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Biomedical subjects

G F Watts

Publications and source records attributed to G F Watts.

At least 127 records · Page 7Linked to original sources
PubMed1994

Role of glycaemic control in development of microalbuminuria in patients with insulin dependent diabetes.

OBJECTIVE: To ascertain which factors determine the progression from very low rates of albumin excretion to persistent microalbuminuria in patients with insulin dependent diabetes mellitus. DESIGN: A 10 year prospective study of a cohort of diabetic patients. SETTING: Outpatient department of the Portsmouth District Hospitals. SUBJECTS: 97 patients with insulin dependent diabetes mellitus who were initially free of microalbuminuria and hypertension. MAIN OUTCOME MEASURE: Urinary albumin: creatinine ratio. RESULTS: Eight of the 97 patients had developed microalbuminuria (urinary albumin:creatinine ratio > 3 mg/mmol in three consecutive early morning samples) by the 10 year follow up. The group who developed microalbuminuria had higher baseline log10 plasma glucose concentrations (mean (SD), 1.210 (0.122) v 0.984 (0.196) mmol/l, P < 0.001) and glycated haemoglobin concentrations (1.112% (0.069%) v 0.997% (0.076%), P < 0.001) and a younger age at onset of diabetes (10.0 (5.5) v 15.6 (7.8) years, P < 0.05). There was no difference in baseline duration of diabetes, smoking, sex, insulin dose, body mass index, serum creatinine concentration, or systolic, diastolic, or mean arterial blood pressure between the two groups. Multiple linear regression analysis showed that urinary albumin:creatinine ratio at 10 years was influenced by initial albumin:creatinine ratio (P = 0.006), initial glycated haemoglobin concentration (P = 0.002), and duration of diabetes (P = 0.045). Genotype for angiotensin converting enzyme was not related to the development of microalbuminuria nor, in a larger group of patients, the presence of any degree of diabetic nephropathy. CONCLUSION: In patients with insulin dependent diabetes mellitus the progression of minimal albuminuria and the development of microalbuminuria is determined primarily by poor long term glycaemic control. There is a weaker relation with longer duration of disease and younger age at onset of diabetes, but blood pressure does not seem to be implicated. Gene polymorphism for angiotensin converting enzyme is not linked to the development of microalbuminuria or established diabetic nephropathy.

Adolescent↗
PubMed1994

Sex differences in endothelial function in normal and hypercholesterolaemic subjects.

Acetylcholine stimulates endothelial synthesis of nitric oxide from L-arginine. To investigate the influence of sex on endothelial function, we measured vasodilator responses to brachial artery administration of acetylcholine in hypercholesterolaemic and control men and women. Mean response to acetylcholine was impaired (55% of that in controls at 15 micrograms/min) in hypercholesterolaemic men but not in hypercholesterolaemic women. L-arginine normalised responses to acetylcholine in hypercholesterolaemic men, but had similar effects in hypercholesterolaemic and control women. These results suggest that women are protected against adverse effects of hypercholesterolaemia on the L-arginine/nitric-oxide pathway.

Acetylcholine↗
PubMed1994

Nutrient intake and progression of coronary artery disease.

The relation between nutrient intake and progression of coronary artery disease was examined in 50 men receiving a lipid-lowering diet or usual care in the St. Thomas' Atherosclerosis Regression Study. Nutrient intake was assessed by diet history. Changes in coronary angiograms were measured by quantitative image analysis. In univariate linear regression analysis progression of disease over 39 months, as measured by decrease in minimum absolute width of coronary segments, was directly related to dietary energy (p < 0.001) and to the absolute intakes of total fat (p < 0.001), saturated fat (p < 0.001), monounsaturated fat (p = 0.016) and cholesterol (p = 0.06). No significant associations were seen with polyunsaturated fat, carbohydrate, protein, fiber, alcohol or with the ratio of intakes of polyunsaturated fatty acids to saturated fatty acids. In multiple linear regression analysis the associations of change in minimum absolute width of coronary segments with total or saturated fat persisted when adjusted for plasma low-density lipoprotein cholesterol concentration, age, weight, blood pressure, smoking or treatment group assignment. The findings suggest that in middle-aged men, progression of CAD is strongly influenced by intake of saturated fatty acids, an effect mediated in part by mechanisms other than the influence of this nutrient on plasma cholesterol and low-density lipoprotein cholesterol.

