K M Shaw

Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity

Objective  Current research has focused upon the potential links between novel markers of vascular risk such as endothelial dysfunction, oxidative stress, inflammation and insulin resistance in the pathogenesis of Type 2 diabetes and its complications. Grape seed extract (GSE), a flavonoid‐rich product, is a potential moderator of these markers. This study aimed to test the hypothesis that GSE may improve these markers in high‐risk cardiovascular subjects with Type 2 diabetes.

Cardiovascular risk in women with polycystic ovarian syndrome (PCOS)

Aims: Studies have suggested that polycystic ovary syndrome (PCOS) is associated with increased cardiovascular risk. The aim of this study was to examine cardiovascular risk profiles in women with PCOS compared with healthy age and weight matched control subjects using novel biochemical and biophysical markers. Methods: After ethics committee approval, 11 women with PCOS and 12 controls were recruited (mean age, 32; SD, 6.5 years; mean body mass index (BMI), 33.1; SD, 5.9 kg/m2). Serum was analysed for lipid and lipoprotein profile (total and high density lipoprotein cholesterol, triglycerides, apolipoprotein B-100, apolipoprotein A1, lipoprotein (a)), and sialic acid, fibrinogen, homocysteine, and C reactive protein (CRP) concentrations. Endothelial function was also assessed by a standard venous occlusion plethysmography technique to measure reactive hyperaemic forearm blood flow (RH), and expressed as per cent increase from baseline. Results: There were no significant differences in glucose, lipid, or lipoprotein concentrations between the two groups. Furthermore, sialic acid (PCOS: mean, 70.5; SD, 149 mg/litre; controls: mean, 71.3; SD, 112 mg/litre), fibrinogen (PCOS: mean, 3.1; SD, 1.0 g/litre; controls: mean, 3.3; SD, 0.7 g/litre), CRP (PCOS: mean, 4.6; SD, 4.2 mg/litre; controls: mean, 5.4l SD, 5.5 mg/litre), and RH (PCOS: mean, 158.7; SD, 135.5%; controls: mean, 200.1; SD, 114.2%) were similar. Conclusions: There were no differences in surrogate markers of the processes linked to enhanced cardiovascular risk between patients with PCOS and weight matched controls.

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

Abstract 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 log 10 plasma glucose concentrations (mean (SD), 1.210 (0.122) (upsilon) 0.984 (0.196) mmol/l, P < 0.001) and glycated haemoglobin concentrations (1.112% (0.069%) (upsilon) 0.997% (0.076%), P < 0.001) and a younger age at onset of diabetes (10.0 (5.5) (upsilon) 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.

Endothelial dysfunction in Type 1 diabetic subjects with and without microalbuminuria

Aims The primary aim of this study was to determine whether micro‐ albuminuria is associated with endothelial dysfunction in Type 1 diabetes mellitus. The secondary aim was to determine whether any reported bio‐ chemical markers of cardiovascular risk are associated with endothelial dysfunction in this group.

Serum lipids and lipoproteins in insulin-dependent diabetic patients with persistent microalbuminuria.

Serum lipid and lipoprotein concentrations were measured in 18 insulin‐dependent diabetic patients with persistent microalbuminuria and an equal number with persistently normal albumin excretion. The groups were matched for sex, age, duration of diabetes, body mass index, insulin dose, and glycosylated haemoglobin. Diabetic patients with persistent microalbuminuria were found to have a significantly lower high density lipoprotein (HDL) cholesterol concentration (difference 0.29,95 % Cl 0.12 to 0.46, mmol l−1, p < 0.01) and a higher low density lipoprotein (LDL) cholesterol:HDL cholesterol ratio (difference 0.97, 95% Cl 0.29 to 1.65, p < 0.01) than patients with normal albumin excretion. No significant differences were found in total cholesterol, triglycerides, LDL cholesterol, apolipoprotein (apo) A‐***I and apo B concentrations. Compared to an age and sex‐matched group of non‐diabetic subjects with normal albumin excretion, diabetic patients with persistent microalbuminuria had significantly higher concentrations of total cholesterol (p < 0.05), LDL cholesterol (p < 0.05) and apo B (p < 0.01), but a lower concentration of HDL cholesterol (p < 0.05). No significant differences were found in serum lipids and lipoproteins between diabetic patients with normal albumin excretion and non‐diabetic subjects.

