PubMed Health⌕ Search

Biomedical subjects

J R Petrie

Publications and source records attributed to J R Petrie.

At least 19 recordsLinked to original sources
PubMed2007

Effects of low-dose continuous combined hormone replacement therapy on glucose homeostasis and markers of cardiovascular risk in women with type 2 diabetes.

BACKGROUND: Low-dose hormone replacement therapy (HRT) has attracted interest for the treatment of postmenopausal symptoms in diabetes because of concerns about increased risk of coronary heart disease (CHD) and stroke with conventional HRT containing conjugated equine oestrogens (CEEs) and medroxyprogesterone acetate (MPA). OBJECTIVES: We assessed the effects on glucose homeostasis and cardiovascular risk factors of continuous oral 17beta oestradiol (1 mg) and norethisterone (0.5 mg) in postmenopausal women with type 2 diabetes. DESIGN: Double-blind, randomized placebo-controlled trial. ASSESSMENTS: Hyperinsulinaemic isoglycaemic clamp and cardiovascular risk factors were assessed before and after 3 months of treatment. RESULTS: Twenty-eight women completed the study. HRT decreased fasting glucose compared with placebo [-9.4% with HRT vs.+2.3% for placebo, 95% confidence interval (CI) -23.2 to -0.3] and total cholesterol (-13.7 vs.+1.0%, 95% CI -22.4 to -3.1%) No significant effect was seen on metabolic clearance rate of glucose, glycated haemoglobin (HbA1c), triglycerides, high density lipoprotein (HDL)-cholesterol or C-reactive protein (CRP). CONCLUSIONS: In women with type 2 diabetes, low-dose HRT decreased fasting glucose and total cholesterol without detectable adverse effects on glucose clearance, triglycerides and CRP as reported with conventional HRT.

Blood Glucose↗
PubMed2005

Implementation of national diabetes retinal screening programme is associated with a lower proportion of patients referred to ophthalmology.

AIMS: To examine the impact of a new national retinal screening programme on screening attendance, technical quality of images, and referrals to the ophthalmology clinic. METHODS: Results from the previous ad hoc retinal screening service were compared with data from the first year of the new Scottish Diabetes Retinal Screening Programme in Dundee, which was administered according to criteria recommended by the Health Technology Board Scotland. RESULTS: Of 5150 patients invited for screening, 10.3% of patients did not attend. Overall, 4574 patients underwent single-field digital retinal photography and 25.4% required mydriasis for an adequate image. After screening, 1.9 and 90.5% were recalled for repeat photography at 6 months and 1 year, respectively, whilst 4.6% were ungradable and 3.0% were referred to the ophthalmology clinic. Compared with the last 18 months of the previous scheme, with the new programme a smaller proportion of patients were referred to ophthalmology (3.0 vs. 5.9%; P < 0.001, difference 2.9%: 95% confidence interval 2.1-3.7%). Moreover, the attendance was higher (89 vs. 82%; P < 0.01) and there were fewer ungradable images (4.6 vs. 7.1%; P < 0.001). CONCLUSIONS: Introduction of a systematic retinal screening programme can reduce the proportion of patients referred to the ophthalmology clinic, and use ophthalmology services more efficiently.

Adult↗
PubMed2004

Higher carotid-radial pulse wave velocity in healthy offspring of patients with Type 2 diabetes.

