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D R Matthews

Publications and source records attributed to D R Matthews.

At least 37 records · Page 2Linked to original sources
PubMed2002

Effects of acute administration of doxazosin on fasting and postprandial haemodynamics and lipid metabolism in healthy subjects.

The selective alpha1 -adrenoceptor antagonist doxazosin has apparently beneficial effects on insulin sensitivity and on plasma lipid concentrations. In order to understand these effects better, we investigated the acute effects of doxazosin on adipose tissue and forearm blood flow and on postprandial lipid metabolism in healthy subjects. Nine subjects were studied in a balanced, placebo-controlled design. Pulse rate, blood pressure, forearm and subcutaneous adipose tissue blood flow were measured before and for 6 h after a mixed meal, with concomitant measurements of blood metabolites and insulin. Doxazosin increased pulse rate (p = 0.02) and forearm blood flow (p < 0.01 in fasting state), and decreased vascular resistance in forearm (p < 0.05 for fasting values) and subcutaneous abdominal adipose tissue (p = 0.04). Fasting plasma non-esterified fatty acid concentrations were increased by 40 % (p < 0.05). No other metabolic effects were detected. The effects on adipose tissue vascular resistance and lipolysis (reflected in elevated non-esterified fatty acid concentrations) were unexpected, as these are usually considered to be mediated by the balance of alpha2 - and beta-adrenoceptor activity in humans. We conclude that alpha1 -adrenoceptor activity may be more important in regulation of human lipid metabolism than previously recognized.

Adipose Tissue↗
PubMed2002

Children with type 2 diabetes: the risks of complications.

Type 2 diabetes is an increasing problem in children. Two decades ago it had been described only in selected groups, e.g. the Pima Indians. Childhood type 2 diabetes appears to be similar to the metabolic syndrome in adults and is characterized by obesity, hyperglycaemia and insulin resistance. It can present a diagnostic challenge in children, as they can present with diabetic ketoacidosis; the measurement of autoantibodies and C-peptide levels may be helpful. The logarithmic association between the risk of complications with increasing glycaemia which has been established for adults with type 2 diabetes is likely to hold true for children but the conclusions of trials in adults must be extrapolated with caution. Little is known about the onset and progression of macrovascular disease in affected children but it is almost certain that they will develop an excess of premature cardiovascular disease. However, the importance of reducing glycaemia in younger adults with diabetes, in order to minimize the incidence of microvascular complications, has been unequivocally demonstrated in the Diabetes Control and Complications Trial (DCCT). Diet and exercise have a major role to play in the treatment and prevention of type 2 diabetes in children as well as adults - the escalation of type 2 diabetes throughout the developed world is a major public health problem. Extrapolating data from adults, metformin appears to be the logical first-line treatment in children with type 2 diabetes; sulphonylureas are also used but neither of these agents have been evaluated in trials in children and are not licensed for such use. With regard to other newer agents, it seems wise to use well-established drugs with a long track record and for which the long-term safety data are available.

Child, Preschool↗
PubMed2001

UKPDS 50: risk factors for incidence and progression of retinopathy in Type II diabetes over 6 years from diagnosis.

AIMS/HYPOTHESIS: To determine risk factors related to the incidence and progression of diabetic retinopathy over 6 years from diagnosis of Type II (non-insulin-dependent) diabetes mellitus. METHODS: This report describes 1919 patients from within the United Kingdom Prospective Diabetes Study (UKPDS), with retinal photographs taken at diagnosis and 6 years later and with complete data available. Photographs were centrally graded for lesions of diabetic retinopathy using the modified Early Treatment of Diabetic Retinopathy Study Final scale. Risk factors were assessed after 3 months diet from the time of diagnosis of diabetes. Patients were seen every 3 months in a hospital setting. Biochemical measurements were done by a central laboratory. End points of vitreous haemorrhage and photocagulation were confirmed by independent adjudication of systematically collected clinical data. The main outcome measures were incidence and progression of retinopathy defined as a two-step Early Treatment of Diabetic Retinopathy Study (ETDRS) final scale change. RESULTS: Of the 1919 patients, 1216 (63 %) had no retinopathy at diagnosis. By 6 years, 22 % of these had developed retinopathy, that is microaneurysms in both eyes or worse. In the 703 (37 %) patients with retinopathy at diagnosis, 29 % progressed by two scale steps or more. Development of retinopathy (incidence) was strongly associated with baseline glycaemia, glycaemic exposure over 6 years, higher blood pressure and with not smoking. In those who already had retinopathy, progression was associated with older age, male sex, hyperglycaemia (as evidenced by a higher HbA1c) and with not smoking. CONCLUSION/INTERPRETATION: The findings re-emphasise the need for good glycaemic control and assiduous treatment of hypertension if diabetic retinopathy is to be minimised.