The quality of photographs produced by the non-mydriatic fundus camera in a screening programme for diabetic retinopathy: a 1 year prospective study

A prospective study was performed on the quality of photographs produced by the non-mydriatic fundus camera used in a hospital-based screening programme for diabetic retinopathy. In 1 year 981 binocular patients were photographed. A photograph of acceptable quality was obtained from 90.5% of eyes and 84.4% of patients had an acceptable photograph of both eyes. The photograph of the second eye was more often unacceptable than that of the first. This tendency was significant in females (p = 0.0196) and when considering the sexes together (p = 0.0044), but not significant in males (p = 0.1042). Photographs of unacceptable quality were obtained significantly more often in patients aged over 55 years for both right and left eyes (p = 0.0001). An overall improvement in photographic quality might be achieved by allowing full recovery of flash-induced pupil constriction before taking the second photograph and by dilating those aged over 55 years.

Plasma homocysteine, oxidative stress and endothelial function in patients with Type 1 diabetes mellitus and microalbuminuria

Aims  The purpose of this study was to examine the associations between endothelial function, plasma homocysteine and oxidative stress in patients with Type 1 diabetes mellitus (DM) and microalbuminuria compared with DM patients with normoalbuminuria and non‐diabetic control subjects. We wished to test the hypothesis that increased cardiovascular risk in patients with Type 1 diabetes and microalbuminuria may be in part as a result of hyperhomocysteinaemia‐mediated oxidative stress leading to impaired endothelial function.

The effect of oral folic acid upon plasma homocysteine, endothelial function and oxidative stress in patients with type 1 diabetes and microalbuminuria.

Aims:  The purpose of this study was to investigate the effect of oral folic acid supplementation upon plasma homocysteine (HCY), endothelial function and oxidative stress on patients with type 1 diabetes and microalbuminuria to test the hypothesis that oral folic acid would lower plasma HCY and thereby improve endothelial function and reduce oxidant stress in this high‐risk group of patients.

Serum Sialic Acid and the Long‐term Complications of Insulin‐dependent Diabetes Mellitus

Elevated serum sialic acid (SSA) predicts cardiovascular disease in the non‐diabetic population and is also associated with the presence of microalbuminuria and clinical proteinuria in patients with insulin‐dependent diabetes (IDDM). We have studied 121 patients with IDDM of long duration (mean duration 25.2 years) to investigate the relationship of SSA concentrations to the presence of retinopathy, nephropathy, and neuropathy. SSA levels were elevated in patients with retinopathy (0.578 ± 0.161 g l−1, n = 98) when compared with those without retinopathy (0.468 ± 0.145 g l−1, n = 23, p = 0.002). Patients with nephropathy (urinary albumin:creatinine ratio of > 3 mg mmol−1 in all of three early morning specimens of urine) also had raised SSA levels (0.625 ± 0.169 g l−1, n = 30) compared with those without nephropathy (0.533 ± 0.160 g l−1, n = 91, p = 0.006). There was a significant correlation of SSA with urinary albumin:creatinine ratio (correlation coefficient 0.33, p < 0.001). SSA levels were not related to the presence or absence of neuropathy (0.567 ± 0.181 g l−1, n = 28, vs 0.533 ± 0.160 g l−1, n = 93, p = 0.92, respectively). In conclusion, retinopathy and nephropathy but not neuropathy are associated with increased SSA levels in patients with IDDM. The significance of this is not yet clear but it is possible that sialic acid is involved in the pathophysiology of microvascular disease in IDDM.

Urinary Infection and Albumin Excretion in Insulin-dependent Diabetes Mellitus: Implications for the Measurement of Microalbuminuria.

The frequency of urinary infection was determined using quantitative microbiology in 172 insulin‐dependent diabetic patients repeatedly being tested for microalbuminuria over 18 months on at least six occasions. The point prevalence of urinary infection at first screening for microalbuminuria was 3 %. Over the period of study, 20 of the patients (12 %) showed evidence of urinary infection, defined as a pure growth of a recognized pathogen >107 l−1. Infection was more common in women than men (20 % vs 5 %, p<0.01) and was significantly associated with the presence of peripheral neuropathy (p<0.05). Infection was not related to patient age, duration of diabetes, glycaemia, blood pressure, retinopathy or autonomic neuropathy. There were no significant within‐patient differences in albumin excretion, glycaemic control or blood pressure in relation to the presence and absence of urinary infection. In only one patient (5 %) did urinary infection significantly increase the urinary albumin excretion and this was associated with pyuria. We conclude that the presence of urinary infection does not apparently affect the measurement of urinary albumin excretion unless pyuria is present. Unless diabetic patients are symptomatic, examination of the urine for infection is probably unwarranted when testing for microalbuminuria.