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Biomedical subjects

S M Marshall

Publications and source records attributed to S M Marshall.

At least 37 records · Page 2Linked to original sources
PubMed2000

Increased left ventricular mass index and nocturnal systolic blood pressure in patients with Type 2 diabetes mellitus and microalbuminuria.

AIMS: To compare left ventricular mass (LVM) index and function in patients with Type 2 diabetes mellitus with and without microalbuminuria and to investigate the clinical determinants of left ventricular hypertrophy. METHODS: Echocardiography, electrocardiography and 24-h ambulatory blood pressure monitoring were performed in microalbuminuric (n = 29) and normoalbuminuric (n = 29) patients with Type 2 diabetes and no clinical evidence of heart disease. Groups were individually matched for age, sex and diabetes duration and smoking status. RESULTS: LVM index (62 (34-87) vs. 52 (33-89) g/m2.7, P = 0.04) and LVH prevalence, using two out of three definitions, were greater in patients with microalbuminuria (LVM/height2.7: 72 vs. 59%, P = 0.27, LVM/height: 66 vs. 38%, P = 0.04, LVM/body surface area: 59 vs. 31%, P = 0.03). Night-time systolic blood pressure (126 (99-163) vs. 120 (104-157) mmHg, P = 0.005) and the night/day systolic blood pressure ratio (0.92 (0.08) vs. 0.88 (0.06), P = 0.04) were higher in those with microalbuminuria. Systolic and diastolic function were similar in both groups. Linear regression analyses showed that body mass index (BMI) was significantly related to loge LVM index (R2 = 11.8%, P = 0.005) and a relationship with night/day systolic blood pressure was also suggested (R2 = 4.6%, P = 0.057). CONCLUSIONS: In patients with Type 2 diabetes, LVH is more common and severe in those with microalbuminuria. Its presence may be related to raised night/day systolic blood pressure ratio and is significantly related to BMI. The high prevalence of LVH strengthens the case for echocardiographic screening in Type 2 diabetes to identify high risk patients who might benefit from aggressive cardiovascular risk factor intervention.

Aged↗
PubMed2000

Abnormal thiol group modulation of sodium-lithium countertransport and membrane fluidity is associated with a disturbed relationship between serum triacylglycerols and membrane function in type II diabetes.

In essential hypertension and diabetic nephropathy, sodium-lithium countertransport (Na-Li CT) is an inherited marker, subject to metabolic influences, of cardiovascular risk. Studies in Type II diabetes, taking clinical phenotypes as their starting point, are conflicting. We sought to identify Na-Li CT kinetic abnormalities in Type II diabetes, and only subsequently to seek relationships with clinical variables. Na-Li CT kinetics, membrane fluidity and their modulation by thiol proteins were measured in erythrocytes from 38 patients with Type II diabetes and in 16 normal control subjects. In untreated erythrocytes, Na-Li CT kinetics were similar. Thiol protein alkylation with N-ethylmaleimide generally caused both V(max) and K(m) to fall, but caused K(m) to rise in erythrocytes from 13 out of 38 diabetic subjects, whose native K(m) was low (P=0. 0013 compared with control). V(max) and serum triacylglycerol levels were related in normal controls (r(s)=0.54, P=0.038) and in diabetic subjects whose K(m) fell after N-ethylmaleimide (n=25, r(s)=0.62, P=0.001). Where the K(m) rose after N-ethylmaleimide, V(max) and triacylglycerol levels were not related (n=13, r(s)=-0.39, P=0.183) and membrane fluidity did not increase after N-ethylmaleimide. However, these subgroups were indistinguishable in terms of blood pressure, albuminuria, glycaemia or lipid profiles. Thus abnormalities in the regulation of Na-Li CT and membrane fluidity by key thiol proteins, resembling those seen in essential hypertension and diabetic nephropathy, were apparent in one-third of subjects with Type II diabetes. Membrane abnormalities may indicate a common pathological mechanism. The prognostic significance of Na-Li CT kinetic abnormalities in Type II diabetes must now be confirmed.

Adult↗
PubMed1999

Silent myocardial ischemia and microalbuminuria in asymptomatic subjects with non-insulin-dependent diabetes mellitus.