Age Factors↗
PubMed2001

The effect on adipose tissue blood flow of isoenergetic meals containing different amounts and types of fat.

OBJECTIVE: To investigate the factors regulating the increase in adipose tissue blood flow following meals. DESIGN: Eight subjects were fed three isoenergetic meals; two high-fat meals rich in either saturated or polyunsaturated fatty acids and one low-fat, high-carbohydrate meal. MEASUREMENTS: Blood samples were taken and adipose tissue blood flow was measured before and for 6 h after the meal. Plasma glucose, insulin, non-esterified fatty acid, total and chylomicron-triacylglycerol and catecholamine concentrations were measured. RESULTS: Adipose tissue blood flow rose to a peak after all three meals (P<0.05 for each). The three meals stimulated adipose tissue blood flow at similar times. There was a marked and statistically significant similarity in the time course of changes in blood flow and insulin concentrations. In contrast, noradrenaline concentrations peaked later than adipose tissue blood flow (P=0.014). CONCLUSION: Adipose tissue blood flow may be 'carbohydrate-stimulated' rather than 'fat-stimulated', with insulin having a vasodilatory role in adipose tissue as in skeletal muscle.

Adipose Tissue↗
PubMed2001

Relationship between the severity of retinopathy and progression to photocoagulation in patients with Type 2 diabetes mellitus in the UKPDS (UKPDS 52).

AIM: to establish the degree to which the severity of retinopathy determines the risk for the need for subsequent photocoagulation in those with newly diagnosed Type 2 diabetes mellitus. METHODS: Of 5102 patients entered into the UK Prospective Diabetes Study (UKPDS), 3709 had good quality retinal photographs that could be graded at entry. They were followed until the end of the study or until lost to follow-up, or until they received photocoagulation. Retinopathy severity was categorized as no retinopathy, microaneurysms (MA) only in one eye, MA in both eyes or more severe retinopathy features. The risk of photocoagulation was assessed in relation to severity of retinopathy at baseline, 3 and 6 years. RESULTS: Of the 3709 patients assessed at entry to the UKPDS, 2316 had no retinopathy. Of these 0.2% needed photocoagulation at 3 years, 1.1% at 6 years and 2.6% at 9 years. Those with MA in one eye only (n = 708) were similar, with 0%, 1.9% and 4.7% needing photocoagulation by 3, 6 and 9 years, respectively. Amongst those who had more retinopathy features at entry (n = 509), 15.3% required photocoagulation by 3 years, and 31.9% by 9 years. When those without retinopathy at 6 years (n = 1579) were examined 3 and 6 years later (9 and 12 years after diagnosis), 0.1% and 1.8% required photocoagulation. Those with more severe retinopathy (n = 775) needed earlier treatment, 6.6% after 3 years and 13.3% after 9 years. The commonest indication for laser therapy was maculopathy, but those with more severe retinopathy were more likely to be treated for proliferative retinopathy and to need both eyes treated. CONCLUSION: Few type 2 diabetic patients without retinopathy progress to photocoagulation in the following 3-6 years, while patients with more severe retinopathy lesions need to be monitored closely.

Blood Glucose↗
PubMed2001

The hospital and home use of a 30-second hand-held blood ketone meter: guidelines for clinical practice.

AIMS: To establish the role of the measurement of beta-hydroxybutyrate (beta-OHB) in distinguishing simple hyperglycaemia from ketosis, and as an indicator of adequate resolution of ketoacidosis, using an electrochemical blood ketone meter. The aim of the study is to assess the accuracy and precision of the meter and to develop clinical guidelines for the use of the ketone meter at home and in hospital. PATIENTS AND METHODS: Twenty patients with poor glycaemic control (mean HbA1c 10.2%) were recruited from the diabetes clinic and 14 patients admitted with diabetic ketoacidosis (DKA) were recruited from two Accident and Emergency Departments. The blood obtained at each routine fingerprick test for glucose measurement was tested for beta-OHB using the ketone meter. Plasma beta-OHB concentrations were also measured on admission using a laboratory enzymatic method. RESULTS: Paired glucose and beta-OHB meter readings (n = 1099) in clinic patients demonstrated that, in the absence of intercurrent illness, beta-OHB levels did not exceed 1 mmol/l, irrespective of glucose readings. In the 14 ketoacidotic patients, the mean plasma beta-OHB concentration, measured in the laboratory, on admission was 7.4 mmol/l (range 3.9-12.3 mmol/l). The median half-life of beta-OHB was 1.64 h (1st IQR 2.27 h, 3rd IQR 1.34 h). The median time taken, from the initiation of treatment, for beta-OHB concentrations to fall to below 1 mmol/l was 8.46 h (range 5-58.33 h). CONCLUSION: Near patient blood ketone testing is a useful adjunct to blood glucose monitoring in distinguishing between ketosis and simple hyperglycaemia. The data suggest that beta-OHB levels > or = 1 mmol/l require further action and levels > 3 mmol/l necessitate medical review. In addition, the rate of fall of beta-OHB in DKA can be used as an indicator of the adequacy of treatment.

