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Biomedical subjects

R H Knopp

Publications and source records attributed to R H Knopp.

At least 163 records · Page 9Linked to original sources

Carbohydrate metabolism in pregnancy. 8. Metabolism of adipose tissue isolated from fed and fasted pregnant rats during late gestation.

The effects of late pregnancy on adipose tissue metabolism have been examined in fed and fasted rats. Lumbar fat was excised from 19-day pregnant and age-matched virgin rats which had been given unrestricted access to food ("fed") or fasted for 48 hr before sacrifice. In the fed state, adipose tissue from pregnant rats displayed an increased content of free fatty acids (FFA). This coincided with augmented cleavage of preformed glycerides during incubation in vitro as evidenced by greater net production of FFA and glycerol, and altered disposition of labeled glucose. The enhanced lipolysis was independent of the availability of glucose and was not accompanied by impaired responsiveness to the antilipolytic or to the lipogenic actions of added insulin. In the presence of glucose and albumin, esterification as well as lipolysis was greater in adipose tissue from pregnant than nongravid animals. All the differences were exaggerated by prior fasting. These properties of adipose tissue during late gestation have been ascribed to a primary activation of lipolysis rather than impaired esterification or resistance to insulin. It has been suggested that the hormones of pregnancy may be responsible. Although increased intake of food and heightened availability of insulin may offset the net lipolytic effects in the fed state, a heightened turnover of adipose stores is always present. Thus, the pregnant animal appears better poised to mobilize preformed fat whenever exogenous nutrients are withheld.

Adipose Tissue↗

Carbohydrate metabolism in pregnancy. VI. Plasma fuels, insulin, liver composition, gluconeogenesis, and nitrogen metabolism during late gestation in the fed and fasted rat.

The effects of late pregnancy on metabolic fuels, liver composition, gluconeogenesis, and nitrogen metabolism have been examined in fed and fasted rats. Plasma free fatty acid (FFA) and immunoreactive insulin (IRI) are greater and glucose and ketones are lower in fed 19-day pregnant than they are in agematched virgin rats. A 48 hr fast elicits greater increases in FFA and ketones and more profound reductions in glucose in the pregnant rats and obliterates the differences in IRI. Fetal weight is not modified by such fasting but maternal weight losses exceed that of the nongravid rats. Livers from rats 19 days pregnant contain more and larger hepatocytes. Per mumole hepatic deoxyribonucleic acid (DNA)-phosphorus, water and protein are more abundant, whereas glycogen is unaffected. Livers from fed pregnant rats contain more lipid phosphorus and less neutral lipid fatty acid. After a 48 hr fast, hepatic steatosis supervenes in gravid animals due to accumulated neutral fat. The contents of hepatic acetyl-coenzyme A (CoA) and citric acid are not different in fed pregnant and virgin rats but are greater in the pregnant rats after fasting. Formation of glucose-(14)C and glycogen-(14)C from administered pyruvate-(14)C are the same in fed pregnant and virgin rats, but greater in the pregnant ones after a 24 or 48 hr fast. Pregnancy does not affect creatinine excretion, and urinary urea is not different in fed pregnant, virgin, and postpartum animals. Contrariwise, more nitrogen, potassium, and phosphorus are excreted by the pregnant animals during a 2 day fast. The increment in urinary nitrogen is due largely to urea on the 1st day, whereas heightened ammonia accounts for half the increase on the 2nd and correlates with the enhanced ketonuria. Muscle catabolism, gluconeogenesis, and diversion to fat are activated more rapidly and to a greater degree when food is withheld during late gestation in the rat. These catabolic propensities are restrained in the fed state. The capacity for "accelerated starvation" may confer survival benefit upon an intermittently eating mother in the presence of a continuously feeding fetus.

Animals↗

Changes in plasma lipids and dietary intake accompanying shifts in perceived workload and stress.

Plasma lipids, dietary intake, and self-reported stress and workload were assessed in 14 employees twice before major work deadlines (high workload), and once during a comparatively quiescent period of work (low workload). Increases in self-reported stress and workload between the high and low workload periods were significantly positively associated with increases in plasma total cholesterol, although lipid levels were not increased in the group as a whole during the high workload periods. Dietary intake of calories, total fat, and percentage of calories from fat were significantly higher during high workload during a period of high workload is associated with elevated total cholesterol and that dietary intake of foods which raise cholesterol levels is also increased. Further studies of larger groups of subjects may be required to show a frank increase in cholesterol with increased workload.

Adult↗

Acute psychological stress and epinephrine infusion in normolipidemic and hyperlipidemic men: effects on plasma lipid and apoprotein concentrations.