AIMS: To determine whether carotid-radial pulse wave velocity (crPWV), a simple non-invasive measurement of muscular artery structure and function, is increased in offspring of patients with Type 2 diabetes compared with well-matched controls with no family history of diabetes. Serum levels of intercellular adhesion molecule-1 (sICAM-1) were also examined. METHODS: Offspring (n = 19, M = 8) were recruited via contact with patients attending clinics. Controls (n = 19, M = 8) were recruited by advertisement. crPWV was measured using COMPLIOR. Blood pressure and heart rate were determined and fasting blood taken for measurement of metabolic and endothelial parameters. RESULTS: Offspring and controls were well matched [mean (sd)] for age [33.1 (9.6) vs. 32.8 (9.5) years], body mass index [24.8 (4.9) vs. 24.3 (3.4) kg/m2], waist circumference [78.3 (2.3) vs. 76.3 (2.5) cm], and systolic blood pressure [120 (9.3) vs. 119 (14.2) mmHg]. crPWV was 10% higher in the offspring [9.94 (1.3) m/s] compared with controls [9.01 (1.2) m/s, P = 0.02] despite similar pulse pressure [52 (10.5) vs. 53.5 (9.3) mmHg] and resting heart rate [71 (8.7) vs. 69 (14.0) beats/min]. They also showed a trend toward higher sICAM-1 [217 (55) vs. 188 (40) ng/ml, P = 0.07] concentrations which were also strongly correlated to crPWV in offspring (r = 0.63, P = 0.004). CONCLUSIONS: Vascular dysfunction in the form of increased muscular artery stiffness is present from an early stage in subjects at higher risk of developing diabetes. This may be secondary to impaired activation of endothelial signalling pathways in the context of inherited insulin resistance.

Adult↗
PubMed2003

Glucocorticoids and insulin sensitivity: dissociation of insulin's metabolic and vascular actions.

Insulin sensitivity in tissues such as a skeletal muscle and fat is closely correlated with insulin action in the vasculature, but the mechanism underlying this is unclear. We investigated the effect of dexamethasone on insulin-stimulated glucose disposal and vasodilation in healthy males to test the hypothesis that a reduction in glucose disposal would be accompanied by a reduction in insulin action in the vasculature. We performed a double-blind, placebo-controlled, cross-over trial comparing insulin sensitivity (measured by the euglycemic hyperinsulinemic clamp) and vascular insulin action (measured by small vessel wire myography) in young healthy males allocated to placebo or 1 mg dexamethasone twice daily for 6 d, each in random order. Six days of dexamethasone therapy was associated with a 30% (95% confidence interval, 19.1-40.0%) fall in insulin sensitivity. Despite this, there was no difference in insulin-mediated vasodilation between phases. Dexamethasone had no effect on circulating markers of endothelial function, such as D-dimer, von Willebrand factor, and tissue plasminogen activator. By short-term exposure to high dose dexamethasone we were able to differentially affect the metabolic and vascular actions of insulin. This implies that, using this model, there is physiological uncoupling of the effects of insulin in different tissues.

Acetylcholine↗
PubMed2002

Hormone replacement therapy can augment vascular relaxation in post-menopausal women with type 2 diabetes.

BACKGROUND: Diabetes is a major risk factor for coronary heart disease in women and event rates increase substantially after the menopause. Observational studies have suggested that estrogens may provide cardioprotection by regulating endothelial nitric oxide synthase. METHODS: In order to examine the effect of hormone replacement therapy (HRT) on endothelium-dependent and -independent vascular relaxation in post-menopausal women with type 2 diabetes, an open study was conducted in which gluteal biopsies were collected from 17 women before and after 6 months of transdermal 17 beta-estradiol (80 microg twice weekly) in combination with oral norethisterone (1 mg daily). Small arteries (<550 microm) were dissected from fat and mounted on a wire myograph for assessment of relaxation in response to acetylcholine (ACh), bradykinin (BK) and sodium nitroprusside (SNP). RESULTS: Maximal relaxation responses to ACh, BK and SNP in women with diabetes and non-diabetic control subjects were 52 +/- 8 versus 96 +/- 2% (P < 0.05), 76 +/- 7 versus 97 +/- 1%, (P < 0.05) and 91 +/- 2 versus 98 +/- 1% (P < 0.05) respectively. After 6 months of HRT, maximal relaxation responses to ACh, BK and SNP in women with diabetes (compared with pre-HRT) were: 88 +/- 4 (P < 0.05), 93 +/- 3 (P < 0.05) and 98 +/- 1% (P < 0.05) respectively. At baseline and after HRT, EC50 (concentration required to obtain 50% of maximum response) data exhibited similar changes. CONCLUSIONS: HRT had potentially beneficial effects on vascular relaxation. Data were consistent with improvements in endothelial function, vascular smooth muscle function, or both. Controlled studies are required to confirm and extend these findings.

