Biomedical subjects

R H Knopp

Publications and source records attributed to R H Knopp.

At least 19 recordsLinked to original sources

PubMed1992

Protein transfer between A-I-containing lipoprotein subpopulations: evidence of non-transferable A-I in particles with A-II.

Transfer of apolipoproteins (apo) between the two subpopulations of apo A-I-containing lipoproteins in human plasma: those with A-II [Lp(AI w AII)] and those without [Lp(AI w/o AII)], were studied by observing the transfer of 125I-apo from a radiolabeled subpopulation to an unlabeled subpopulation in vitro. When Lp(AI w AII) was directly radioiodinated, 50.3 +/- 7.4 and 19.5 +/- 7.7% (n = 6) of the total radioactivity was associated with A-I and A-II, respectively. In radioiodinated Lp(AI w/o AII), 71.5 +/- 6.8% (n = 6) of the total radioactivity was A-I-associated. Time-course studies showed that, while some radiolabeled proteins transferred from one population of HDL particles to another within minutes, at least several hours were necessary for transfer to approach equilibrium. Incubation of the subpopulations at equal A-I mass resulted in the transfer of 51.8 +/- 5.0% (n = 4) of total radioactivity from [125I]Lp(AI w/o AII) to Lp(AI w AII) at 37 degrees C in 24 h. The specific activity (S.A.) of A-I in the two subpopulations after incubation was nearly identical. Under similar incubation conditions, only 13.4 +/- 4.6% (n = 4) of total radioactivity was transferred from [125I]Lp(AI w AII) to Lp(AI w/o AII). The S.A. of A-I after incubation was 2-fold higher in particles with A-II than in particles without A-II. These phenomena were also observed with iodinated high-density lipoproteins (HDL) isolated by ultracentrifugation and subsequently subfractionated by immunoaffinity chromatography. However, when Lp(AI w AII) radiolabeled by in vitro exchange with free [125I]A-I was incubated with unlabeled Lp(AI w/o AII), the S.A. of A-I in particles with and without A-II differed by only 18% after incubation. These data are consistent with the following: (1) in both populations of HDL particles, some radiolabeled proteins transferred rapidly (minutes or less), while others transferred slowly (hours); (2) when Lp(AI w AII) and Lp(AI w/o AII) were directly iodinated, all labeled A-I in particles without A-II were transferable, but some labeled AI in particles with A-II were not; (3) when Lp(AI w AII) were labeled by in vitro exchange with [125I]A-I, considerably more labeled A-I were transferable. These observations suggest the presence of non-transferable A-I in Lp(AI w AII).

Adult↗

PubMed1992

Physiologic testosterone levels in normal men suppress high-density lipoprotein cholesterol levels.

OBJECTIVE: To investigate the role of physiologic levels of testosterone in the control of lipoproteins in healthy men. DESIGN: A double-blind, randomized study. SETTING: A university community. PARTICIPANTS: Fifteen healthy men, ages 20 to 36 years. INTERVENTION: We induced acute, reversible hypogonadism in five normal men by administering daily subcutaneous injections of the gonadotropin-releasing-hormone (GnRH) antagonist, Nal-Glu, for 6 weeks. Another group of five normal men received Nal-Glu plus weekly injections of testosterone enanthate, 100 mg/wk, thereby maintaining normal serum testosterone levels. Five additional men received placebo injections. MEASUREMENTS: Plasma lipids, including high-density lipoprotein (HDL) subfractions HDL2 and HDL3, apoprotein A1, and serum levels of gonadotropins, estradiol, and testosterone were measured before, during, and after treatment. RESULTS: At the end of the treatment period, HDL cholesterol levels in men receiving Nal-Glu increased by 26% (95% CI, 18% to 34%; P less than 0.05). Levels of HDL2, HDL3, and apoprotein A1 increased by 63% (CI, 16% to 110%), 17% (CI, 3% to 31%), and 17% (CI, 5% to 29%), respectively (P less than 0.05 for each parameter). Total cholesterol increased by 12% (CI, 2% to 22%). Low-density lipoprotein (LDL) cholesterol and triglyceride concentrations did not change. No statistically significant changes occurred in any lipid measurement in men receiving Nal-Glu plus androgen replacement or placebo (P greater than 0.05). CONCLUSIONS: Experimental hypogonadism induced by administration of a GnRH antagonist results in a statistically significant increase in HDL cholesterol, including HDL2 and HDL3. These effects are most likely due to decreased androgen levels because they are reversed by administration of antagonist together with testosterone. Our results imply that androgen levels in the normal adult male range have a suppressive effect on HDL cholesterol concentration and may contribute to the increased risk for coronary artery disease in men.

