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Biomedical subjects

M F Laker

Publications and source records attributed to M F Laker.

At least 37 records · Page 2Linked to original sources
PubMed1995

The effects of lipid lowering drugs on metabolic control and lipoprotein composition in type 2 diabetic patients with mild hyperlipidaemia.

Patients with Type 2 diabetes are at increased risk from macrovascular disease whether or not they are hyperlipidaemic. Several factors may contribute to this increased risk including abnormalities of lipoprotein composition. The aim of our study was to determine the effects of lipid lowering drugs on lipoprotein composition (lipoprotein fractions were separated by sequential flotation ultracentrifugation) and insulin sensitivity (measured by a modified Harano technique) in 44 patients with mild hyperlipidaemia. All patients had total cholesterol concentrations between 5.2 and 6.5 mmol l-1 and total triglyceride concentrations < 3.0 mmol l-1, and were randomized by minimization to receive treatment for 12 weeks with bezafibrate, acipimox, simvastatin or placebo. Total cholesterol concentrations were decreased by simvastatin, 5.7 +/- 0.4 to 3.7 +/- 0.6 mmol l-1 (p < 0.05), due mainly to reduced LDL-cholesterol levels (-1.25 mmol l-1; p < 0.05), and bezafibrate 5.7 +/- 0.6 to 4.6 +/- 0.4 mmol l-1 (p < 0.05). The LDL:HDL-cholesterol ratio was reduced in the simvastatin group 2.0 +/- 0.5 to 1.2 +/- 0.3 (p < 0.005). There was no effect of the drugs on glycated haemoglobin or insulin sensitivity. In conclusion bezafibrate and simvastatin improve the lipid profile in Type 2 diabetic patients without adversely affecting diabetic control.

Apolipoproteins B↗
PubMed1995

Assessing the impact of blood sample type on the estimated prevalence of impaired glucose tolerance and diabetes mellitus in epidemiological surveys.

In a prospective study of 353 patients who had undergone coronary artery bypass graft surgery a 75 g oral glucose tolerance test was performed at 3 months and 12 months after surgery. Venous whole blood glucose and venous plasma glucose samples were assayed on a bench-top analyser. The World Health Organization diagnostic criteria for impaired glucose tolerance and diabetes mellitus were applied to venous whole blood glucose and venous plasma glucose measurements. The difference between the plasma and whole blood concentration of glucose was 0.79-0.86 mmol l-1 at a plasma glucose of 7.8 mmol l-1 and 1.22-1.24 mmol l-1 at a plasma glucose of 11.1 mmol l-1 (compared to 1.1 mmol l-1 by World Health Organization criteria at both cut-points). Despite this, in our subject population with a high prevalence of impaired glucose tolerance (20.3% at 3 months, 15.3% at 12 months) and diabetes mellitus (10.1% at 3 months and 12 months), there was no significant difference in the proportion classified impaired glucose tolerance or having diabetes mellitus using venous whole blood glucose compared to venous plasma glucose. We conclude that despite the minor anomaly between WHO diagnostic criteria based on venous whole blood glucose and venous plasma glucose measurements, these criteria are robust and give broadly comparable population prevalence of diabetes mellitus and impaired glucose tolerance irrespective of blood sample choice.

Autoanalysis↗
PubMed1995

Effect of storage at 4 degrees C and -20 degrees C on lipid, lipoprotein, and apolipoprotein concentrations.

We have investigated the effects on lipid, apolipoprotein, and lipoprotein measurements of storing unfractionated serum at 4 degrees C for 10 days and at -20 degrees C for 10 days or 3 months. Total serum concentrations of lipids were stable, although apolipoprotein B showed a 5.3% increase after 3 months at -20 degrees C (P < 0.001). Increases in low-density (LDL) and high-density lipoprotein (HDL) triglyceride and very-low-density lipoprotein (VLDL) esterified cholesterol concentrations and decreases in free cholesterol concentrations in LDL and HDL after storage of serum for 10 days at 4 degrees C were verified by fractionation of lipoproteins by sequential flotation ultracentrifugation. Ten days' storage of serum at -20 degrees C resulted in increases in VLDL triglyceride and phospholipid concentrations, with decreases in HDL concentrations in triglycerides and phospholipids; changes were more extensive after 3 months at -20 degrees C. We conclude that ultracentrifugation of serum for lipoprotein analysis should be performed as soon as possible after collection.