Acetylcholine↗
PubMed2002

Is estradiol cardioprotection a nitric oxide-mediated effect?

BACKGROUND: Estradiol exerts a number of biological effects that support extensive observational data suggesting a protective role for estrogen in cardiovascular disease prevention. These include effects on lipid and carbohydrate metabolism, coagulation/fibrinolysis as well as a possible effect on vascular reactivity. It has been proposed that this might be mediated by vascular endothelial nitric oxide (NO) production. Accordingly, we designed complementary in-vivo and in-vitro studies to investigate this hypothesis further. METHODS: Firstly, in a group of 10 healthy post-menopausal women, bilateral venous occlusion plethysmography was used to examine forearm vasoconstrictor responses to intrabrachial N(G)-monomethyl-l-arginine (l-NMMA; a substrate inhibitor of nitric oxide synthase) both before and after 4 weeks of treatment with transdermal 17beta-estradiol (E(2)) (80 microg/day). Secondly, we examined the direct effects of acute (24 h) and chronic (7 days) treatment with E(2) (10 pmol/l and 10 nmol/l) on endothelial nitric oxide synthase (eNOS) gene expression in cultured human aortic endothelial cells. RESULTS: No significant differences were observed between the vasoconstrictor responses to l-NMMA (2, 4, 8 micromol/min) before and after E(2) treatment. Comparison of E(2)-treated endothelial cells with control cells showed no significant increase in eNOS mRNA expression following either acute or chronic estradiol treatment. CONCLUSIONS: The present studies do not provide evidence for an eNOS-mediated cardioprotective response to estrogen and therefore suggest that additional mechanisms other than the endothelial NO system may have an important role in the cardiovascular effects of estrogen.

Administration, Cutaneous↗
PubMed2001

The effects of transdermal estradiol in combination with oral norethisterone on lipoproteins, coagulation, and endothelial markers in postmenopausal women with type 2 diabetes: a randomized, placebo-controlled study.

People with type 2 diabetes have a substantially increased risk of coronary heart disease (CHD). Short-term studies with unopposed oral estradiol in women with diabetes have suggested potentially beneficial effects on lipids, thrombotic factors, and insulin sensitivity. However, most (nonhysterectomized) postmenopausal women require combined estrogen-progesterone preparations. We randomized 43 women with type 2 diabetes either to continuous transdermal estradiol (80-microg patches) in combination with oral norethisterone (1 mg daily) or to identical placebos. Blood samples were taken before and after 6 months for measurement of lipoproteins, coagulation factors, and endothelial markers. Total cholesterol and triglyceride concentrations decreased by 8% and 22%, respectively, in those receiving hormone replacement therapy (P < 0.05 relative to change in placebo group after adjustment for baseline concentrations). There was a trend toward a reduction in high density lipoprotein cholesterol concentration (P = 0.06). Factor VII activity decreased by 16% (P < 0.001), and von Willebrand factor antigen decreased by 7% (P = 0.014) with active treatment. Levels of fibrinogen, tissue plasminogen activator, fibrin D dimer, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, lipoprotein(a), and leptin were not significantly altered. No change in glycemic control was detected. Overall, lipid changes may be considered slightly beneficial with respect to CHD risk. The significant decrease in factor VII activity in this study is notable, because elevated factor VII activity has been associated with an increased risk of coronary thrombosis and normally increases with administration of oral estrogen-containing preparations. In addition, a reduction in von Willebrand factor antigen is consistent with an improvement in endothelial function. We suggest that the regimen used in this study may have the potential to reduce CHD risk in women with type 2 diabetes.

Administration, Cutaneous↗
PubMed2001

Low grade chronic inflammation in women with polycystic ovarian syndrome.