Microalbuminuria is an increase in urinary albumin not detected by conventional dipstick testing and is present in 20% of patients with non-insulin-dependent diabetes mellitus (NIDDM). Mortality in NIDDM patients with microalbuminuria is 60% at 8 years and is mainly due to cardiovascular disease. Because many deaths occur without warning symptoms, we have compared the prevalence and severity of silent myocardial ischemia in asymptomatic NIDDM patients with and without microalbuminuria. We have performed a cross-sectional, case-control study of asymptomatic NIDDM patients attending hospital diabetes clinics. Forty-three patients with microalbuminuria were matched for age, gender, diabetes duration, and smoking status with 43 normoalbuminuric patients. A symptom-limited exercise stress test was performed and reported blind to patient status. The degree of electrocardiographic ST-segment depression, exercise time, work performed, and maximum heart rate with exercise were recorded. Patients with microalbuminuria had a higher prevalence of ischemic response (>1 mm ST depression) (65% vs 40%, p = 0.016), reduced total exercise time (5 vs 7 minutes, p <0.001), reduced work (6 vs 8 METs, p <0.001), and reduced age-predicted maximum heart rate (94% vs 101%, p = 0.004). In multiple logistic regression, albumin excretion rate was shown to be the strongest independent predictor of ischemic response (p = 0.03). Silent myocardial ischemia is common in asymptomatic NIDDM patients but is more common in those with microalbuminuria. In these subjects, the higher prevalence of ischemic response at low workloads suggests a higher probability of future coronary events, and possibly a higher probability of potentially treatable coronary artery disease.

Aged↗
PubMed1999

Dysregulation of PMN antigen expression in Type 2 diabetes may reflect a generalized defect of exocytosis: influence of hypertension and microalbuminuria.

Defective exocytosis could underlie clinical and metabolic abnormalities in Type 2 diabetes. Because many SNARE proteins appear to be common mediators of exocytosis, we examined phorbol myristate acetate-stimulated expression of CD11b and CD69 on polymorphonuclear leukocytes (PMN) from Type 2 diabetic subjects with hypertension and microalbuminuria (D-htma), hypertension only (D-ht) or uncomplicated (D-uc), and normal controls (NC) by flow cytometry. CD11b expression was rapid (half maximal by 7 min), initially on all PMN. CD69 expression took place subsequently but on PMN that did not express CD11b. The proportion of CD11b-positive PMN at 30 min was higher in all diabetic groups than in NC. Expression of CD11b was higher and CD69 lower in D-uc and D-htma but were similar in NC and D-ht. In Type 2 diabetes the transition from the CD11b-positive to CD69-positive state is impaired. The defect in the process of CD69 expression appeared most marked in diabetic subjects with hypertension and microalbuminuria.

Adult↗
PubMed1999

Blood pressure control, microalbuminuria and cardiovascular risk in Type 2 diabetes mellitus.

Type 2 (noninsulin-dependent) diabetes mellitus (DM) affects about 3% of the UK population. Diabetes often coexists with a cluster of other potent cardiovascular risk factors, including hypertension, dyslipidaemia and increased tendency for thrombosis, and increases the risk of early death from cardiovascular causes by about threefold. Microalbuminuria or proteinuria also may be present, further increasing the risk of cardiovascular mortality. Cardiovascular risk factors must be treated aggressively in patients with Type 2 diabetes and control of blood pressure at 140/85 mm Hg or lower is a priority. The management of hypertension in patients from some ethnic groups demands special consideration because they have a high incidence of diabetes and hypertensive complications. Patients must be urged to adopt appropriate lifestyle changes in the first instance but additional drug treatment for hypertension is usually required. All the major classes of antihypertensive agents lower blood pressure in Type 2 diabetic patients but have different effects on metabolic risk factors in different ways. Low-dose thiazide diuretics, beta-blockers, calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors have been shown to reduce cardiovascular risk. Individually, the effects of low-dose thiazide diuretics and beta-blockers on glucose and lipid metabolism is clinically insignificant, though in combination much larger metabolic effects are seen. ACE inhibitors and calcium channel blockers have no, or small, beneficial effects on glucose and lipid metabolism, while the greater beneficial effects of alpha1-blockers on lipid profiles may render them especially useful in the Type 2 diabetic patient. Long-acting calcium-channel blockers and ACE inhibitors protect renal function and are suitable as first line therapy in patients with microalbuminuria or proteinuria. Until results from the current batch of randomized, placebo-controlled trials comparing different classes of antihypertensive agents are available, the choice of antihypertensive agent is difficult. Addressing overall cardiovascular risk factors, rather than hypertension alone, is essential in the management of the hypertensive Type 2 diabetic patient.