This study examined whether psychological stress and the infusion of epinephrine increase plasma lipid and apoprotein concentrations in normolipidemic and hyperlipidemic men. Subjects were studied during three separate 6-hour laboratory sessions: a control session, during which subjects rested quietly while blood samples and hemodynamic measurements were obtained; a stress session, during which subjects were presented with two challenging mental tasks, followed by quiet rest; and an epinephrine infusion session, during which subjects received a low-dose infusion of epinephrine followed by quiet rest. The stress and epinephrine infusion manipulations produced the expected changes in plasma epinephrine and norepinephrine levels, blood pressure, and heart rate. Free fatty acid concentration increased markedly during epinephrine infusion and less dramatically but consistently during mental stress. Both stress and epinephrine infusion produced acute increases in plasma total, low-density lipoprotein, very low-density lipoprotein, and high-density lipoprotein cholesterol and apoprotein B concentrations, but comparable increases during the control session were not observed. Changes in albumin concentration (an index of plasma volume) were associated with changes in lipid concentrations during psychological stress. Epinephrine increases during psychological stress were correlated with increases in free fatty acid and triglyceride levels both during and after task administration. It was concluded that psychological or pharmacological stress induced in the laboratory produces changes in lipid concentrations, which at least during psychological stress, may be attributed to concomitant changes in plasma volume. The association between task-induced changes in epinephrine and changes in free fatty acid and triglyceride levels, also supports the hypothesis that psychological stress increases lipolysis.

Adult↗

Hyperlipidemia in the Pacific Northwest Bell Telephone Company Health Survey. Part 1. Lipoprotein cholesterol and triglyceride concentrations.

Lipoprotein triglyceride and cholesterol concentrations and characteristics are described in normolipidemic and in three categories of hyperlipidemic subjects participating in the Pacific Northwest Bell Telephone Company Health Survey. For this study, 350 white participants 20 to 59 years of age with cholesterol or triglyceride values exceeding the age, sex, and hormone-use specific, population-based 90th percentile values were defined as having hypercholesterolemia, hypertriglyceridemia, or combined hyperlipidemia; 722 participants were classified as normolipidemic. In hypercholesterolemia, very low density lipoprotein cholesterol and triglyceride and high density lipoprotein cholesterol concentrations were higher than in normolipidemia. In hypertriglyceridemia, high density lipoprotein cholesterol was significantly lower in men and women not using sex hormones and low density lipoprotein triglyceride was significantly higher in men and women using hormones compared to normolipidemia. In combined hyperlipidemia, high density lipoprotein cholesterol concentrations were lower than in normolipidemia, but higher than in pure hypertriglyceridemia. The presence of beta migrating very low density lipoprotein and chylomicrons was seen primarily in hypertriglyceridemic or combined hyperlipidemic men. Sinking prebeta lipoprotein was equally common (20%) among all normolipidemic and hypercholesterolemic subjects, but was less common (5% to 10%) in hypertriglyceridemic and combined hyperlipidemic men and female hormone users. Quantitative and qualitative lipoprotein abnormalities associated with hyperlipidemia were found to vary by gender and by sex hormone use in women and were often, but not always, more marked in men.

Adult↗

Hyperlipidemia in the Pacific Northwest Bell Telephone Company Health Survey. Part 2. Lipoprotein lipid interrelationships.

The relationships of lipoprotein cholesterol and triglyceride among lipoprotein fractions have potential significance for understanding atherogenesis and distinguishing among different classes of hyperlipidemia. We have compared these relationships in normolipidemic, hypercholesterolemic, hypertriglyceridemic, and combined hyperlipidemic participants in the Pacific Northwest Bell Telephone Company Health Survey. The cholesterol/triglyceride ratio in each lipoprotein fraction was moderately higher (1% to 26%) in hypercholesterolemia but significantly lower (20% to 50%) in hypertriglyceridemia, compared to normolipidemia. In combined hyperlipidemia, the very low density lipoprotein ratios were lower than in normolipidemia, but larger than in hypertriglyceridemia. These changes were directionally the same, but differed quantitatively, in both men and women. Correlation coefficients between cholesterol and triglyceride within each fraction varied by gender and sex hormone use. The largest correlations were seen in combined hyperlipidemic men for very low density lipoproteins, normolipidemic men for low density lipoproteins, and combined hyperlipidemic women taking hormones for high density lipoproteins. The correlation of very low and low density lipoprotein cholesterol was generally negative and was strongest for hormone users (r = -0.81) and weakest for nonusers (r = -0.06). Very low density lipoprotein triglyceride and high density lipoprotein cholesterol correlations were generally negative and were strongest in hypertriglyceridemic women not taking hormones (r = -0.55) and weakest in normolipidemic hormone users (r = -0.10). This correlation was positive for hypertriglyceridemic and combined hyperlipidemic hormone users.

Adult↗

Physiologic and supraphysiologic increases in lipoprotein lipids and apoproteins in late pregnancy and postpartum. Possible markers for the diagnosis of "prelipemia".

