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Biomedical subjects

W Richmond

Publications and source records attributed to W Richmond.

At least 19 recordsLinked to original sources
PubMed1992

The response of hepatic lipase and serum lipoproteins to acute hyperinsulinaemia in type 2 diabetes.

Hepatic lipase has a putative role in the catabolism of HDL particles and, while its activity is dependent upon insulin in the rat, no such insulin responsiveness has been demonstrated in man. We studied 21 patients with type 2 diabetes to examine whether hepatic lipase activity was influenced by hyperinsulinaemia during a 2-4 h isoglycaemic clamp study. Acute changes in lipids, lipoproteins and apolipoproteins were also documented in pre- and post-clamp serum. Hepatic lipase activity during hyperinsulinaemia was compared with activity measured after an equivalent period without insulin. For comparison, nine non-diabetic subjects (matched for age and body mass index) underwent similar clamp studies. In the control experiment without insulin, hepatic lipase activity did not change significantly (mean 9.7 (range 2.3-22.3) in the morning and 9.9 (3.0-22.5) mmol h-1 l-1 in the afternoon, NS). In contrast, after the hyperinsulinaemic clamp, hepatic lipase activity fell significantly in diabetic subjects from 12.8 (4.4-30.6) to 10.4 (3.3-31.3) mmol h-1 l-1, P less than 0.0002 along with serum triglycerides and total and LDL cholesterol. The change in hepatic lipase activity was positively related to the fasting apoprotein B concentration (Spearman r = 0.54, P = 0.016). In the normal subjects, a similar decline in hepatic lipase activity was observed during hyperinsulinaemia (from 15.1 (9.8-32.7) to 12.6 (6.3-28.3) mmol h-1 l-1, P less than 0.01) along with decreases in total, HDL and LDL cholesterol, triglycerides and apoproteins A1 and B.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Determinants of mild fasting hypertriglyceridaemia in non-insulin-dependent diabetes.

Factors contributing to fasting hypertriglyceridaemia were studied in 20 patients with non-insulin-dependent diabetes--nine with normal triglyceride concentrations [fasting triglyceride 0.94 (range 0.58-1.23) mmol l-1] and eleven with mild fasting hypertriglyceridaemia [fasting triglyceride 2.4 (1.82-4.0) mmol l-1]. The patients with hypertriglyceridaemia were more obese [body mass index 29.0 (24.6-33.8) vs. 25.7 (21.9-30.1) kg m-2, P less than 0.05] and demonstrated impaired glucose disposal in response to exogenous insulin at isoglycaemia [insulin sensitivity index, SIp 0.7 (0.27-2.5) vs. 2.4 (0.62-5.1) ml m-2 min per mU l-1, P less than 0.001]. Basal non-esterified fatty acid (NEFA) and glycerol concentrations were higher and were suppressed to a lesser extent during isoglycaemic hyperinsulinaemia. Fasting glucose and apolipoprotein B concentrations were higher in the hypertriglyceridaemic patients, but lipoprotein lipase activities were similar in the two groups. When the effect of obesity was removed (by weight-matching six normotriglyceridaemic with seven hypertriglyceridaemic patients) basal NEFA and glycerol concentrations and the suppression of NEFA in response to insulin remained significantly different between the two groups. We propose that defects in both the glucoregulatory and antilipolytic actions of insulin contribute to mild fasting hypertriglyceridaemia in NIDDM, and that these defects cannot be attributed solely to obesity. These disorders of insulin action may also have important implications for the postprandial metabolism of triglyceride-rich lipoproteins and hence atherogenesis.

Adult↗
PubMed1991

The influence of regional adiposity on atherogenic risk factors in men and women with type 2 diabetes.