Adult↗

PubMed1992

The Diabetes in Early Pregnancy Study: changes in cholesterol, triglycerides, body weight, and blood pressure. The National Institute of Child Health and Human Development--the Diabetes in Early Pregnancy Study.

This study examined changes in cholesterol, triglycerides, body weight, and blood pressure during pregnancy in 312 diabetic and 356 control women recruited within 21 days after conception. Cholesterol values rose in both groups but were significantly lower in diabetic women at each time point (166 vs 178 mg/dl at week 12, p = 0.0004). Triglyceride values also rose in both groups. Triglyceride levels did not differ between groups up to week 8 of gestation, but by weeks 10 to 12 they were significantly lower in diabetic women than in controls (75 vs 89 mg/dl at week 12, p = 0.0004). Although they were no heavier at entry, diabetic women gained significantly more weight between weeks 6 and 8 (p less than 0.001), resulting in a mean difference between groups of 1 kg. Systolic blood pressure increased steadily and significantly in the diabetic but not the control women (115.8 +/- 16.2 SD vs 109.3 +/- 11.8 mm Hg, p = 0.0006 at term). Diastolic blood pressure was higher in diabetic women on entry (70.7 vs 67.3 mm Hg, p = 0.0006) and throughout gestation. Significant correlations were found in the diabetic group between maternal blood pressure and lipids and infant birth weight. These newly found differences in cholesterol and triglyceride levels, weight gain, and blood pressure between type I diabetic and control women during gestation may have long-term cardiovascular implications.

Adult↗

PubMed1992

Double-blind comparison of bezafibrate versus placebo in male volunteers with hyperlipoproteinemia.

The efficacy and safety of bezafibrate were evaluated in 83 patients with type IIa, IIb, or IV hyperlipoproteinemia. Following a 12- to 14-week placebo period on a coronary-prudent diet (Period 1), patients were assigned randomly to receive either bezafibrate 600 mg/day or placebo, plus diet in a double-blind, 12-week treatment period (Period 2). The return of lipid and lipoprotein levels toward baseline was evaluated in a subsequent 8-week period on placebo plus diet (Period 3). In patients with type IIa hyperlipoproteinemia, bezafibrate significantly lowered total (14.6%, P less than 0.001) and LDL-cholesterol (16.4%, P less than 0.001) and total (29.9%, P less than 0.001) and VLDL-triglyceride (44.0%, P less than 0.001) and significantly increased HDL cholesterol (9.5%, P less than 0.001). In patients with type IIb, bezafibrate had a qualitatively similar effect to that seen in type IIa on each of these lipoproteins, but the sample size was too small for statistical evaluation. In patients with type IV, bezafibrate lowered total (48.3%, P less than 0.01) and VLDL-triglyceride (57.7%, P less than 0.001) and VLDL-cholesterol (56.8%, P less than 0.001) and increased HDL-cholesterol (16.6%, P less than 0.05). All values returned toward baseline during Period 3. Only two bezafibrate patients experienced adverse events that were considered definitely treatment related; one was dropped from the study because of elevations in SGOT and SGPT, 1.5- and 4-times the upper limit of normal, respectively. For other laboratory parameters, trends upward or downward were small and of doubtful clinical significance. Bezafibrate appears to be effective and safe for modifying lipid and lipoprotein levels in patients with types IIa, IIb and IV hyperlipoproteinemia.

Adolescent↗

PubMed1992

Metabolism of very-low-density lipoprotein triglyceride by human placental cells: the role of lipoprotein lipase.