Apolipoproteins↗
PubMed1994

Reduced serum lipoprotein(a) levels in patients with primary biliary cirrhosis.

Lipoprotein(a) (Lp(a)) is a unique lipoprotein, elevated serum levels of which are independently associated with an increased risk of coronary heart disease (CHD). Primary biliary cirrhosis (PBC) is often associated with high serum cholesterol, itself a risk factor for CHD. Despite this, patients with PBC are thought to have a lower than expected incidence of CHD. We hypothesised that this may be related to low serum levels of Lp(a) in PBC patients. This was investigated by collecting fasting blood samples from 42 patients with PBC, 39 age- and sex-matched subjects with non-PBC liver disease and 432 community control subjects. Serum was analysed for total cholesterol, triglycerides, high density lipoprotein (HDL) cholesterol and apolipoproteins A1 and B (apo A1 and apo B). Lp(a) was measured by an enzyme-linked immunosorbent assay (ELISA) technique. There was a significant reduction of Lp(a) concentrations in the PBC group compared with the healthy controls (median value 28.5 mg/l vs. 75.0 mg/l, P < 0.005) and between the non-PBC liver disease group (median value 52.0 mg/l) and control group (P = 0.001). Within both the liver disease and PBC patient groups there were significant negative correlations between Lp(a) levels and bilirubin (R = -0.564, P < 0.001 and R = -0.395, P = 0.010 respectively). This preliminary study has demonstrated reduced Lp(a) levels in PBC patients which may be a contributory factor to explain a possible cardioprotective effect in such patients, despite elevated LDL cholesterol levels.

Bilirubin↗
PubMed1994

Simvastatin in non-insulin-dependent diabetes mellitus: effect on serum lipids, lipoproteins and haemostatic measures.

The clinical efficacy of the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMGCoA) reductase inhibitor simvastatin in the treatment of hypercholesterolaemia in non-insulin-dependent diabetes (NIDDM), was examined in a double-blind placebo-controlled study of 6 months in 70 patients with NIDDM (age 25-70 years), of whom 57 were randomised to placebo (29 patients) or simvastatin for 6 months, following a 3-month run-in on diet. Patients were hypercholesterolaemic (7.8 (7.6-8.0) (mean (95% confidence intervals)) mmol/l simvastatin vs. 8.0 (7.7-8.5) mmol/l placebo) and mildly hypertriglyceridaemic (2.6 (2.2-3.0) simvastatin vs. 2.9 (2.3-3.5) placebo). Other lipid measures and estimates of glycaemic control and haemostasis were similar in both groups. There were no significant changes in lipids, haemostatic factors, or measures of glycaemic control in the placebo treatment group. Conversely by the end of 24 weeks, simvastatin produced a 28% reduction in cholesterol (to 5.6 (5.0-6.2) mmol/l (P < 0.001)), a 38% reduction in LDL cholesterol (from 5.5 (5.4-5.6) mmol/l to 3.4 (2.8-4.0) mmol/l, P < 0.001), a 15% reduction in triglyceride (to 2.2 (1.8-2.6) mmol/l, P < 0.05, and a 9% rise in HDL (from 1.16 (1.07-1.25) to 1.23 (1.14-1.32) mmol/l, P < 0.05). Improvements in apolipoprotein B (apo B) (-28%, P < 0.001), the LDL cholesterol to apo B ratio (-20%, P < 0.001), and apo A1 (+15%, P < 0.001) were recorded. There were no effects upon fibrinogen, factor VII activity, factor VIII activity, or measures of glycaemic control (fasting glucose, insulin, C-peptide, or HbA1).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Circulating lipids and glycaemic control in insulin dependent diabetic children.

