Elevated Serum Lipid Research Articles

HMG-COA REDUCTASE INHIBITORS SIGNIFICANTLY IMPROVE SURVIVAL IN CLINICAL LUNG TRANSPLANTATION, A RETROSPECTIVE ANALYSIS OF MORE THAN 500 PATIENTS

P647 Aims: 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) are known as effective lipid-lowering agents. Recently, increased survival times were demonstrated after transplantation (heart, kidney, liver) in patients, receiving statins and there is data suggesting a lipid lowering independent effect, as statins act as direct inhibitors of induction of MHC class-II expression and thus as indirect repressors of T-cell activation. We evaluated the effects of statins after lung transplantation through a retrospective analysis of 500 lung-allograft recipients, of whom77 received statins for excessive serum lipid levels. Methods: We performed a retrospective analysis of 502 recipients after lung transplantation (1988-2003). In order to allow for comparability of the patients receiving statins with those who did not, patients who died before the post operative day of first statin administration were excluded (n=77). 3 Patients had to be excluded from the statin group, due to missing clinical data. Statistical analysis included survival, as well as lung function analyses. BOS was defined by loss of FEV1, with BOS 0 = 80-100% of best FEV1, BOS 1 = 65-80% of best FEV1, BOS 2 = 50-65% of best FEV1 and BOS 3 = <50% of best FEV1. Results: Out of 502 patients undergoing lung transplantation between 1988 and 2003, 77 received pravastatin, 2 received lovastatin and 6 simvastatin for treatment of elevated serum lipid levels. Comparison of the two cohorts showed a significant increase in survival in the statin group (2435.31±1260.51 day vs.1595.10±1338.50 day, P<0.0001). Also, lung function was preserved at a significantly higher level in the group receiving statins (FVCBEST: 3809±1094.63ml vs 3509±1170.36ml, P<0.05; FEV1BEST: 2975±967.99ml vs 2695±1014.18ml, P<0.05). Conclusions: Pravastatin significantly improves long-term survival after lung transplantation in a retrospective analysis. Thus, we have added pravastatin to our standard immunosuppressive regimen. As the underlying mechanism is still unclear, we have initiated animal experiments to further analyze this question.

Acute Insulin Responses Following Exercise and Relationship to Lipid Changes

0153 The metabolic syndrome is associated with elevated serum lipids, insulin, and glucose concentrations. Frequent exercise is often prescribed as a method of reducing risk of developing both diabetes and hyperlipidemia; however, relatively little data exists documenting the acute response of insulin with respect to serum lipids following exercise. PURPOSE: To determine the response of fasted insulin and glucose concentrations following four days of exercise and to determine if this response was related to variables associated with serum lipid concentrations. METHODS: Participants (N = 15 males, mean ±sd age = 50±2 y, BMI = 31.9±1.2 kg/m2, %fat = 29±1, total cholesterol = 253±11 mg/dl, triglycerides = 266±38 mg/dl, HDL-C = 32±1 mg/dl) performed 350 kcal of treadmill exercise at ∼70%VO2peak on four consecutive days. Fasting insulin (μU/ml) and glucose (mM) concentrations, adjusted for plasma volume changes, were measured prior to each of the four exercise sessions and 24 h and 72 h following the fourth exercise session. RESULTS: As revealed by oneway repeated measures ANOVA, fasting insulin concentration was significantly (p<0.05) reduced by repeated days of exercise.Table: Means±sd. Same superscripts are not different (p<0.05).The change in insulin concentration from baseline to 24 h following four days of exercise was significantly (p<0.05) correlated with percent body fat (r = 0.64) and the previously reported (MSSE 33(5): No. 1211, p. S215, 2001) change (−30%) in triglyceride concentration (r = 0.31) and (MSSE 34(5): No. 113, p. S21, 2002) change (−5.1%) in hepatic lipase activity (r = 0.49). CONCLUSION: These data suggest that four consecutive days of exercise decrease fasting insulin concentrations. Furthermore, a reduction in post-exercise fasting insulin is associated with markers of lipid metabolism.

Incorporating clinical monitoring into electronic orders for antipsychotics.

Incorporating clinical monitoring into electronic orders for antipsychotics.