Basal Metabolism↗
PubMed1994

Short-term effects of mepacrine on serum lipids, lipoproteins, and apolipoproteins in patients with non-insulin-dependent diabetes mellitus.

We investigated the effects of 7 days' treatment with oral mepacrine hydrochloride 100 mg three times daily on fasting serum levels of glucose, insulin, lipids, lipoproteins, and apolipoproteins in 16 patients with non-insulin-dependent diabetes mellitus (NIDDM) in a double-blind placebo-controlled study. Mepacrine treatment decreased fasting levels of total cholesterol (7.0 +/- 0.6 to 5.6 +/- 0.4 mmol/L, P < .01), low-density lipoprotein (LDL) cholesterol (4.7 +/- 0.5 to 3.5 +/- 0.3 mmol/L, P < .01), and apolipoprotein (apo) B (1.20 +/- 0.14 to 1.02 +/- 0.08 g/L, P < .05), and the ratio of LDL cholesterol to high-density lipoprotein (HDL) cholesterol (P < .05). There was no change in fasting levels of serum glucose, insulin, C-peptide, nonesterified free fatty acids, triglycerides, or lipoprotein(a). In conclusion, a short course of oral mepacrine treatment has a potentially beneficial effect on LDL cholesterol and apo B levels in patients with NIDDM and warrants further investigation in this situation.

Adult↗
PubMed1994

The effect of growth hormone replacement on serum lipids, lipoproteins, apolipoproteins and cholesterol precursors in adult growth hormone deficient patients.

OBJECTIVE: Adult patients with growth hormone deficiency are thought to be at higher risk of mortality from cardiovascular disease. We therefore investigated the effect of recombinant human growth hormone (rhGH) replacement therapy on fasting serum concentrations of lipids, lipoproteins and cholesterol precursors in adult growth hormone deficient patients. DESIGN: Double-blind placebo controlled trial. Patients were randomly allocated to placebo or rhGH replacement therapy (0.018 U/kg/day for 1 month followed by 0.036 U/kg/day for 1 month). PATIENTS: Eighteen patients with severe growth hormone deficiency. MEASUREMENTS: Fasting lipid, lipoprotein and cholesterol precursors (lathosterol and mevalonic acid) were measured at baseline and after 2 months. RESULTS: In the rhGH treated group there was a significant fall in serum cholesterol (P < 0.01) (6.44 +/- 0.49 to 5.71 +/- 0.48 mmol/l), LDL cholesterol (P < 0.02) (4.29 +/- 0.49 to 3.62 +/- 0.44 mmol/l), LDL cholesterol/HDL cholesterol ratio (P < 0.02) (3.99 +/- 0.62 to 3.26 +/- 0.39), apolipoprotein B (P < 0.01 (1.30 +/- 0.11 to 1.15 +/- 0.11 g/l) and mevalonic acid (P < 0.05) (13.4 +/- 10.96 to 6.21 +/- 1.91 micrograms/l). There were no significant changes in triglycerides, HDL cholesterol, apolipoprotein A1, lipoprotein (a) or lathosterol concentrations. In the GH treated group the rise in serum insulin was inversely correlated with the fall in cholesterol (P < 0.05), LDL cholesterol (P < 0.01) and apolipoprotein B (P < 0.01). There were no significant changes in any of the measured variables in the placebo group. CONCLUSION: We conclude that GH may be involved in the regulation of lipid and lipoprotein metabolism and that rhGH replacement therapy of adult GHD patients is associated with beneficial changes in lipid and lipoprotein profiles. The reduction in mevalonic acid is consistent with up-regulation of hepatic LDL receptors caused by GH and this may explain the fall in LDL cholesterol and apolipoprotein B concentrations.

Adult↗
PubMed1994

Ethnic differences in lipid and lipoprotein metabolism in pregnant women of African and Caucasian origin.

