 codes. The primary outcome was inpatient mortality and secondary outcomes included length of hospital stay, total Hospital charges, Sepsis, Septic Shock, Acute Kidney Injury (AKI), and Acute Respiratory Failure (ARF). Multivariate regression analysis was done to adjust for confounders. Results: Out of the 42 740 hospitalizations with HHS, about 17 040 had HTG. The in-hospital mortality for patients with HHS was 305 overall, out of which 70 patients had HTG as secondary diagnosis. Compared with patients without HTG, patients with HTG had lower odds of in- hospital mortality (0.30, 95% CI 0.157–0.56, p<0.005) when adjusted for patient and hospital characteristics. Patients with HHS and HTG had decreased length of hospital stay, less total Hospital charges, lower odds of Sepsis and Septic Shock, but similar odds of AKI and ARF in comparison to patients without HTG. Conclusion: Our study shows that HTG is associated with lower odds of in-hospital mortality in patients with HHS, even though the odds of AKI and ARF was same in both groups. A similar inverse relationship has already been reported between TG levels and mortality in stroke patients. Though the mechanism of this effect is unclear, one possible explanation could be that patients with HTG are more likely to be treated with statins and fibrates which have known anti-inflammatory effects. Further studies are required to evaluate this possible positive prognostic effect of TG.

All-trans-retinoic acid as a possible cause of acute pancreatitis even in the absence of hypertriglyceridemia

The standard therapy for patients affected by acute promyelocytic leukemia (APL) is the administration of all-trans-retinoic acid (ATRA). ATRA therapy is usually well-tolerated, but it also has the potential to induce toxicity. The most severe side effect of ATRA is retinoic acid syndrome; the next is acute pancreatitis, which is a rare but serious adverse event mostly due to hypertriglyceridemia. We herein report a patient who developed ATRA-induced acute pancreatitis without hypertriglyceridemia. A 17-year-old female presented to our hospital complaining of a 3-week history of dyspnea. Her peripheral blood counts were: Hb: 4.5 g/dL, WBC: 0.96 9 10/L with 9% blasts, and platelets: 48 9 10/L. The biochemistry findings were significant only regarding the serum lactate dehydrogenase level of 276 IU/L. A bone marrow examination revealed an abnormal cellularity, thus indicating APL, while a cytogenetic study showed the presence of t(15;17) (q22;q21). The patient was treated with ATRA for the purpose of remission induction. On the second day of ATRA treatment, she suffered acute epigastric and upper left quadrant pain, and laboratory tests showed an elevation of amylase to 7,600 IU/L (normal range: 49–136 IU/L) and lipase to 1,680 IU/L (normal range: 11–53 IU/L), with no marked increases in triglyceride (TG). Computed tomography of the abdomen revealed no abnormal findings in either the biliary ducts or pancreas. With the cessation of ATRA, the symptoms rapidly disappeared and the pancreas-derived enzyme level thereafter decreased to the normal range. The peak level of TG was only 145 mg/dL (normal range: 30–149 mg/dL) throughout the entire course. The patient was then treated with arsenic trioxide therapy without experiencing any subsequent complications, and she has since remained in complete remission for 8 months after starting the induction treatment. Four cases of acute pancreatitis associated with the use of ATRA have been described [1–4], but only one of these presented without hypertriglyceridemia, which is one of the common side effects of ATRA [4, 5]. Our case is the second such case. The pathogenesis of ATRA-induced acute pancreatitis without hypertriglyceridemia is not clear. Cytokines, such as IL-8, IL-1beta, and TNF-alpha, have been shown to be intimately involved in the inflammatory response to acute pancreatitis in general [6]. Teng et al. suggested that the increased expression of these cytokines in APL cells induced by ATRA may also play a role in the pathogenesis of ATRA-induced acute pancreatitis [4, 7]. As far as the case of Teng et al. is concerned, however, this suggestion remains controversial because of the recurrence of an elevated lipase level with a second ATRA treatment even after achieving complete remission in his case. His case rather suggests that either allergic or autoimmune mechanisms might play critical roles in the development of ATRA-induced acute pancreatitis. On the other hand, the activation of pancreatic stellate cells (PSCs) is known to be implicated in the production of pancreatic fibrosis and associated with the loss of retinol-containing fat droplets, which are stored in quiescent PSCs. Recent studies have demonstrated that retinol and its ATRA metabolites induce quiescence in activated PSCs and decreased collagen synthesis [8]. Pancreatic fibrosis, which is the process of repair after pancreatic injury, is prevented by ATRA, and then proinflammatory cytokines might be upregulated and lead to ATRA-induced acute pancreatitis. T. Hoshino (&) N. Hatsumi S. Takada T. Sakura S. Miyawaki Leukemia Research Center, Saiseikai Maebashi Hospital, Kamishinden-machi, 564-1, Maebashi, Gunma 371-0821, Japan e-mail: takumihoshino4249@yahoo.co.jp