Several studies have shown lipoprotein lipase (LPL) activity in human placenta, but the quantitative significance and cellular specificity of LPL in this organ are unknown. The objective of this report is to investigate the metabolism of very-low-density lipoprotein triglycerides (VLDL-TG) by the placenta, the role of LPL in this process, and the types of cells involved. Placental cells were obtained by enzymatic digestion (collagenase, hyaluronidase, and DNA-ase) and separated on a 40% Percoll gradient. The trophoblasts were the predominant cell type (80% to 85% pure) isolated at d = 1.033 to 1.048 and macrophages were predominant at d = 1.077 to 1.100 (greater than 95% pure), as characterized by eight immunocytochemical assays using cell protein-specific monoclonal antibodies. Macrophages represented 50% to 60% of cells isolated, and trophoblasts, 40% to 50%. LPL activity was assessed by VLDL-TG hydrolysis in primary 3- to 4-day tissue culture. In a representative experiment, LPL activity (nmol fatty acids (FA)/mg protein/24 h) was 101.3 +/- 5.3 in macrophages and 29.9 +/- 6.5 in the predominant trophoblast cell types, with approximately 20% of these amounts incorporated and reesterified. VLDL-TG hydrolysis and cell lipid uptake in both placental cell types was essentially abolished by a monoclonal anti-LPL antibody. When compared with a model of hepatocytes (Hep G2 cells), the hydrolysis of VLDL-TG was almost undetectable in these cells. In contrast, free fatty acids (FFA) uptake by Hep G2 cells was fourfold to sixfold greater than that by macrophages and trophoblasts, respectively. In conclusion, macrophages and trophoblasts are the two predominant placental cells isolated by enzymatic digestion.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗

PubMed1992

Prediction of infant birth weight by GDM screening tests. Importance of plasma triglyceride.

OBJECTIVE: We measured plasma glucose, GHb, GPro, IRI and TG at 24-28-wk gestation to determine the extent of elevations in GDM and relationships to glucose intolerance and infant macrosomia. RESEARCH DESIGN AND METHODS: Plasma samples were obtained 1 h after ingestion of 50 g glucose after an overnight fast in 521 randomly selected negative screenees, 264 positive screenees with GTT-, and 96 positive screenees with GTT+ (GDM). RESULTS: Screening test values in GDM subjects exceeded the GTT- group, whose values exceeded those of negative screenees: glucose, 9.6*, 8.7*, 6.3 mM; GHb, 5.2*, 4.9*, 4.7%; GPro, 3.1*, 3.0*, 2.8%; IRI, 791*, 662*, 410 pM; and TG, 2.3*, 1.9, 1.9 mM, (*P < 0.005 vs. negative screenees). TG was the only test elevated in the GDM but not in the GTT- groups. Screening test values correlated with GTT values in the following order (strongest to weakest): glucose* > TG* > GHb* > IRI > GPro (*statistical significance). Plasma TG was the only screening test significantly associated with birth weight corrected for gestational age (birth-weight ratio) (r = 0.09-0.16) (P < 0.05 to < 0.01) and was of the same order as 1- and 2-h GTT associations with birth weight (r = 0.13 and 0.14, respectively) (P < 0.05 to < 0.01). Plots of TG/birth-weight ratio increased linearly to the 80-90th TG percentile in negative screenees and GTT- subjects. GDM subjects followed this trend but with more variation. Above the 90th percentile for TGs, birth-weight ratio trended lower, significantly so when the groups were combined (P < 0.05). In multivariate analysis, TG was associated with birth-weight ratio even when maternal prepregnancy weight and pregnancy weight gain associations with TG and birth-weight ratio were controlled (P < 0.019). CONCLUSIONS: Of the five screening tests evaluated, all were elevated in GDM, but TG is the best discriminator of GDM from the GTT- group, and it is the only test significantly related to birth-weight ratio--and to glucose intolerance besides glucose itself. The TG association with birth weight is not explained fully by maternal weight. The results suggest that plasma TG may be a physiological contributor to infant birth weight. Further evaluation of plasma TG in GDM screening is justified, but GHb, GPro, and IRI appear to hold less promise.