Lipid-lowering drug atorvastatin as an adjunct in the management of diabetic macular edema

Purpose To determine the efficacy of the lipid-lowering drug atorvastatin in reducing retinal hard exudates and subfoveal lipid migration after focal/grid laser photocoagulation in clinically significant macular edema in patients with diabetes with elevated serum lipids. Design Randomized case trial. Methods Thirty patients with type 2 diabetes with clinically significant macular edema, dyslipidemia, and hard exudates of grade 4 and above were assessed in an institutional setting. All patients were subjected to strict metabolic control within 4 to 6 weeks of enrollment. In addition, 15 patients in group A received atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A inhibitor; 15 members of group B did not receive any lipid-lowering therapy. All received laser photocoagulation after a metabolic control period and were followed up for a minimum of 18 weeks. The outcome measures were reduction in hard exudates, subfoveal lipid migration, status of macular edema, and visual acuity. Results The study included 21 men and nine women with noninsulin-dependent diabetes mellitus who could achieve good metabolic control within 4 to 6 weeks of inclusion in the study. All patients had elevated serum lipids at baseline. Ten (66.6%) of 15 patients in treatment group A and two (13.3%) of 15 patients in control group B showed reduction in hard exudates ( P = .007). None of the patients in group A and five (33.3%) of 15 in group B showed subfoveal lipid migration after laser photocoagulation ( P = .04). Regression of macular edema was seen in nine eyes in group A and five in group B ( P = .27). None of the eyes in group A and three eyes in group B showed worsening of visual acuity ( P = .22). Conclusion Oral atorvastatin therapy in patients with type 2 diabetes with dyslipidemia reduces the severity of hard exudates and subfoveal lipid migration in clinically significant macular edema and could be an important adjunct in the management of clinically significant macular edema.

Reduced atherosclerosis in MyD88-null mice links elevated serum cholesterol levels to activation of innate immunity signaling pathways.

Atherosclerosis, the leading cause of death in developed countries, has been linked to hypercholesterolemia for decades. More recently, atherosclerotic lesion progression has been shown to depend on persistent, chronic inflammation in the artery wall. Although several studies have implicated infectious agents in this process, the role of infection in atherosclerosis remains controversial. Because the involvement of monocytes and macrophages in the pathogenesis of atherosclerosis is well established, we investigated the possibility that macrophage innate immunity signaling pathways normally activated by pathogens might also be activated in response to hyperlipidemia. We examined atherosclerotic lesion development in uninfected, hyperlipidemic mice lacking expression of either lipopolysaccharide (LPS) receptor CD14 or myeloid differentiation protein-88 (MyD88), which transduces cell signaling events downstream of the Toll-like receptors (TLRs), as well as receptors for interleukin-1 (IL-1) and IL-18. Whereas the MyD88-deficient mice evinced a marked reduction in early atherosclerosis, mice deficient in CD14 had no decrease in early lesion development. Inactivation of the MyD88 pathway led to a reduction in atherosclerosis through a decrease in macrophage recruitment to the artery wall that was associated with reduced chemokine levels. These findings link elevated serum lipid levels to a proinflammatory signaling cascade that is also engaged by microbial pathogens.

Retrospective study of the efficacy of narrowband UVB and acitretin for the treatment of psoriasis

Background: In this retrospective analysis the effect of narrowband ultraviolet B treatment in combination with acitretin is reviewed in 40 patients with plaque psoriasis. Narrowband UVB is highly effective for plaque psoriasis, but requires multiple phototherapy treatments, making patient compliance problematic. Oral acitretin is moderately effective as monotherapy, but when combined with ultraviolet B or PUVA, its use has reduced the number of treatments required for clearing, and has resulted in clearing of patients otherwise refractory to these phototherapeutic modalities. There is only sparse data on the combination of acitretin with narrowband UVB. We therefore analyzed data on 40 patients treated with this combination. Results: The majority of patients treated had psoriasis that was refractory to treatment with broadband ultraviolet B, monotherapy with narrowband UVB, monotherapy with acitretin, or the combination of acitretin and broadband UVB. In this difficult-to-treat group of patients, the combination of low dose acitretin (25 mg po daily) and narrowband UVB 3 × per week resulted in greater than 75% improvement in 29 (72.5%) patients. Only 5 (12.5%) patients had less than 50% improvement. The combination was well tolerated and associated with typical retinoid and narrowband UVB side effects including elevation of serum lipids, burn and cheilitis. Conclusions: The combination of acitretin with narrowband UVB results in faster improvement even in more difficult-to-treat psoriasis patients. In combination the treatments appear to have synergistic effects. (J Dermatol Treat (2003) 14 (suppl 2): 17–20