The prevalence of dyslipidaemia in children with insulin dependent diabetes mellitus (IDDM) and its relation to glycaemic control was studied in a group of 51 diabetic children and a control population of 132 schoolchildren. The prevalence of dyslipidaemia in the fasting state was increased in the diabetic group (39%) compared with control subjects (17%). Serum cholesterol concentration alone was raised in 25% of diabetic subjects while serum cholesterol and triglycerides were raised in 14%, compared with 16% and 0.7% respectively in control subjects. Serum total cholesterol (5.1 v 4.5 mmol/l), low density lipoprotein cholesterol (3.2 v 2.6 mmol/l), non-esterified fatty acids (0.91 v 0.50 mmol/l), and triglycerides (0.94 v 0.76 mmol/l) were higher in diabetic children. Serum total cholesterol, triglycerides, and apolipoprotein (apo)B concentrations increased with worsening control, while serum high density lipoprotein cholesterol and apoA-I concentrations were unaltered. There were also positive correlations between glycated haemoglobin and total cholesterol, triglycerides, and apoB in diabetic children. Thus, abnormalities in circulating lipids are common in young subjects with IDDM but largely disappear if blood glucose concentrations are reasonably controlled.

Adolescent↗
PubMed1994

Coronary artery disease is associated with increased lipoprotein(a) concentrations independent of the size of circulating apolipoprotein(a) isoforms.

Lipoprotein(a) [Lp(a)] concentration and apolipoprotein(a) [apo(a)] isoforms (identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE] and Western blotting) were determined in a group of 508 asymptomatic Caucasian members of the community and in 318 Caucasian patients with angiographically defined coronary artery disease (CAD). Conventional risk factors for CAD were also measured. Lp(a) concentration was almost twice as high in subjects with CAD (geometric mean, 152 mg/L [geometric SD, 10 to 1398 mg/L]) as in asymptomatic control subjects (geometric mean, 84 mg/L [geometric SD, 21 to 334 mg/L]). Asymptomatic women had higher concentrations of Lp(a) than asymptomatic men. Patients with CAD were older and were more likely to have smoked and to have a first-degree relative with premature CAD (< 55 years of age), and a higher proportion were male. Patients with CAD had higher concentrations of Lp(a) independently of the number of isoform bands expressed. When apo(a) isoforms were allocated to 1 of 10 classes on the basis of their molecular size (Rf versus apoB in SDS-PAGE), patients with CAD did not express an excess of low-molecular-mass (higher concentration) isoforms but did express a higher proportion of double-band phenotypes with fewer "null" phenotypes. The relationship between the two isoform bands in a double-band phenotype was the same in both populations. Isoform mobility was defined as a continuous variable equal to the mobility of a single isoform band (single-band phenotypes) or the mean of the two isoforms in a double-band phenotype. Two variables, isoform mobility and the number of isoform bands expressed, were used to summarize the large range of isoform patterns (at least 45) that could be identified. Isoform mobility, the number of isoform bands expressed, and the presence of CAD were the three most important independent predictors of Lp(a) concentration (descending order). Only sex and LDL cholesterol were additional independent predictors of Lp(a) concentration in step-wise regression models including a wide range of demographic factors and lipid and glycemic risk factors. We conclude that Lp(a) concentration is associated with CAD independently of the isoform pattern expressed. The apo(a) gene locus exerts a strong control over circulating Lp(a) concentration, and a better understanding of the control of expression of the apo(a) gene will be essential to understand the relationship between Lp(a) and CAD.

Apolipoproteins A↗
PubMed1994

Lipid levels in schoolchildren in north east England: effects of feeding and age.

Serum total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein (apo) A-I and apoB concentrations were estimated and low-density lipoprotein (LDL) cholesterol levels were calculated in 132 children aged 11.4-17.3 years. The effect of feeding was investigated by estimating postprandial values and also by studying the effects of a test meal. The distribution of all data was consistent with Gaussian apart from triglycerides which was log normal. Overall fasting values were [mean (standard deviation; SD)] cholesterol 4.5 (0.8) mmol/L, HDL cholesterol 1.5 (0.4) mmol/L, LDL cholesterol 2.6 (0.8) mmol/L, apoA-I 1.5 (0.3) g/L, apoB 1.0 (0.4) g/L and triglycerides 0.76 (0.38-1.51) mmol/L, the values for triglycerides being mean (95% confidence intervals). Girls had higher triglycerides than boys [0.82 (0.43-1.54) versus 0.70 (0.36-1.33)] and different effects of age on lipids were found, HDL cholesterol being negatively correlated with age in boys (r = -0.37; P < 0.001), but not in girls, and apoA-I being negatively correlated with age in boys (r = -0.31; P = 0.006), but positively correlated with age in girls (r = 0.32; P = 0.008). Triglycerides rose and HDL cholesterol fell following feeding and inconsistent effects were seen on apoA-I and apoB.