Analysis of Variance↗

PubMed1992

Early sonographic evaluation for fetal growth delay and congenital malformations in pregnancies complicated by insulin-requiring diabetes. National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study.

OBJECTIVE: It has been reported that early fetal growth retardation may be a useful marker for congenital malformations in diabetic pregnancies. To test this hypothesis, diabetic and nondiabetic women were sonographically evaluated during the first trimester. RESEARCH DESIGN AND METHODS: Fetal crown-rump lengths were measured sonographically at least once during the first 15 wk of pregnancy in 329 nondiabetic and 312 diabetic women. Of these, 289 nondiabetic and 269 diabetic women had sonograms before 10 wk of gestation and 283 nondiabetic and 269 diabetic women had sonograms between 10 and 15 wk of gestation. Early fetal growth delay was defined as a sonographic gestational age of greater than or equal to 6 days less than menstrual gestational age. RESULTS: The mean crown-rump lengths at 8 wk were 17.9 +/- 4.6 mm in the diabetic and 18.7 +/- 4.9 mm in the nondiabetic groups (P = 0.13). At 12 wk, the mean fetal crown-rump length was 58.5 +/- 8.8 mm for diabetic subjects and 60.6 +/- 8.7 mm for nondiabetic subjects (P = 0.04). Between 5 and 9 wk, 28 of 289 (9.7%) fetuses of nondiabetic subjects, 34 of 259 (13.1%) normal fetuses of diabetic subjects, and 2 of 10 (20%) malformed fetuses of diabetic subjects demonstrated growth delay (P = 0.31, normal vs. malformed diabetic). Between 10 and 15 wk of gestation, 28 of 283 (9.9%) fetuses of nondiabetic subjects, 32 of 256 (12.5%) normal fetuses of diabetic subjects, and 4 of 13 (30.8%) malformed fetuses of diabetic subjects demonstrated growth delay (P = 0.06, normal vs. malformed diabetic). Early fetal growth delay did not predict a reduced birth weight at term. CONCLUSIONS: Among insulin-dependent diabetic subjects who were moderately well controlled at conception, statistically significant but mild early fetal growth delay was present but did not appear to be useful clinically in predicting congenital malformations. Recommendations that growth delay demonstrated on early ultrasound be used as a predictor of congenital malformation require careful reexamination.

Adult↗

PubMed1991

A mutation in the human apolipoprotein A-I gene. Dominant effect on the level and characteristics of plasma high density lipoproteins.

Epidemiologic and genetic data suggest an inverse relationship between plasma high density lipoprotein (HDL) cholesterol and the incidence of premature coronary artery disease. Some of the defects leading to low levels of HDL may be a consequence of mutations in the genes coding for HDL apolipoproteins A-I and A-II or for enzymes that modify these particles. A proband with plasma apoA-I and HDL cholesterol that are below 15% of normal levels and with marked bilateral arcus senilis was shown to be heterozygous for a 45-base pair deletion in exon four of the apoA-I gene. This most likely represents a de novo mutation since neither parent carries the mutant allele. The protein product of this allele is predicted to be missing 15 (Glu146-Arg160) of the 22 amino acids comprising the third amphipathic helical domain. The HDL of the proband and his family were studied. Using anti-A-I and anti-A-II immunosorbents we found three populations of HDL particles in the proband. One contained both apoA-I and A-II, Lp(A-I w A-II); one contained apoA-I but no A-II, Lp(A-I w/o A-II); and the third (an unusual one) contained apoA-II but no A-I. Only Lp(A-I w A-II) and (A-I w/o A-II) were present in the plasma of the proband's parents and brother. Analysis of the HDL particles of the proband by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed two protein bands with a molecular mass differing by 6% in the vicinity of 28 kDa whereas the HDL particles of the family members exhibited only a single apoA-I band. The largely dominant effect of this mutant allele (designated apoA-ISeattle) on HDL levels suggests that HDL particles containing any number of mutant apoA-I polypeptides are catabolized rapidly.

Amino Acid Sequence↗

PubMed1991

Maternal postprandial glucose levels and infant birth weight: the Diabetes in Early Pregnancy Study. The National Institute of Child Health and Human Development--Diabetes in Early Pregnancy Study.