Low grade chronic inflammation as reflected by increased C-reactive protein (CRP) concentrations independently predicts those at risk for coronary heart disease (CHD) and type 2 diabetes. Women with polycystic ovarian syndrome (PCOS) are insulin resistant and have increased risk for CHD and type 2 diabetes, but currently there are no data on markers of inflammation in women with PCOS. Seventeen women with PCOS (defined on the basis of elevated testosterone and oligomenorrhea) and 15 healthy women matched as a group for body mass index were recruited. Measurement of CRP concentrations was made using a highly sensitive assay. Insulin resistance was assessed using the hyperinsulinemic euglycemic clamp technique. The women with PCOS had significantly elevated CRP concentrations relative to controls (geometric means, 2.12 and 0.67 mg/L, respectively; P = 0.016). Log CRP correlated with body mass index in both PCOS and controls (r = 0.58; P < 0.05 and r = 0.78; P < 0.01, respectively) and inversely with insulin sensitivity (r = -0.57; P < 0.05 and r = -0.69; P < 0.01). Total testosterone did not correlate with log CRP in either group. On adjustment for body mass index and age, there remained a significant difference in log CRP between PCOS and controls (t = 2.13; P < 0.05). On further adjustment for insulin sensitivity, log CRP was no longer significantly different between groups (t = 1.51; P = 0.14). We conclude that women with PCOS have significantly increased CRP concentrations relative to women with normal menstrual rhythm and normal androgen levels. We propose low grade chronic inflammation as a novel mechanism contributing to increased risk of CHD and type 2 diabetes in these women.

Adult↗
PubMed2000

Insulin action is associated with endothelial function in hypertension and type 2 diabetes.

A primary defect in the vascular action of insulin may be a key intermediate mechanism that links endothelial dysfunction with reduced insulin-mediated cellular glucose uptake in metabolic and cardiovascular disorders. The present study was designed to characterize more fully the relations between insulin action and endothelial function in male patients with essential hypertension (H, n=9) or type 2 diabetes (D, n=9) along with healthy control subjects (C) matched for age, body mass index, and lipid profile. They attended for measurement of whole-body insulin sensitivity (MCR) by the hyperinsulinemic clamp technique (day 1) and forearm vasoreactivity in response to intra-arterial infusions of insulin/glucose (day 2) and N(G)-monomethyl-L-arginine (L-NMMA) and norepinephrine (day 3) by bilateral venous-occlusion plethysmography. Results expressed as mean+/-SE MCR (mL/kg per minute) were 7.22+/-0. 99 (C), 6.32+/-0.78 (H), and 5.06+/-0.53 (D). Insulin/glucose-mediated vasodilation (IGMV) was 17.1+/-5.6% (C), 17. 2+/-5.5% (H), and 12.3+/-6.4% (D). L-NMMA vasoconstriction (LNV) was 37.9+/-5.1% (C), 37.5+/-2.3% (H), and 33.6+/-2.8% (D). There were no significant differences among groups for these parameters. Pooled correlation analyses revealed associations between MCR and IGMV (r=0. 46, P<0.05), MCR and LNV (r=0.44, P<0.05), and IGMV and LNV (r=0.52, P<0.01). This study supports functional coupling between insulin action (both metabolic and vascular) and basal endothelial nitric oxide production in humans.

Age Factors↗
PubMed2000

Trandolapril does not improve insulin sensitivity in patients with hypertension and type 2 diabetes: a double-blind, placebo-controlled crossover trial.