AIMS: To investigate differences in serum lipid, lipoprotein and apolipoprotein concentrations in pregnant women of different ethnic origin. METHODS: Serum lipid, lipoprotein and apolipoprotein concentrations were measured in 232 women (114 Caucasians, 118 Africans/Afro-Caribbeans), who presented consecutively for screening for gestational diabetes in the third trimester of pregnancy. RESULTS: African/Afro-Caribbean pregnant women had lower serum concentrations of total cholesterol, low density lipoprotein cholesterol, triglycerides, and apolipoprotein B and higher high density lipoprotein cholesterol and Lp(a) lipoprotein concentrations compared with Caucasian women. Apolipoprotein A1 concentrations were similar in the two groups. The differences were not attributable to differences in weight, age, parity, or postload plasma glucose levels. CONCLUSION: Ethnic origin is an important determinant of serum lipid, lipoprotein and apolipoprotein concentrations during pregnancy.

Adult↗
PubMed1994

Comparison of immunoturbidimetric and Lowry methods for measuring concentration of very low density lipoprotein apolipoprotein B-100 in plasma.

To assess whether the Lowry-tetramethylurea method for measuring apolipoprotein B-100 (apo-B) in very low density lipoprotein (VLDL) could be replaced by direct assay of VLDL apo-B using a highly practicable immunological method. Seventy five fasting blood samples were collected from patients attending the lipid clinic at this hospital. Plasma was separated immediately and VLDL isolated by preparative ultracentrifugation at solution density 0.93-1.006 kg/l. Apo-B was precipitated from an aliquot of the VLDL fraction using the tetramethylurea (TMU) technique and protein mass determined by the Lowry method (LM); mean apo-B 83.02 micrograms/ml (SD 74.85). Apo-B was also measured in VLDL using direct immunoturbidimetry on the Cobas-Fara analyser; mean apo-B 82.32 micrograms/ml (SD 72.88). There was a very close correlation between methods (immunoturbidimetry = 0.94.LM + 3.95, r = 0.97, p < 0.001). The mean difference between methods (constant error) was small (0.70 microgram/ml) and not significant (p = 0.742). Random error was 13.01 micrograms/ml by analysis of variance. It is concluded that immunoturbidimetry, a more rapid and convenient test, may replace the LM and TMU techniques for measuring VLDL apo-B concentration and that this method could be applied to research studies requiring analysis of large numbers of samples.

Apolipoprotein B-100↗
PubMed1994

Serum lipids, lipoproteins and apolipoproteins in pregnant non-diabetic patients.

AIMS: To investigate the effect of pregnancy on serum concentrations of lipids, lipoproteins, and apolipoproteins. METHODS: Fasting serum concentrations of total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), apolipoproteins AI, AII, and B, and lipoprotein (a) were measured in 178 women with normal glucose tolerance in the second and third trimesters of pregnancy and in a control group of 58 non-pregnant women of similar age. Data were analysed using the unpaired t test and by one-way analysis of variance. RESULTS: The pregnant women had significantly higher concentrations of total cholesterol, triglyceride, LDL cholesterol, HDL cholesterol, and apolipoproteins AI and B (p < 0.001) and apolipoprotein AII (p = 0.003) than the control women. The ratio of apolipoprotein B:apolipoprotein AI was significantly higher in the pregnant women than in the controls (p < 0.001), but the total cholesterol:HDL cholesterol ratio was not significantly different. No significant difference was found in the concentration of lipoprotein (a). CONCLUSIONS: Hyperlipidaemia is common in the second half of pregnancy. This may be a purely physiological response to pregnancy or it may be indicative of pathology in some women. These results warrant a follow up study to investigate whether the hyperlipidaemic response to pregnancy is variable and if so, whether it can predict future hyperlipidaemia in a manner analogous to that of impaired glucose tolerance during pregnancy, predicting non-insulin dependent diabetes in later life.

Adult↗
PubMed1994

Metabolic determinants of the course of coronary artery disease in men.