The cause of macrosomia in the infant of the diabetic woman is still not completely defined. The National Institute of Child Health and Human Development--Diabetes in Early Pregnancy Study, which recruited insulin-dependent diabetic and control women before conception, provided an opportunity to address the relationship between maternal glycemia and percentile birth weight. Data were analyzed from 323 diabetic and 361 control women. Fasting and nonfasting venous plasma glucose were measured on alternate weeks in the first trimester and monthly thereafter. Glycosylated hemoglobin was measured weekly in the first trimester and monthly thereafter. More infants of the diabetic women were at or above the 90th percentile for birth weight than infants of control women (28.5% versus 13.1%, p less than 0.001). Although first-trimester nonfasting glucose and glycosylated hemoglobin levels were positively correlated with infant birth weight (p less than 0.001 and p = 0.008), when the analyses were adjusted for the variables of the subsequent trimesters the values became insignificant, whereas the third-trimester nonfasting glucose levels adjusted for values in prior trimesters emerged as the stronger predictor of percentile birth weight (p = 0.001). After adjusting for maternal hypertension, smoking, and ponderal index, the above relationships remained. In conclusion, monitoring of nonfasting glucose levels rather than the fasting levels, which are more commonly monitored in clinical practice, are necessary to prevent macrosomia.

Blood Glucose↗

PubMed1991

Hypocaloric diets and ketogenesis in the management of obese gestational diabetic women.

The extent to which given levels of caloric restriction will improve glycemic status but increase plasma ketone bodies in gestational diabetic women has received little attention. After reviewing the underlying physiology, we present data on two feeding studies investigating the question. In the first, a weight-maintaining approximately 2400-kcal/day diet was fed on a metabolic ward to 12 gestational diabetic women for 1 week. In the second week, subjects were randomized to a continuation of the 2400-kcal/day diet or to a 1200-kcal/day diet. Twenty-four-hour mean glucose levels remained unchanged in the control group but declined in the calorie-restricted group (6.7 mM or 121 mg/dl in week 1 vs 5.4 mM or 97.3 mg/dl in week 2) (p less than 0.01). Nine-hour overnight fasting plasma insulin also declined but oral glucose tolerance did not improve with caloric restriction. Fasting plasma beta-hydroxybutyrate rose in the calorie-restricted group, along with an increase in ketonuria, but not in the control group. A second study compared the impact of a 33% calorie-restricted diet or insulin to a full-calorie diet in a similar 2-week experimental design and measured hepatic glucose output and insulin sensitivity with dideuterated glucose before and during an insulin clamp. Diet in three subjects improved fasting and 24-hr mean glucose by 22 and 10%, respectively, whereas prophylactic insulin in three subjects produced 0 and 4% reductions, respectively. On average, ketonuria after a 9-hr fast declined to an equivalent degree with both treatments. Hepatic glucose output and insulin sensitivity were not statistically significantly altered by gestational diabetes or the therapeutic interventions compared to nondiabetic normal weight or obese pregnant controls. In conclusion, 50% caloric restriction improves glycemic status in obese women with gestational diabetes but is associated with an increase in ketonuria, which is of uncertain significance. An intermediate 33% level of caloric restriction (to 1600-1800 kcal daily) may be more appropriate in dietary management of obese woman with gestational diabetes mellitus and more effective than prophylactic insulin. Further studies are required to confirm these findings.

Animals↗

PubMed1991

Changes in vitamin and mineral intakes and serum concentrations among free-living men on cholesterol-lowering diets: the Dietary Alternatives Study.