Hyperlipidemia is a risk factor for lymphatic metastasis in superficial esophageal carcinoma

Although increased dietary fat or cholesterol has been reported to be a risk factor for the development of certain cancers, the effect of the serum lipid level on tumor metastasis has not been well documented. Fasting serum levels of total cholesterol (TC) and triglycerides (TG) were examined in 54 patients with superficial esophageal cancer (SEC) invading lamia musucularis or submucosal layer who underwent esophagectomy with classical lymphadenectomy. The association between lymph node metastasis and the preoperative serum lipid levels as well as the pathological findings was retrospectively analyzed. The levels of TC and TG were significantly higher in 18 node-positive than in 36 node-negative patients (TC: 205.4±38.9 vs. 174.5±26.8 mg/dl, P<0.01; TG: 152.0±68.5 vs. 88.7±28.6 mg/dl, P<0.001). Patients with hypercholesterolemia (TC≧220 mg/dl) and hypertriglyceridemia (TG≧150 mg/dl) showed extremely high rates of nodal metastasis (80 and 91%, respectively), that were significantly higher than those of patients with normal lipid levels ( P<0.01 and P<0.001). When hyperlipidemia was defined as the presence of either hypertriglyceridemia or hypercholesterolemia, hyperlipidemia was an independent risk factor for nodal metastasis in SEC. Elevated serum lipid levels might bring favorable circumstances for the development of lymph node metastasis in the early stage of EC. Hyperlipidemia might prompt us to perform more studies to investigate possible metastasis.

Elevated Serum Lipids and Periodontal Disease

Elevated Serum Lipids and Periodontal Disease

Histopathology and regression of retinal hard exudates in diabetic retinopathy after reduction of elevated serum lipid levels

Purpose To describe a regression of retinal hard exudates in 2 patients with diabetic maculopathy, and to report immunohistologic findings reflecting lipid deposition in the retina. Design Two interventional case reports. Methods Two patients with exudative diabetic maculopathy were treated to normalize serum lipids. Histologic examination and immunohistochemistry of each patient's eyes were performed to assess the localization of apolipoprotein B and cholesteryl ester, both of which are principal components of low-density lipoprotein. Results Both patients showed a dramatic regression of retinal hard exudates after correction of dyslipidemia. Histopathology revealed diffuse lipids and cholesteryl ester in the retina. Apolipoprotein B and macrophages were colocalized in the perivascular space. Conclusions The regression of hard exudates was most likely due to the aggressive lipid lowering in both patients. The novel histopathologic findings of hard exudate and diabetic maculopathy are similar to the pathologic changes observed in larger atherosclerotic lesions, except that they occur in the intraretinal perivascular space.

Leptin-resistant obese mice do not form biliary crystals on a high cholesterol diet

Introduction: Human obesity is associated with leptin resistance, elevated serum lipids, hepatic steatosis, and cholesterol gallstone formation. We have previously demonstrated that leptin-resistant (Lepdb) obese mice fed a low cholesterol diet have enlarged gallbladders, but a decreased cholesterol saturation index, despite marked hepatic steatosis and elevated serum cholesterol. However, obese humans typically consume a high cholesterol diet and are prone to form gallstones. Therefore, we tested the hypothesis that on a high cholesterol diet, leptin-resistant obese mice would have large gallbladders, cholesterol saturated bile, and would readily form biliary crystals. Methods: Eight week old female lean control (C57BL/6J, n = 70) and leptin-resistant (Lepdb, n = 72) mice were fed a 1% cholesterol diet for four weeks. At 12 weeks, all animals were fasted overnight and underwent cholecystectomies. Gallbladder volume (μl) was measured and grouped into 7 lean control and 12 Lepdb pools for determination of cholesterol saturation index (CSI). Bile was examined for cholesterol crystals under polarized light microscopy (#/hpf). Serum cholesterol (mg/dl) and leptin levels (ng/ml) also were measured. Results were analyzed using the Student’s t-test. TABLE—ABSTRACT P57GB volCSICrystalsSerum XOLLeptinLean19.1 ± 0.91.15 ± .102.2 ± 0.5131 ± 76 ± 0Lepdb35.8 ± 2.2∗0.91 ± .10†0.0 ± 0.0∗278 ± 10∗229 ± 8∗∗P < 0.001.†P < 0.03 vs C57b lean controls.Conclusions: These data suggest that leptin-resistant obese mice fed a high cholesterol diet have 1) increased gallbladder volume, 2) decreased biliary cholesterol saturation and crystal formation despite 3) elevated serum cholesterol compared to lean control mice. Therefore, we conclude that the link among obesity, diet, and gallstone formation does not require hypersecretion of biliary cholesterol and may be related to gallbladder stasis.