3-Hydroxybutyric Acid↗
PubMed2001

Serum cortisol and 17-hydroxyprogesterone interrelation in classic 21-hydroxylase deficiency: is current replacement therapy satisfactory?

One of the main aims in the management of patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency is to achieve adequate suppression of the adrenal cortex with the smallest possible dose of glucocorticoid substitution. To evaluate the administration schedule of current replacement therapy regimens, we investigated the cortisol-17-hydroxyprogesterone interrelation in 36 patients (13 males and 23 females; median age, 12.3 yr; range, 6.1-18.8 yr) with salt-wasting congenital adrenal hyperplasia. As sufficient variation in 17-hydroxyprogesterone concentrations was required to allow analysis of the cortisol-17-hydroxyprogesterone interrelation, patients were divided into 2 groups depending on the adequacy of hypothalamic-pituitary-adrenal axis suppression. The first group consisted of 17 patients with suppressed 17-hydroxyprogesterone concentrations (group 1), and the second group consisted of 19 patients with nonsuppressed 17-hydroxyprogesterone concentrations (group 2). We determined serum cortisol and 17-hydroxyprogesterone concentrations at 20-min intervals for a total of 24 h while patients were receiving their usual replacement treatment with hydrocortisone and 9alpha-fludrocortisone. We also determined the lowest dose of dexamethasone required to suppress the 0800 h serum ACTH concentrations when administered as a single dose (0.3 or 0.5 mg/m(2)) the night before. Mean 24-h cortisol and 17-hydroxyprogesterone concentrations were 3.9 microg/dl (SD = 2.1) and 66.2 ng/dl (SD = 92.7), respectively, in group 1 and 4.1 microg/dl (SD = 2.5) and 4865.7 ng/dl (SD = 6951) in group 2. The 24-h 17-hydroxyprogesterone concentrations demonstrated circadian variation, with peak values observed between 0400-0900 h. In group 2, 17-hydroxyprogesterone concentrations decreased gradually in response to the rise in cortisol concentrations during the day, but remained low during the night despite the almost undetectable cortisol concentrations between 1600-2000 h. Mean 0800 h androstenedione concentrations correlated strongly with integrated 17-hydroxyprogesterone concentrations (r = 0.81; P < 0.0001), but not with integrated cortisol concentrations. There was a significant negative correlation between cortisol and 17-hydroxyprogesterone at lag time 0 min (r = -0.187; P < 0.0001), peaking at lag time 60 min (r = -0.302; P < 0.0001), with cortisol leading 17-hydroxyprogesterone by these time intervals. Finally, 0800 h serum ACTH concentrations were sufficiently suppressed after a dexamethasone dose of 0.3 mg/m(2) in all but three patients. These findings indicate that in classic 21-hydroxylase deficiency, hydrocortisone should be administered during the period of increased hypothalamic-pituitary-adrenal axis activity, between 0400-1600 h, with the biggest dose given in the morning. Blood investigations performed as part of monitoring of congenital adrenal hyperplasia patients should include androstenedione and 17-hydroxyprogesterone concentrations determined in the morning before the administration of hydrocortisone. It should also be emphasized that blood investigations are only complementary to the overall assessment of these patients, which is primarily based on the evaluation of growth and pubertal progress.

17-alpha-Hydroxyprogesterone↗
PubMed2001

Joint growth hormone and cortisol spontaneous secretion is more asynchronous in older females than in their male counterparts.