Adolescent↗
PubMed1994

The contribution of lipids to coronary heart disease in diabetes mellitus.

Cardiovascular disease is two to three times more common in diabetic patients than in the non-diabetic population. Although risk factors that affect the general population such as age, cigarette smoking, hypertension, obesity and hypercholesterolaemia also affect diabetic subjects, the increased prevalence of hypertension and obesity in non-insulin-dependent diabetes mellitus (NIDDM) only partially explains the increased morbidity and mortality from coronary heart disease (CHD). Other factors must therefore be considered in this group of patients. Triglyceride concentrations, particularly post-prandial levels, may be important. Diabetic subjects have increased very-low-density-lipoprotein (VLDL), increased intermediate-density-lipoprotein (IDL) and low high-density-lipoprotein (HDL) concentrations, and differences in lipoprotein composition may partly explain increased atherogenesis. Although LDL levels of diabetic patients are not different from those of control subjects. LDL particles are potentially atherogenic as they are smaller, more dense and prone to oxidative modification. NIDDM subjects also have altered apolipoprotein concentrations, including increased apoB, apoC-III, and decreased apoA-I; in addition, apoE-2 may be over-represented in diabetic populations. Thus, apart from the traditional risk factors, there are several lipoprotein compositional abnormalities that may contribute to the increased prevalence of CHD in diabetes.

Apolipoproteins↗
PubMed1993

Association between impaired glucose tolerance and circulating concentration of Lp(a) lipoprotein in relation to coronary heart disease.

OBJECTIVE: To examine whether impaired glucose tolerance and raised Lp(a) lipoprotein concentrations are associated in subjects with coronary artery disease. DESIGN: Study of two subject populations, one with and one without symptomatic coronary artery disease. Case-control analysis of patients with impaired glucose tolerance and normal glucose tolerance performed in each subject population independently. SETTING: A general practice and a hospital ward in Newcastle upon Tyne. SUBJECTS: 517 apparently healthy subjects, 13 with impaired glucose tolerance, and 245 patients who had undergone coronary artery bypass graft surgery 12 months before, 51 with impaired glucose tolerance. MAIN OUTCOME MEASURES: Serum Lp(a) lipoprotein concentration, plasma glucose concentration before and after oral challenge with 75 g glucose monohydrate, and Lp(a) lipoprotein isoforms. RESULTS: In both the asymptomatic subjects and the subjects with coronary artery disease there was no significant difference between subjects with impaired glucose tolerance and subjects with normal and body mass index in serum Lp(a) lipoprotein concentrations (geometric mean 61 (geometric SD 4) mg/l v 83 (5) mg/l for asymptomatic subjects, 175 (3) v 197 (2) for subjects with heart disease), nor was there any difference in the proportion of subjects who had Lp(a) lipoprotein concentrations > 300 mg/l (31% v 23% for asymptomatic subjects, 37% v 37% for subjects with heart disease). For both subject groups there was no significant correlation between Lp(a) lipoprotein concentration and plasma glucose concentration after a glucose tolerance test, nor did Lp(a) lipoprotein concentration vary by quintile of glucose concentration after the test. Examination of Lp(a) lipoprotein isoforms in the subjects with coronary artery disease revealed an inverse relation between isoform size and plasma Lp(a) lipoprotein concentration, but there was no evidence that impaired glucose tolerance was associated with particular Lp(a) lipoprotein isoforms. CONCLUSION: Raised Lp(a) lipoprotein concentrations are not responsible for the association between impaired glucose tolerance and coronary artery disease.

Blood Glucose↗
PubMed1993

Analysis of multiple sugar probes in urine and plasma by high-performance anion-exchange chromatography with pulsed electrochemical detection. Application in the assessment of intestinal permeability in human immunodeficiency virus infection.

