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Biomedical subjects

M B Mattock

Publications and source records attributed to M B Mattock.

34 records · Page 2Linked to original sources

Plasma lipid and coagulation factor concentrations in insulin dependent diabetics with microalbuminuria.

OBJECTIVE: To determine whether insulin dependent diabetics with microalbuminuria have significant abnormalities in concentrations of lipoproteins, apolipoproteins AI and B, fibrinogen, and clotting factor VII which could result in increased cardiovascular risk. DESIGN: Case-control study. SETTING: Outpatient department of a metabolic ward. PATIENTS: Group of 20 insulin dependent diabetics with urinary albumin excretion rates greater than 30 micrograms/min (microalbuminuria) and 20 individually matched insulin dependent diabetics with normal urinary albumin excretion rates (below 30 micrograms/min) matched for age, sex, and duration of diabetes. INTERVENTIONS: Fasting venous blood samples were taken for determination of concentrations of glucose, glycated haemoglobin, lipoproteins, apolipoproteins AI and B, fibrinogen, and factor VII. Height, weight, arterial pressure, and usual insulin dose were recorded, and each patient was given a dietary questionnaire to be completed at home. END POINT: Comparison of blood pressure and concentrations of lipoproteins, apolipoproteins AI and B, and fibrinogen in the diabetics with microalbuminuria and the controls. MEASUREMENTS AND MAIN RESULTS: Patients with microalbuminuria had significantly higher concentrations of low density lipoprotein cholesterol (mean 3.33 (SE 0.20) v 2.84 (0.12) mmol/l) and very low density lipoprotein cholesterol (0.30 (0.05) v 0.17 (0.03) mmol/l) than controls but significantly lower concentrations of high density lipoprotein 2 subfraction cholesterol (0.32 (0.04) v 0.54 (0.04) mmol/l). Concentrations of total triglyceride (1.11 (0.14) v 0.68 (0.08) mmol/l), very low density lipoprotein triglyceride (0.56 (0.10) v 0.30 (0.05) mmol/l), apolipoprotein B (0.88 (0.06) v 0.67 (0.03) g/l) and fibrinogen (2.2 (0.1) v 1.9 (0.1) g/l), and diastolic arterial pressure (80 (2) v 74 (2) mm Hg), were also higher in patients with microalbuminuria. CONCLUSIONS: Cardiovascular risk factors--namely, disturbances in lipoprotein and apolipoprotein concentrations, increased fibrinogen concentration, and increased arterial pressure--are already present in insulin dependent diabetics with microalbuminuria. The increased risk of coronary heart disease in patients with clinical proteinuria may result from prolonged exposure to these risk factors, which are present before any impairment of renal function.

Albuminuria↗

Coronary heart disease and urinary albumin excretion rate in type 2 (non-insulin-dependent) diabetic patients.

Associations between overnight urinary albumin excretion rate and prevalent coronary heart disease and its major risk factors were examined in a cross-sectional study of 141 Type 2 (non-insulin-dependent) diabetic patients. Mean albumin excretion rate was higher in men (geometric mean 13.5 micrograms/min; 95% confidence interval 10.3-17.6) than women (7.5 micrograms/min; 5.7-9.8, p less than 0.01). In diabetic men and women mean albumin excretion rate was higher in those with electrocardiographic and/or symptomatic evidence of coronary heart disease than in those without (men, 23.1 micrograms/min; 95% confidence interval 13.7-39.0 versus 10.6 micrograms/min; 7.9-14.2, p less than 0.01, women, 13.7 micrograms/min; 8.0-23.5 versus 5.4 micrograms/min; 4.2-6.8, p less than 0.01). Multiple logistic regression analysis was used to allow for confounding between variables. In the diabetic group as a whole, raised albumin excretion rate (p less than 0.001), gender (p less than 0.05) and systolic blood pressure (p = 0.06) entered the "best" model for coronary heart disease prediction. In women, albumin excretion rate alone (p less than 0.01) and in men albumin excretion rate (p less than 0.01) and age (p = 0.05) entered the "best" models. We conclude that albumin excretion rate is significantly associated with coronary heart disease morbidity after taking into account the confounding effects of raised blood pressure and other cardiovascular risk factors.