Leptin-resistant obese mice have paradoxically low biliary cholesterol saturation

Background. Human obesity is associated with leptin resistance, elevated serum glucose and lipids, hepatic steatosis, and cholesterol gallstone formation. These gallstones are thought to result from hypersecretion of biliary cholesterol as well as biliary stasis. Leptin-resistant Lepdb obese mice, which are known to have elevated serum leptin, glucose, and lipids, as well as hepatic steatosis, should be an appropriate model for human gallstone formation. Therefore, we tested the hypothesis that leptin-resistant mice would have increased gallbladder volume, biliary cholesterol saturation, and cholesterol crystal formation. Methods. Sixty lean control mice and 60 Lepdb obese mice on a low cholesterol chow diet were studied. Gallbladder volumes were measured and bile was pooled to calculate cholesterol saturation index. Serum cholesterol, glucose, and leptin levels were determined from pooled serum. Hepatic fat vacuoles were counted. Bile from a second group of 90 lean control and 59 obese mice was observed microscopically for cholesterol crystal formation. Results. Leptin-resistant obese mice have significantly higher serum cholesterol, glucose, and leptin levels, hepatic fat vacuoles, and gallbladder volume than lean control mice. However, biliary cholesterol saturation index and cholesterol crystal formation were significantly diminished in the obese mice. Conclusions. These data suggest that leptin-resistant Lepdb obese mice have (1) increased gallbladder volume, (2) decreased biliary cholesterol saturation despite elevated serum cholesterol and hepatic steatosis, and (3) decreased in vitro cholesterol crystal formation. We conclude that the link between obesity and gallstone formation does not require hypersecretion of biliary cholesterol. (Surgery 2003;134:372-7.)

Polyphenols of Melaleuca quinquenervia leaves--pharmacological studies of grandinin.

Four polyphenolic acid derivatives and three ellagitannins were isolated from the leaves of Melaleuca quinquenervia (Clav.) S. T. Blake for the first time. Their structures were elucidated as gallic acid (1), ellagic acid (2), 3-O-methylellagic acid (3), 3,4,3'-tri-O-methylellagic acid (4), 2,3-O-hexahydroxydiphenoyl-(alpha/beta)-D-(4)C(1)-glucopyranose (5), castalin (6) and grandinin (7) on the basis of chemical, mass spectrometric (-ve ESI-MS) and spectroscopic (UV, (1)H-, (13)C NMR, (1)H,(1)H-, (1)H,(13)C-COSY, (1)H,(1)H-TOCSY and HMBC) analyses. Grandinin (the major compound) showed radical scavenging properties by its reaction with 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical [EC(50) = 4.3 +/- 0.3 micro g mL(-1)]. It was found to be relatively nontoxic in mice [LD(50) = 316 mg Kg(-1) b.wt.]. It exhibited a significant dose-dependent (35-70 mg Kg(-1)) hypoglycemic effect by significantly reducing blood glucose level in basal condition and after heavy glucose load in normal mice. Moreover, it reduced the elevated blood glucose level in STZ-induced diabetic mice. In addition, grandinin reduced the elevated blood urea nitrogen and serum lipid peroxides in STZ-induced diabetic mice.

Endothelium-dependent effects of statins.