Mice deficient in mitochondrial glycerol-3-phosphate acyltransferase-1 have diminished myocardial triacylglycerol accumulation during lipogenic diet and altered phospholipid fatty acid composition

Glycerol-3-phosphate acyltransferase-1 (GPAT1), which is located on the outer mitochondrial membrane comprises up to 30% of total GPAT activity in the heart. It is one of at least four mammalian GPAT isoforms known to catalyze the initial, committed, and rate-limiting step of glycerolipid synthesis. Because excess triacylglycerol (TAG) accumulates in cardiomyocytes in obesity and type 2 diabetes, we determined whether lack of GPAT1 would alter the synthesis of heart TAG and phospholipids after a 2-week high-sucrose diet or a 3-month high-fat diet. Even in the absence of hypertriglyceridemia, TAG increased 2-fold with both diets in hearts from wildtype mice. In contrast, hearts from Gpat1 −/− mice contained 20–80% less TAG than the wildtype controls. In addition, hearts from Gpat1 −/− mice fed the high-sucrose diet incorporate 60% less [ 14C]palmitate into heart TAG as compared to wildtype mice. Because GPAT1 prefers 16:0-CoA to other long-chain acyl-CoA substrates, we determined the fatty acid composition of heart phospholipids. Compared to wildtype littermate controls, hearts from Gpat1 -/- −/− mice contained a lower amount of 16:0 in phosphatidylcholine, phosphatidylethanolamine, and phosphatidylserine/phosphatidylinositol and significantly more C20:4n6. Phosphatidylcholine and phosphatidylethanolamine from Gpat1 -/- −/− hearts also contained higher amounts of 18:0 and 18:1. Although at least three other GPAT isoforms are expressed in the heart, our data suggest that GPAT1 contributes significantly to cardiomyocyte TAG synthesis during lipogenic or high-fat diets and influences the incorporation of 20:4n6 into heart phospholipids.

Impact of lowering triglycerides on raising HDL-C in hypertriglyceridemic and non-hypertriglyceridemic subjects

Although an inverse association between triglyceride (TG) and (HDL-C) is well documented, the impact of lowering TG on HDL-C levels has not been well established. Therefore, data were analyzed in 151 consecutive dyslipidemic patients who made multiple visits ( n = 1830) to the University of Maryland Preventive Cardiology Center between 1991 and 2005. At baseline, fasting TG levels at or above the median (178 mg/dL) were associated with significantly lower HDL-C than TG levels below the median (32.6 ± 11.1 mg/dL versus 45.1 ± 14.2 mg/dL; P < 0.0001). Following baseline evaluation, various therapies were employed (i.e., dietary, exercise, medication) to reduce mean LDL (147.3 ± 53.4 mg/dL) and TG (306.1 ± 414.9 mg/dL). Using a fully adjusted mixed regression model, each 50 mg/dL reduction in TG was independently associated with a 0.5 mg/dL increase in HDL-C in hypertriglyceridemic subjects (e.g., TG ≥ 200 mg/dL) and a 1.7 mg/dL increase in HDL-C in the absence of elevated TG ( P < 0.0001). The use of niacin ( P < 0.0001), statins ( P = 0.0003) and fibrates ( P = 0.03) were also associated with significant increases in HDL-C beyond that anticipated with TG reduction. These data indicate that lowering TG is independently and inversely correlated with HDL-C, effects that are most pronounced in the absence of hypertriglyceridemia.

Low serum high‐density lipoprotein cholesterol in obese subjects with normal serum triglycerides: the role of insulin resistance and inflammatory cytokines

The cause of obesity-related low HDLc in the absence of hypertriglyceridemia is not known. A total of 32 subjects with a body mass index (BMI)(kg/m(2)) greater than 30 and normal serum triglycerides (<150 mg/dl) were identified. People with low HDLc (n = 16) compared to those with normal HDLc (n = 16) had higher BMI (37.53 +/- 4.54 vs. 33.99 +/- 3.65 kg/m(2), p < 0.021), higher body fat weight (42.59 +/- 9.51 vs. 34.76 +/- 8.7 kg, p < 0.023), and higher insulin resistance index (3.75 +/- 2.51 vs. 1.95 +/- 1.10, p < 0.013). Seven subjects with low HDLc and none of those with normal HDLc, had elevated serum tumor necrosis factor alpha and/or interleukin-6 (p < 0.010). Low HDLc levels can occur in obesity independently of elevated serum triglycerides and may be secondary to elevated serum levels of inflammatory cytokines.