Adult↗

The relationship of high density lipoprotein subfractions to alcohol consumption, other lifestyle factors, and coronary heart disease.

Serum high density lipoprotein (HDL) levels are inversely related to the risk of coronary heart disease. Controversy exists regarding the relative importance of HDL subfractions, and few studies have related subfraction levels to lifestyle factors associated with coronary risk. We examined the relationship of the major subfractions, HDL2 and HDL3, to alcohol consumption, cigarette smoking, physical exercise, body mass index, and socioeconomic status in 88 men and 49 women aged 35-64 years. Body mass index was inversely related to HDL2-cholesterol (C), particularly in men, but had no significant relationship with HDL3-C. Cigarette smoking and degree of physical exercise were not significantly related to either HDL subfraction. Alcohol consumption had a strong positive correlation with HDL3-C in both sexes; this association was statistically significant after controlling for cigarette smoking, body mass index, and serum triglyceride. Minnesota-coded ECG abnormalities and positive responses to the WHO chest pain questionnaire were associated with lower levels of HDL-C and HDL2-C in both sexes, and significantly lowered levels of HDL3-C in men but not women. These findings suggest that HDL3-C, as well as HDL2-C, may be related to coronary risk, and indicate that the protective effects of alcohol consumption may be mediated via this subfraction.

Adult↗

Increased platelet and red cell counts, blood viscosity, and plasma cholesterol levels during heat stress, and mortality from coronary and cerebral thrombosis.

Recorded deaths from coronary and cerebral thrombosis rise markedly in heat waves. In a British heat wave with little or no distortion due to air-conditioning, outside temperatures of 34.6 degrees C (maximum) and 20.8 degrees C (minimum) were followed by peak mortalities from coronary and cerebral thrombosis one to two days later. Experimental exposure of volunteers to moving air at 41 degrees C for six hours caused core temperature to rise 0.84 degree C, weight to fall 1.83 kg with sweating despite access to water, heart rate to increase 32 beats per minute, and arterial pressure to fall, particularly on standing. The red blood cell count increased 9 percent, and blood viscosity increased 24 percent, mostly after the first hour. The platelet count rose 18 percent, and the platelet volume fell, mostly in the first hour. The plasma cholesterol level increased 14 percent without a change in distribution among lipoprotein fractions. The changes seem able to explain the increased mortality from arterial thrombosis in hot weather.

Adult↗

High density lipoprotein subfractions in insulin-dependent diabetic and normal subjects.

Serum lipoproteins have been separated by preparative ultracentrifugation in randomly selected groups of insulin-dependent diabetics and in age- and sex-matched non-diabetic controls. The major high density lipoprotein (HDL) subclass; HDL2 (density (d) 1.063-1.125 kg X m-3) and HDL3 (d greater than 1.125) and the further fractions of HDL2:HDL2b (d 1.063-1.100) and HDL2a (d 1.100-1.125) were also separated and their cholesterol (C) concentrations determined. These diabetic men and women were relatively normolipaemic and the major difference from controls was a significantly raised total HDL-C in men which was confirmed by a separate chemical precipitation method. This increase was associated with a significant rise in HDL2a-C and in total HDL2-C concentration. The non-significant increase in diabetic women compared to men was associated with poorer metabolic control. Among factors influencing serum HDL2-C concentration, the most important was the negative association with the level of very low density lipoprotein-triglycerides. Although insulin-dependent diabetics have an increased risk of atherosclerotic coronary heart disease (CHD), this is not reflected in their HDL subfraction-C distribution which, if present in non-diabetics, would be expected to confer protection from CHD.

Adult↗

Mechanism of carbohydrate-induced hypertriglyceridemia: plasma lipid metabolism in mice.

