H. A. W. Neil

Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study

Abstract Objective: To determine the relation between systolic blood pressure over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes. Design: Prospective observational study. Setting: 23 hospital based clinics in England, Scotland, and Northern Ireland. Participants: 4801 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk. Outcome measures: Primary predefined aggregate clinical outcomes: any complications or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, lower extremity amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photocoagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 10 mm Hg decrease in updated mean systolic blood pressure adjusted for specific confounders Results: The incidence of clinical complications was significantly associated with systolic blood pressure, except for cataract extraction. Each 10 mm Hg decrease in updated mean systolic blood pressure was associated with reductions in risk of 12% for any complication related to diabetes (95% confidence interval 10% to 14%, P<0.0001), 15% for deaths related to diabetes (12% to 18%, P<0.0001), 11% for myocardial infarction (7% to 14%, P<0.0001), and 13% for microvascular complications (10% to 16%, P<0.0001). No threshold of risk was observed for any end point. Conclusions: In patients with type 2 diabetes the risk of diabetic complications was strongly associated with raised blood pressure. Any reduction in blood pressure is likely to reduce the risk of complications, with the lowest risk being in those with systolic blood pressure less than 120 mm Hg.

The relation between dietary flavonol intake and coronary heart disease mortality: a meta-analysis of prospective cohort studies

Objective: To assess the association of dietary flavonol intake with the subsequent risk of coronary heart disease (CHD) mortality.Design: Meta-analysis of prospective cohort studies published before September 2001. Studies were identified by MEDLINE and EMBASE searches and by scanning relevant reference lists. The following information was extracted from published reports: size of cohort, mean age, mean duration of follow-up, number of fatal CHD events, mean flavonol intake, main sources of flavonol intake, degree of adjustment for potential confounders, and the relation of CHD mortality to dietary flavonol intake measured at baseline.Results: Seven prospective cohorts of men and women were identified including a total of 2087 fatal CHD events. Comparison of individuals in the top third with those in the bottom third of dietary flavonol intake yielded a combined risk ratio of 0.80 (95% CI 0.69–0.93) after adjustment for known CHD risk factors and other dietary components.Conclusion: This overview of prospective cohort studies indicates that high dietary intake of flavonols from a small number of fruits and vegetables, tea and red wine may be associated with a reduced risk from CHD mortality in free-living populations.Sponsorship: Institute for International Health, University of Sydney.

Current methods of transfer of young people with Type 1 diabetes to adult services

Aims To determine the efficacy and patient perception of various transfer procedures from paediatric to adult diabetes services.

Randomised controlled trial of use by hypercholesterolaemic patients of a vegetable oil sterol-enriched fat spread

Plant sterols may be a useful additive therapy in the treatment of hypercholesterolaemic patients. The purpose of this study was to determine the effect of a fat spread enriched with vegetable oil sterols on plasma lipid, lipoprotein and apolipoprotein concentrations. A randomised double blind placebo-controlled crossover trial with two consecutive periods of 8 weeks was conducted. 30 patients with heterozygous familial hypercholesterolaemia treated concurrently with an HMG-CoA reductase inhibitor (statin) and 32 patients with type IIa primary hypercholesterolaemia with a total cholesterol concentration >6.5 mmol/l not taking lipid-lowering drug therapy were recruited from a hospital lipid clinic. The active treatment was a fortified fat spread (25 g/day) providing 2.5 g of plant sterols. The control spread was indistinguishable in taste and appearance. Comparison at the end of the two 8-week trial periods showed a statistically significant reduction in total and LDL-cholesterol with use of the fortified spread but the results were confounded by a carry-over effect, which was partly explained by changes in the background diet. Because a carry-over effect was present, further analyses were restricted to the parallel arms of the first treatment period and were conducted on an intention to treat basis. After 4 weeks, LDL-cholesterol had decreased by 0.04 mmol/l ([0.8%] 95% confidence interval -0.44-0.37 NS) in the placebo group and decreased by -0.76 mmol/l ([15.0%] 95% CI -1.03--0.48, P<0.0001) in the active treatment group. After 8 weeks, the corresponding results were 0.0 mmol/l ([0.0%] 95% CI -0.26-0.24 NS) and -0.51 mmol/l ([10.0%] 95% CI -0.73--0.29 P<0.0001). There were no significant changes in apolipoprotein AI or B concentrations in the placebo group, but there was a small but statistically significant increase in apolipoprotein AI and a decrease in apolipoprotein B in the active treatment group. HDL cholesterol and triglyceride concentrations were unchanged. There was no difference in response between patients with statin-treated familial hypercholesterolaemia and patients with type IIa hyperlipoproteinaemia. We conclude that a fortified fat spread enriched with vegetable oil sterols reduces LDL-cholesterol by 10-15% with no difference in response between hypercholesterolaemic patients prescribed statins and those not taking lipid-lowering drug therapy.