Association of Pancreatitis with Administration of Contrast Medium and Intravenous Lipid Emulsion in a Patient with the Acquired Immunodeficiency Syndrome

Computed tomography is widely used to diagnose acute pancreatitis. Iodinated contrast medium lengthens the duration of pancreatitis and may increase the incidence of local or systemic complications. Total parenteral nutrition including IV lipid emulsion plays an important role in the management of patients with pancreatitis. Induction of pancreatitis by IV lipid emulsion is exceedingly rare. We report a 30-year-old patient with the acquired immunodeficiency syndrome in whom pancreatitis was exacerbated by oral and IV contrast medium and also by IV lipid emulsion in the absence of hypertriglyceridemia. Exclusion of the lipid emulsion resulted in prompt reduction of lipase levels on three separate occasions. This case is the first to implicate IV lipid emulsion in the exacerbation of pancreatitis in a patient with acquired immunodeficiency syndrome and normal baseline triglyceride levels. Thus, this case report suggests that we must exercise caution in the use of contrast medium and IV lipids in the diagnosis and management of acute pancreatitis.

Elevated hepatic lipase activity and low levels of high density lipoprotein in a normotriglyceridemic, nonobese Turkish population

Low levels of high density lipoprotein cholesterol (HDL-C) are associated with increased risk of coronary heart disease and, in the United States, are often associated with hypertriglyceridemia and obesity. In Turkey, low HDL-C levels are highly prevalent, 53% of men and 26% of women having HDL-C levels <35 mg/dl, in the absence of hypertriglyceridemia and obesity. In this study to investigate the cause of low HDL-C levels in Turks, various factors affecting HDL metabolism were assessed in normotriglyceridemic Turkish men and women living in Istanbul and in non-Turkish men and women living in San Francisco. Turkish men and women had significantly lower HDL-C levels than the San Francisco men and women, as well as markedly lower apolipoprotein A-I levels (25 and 39 mg/dl lower, respectively). In both Turkish and non-Turkish subjects, the mean body mass index was <27 kg/m2, the mean triglyceride level was <120 mg/dl, and the mean total cholesterol was 170–180 mg/dl. The mean hepatic triglyceride lipase activity was 21% and 31% higher in Turkish men and women, respectively, than in non-Turkish men and women, and remained higher even after subjects with a body mass index >50th percentile for men and women in the United States were excluded from the analysis. As no dietary or behavioral factors have been identified in the Turkish population that account for increased hepatic triglyceride lipase activity, the elevation most likely has a genetic basis. —Bersot, T. P., G. L. Vega, S. M. Grundy, K. E. Palaoğlu, P. Atagündüz, S. Özbayrakçi, O. Gökdemir, and R. W. Mahley. Elevated hepatic lipase activity and low levels of high density lipoprotein in a normotriglyceridemic, nonobese Turkish population. J. Lipid Res.40: 432–438.

Elevation of plasma lipid peroxides in non-insulin dependent diabetics with multiple lacunar infarcts.

Our purpose was to determine whether lipid peroxides are elevated in the plasma of patients with non-insulin dependent diabetes with multiple lacunar infarcts as detected by magnetic resonance imaging (MRI), and to confirm whether peroxide levels correlate with glycemic controls and blood lipid levels. The level of lipid peroxide (measured as thiobarbituric acid reactive substances (TBARS)) was measured in 23 healthy controls and 28 diabetics showing normal MRI findings and 22 diabetics with multiple lacunar infarcts. These groups were age-matched. In patients with multiple lacunar infarcts, systolic blood pressure, diastolic blood pressure and TBARS levels were significantly higher than in diabetics without such infarcts (p < 0.05). When the diabetic patients were divided into two groups according to the presence or absence of hypertriglyceridemia or hyperglycemia, in both groups plasma TBARS levels in patients with multiple lacunar infarcts were significantly higher than in patients without such infarcts. Multivariate analysis showed systolic blood pressure and plasma TBARS levels to be independent predictors of multiple lacunar infarcts. Among diabetics, total plasma TBARS levels were positively correlated with fasting blood glucose, HbA1c and triglyceride levels, but not with total cholesterol levels and age. In conclusion plasma lipid peroxides were elevated in diabetics with multiple lacunar lesions, and are related to the metabolic imbalance of plasma glucose and lipids.