Albuminuria↗
PubMed1999

Episodic hyperglycaemia in pregnant women with well-controlled Type 1 diabetes mellitus: a major potential factor underlying macrosomia.

AIMS: To test the common assumption that pregnant women who are sufficiently motivated to achieve very good HbA1c levels will record home blood glucose data accurately. METHODS: A new device was used to download information from electronic blood glucose meters to assess the extent of selectivity in patient glucose diary-keeping. RESULTS: In an index case, a woman with excellent ambient HbA1c (5.9%; upper limit of normal 6.1%) was observed to have 68% of preprandial blood glucose readings above the target range of 3.5-6.5 mmol/l and a mean (+/- SD) level of 8.9+/-3.9 mmol/l in the corresponding period. No such impression was conveyed by the home monitoring diary. Six pregnant women with well controlled Type 1 diabetes (mean HbA1c 6.6+/-0.2%) exhibited between 42 and 68% of preprandial readings above the target range. CONCLUSIONS: The frequency of hyperglycaemia has hitherto been underestimated in well controlled pregnant women whose near-perfect home monitoring record is apparently corroborated by near-normal HbA1c levels. These observations provide a hypothesis for understanding of the disappointing continuance of macrosomia despite excellent HbA1c levels throughout pregnancy.

Adult↗
PubMed1999

Rapid identification of Campylobacter, Arcobacter, and Helicobacter isolates by PCR-restriction fragment length polymorphism analysis of the 16S rRNA gene.

A rapid two-step identification scheme based on PCR-restriction fragment length polymorphism (PCR-RFLP) analysis of the 16S rRNA gene was developed in order to differentiate isolates belonging to the Campylobacter, Arcobacter, and Helicobacter genera. For 158 isolates (26 reference cultures and 132 clinical isolates), specific RFLP patterns were obtained and species were successfully identified by this assay.

Arcobacter↗
PubMed1998

British Diabetic Association guidelines on genetic and immune screening for type 1 diabetes mellitus.

The following article is a report from the Chairman of the Professional Advisory Committee of the British Diabetic Association. The committee, with the help of a number of experts currently working in the field, produced a set of guidelines intended for use by health care professionals on the issues around genetic screening for Type 1 diabetes mellitus. The guidelines were approved by the Board of Management of the British Diabetic Association and we publish them here.

Autoantibodies↗
PubMed1998

Autonomic neuropathy in asymptomatic subjects with non-insulin-dependent diabetes mellitus and microalbuminuria.

Patients with non-insulin-dependent diabetes mellitus (NIDDM) and microalbuminuria (MA) are at increased risk of early death. In NIDDM patients without evidence of heart disease, we examined the links between MA and autonomic neuropathy (AN) and reduced heart rate variability (HRV), both of which have been linked to a poor prognosis. We have studied 43 asymptomatic NIDDM patients with MA and have matched them with 43 normoalbuminuric patients for age, gender, diabetes duration, and smoking status. AN was assessed by heart rate changes to deep breathing, Valsalva, and posture and blood pressure changes to posture and hand grip. Twenty-four hour Holter monitoring was used to evaluate HRV. Patients with MA showed evidence of AN and reduced HRV when compared with normoalbuminuric patients. In multivariate analysis, with measures of AN and HRV as outcome variables, Log albumin excretion rate was a significant independent predictor but stronger predictors were the presence of diabetic retinopathy, age, body mass index, claudication, alcohol consumption, and calcium channel blocker use. The presence of MA is linked to AN and reduced HRV in asymptomatic NIDDM patients. The nature of the relationship is complex, involving multiple relationships with other clinical parameters.

