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OBJECTIVE: To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes. DESIGN: Randomised controlled trial comparing tight control of blood pressure aiming at a blood pressure of

Objective: To determine the prevalence of hypertension in newly diagnosed type 2 diabetic patients and its association with risk factors for cardiovascular and diabetic complications.Design: Cross-sectional study.Patients: Newly diagnosed type 2 diabetic patients (n = 3648, mean age 52 years, 59% male) recruited for the UK Prospective Diabetes Study (UKPDS).Measurements: Blood pressure, body mass index, waist:hip ratio, ECG signs of ischaemia and of left ventricular hypertrophy (Minnesota code), fasting plasma glucose, urate, creatinine, insulin, triglycerides, high-density lipoprotein-, low-density lipoprotein- and total cholesterol, urinary albumin: creatinine ratio, retinopathy grading.Results: Thirty-nine per cent of the patients (35% of the males, 46% of the females) were hypertensive (mean blood pressure greater-than-or-equal-to 160 systolic and/or greater-than-or-equal-to 90 mmHg diastolic 2 and 9 months after diagnosis of diabetes, or taking antihypertensive therapy). The hypertensive patients had a greater mean body mass index (30.1 versus 28.0 kg/m2, P 5.0 g/mol; 24 versus 14%, P < 0.0001), of ECG signs of probable and possible ischaemia (24 versus 14%, P < 0.0001) and of left ventricular hypertrophy (8.5 versus 3.8%; P < 0.0001). The prevalence of retinopathy was similar in the two groups.Conclusions: Hypertension is common in newly diagnosed type 2 diabetes and is associated with obesity. The association between hypertension and higher triglyceride and insulin levels may be secondary to obesity in this population. An association between hypertension and cardiovascular complications is already apparent at diagnosis of diabetes.

The objective of this study was to investigate the effects and tolerability of an omega-3 ethyl ester concentrate (Omacor(trade mark)) on serum lipid concentrations in patients with hyperlipidaemia. A multicentre, double-blind, randomised, placebo-controlled trial was performed in the hospital and general practice setting. 84 patients with hyperlipidaemia were given a therapeutic lipid-lowering diet for 10 weeks. Of these, 55 patients were randomised to a 12-week treatment period. 47 patients completed the study and two patients withdrew because of adverse events. Randomised patients received omega-3 ethyl ester concentrate or corn oil (placebo), both administered at a dose of 2g twice daily in soft gelatin capsules. Main outcome measures included changes in eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA) content of serum phospholipids, total serum triglycerides, total serum cholesterol, and high density lipoprotein (HDL) cholesterol between baseline (week 10) and the end of treatment (week 22). After 12 weeks of treatment, patients receiving the omega-3 ethyl ester concentrate showed a significant increase in the EPA/DHA content of serum phospholipids (p < 0.0001). No significant changes in serum phospholipids were observed in the patients given placebo. A mean [standard deviation (SD)] reduction in serum triglyceride of 28.3 (19.1)% (p = 0.0001) occurred in patients given the omega-3 ethyl ester concentrate. Patients receiving corn oil showed a nonsignificant mean (SD) increase in serum triglyceride of 9.1 (24.8)%. Therefore, a difference between the groups of 37.4% in favour of active treatment was found (p < 0.0001). Total serum cholesterol did not change significantly in either treatment group. Mean (SD) HDL cholesterol concentrations showed an increase of 0.9 (21.6)% in patients receiving omega-3 ethyl ester concentrate and 3.6 (24.3)% in the corn-oil group; however, neither increase was significant. In conclusion, omega-3 ethyl ester concentrate, 4 g/day, produced a significant reduction in mean serum triglyceride concentration in patients with hyperlipidaemia and was well tolerated.

In a single blind crossover study, ciclazindol, 10-(m-chlorophenyl)-2, 3, 4, 10-tetrahydropyrimide (1, 2 alpha) indol-10-ol hydrochloride (Fig. 1), has been found to have hypoglycaemic action, and to produce reduction in appetite and weight. The mode of action appears to be different from either biguanides or sulphonylureas. Side-effects were few and mild. Metformin 500 mg b.d. had comparable hypoglycaemic effect but did not suppress appetite. Ciclazindol may be useful as a mild oral hypoglycaemic agent for obese patients, and would be suitable for once daily administration.