In humans, cortisol and GH are secreted in a pulsatile manner, and an interaction between GH and the hypothalamic-pituitary-adrenal axis has been established. In view of the sexually dimorphic pattern in GH secretion, we investigated the GH-cortisol bihormonal secretory dynamics in male and female healthy older individuals. We studied the GH and cortisol secretory patterns in 83 healthy subjects (45 men and 38 women; age range, 59.4-73.0 yr) by determining serum GH and cortisol concentrations at 20-min intervals for 24 h. The irregularity of GH and cortisol secretion was assessed using approximate entropy (ApEn), a scale- and model-independent statistic. The synchrony of joint GH-cortisol spontaneous secretion was quantified using the cross-ApEn statistic. Cross-correlation analysis of GH and cortisol patterns was computed at various time lags covering the 24-h period. Mean 24-h serum GH concentrations were significantly higher in females (mean, 1.31 mU/L; SD, 0.87) than in males (mean, 0.88 mU/L; SD, 0.42; P = 0.009), whereas mean 24-h serum total cortisol concentrations were higher in males (mean, 9.0 microg/dL; SD, 1.4) than in females (mean, 7.3 microg/dL; SD, 1.4; P = 0.0001). GH secretion was more irregular in females (mean ApEn, 0.81; SD, 0.23) than in males (mean ApEn, 0.60; SD, 0.20; P < 0.001). No significant difference in the regularity of cortisol secretion was noted between sexes. Cross-ApEn values of paired GH-cortisol were higher in females (mean, 1.15; SD, 0.18) than in males (mean, 1.01; SD, 0.16; P = 0.0003). Stepwise multiple linear regression analysis indicated that estradiol and insulin-like growth factor-binding protein-3 concentrations were independently related to GH ApEn values (r(2) = 0.14; P = 0.01), whereas cross-ApEn values of paired GH-cortisol were best predicted by FSH concentrations (r(2) = 0.37; P = 0.003). Cross-correlation analysis revealed a significant positive correlation between GH and cortisol, peaking at lag time of 4.7 h in males (r = 0.30; P < 0.0001) and 4.3 h in females (r = 0.14; P < 0.0001), with GH leading cortisol by these time intervals. In addition, a significant negative correlation between the two hormones was noted over time, peaking at 4.7 h in males (r = -0.21; P < 0.0001) and 6.3 h in females (r = -0.25; P < 0.0001), with cortisol leading GH by these time intervals. The above results indicate that in the elderly, females have a more disordered GH secretory pattern and a more asynchronous joint GH-cortisol secretion than their male counterparts. These observations most likely reflect bidirectional interactions between the GH and hypothalamic-pituitary-adrenal axis in humans as well as diminution of subsystem integrity and synchronous control of interconnected hormonal systems with advancing age.

Aged↗
PubMed2001

Decreased insulin secretion in type 2 diabetes: a problem of cellular mass or function?

Type 2 diabetes is characterized by diminished or inappropriate secretion of insulin, which could be a defect of either islet cell function or beta-cell mass. Quantitation of islet cell populations in postmortem pancreas demonstrates little change of beta-cell mass in type 2 diabetes. Reduction of islet cell mass (up to 30%) is associated largely with islet amyloid deposition, and the degree of amyloidosis is independent of the duration of the disease. Insulin secretory capacity is dependent on both function and mass of cells. beta-Cell secretion is heterogeneous; increasing glucose concentrations result in recruitment of beta-cells into the secretory pool, indicating a large reserve of secretory capacity that can be recruited in insulin resistant conditions. The Starling curve of islet function describes the relationship of insulin secretion to increasing levels of insulin resistance and hyperglycemia in type 2 diabetes. Longitudinal studies in Macaca mulatta monkeys show that insulin resistance is accompanied by increased islet mass and onset of diabetes is associated with deposition of amyloid and reduction of beta-cells. Increasing the function of unresponsive beta-cells rather than the mass of cells may be a more effective therapeutic target for type 2 diabetes.

Amyloid↗
PubMed2000

Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study.

OBJECTIVE: To determine the relation between exposure to glycaemia over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes. DESIGN: Prospective observational study. SETTING: 23 hospital based clinics in England, Scotland, and Northern Ireland. PARTICIPANTS: 4585 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk. OUTCOME MEASURES: Primary predefined aggregate clinical outcomes: any end point or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photo-coagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 1% reduction in updated mean HbA(1c) adjusted for possible confounders at diagnosis of diabetes. RESULTS: The incidence of clinical complications was significantly associated with glycaemia. Each 1% reduction in updated mean HbA(1c) was associated with reductions in risk of 21% for any end point related to diabetes (95% confidence interval 17% to 24%, P<0.0001), 21% for deaths related to diabetes (15% to 27%, P<0.0001), 14% for myocardial infarction (8% to 21%, P<0.0001), and 37% for microvascular complications (33% to 41%, P<0.0001). No threshold of risk was observed for any end point. CONCLUSIONS: In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia. Any reduction in HbA(1c) is likely to reduce the risk of complications, with the lowest risk being in those with HbA(1c) values in the normal range (<6.0%).