We examined associations between metabolic variables and changes in coronary artery disease (CAD) in the St. Thomas' Atherosclerosis Regression Study (STARS). The course of CAD over 3 years was measured continually by quantitative coronary angiography, i.e., as the per patient change in the mean absolute width of coronary segments (delta MAWS). The decrease in MAWS (progression of CAD) was significantly correlated with in-trial plasma concentrations of cholesterol (P = 0.002), low-density lipoprotein (LDL) cholesterol (P = 0.001), apolipoprotein B (apoB) (P = 0.008), and lipoprotein(a) [Lp(a)] (P = 0.004); no significant associations were found with high-density lipoprotein (HDL) cholesterol, apoA-I, vitamin E, thyroid hormones, fibrinogen, von Willebrand factor, or post-load plasma glucose and insulin concentrations. By multiple regression analysis, LDL cholesterol was the best predictor of delta MAWS, the adjusted model explaining 22% of the variance (P = 0.04). Thus, in men with symptomatic CAD the most important metabolic predictor of change in CAD is plasma LDL cholesterol, there being no advantage in measuring other variables, in particular, apoB or Lp(a).

Adult↗
PubMed1993

Metabolism of apolipoprotein B-100 and of triglyceride-rich lipoprotein particles in the absence of functional lipoprotein lipase.

Cholesterol and triglyceride in the various lipoprotein fractions were determined in five patients without functional lipoprotein lipase (LPL) while on their habitual therapeutic diet of 'low fat' content (20-25 g/day). They were also studied following 3 days on either a 'minimal fat' diet (< 15 g/day) or a 'moderate fat' diet (45-50 g/day). Values obtained were compared with the respective levels measured in five control subjects on a 'normal fat' (70-90 g/day) diet. The patients had hypertriglyceridaemia (type V hyperlipoproteinaemia) under all dietary conditions. Cholesterol and triglyceride levels in plasma and in the chylomicron fraction increased in the patients with increasing dietary fat. In the very low density lipoprotein (VLDL) fraction from the patients, triglyceride levels also increased with the dietary fat intake, but cholesterol levels were similar under all dietary conditions. In the patients, cholesterol concentrations in the low (LDL) and high density (HDL) lipoprotein fractions were significantly lower than the respective levels in controls, but the ratio of cholesterol to triglyceride levels in both of these lipoprotein fractions decreased with the dietary fat intake. VLDL apolipoprotein B-100 (apo B-100) pool size was similar in the patients on the two test diets (P = 0.95) and 3.5-fold higher than in five healthy volunteers on a normal fat diet. Using a stable isotope enrichment method, the kinetics of apo B-100 were investigated in the patients under the last two dietary conditions. The fractional and absolute secretion rates of the apolipoprotein in the patients did not vary with fat intake, but fractional secretion rates were significantly lower and the absolute secretion rates were significantly higher in the patients than the respective values in the controls. These results are consistent with the hypothesis that in the absence of LPL activity the metabolism of chylomicron and VLDL particles in the circulation results in triglyceride-rich LDL and HDL particles that are taken up by the liver at increased rates, thus reducing the plasma LDL and HDL cholesterol concentrations, whereas the products of hydrolysis of these particles induce an increased rate of synthesis of triglyceride and an increased rate of secretion of VLDL apo B-100.

Adult↗
PubMed1993

Effects of chloroquine on the dyslipidemia of non-insulin-dependent diabetes mellitus.

The effects of 3-day oral chloroquine phosphate treatment administered at a dosage of 250 mg four times daily on fasting serum levels of lipids, lipoproteins, and apolipoproteins were studied in 20 patients with non-insulin-dependent diabetes mellitus (NIDDM). Chloroquine reduced the fasting serum concentrations of total cholesterol (6.16 +/- 0.31 to 5.67 +/- 0.31 mmol/L, P < .05), low-density lipoprotein (LDL) cholesterol (4.38 +/- 0.35 to 3.93 +/- 0.32 mmol/L, P < .05), and apolipoprotein (apo) B (1.46 +/- 0.08 to 1.24 +/- 0.06 g/L, P < .01), and the ratio of apo B to apo A-I (0.81 +/- 0.05 to 0.71 +/- 0.03, P < .05). Chloroquine also caused a decrease in fasting plasma glucose levels (11.1 +/- 0.5 to 9.2 +/- 0.4 mmol/L, P < .01) and an increase in fasting plasma insulin levels (0.12 +/- 0.01 to 0.14 +/- 0.01 nmol/L, P < .01). The decrease in total cholesterol and apo B levels correlated with the increase in fasting plasma insulin levels (r = .35, P = .04 and r = .33, P = .03, respectively), but not with changes in plasma levels of glucose or nonesterified fatty acids (NEFA). This study demonstrates that 3 days of oral chloroquine treatment improves abnormalities of lipoprotein metabolism in patients with NIDDM. This may be due to an increase in insulin levels, but there also appears to be a more direct effect of the drug on apo B metabolism.