Aged↗
PubMed1998

Renal autoregulation is normal in newly diagnosed, normotensive, NIDDM patients.

Abnormalities of renal autoregulation with glomerular hyperfiltration and raised intraglomerular pressure have been suggested as important factors in the initiation and development of diabetic nephropathy. Angiotensin converting enzyme (ACE) inhibition appears to have a specific reno-protective role in diabetic nephropathy, possibly by reducing intraglomerular pressure. The acute effects of ACE inhibition on renal haemodynamics in normotensive, non-insulin-dependent diabetes mellitus (NIDDM) have not been previously reported. We measured simultaneous glomerular filtration rate (GFR) and renal plasma flow (RPF) in 29 (4 female) subjects, mean age 52 years (range 27-70), using 51Cr EDTA and 125I Hippuran. Clearances were corrected to 1.73 m(-2). All patients were normotensive (blood pressure < 75th centile for age and sex), newly diagnosed (< 30 days), taking no antihypertensive or hypoglycaemic medication. Subjects were randomly allocated (double blind) to receive the ACE inhibitor trandolapril 4mg day(-1) (H) (hypotensive dose), trandolapril 0.5 mg day(-1)(L) (non-hypotensive dose) or placebo (P) for 10 days after which renal haemodynamics were remeasured. For all subjects baseline GFR, RPF and filtration fraction (FF) were 97+/-21 ml min(-1) mean+/-SD, 439+/-120 ml min(-1) and 22.3+/-2.9 % respectively. Glomerular hyperfiltration (GFR> 120 ml min[-1]) was only demonstrated in 3 subjects (10.3 %). In group H mean arterial pressure (103+/-8 vs 93+/-9 mmHg, p < 0.001) and FF (23.8+/-2.3 vs 20.0+/-4.0%, p = 0.03) fell while RPF increased (376+/-111 vs 426+/-60 ml min(-1), p = 0.02), there was no significant change in GFR. No significant change in mean arterial pressure, GFR, RPF or FF occurred in groups P and L. These studies suggest that in newly diagnosed normotensive NIDDM subjects normal renal autoregulation occurs and glomerular hyperfiltration is uncommon.

Adult↗
PubMed1998

Abnormal regulation of cell membrane fluidity in diabetic nephropathy.

An abnormality of the physical properties of the cell membrane may underlie the defect that unites the clinical and biochemical abnormalities found in subjects with diabetic nephropathy. The cell membrane is linked both structurally and functionally with the cytoskeleton. The fluorescence anisotropy, a measure of membrane fluidity, was studied at baseline and after modulation of cytoskeletal proteins by thiol group alkylation with N-ethylmaleimide (NEM). 1,6-diphenyl-1,3,5-hexatriene (DPH) was used to assess anisotropy in the deep hydrophobic regions of the lipid bilayer and trimethylammonium-diphenylhexatriene (TMA-DPH) was used to assess the superficial, relatively hydrophilic regions. We compared 17 subjects with insulin-dependent diabetes mellitus (IDDM) and nephropathy with 17 control subjects with IDDM and 24 non-diabetic control subjects. Median TMA-DPH anisotropy (0.271 (0.239-0.332) vs 0.269 (0.258-0.281) vs 0.275 (0.246-0.287)) and DPH anisotropy (0.221 (0.193-0.261) vs 0.227 (0.197-0.253) vs 0.226 (0.193-0.245)) were similar in erythrocytes from the three groups. However after alkylation of protein thiol groups with NEM clear differences emerged. In the control subjects with and without IDDM there was a significant fall in TMA-DPH anisotropy compared to the subjects with diabetic nephropathy in whom the addition of NEM had no effect (deltaTMA-DPH anisotropy -0.005 (-0.020 - +0.006) vs -0.005 (-0.011 - +0.016) vs +0.002 (-0.010 - +0.008) p < 0.001). This finding was confirmed when the deep regions of the lipid bilayer were assessed using DPH (deltaDPH anisotropy -0.017 (-0.029 - -0.007.) vs -0.015 (-0.029 - +0.001) vs + 0.003 (-0.021 - +0.018) p < 0.001). We conclude that cytoskeletal modulation of the physical properties of the cell membrane lipids by proteins is abnormal in subjects with diabetic nephropathy. Such an abnormality could explain some of the clinical and metabolic abnormalities found in this condition.