Cataract Extraction↗
PubMed2000

Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study.

OBJECTIVE: To determine the relation between systolic blood pressure over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes. DESIGN: Prospective observational study. SETTING: 23 hospital based clinics in England, Scotland, and Northern Ireland. PARTICIPANTS: 4801 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk. OUTCOME MEASURES: Primary predefined aggregate clinical outcomes: any complications or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, lower extremity amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photocoagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 10 mm Hg decrease in updated mean systolic blood pressure adjusted for specific confounders. RESULTS: The incidence of clinical complications was significantly associated with systolic blood pressure, except for cataract extraction. Each 10 mm Hg decrease in updated mean systolic blood pressure was associated with reductions in risk of 12% for any complication related to diabetes (95% confidence interval 10% to 14%, P<0.0001), 15% for deaths related to diabetes (12% to 18%, P<0.0001), 11% for myocardial infarction (7% to 14%, P<0.0001), and 13% for microvascular complications (10% to 16%, P<0.0001). No threshold of risk was observed for any end point. CONCLUSIONS: In patients with type 2 diabetes the risk of diabetic complications was strongly associated with raised blood pressure. Any reduction in blood pressure is likely to reduce the risk of complications, with the lowest risk being in those with systolic blood pressure less than 120 mm Hg.

Adult↗
PubMed2000

The use of fixed-mixture insulins in clinical practice.

BACKGROUND: Pre-mixed insulins currently represent about 40% of the world market in human insulin. Despite the fact that many patients are being treated with these insulin formulations, there are surprisingly few data about fixed mixtures and comparisons with other administration schedules. The main advantages of using a pre-mixed preparation over a self-mixed insulin are increased accuracy of dosage, efficacy and patient convenience. These benefits may lead to increased compliance resulting in better long-term control of the disease. Insulin mixtures are used by a wide variety of patients with type-1 and type-2 diabetes. Pre-mixed insulins also appear to be useful in elderly and adolescent patients with diabetes, although there are few published data on patients in these groups. CONCLUSIONS: It is likely that, in the future, fixed mixtures containing rapid-acting insulin analogues, such as insulin lispro, and possibly newly formulated intermediate-acting insulin analogues, such as neutral protamine lispro, may allow further improvements in both metabolic control and patient convenience.

Adolescent↗
PubMed2000

Effects of three months' diet after diagnosis of Type 2 diabetes on plasma lipids and lipoproteins (UKPDS 45). UK Prospective Diabetes Study Group.

AIMS: To assess the effect of diet on fasting plasma lipids and lipoproteins in patients with newly diagnosed Type 2 diabetes. METHODS: A total of 2,906 patients each underwent 3 months' diet therapy before allocation to therapy in a randomized controlled clinical trial. Lipids and lipoproteins were measured at diagnosis and after 3 months' diet. RESULTS: The mean body weight at diagnosis was 83 kg. Weight decreased after diet by a mean of 4.5 kg; body mass index (BMI) decreased by 1.51 kg/m2; plasma glucose fell by 3 mmol/l from 11 mmol/l; and HbA1c by 2% from 9%. Triglyceride concentrations were reduced in men by -0.41 (95% confidence interval (CI) -0.47 to - 0.35) mmol/l from a geometric mean 1.8 (1 SD interval 1.0-3.0) mmol/l, and in women by -0.23 (-0.28 to -0.18) mmol/l from a similar level. Cholesterol decreased in men by -0.28 (-0.33 to -0.24) mmol/l from 5.5 (1.1) mmol/l, and in women by -0.09 (-0.14 to -0.04) mmol/l from 5.8 (1.2) mmol/l with corresponding changes in LDL cholesterol. HDL cholesterol increased in men by 0.02 (0.01 to 0.04) mmol/l and in women by 0.01 (0 to 0.02) mmol/l. Triglyceride concentration in the top tertile was reduced by 37% in men (> 2.1 mmol/l) and by 23% in women (> 2.2 mmol/l) with regression to mean accounting for 13% and 6%, respectively. Similarly cholesterol in the top tertile was reduced by 12% in men (> 5.8 mmol/l) and 7% in women (> 6.2 mmol/l) with 6% of the decrease in both men and women accounted for by regression to the mean. CONCLUSIONS: Initial dietary therapy in patients with newly diagnosed Type 2 diabetes substantially reduced plasma triglyceride, marginally improved total cholesterol and subfractions, and resulted in a potentially less atherogenic profile, although this did not eliminate the excess cardiovascular risk in patients with Type 2 diabetes.

Adult↗