Nutritional adequacy of diets with 18-30% of calories from fat was investigated in men with elevated serum cholesterol (n = 396) at the end of diet classes and 1 and 2 y later. On 4-d food records, intakes of vitamin A, beta-carotene, folate, vitamin C, magnesium, vitamin B-6, iron, thiamin, and riboflavin increased from baseline whereas niacin, selenium, vitamin E, and zinc decreased. Median zinc intake, 80% of the recommended dietary allowance (RDA) at baseline, decreased to approximately 75% of the RDA, most markedly when intakes of meat, fish, and poultry were limited to 85 g/d. Nutrient densities generally increased. Of the serum nutrients measured, median beta-carotene and vitamin C increased, whereas vitamin B-6, iron, and zinc were unchanged. Below-normal values were fewer for vitamin C and magnesium. Diets similar to the National Cholesterol Education Program Step-Two Diet [less than 7% saturated fatty acids, less than 200 mg cholesterol/d] appeared to provide increased levels of most micronutrients both short and long term to men receiving comprehensive dietary counseling.

Ascorbic Acid↗

PubMed1991

Metabolic effects of hypocaloric diets in management of gestational diabetes.

Although hypocaloric diets have been advocated for the management of the obese gravida and the obese mother with gestational diabetes, there is no general agreement on how severely calories should be restricted or on how this therapeutic approach compares with insulin therapy. The lack of consensus is in part because of the lack of studies comparing insulin management with the effects of different degrees of hypocaloric feeding and its effects on metabolism and glycemic status. We review the effects of 50 and 33% calorie restriction on glycemic status and intermediary fuel status in obese gestational diabetic subjects and compare the results with the administration of 20 U NPH and 10 U regular insulin every morning, a therapy of proven value in reducing macrosomia in gestational diabetes. When the two calorie-restriction regimens were compared after a 9-h overnight fast, glycemic status improved 10-20% on both. Ketonuria increased about twofold with 50% calorie restriction, but on average no increase in ketonuria was seen on the 33% calorie-restriction regimen. Both calorie-restriction programs led to a reduction in levels of plasma triglyceride, a correlate of infant birth weight. In contrast, the insulin regimen diminished ketonuria, but glycemic status improved little, and plasma triglyceride concentrations did not decline. Although more studies are needed to confirm these trends, the beneficial effect of 33% calorie restriction, which occurred without marked ketonuria, is consistent with previous studies in gestational diabetes. In addition, the simultaneous improvements observed in plasma glucose and triglyceride concentrations suggest that moderate calorie restriction may be valuable in preventing macrosomia in the offspring of the obese subject with gestational diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Mechanism of the HDL2 stimulation of progesterone secretion in cultured placental trophoblast.

Lipoprotein cholesterol (C) supports the high rate of progesterone production by the human placenta as endogenous cholesterol synthesis is low. To study underlying mechanisms whereby lipoproteins, including high density lipoprotein-2 (HDL2), stimulate progesterone secretion, trophoblast cells were isolated from human term placentas and maintained in primary tissue culture. Lipoproteins were added at several concentrations and medium progesterone secretion was determined. HDL2 (d 1.063-1.125 g/ml) as well as low density lipoproteins (LDL) (d 1.019-1.063 g/ml) but not HDL3 (d 1.125-1.21 g/ml) stimulated progesterone secretion in a dose-dependent manner, with HDL2 cholesterol entering the cell and serving as substrate for progesterone synthesis. Conversely, LDL and HDL2 produced a significant decrease in [2-14C]acetate incorporation into cell cholesterol. Cholesterol-depleted lipoproteins did not stimulate progesterone secretion. The stimulating effect of LDL was abolished by apolipoprotein modification by cyclohexanedione or reductive methylation and by the addition of anti-LDL receptor antibody or 10 microM chloroquine to the medium. [14C]acetate conversion into cholesterol was accelerated by these procedures. However, HDL2 stimulation of progesterone secretion and reduction of [14C]acetate incorporation into cholesterol was not blocked by chemical modification of apolipoproteins, anti-LDL receptor antibody, or chloroquine. Treatment of HDL2 with tetranitromethane or dimethylsuberimidate also did not block the stimulation of progesterone. To determine whether the capacity of HDL2 to deliver cholesterol to the trophoblast cells was restricted to subfractions differing in apoE content, HDL2 was chromatographed on heparin-Sepharose and three fractions (A, B, and C) were obtained. Fraction A was poorest in apoE and free cholesterol, fraction B contained the majority of cholesterol, and fraction C was the richest in apoE and free cholesterol. When added to trophoblast cells, fraction A stimulated little progesterone secretion, fraction B stimulated moderately, and fraction C did so greatly. Modification of these subfractions with cyclohexanedione or reductive methylation did not inhibit these effects. In conclusion, HDL2 stimulated progesterone secretion in human trophoblast cell culture. Contrary to LDL, the HDL effect was not mediated by apolipoproteins or the LDL receptor pathway. The ability of HDL2 to stimulate progesterone secretion is consistent with the passive transfer of free cholesterol to the cell membrane from a physicochemically specific subfraction of HDL. This mechanism may be an auxiliary source of cholesterol for human steroidogenic cells.