Mannitol, 3-O-methylglucose and lactulose administered orally are used to investigate small intestinal absorption pathways and mucosal integrity. Current methods of analysis include thin-layer chromatography, gas chromatography (GC) and enzymatic analysis, which require separate estimation of mono- and disaccharides and for GC, prior derivatization. We describe a high-pressure anion-exchange chromatographic method coupled with pulsed electrochemical detection allowing simultaneous measurement of all three sugars and its clinical application in monitoring intestinal damage in human immunodeficiency virus (HIV) infection. Sample preparation is simple and fast. All sugars are resolved within 10 min. Mean recovery is 93.3% for all sugars and the overall relative standard deviation is 4.2%. Intestinal permeability (lactulose/mannitol ratio) rises with disease progression to AIDS, indicating mucosal damage. The greatest increase in permeability is associated with chronic diarrhoea. The method is an ideal non-invasive test to assess gut mucosal damage in HIV infection.

3-O-Methylglucose↗
PubMed1993

Management of hyperlipidaemia: guidelines of the British Hyperlipidaemia Association.

There is considerable evidence to suggest that the identification and treatment of dyslipidaemia will reduce the risk of premature CHD, i.e. before the age of 65. Diagnosis of the cause of raised plasma lipid levels will enable appropriate decisions to be taken with regard to management. The cornerstone of treatment is nutritional counselling and attention to other major risk factors for CHD, particularly smoking and hypertension. For a small percentage of patients with severe hyperlipidaemia drug therapy is indicated. Appropriate drug choices need to be made based on the particular lipid abnormality to be treated. In general those patients with clinical vascular disease are treated more aggressively than those where the aim is primary prevention. More research is needed to determine individual risk more precisely and to allow proper targeting of therapy. Genetic factors, qualitative changes in lipoproteins, lipoprotein (a), fibrinogen, and other coagulation and thrombotic factors are likely to be important in individual risk assessment. There is no doubt that more information is needed from prospective studies of lipid-lowering therapy in terms of risk benefit for affected individuals. Hopefully the major studies currently underway will fill some of the gaps in our knowledge. Until then aggressive therapy with drugs should be reserved for those at highest risk where the benefit is likely to be greatest.

Cholesterol, Dietary↗
PubMed1993

Lipoprotein compositional abnormalities and insulin resistance in type II diabetic patients with mild hyperlipidemia.

Lipoprotein composition was determined using ultracentrifugation in 20 non-insulin-dependent (NIDDM) diabetic patients on diet only (D), 20 NIDDM patients on diet and sulfonylurea therapy (T), and 20 nondiabetic control subjects (C), all of whom had total plasma cholesterol concentrations < 6.5 mmol/L and total plasma triglyceride concentrations < 3.0 mmol/L. Although the groups were well matched for age, body mass index, total triglyceride levels, and total cholesterol concentrations, there were significant compositional abnormalities in the low-density lipoprotein (LDL) fractions of diabetic subjects. The LDL total lipid to apolipoprotein B weight ratio (representing the density distributions of LDL particles) was reduced in both diabetic groups: 3.75 +/- 0.3, 3.50 +/- 0.28, and 3.54 +/- 0.22 in C, D, and T groups, respectively (mean +/- SD; P < .05). This was associated with a significant shift in the hydrated density distributions of LDL in the diabetic groups, with the average peak densities being 1.0320 g/mL (in C), 1.0365 g/mL (in D), and 1.0380 g/mL (in T) (P < .05). The LDL particles were also smaller in the NIDDM patients: 21.1 +/- 0.7, 20.4 +/- 0.5, and 20.6 +/- 0.5 nm in C, D, and T groups, respectively (P < .05). When the NIDDM groups were analyzed together, the LDL peak density was found to correlate with both insulin resistance (measured by a modified Harano technique; r = 0.37, P < .015) and total triglyceride concentrations (r = 0.40, P < .01). The results show that diabetic patients have small, dense LDL particles, which may be related to insulin resistance, and that these occur with minimal elevations of total triglyceride concentrations. These potentially atherogenic changes may contribute to the increased coronary heart disease in diabetic patients with mild hyperlipidemia.

Aged↗