The vascular endothelium is a dynamic endocrine organ that regulates contractile, secretory, and mitogenic activities in the vessel wall and hemostatic processes within the vascular lumen. Risk factors for cardiovascular disease, such as cigarette smoking, hypertension, and elevated serum lipid levels, impair endothelial function and lead to the development of atherosclerotic vessels. Recent studies suggest that statins reduce cardiovascular events in part by improving endothelial function. Statins reduce plasma cholesterol levels, thereby decreasing the uptake of modified lipoproteins by vascular wall cells. There is increasing evidence, however, that statins may also exert effects beyond cholesterol lowering. Indeed, many of these cholesterol-independent or "pleiotropic" vascular effects of statins appear to involve restoring or improving endothelial function through increasing the bioavailability of nitric oxide, promoting re-endothelialization, reducing oxidative stress, and inhibiting inflammatory responses. Thus, the endothelium-dependent effects of statins are thought to contribute to many of the beneficial effects of statin therapy in cardiovascular disease.

Retrospective study of the efficacy of narrowband UVB and acitretin

background: In this retrospective analysis the effect of narrowband ultraviolet B treatment in combination with acitretin is reviewed in 40 patients with plaque psoriasis. Narrowband UVB is highly effective for plaque psoriasis, but requires multiple phototherapy treatments, making patient compliance problematic. Oral acitretin is moderately effective as monotherapy, but when combined with ultraviolet B or PUVA, its use has reduced the number of treatments required for clearing, and has resulted in clearing of patients otherwise refractory to these phototherapeutic modalities. There is only sparse data on the combination of acitretin with narrowband UVB. We therefore analyzed data on 40 patients treated with this combination.results: The majority of patients treated had psoriasis that was refractory to treatment with broadband ultraviolet B, monotherapy with narrowband UVB, monotherapy with acitretin, or the combination of acitretin and broadband UVB. In this difficult‐to‐treat group of patients, the combination of low dose acitretin (25 mg po daily) and narrowband UVB three times per week resulted in greater than 75% improvement in 29 (72.5%) patients. Only 5 (12.5%) patients had less than 50% improvement. The combination was well tolerated and associated with typical retinoid and narrowband UVB side effects including elevation of serum lipids, burn and cheilitis.conclusion: The combination of acitretin with narrowband UVB results in faster improvement even in more difficult‐to‐treat patients. In combination the treatments appear to have synergistic effects.

STATIN THERAPY: RATIONALE FOR A NEW AGENT, ROSUVASTATIN

SUMMARYCardiovascular disease (CVD) remains a major cause of death in industrialised societies, and elevated serum lipids are a significant, highly prevalent and undertreated risk factor for this condition. The 3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase inhibitors (statins) have revolutionised the treatment of hyperlipidaemia, and results from large‐scale, long‐term clinical trials have shown that the substantial reductions in low‐density lipoprotein cholesterol (LDL‐C) achieved with these drugs are associated with dramatic decreases in cardiovascular risk. Results from recent comparative clinical trials that have included a new drug in this class, rosuvastatin (Crestor®), have demonstrated that it is significantly superior to atorvastatin, pravastatin and simvastatin in reducing total cholesterol, LDL‐C and apolipoprotein B (Apo B). It is also significantly more effective than atorvastatin in increasing high‐density lipoprotein cholesterol (HDL‐C) and apolipoprotein A‐I (Apo A‐I). Rosuvastatin was also superior to all these agents in helping patients meet European Atherosclerosis Society (EAS) and National Cholesterol Education Programme (NCEP) goals for LDL‐C. The results of an increasing number of studies indicate that statins have a wide range of pleiotropic properties that almost certainly contribute to their ability to decrease cardiovascular risk and may also make them valuable for treatment of other diseases. These actions include plaque stabilisation, improvement of endothelial function, inhibition of smooth muscle cell proliferation and migration, reduction of expression of adhesion molecules, prevention of cholesterol esterification and accumulation, reduction of secretion of matrix metalloproteinases by macrophages, reduction of platelet activity, reduction of formation of thrombogenic factors, chemoprotection and induction of bone morphogenic protein‐2 (BMP‐2). Further exploration of these actions will provide key information about class effects and properties of specific members of this highly useful group of drugs.

Recognizing Heart Disease: Helping Women Seek Treatment Faster

Despite the great advances in treating coronary heart disease (CHD) and increasing survival rates, heart disease remains the #1 killer of women. But women who experience myocardial infarction (MI) may not have the same presenting symptoms as men, even though they share many of the same risk factors for CHD, such as obesity, elevated serum lipid level and sedentary life‐styles. Therefore, it's critical that health care providers understand, recognize and identify the unique manifestations of CHD and MI in women as an important first step in decreasing the morbidity and mortality associated with these health complications. Here's how to help women get into treatment faster.