Antibodies, Monoclonal↗

PubMed1991

Lipoprotein-cholesterol levels in infertile women with luteal phase deficiency.

OBJECTIVE: To determine if reductions in plasma progesterone (P) secretion seen in luteal phase deficiency (LPD) might be because of reduced availability of circulating low-density lipoprotein (LDL) or high-density lipoprotein (HDL), known substrates for corpus luteum P synthesis. DESIGN: We measured plasma lipoproteins in the luteal phase of the menstrual cycle in 39 infertile women. These women were divided into two groups on the basis of endometrial biopsies; the LPD group had biopsies that were greater than or equal to 3 days out-of-phase. SETTING: All participants were recruited from the Reproductive Endocrinology and Infertility Clinic at the University of Washington, an institutional tertiary care center. PATIENTS, PARTICIPANTS: Eighteen women had in-phase and 21 had out-of-phase LPD biopsies. MAIN OUTCOME MEASURE: Lipoprotein levels were obtained in a fasted state on the day of the luteal phase on which the biopsy was performed. RESULTS: No difference in covariates that affect lipoprotein levels such as obesity, age, and alcohol use were observed between the two groups. No significant differences between groups were found for triglycerides, total cholesterol, very low density lipoprotein, LDL, HDL, HDL2, and HDL3 concentrations. However, LPD was associated with a reduction in the extent to which: age and obesity are associated with higher triglycerides; obesity is associated with a lower HDL2; and alcohol is associated with a higher HDL3-cholesterol. CONCLUSIONS: Lipoproteins on average are not different in LPD, suggesting reasons other than a deficient plasma lipoprotein cholesterol source as the explanation for decreased P secretion. A lesser interaction between LDL or HDL and obesity, age, and alcohol in LPD could signify an influence of the altered hormonal milieu of LPD on the way lipoproteins interact with covariates and could lead to differences in lipoproteins between normal and LPD subjects at the extremes of the lipoprotein distribution.

Biopsy↗

PubMed1990

Efficacy and safety of pravastatin in patients with primary hypercholesterolemia. I. A dose-response study.

This multicenter, double-blind, placebo-controlled, dose-response study was conducted in patients with primary hypercholesterolemia to examine the effects of pravastatin, a selective inhibitor of HMG-CoA reductase, on plasma lipids and lipoproteins. A total of 306 patients on cholesterol-lowering diets received twice daily doses of 5 mg, 10 mg, 20 mg pravastatin, or placebo for 12 weeks. Marked reductions in low density lipoprotein (LDL) cholesterol and total cholesterol were observed after 1 week of treatment; maximum lipid-lowering effects occurred at 4 weeks and were sustained for the duration of the trial. At week 12, pravastatin treatment resulted in dose-dependent mean reductions from baseline in LDL cholesterol of 17.5%, 22.9%, and 30.8% for the 3 doses tested (P less than or equal to 0001 compared with baseline and placebo). The reduction in LDL cholesterol was log-linear with respect to dose; each doubling of dose reduced LDL cholesterol an additional 6.5%. Dose-dependent reductions in total cholesterol from 12.9% to 23.3% also occurred (P less than or equal to 0.001). Triglycerides decreased by as 15.4% (P less than or equal to 0.001) and high-density lipoprotein (HDL) cholesterol increased approximately 7% (P less than or equal to 0.01), but these effects were not dose-dependent. No patient receiving pravastatin was discontinued during the 12-week trial. Transient episodes of rash and headache occurred. Slight increases in mean serum levels of ASAT and ALAT occurred, and 2% of both placebo- and pravastatin-treated patients reported myalgia although there was no clinically significant elevation of creatine kinase. These data indicate that pravastatin favorably affects all lipid parameters and is well tolerated.