Gliquidone (Glurenorm) and glibenclamide were compared in a cross-over study of 20 non insulin dependent diabetics. Both drugs achieved similar levels of control, as measured by self home monitoring, glycosylated haemoglobin and N-acetyl-beta-D-glucosamidase levels. However, with glibenclamide hyperglycaemic control was only achieved at the expense of more hypoglycaemic episodes. The study examined the tailoring of drug dosage to the patients needs and found that in the majority of patients it was necessary to give both glibenclamide and gliquidone thrice daily. It confirmed the acceptability of self glucose monitoring in a home population.

There are two main groups of oral hypoglycaemic compounds — the sulphonylureas and the biguanides. The sulphonylureas act by stimulating release of insulin in the intact pancreas. Animal studies show that the β-cells of the islets may be stimulated to divide. Long-term hypoglycaemic effects cannot be explained solely by the extra release of insulin. Suitable diabetics for sulphonylurea treatment are typically those of maturity onset type and showing no ketonuria. Since weight gain is stimulated, obese subjects are not ideal candidates for sulphonylurea therapy. The ‘second generation’ sulphonylureas are more active weight-for-weight than their predecessors but not necessarily therapeutically superior. Factors such as potency, pharmacokinetic properties, cross reactivity as allergens and cost influence selection for individual patients. Primary or secondary failure of the hypoglycaemic effect of sulphonylureas may often be overcome by adding a biguanide, with its different mode of action. Side-effects of sulphonylureas include rashes, dyspepsia, flushing after alcohol and occasional jaundice or depression of the bone marrow. A few commonly used drugs, notably phenyl- and oxyphenbutazone, may increase the hypoglycaemic activity of the sulphonylureas, while others such as the thiazides and steroids may decrease it. Hypoglycaemia may also be simply an overdose effect. The biguanide compounds do not produce hypoglycaemia in their own right and do not increase insulin output. Rather, peripheral uptake of glucose is increased and, in large doses, intestinal absorption is decreased. Suitable recipients are maturity onset, non-ketotic diabetics of above average weight who have not responded adequately to diet alone. Primary and secondary failures can be treated by adding a sulphonylurea. Of the two commonly used compounds, phenformin carries a slight but significant risk of inducing dangerous lactic acidosis. More common side-effects of both metformin and phenformin are anorexia, nausea, vomiting and diarrhoea with malaise. Slow increase in dosage can largely avoid these side-effects. Long-term large dose treatment may produce malabsorption of various dietary elements, such as vitamin B12 and folate. The University Group Diabetes Program (UGDP) study on early diabetics brought to light possible serious cardiovascular toxicity of both tolbutamide and phenformin, but other studies have tended to indicate possible benefit to cardiovascular morbidity. The fact that the diet-treated group fared better than the tablet-treated group has however, stressed the importance of diet as the main treatment of early diabetes.

N-Acetyl-beta-D-glucosaminidase (NAG) activity has been measured in the serum and urine of primary and secondary diabetics and in primary diabetics with microangiopathy. NAG activity has also been measured in the tears of diabetics with ocular complications and diabetics with no ocular changes. Results have shown significantly higher levels of urinary NAG in diabetics with proteinuria (p less than 0.001) and proteinuria and retinopathy (p less than 0.001). There was no correlation between urinary NAG activity and serum creatinine (r = 0.28) or urinary NAG and the degree of proteinuria (r = 0.24). Increased urinary NAG levels were also observed in secondary diabetes associated with haemochromatosis and acromegaly. Significantly higher serum NAG levels were found in newly diagnosed diabetics (p less than 0.01) and significantly lower levels in chemical diabetics (p less than 0.01). Compared to non-diabetic controls tear NAG levels were significantly higher in the diabetic controls (p less than 0.01), in diabetics with retinopathy (p less than 0.01), and in diabetics with cataract formation (p less than 0.05). An assessment of this enzyme is made in relation to the development of diabetic microangiopathy.

An insulin injection device, NovoPen, incorporating cartridged U100 Human Actrapid insulin was used in a group of 31 insulin-dependent diabetic patients aged 31.4 +/- 11.2 years (mean +/- S.D.; range 16.5-57.0) to assess its acceptance and suitability in a regimen involving an injection before each of their three main meals plus an evening injection of Human Monotard insulin from a conventional syringe. Twenty-seven patients completed 48 weeks of NovoPen therapy and preferred to continue with the multiple injection regimen in the long term. The device was well accepted and may make multiple injection regimens more feasible.