Adult↗
PubMed1993

Growth hormone treatment improves serum lipids and lipoproteins in adults with growth hormone deficiency.

The effects of 6 months' treatment with recombinant human growth hormone (rhGH) on serum lipids and lipoproteins were assessed in 24 adult patients with GH deficiency in a double-blind, placebo-controlled trial. Compared with age-, weight-, and sex-matched controls, the patients had significantly higher serum concentrations of total cholesterol (P = .002), low-density lipoprotein (LDL) cholesterol (P < .001), apolipoprotein B ([apoB] P = .011), and triglyceride (P = .017), and lower concentrations of high-density lipoprotein (HDL) cholesterol (P < .001). The prevalence of elevated serum cholesterol, triglyceride, LDL cholesterol, and apo B levels was 39%, 26%, 39%, and 25%, respectively; 75% of patients had decreased concentrations of HDL cholesterol. Treatment with rhGH (0.07 U/kg daily) resulted in decreases in total cholesterol level (5.8 +/- 0.3 to 5.1 +/- 0.3 mmol.L-1 over 6 months; P = .01 compared with placebo), LDL cholesterol level (4.22 +/- 0.25 to 3.19 +/- 0.23 mmol.L-1; P = .0003), LDL:HDL cholesterol ratio (5.57 +/- 0.47 to 3.29 +/- 0.33; P = .03), apo B level (1.07 +/- 0.06 to 0.84 +/- 0.07 g.L-1; P = .003), and apo B: A-1 ratio (0.73 +/- 0.05 to 0.69 +/- 0.05; P = .01). HDL cholesterol and apo A-1 levels did not change following rhGH treatment. The changes in lipid and lipoprotein levels were not significantly related to changes in insulin, thyroid hormones, insulin-like growth factor-1 (IGF-1), or indices of adiposity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Independent associations between plasma lipoprotein subfraction levels and the course of coronary artery disease in the St. Thomas' Atherosclerosis Regression Study (STARS).

Associations between plasma lipoprotein subfractions and changes in coronary artery diseases (CAD) were examined in 74 men who completed the St. Thomas' Atherosclerosis Regression Study (STARS). Plasma lipoproteins were isolated by stepwise, preparative ultracentrifugation at repeated intervals during the 38-month trial. Paired coronary angiograms were quantitatively analyzed by a computerized method. In univariate linear regression analysis, changes in mean absolute width (delta MAWS) and minimum absolute with (delta MinAWS) of coronary segments were significantly correlated with in-trial concentrations of cholesterol in intermediate-density lipoprotein ([IDL] d = 1.006 to 1.019 kg/L), low-density lipoprotein ([LDL2] d = 1.019 to 1.040 kg/L; LDL3, d = 1.040 to 1.063 kg/L), and high-density lipoprotein ([HDL3] d = 1.125 to 1.210 kg/L) subfractions; no significant associations were found with other lipoproteins. IDL, LDL3, and HDL3 cholesterol were then selected for multiple linear regression analysis because these variables were not co-correlated and because they attained a significance of P less than or equal to .1 in univariate regression. In this analysis, only LDL3 cholesterol level was a significant negative predictor (P < .05) of both delta MAWS and delta MinAWS; a positive association between delta MinAWS and HDL3 cholesterol level just failed to reach conventional statistical significance (P = .066). Correlations between changes in coronary luminal dimensions and LDL3 cholesterol level were independent of age, smoking, weight, and blood pressure. Most patients showing regression of coronary atherosclerosis had an LDL3 cholesterol level of less than 1.8 mmol/L. The findings suggest that LDL3 is the plasma lipoprotein subfraction that exerts the single most powerful effect on the course of CAD in middle-aged men with hypercholesterolemia.