Adult↗
PubMed1997

Lack of association of angiotensin II type 1 receptor gene polymorphism with diabetic nephropathy in insulin-dependent diabetes mellitus.

Several observations suggest that inherited factors are influential in the development of nephropathy in patients with insulin-dependent diabetes mellitus (IDDM). Genetic components of the renin angiotensin system are possible candidate genes. The aim of this study was to determine the role of the hypertension associated angiotensin II type 1 receptor (AT1R) gene A1166C polymorphism in susceptibility to nephropathy in IDDM. We examined 264 Caucasoid patients with IDDM and overt nephropathy (as defined by persistent proteinuria in the absence of other causes, hypertension and retinopathy), 136 IDDM patients with long duration of diabetes and no nephropathy (LDNN group), 200 recently diagnosed IDDM patients (Sporadic Diabetic group), and 212 non-diabetic subjects. The AT1R gene polymorphism was assessed using the polymerase chain reaction and restriction isotyping. Genotype frequencies did not differ significantly between the sporadic diabetic group and the nephropathy group (p = 0.245), nor between the long duration non-nephropathy group and the nephropathy group (p = 0.250). Allele frequencies were not significantly different between the three groups (p = 0.753). We conclude that there is no significant association between the hypertension associated AT1R gene polymorphism and diabetic nephropathy in patients with IDDM in the UK.

Adolescent↗
PubMed1997

Thiol group modulation of sodium-lithium countertransport kinetics in diabetic nephropathy.

Abnormal erythrocyte sodium-lithium countertransport (Na-Li CT) activity, traditionally measured at a single sodium concentration of 140 mmol.l-1 (V140), may represent an inherited risk marker for diabetic nephropathy. The membrane defect underlying this association is poorly understood, though modulation by key protein thiol groups appears to be important in essential hypertension. To improve understanding of this abnormality, Na-Li CT kinetics in untreated erythrocytes and after thiol group alkylation with N-ethylmaleimide were investigated in 18 subjects with diabetic nephropathy, 20 normoalbuminuric insulin-dependent diabetic (IDDM) subjects and 18 non-diabetic individuals. Using the traditional assay, V140 was similar in subjects with diabetic nephropathy compared to IDDM control subjects vs 0.311 (0.152-0.475) (0.247 (0.111-0.498) mmol Li.h-1.l erythrocytes-1). Kinetic parameters were abnormal in subjects with diabetic nephropathy compared with diabetic and non-diabetic control subjects with both Vmax (maximal Na-Li CT activity) (0.454 (0.257-0.963) vs 0.338 (0.183-0.972) vs 0.332 (0.213-0.603) mmol Li.h-1.l erythrocytes-1, p < 0.05), and Vmax/Km(So) ratio, reflecting ion association (6.03 (2.3-9.6) vs 4.73 (2.0-10.4) vs 4.48 (1.5-7.1), p < 0.01), significantly higher. N-ethylmaleimide decreased K(m)(So) and Vmax abolishing differences in Vmax/Km(So) ratio between groups (2.45 (1.18-4.21) vs 2.23 (0.96-4.3) vs 2.44 (1.4-3.7), but enhancing the differences in Vmax (0.186 (0.090-0.315) vs 0.120 (0.051-0.256) vs 0.128 (0.080-0.206) mmol Li.h-1.l erythrocytes-1, p < 0.0001). Of subjects with diabetic nephropathy, 78% were outside the 75th percentile of the non-diabetic control subjects when Vmax and Vmax/Km(So) ratio were combined, compared to 20% of the normoalbuminuric control subjects. We conclude that the traditional assay, V140, is poor at detecting individuals with diabetic nephropathy. Study of the kinetic parameters of the transporter, including thiol group modulation, suggests that increased ion association, Vmax/Km(So) ratio may represent the inherited defect and improves identification of subjects with diabetic nephropathy.

Adult↗