Systemic considerations in the management of diabetic retinopathy

PURPOSE: To highlight the systemic factors which affect onset and/or progression of diabetic retinopathy (DR) and to emphasize the role and responsibilities of ophthalmologists and other eye care providers to ensure that appropriate systemic medical evaluation of the patient with diabetes is being pursued. DESIGN: Literature review of publications relevant to diabetic retinopathy, blood glucose control, diabetes mellitus type, hypertension, renal disease, elevated serum lipids, exercise, pregnancy, anticoagulation, thrombolysis, smoking, anemia and antioxidant ingestion. FINDINGS: Intensive blood glucose control and control of systemic hypertension reduce the risk of new onset DR and slow the progression of existing DR. Severe DR may be an indicator of renal disease while severe renal disease and its treatment can affect the progression of DR. Elevated serum lipids are associated with macular exudate and moderate visual loss. Certain types of excessive exercise in patients with advanced stages of retinopathy may aggravate vitreous hemorrhage. During pregnancy, DR should be monitored closely as transient progression of DR can occur. Therapeutic anticoagulation and thrombolysis are not contraindicated at any stage of DR. Anemia can result in progression of DR, smoking in general should be discouraged, and the role of antioxidant therapy requires further study. CONCLUSIONS: Blindness from diabetic retinopathy is now largely preventable with timely detection and appropriate interventional therapy. Routine, repetitive, lifelong, expert clinical retinal examination is essential for the fundamental ophthalmic care of the patient with diabetes. However, diabetes mellitus is a systemic disease and thus optimal ophthalmic care must include diligent evaluation and treatment of concomitant systemic disorders that influence the development, progression and ultimate outcome of diabetic retinopathy. Optimization of these systemic considerations through an intensive, multi-disciplinary, healthcare team-based approach will maximize the ophthalmic and general health of these patients. Ophthalmologists and other eye care providers are critical members of this team with unique responsibilities to ensure that appropriate systemic medical evaluation is being pursued.

Suppressive Effects of Thyroxine on Glucocorticoid (GC)-induced Metabolic Changes and Cataract Formation on Developing Chick Embryos

To prevent cataracts induced by glucocorticoids (GC) as a systemic disease, the suppression of oxidative stress caused by GC in the hepatic metabolism is of significant interest. In this study, to elucidate the formative mechanism of GC-induced cataracts, we examined the preventive effect and then analysed the mechanisms of thyroxine on GC-induced cataract formation. Fifteen day old chick embryos were administered with 0.25μ mol hydrocortisone succinate sodium (HC), and then 12–30nmol of thyroxine 4hr after HC administration. At the indicated time after HC treatment, we examined the incidence of cataract formation, the levels of serum glucose and lipids, lenticular and hepatic glutathione (GSH), and lipid peroxide (LPO) in the lens, blood and liver. Almost all lenses (96%) removed 48hr after HC administration were opaque. Thyroxine prevented HC-induced cataract formation effectively, and suppressed the elevations of serum glucose and LPO in the lens, blood and liver. The treatment prevented the decreased lenticular GSH level at 48hr, but the hepatic GSH level at 24hr remained lowered in contrast to the results of previous studies using insulin. Moreover, thyroxine did not decrease the elevated serum lipid level (triglyceride and non-esterified fatty acid) caused by HC. Under thyroxine treatment, in constant to insulin, acceleration of GSH-GSSG cycle rather than GSH de novo synthesis keeps a certain level of hepatic GSH necessary for diminishing the elevation of LPO as a risk factor of GC-induced cataract formation. The regulation of metabolic changes ensured the maintenance of hepatic GSH level, which is necessary to reduce oxidative stress produced by GC and to protect the lens from oxidative stress leading to opacification.

