M. Small

Free Radical Activity in Type 2 Diabetes

Free radical activity has been implicated in the development of diabetic vascular complications in Type 1 diabetes. The aim of the present study was to investigate the levels of free radical scavengers, particularly erythrocyte superoxide dismutase, plasma and erythrocyte lysate thiol, and caeruloplasmin in 22 Type 2 diabetic patients clinically free of complications, and 15 comparable non‐diabetic control subjects. The concentration (median (range)) of both superoxide dismutase (23 (10–39) vs 45 (25–75) μmol I−1; p < 0.001) and plasma thiol (374 (172–523) vs 460 (386–595) μmol I−1; p < 0.01) were reduced in the diabetic group. There were no significant differences in the concentration of erythrocyte lysate thiol (199 (114–520) vs 188 (114–328) μmol I−1) or plasma caeruloplasmin (18 (9–31) vs 24 (6–50) μmol I−1) between the groups. This reduction in superoxide dismutase and the imbalance in the redox status of the plasma and lysate thiol demonstrated is consistent with an increase in free radical activity in Type 2 diabetes.

Free Radical Activity and Hemostatic Factors in NIDDM Patients With and Without Microalbuminuria

In non-insulin-dependent diabetes mellitus (NIDDM) patients, microalbuminuria predicts early mortality, predominantly from cardiovascular disease. Increased free radical activity and abnormalities in hemostasis have been implicated in the development of vascular disease. Therefore, we measured markers of free radical activity (nonperoxide-conjugated diene isomer of linoleic acid [PL-9,11-LA′] and lipid peroxides expressed as malondialdehyde [MDA]) along with the hemostatic variables: fibrinogen, von Willebrand factor (vWf), plasminogen activator inhibitor (PAI-1), tissue plasminogen activator (t-PA), and plasmin activity (Bβ15–42) in 24 NIDDM patients (12 patients with microalbuminuria and 12 without microalbuminuria) and in 12 age-matched control subjects. There were no differences in linoleic acid (PL-9,12-LA) concentrations between the three groups. PL-9,11-LA′ was elevated in the microalbuminuric patients compared with control subjects (P < 0.05), but there was no difference between the two diabetic groups. MDA was elevated in the microalbuminuric diabetic patients compared with those patients without microalbuminuria (P < 0.05) and control subjects (P < 0.001). MDA was also increased in the patients without microalbuminuria compared with control subjects (P < 0.01). Except for Bβ15–42, all the hemostatic variables were increased (P < 0.05) in the diabetic patients compared with control subjects. The microalbuminuric diabetic patients had further increases in vWf (P < 0.03) and t-PA (P < 0.03) compared with patients with microalbuminuria. Our study suggests that there is an increase in free radical activity and abnormalities in hemostatic variables favoring a hypercoagulable state in NIDDM, especially in those with microalbuminuria. These changes may contribute to vascular disease, which is particularly prevalent in NIDDM patients with microalbuminuria.

Hormone replacement therapy and sensitive C-reactive protein concentrations in women with type-2 diabetes

C-reactive protein concentrations as a marker of inflammation predicts vascular risk and is raised in type-2 diabetes. In a 6-month double-blind placebo controlled trial, a combination of transdermal oestradiol 80 microg with continuous oral norethisterone 1 mg significantly reduced C-reactive protein concentrations in postmenopausal women with type-2 diabetes.

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).

THROMBOEMBOLIC COMPLICATIONS IN CUSHING'S SYNDROME

Thromboembolic events are thought to occur with increased frequency in Cushings syndrome due to the predisposing factors, obesity, hypertension, a raised haematocrit and major surgery plus a ‘hypercoagulable state’. To examine this postulate further we have studied 43 patients with Cushings syndrome retrospectively and 10 patients prospectively to determine the incidence of arterial and venous thrombosis, both spontaneous and post‐operative.

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.

Glycated haemoglobin values: problems in assessing blood glucose control in diabetes mellitus

Abstract Objective: To see whether two measures of glycated haemoglobin concentration - the haemoglobin A1 (HbA1) value and the haemoglobin A1c (HbA1c) value - assess blood glucose control differently in diabetes. Design: Diabetic patients had glycaemic control assessed on the basis of HbA1 and HbA1c values measured by the same high performance liquid chromatography instrument and on the basis of HbA1 measured by electrophoresis. Setting: A diabetic outpatient clinic. Subjects: 208 diabetic patients and 106 non-diabetic controls. Main outcome measures: Glycated haemoglobin concentrations classified according to European guidelines as representing good, borderline, or poor glycaemic control by using standard deviations from a reference mean. Results: Fewer patients were in good control (25;12%) and more poorly controlled (157;75%) as assessed by the HbA1c value compared with both HbA1 assays (39 (19%) and 130 (63%) respectively when using high performance liquid chromatography; 63 (30%) and 74 (36%) when using electrophoresis). The median patient value was 8.0 SD from the reference mean when using HbA1c, 5.9 when using HbA1 measured by the same high performance liquid chromatography method, and 4.1 when using HbA1 measured by electrophoresis. Conclusions: Large differences exist between HbA1 and HbA1c in the classification of glycaemic control in diabetic patients. The HbA1c value may suggest a patient is at a high risk of long term diabetic complications when the HbA1 value may not. Better standardisation of glycated haemoglobin measurements is advisable.

Tissue Plasminogen Activator Inhibition in Diabetes Mellitus

Depression of fibrinolysis may be relevant to the vascular complications of diabetes mellitus. Plasminogen activator inhibitor (PAI) is an important inhibitor of fibrinolysis in humans, and we have found basal activities of PA inhibition to be elevated in patients with diabetes compared with a reference group of healthy subjects (mean ± SD 268 ± 268 vs. 105 ± 48%; P < .0001). With a monoclonal antibody, it was shown that high inhibition values were due to PAI-1. No differences in PA inhibition were noted in relation to type of diabetes, diabetic treatment, or presence or absence of vascular complications. Basal PA inhibition did not correlate with in vivo (Bβ15-42 antigen) or ex vivo (fibrin plate) fibrinolytic activity or HbA,. In patients with noninsulin- dependent diabetes mellitus, treatment with the anabolic steroid stanozolol significantly reduced PA inhibition. These findings suggest a further abnormality of fibrinolysis in diabetes, but the lack of a relationship among other measures of fibrinolysis renders its biologic significance uncertain

Alteration of hormone levels in normal males given the anabolic steroid stanozolol.

Anabolic steroids have widespread metabolic effects but, to date, their proven clinical indications have been limited. Recently the 17 α‐alkylated steroid, stanozolol, has been shown to be of value in a variety of commonly occurring vascular diseases. Its endocrine effects have received little attention and we have investigated the effect of administering a 14 d course of stanozolol (10 mg orally per day) on a variety of important hormonal pathways in nine healthy male subjects. Significant changes occurred as follows: a 55% reduction in serum testosterone levels was noted and was accompanied by reductions in ‘derived’ free testosterone, sex hormone binding globulin and LH levels; total T4 and T3 levels fell in association with a decrease in thyroxine binding globulin, but no alteration was detected in TSH or free T4 levels. Changes in vitamin D status, with falls in 25‐hydroxycholecalciferol and vitamin D binding globulin were also observed. These effects were reversible on stopping treatment. Stanozolol therapy therefore leads to a number of hormonal changes, probably by an action at both pituitary and hepatic levels.

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).