A supraphysiologic (greater than 95th percentile) rise in plasma lipids in pregnancy may serve as a marker for "prelipemia" in the same way that gestational diabetes is a marker for prediabetes. To qualify as prelipemic, subjects with an abnormal lipid rise antepartum must return to normal postpartum but may have other identifying characteristics. This paper describes the antepartum-postpartum changes of lipoprotein lipids and apoproteins at 34 to 38 weeks of gestation and 6 and 20 weeks postpartum in 23 subjects with physiologic and six subjects with supraphysiologic plasma lipid increases during pregnancy. These results are compared to measurements in 23 nonpregnant controls matched for weight, age, and race. In subjects with a physiologic antepartum lipid rise, postpartum total triglyceride and very low density lipoprotein (VLDL) lipids (cholesterol and triglyceride) and apo B returned to baseline within 6 weeks. In contrast, low density lipoprotein (LDL) showed a slow postpartum decline in lipids and apo B with elevations remaining at 20 weeks postpartum. High density lipoprotein (HDL) cholesterol concentrations, elevated in pregnancy, remained elevated at 6 weeks postpartum, but fell to baseline by 20 weeks postpartum. HDL triglyceride and apo A-l concentrations, both elevated in pregnancy, returned to baseline by 6 weeks postpartum. A supraphysiologic triglyceride rise in pregnancy was associated with a slower return of total triglycerides and VLDL to baseline, reduced HDL cholesterol ante- and postpartum, atypical changes in LDL cholesterol during pregnancy and postpartum, and evidence of hyperlipidemia among family members. Two subjects with hypercholesterolemia in the nonpregnant state showed no marked exaggeration of total or LDL cholesterol concentrations in pregnancy. The data support the hypothesis that a supraphysiologic rise in plasma triglyceride concentrations in late pregnancy may serve as a marker of prelipemia. Proof of the hypothesis requires further investigation and longer follow-up.

Adult↗

Effects of fenofibrate on plasma lipids. Double-blind, multicenter study in patients with type IIA or IIB hyperlipidemia.

Of 240 patients with Type IIa and IIb hypercholesterolemia recruited in 11 centers, 227 were randomized to double-blind treatment with either fenofibrate (100 mg three times daily) or matching placebo for 24 weeks. A group of 192 of these patients were studied for a further 24 weeks during which all received fenofibrate in open label fashion. For the 92 Type IIa patients receiving fenofibrate in the double-blind phase, there were significant reductions (p less than 0.01 compared to baseline) in total plasma cholesterol (-18%), LDL-cholesterol (-20%), VLDL-cholesterol (-38%) and total triglycerides (-38%). Mean plasma HDL-cholesterol in these patients increased by 11% (p less than 0.01). With the exception of LDL, which was not high before treatment, similar changes were seen in the 24 fenofibrate-treated Type IIb subjects. Lipid parameters of placebo-treated patients did not change significantly. This pattern of change was repeated in the open period for the 94 patients previously on placebo, while the 98 who had been on fenofibrate remained stable with small further reductions in total and LDL cholesterol (-38% and -5.5% respectively). Adverse effects were some allergic-type skin reactions early in treatment and an occasional increase in transaminases, BUN, or creatinine. The results were similar to those obtained in European open trials of fenofibrate and were better than the lipid changes seen at comparable times in the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT) cholestyramine study.

Cholesterol↗

Relationships of lipoprotein lipids to mild fasting hyperglycemia and diabetes in pregnancy.

The available data have been examined to determine if plasma lipids or lipoproteins are altered in pregnant subjects with adult-onset (type II) diabetes, gestational diabetes, or the hyperglycemic extreme of a randomly selected group of pregnant women attending a prepaid health plan. In each of these groups, a trend is observed toward an increase in total plasma and very low density lipoprotein triglycerides and a decrease in high density lipoprotein (HDL) cholesterol. These observations indicate that measurements of plasma triglyceride and HDL cholesterol may be valuable in identifying and quantifying the metabolic abnormality in gestational diabetes and in prognosticating fetal outcome.

Adult↗

Management of hyperlipidemia in women with diabetes.

OBJECTIVE: To review gender-related factors in coronary artery disease, possible mechanisms for increased atherogenesis in women with diabetes, and potential therapeutic strategies for hyperlipidemia. METHODS: Pertinent published studies and personal experiences are discussed, and lipoprotein profiles are outlined. RESULTS: In the normal population, the increase in atherosclerotic vascular disease with aging in women lags behind that in men by 10 to 15 years. With the presence of diabetes, however, the atherosclerotic changes are similar in men and women. Several studies have substantiated that triglyceride levels are a stronger risk factor than cholesterol in men and women with diabetes who have coronary artery disease. In general, hypertriglyceridemia is a stronger risk factor for cardiovascular disease in women than in men. Gender differences in lipid levels can be explained physiologically by the presence of estrogen in female patients, which accelerates the rate of metabolism of lipoproteins and, in a setting of insulin deficiency, induces hypertriglyceridemia. Dietary measures and various classes of drugs, including reductase inhibitors, are used alone or in combination for management of the combined hyperlipidemia typically found in subjects with insulin resistance, diabetes, or both. CONCLUSION: Gender-related differences in lipoprotein-associated cardiovascular risk should be considered in choosing treatment options for patients with diabetes and hyperlipidemia.

Journal Article↗