Angiotensin-converting enzyme (ACE) inhibitors are increasingly used as first-line therapy for hypertension in type 2 diabetes mellitus and are widely believed to improve insulin sensitivity (M). However, the evidence for the latter effect does not stand close scrutiny. We have assessed the effect of the ACE inhibitor trandolapril on M in 16 patients (mean +/- SD age, 58 +/- 10.6 yr) with mild-to-moderate essential hypertension (initial blood pressure, 173 +/- 14.5/93 +/- 8.0 mm Hg), obesity (body mass index, 30 +/- 5.4 kg/m2), and impaired glucose intolerance (n = 4) or type 2 diabetes (n = 12) in a double-blind, placebo-controlled crossover design. All patients underwent three 3-h euglycemic hyperinsulinemic clamp studies (soluble insulin, 1.5 mU/kg x min) after a 2-week placebo run-in and at the end of two 4-week periods of treatment with 2 mg trandolapril or placebo (2-week washout). M (mean +/- SD) did not change with trandolapril: placebo (run-in), 5.2 +/- 1.98 mg/kg x min; placebo, 5.3 +/- 1.70 mg/kg x min; trandolapril, 5.1 +/- 1.65 mg/kg x min; P = 0.58; 95% confidence intervals, -0.74, 0.43 (trandolapril vs. placebo); 95% power to exclude an 8% increase in M. In conclusion, trandolapril had no clinically relevant effect on M in patients with hypertension and type 2 diabetes. Previous reports of improved M during ACE inhibitor treatment may be attributable to suboptimal study design and/or use of surrogate measures of M.

Adult↗
PubMed2000

Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease.

Low-grade chronic inflammation, characterized by elevated plasma concentrations of C-reactive protein (CRP), is associated with an increased risk of atherosclerotic cardiovascular disease. Endothelial cell activation is an early event in atherogenesis, and previous studies have reported correlations between indirect markers of endothelial cell activation and CRP concentration. Therefore, in the present study, we measured CRP concentration (and leptin concentration as an index of fat mass) in nine healthy subjects (mean age 53+/-8.1 years; body mass index 27+/-3.2 kg/m(2); mean arterial blood pressure 101+/-9.0 mmHg) undergoing measurement of basal endothelial nitric oxide (NO) synthesis using intra-brachial infusions of N(G)-monomethyl-L-arginine (L-NMMA; a substrate inhibitor of endothelial NO synthase) and noradrenaline (a non-specific control vasoconstrictor). In univariate analysis, CRP concentration was correlated with (i) the percentage decrease in forearm blood flow (FBF) during L-NMMA infusion (r=0.85, P=0.004); and (ii) the serum leptin concentration (r=0.65, P=0.05). In multivariate analysis, the relationship between CRP concentration and the FBF response to L-NMMA remained significant when age and leptin (t=2.65, P=0.045), age and BMI (t=3.69, P=0.014), or age and low-density-lipoprotein-cholesterol plus high-density-lipoprotein-cholesterol (t=3.37, P=0.044), were included in regression models. In contrast, the response of FBF to noradrenaline was not significantly related to CRP concentration. These data demonstrate for the first time a relationship between low-grade chronic inflammation and basal endothelial NO synthesis (measured using an invasive method), and support the notion that endothelial dysfunction is a critical intermediate phenotype in the relationship between inflammation and cardiovascular disease.

Adult↗
PubMed1999

Angiotensin-converting enzyme gene and diabetes mellitus.

AIMS: The association of the insertion/deletion polymorphism in the angiotensin-converting enzyme (ACE) gene with cardiovascular disease and diabetic nephropathy remains a controversial issue. This review aims to give an overview of the research to date assessing the impact of the ACE polymorphism in Type 1 and Type 2 diabetes mellitus (DM). METHODS: A systematic review of the literature was performed in the databases of MEDLINE, PubMed and EMBASE for the key words 'diabetes mellitus', 'diabetic nephropathy', 'ACE polymorphism' and 'genotype' and relevant articles were considered. RESULTS: A meta-analysis assessing the influence of the ACE polymorphism on disease susceptibility demonstrated significant odds ratios in individuals with the DD genotype for coronary heart disease, myocardial infarction and both diabetic and nondiabetic renal disease. No association was found for left ventricular hypertrophy or hypertension in nondiabetic subjects. CONCLUSIONS: The ACE polymorphism appears to have a significant impact on the progression of diabetic nephropathy and may have therapeutic implications for identifying those individuals resistant to the effects of ACE inhibitors. It also appears to be indicative of an increased vascular risk in diabetic patients; however, larger prospective studies are required to clarify this situation.

Diabetes Mellitus↗