Anticholesteremic Agents↗

PubMed1990

Divergent lipoprotein responses to fish oils with various ratios of eicosapentaenoic acid and docosahexaenoic acid.

To determine if the ratio of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in fish oil had an effect on plasma lipid responses, we randomly fed eight normolipidemic men three 36%-fat diets containing primarily butter, EPA-rich pollock oil, or DHA-rich tuna or salmon-blend oils. Plasma EPA and DHA reflected the amounts in the diets. Compared with values for the butter diet, very-low-density lipoprotein (VLDL) triglycerides decreased equally (71-78%) with all diets; low-density lipoprotein (LDL) cholesterol (LDL-C) and apolipoprotein B decreased 26% and 13%, respectively, on the tuna and salmon-blend oil but did not change (-1%) and increased 19% with the pollock diet; high-density lipoprotein cholesterol (HDL-C) and lipoproteins A-I and A-II decreased with all diets but more with the pollock diet than with the tuna and salmon diets. The 23-31% decrease in total cholesterol on the tuna and salmon diets resulted mostly from decreased LDL-C whereas the 16% decrease on pollock oil resulted mostly from a decrease in HDL-C.

Butter↗

PubMed1990

Metabolic effects of 1200-kcal diet in obese pregnant women with gestational diabetes.

Calorie restriction is widely used as a primary therapy for obese pregnant women with gestational diabetes. To better understand the metabolic consequences of marked calorie restriction, we performed a randomized prospective trial under metabolic ward conditions. Obese gestationally diabetic women were randomized to control (n = 5) and calorie-restricted (n = 7) groups. All patients consumed an approximately 2400-kcal/day diet during the 1st wk of the study, and at the end of the 1st wk, metabolic features of the two groups were statistically indistinguishable. During the 2nd wk, the control group continued to consume approximately 2400 kcal/day, whereas the calorie-restricted group consumed approximately 1200 kcal/day. Twenty-four-hour mean glucose levels remained unchanged in the control group (6.7 +/- 0.8 mM wk 1 vs. 6.8 +/- 0.8 mM wk 2), although they dropped dramatically in the calorie-restricted group (6.7 +/- 1.0 mM wk 1 vs. 5.4 +/- 0.5 mM wk 2, P less than 0.01). Fasting plasma insulin also declined in the calorie-restricted group (265 +/- 165 pM wk 1 vs. 145 +/- 130 pM wk 2), resulting in a significant change between groups (P less than 0.02). Surprisingly, fasting plasma glucose and glucose tolerance measured by the 3-h oral glucose tolerance test did not change within or between groups. Fasting levels of beta-hydroxybutyrate rose in the calorie-restricted group (290 +/- 240 microM wk 1 vs. 780 +/- 30 microM wk 2) but not in the control group (P less than 0.01). Finally, urine ketones increased significantly (P less than 0.02) in the calorie-restricted group, whereas they remained absent in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Effects of sex steroid hormones on lipoprotein levels in pre- and post menopausal women.

Women are affected by disorders of lipid metabolism in the same way as men. Sex steroids given as oral contraceptives at all doses have clearcut, formulation-specific effects on lipoprotein levels in reproductive-aged women. In estrogen-dominant versus androgenic progestin-dominant formulations, LDL cholesterol levels were unchanged and significantly increased, respectively, and HDL cholesterol was increased and decreased, respectively. The greatest HDL lowering is seen with the most androgenic formulations. Major increases in LDL cholesterol confer risk for cardiovascular disease on this group, so caution is recommended in formulation selection. In general, cardiovascular disease risk in post menopausal women using estrogen is reduced 30 to 70%. Concurrent administration of progestin with post menopausal estrogen appears to reduce the beneficial rise in HDL associated with estrogen administration alone. Cardiovascular disease is likely to be reduced by estrogen in post menopausal women.

Adolescent↗