Limitations of the Friedewald formula for estimating low-density lipoprotein cholesterol in alcoholics with liver disease

The accuracy of the Friedewald formula in estimating low-density lipoprotein (LDL) cholesterol was investigated in 47 alcoholic patients with liver disease (21 minimal-change, 26 cirrhotic) by comparing the results with those obtained by sequential preparative ultracentrifugation. In 14% of subjects with minimal-change disease, the error in the estimated LDL cholesterol was 50% +/- 9% (mean +/- SD; range 40-59%) and was related to the degree of attendant hypertriglyceridemia (r = 0.98; P < 0.001). A similar degree of error was observed in patients with cirrhosis, despite the absence of hypertriglyceridemia; an abnormal VLDL cholesterol: triglyceride ratio was the contributory factor in the discrepancy. We conclude that, as is the case in other clinical pathologies in which abnormalities of lipoprotein composition have been described (e.g., diabetes), the Friedewald formula to estimate LDL cholesterol may be inappropriate in chronic alcoholics, particularly those in whom a degree of hepatic dysfunction may be suspected.

Increased apo A-I and apo A-II fractional catabolic rate in patients with low high density lipoprotein-cholesterol levels with or without hypertriglyceridemia.

Low HDL-cholesterol (HDL-C) levels may elevate atherosclerosis risk, and often associate with hypertriglyceridemia (HTG); however, the metabolic causes of low HDL-C levels with or without HTG are poorly understood. We studied the turnover of radioiodinated HDL apolipoproteins, apo A-I and apo A-II, in 15 human subjects with low HDL-C, six with normal plasma TG levels (group 1) and nine with high TG (group 2), and compared them to 13 control subjects with normal HDL-C and TG levels (group 3). The fractional catabolic rate (FCR) was equally elevated in groups 1 and 2 vs. group 3 for both apo A-I (0.313 +/- 0.052 and 0.323 +/- 0.063 vs. 0.245 +/- 0.043 pools/d, P = 0.003) and apo A-II (0.213 +/- 0.036 and 0.239 +/- 0.037 vs. 0.185 +/- 0.031 pools/d, P = 0.006). Thus, high FCR characterized low HDL-C regardless of the presence or absence of HTG. In contrast, transport rate (TR) of apo A-I did not differ significantly among the groups and the apo A-II TR differed only between groups 2 and 3 (2.15 +/- 0.57, 2.50 +/- 0.39, and 1.83 +/- 0.48 mg/kg per d for groups 1 to 3, respectively, P = 0.016). Several HDL-related factors were similar in groups 1 and 2 but differed in group 3, as with FCR, including the ratio of lipoprotein lipase to hepatic lipase activity (LPL/HL) in post-heparin plasma, the ratio of the HDL-C to apo A-I plus apo A-II levels, and the percent of tracer in the d greater than 1.21 fraction. In linear regression analysis HDL-C levels correlated inversely with the FCR of apo A-I and apo A-II (r = -0.74, P less than 0.0001 for both). Major correlates of FCR were HDL-C/apo A-I + apo A-II, LPL/HL, and plasma TG levels. We hypothesize that lipase activity and plasma TG affect HDL composition which modulates FCR, which in turn regulates HDL-C. Thus, HTG is only one of several factors which may contribute to elevated FCR and low HDL-C. Given the relationship of altered HDL composition with high FCR and low HDL-C levels, factors affecting HDL composition may increase atherosclerosis susceptibility.

Accelerated turnover of very low density lipoprotein triglycerides in chronic alcohol users: A possible mechanism for the up-regulation of high density lipoprotein by ethanol

The concentration of high density lipoproteins (HDL) is related to the catabolism of triglyceride-rich lipoproteins. In order to elucidate the mechanisms by which alcohol increases plasma HDL levels we measured the turnover kinetics of very low density lipoprotein (VLDL) triglycerides in 10 alcoholic men without liver disease and in nonalcoholic control men matched for age, weight and plasma VLDL triglyceride level. The study was repeated in the alcoholics after a 2-week abstinence period. The alcoholic men had elevated HDL cholesterol but reduced low density lipoprotein (LDL) cholesterol as compared to the controls. The fractional catabolic rate and the total turnover (production) rate of VLDL triglycerides were both significantly increased ( P < 0.05) in the alcoholic men before abstinence. After withdrawal of alcohol both the synthetic rate and the catabolic rate of VLDL triglycerides returned to normal and the HDL (11131-2 and HDL 3) cholesterol fell. The percent decrease in HDL 2 cholesterol during abstinence was positively correlated to the respective fall of VLDL triglyceride fractional catabolic rate ( r= +0.51). The results suggest that the absence of hypertriglyceridemia and the elevated levels of HDL in regular alcohol users may be partly based on increased metabolic clearance of VLDL particles and on subsequent accelerated transfer of the VLDL surface components to HDL.