A group of mice were fed on a basal diet for 2 wk and thereafter maintained on a fat free high sucrose or starch diet for 5-6 wk. Hypertriglyceridemia was induced in the mice on feeding the high carbohydrate diets. The triglyceride levels reached maximum in 12 and 14-18 days on high sucrose and starch diets, respectively. This was associated with increased pre-beta-lipoproteins in plasma. Though males had higher levels of triglycerides than females on both the diets, this attained statistical significance only in the sucrose-fed group. Cholesterol and phospholipids recorded a significant increase only towards the end of the experimental period. The plasma lipid levels correlated with their secretion rates from the liver following an injection of Triton WR 1339. Furthermore, the hypertriglyceridemia appeared to be due to defective plasma triglyceride removal as seen by the reduced postheparin lipolytic activity (PHLA) of plasma and decreased triglyceride removal (intravenous fat tolerance test) in these animals. The triglycerides returned to almost normal levels when feeding was continued on the diets. During this adaptation, PHLA and fat tolerance of animals increased significantly. Higher triglycerides in the sucrose group seem to be due to a higher rate of secretion as well as slower removal of triglycerides in this group. The sex difference noticed in the plasma triglycerides at peak hypertriglyceridemia appeared to be mainly due to sex difference in removal rates. Blood sugar raised significantly in the animals maintained on both the diets.

Animals↗

Corticosteroid treatment, serum lipids and coronary artery disease.

Serum lipids and the cholesterol concentrations in the high density lipoprotein (HDL) fractions were measured in patients receiving long-term corticosteroid treatment for connective tissue disorders and asthma. Patients who were not receiving corticosteroid treatment had blood lipid levels which did not differ from those of healthy people. However, female (but not male) patients who had received prednisolone for a mean period of 3.1 years had a significant elevation in total cholesterol and a large decrease in HDL cholesterol. It seems possible that high levels of corticosteroids may increase the incidence of premenopausal ischaemic heart disease in females.

Adolescent↗

Sex-dependence in triglyceride metabolism in response to dietary carbohydrates.

In humans, as well as in mice, fed on high carbohydrate diets, there was a significant sex difference in the plasma tirglycerides in that males had higher levels than females. This was mainly due to the difference in their removal rate of circulating triglycerides in the animals of both sexes. In mice, males had higher levels of liver triglycerides as well as higher rate of incorporation of U- 14C-glucose into liver triglycerides when compared to females.

Adult↗

Lipoproteins and plasma cholesterol esterification in normal and diabetic subjects.

Serum lipoproteins, separated by preparative ultracentrifugation and the activity of the plasma enzyme lecithin: cholesterol acyltransferase (LCAT) have been measured in insulin-dependent diabetics, non-insulin-dependent diabetics and in age-matched non-diabetic controls. In the insulin-dependent diabetics, mean total serum cholesterol and high density lipoprotein cholesterol (HDL-C) concentrations were significantly higher than in controls. Non-insulin-dependent diabetics had significantly raised total triglycerides and cholesterol, but HDL-C levels were essentially normal. The increased low density lipoprotein cholesterol (LDL-C) in both diabetic groups was statistically significant in men. A methodological study of HDL separation techniques was carried out to facilitate interpretation of these findings. Mean LCAT activity, by a method reflecting combined enzyme and substrate effects was significantly increased in these diabetic groups. The results confirm recent reports of a raised HDL-C in those insulin-dependent diabetics who are prone to coronary heart disease.

Cholesterol↗

Lecithin-cholesterol acyltransferase activity in carbohydrate-induced hypertriglyceridemia in mice.

Feeding to mice of both basal as well as high sucrose diet led to increased levels of plasma triglycerides, which was associated with increased lecithin-cholesterol acyltransferase activity. Although males had significantly higher LCAT activity than females in all the dietary groups, sex difference in the plasma triglycerides was observed in high sucrose group only. Increase in plasma triglycerides in experimental groups was associated with an increase in LCAT activity.

Animals↗