To determine firstly whether body fat distribution could predict the presence of atherogenic risk factors better than overall adiposity in Type 2 diabetes, and secondly whether sex differences in these risk factors could be explained by sex differences in fat distribution, waist-to-hip girth ratio (WHR), serum lipids, lipoproteins, apolipoproteins, plasma lipolytic activity, and blood pressure were assessed in 47 patients with Type 2 diabetes, 21 women matched for age, body mass index (BMI) and blood glucose control with 26 men. The men had higher WHR (0.95 (range 0.83-1.07) vs 0.82 (0.74-0.94), p less than 0.001), lower HDL-cholesterol (1.03 +/- 0.05 vs 1.38 +/- 0.06 mmol l-1, p less than 0.001) and apolipoprotein A1 (1.40 +/- 0.06 vs 1.76 +/- 0.06 gl-1, p less than 0.001) concentrations, and higher hepatic lipase activities (16.2 (6.4-38.0) vs 8.6 (2.3-23.1) mmol h-1 l-1, p less than 0.01). In both men and women, BMI and WHR were positively related to serum triglyceride, insulin and C-peptide concentrations. In women, HDL-cholesterol was negatively related to BMI (r = -0.45, p less than 0.05) but only possibly related to WHR (r = -0.33, NS). In men, by contrast, WHR was related negatively to HDL-cholesterol (r = -0.60, p less than 0.005), HDL2-cholesterol (r = -0.43, p less than 0.05), and apolipoprotein A1 (r = -0.70, p less than 0.001) and positively to hepatic lipase activity (r = 0.65, p less than 0.001), whereas the same relationships with BMI were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1991

The role of insulin insensitivity and hepatic lipase in the dyslipidaemia of type 2 diabetes.

Fourteen male patients with Type 2 diabetes were studied to identify relationships between insulin-mediated glucose disposal, basal and glucose-stimulated insulin secretion, fasting lipoproteins and apolipoproteins, and the activities of lipoprotein lipase and hepatic lipase. Sensitivity of glucose disposal to exogenous insulin correlated positively with HDL-cholesterol (r = 0.65, p less than 0.05), HDL2-cholesterol (r = 0.59, p less than 0.05), and apolipoprotein A1 (r = 0.57, p less than 0.05) and negatively with apolipoprotein B (r = -0.53, p less than 0.05) and total: HDL-cholesterol ratio (r = -0.68, p less than 0.01). Fasting C-peptide correlated negatively with HDL-cholesterol (r = -0.76, p less than 0.01), HDL2-cholesterol (r = -0.80, p less than 0.001) and apoprotein A1 (r = -0.56, p less than 0.05) and positively with total: HDL-cholesterol ratio (r = 0.64, p less than 0.05). Neither fasting plasma glucose nor the indices of stimulated insulin secretion (glucose-stimulated plasma insulin and C-peptide) were related to any of the lipoprotein measures. Insulin insensitivity and hyperinsulinaemia were both associated with higher levels of hepatic lipase activity but did not influence lipoprotein lipase activity. In multiple linear regression analysis, hepatic lipase activity was related to HDL-cholesterol independent of insulin insensitivity. In addition, fasting C-peptide alone accounted for 70% of the variance in hepatic lipase activity and this was independent of insulin sensitivity and body mass index. We propose that the abnormalities of HDL-cholesterol in Type 2 diabetes are closely related to enhanced hepatic lipase activity brought about by increased insulin secretion which, in turn, is secondary to the defect in insulin action.

Adult↗
PubMed1991

Association of high density lipoprotein cholesterol with plasma lipolytic activity and C-peptide concentration in type 2 diabetes.

In order to assess whether insulin concentration or plasma lipolytic activity has any role in the regulation of HDL cholesterol concentrations in type 2 diabetes, fasting plasma C-peptide and HDL2-cholesterol concentrations and the post-heparin plasma activities of lipoprotein lipase and hepatic endothelial lipase were measured in 148 patients with type 2 diabetes (76 male, 72 female). HDL2-cholesterol was related negatively to hepatic lipase activity in men (r = -0.49, p less than 0.001) and women (r = -0.43, p less than 0.001) and positively to lipoprotein lipase activity in men (r = -0.33, p less than 0.01) and women (r = 0.36, p less than 0.01). A significant inverse relationship was confirmed between C-peptide and the HDL2-cholesterol subfraction in both sexes (men, r = -0.40, p less than 0.001, women r = -0.51, p less than 0.001). This persisted after adjustment for the effects of alcohol intake, mode of hypoglycaemic treatment, plasma glucose and body mass index. The relationship was lost in men and greatly diminished in women when hepatic lipase activity was included in multiple linear regression analysis, whereas the inclusion of lipoprotein lipase activity in the analysis had little effect on the relationship between C-peptide and HDL2-cholesterol. We suggest that hepatic lipase may be partly responsible for the commonly observed inverse relationship between measures of insulin secretion and HDL-cholesterol concentrations. We speculate that this may occur through a direct stimulatory effect of insulin on the enzyme's activity.