Analysis of Variance↗
PubMed1993

Plasma coenzyme Q (ubiquinone) concentrations in patients treated with simvastatin.

Plasma coenzyme Q (CoQ) was measured in 20 hyperlipidaemic patients treated with diet and simvastatin (an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase); 22 hyperlipidaemic patients treated with diet with alone; and 20 normal controls. Patients treated with simvastatin had a significantly lower plasma CoQ and CoQ: cholesterol ratio than either patients receiving diet alone or normal controls. Use of simvastatin was inversely and independently correlated with both CoQ (p < 0.0001) and CoQ: cholesterol ratio (p < 0.01). There was a significant inverse association between CoQ and dose of simvastatin (p < 0.001). It is concluded that simvastatin may lower the plasma CoQ concentration and this may be greater than the reduction in cholesterol. The possible adverse effect of simvastatin on the metabolism of CoQ may be clinically important and requires further study.

Adult↗
PubMed1993

Lipoprotein (a) as an independent risk factor for myocardial infarction in patients with common hypercholesterolaemia.

AIMS: To examine whether lipoprotein (a) (Lp(a)) increases the risk of myocardial infarction (MI) in patients with common hypercholesterolaemia. METHODS: 15 middle aged men with common hypercholesterolaemia (mean serum low density lipoprotein (LDL) cholesterol 4.94 mmol/l, SD 1.0) and a history of MI were selected consecutively from referrals to a lipid clinic. A control group that had not sustained an MI and with similar age, sex, cigarette smoking and blood pressure characteristics was also selected from the same clinic. Serum cholesterol, triglyceride, LDL cholesterol, high density lipoprotein cholesterol, apolipoproteins AI and B and Lp(a) were measured in both groups. Lp(a) was assayed by immunoturbidity. RESULTS: The serum concentration of Lp(a) was significantly higher in patients with MI (geometric mean 0.64 (95% confidence interval 0.36 to 1.14) v 0.30 (0.21 to 0.42) g/l, p = 0.02), but there were no significant differences in other variables. Stepwise logistic regression analysis showed that Lp(a) was the only significant predictor of MI (p < 0.02). The odds ratio of MI (adjusted for age, smoking, blood pressure and apolipoprotein B) for an Lp(a) of > 0.57 g/l was 16.5, 95% confidence interval 2.3 to 125.4 (p = 0.001). CONCLUSION: In middle aged men with common hypercholesterolaemia the serum concentration of Lp(a) is a powerful and independent risk factor for MI. Lp(a) should probably be routinely measured in all patients referred to a lipid clinic.

Apolipoprotein A-I↗
PubMed1993

Human lymphocyte sodium-hydrogen exchange. The influences of lipids, membrane fluidity, and insulin.

The relation between serum lipids, membrane fluidity, insulin, and the activity of the sodium-hydrogen exchanger was investigated in human lymphocytes from 83 subjects. Subjects had a wide range of serum lipids and no concurrent disease. Lymphocyte membrane anisotropy (inversely related to membrane fluidity) was measured with a fluorescence polarization method. Sodium-hydrogen exchange maximal proton efflux rate, affinity for external sodium, and resting pH were determined with the intracellular pH-sensitive fluorochrome 2',5'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Sodium-hydrogen exchange maximal proton efflux rate was negatively correlated with the age of the subject (p = 0.03). Membrane anisotropy correlated with serum triglyceride (p = 0.04). Multiple regression analysis demonstrated that the maximal proton efflux rate in human lymphocytes was significantly related to age (p = 0.005), systolic blood pressure (p = 0.04), membrane anisotropy (p = 0.03), and serum cholesterol (p = 0.03). Incubation of lymphocytes with insulin failed to affect sodium-hydrogen exchange kinetics, intracellular buffering power, or resting intracellular pH. These results suggest that membrane-bound transport proteins may be influenced by serum lipids and the fluidity of the lipid membrane in which they are bound, but they are unlikely to be affected by insulin.

Adult↗