The Oxford Community Diabetes Study: evidence for an increase in the prevalence of known diabetes in Great Britain.

A prevalence survey for known diabetes was conducted in a geographically defined population of nearly 40 100 in Oxford in April 1982. The age‐adjusted prevalence rate was 10.4/1000 which did not differ significantly from age‐adjusted rates of 9.5/1000 in Poole and 10.5/1000 in Southall. The prevalence increased with age and was higher in men than women over the age of 30 years. Our results confirm that there has been a change in the male to female sex ratio and suggest that there are about 500 000 diagnosed diabetics in England and Wales including about 190 000 insulin‐treated patients. These findings are consistent with a secular increase in the prevalence of diagnosed diabetes over the last two decades which has important implications for the planning and provision of resources for care.

Diabetes in the Elderly: The Oxford Community Diabetes Study

Most diabetic patients are elderly but their clinical characteristics remain poorly defined. A population survey identified 259 known diabetic patients aged 60 years or more giving a prevalence of 3% in this age group. A total of 193 patients (75%) were interviewed and examined, 155 (80%) of whom had been diagnosed at under 70 years of age. Forty‐two patients (22%) were insulin‐treated but clinical characteristics suggested that at least 95% of all elderly patients had Type 2 diabetes. Blood glucose control was poor with median HbA1 9.7% (range 4.9–17.1%, normal reference range 5.0–7.5%), and 55% were either overweight or obese. There was a high morbidity from diabetes and other conditions: the prevalence of hypertension (untreated blood pressure of 160/95 mmHg or more or antihypertensive medication) was 52%, of stroke 5%, of nephropathy (urinary albumin concentration ≥300 mg I−1) 3%, of lower limb amputations 4%, and of foot ulcers 7%. The prevalence of symmetrically impaired distal vibration perception was 23%, and 54% of patients either needed or were receiving chiropody. The prevalence of a corrected distant visual acuity of 6/12 or worse was 32% and of retinopathy of any degree was 26%. There was extensive co‐morbidity which was not confined to a single subgroup of patients.

Diabetic Autonomic Neuropathy: the Prevalence of Impaired Heart Rate Variability in a Geographically Defined Population

The prevalence of diabetic autonomic neuropathy and its relationship with other diabetic complications were studied in a geographically defined population. Heart rate variability was measured by a computerized technique at rest and in response to both a single deep breath and a Valsalva manoeuvre. Among 43 Type 1 (insulin‐dependent) and 202 Type 2 (non‐insulin‐dependent) patients results below the 2.5 centile for age‐related normal ranges occurred in 9 Type 1 and 32 Type 2 patients (16.7, 95% Cl 12.6 to 21.9, %). Symptomatic autonomic neuropathy was uncommon but was significantly more frequent in Type 1 than Type 2 patients (5 Type 1, 1 Type 2, p < 0.001 Fishers exact test). In Type 1 diabetes, cardiovascular autonomic dysfunction was significantly associated with impaired vibration perception and a higher logarithmic urinary albumin concentration and, in Type 2 diabetes, it was associated with a significantly higher body mass index, systolic blood pressure, and logarithm of the urinary albumin and fasting insulin concentrations. The aggregation of these factors with cardiovascular autonomic dysfunction suggests that mortality might be increased in Type 2 patients with asymptomatic autonomic neuropathy.