C-Peptide↗
PubMed1990

Acute changes in atherogenic and thrombogenic factors with cessation of smoking.

Tobacco smoking is associated with alterations in several factors considered to be important in the atherosclerotic process. Thirty chronic smokers were studied 2 weeks before and 2 weeks after complete tobacco withdrawal. Significant reductions in fibrinogen, haematocrit, plasma viscosity and whole blood viscosity as well as a significant increase in HDL-cholesterol were observed. As these factors are important in both atherogenesis and thrombogenesis, these observations may give insight into tobacco-induced atherosclerotic disease and may be responsible for the more rapid reduction in the incidence of cardiovascular disease that is believed to occur after stopped smoking.

Adult↗
PubMed1990

Alpha-blocker therapy; a possible advance in the treatment of diabetic hypertension--results of a cross-over study of doxazosin and atenolol monotherapy in hypertensive non-insulin dependent diabetic subjects.

Hyperglycaemia, a raised fibrinogen, an increased serum triglyceride and a reduced HDL-cholesterol are common metabolic features of non-insulin dependent diabetes mellitus (NIDDM). Hypertension is frequently associated with NIDDM, however the influence of antihypertensive therapy on these combined factors in the diabetic is at present unclear. In a double-blind placebo-controlled crossover study in 20 stable NIDDM subjects with hypertension, the metabolic effects of 6 weeks' treatment with the alpha-blocker, doxazosin, was compared with treatment with the beta-blocker, atenolol. Similar and significant reductions in BP were produced by both drugs. Significant increases in weight, HbA1, apoprotein B, serum triglyceride and cholesterol/HDL ratio were observed with atenolol therapy. Doxazosin therapy was associated with opposite patterns of changes in fasting glucose, lipids and lipoproteins but only for serum triglyceride was difference between treatments significant. Fibrinogen was not altered by either treatment. Conclusions from this study indicate; 1) adrenergic mechanisms may be an important influence on glucose homeostasis and lipid metabolism in NIDDM and 2) the beta-blocker, atenolol, has a small adverse effect on weight, glycaemic control and the atherogenic lipid profile, whereas the alpha-blocker, doxazosin, has no such effect and may, in part, correct the disturbances of lipoprotein metabolism characteristic of NIDDM.

Adrenergic alpha-Antagonists↗
PubMed1990

Total phospholipid choline concentration of amniotic fluid in the assessment of foetal gestational and lung maturity. I. Establishment of a direct enzymic method.

An enzymic assay of the choline-containing phospholipids of amniotic fluid which does not require lipid solvent extraction has been developed. Lecithin and sphingomyelin are the dominant phospholipids in mature lung surfactant. The total phospholipid choline content of amniotic fluid, which represents the molar sum of lecithin and sphingomyelin, may be expected to correlate with foetal lung maturity. The merits of our new analytical method of determination of total phospholipid choline concentration in amniotic fluid are discussed.

Amniotic Fluid↗
PubMed1989

The reduction of low density lipoprotein cholesterol by metformin is maintained with long-term therapy.

Changes in serum lipoproteins were studied in 14 non-insulin dependent diabetics on long-term metformin therapy, after 6 weeks' placebo, and again 6 weeks after restarting active drug therapy. Withdrawal of metformin resulted in a rise of fasting blood glucose, HbA1, serum total and low density lipoprotein (LDL) cholesterol. Restarting the drug reversed these changes. Multivariate analysis showed that serum total and LDL cholesterol varied with treatment but not with glycaemic control. Metformin can lower serum total and LDL cholesterol in non-insulin dependent diabetics and this effect is maintained long term.