Maternal Serum Triglyceride at 24–32 Weeks' Gestation and Newborn Weight in Nondiabetic Women With Positive Diabetic Screens

In Brief Objective To determine whether elevated midpregnancy maternal serum lipid levels predict newborn weight at term and the risk of large for gestational age (LGA) infants in women with positive diabetic screen but normal glucose tolerance test. Methods Japanese gravidas who had positive diabetic screens and normal 75-g oral glucose tolerance tests (GTT) at 24–32 weeks were enrolled. Subjects with complications, including diabetes, hypertension, or fetal anomalies were excluded, as were women with multifetal gestations. Fasting serum triglyceride, free fatty acids, and total cholesterol levels were measured at the time of GTT. We tested the association between maternal variables and birth weight by univariable analysis. We used multivariable analysis to test whether the association between fasting lipids and birth weight was independent of prepregnant maternal body mass index (BMI), maternal weight gain during pregnancy, and plasma glucose levels at GTT. We also used multiple logistic regression analysis to determine whether maternal hyperlipidemia, defined as more than the 75th percentile of each lipid, is a risk factor for having an LGA infant. Results We enrolled 146 subjects. Among measured maternal lipids, only triglyceride levels correlated with birth weight in univariable analysis (r = 0.22, P = .009). Birth weight also was correlated with prepregnant maternal BMI (r = 0.18, P = .04) and fasting plasma glucose levels (r = 0.17, P = .04). The association between maternal fasting triglyceride level and birth weight remained significant after adjusting for prepregnant BMI, maternal weight gain, fasting plasma glucose levels, fetal gender, and gestational age at birth (P = .01). Logistic regression analysis showed that fasting maternal hypertriglyceridemia (over 259 mg/dL) was the significant predictor of LGA infants, independent of prepregnant BMI, maternal weight gain, and maternal plasma glucose levels (odds ratio 11.6; 95% confidence interval 1.1, 122; P = .04). Conclusion In women with positive diabetic screens but normal GTTs, fasting triglyceride levels at 24–32 weeks correlated positively with newborn weight at term, independent of maternal plasma glucose levels and obesity. Maternal fasting serum triglyceride levels in midpregnancy might be an independent predictor of fetal macrosomia in those women. Elevated fasting serum triglyceride levels in midpregnancy were positively associated with newborn weight in nondiabetic women with positive diabetic screen, independent of maternal glucose levels and obesity.

Maternal serum triglyceride at 24–32 weeks’ gestation and newborn weight in nondiabetic women with positive diabetic screens

Objective: To determine whether elevated midpregnancy maternal serum lipid levels predict newborn weight at term and the risk of large for gestational age (LGA) infants in women with positive diabetic screen but normal glucose tolerance test. Methods: Japanese gravidas who had positive diabetic screens and normal 75-g oral glucose tolerance tests (GTT) at 24–32 weeks were enrolled. Subjects with complications, including diabetes, hypertension, or fetal anomalies were excluded, as were women with multifetal gestations. Fasting serum triglyceride, free fatty acids, and total cholesterol levels were measured at the time of GTT. We tested the association between maternal variables and birth weight by univariable analysis. We used multivariable analysis to test whether the association between fasting lipids and birth weight was independent of prepregnant maternal body mass index (BMI), maternal weight gain during pregnancy, and plasma glucose levels at GTT. We also used multiple logistic regression analysis to determine whether maternal hyperlipidemia, defined as more than the 75th percentile of each lipid, is a risk factor for having an LGA infant. Results: We enrolled 146 subjects. Among measured maternal lipids, only triglyceride levels correlated with birth weight in univariable analysis ( r = 0.22, P = .009). Birth weight also was correlated with prepregnant maternal BMI ( r = 0.18, P = .04) and fasting plasma glucose levels ( r = 0.17, P = .04). The association between maternal fasting triglyceride level and birth weight remained significant after adjusting for prepregnant BMI, maternal weight gain, fasting plasma glucose levels, fetal gender, and gestational age at birth ( P = .01). Logistic regression analysis showed that fasting maternal hypertriglyceridemia (over 259 mg/dL) was the significant predictor of LGA infants, independent of prepregnant BMI, maternal weight gain, and maternal plasma glucose levels (odds ratio 11.6; 95% confidence interval 1.1, 122; P = .04). Conclusion: In women with positive diabetic screens but normal GTTs, fasting triglyceride levels at 24–32 weeks correlated positively with newborn weight at term, independent of maternal plasma glucose levels and obesity. Maternal fasting serum triglyceride levels in midpregnancy might be an independent predictor of fetal macrosomia in those women.