Freezing method affects the concentration and variability of urine proteins and the interpretation of data on microalbuminuria

Aims Microalbuminuria and, to a lesser extent, renal tubular proteins are widely used in the early detection of incipient nephropathy in diabetes mellitus. Recent reports have indicated detrimental effects of storage at −20°C on urine proteins. This study investigated the effects of storage on the measurement of urine proteins and discusses implications for the interpretation of data.

The relative risks of hyperglycaemia, obesity and dyslipidaemia in the relatives of patients with Type II diabetes mellitus.

Summary Type II (non-insulin-dependent) diabetes mellitus has a substantial genetic component; however, its molecular basis remains largely unknown. The mode of inheritance is likely to be polygenic, with penetrance influenced by environmental factors. Although the familial aggregation of Type II diabetes is acknowledged, there is little data concerning the prevalence of diabetes in the relatives of subjects with diabetes in comparison with the general population, and our objective was to address this question in the defined geographic region of Oxfordshire, England. We studied 139 first degree relatives of 90 probands with Type II diabetes who attended routine diabetes clinics in Oxfordshire and documented the fasting plasma glucose, triglyceride and HDL-cholesterol concentrations and BMI of these subjects. The probands were selected without regard to family history of diabetes. The control population data were derived from two large-scale Oxford community studies which documented the prevalences of known and newly diagnosed diabetes. The prevalences of newly diagnosed and known diabetes were calculated for each group. The mean BMI, and concentrations of fasting glucose, triglyceride and HDL-cholesterol were compared and prevalence ratios for obesity (defined as BMI > 30 kg/m2), hyperglycaemia (defined as fasting plasma glucose ≥ 6.1 mmol/l), and dyslipidaemia (defined as triglyceride > 2.0 mmol/l, HDL < 1.0 mmol/l) were calculated. There was a fourfold higher prevalence of hyperglycaemia in the first degree relatives of subjects with Type II diabetes compared with the control population: the prevalence ratio after adjustment for age, sex and BMI was 4.32 (95 % confidence interval 2.29–8.17). The relatives had a considerably higher fasting plasma glucose concentration than the control population (5.18 ± 0.67 mmol/l (mean ± 1 SD) vs 4.76 ± 1.59 mmol/l, p = 0.0001), and this difference remained statistically significant after adjustment for age, sex and obesity. The relatives were significantly more obese, had higher fasting plasma insulin concentrations and had lower HDL-cholesterol concentrations. In conclusion, there is a strong familial aggregation of hyperglycaemia and obesity in the relatives of subjects with Type II diabetes and these subjects have higher fasting plasma insulin concentrations and lower HDL-cholesterol than the general population. These data indicate the particular relevance of screening the first degree relatives of subjects with Type II diabetes, as intervention strategies which aim to improve the metabolic profile are indicated for a large proportion of these subjects. [Diabetologia (1999) 42: 24–27]

A Population-based Study of the Incidence of Complications Associated with Type 2 Diabetes in the Elderly

One hundred and eighty‐eight known Type 2 diabetic patients aged over 60 years identified by a geographically based survey of a population of 40 076 were followed for a median of 6 years to determine the incidence of various complications. There were 63 deaths and two patients were lost to follow‐up. The presence of complications was determined using a structured questionnaire and clinical examination. Incidence rates of ischaemic heart disease, stroke, and peripheral vascular disease (PVD) were 56 (95% CI 41–75), 22 (13–35), and 146 (117–174) 1000‐person‐years−1 of follow‐up, respectively. Rates of stroke and PVD rose significantly with age. Retinopathy occurred at a rate of 60 (42–83) 1000‐person‐years−1 and cataract at 29 (17–46) 1000‐person‐years−1 although visual acuity in survivors did not deteriorate overall, probably reflecting the high mortality associated with cataract. The rate of proteinuria (albumin concentration > 300 mg l−1) was 19 (9–34) 1000‐person‐years−1. Incidence rates were unrelated to sex or duration of diabetes. Diabetes is associated with a continuing incidence of complications into old age. Adequate facilities are required to assess and treat the resulting morbidity in a population with an increasing proportion of elderly people.