Cholesterol↗
PubMed1988

Serum lipids, lipoproteins and macrovascular disease in non-insulin-dependent diabetics: a possible new approach to prevention.

The relationship between macrovascular disease and serum lipids, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL), and subfraction cholesterol, and apolipoproteins has been examined in 53 female and 95 male patients with non-insulin-dependent diabetes mellitus (NIDDM). In males, those with macrovascular disease had higher serum and LDL cholesterol concentrations than those without. In females, those with macrovascular disease had higher levels of serum triglyceride, cholesterol, LDL cholesterol, as well as lower HDL, HDL2, and HDL3 cholesterol and apoprotein A-1, than those without. On multivariate analysis, LDL cholesterol was the most important association with macrovascular disease in males and apoprotein A-1 in females. In a subgroup of 36 patients, a double-blind placebo controlled study using bezafibrate or placebo, in addition to conventional oral hypoglycaemic therapy over 4 months, showed falls in serum and LDL cholesterol and in serum triglyceride and a rise in HDL cholesterol in the treated group. These changes should reduce the incidence of macrovascular disease in NIDDM and we suggest further prospective studies of such therapy in addition to conventional oral hypoglycaemic agents.

Aged↗
PubMed1988

The effect of glibenclamide and metformin on serum lipoproteins in type 2 diabetes.

In a cross-over study, the effects of 3 months treatment with metformin or glibenclamide on body weight, blood glucose control, and serum lipoproteins were compared in 35 Type 2 diabetic patients, inadequately controlled by dietary therapy alone. Glibenclamide alone increased body weight (mean change +2.75 kg; 95% confidence intervals +1.95 to +3.55 kg; p less than 0.0001). Glibenclamide and metformin achieved equivalent blood glucose control, independent of initial body mass index. Neither drug affected serum triglyceride concentration. Metformin alone significantly reduced low density lipoprotein cholesterol (mean change -0.34 mmol l-1; 95% confidence intervals -0.12 to -0.57 mmol l-1; p less than 0.01). Neither drug altered high density lipoprotein or subfraction cholesterol.

Blood Glucose↗
PubMed1988

Beta-blockers, lipoproteins and non-insulin dependent diabetes.

In a study on 138 hypertensive non-insulin dependent diabetic subjects, factors influencing lipoproteins were assessed. Multiple regression analyses were carried out in order to assess the influence of beta-blocker antihypertensive therapy while making allowances for other confounding variables. In males, but not in females, on a beta-blocker for hypertension, total high density lipoprotein- (HDL-) and HDL-subfraction cholesterol were significantly lower while the serum triglyceride was increased, though not significantly. In male non-insulin dependent diabetics, regimens containing a beta-blocker may worsen an already abnormal lipoprotein profile and antihypertensive agents other than beta-blocking agents should be used if possible.

Adrenergic beta-Antagonists↗
PubMed1988

Acute lipoprotein changes associated with atenolol therapy for hypertension in non-insulin dependent diabetes.

In a study on 11 stable hypertensive non-insulin dependent diabetic subjects the influence of beta-blocker (atenolol 100mg) withdrawal and reintroduction was assessed. After a three week placebo phase significant increases in pulse rate, high density lipoprotein- and high density lipoprotein2-cholesterol and a significant decrease in triglyceride were observed. Three weeks after recommencement of atenolol therapy the pulse, lipid and lipoprotein changes were reversed and significantly so. Weight and blood pressure remained constant throughout. Results from this study indicate that in non-insulin dependent diabetes, atenolol-induced lipid and lipoprotein changes are reversible in the short term and occur in the absence of significant changes in blood pressure control. The lipoprotein changes observed involved an alteration in high density lipoprotein composition. As a reduced high density lipoprotein cholesterol is associated with macrovascular disease, future studies on the association of lipoproteins and diabetic complications should take into account these changes in lipoproteins with beta-blocker hypotensive therapy.

Adult↗